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Biomedical subjects

E Doyle

Publications and source records attributed to E Doyle.

At least 91 records · Page 5Linked to original sources
PubMed1990

Learning-induced change in neural activity during acquisition and consolidation of a passive avoidance response in the rat.

Time-dependent alterations in neural activity have been established during the acquisition and consolidation of a stepdown passive avoidance paradigm. Change in neural activity was established by administering a glucose analogue, [3H]2-deoxyglucose, 50min prior to sacrifice and estimating perchloric acid soluble counts in nine hand dissected brain regions. Change in [3H]2-deoxyglucose uptake was closely paralleled in both trained and yoked animals for up to 40min following task acquisition however the striatum was the only area to exhibit a task-specific increase in [3H]2-deoxyglucose uptake at 20-30min after training. Longterm changes in neural activity were also apparent as the amygdala and brainstem showed increased [3H]2-deoxyglucose uptake at the 24 h time point. No further paradigm-specific changes were apparent at 48 h. These findings are concluded to suggest that the striatum is involved in the early events of acquiring a passive avoidance response and the amygdala and brainstem during the later events.

Amygdala↗
PubMed1989

Case-control study of lung cancer in Los Angeles county welders.

A case-control study of lung cancer in white male welders was undertaken to investigate possible environmental and occupational causes of a 50% excess of lung cancer observed in this occupational group. The subjects were identified from a population-based cancer registry in Los Angeles County. A standardized questionnaire was administered to either subjects or proxy informants of 90 lung cancer cases and 116 non-lung-cancer controls. Significantly increased risks of lung cancer were associated with tobacco smoking (odds ratio 7.6, p less than .005) and shipyard welding with at least a 10-year latency since first exposure (odds ratio 1.7, p less than .05). Although there were elevated risks associated with some specific welding processes, none were statistically significant. Control subjects were more likely to have had exposure to confined-space welding (odds ratio 0.6, 95% CI = 0.3-1.2), and this association was greatest where there had been at least a 20-year latency since first exposure (0.5, 95% CI = 0.3-1.0). We conclude that the excess of lung cancer in this welding population is contributed to by a higher frequency of smoking and probable exposure to asbestos in shipyards. Other factors may be important, but probably because of limited power and reliance on proxy information, this study failed to detect other statistically significant risks.

Adult↗
PubMed1989

Sample preparation for the HPLC analysis of drugs in biological fluids.

Sample preparation for the analysis of drugs in biological fluids consists of a number of unit operations that are used for (i) release of the drug from a conjugate or biological matrix; (ii) removal of endogenous compounds that could interfere with the assay; and (iii) techniques for liquid handling. The trends in sample preparation that have occurred over the past 10 years in the authors' laboratory are discussed. In general, there has been a move from the traditional liquid-liquid extraction to methods using bonded-silica which permit rapid throughput and efficient extraction. Automation of sample preparation has seen further gains in productivity; however, the present generation of equipment lack the control and communication systems that are essential for the development of the automated integrated laboratory of the future.

Automation↗
PubMed1987

Analysis of drugs from biological fluids using disposable solid phase columns.

The traditional liquid-liquid extraction method for the removal of drug from biological matrix is being superseded by solid phase extraction. This involves the selection of an appropriate sorbent (normal-phase, reversed-phase, ion-exchange etc.), but once this has been achieved the method is quick and simple to operate. Most sample handling losses are avoided so recovery of drug is high and it is easily automated. Disposable columns have several advantages. Samples of 0.05-2.0 ml can be analysed routinely. Several wash stages can be included in a method to provide a specific extraction prior to a quick analysis by high-performance liquid chromatography (HPLC), radioimmunoassay, UV etc. A potential problem is that retention of the drug may involve more than one mechanism. Elution of drug may therefore require a stronger eluting solvent than analytical HPLC systems using the same stationary phase.

Antihypertensive Agents↗
PubMed1986

Measurement of concentrations of the histamine H1 receptor antagonist temelastine in biological fluids.

A high-performance liquid chromatographic analysis of temelastine in biological fluids with UV detection at 229 nm is presented. The method involves ether extraction followed by re-extraction into phosphoric acid and chromatography on a reversed-phase column. The method has a lower limit of detection of 0.05 mg L-1 and is adequate for use in pharmacokinetic studies following oral administration.

Bile↗
PubMed1984

Isosorbide dinitrate plasma concentrations and bioavailability in human subjects after administration of standard oral and sublingual formulations.

The bioavailability of isosorbide dinitrate from formulations containing 5, 10, and 20 mg in tablets and 10 mg in solution for oral use and 5 mg in tablets for sublingual use, has been compared. When adjusted for dose, the peak mean plasma drug concentrations after oral administration were similar (e.g., 9.2 ng/mL after a 10-mg tablet) and about one-half that obtained after sublingual administration. Drug concentrations declined monoexponentially with mean half-lives ranging from 25-36 min. The relative bioavailability of isosorbide dinitrate from the oral formulations was not significantly different (p greater than 0.05) over the dose range studied, whereas the relative bioavailability after sublingual administration was about twice as great (p less than 0.01) as that after oral administration. The plasma drug concentration-time profile after administering the 5-mg sublingual tablet was similar to that obtained after administering orally a solution containing 10 mg, indicating that the latter should be as clinically effective as the former.

Administration, Oral↗
PubMed1984

The pharmacokinetics in man of SK&F 93319--a new antagonist of histamine H1 and H2 receptors.

SK&F 93319, a potent histamine H1- and H2-receptor antagonist, is rapidly absorbed with a low rate of plasma clearance primarily by metabolism. Excretion is divided evenly between urine and faeces (probable biliary elimination) with little unchanged drug in the urine. Serum protein binding at low concentrations is very extensive and appears to restrict distribution of SK&F 93319. At higher concentrations (higher dose levels) reduced protein binding results in a marked proportional increase in available free drug with a consequent increase in distribution and clearance. Bioavailability is reduced at higher dose levels. The importance of factors contributing to non-linear pharmacokinetics and the potential clinical consequences are demonstrated.

Adult↗
PubMed1983

Bioavailability of isosorbide dinitrate and its two mononitrate metabolites from sustained-release formulations.

Plasma concentrations and bioavailability of isosorbide dinitrate (ISDN) and its active metabolites isosorbide 2-mononitrate (2-ISMN) and isosorbide 5-mononitrate (5-ISMN) from two sustained-release formulations and one standard-release formulation of isosorbide dinitrate were compared. Means of peak drug concentrations of ISDN, 2-ISMN, and 5-ISMN after administration of the 20-mg sustained-release formulation were 5.5, 24.4, and 129.1 ng/ml, respectively, at 3.1, 4.2, and 4.5 h; after the 40-mg sustained-release formulation, they were 10.9, 44.0, and 214.5 ng/ml, respectively, at 4.2, 6.3, and 6.7 h; and after the 20-mg standard formulation, they were 19.1, 34.7, and 159.2 ng/ml, respectively, at 0.5, 1.0, and 1.5 h. As might be expected, peak concentrations and their times of occurrence were statistically significantly different when results from the sustained-release formulation were compared to those from the standard formulation. Plasma drug concentrations were detectable for longer after administration of the sustained-release formulations. The extent of bioavailability of ISDN, 2-ISMN, and 5-ISMN from the three formulations as estimated from the areas under the plasma drug concentration - time curves were not statistically significantly different (p greater than 0.05). The ratios for relative drug bioavailability from the respective formulations were similar whether ISDN, 2-ISMN, or 5-ISMN data were used for calculation. Reasons are discussed for the biphasic decline of plasma ISDN concentrations (half-lives 26 min and 5.1 h) obtained after administration of the standard-release formulation.

Adolescent↗
PubMed1982

Comparative pharmacokinetics of frusemide in female rhesus monkeys, cynomolgus monkeys and baboons.

1. The pharmacokinetics of frusemide have been compared in 3 non-human primate species after single intravenous dose of 3 mg/kg of the drug. 2. Peak mean plasma concentrations of frusemide were 31.6, 33.6, 43.6 micrograms/ml in the rhesus monkey, cynomolgus monkey and baboon respectively, and concentrations declined with a half-life of about 20 min. 3. There were no notable differences in the pharmacokinetic parameters estimated from either a one-compartment or two-compartment open model. 4. There were statistically significant species-related differences in clearance, half-lives and volumes of distribution adjusted for bodyweight. 5. The pharmacokinetics of frusemide in the cynomolgus monkey are closer to those in man than are those in the rhesus monkey, the baboon or other commonly used laboratory animal species.

Animals↗
PubMed1982

Medical students' evaluation of tutors in a group-learning curriculum.

This study focused on students' evaluation of tutors' effectiveness during an academic term, using a nineteen-item questionnaire. The study took place within an integrated problem-solving medical course. Four major factors in the tutor's behaviour were identified as having importance in the rating process: the ability to care for students, a knowledge of course structure and teaching staff philosophy, the ability to encourage independent thinking in students and a knowledge of the specific medical problems being studied. Further analysis suggested that students distinguish between good and bad tutors, those in different medical strands and with differing status. In general, the findings complement those dealing with student evaluation of lectures and to some extent, patient satisfaction with doctors.

Australia↗
PubMed1982

Evoked potential changes produced by positioning for retromastoid craniectomy.

Reversible changes in brain stem auditory evoked potentials (BAEPs) occurred in a patient with hemifacial spasm when she was positioned for retromastoid craniectomy. The peak latencies increased and the amplitudes decreased. These alterations persisted for 3 hours, but returned immediately toward normal when the head was removed from pin fixation and the neck was returned to a neutral position. Similar BAEP changes were documented during a second procedure. Audiograms were normal pre- and postoperatively, although minimal BAEP changes were seen after operation. Our observation sheds light on possible mechanisms of intraoperative BAEP alteration and provides new information about the degree and duration of intraoperative BAEP distortion that can be tolerated in at least some cases without permanent neurological sequelae.

Brain Stem↗
PubMed1982

Intraoperative monitoring of brain-stem auditory evoked potentials.

Brain-stem auditory evoked potentials (BAEP) were monitored during 545 neurosurgical operations in the cerebellopontine angle. The BAEP were irreversibly obliterated in five patients who required deliberate section of the auditory nerve. Technical difficulties interfered with monitoring in three cases, and three patients had deafness and absent BAEP preoperatively. Reversible alterations in BAEP were seen during 32 operations, with recovery after as long as 177 minutes of virtually complete obliteration. Changes in BAEP were associated with surgical retraction, operative manipulation, positioning of the head and neck for retromastoid craniectomy, and the combination of hypocarbia and moderate hypotension. In 19 cases, waveforms improved after specific interventions made by the surgeon or anesthesiologist because of deteriorating BAEP. In 13 other cases, BAEP recovered after maneuvers not specifically related to the electrophysiological monitoring, most often completion of operative manipulation. Whenever BAEP returned toward normal by the end of anesthesia, even after transient obliteration, hearing was preserved. Irreversible loss of BAEP occurred only when the auditory nerve was deliberately sacrificed. The authors conclude that monitoring of BAEP may help prevent injury to the auditory nerve and brain stem during operations in the cerebellopontine angle.

Adult↗