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Biomedical subjects

E Doyle

Publications and source records attributed to E Doyle.

At least 73 records · Page 4Linked to original sources
PubMed1993

High-performance liquid chromatographic determination of concentrations of the reversible H+/K+ ATPase inhibitor SK&F 97574 in plasma.

A reversed-phase high-performance liquid chromatographic (HPLC) assay using ultraviolet spectrophotometric detection has been developed for the determination of the concentration of 3-butyryl-4-(2-methylphenylamino)-8-(2-hydroxyethoxy)quinoline (I) in rat, dog and human plasma. Prior to analysis, the protein in plasma samples was precipitated with acetonitrile containing 3-butyryl-4-(2-methylphenylamino)-8-methoxyquinoline to act as an internal standard. The supernatant layer was injected onto the HPLC column with no further clean-up. The assay requires 200 microliters of plasma and is precise and accurate within the range 25-1000 ng/ml. The mean within-run and between-run coefficients of variation were < 6% at 25 ng/ml and greater concentrations. The mean accuracy of quality control standards was generally within +/- 5% of the nominal concentration. Recovery of I and internal standard from plasma was approximately 100% over the entire assay range irrespective of species.

Aminoquinolines↗
PubMed1993

Cholinergic and dopaminergic agents which inhibit a passive avoidance response attenuate the paradigm-specific increases in NCAM sialylation state.

The influence of cholinergic and dopaminergic agents on the acquisition of a passive avoidance response in the rat is demonstrated. Trifluoperazine (0.12 mg/kg), a dopamine antagonist, inhibited task acquisition when present during training or later, during consolidation, at the 10-12 h post-training period and at no other intervening time point. Induction of amnesia was dose-dependent and was not apparent when the dose exceeded 0.12 mg/kg. This effect appears to be due to an increase in dopamine release through presynaptic receptor antagonism as similar results could be obtained by the administration of apomorphine (0.5 mg/kg), a dopamine agonist, and this effect could be antagonized by the D1 receptor selective antagonist SCH-23390. Scopolamine (0.15 mg/kg), a muscarinic antagonist, impaired acquisition of the passive avoidance response when administered during training and, separately, at the 6 h post-training period. This could not be attributed to presynaptic antagonism as oxotremorine (0.2 mg/kg), a muscarinic agonist, had no amnesic action. Administration of apomorphine or scopolamine during training and at the appropriate post-training period prevented subsequent paradigm-specific increases of neural cell adhesion molecule sialylation state in hippocampal immunoprecipitates obtained at 24 h after task acquisition and 4 h following intraventricular infusion of the labelled sialic acid precursor - N-acetyl-D-mannosamine. Oxotremorine alone did not influence neural cell adhesion molecule sialylation state. These observations provide further evidence of a regulatory role for neural cell adhesion molecule sialylation state in information storage processes.

Amnesia↗
PubMed1993

IV anaesthesia with propofol using a target-controlled infusion system: comparison with inhalation anaesthesia for general surgical procedures in children.

We studied 40 children undergoing general surgical procedures. They were allocated randomly to receive induction of anaesthesia with propofol 3-5 mg kg-1 followed by maintenance with halothane and an appropriate regional block, or induction and maintenance of anaesthesia with a computerized, target-controlled infusion of propofol with a regional block. All patients breathed a mixture of 67% nitrous oxide in oxygen via a laryngeal mask airway. Both techniques provided adequate anaesthesia and operating conditions. There were no significant differences between the groups in heart rate, mean arterial pressure and end-expired carbon dioxide concentration during anaesthesia. There was no significant difference in the recovery times of the two groups.

Anesthesia Recovery Period↗
PubMed1993

Comparison of patient-controlled analgesia with and without a background infusion after lower abdominal surgery in children.

Forty children aged 6-12 yr undergoing appendicectomy were allocated randomly to receive postoperative i.v. morphine by a patient-controlled analgesia (PCA) system (bolus dose 20 micrograms kg-1 with a lockout interval of 5 min) or the same PCA with a background infusion of morphine 20 micrograms kg-1 h-1. Patients breathed air and oxygen saturation was monitored by continuous pulse oximetry. Scores for pain, sedation and nausea were recorded hourly. Patients with PCA + background infusion received significantly more morphine than those with PCA only. Both groups self-administered similar amounts of morphine using the PCA machine. There were no significant differences in the pain scores of the two groups. Patients with PCA+background infusion suffered more nausea (P < 0.01), more sedation (P < 0.05) and hypoxaemia (P < 0.001) than those with PCA only. They also had a better sleep pattern than those with PCA only.

Analgesia, Patient-Controlled↗
PubMed1993

Patient-controlled analgesia with low dose background infusions after lower abdominal surgery in children.

Forty-five children (aged 6-12 yr) undergoing appendicectomy received one of three analgesic regimens using patient-controlled analgesia (PCA) with morphine: no background infusion (BO); background infusion 4 micrograms kg-1 h-1 (B4); background infusion 10 micrograms kg-1 h-1 (B10). Total consumption of morphine was greater in group B10 compared with groups B0 (P < 0.01) and B4 (P < 0.05). There was no significant difference in morphine consumption in groups B0 and B4. All three groups self-administered similar amounts of morphine and there were no significant differences in pain scores or incidence of excessive sedation. Group B4 suffered less hypoxaemia compared with groups B0 (P < 0.01) and B10 (P < 0.001). Group B10 suffered more nausea and vomiting than groups B0 (P < 0.001) and B4 (P < 0.001), but there was no significant difference in the incidence of nausea and vomiting between groups B0 and B4. Groups B4 and B10 spent more time at night asleep than group B0 (P < 0.05). There were no significant differences between the groups in the amount of time spent asleep during the day. Inclusion of a background infusion of morphine 4 micrograms kg-1 h-1 in a PCA regimen for children did not increase the incidence of side effects and was associated with less hypoxaemia and a better sleep pattern than no background infusion.

Analgesia, Patient-Controlled↗
PubMed1993

An evaluation of a new self-adhesive patch preparation of amethocaine for topical anaesthesia prior to venous cannulation in children.

A new preparation of amethocaine in the form of a self-adhesive patch, designed to provide topical cutaneous anaesthesia prior to venous cannulation, was evaluated in an open study of 189 children. The new preparation of amethocaine was in place for a mean time of 48 min (SD 3.9). Eighty percent of patients had a satisfactory degree of analgesia for venous cannulation. Nine percent of patients experienced moderate pain and 11% experienced severe pain during venous cannulation. In 26% of patients there was slight (24%) or moderate (2%) erythema at the site of application, and in 5% slight oedema was noted at the site of application. Eight percent of patients had slight itching and 1% had moderate itching at the site of application. There was a clinical impression that venous dilatation made cannulation easier than with EMLA cream. These results suggest that this convenient preparation of amethocaine is highly effective at providing adequate topical cutaneous anaesthesia with a short onset time and a low incidence of minor side effects with no evidence of systemic toxicity.

Administration, Cutaneous↗
PubMed1993

Nefiracetam (DM-9384) preserves hippocampal neural cell adhesion molecule-mediated memory consolidation processes during scopolamine disruption of passive avoidance training in the rat.

Scopolamine (0.15 mg/kg), a muscarinic antagonist, when administered during training or at a discrete 6-h posttraining time point, is demonstrated to inhibit the recall of a step-down passive avoidance response when tested at 24 and 48 h after task acquisition. Nefiracetam (3 mg/kg), a piracetam-related nootropic, when given with scopolamine during training tended to improve task recall, and this effect was more pronounced when given at the 6-h posttraining time. Co-administration of nefiracetam with scopolamine was not necessary to achieve the antiamnesic action, as nefiracetam given during training significantly improved the memory deficits produced by scopolamine at the 6-h posttraining time. The paradigm-specific increase in hippocampal neural cell adhesion molecule sialylation, which is observed during consolidation of a passive avoidance response, was attenuated by the presence of scopolamine during training and at the 6-h posttraining time, and this effect was reversed by co-administration of nefiracetam, albeit in a paradigm-independent manner. These results suggest nefiracetam exerts a neurotrophic action that protects memory consolidation from drug interventive insults.

Animals↗
PubMed1992

Hippocampal NCAM180 transiently increases sialylation during the acquisition and consolidation of a passive avoidance response in the adult rat.

Synaptic connectivity change is a consistent anatomical feature of memory formation and the possibility that this is mediated by a replay of neurodevelopmental events has been investigated by measuring change in neural cell adhesion molecule sialylation state during the acquisition and consolidation of a passive avoidance response in the adult rat. The avoidance response was always generated after two to three trials and the animals remained on the platform for the criterion time of 5 min. In all cases training was complete within 5-8 min. Change in sialylation state was monitored following intraventricular infusion of the 3H-ManNAc precursor at 4 hr prior to the reference point. No task-specific change in general glycoconjugate sialylation was apparent in hippocampal P2 pellets at increasing times following training. Increased sialylation state was observed only in neural cell adhesion molecule (NCAM) immunoprecipitates of hippocampal membrane fractions at 12 and 24 hr after training. Change in hippocampal sialylation state could not be attributed to an increased accumulation of NCAM as detected by an immunoabsorbent assay. Immunoblotting of antibody precipitated NCAM demonstrated the 3H-ManNAc to be incorporated into the synapse-specific, 180 kDa isoform of NCAM and a novel 210 kDa isoform. Immunoprecipitation and immunoblotting procedures with an antibody specific for a2-8-polysialic acid showed the 180 and 210 kDa isoforms to be polysialylated. The role of NCAM180 sialylation as a mechanism for synapse selection in information storage is discussed.

Animals↗
PubMed1992

Intraventricular infusions of anti-neural cell adhesion molecules in a discrete posttraining period impair consolidation of a passive avoidance response in the rat.

Intraventricular infusions of anti-neural cell adhesion molecule (anti-NCAM) are demonstrated to inhibit consolidation of a passive avoidance response when administered in the 6-8 h posttraining period. Anti-NCAM was ineffective when administered during training or at any other time up to 10 h thereafter, and no amnesic effects were observed with absorbed anti-NCAM or anti-neurofilament protein. Amnesia was observed only at the 48-h recall time, and this could not be attributed to poor antibody penetration or a prolonged residence time, as studies with 125I-labelled anti-NCAM in trained animals demonstrated a rapid accumulation into all brain regions, and this was marked in the olfactory bulb and hippocampus, areas showing an inherent and paradigm-specific increase in NCAM sialylation state, respectively. The lack of an amnesic action at the 24-h recall time is attributed to anti-NCAM-impaired synapse structuring becoming apparent following the paradigm-specific increases in NCAM sialylation state.

Amnesia↗
PubMed1992

Thrombolysis with low dose tissue plasminogen activator.

Two cases of vena caval thrombosis in infants were successfully treated with low dose (0.01-0.05 mg/kg/hour) local infusions of tissue plasminogen activator after conventional anticoagulant treatment had been unsuccessful. This approach is useful for clots associated with indwelling intravascular catheters, and a low dose infusion of tissue plasminogen activator as a regional application is recommended to achieve clot lysis with minimal systemic effects.

Catheters, Indwelling↗
PubMed1992

Direct injection/h.p.l.c. methods for the analysis of drugs in biological samples.

1. Direct injection h.p.l.c. methods for zaprinast, and pantoprazole and its sulphone metabolite were developed. 2. Optimal recovery of pantoprazole and its sulphone metabolite was effected by the absence of transfer losses and the effective adjustment of sample pH on-line. 3. Acetonitrile reduced the recovery of pantoprazole and its sulphone metabolite at acetonitrile concentrations greater than 5% in serum. 4. Direct injection h.p.l.c. methods minimize sample handling losses, reduce human contact with biological samples and are sufficiently accurate and reproducible to be used to support pharmacodynamic and toxicokinetic studies.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1990

High-performance liquid chromatographic determination of the H+/K+ ATPase inhibitor (BY 1023/SK&F 96,022) and its sulphone metabolite in serum or plasma by direct injection and fully automated pre-column sample clean-up.

A fully automated high-performance liquid chromatographic method is described for the determination of the new H+/K+ ATPase inhibitor BY 1023/SK&F 96,022 and its major metabolite occurring in dog serum. The method uses direct sample injection of up to 200 microliters and a pre-column switching technique. In order to optimize the recovery, pre-column conditions were varied systematically with respect to the pH of the pre-column eluent, its buffering capacity and content of acetonitrile. Optimization resulted in near 100% recovery for both compounds, thus allowing the use of external standardization. The linearity range, precision and detection limits were determined and the method shown to be applicable to both serum and plasma. The method was applied to define the pharmacokinetics in dogs and humans.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1990

Intraventricular infusions of antibodies to amyloid-beta-protein precursor impair the acquisition of a passive avoidance response in the rat.

Intraventricular infusions of an antiserum raised against a 14 amino acid residue in the extracellular domain of amyloid-beta-protein precursor significantly decreased stepdown latency, at both 24 h and 48 h recall times, in rats trained to avoid an electroshock by remaining on a platform. The antiserum was effective when infused up to 2.5 h following training and no retention deficit was noted when it was administered at 4h or 6h after training. An antiserum generated against a 17 amino acid residue of the A4 amyloid peptide had no effect on learning. Thus the amyloid precursor protein, which is aberrantly processed in Alzheimer's disease, appears to be directly involved in memory formation.

Adult↗
PubMed1990

Two systems for the automated analysis of drugs in biological fluids using high-performance liquid chromatography.

This paper describes two fully automated assays. One for zaprinast, a cGMP specific phosphodiesterase inhibitor, which uses the Gilson-Advanced Automated Sample Processor combination, and the other for an H+/K+ ATPase inhibitor and its sulphone metabolite, which uses direct injection. Both assays were developed to support pharmacokinetic studies at therapeutic doses in small animals as well as in man. Plasma or serum (20-200 microliters) is placed directly into an autosampler and all subsequent manipulations are performed mechanically.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1990

Determination of temelastine and a hydroxymethyl-pyridyl metabolite in biological fluid by high-performance liquid chromatography.

A high-performance liquid chromatographic method for the analysis of temelastine (1) and 2-[4-(5-bromo-3-methylpyrid-2-yl)-butylamino]-5-[6-hydroxymethy lpyrid-3- ylmethyl]-pyrimidin-4(1H)-one (1-A) in biological fluid is presented. The method combines the previously reported extraction procedure and new chromatography conditions capable of resolving 1, 1-A, and structurally similar compounds formed by the oxidation of 1. The modified method has been used to measure concentrations of 1 and 1-A in biological fluids taken from the rat and dog, and to look for the presence of 1-A in humans following administration of 1.

Animals↗