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Biomedical subjects

R A Webster

Publications and source records attributed to R A Webster.

At least 19 recordsLinked to original sources
PubMed1992

Patterns of service utilisation following the 1989 Newcastle earthquake: findings from phase 1 of the Quake Impact Study.

A screening questionnaire was distributed to 5,000 adult members of the community six months after the 1989 Newcastle earthquake, with a response rate of 63 per cent (n = 3,007). The mean age of respondents was 46.7 years and 58 per cent were female. Subjects' earthquake experiences were rated in terms of weighted indices of exposure to threat and disruption. Psychological morbidity was measured using the General Health Questionnaire and the Impact of Event Scale. Subjects were asked to indicate which of a range of general and disaster-related support services they had used in dealing with the stressful effects of the earthquake. It was estimated that 21.3 per cent of the adult population used general and/or disaster-related support services. Users of these services reported greater exposure to threat and/or disruption and had higher levels of psychological distress than nonusers. However, a high level of use of general services and reliance on medical services were related more to psychological morbidity than degree of exposure to earthquake-related events. Overall, the Newcastle community's needs for assistance in the aftermath of the earthquake were effectively absorbed by the existing support services and the resources marshalled to supplement those services. Individuals and organisations mobilised following natural disasters need to be strengthened by enhancing the capacity of support service workers to identify and manage psychological distress in their clients.

Adult↗
PubMed1991

The development of a classification system for nurses' work methods.

This study describes the development of a classification system for the clarification, understanding and measurement of nurses' work methods. The theoretical basis of the classification system is described. The system offered distinguishes between three common work methods: primary, team and task nursing; the strength of opportunity for nurse-patient interaction in each method being determined as either 'strong', 'moderate' or 'weak', according to how effectively they are practised. Preliminary testing of the system on 32 wards in 13 hospitals is described. It is concluded that further testing and possible refinement is required for validation of the system.

Decision Making↗
PubMed1991

Effect of compounds modulating amino acid neurotransmission on the development and control of bicuculline-induced epileptogenic spiking in the rat.

Dose-related EEG spiking was induced and monitored in urethane-anaesthetised rats by cortical superfusion of bicuculline methiodide, through a cortical cup incorporating recording electrodes. The total integrated spike voltage, total number of spikes as well as the average size of the spikes were monitored. Extracellular recording showed that each individual EEG spike coincided with the sudden, synchronous firing of a group of superficial cortical cells (layer II-III). gamma-Aminobutyric acid reduced both the size and frequency of the spikes, whilst muscimol and clonazepam mainly reduced the size of the spikes. (+/-) Baclofen reduced the frequency of the spikes, with no effect on their size. The NMDA receptor antagonists, AP5 and AP7 reduced spiking by attenuating size, with no effect on frequency. The NMDA channel blocker MK801 also reduced the size of the spikes but increased their frequency at large concentrations; increasing magnesium in the artificial CSF, from 1 to 10 mM, had a similar effect. Compounds believed to preferentially block non-NMDA receptors, GAMS and CNQX, reduced activity by mainly reducing the frequency of spikes. It is concluded that activation of non-NMDA and GABAB receptors are important for controlling the initiation of bicuculline-induced spikes and NMDA and GABAA receptors, for the control of their subsequent development.

Amino Acids↗
PubMed1990

In-hospital counselling for first-time myocardial infarction patients and spouses: effects on satisfaction.

Self-ratings of satisfaction were studied over 6 months in 60 male first-time myocardial infarction patients and their wives. Couples were randomly assigned to either a treatment group, where they received a simple programme of education and psychological support in addition to routine care, or to a control group, where they received routine care only. All patients completed visual analogue scales measuring satisfaction regarding their general health, life in general, care and information received. All wives completed visual analogue scales measuring satisfaction regarding information received and care the patient received. Patients and wives in the treatment group reported statistically significantly more satisfaction than those in the control group. This effect was sustained for 6 months after counselling.

Consumer Behavior↗
PubMed1990

The effect of benserazide on the peripheral and central distribution and metabolism of levodopa after acute and chronic administration in the rat.

1. The effects of levodopa alone (50 mg kg-1) and levodopa (10 mg kg-1) plus benserazide (50 mg kg-1) were tested on the levels of dopa, dopamine, 3-methoxytyrosine (3-MT), 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), measured by h.p.l.c. with electrochemical detection, in samples of plasma, CSF, urine, striatum and hypothalamus of rats taken 30 min after injection. Levodopa plus benserazide produced significantly higher levels of dopa in plasma and brain than levodopa alone and reduced the peripheral synthesis and metabolism of dopamine. 2. When given chronically over 6 weeks the advantages of adding benserazide (50 mg kg-1 day-1) to levodopa (40 mg kg-1 day-1) were less marked and although more dopamine was present in the striatum than with levodopa given alone (200 mg kg-1 day-1) there was no evidence of any increase in its metabolites (HVA and DOPAC) and therefore of its turnover and utilisation. 3. The most striking effect of chronic treatment with levodopa plus benserazide was the appearance of large quantities of 3-MT in plasma, CSF and brain. 4. When levodopa alone, or levodopa plus benserazide, was given as an acute challenge to animals receiving the same treatment chronically, it was found that levodopa alone still produced increases in striatal dopamine, DOPAC and HVA in those animals dosed chronically on levodopa, but it was less effective in this respect when given with benserazide to the animals dosed with levodopa plus benserazide. 5. It is concluded that this difference in levodopa distribution may depend on the persistence in benserazide-treated animals of 3-MT, which has a long half-life and may compete with dopa for transport into the blood and brain. 6. The implication of these findings to the treatment of Parkinsonism is discussed.

Animals↗
PubMed1989

Neuronal activity, amino acid concentration and amino acid release in the substantia nigra of the rat after sodium valproate.

The effects of sodium valproate on extracellularly recorded spontaneous neuronal activity and striatal-evoked inhibition in the substantia nigra zona reticulata of the rat were compared with its effects on the tissue concentration of endogenous amino acids and their spontaneous release into perfusates of this region obtained with a push-pull cannula. Valproate (200 mg/kg i.p.) produced a rapid and sustained reduction in the firing rate of all reticulata neurones tested and a concomitant increase in the duration of striatal-evoked inhibition. No change in the spontaneous release of any amino acid was observed. A significant elevation of nigral gamma-aminobutyric acid concentration was seen in both anaesthetized and non-anaesthetized animals, but this occurred only after 60 minutes. Valproate produced a rapid decline in nigral aspartate in non-anaesthetized but not in anaesthetized animals. The results of this study suggest that the acute depressant effect of valproate is unrelated to its ability to alter the concentration of GABA or aspartate in brain and is most likely due to a postsynaptic action.

Action Potentials↗
PubMed1989

Compartmental distribution of endogenous amino acids in the substantia nigra of the rat.

Using a push-pull cannula we have monitored the spontaneous efflux of 8 endogenous amino acids into perfusates of the substantia nigra of the rat. The extracellular concentrations of the amino acids were estimated and compared to their respective tissue levels. High intra-/extracellular concentration ratios were found for gamma-aminobutyric acid (GABA), aspartate, glutamate and taurine. Much lower values were found for glycine, alanine, serine and glutamine. These results provide evidence for possible neurotransmitter roles for aspartate, glutamate and taurine in the substantia nigra in addition to that, long recognized, for GABA.

Amino Acids↗
PubMed1989

Synthesis and anthelmintic activity of a series of pyrazino[2,1-a][2]benzazepine derivatives.

A series of 1,2,3,4,6,7,8,12b-octahydropyrazino[2,1-alpha][2] benzazepine derivatives was prepared and the cestocidal activity of the compounds evaluated in an in vitro Taenia crassiceps screen. Many of these derivatives proved to be highly active, and 2-(cyclohexylcarbonyl)-4-oxo-1,2,3,4,6,7,8,12b- octahydropyrazino[2,1-alpha][2]benzazepine, epsiprantel (BAN) (22), was selected for further development. The structure-activity relationships are discussed.

Animals↗
PubMed1988

Inhibition of mammalian 5-lipoxygenase by 2-benzylaminophenols.

A number of 2-benzylaminophenols, prepared from the corresponding 2-aminophenols by reductive alkylation, have been identified as highly potent inhibitors of 5-lipoxygenase with IC50 values in the nanomolar range. Most compounds were also shown to inhibit the release of the peptidoleukotrienes when administered intraperitoneally in a rat model of peritoneal anaphylaxis. Two compounds evaluated for their effects on anaphylactic contractions in isolated human lung were shown to attenuate the leukotriene-induced component of the response.

Aminophenols↗
PubMed1987

Hyperactivity induced by dexamphetamine/chlordiazepoxide mixtures in rats and its attenuation by lithium pretreatment: a role for dopamine?

Dexamphetamine (DEX) and chlordiazepoxide (CDZP) given together as mixtures have previously been shown to induce a characteristic "compulsive" form of locomotor hyperactivity in rats placed in unfamiliar environments, which was much greater than activity obtained with any dose of either drug given separately; acute pretreatment with lithium counteracted mixture-induced hyperactivity. The role of dopamine in these effects was investigated by measuring concurrently the levels of dopamine (DA), dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the striatum. DEX (0.02-2 mg kg-1) increased horizontal (entries) and vertical (rears) activity, and increased DA and decreased DOPAC and HVA in the striatum. Chlordiazepoxide (CDZP) (12.5 or 20 mg kg-1) increased horizontal activity but did not affect vertical activity or DA or its metabolites. Lithium by itself in acute (2 meq kg-1, 24 and 4 h before test) or extended (2 meq kg-1 daily for 9 days) dosage had little effect on horizontal or vertical activity or levels of DA or DOPAC. Given together, DEX and CDZP (1.18 mg kg-1 + 12.5 mg kg-1), as expected, increased entries much more than did either drug given separately, but rears and levels of DA and metabolites remained similar to those with DEX given alone. Acute lithium pretreatment counteracted the mixture-induced increase in entries. Neither acute nor extended lithium pretreatment significantly altered DEX-induced changes in activity or levels of DA or DOPAC.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dihydroxyphenylacetic Acid↗
PubMed1987

Isothiourea derivatives of 6-phenyl-2,3,5,6-tetrahydroimidazo[2,1-b]thiazole with broad-spectrum anthelmintic activity.

A series of isothiourea derivatives of 6-phenyl-2,3,5,6-tetrahydroimidazo[2,1-b]thiazole (tetramisole) is described. The compounds are prepared by the S-alkylation of the thioureas that were obtained either by the reaction of an amine with 6-(3-isothiocyanatophenyl)-2,3,5,6-tetrahydroimidazo[2,1-b] thiazole or by the reaction of an isothiocyanate with 6-(3-aminophenyl)-2,3,5,6-tetrahydroimidazo[2,1-b]thiazole. These derivatives have an improved spectrum of activity over tetramisole and are active against nematodes, cestodes, and trematodes. The structure-activity relationships are discussed.

Animals↗
PubMed1987

Novel 1H-benzimidazol-4-ols with potent 5-lipoxygenase inhibitory activity.

The synthesis and structure--activity profile of 2-substituted benzimidazol-4-ols as inhibitors of cell-free RBL-1 5-lipoxygenase are discussed, and their potency is compared with that of the standard inhibitors phenidone, AA 861, BW 755C, and nordihydroguaiaretic acid. In contrast to the standard compounds, most did not inhibit the release of slow-reacting substance of anaphylaxis (SRS-A) in vivo when administered at 200 microM ip to rats subjected to peritoneal anaphylaxis, although five compounds containing a methoxylated benzyl group (compounds 36, 39, 42, and 43) or hydroxylated benzyl group (41) showed similar activity to that of phenidone, nordihydroguaiaretic acid, and AA 861. Of the many compounds tested, two, 5-tert-butyl-7-methyl-2-(trifluoromethyl)-1H-benzimidazol-4-ol (57) and 2-(4-methoxybenzyl)-7-methyl-1H-benzimidazol-4-ol (36), like dexamethasone, inhibited monocyte accumulation in a pleural exudate model of inflammation. Standard lipoxygenase inhibitors such as phenidone, BW 755C, and AA 861 were inactive in this system.

Animals↗
PubMed1987

Specific sources and patterns of anxiety in male patients with first myocardial infarction.

Anxiety was studied on four occasions over one year in 76 men under 66 years of age, who were admitted to hospital with a first acute myocardial infarction. Anxiety was measured by the Spielberger State-Trait Anxiety Inventory, and by a self-rating questionnaire. Average levels of State and self-rated anxiety fluctuated over the study period with levels peaking after admission, falling at the fifth day, rising at six weeks, and falling to their lowest level at one year. Reported specific sources of anxiety, including the myocardial infarction, return to work, the future and possible complications, ranked highest in hospital and at six weeks post-discharge.

Adult↗
PubMed1986

The role of GABA and excitatory amino acids in the development of the leptazol-induced epileptogenic EEG.

The developing epileptogenic electroencephalogram (EEG), seen during the slow intravenous infusion of leptazol, is sensitive to various anticonvulsant drugs, particularly those known to augment the function of gamma-aminobutyric acid (GABA), such as clonazepam and sodium valproate, which specifically prolong the earlier wave-like (pre-spiking) phases. Thus, whilst antagonism of GABA may be responsible for spiking, the early wave-like phases may be due to GABA released in the cortex as a feedback control to delay spiking. Intravenous infusion of the GABA antagonists, bicuculline and picrotoxin, produced a developing EEG with spiking the first abnormal feature noted and no wave-like phase, like that seen with leptazol. Cortical superfusion of GABA during the infusion of leptazol, enhanced kand prolonged the wave-like phase, whilst bicuculline reduced it. Cortical superfusion of leptazol, picrotoxin or larger concentrations of bicuculline produced spiking but no wave-like activity. When leptazol and GABA were superfused together they produced wave-like activity similar to that seen during infusions of leptazol. Of the excitatory amino acid antagonists, only those active at receptors for N-methyl-D-aspartate (NMDA) influenced the EEG changes induced by leptazol. It is suggested that leptazol produces waves in the EEG by stimulating subcortical pathways to release GABA in the cortex and that spiking occurs as the cortex is further stimulated by GABA antagonism and the release of excitatory amino acids.

Allylglycine↗
PubMed1986

The effects of beta-carboline carboxylic acid ethyl ester and its free acid, administered ICV, on the anticonvulsant activity of diazepam and sodium valproate in the mouse.

The effects of intracerebroventricular (ICV) beta-carboline carboxylic acid ethyl ester (beta-CCE) and its free acid on the protective effects of diazepam against leptazol- and R05-3663-induced convulsions were investigated in mice and compared with their effects on the antileptazol effect of sodium valproate, in an attempt to demonstrate a specific central effect of beta-CCE on benzodiazepine function. The results show that a small dose (1 microgram) of beta-CCE but not its free acid (in doses of up to 100 micrograms) was able to reverse the protective effects of diazepam against leptazol- and R05-3663-induced convulsions, whereas the effects of sodium valproate, a nonbenzodiazepine anticonvulsant, could not be reversed by these beta-carboline derivatives.

Animals↗