Search PubMed⌕ Search

Biomedical subjects

G Edwards

Publications and source records attributed to G Edwards.

At least 19 recordsLinked to original sources
PubMed1992

Selective determination, in plasma, of artemether and its major metabolite, dihydroartemisinin, by high-performance liquid chromatography with ultraviolet detection.

A sensitive and selective reversed-phase high-performance liquid chromatographic method for the determination of artemether and its major metabolite dihydroartemisinin in plasma has been developed. It involves extraction of plasma with dichloromethane, solid-phase separation of the two analytes and acid decomposition prior to chromatography on a C18 Spherisorb column with a mobile phase of acetonitrile-water (50:50, v/v). Run time is 30 min. The assay satisfies all of the criteria required for use in clinical pharmacokinetic studies.

Artemether↗
PubMed1992

The effect of malaria infection on 3'-azido-3'-deoxythymidine and paracetamol glucuronidation in rat liver microsomes.

The effect of malaria infection on UDP-glucuronosyltransferase (UDPGT) activity was investigated in rat liver microsomes using 3'-azido-3'-deoxythymidine and paracetamol. The Michaelis-Menten parameters, Km and Vmax were calculated and intrinsic clearance values were estimated for normal and infected livers. The results show that malaria infection alters the activity of UDPGT.

Acetaminophen↗
PubMed1992

Cocaine in perspective.

In a medical text published in 1883, Dr Benjamin Ward Richardson FRS denounced the evils of tea drinking, suggesting that it commonly gave rise to an 'Extremely nervous semi-hysterical condition'. That this distinguished Victorian physician could take such a view invites a sensitivity toward the perspective within which any debate on drugs is conducted--the historical, cultural and professional assumptions which will colour views as to what needs to be explained and how explanation is to be accomplished. The reality and significance of 'perspective' is further illustrated by examples drawn from contemporary literature which contrast the laboratory and social science approaches to study of cocaine. No one narrow disciplinary perspective on the cocaine problem will suffice; the challenge is to build bridges.

Animals↗
PubMed1992

Role of immersion refractometry for investigating laser-induced effects in cells.

The broad background of scattered light observed in spectra of cell suspensions is reduced by factors of up to 20 by immersion refractometry allowing for improved spectroscopic determination of the absorption properties of cells in the 325-820 nm range. Refractive-index matched spectra of E. coli C1a exhibit a set of resonant features near 422, 561, and 582 nm. Exposure wavelengths are chosen based on this spectrum and cell viability is investigated in E. coli suspensions exposed to 350, 400, 422, 440, and 700 nm radiation delivered in nanosecond pulses with total doses from 500 millijoules to 60 Joules. We observe a loss in cell viability for doses greater than 1 Joule at 422 nm and for all doses at other wavelengths; exposures of less than 1 Joule at 422 nm enhance growth. Excluding exposures at wavelengths within the resonant feature, longer wavelengths are less effective at reducing the viability of E. coli C1a. This indicates the occurrence of at least two absorption processes.

Absorption↗
PubMed1992

Hearing the noise in the system. Exploration of textural analysis as a method for studying change in drinking behaviour.

This paper explores how treatment research is to catch within its design those many unplanned influences which lie outside therapeutic control, but which may influence processes of change. These factors are excluded from the conventional controlled trial. The background literature is briefly reviewed. A study is then described which employed a computer assisted method of textual analysis and an entirely open-ended coding system. The material which was analysed derived from interviews with 49 subjects whose accounts were tape recorded 10 years after treatment contact. Episodes of successful or unsuccessful 'change attempt' (CA) were identified. The two types of CA were compared in relation to coded issues pertaining to the periods before, during and after the episode. A number of significant findings are reported. In the pre-attempt phase 'Success' CAs were significantly associated with traumatic events in the person's life, and with a variety of positive and negative events. During the 'attempt' phase, 'Success' was associated with choice of an abstinence goal. For 'post-attempt', 'Success' was associated with 'Substitution', 'Altruism', 'Fulfillment', and finding the process 'Difficult'. The very preliminary nature of these findings is stressed and the need for further rigorous methodological development.

Adult↗
PubMed1992

Engaging patients with alcohol problems in treatment: the first consultation.

This paper considers the impact of the first consultation at a specialist alcohol clinic on patients' perceptions of their drink problem and on their expectations of help from three sources: an alcohol clinic, general practitioners and Alcoholics Anonymous. At intake, males had higher expectations than females of help from the alcohol clinic while people in manual occupations and those in the 'less heavy' drinking category had higher expectations of general practitioner help than other patients. Change was found to occur during the first clinic consultation so that by the end of the session patients had raised their rating of problem severity and their expectations of help from the three sources examined. Overall, patient perceptions of the clinic assessment session were positive. The study highlights the importance of obtaining a full understanding of the process of engagement in treatment and indicates the potential of a clinical assessment to effect change in patient attitudes.

Adult↗
PubMed1992

The use of services for alcohol problems: general practitioner and specialist alcohol clinic.

A sample of 40 patients referred to a specialist alcohol clinic were given a full assessment by a clinician and then randomly allocated to one of two groups. The first group received continuing care from the clinic. The second group were returned to the management of their general practitioners who were offered specialist support in caring for their patients. Patients and general practitioners were followed-up 6 months after the clinic assessment. This paper reports on the uptake of clinic and general practice services by patients and examines the possible factors associated with continuing attendance, including patient attributes, service activity, patients' self-assessments of their drink problem and their expectations of help from services. Qualitative data is used to examine patients' perceptions and experiences of clinic and general practice-based care for drinking problems. The findings highlight some of the difficulties reported by patients in receiving help for their problems particularly from general practitioners.

Adult↗
PubMed1992

Inhibition by adrenergic neurone blocking agents of the relaxation induced by BRL 38227 in vascular, intestinal and uterine smooth muscle.

1. The adrenergic neurone blocking agents, guanethidine and bretylium, have been tested for inhibitory activity against the actions of some relaxant drugs (BRL 38227, noradrenaline, sodium nitroprusside, theophylline) in vascular, intestinal and uterine smooth muscle. 2. In guinea-pig isolated taenia caeci pre-contracted with KCl (25 mM), BRL 38227 (0.1-10 microM) and noradrenaline (10 nM-100 microM) each caused concentration-dependent relaxation. Guanethidine and bretylium (50 microM) each antagonized the relaxation to BRL 38227 but not that to noradrenaline. At high concentration (500 microM), the adrenergic neurone blocking agents antagonized the action of BRL 38227 and, to some extent, that of noradrenaline. 3. In rat isolated aorta pre-contracted with noradrenaline (300 nM), BRL 38227 (0.0125-3.2 microM) and sodium nitroprusside (0.3-100 nM) each produced concentration-dependent smooth muscle relaxation. Guanethidine and bretylium (5-500 microM) each antagonized the action of BRL 38227 without antagonizing that of sodium nitroprusside. 4. Rats were pretreated with 17-beta oestradiol benzoate. Tension waves were then induced from segments of isolated, oestrogen-dominated uterus by transmural electrical stimulation or by oxytocin (0.2 nM). These tension waves were inhibited by BRL 38227 (0.025-3.2 microM) or theophylline (0.05-0.8 mM) in a concentration-dependent manner. Guanethidine (50 microM) antagonized the action of BRL 38227 in both the electrically- and oxytocin-driven tissues. In the electrically-driven tissues, guanethidine (50 microM) did not antagonize the inhibition to theophylline. 5. In KCl (25 mM)-treated guinea-pig taenia caeci, guanethidine (50 microM) inhibited the efflux of 86Rb+ evoked by BRL 38227 (10 microM) but not that evoked by noradrenaline (10 microM). In contrast, apamin(100 nM) reduced the efflux of 86Rb+ which was promoted by noradrenaline, but did not affect efflux induced by BRL 38227.6. It is concluded that the adrenergic neurone blocking agents, guanethidine and bretylium (each at 50 microM), selectively inhibit the relaxant action of BRL 38227 in vascular, intestinal and uterine smooth muscle. If this inhibition reflects direct blockade of the K+-channel (KKCO) which is opened by BRL 38227, then the adrenergic neurone blocking agents act as inhibitors selective for KKCO as opposed to the small, apamin-sensitive (SKCa) and large (BKca) conductance, Ca2"-dependent K+-channels.

Animals↗
PubMed1992

Potassium channel modulation in rat portal vein by ATP depletion: a comparison with the effects of levcromakalim (BRL 38227).

1. The effects of levcromakalim and of adenosine 5'-triphosphate (ATP) depletion on membrane potential and ionic currents were studied in freshly-dispersed smooth muscle cells of rat portal vein by use of combined voltage- and current-clamp techniques. 2. Levcromakalim (1 microM) induced a glibenclamide-sensitive, non-inactivating K-current (IKCO) and simultaneously inhibited the slow, transient outward, delayed rectifier K-current (ITO). Levcromakalim also hyperpolarized the portal vein cells by approximately 20 mV. 3. Reduction of intracellular ATP by removal of glucose and carboxylic acids from the recording pipette and of glucose from the bath fluid, induced a slowly-developing, non-inactivating and glibenclamide-sensitive K-current (Imet) within 60-300 s after breaking the membrane patch. Imet reached peak amplitude after 300-900 s, remained at a plateau for 200-800 s and then slowly ran down. At the peak of Imet, the cells were hyperpolarized by approximately 20 mV and their input conductance was increased by 42%. 4. At the time of maximum development of Imet, the delayed rectifier current, ITO, was reduced by 48%. 5. In the absence of glucose and carboxylic acids, addition of 1 microM free ATP to the recording pipette almost doubled the magnitude of Imet. At a holding potential of -10 mV, Imet was increased from 124 +/- 11 pA to 228 +/- 54 pA whereas the time-course of development and run-down of Imet was unaffected. 6. During the development and after the run-down of Imet, levcromakalim (1-10 microM) failed to induce IKCO. 7. Stationary fluctuation analysis of the current noise associated with Imet revealed a unitary conductance of between 10-20 pS in a physiological potassium gradient. A second contaminating current with an underlying unitary conductance of approximately 150 pS remained after Imet had run down. 8. It is concluded that IKCO induced by levcromakalim and Imet are carried by the same population of relatively small conductance, glibenclamide-sensitive K-channels. The open state of these is increased by procedures designed to lower intracellular ATP concentrations. 9. The simultaneous inhibition of the delayed rectifier current (ITO) by both levcromakalim and during the development of Imet is highly significant. It suggests that levcromakalim could modify the interaction of ATP with sites linked to more than one type of K-channel. This results in the opening of those channels which underlie IKCO (and which are normally inhibited by ATP binding) together with the modulation of phosphorylation-dependent channels such as those which underlie ITO.

Adenosine Triphosphate↗
PubMed1992

The involvement of potassium channels in the action of ciclazindol in rat portal vein.

1. In whole portal veins, ciclazindol (0.3-10 microM) increased the amplitude and duration, but decreased the frequency of spontaneous contractions. Glibenclamide (0.3-10 microM) produced a small increase in contraction amplitude and duration with a small reduction in contraction frequency. 2. In whole portal veins, ciclazindol (1-10 microM) antagonized the relaxant effects of BRL 38227 in a non-competitive manner. Under identical conditions, the effects of glibenclamide (0.3-10 microM) appeared to be competitive. 3. In whole portal veins loaded with 42K, ciclazindol itself (up to 3 microM) had no detectable effect on basal 42K exchange. However, the increase in 42K efflux produced by BRL 38227 (5 microM) was antagonized by ciclazindol (3 microM). Similar effects were produced by glibenclamide (up to 3 microM). 4. In freshly-isolated portal vein cells examined by the whole-cell voltage-clamp technique, ciclazindol (1-100 microM) inhibited the slowly-activating and inactivating transient outward current (ITO) which could be generated at potentials more positive than -30 mV. In addition ciclazindol (1-10 microM) inhibited the non-inactivating K-current (IKCO) induced by BRL 38227 (10 microM). 5. In freshly-isolated portal vein cells under current-clamp conditions, the hyperpolarization produced by BRL 38227 (10 microM) was reversed by ciclazindol (1-10 microM). 6. In porcine brain membrane fragments, glibenclamide (0.65 nM) displaced 50% of the binding of [3H]-glibenclamide whereas ciclazindol (up to 10 microM) had no effect. 7. It is concluded that ciclazindol is a K-channel blocker. Its action is not selective for the channel(s) which carry IKCO but also extends to those which carry ITO.Its inability to displace [3H]-glibenclamide from porcine brain fragments may indicate that antagonism of BRL 38227 by ciclazindol in smooth muscle is exerted at a site different from that of glibenclamide.

Animals↗
PubMed1992

Characterization of potassium currents modulated by BRL 38227 in rat portal vein.

1. Smooth muscle cells of the rat portal vein were dispersed by enzymatic treatment and recordings of whole-cell membrane potassium currents were made by the voltage-clamp technique. In isolated cells by use of combined voltage- and current-clamp the effect of BRL 38227 on membrane potential and ionic currents was also studied. 2. BRL 38227 (0.1 to 10 microM) induced a non-inactivating potassium current (IKCO) which developed slowly (900 s to 300 s, respectively) to its full size. These effects of BRL 38227 were reversible. 3. In addition to its K-channel opening properties, BRL 38227 (1 to 10 microM) inhibited the amplitude and changed the activation and inactivation characteristics of a slowly-inactivating, calcium influx-independent, outward potassium current (I(TO)). 4. Application of stationary fluctuation analysis to IKCO, showed a mean single channel current of 0.65 pA at -10 mV under a quasi-physiological potassium gradient. 5. In a combined voltage-clamp/current-clamp configuration, BRL 38227 (1 microM) induced a mean hyperpolarization of 22 mV. 6. The induction of IKCO by BRL 38227 and the associated hyperpolarization were suppressed by glibenclamide (1 to 10 microM) in a concentration-dependent manner. Glibenclamide (1 microM) had no effect on the inhibition of I(TO) by BRL 38227 (1 microM).

Algorithms↗
PubMed1992

The binding of the antimalarial arteether to human plasma proteins in-vitro.

The binding of the novel antimalarial drug, arteether, to human plasma, pure albumin and alpha 1-acid glycoprotein has been investigated by ultrafiltration, using [14C]arteether. The protein binding in plasma obtained from 11 healthy male subjects ranged from 73.4 to 81.8% bound, with a mean of 78.7 +/- 2.1%. The binding of drug in plasma was mainly accounted for by binding to albumin and alpha 1-acid glycoprotein. Scatchard analysis of the binding data revealed that the binding affinity of arteether to alpha 1-acid glycoprotein is much greater (20-fold) than that to albumin. This suggests that alpha 1-acid glycoprotein is the more important binding protein in plasma. This may have clinical importance due to alterations in plasma protein binding in patients with malaria, as the concentration of alpha 1-acid glycoprotein is markedly increased during malarial infection.

Adult↗
PubMed1992

Biochemical diagnosis of pheochromocytoma by simultaneous measurement of urinary excretion of epinephrine and norepinephrine.

The utility of specific assay of urinary catechols in pheochromocytoma diagnosis was examined by reviewing our data on the investigation of pheochromocytoma in a population of 2476 patients investigated over a six-year period. We used specific gas-chromatographic/mass-spectrometric (GC/MS) analysis for the simultaneous measurement of norepinephrine, dopamine, and the neuronal metabolites 3,4-dihydroxyphenylglycol (DHPG) and 3,4-dihydroxyphenylacetic acid (DOPAC) in all samples; the last two years of data collection (from 1101 patients) also included the specific GC/MS assay of epinephrine. The importance of assaying epinephrine as well as norepinephrine was shown by these latter data. During this latter period, 19 of 1101 patients were found to have pheochromocytoma; of these, nine had tumors that exclusively secreted norepinephrine, six had tumors that exclusively secreted epinephrine, and four exhibited excess production of both norepinephrine and epinephrine. Neither dopamine nor DOPAC was useful in the diagnosis of pheochromocytoma. A substantial proportion of patients may have uniquely epinephrine-secreting pheochromocytomas, previously considered a rarity. Thus we recommend that the biochemical testing for pheochromocytoma include the specific measurement of both norepinephrine and epinephrine.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1991

Comparison of the effects of several potassium-channel openers on rat bladder and rat portal vein in vitro.

1. The ability of several K-channel openers to inhibit KCl-induced contractions of rat bladder detrusor and spontaneous mechanical activity in rat portal vein was examined. 2. Lemakalim, pinacidil, Ro 31-6930, RP 49356, P1060 and S 0121 dose-dependently relaxed rat detrusor, precontracted with 20 mM KCl. With the exception of pinacidil, concentrations of these agents below 30 microM did not inhibit 80 mM KCl-included contractions. Pinacidil (10 microM) produced a small, but significant (P < 0.05) relaxation of 80 mM KCl-induced mechanical activity. Minoxidil sulphate and BRL 38226 produced some relaxation of 20 mM but not 80 mM KCl-induced contractions. 3. Glibenclamide (0.3-3 microM) antagonized the relaxant effects of lemakalim, pinacidil, Ro 31-6930, RP 49356, P1060 and S 0121 in a competitive manner (pA2 values 6.3-6.6). The effects of minoxidil sulphate and BRL 38226 were fully antagonized by 3 microM glibenclamide. 4. Lemakalim, pinacidil, S 0121, BRL 38226 and minoxidil sulphate were each approximately 8 times more potent as inhibitors of the spontaneous contractions of rat portal vein than KCl-induced contractions of the rat detrusor. Minoxidil sulphate was approximately 30 times more potent in the rat portal vein than in the bladder. This may indicate that either minoxidil sulphate is acting at different recognition sites in these two tissues, or that this compound has an additional mechanism of action in the portal vein. 5. With the exception of minoxidil sulphate, all the compounds tested stimulated 86Rb efflux and 42K efflux from preloaded rat detrusor strips. The stimulated 86Rb efflux was qualitatively but not quantitatively similar to the stimulated 42K efflux. Minoxidil sulphate stimulated 42K efflux from rat portal vein but not from rat bladder. 6. It is concluded that all the compounds tested cause relaxation of rat detrusor predominantly by Kchannel opening. Selectivity for bladder rather than vascular smooth muscle was not shown by any compound.

Animals↗