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Biomedical subjects

B Boucher

Publications and source records attributed to B Boucher.

32 records · Page 2Linked to original sources

L-dopa pharmacokinetics in plasma and cisternal and lumbar cerebrospinal fluid of monkeys.

The pharmacokinetics of levodopa (L-dopa) in plasma and in cisternal and lumbar cerebrospinal fluid (CSF) were studied in Rhesus monkeys that were given 2- to 3-hour intravenous infusions of L-dopa. Steady-state L-dopa concentrations in cisternal CSF correlated well with plasma levels, and yielded a CSF:plasma ratio of 0.17. The disappearance of L-dopa from plasma and cisternal CSF compartments fits an open, two-compartment pharmacokinetic model. Although slower, the distribution and elimination half-lives for L-dopa from cisternal CSF (8.9 and 49.2 minutes, respectively) were of a similar magnitude to those from plasma (4.9 and 33.2 minutes, respectively). If cisternal CSF reflects brain extracellular fluid, then plasma pharmacokinetics of L-dopa are a reasonable approximation of those in the brain. In contrast to cisternal CSF, the disappearance of L-dopa from lumbar CSF fits an open, one-compartment model with an elimination half-life of 100 minutes. This indicates that the lumbar CSF compartment is unsuitable for investigation of the pharmacokinetics of L-dopa in the brain.

Animals↗

The short-duration response to apomorphine: implications for the mechanism of dopaminergic effects in parkinsonism.

The pharmacological basis of the short-duration response to dopaminergic stimulation in parkinsonism is not completely understood. Whereas it is generally assumed that the response reflects concurrent dopamine receptor occupancy, it is also possible that receptor activation triggers events that outlast the time that receptors are occupied by agonist. To distinguish between these two possibilities, we administered apomorphine, a mixed D1-D2 agonist with rapid equilibration between plasma and brain, to patients with parkinsonism. The clinical response to apomorphine injections lagged behind peak plasma concentrations and persisted beyond the time plasma concentrations following ineffective doses. We conclude that dopaminergic stimulation triggers effects that outlast the period of receptor occupancy by agonist. Understanding these steps may offer new pharmacological therapies for parkinsonism.

Aged↗

Peripheral pharmacokinetics of apomorphine in humans.

Apomorphine, a potent dopamine agonist, has been used in acute and chronic studies of parkinsonism and other neurological disorders. To define its peripheral pharmacokinetics, we administered apomorphine by subcutaneous injection, by subcutaneous infusion, and by intravenous infusion to 15 patients with parkinsonism and measured plasma apomorphine levels by high-performance liquid chromatography with electrochemical detection. The peak drug levels and area under the curve were closely correlated with the dose administered; time to peak was brief and was independent of dose. The variation in absorption was high between subjects but low within individual subjects. In 11 of 15 subjects, the disappearance of drug could be described by a two-compartment model, with a distribution half-life of 5 minutes and an elimination half-life of 33 minutes. The drug absorption, volume of distribution, plasma clearance, and half-lives were similar for subcutaneous injection, subcutaneous infusion, and intravenous infusion. We conclude that apomorphine is rapidly and completely absorbed from subcutaneous tissue, correlating with the rapid onset of clinical effects, and that the brief duration of clinical action of the drug is explained by its rapid clearance.

Adult↗

Cold synchronization for the study of peripheral blood and bone marrow chromosomes in leukemias and other hematologic disease states.

A method of cold-shock synchronization of immature granulocytic cells from peripheral blood or bone marrow is described. It is shown that this method provides an increased yield of early metaphases and offers advantages over others currently employed. The peaks of mitotic activity following the cold-shock treatment differ for patients with acute nonlymphoblastic leukemia (ANLL) and patients with chronic myeloid leukemia (CML) by an interval of 2 h. This method is considered to be suitable for routine cytogenetic studies on hematological patients.

Acute Disease↗

Quantitative effect of oral feeding on gastrointestinal myoelectric activity in the conscious dog.

Gastrointestinal myoelectric activity was recorded in seven studies in five dogs during two hours of fasting immediately followed by feeding and subsequent recording for four hours. In four studies serial plasma samples were taken for radioimmunoassay of insulin and gastrin. In all animals there was a significant reduction (P less than 0.01) in gastric basic electrical rhythm (BER) frequency on feeding which was sustained throughout the postprandial period. There was no change in the duodenal BER. Feeding induced a significant (P less than 0.01) increase in overall jejunal and ileal (but not duodenal) spike activity. Ileal (but not jejunal) spike activity again increased significantly (P less than 0.05) after the first two post-prandial hours. The changes in serum gastrin or in serum insulin did not appear to account for most of the observed changes in myoelectric activity, suggesting that other humoral and/or neural factors mediate the response to food.

Animals↗

International comparison of awareness and attitudes towards coronary risk factor reduction: the HELP study. Heart European Leaders Panel.

BACKGROUND: An international survey was conducted to assess public awareness and attitudes to coronary heart disease and to establish the frequency with which certain health-related behaviours are practised in five European countries. METHODS: Members of the general public (n=5013), individuals at increased risk of coronary disease (n=2500), patients who had suffered a myocardial infarction (n=1256) and members of their families (n=1249) were interviewed in a study conducted in France, Germany, Italy, Sweden and the UK. Questions were asked about respondents' attitudes to their health and about their current health practices. RESULTS: The survey revealed a considerable degree of indifference to coronary heart disease, despite the possession of a reasonable level of knowledge of the risks involved, even among patients who had suffered a myocardial infarction. At the same time, respondents declared themselves satisfied with the quality of advice about coronary health that they obtained from the medical profession and regarded these sources of information as highly credible. Media health campaigns, by contrast, had comparatively little impact. CONCLUSION: A survey of five European countries shows that individuals possess reasonable levels of knowledge about coronary heart disease. They also have access to sources of heart health information that are perceived as highly credible. Nonetheless, such information has a very limited impact on their practice of health-related behaviours.

Adult↗