Biomedical subjects

L K Fellows

Publications and source records attributed to L K Fellows.

6 recordsLinked to original sources

PubMed1998

Competency and consent in dementia.

Health care for demented older persons presents a range of ethical dilemmas. The disease process affects cognitive abilities, making competency a central issue. The syndrome of dementia carries a complex social overlay that colors perceptions of these patients and of their capacity for making decisions. An argument is made for a coherent, ethically based decision-making process that can be applied across the whole spectrum of dementia severity. The major ethical principles implicated in assessing a patient's ability to consent to treatment are reviewed. A sliding scale model of capacity is presented, in which the patient's ability to decide is weighed against the risk associated with the treatment decision in question. This model preserves the autonomy of the demented patient while minimizing the potential for harm. In situations where the patient is deemed incapable, two approaches that can be applied to making treatment decisions are contrasted. The 'prior competent choice' standard stresses the values that the patient held while competent. The 'best interests' standard moves the focus to the patient's subjective experience at the time the treatment is considered. The relative merits of these two concepts are evaluated in the context of dementia. Surveys of actual decision-making practice are contrasted with ethical and legal principles. The challenges inherent to applying the best interests standard are discussed. Despite the pitfalls, this standard offers an opportunity to restore the demented patient's sense of self.

Advance Directives↗

PubMed1993

Rapid changes in extracellular glucose levels and blood flow in the striatum of the freely moving rat.

The dynamics of regional cerebral blood flow and brain extracellular glucose were studied in the freely moving rat. These two variables were measured in the striatum during and following both mild tail pinch and restraint stress. Blood flow was monitored using a refinement of the hydrogen clearance technique that allowed repeated measurements at 5-min intervals. A slow stream of hydrogen was directed at the rat's snout for 10-20 s through lightweight tubing attached to the animal's head and detected at a chronically implanted platinum electrode. Extracellular glucose was monitored with microdialysis in a separate group of animals using an on-line, enzyme-based assay that provided 2.5-min time resolution. Mean striatal blood flow 24 h following implantation was 89.9 +/- 2.5 ml.(100 g)-1.min-1. A 5-min tail pinch caused flow to increase immediately to 169.5 +/- 20 ml.(100 g)-1.min-1. In contrast, there was no change in blood flow during restraint stress, although there was a small increase following the end of the stress. Significant increases in blood flow were also observed in the striatum during periods of eating and grooming. Extracellular glucose levels increased following both forms of stress, to a maximum of 170 +/- 22% of baseline with restraint compared to 110 +/- 2% with tail pinch. In both cases, the increase occurred after the stress had ended and persisted while blood flow returned to basal levels.

Animals↗

PubMed1993

Physiological stimulation increases nonoxidative glucose metabolism in the brain of the freely moving rat.

The effects of mild stress on nonoxidative glucose metabolism were studied in the brain of the freely moving rat. Extracellular lactate levels in the hippocampus and striatum were monitored at 2.5-min intervals with microdialysis coupled with an enzyme-based flow injection analysis system. Ten minutes of restraint stress led to a 235% increase in extracellular lactate levels in the striatum. A 5-min tail pinch caused an increase of 193% in the striatum and 170% in the hippocampus. Local application of tetrodotoxin in the striatum blocked the rise in lactate following tail pinch and inhibited the subsequent clearance of lactate from the extracellular fluid. Local application of the noncompetitive N-methyl-D-aspartate receptor antagonist MK-801 had no effect on the tail pinch-stimulated increase in lactate in the striatum. These results show that mild physiological stimulation can lead to a rapid increase in nonoxidative glucose metabolism in the brain.

Animals↗

PubMed1993

ATP-sensitive potassium channels and local energy demands in the rat hippocampus: an in vivo study.

Microdialysis coupled with an enzyme-based flow injection analysis was used to monitor brain extracellular lactate and glucose in the freely moving rat. Glucose levels reflect the balance between supply from the blood and local utilisation, and lactate efflux indicates the degree of local nonoxidative glucose metabolism. Local application of tolbutamide, a blocker of the ATP-sensitive potassium channel, decreased extracellular glucose and lactate levels in the hippocampus but not in the striatum. The increase in glucose and lactate levels following mild behavioural stimulation was also reduced by tolbutamide in the hippocampus. Similar effects on both basal and stimulated lactate levels were obtained with local application of 10 mM glucose. These results indicate that ATP-sensitive potassium channels are active under physiological conditions in the hippocampus and that the effects of tolbutamide can be mimicked by physiological glucose levels.

Adenosine Triphosphate↗

PubMed1992

Enzyme packed bed system for the on-line measurement of glucose, glutamate, and lactate in brain microdialysate.

Rapid measurement of glucose, glutamate, and lactate is important in understanding the dynamics of the energy balance of the brain. Glutamate is also the main excitatory neurotransmitter. A general immobilized enzyme-based flow injection assay system is described which uses oxidase and peroxidase enzymes to convert the analyte into an oxidized ferrocene species which is detected electrochemically by reduction. The enzymes glucose oxidase, glutamate oxidase, lactate oxidase, and horseradish peroxidase are immobilized with near 100% efficiency onto 10-microns tresyl-activated silica beads (1000- and 500-A pore size). The beads are slurry-packed into 2- x 20-mm columns to give beds for glucose, glutamate, or lactate which are stable for greater than 40 days. The flow injection assays described have detection limits from 1.8 to less than 20 pmol and have been configured to have linear calibration responses over the range of basal and stimulated levels of the three compounds found in 5-microL microdialysate samples from the rat striatum. The assays are used for automated on-line measurement of glucose, glutamate, and lactate in striatal microdialysate at 2.5-min intervals.

Animals↗

PubMed1992

Extracellular brain glucose levels reflect local neuronal activity: a microdialysis study in awake, freely moving rats.

The relationship between brain extracellular glucose levels and neuronal activity was evaluated using microdialysis in awake, freely moving rats. The sodium channel blocker tetrodotoxin and the depolarizing agent veratridine were administered through the dialysis probe to provoke local changes in neuronal activity. The extracellular glucose content was significantly increased in the presence of tetrodotoxin and decreased sharply following veratridine application. The systemic injection of a general anaesthetic, chloral hydrate, led to a large and prolonged increase in extracellular glucose levels. The brain extracellular glucose concentration was estimated by comparing dialysate glucose efflux over a range of inlet glucose concentrations. A mean value of 0.47 mM was obtained in five animals. The results are discussed in terms of the coupling between brain glucose supply and metabolism. The changes observed in extracellular glucose levels under various conditions suggest that supply and utilization may be less tightly linked in the awake rat than has previously been postulated.

Animals↗