Search PubMed⌕ Search

Biomedical subjects

G Edwards

Publications and source records attributed to G Edwards.

At least 91 records · Page 5Linked to original sources
PubMed1994

Mortality in men with drinking problems: a 20-year follow-up.

This study presents mortality data from a 20-year follow-up of 99 married men with drinking problems. Forty-four of the sample had died and death certificates were obtained on 43. Cause of death was classified according to the Ninth Revision of the International Classification of Diseases. Most of the mortality excess was in the 45-54 year age group. The observed/expected mortality ratio was 3.64 for the group as a whole, 2.93 for the moderately dependent group and 4.41 for the severely dependent group. The commonest causes of death were carcinoma of the bronchus and diseases of the circulatory system. Cause of death was analysed in terms of years of life lost. The number of years of life lost per death was highest for injury and poisoning. Only four of the 43 death certificates obtained mentioned "chronic alcoholism".

Adult↗
PubMed1994

A test of the matching hypothesis: alcohol dependence, intensity of treatment, and 12-month outcome.

The "matching hypothesis"--the concept that treatment will be improved if matched to individual needs or characteristics--has, over recent years, attracted attention, and some research to test its validity has been conducted. These studies are briefly reviewed and an analysis then reported which focuses on exploration of the possible interaction between treatment intensity, patient characteristics with particular reference to degree of dependence on alcohol, and 12-month treatment outcome. The data derive from a controlled trial in which patients were randomized between "Treatment" and "Advice". No significant interactions of the kind postulated were identified and, at least for this data set, the matching hypothesis is not confirmed. Possible interpretations of these findings are discussed.

Alcoholism↗
PubMed1994

Pharmacokinetics of artemether after oral administration to healthy Thai males and patients with acute, uncomplicated falciparum malaria.

1. The pharmacokinetics of artemether were investigated (a) in six healthy male Thai volunteers after single 200 mg oral doses and (b) in eight male Thai patients with acute uncomplicated falciparum malaria after an initial 200 mg oral dose followed by 100 mg at 12 h then 100 mg daily for 4 days. 2. In the healthy subjects, median (range) maximum plasma concentrations of artemether of 118 (112-127) ng ml-1 were reached at 3 (1-10) h. Thereafter, drug concentrations declined monoexponentially with a median (range) t1/2.z of 3.1 (1.0-9.6) h. The median (range) AUC and MRT values were 1.10 (0.33-4.44) micrograms ml-1 h and 8.3 (3.5-20.8) h. The median Cmax value of dihydroartemisinin, an active metabolite, was 379 (162-702) mg ml-1 at 6 (2-12) h. Its median AUC value was 6.6 (0.83-38.7) micrograms ml-1 h; the apparent t1/2.z was 10.6 (4.7-19.2) h and the median MRT value was 16.0 (5.0-41.0) h. 3. In the patients, a higher Cmax value of parent drug than those observed in healthy subjects (median and range of 231 (116-411) ng ml-1), was reached at 3 (1-3) h after the first dose. Steady state was reached after the third dose (24 h) and concentrations fluctuated over the range of 36-60 ng ml-1. The respective median (range) values of AUC and t1/2.z were 5.8 (3.76-12.9) micrograms ml-1 h and 4.2 (2.5-5.3) h.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1994

Ion channel modulation by NS 1619, the putative BKCa channel opener, in vascular smooth muscle.

1. The effects of NS 1619, the putative BKCa channel opener, were investigated on rat intact portal veins and on single smooth muscle cells enzymatically separated from the same tissue. 2. Under whole-cell patch clamp conditions with K-rich pipettes, exposure of single cells held at -10 mV to NS 1619 (10-33 microM) induced a noisy, outward current which reached a maximum (33 microM NS 1619; mean 35.8 +/- 17 pA, n = 8) within about 6 min. 3. On stepping to test potentials (range -50 to +50 mV) from a holding potential of -10 mV, the NS 1619-induced noisy current exhibited time-dependent activation and marked outward rectification. 4. The stimulation of outward currents by NS 1619 at -10 mV was independent of the presence of Ca2+ in the bath or pipette solutions but was antagonized by either charybdotoxin (250 nM) or penitrem A (100 nM) in the bath solution. 5. Stationary fluctuation analysis of the noisy current induced by NS 1619 at -10 mV yielded a value of 70 +/- 8 pS (n = 4) (under the quasi-physiological conditions of the experiment) for the unitary conductance of the channel involved. 6. At -10 mV, NS 1619 (10-33 microM) rapidly inhibited spontaneous transient outward currents. 7. With a holding potential of -90 mV, NS 1619 (10-33 microM) produced a reduction of outward currents evoked by depolarizing steps to +50 mV, an effect associated with marked inhibition of the delayed rectifier current, IK(V). 8. NS 1619 (3-100 microM) produced a concentration-dependent inhibition of spontaneous activity in rat portal vein characterized by a reduction in the amplitude and duration of the tension waves. This inhibition was slightly potentiated in the presence of either charybdotoxin (250 nM) or penitrem A (1 microM). NS 1619 also totally inhibited contractions of rat aorta induced by KCl (both 20 mM and 80 mM). 9. Under whole-cell recording conditions and using Cs-rich pipettes, Ca-currents evoked in portal vein cells by stepping from a holding potential of - 90 mV to test potentials in the range - 30 to + 50 mV were totally inhibited in the presence of 33 JAM NS 1619.10. NS 1619 (33 JAM) inhibited the induction of IK(ATP) by levcromakalim (10 JAM).11. It is concluded that NS 1619 activates the large conductance, Ca2+-sensitive channel, BKca and over the same concentration range it inhibits both KV and L-type Ca-channels. The observed NS 1619-induced mechanical inhibition in rat portal vein and aorta seems most likely to be due to the observed inhibition of Ca-currents.

Animals↗
PubMed1994

Possible isozyme-specific effects of experimental malaria infection with Plasmodium berghei on cytochrome P450 activity in rat liver microsomes.

We have investigated the effect of experimental malaria infection on rat cytochrome P450-mediated drug metabolism using ethoxyresorufin and metoprolol as probe compounds. Malaria infection caused a significant reduction in total intrinsic clearance of ethoxyresorufin in both low and high parasitaemia malaria compared with control (control 18.7 +/- 7.2; low parasitaemia 10.5 +/- 4.1; high parasitaemia 4.3 +/- 1.4 mL min-1). However, clearance of metoprolol was unchanged in malaria infection compared with control (control 2.7 +/- 1.2; malaria 4.0 +/- 1.7 mL min-1). The change in clearance of ethoxyresorufin was the result of a decrease in Vmax, with no apparent change in Km. There was no change in either Vmax or Km of metoprolol. These results indicate a possible isozyme-selective effect of experimental malaria.

Acetylation↗
PubMed1994

Clinical pharmacokinetics in the treatment of tropical diseases. Some applications and limitations.

In recent years major advances have been made in the clinical pharmacology of many drugs used for the treatment of tropical diseases, particularly in the design and development of dosage regimens for the treatment of severe malaria. For example, by careful manipulation of its rate of administration, chloroquine has been shown to be well tolerated when used for treatment of severe disease caused by susceptible parasites. Similarly, important advances have been made in the rational design of quinine dosage regimens for patients in South East Asia and Africa. Investigation of the pharmacokinetics of mefloquine has drawn attention to the problems associated with its administration as combination therapy with pyrimethamine and sulfadoxine in Thailand. Similarly, evaluation of the pharmacokinetic properties of halofantrine has led to the demonstration that poor and erratic absorption could be just as likely to explain therapeutic failure as resistance of the parasite to effects of this drug. Disposition of the antimalarial biguanides has highlighted the role of host-related effects in the determination of drug response. For example, a small percentage of individuals are unable to convert proguanil (chloroguanide) to its active triazine metabolite, cycloguanil. Finally, agents that reverse chloroquine resistance are currently under development for the treatment of malaria. The importance of assessing the clinical pharmacokinetic properties of potential resistance reversers must be recognised. While limited success has been achieved in antifilarial chemotherapy, other parasitic diseases have been largely neglected with advances in the laboratory still awaiting full recognition of their clinical application. For example, clinical pharmacokinetic concepts may be used to improve the therapy of human hydatid disease. We believe that clinical management of tropical diseases can be improved by the application of clinical pharmacokinetic principles. However, this may not be universally advantageous. For example, the artemisinin (qinghaosu) derivatives are among the most recently developed antimalarials that have great therapeutic promise. Recent evidence suggests that pharmacokinetic data would be of limited value in the design and optimisation of dosage regimens because of its chemical reactivity and the unusual mechanism by which these drugs kill parasites. Similar limitations may apply to the microfilaricidal drug, ivermectin.

Chloroquine↗
PubMed1994

Effect of malaria infection on the pharmacokinetics of paracetamol in rat.

1. Paracetamol (P; 50 and 300 mg/kg i.v.) was administered to the control and malaria-infected (MI) male Wistar rat in order to assess the effect of MI on the metabolism of paracetamol to its glucuronide (PG) and sulphate (PS) conjugates and their excretion in urine. 2. At a dose of 50 mg/kg, neither total clearance (ClT) (controls, 20.3 +/- 0.5; MI, 19.9 +/- 0.9, ml/min/kg; mean +/- SD, p > 0.05) nor the renal clearance of P (ClR) were affected by MI. Although the formation clearance of PG (Clf PG) was decreased by about 40% (controls, 6.6 +/- 1.1; MI, 3.9 +/- 0.9, ml/min/kg, p < 0.05), the formation clearance of PS (Clf PS) was increased by 30% in the MI rat (controls, 8.8 +/- 0.9; MI, 11.2 +/- 1.7, ml/min/kg, p < 0.05), and therefore Clm (controls, 19.7 +/- 0.5; MI, 19.2 +/- 0.8, ml/min/kg, p > 0.05) was unchanged by MI. 3. At a dose of 300 mg/kg, MI produced a significant decrease in the total clearance of P (ClT) (controls, 16.9 +/- 1.0; MI, 11.9 +/- 0.9, ml/min/kg, p < 0.05), metabolic clearance (Clm) (controls, 15.9 +/- 1.4; MI, 11.3 +/- 0.9, ml/min/kg, p < 0.05) and the formation clearance of PG (Clf PG) (controls, 7.9 +/- 1.3; MI, 4.7 +/- 1.5, ml/min/kg, p < 0.05) without affecting Clf PS and ClR of P. 4. These findings indicate that MI impairs the glucuronidation of paracetamol in rat in vivo at both the low and high doses of P. Increased sulphate formation appeared to compensate for decreased glucuronidation at the lower dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetaminophen↗
PubMed1994

Effect of an experimental malaria infection on the metabolism of phenacetin in the rat isolated perfused liver.

1. The effect of infection with the rodent malaria parasite Plasmodium berghei on the metabolism of phenacetin has been investigated in a rat isolated perfused liver preparation. 2. A bolus dose of phenacetin (10 mg) was introduced into the perfusate reservoir of both control (n = 4) and malaria-infected (n = 4) liver preparations, and samples of bile and perfusate were collected (0-4 h) for hplc analysis of phenacetin, paracetamol and its phase II metabolites. 3. Whereas malaria had no effect on the hepatic clearance of phenacetin (control: 0.64 +/- 0.15 versus malaria: 0.66 +/- 0.14 ml min-1), there was a significant reduction in the hepatic clearance of generated paracetamol (control: 1.22 +/- 0.15 versus malaria: 0.41 +/- 0.08 ml min-1) and the total recovery in bile and perfusate of paracetamol glucuronide (control: 1.18 +/- 0.44 versus malaria: 0.29 +/- 0.20 mg). There was no significant change during malaria infection in the total recovery of either phenacetin (control: 1.30 +/- 0.73 versus malaria: 0.79 +/- 0.36 mg) or paracetamol sulphate (control: 0.81 +/- 0.25 versus malaria: 0.74 +/- 0.16 mg),

Acetaminophen↗
PubMed1994

Carriers of healthcare's load of information.

As the market for telemedicine products and services expands, many long distance telecommunications carriers and regional Bell operating companies developed strategies for meeting healthcare's needs. Some initiated projects to display their capabilities or to receive returns on investments in telecommunications infrastructures. Their capabilities and use of advanced technologies vary. The level of their healthcare commitment and involvement also varies. Regional Bell companies compete fiercely with each other and with national carriers for consulting and implementation contracts, unrestricted by service area boundaries. On the following pages, representatives from most of the major telecommunications carriers express their firms' healthcare strategies and offer synopses of their notable healthcare projects. For many, their resources are vast, their expertise undisputed. Access to high-quality healthcare services stands to benefit from their involvement.

Health Services Needs and Demand↗
PubMed1994

The chemotherapy of onchocerciasis XVII. A clinical evaluation of albendazole in patients with onchocerciasis; effects of food and pretreatment with ivermectin on drug response and pharmacokinetics.

Three pharmacokinetic studies were conducted in Ghanaian patients in support of investigations of albendazole and its combination with ivermectin in the treatment of onchocerciasis. These included dose-finding studies, investigations into the influence of a fatty meal on the relative bioavailability of albendazole as assessed by the measurement of concentrations of albendazole sulphoxide and the effect of prior treatment with ivermectin on antiparasitic efficacy and plasma concentrations of albendazole suphoxide. Increasing the dose of albendazole from 800 mg x 3 daily to 1200 mg x 3 daily produced no additional antiparasitic effects although plasma concentrations of albendazole sulphoxide were increased in proportion to dose size. Moreover, the plasma concentration vs time profiles suggest that most of the effects observed may have been due to the first 800 mg dose. Administration of ivermectin had no effect on the pharmacokinetics of albendazole sulphoxide and there was no additive effect on the parasite. Albendazole was well tolerated and its administration 5-7 days after ivermectin produced little additional reaction. Although it is not macrofilaricidal, it does possess important chemosterilant properties which are enhanced by its administration with a fatty breakfast. Under these conditions, the relative bioavailability of albendazole is increased four-fold. These studies support further work with albendazole administered with food either as a single dose, as multiple single doses repeated at intervals of several months and its coadministration with ivermectin. They also encourage the belief that a more potent and bioavailable benzimidazole may be macrofilaricidal or a permanent chemosterilant for Onchocerca volvulus on single dosage.

Adolescent↗
PubMed1993

Transcription factor E2F binds DNA as a heterodimer.

E2F is a mammalian transcription factor that appears to play an important role in cell cycle control. DNA affinity column-purified E2F from HeLa cells reproducibly exhibits multiple protein bands when analyzed by SDS/PAGE. After electrophoretic purification, electroelution, and refolding of the individual protein components, the E2F DNA binding activity of the individual proteins was poor. However, upon mixing the individual components together, a dramatic (100- to 1000-fold) increase in specific DNA binding activity was observed. The five protein bands isolated can be separated into two groups based on apparent molecular mass. Optimal reconstitution of activity requires one of the two proteins found in the group of larger molecular mass (approximately 60 kDa) and one of the three proteins in the smaller-sized group (approximately 50 kDa). The reconstituted heterodimer is identical to authentic affinity-purified E2F by three criteria: DNA-binding specificity, DNA pattern, and binding to the retinoblastoma gene product. A recently cloned protein with E2F-like activity, RBP3/E2F-1, is related to the protein components of the group of larger molecular mass, as determined by Western blot analysis and reconstitution experiments. These data suggest that E2F, like many other transcription factors, binds DNA as an oligomeric complex composed of at least two distinct proteins.

Adenoviruses, Human↗
PubMed1993

Effect of malaria infection and endotoxin-induced fever on phenacetin O-deethylation by rat liver microsomes.

We have investigated the effect of malaria infection with the rodent parasite Plasmodium berghei and fever induced by Escherichia coli endotoxin on the metabolism of phenacetin to paracetamol by rat liver microsomes from young (4 weeks old) male Wistar rats (N = 5 in control and fever groups; N = 10 in malaria-infected group). Following determination of % parasitaemia, the malaria-infected group was divided into a low parasitaemia subgroup (N = 5; mean % parasitaemia = 9.87 +/- 2.6) and a high parasitaemia subgroup (N = 5; mean % parasitaemia = 36.6 +/- 8.1). The control group received normal saline. Total microsomal protein was not significantly affected by fever or malaria infection while cytochrome P450 levels were reduced by approximately 50% in the high parasitaemia subgroup, 20% in the low parasitaemia subgroup and 20% in the endotoxin-treated group. Phenacetin-O-deethylation kinetics were biphasic in both control and malaria-infected rats, but monophasic in endotoxin-treated rats. Total apparent intrinsic clearance (CL(int),total; calculated as Vmax/Km; Vmax is maximum velocity, Km is Michaelis constant) of phenacetin was reduced approximately 6-fold in low parasitaemia, 30-fold in high parasitaemia and 35-fold in fever. There was a poor correlation between CL(int),total and % parasitaemia (r = -0.6). However, log CL(int),total correlated inversely with % parasitaemia (r = -0.9), suggesting that Cl(int),total decreased exponentially with an increase in % parasitaemia. Phenacetin O-deethylation is a marker for cytochrome P4501A2 activity and the results of the present study suggest that both malaria infection and fever might specifically reduce P4501A2 activity in the rat.

Acetaminophen↗
PubMed1993

Effect of malaria infection and endotoxin-induced fever on the metabolism of antipyrine and metronidazole in the rat.

Antipyrine and metronidazole were administered as a cocktail to young (4 weeks old) male Wistar rats (N = 12 for each treatment) to investigate the effect of malaria infection due to the rodent parasite Plasmodium berghei and Escherichia coli endotoxin-induced fever on the metabolism of the two compounds in vivo. Control rats received normal saline. Antipyrine and metronidazole clearances were estimated from a single saliva sample while the formation clearances of their metabolites (in malaria-infected and control rats) were estimated from the product of clearance of parent drug and the fraction of the administered dose excreted as metabolites in urine in 24 hr. Rats treated with endotoxin produced no urine during this period. Malaria infection had no effect on clearance of antipyrine or on formation clearance of any of its metabolites. However, the clearance of metronidazole was reduced by approximately 20% compared with controls as a result of decreased formation of hydroxymetronidazole. Fever decreased clearance of both antipyrine and metronidazole by approximately 36% and 23%, respectively. These results demonstrate that both malaria infection and fever can influence P450-dependent drug metabolism and the effects seen appear to be isozyme-selective.

Animals↗
PubMed1993

Bupivacaine and Kaltostat reduces post-operative donor site pain.

A prospective double blind controlled trial was carried out to examine the differences in post-operative split skin graft donor site pain between sites dressed with three differently treated types of dressing; a dry calcium alginate dressing (Kaltostat Britcair), a saline moistened Kaltostat dressing and a bupivacaine hydrochloride (0.5%) moistened Kaltostat dressing. There was a significant reduction in post-operative pain in the Kaltostat and bupivacaine group (group 3) at 24 and 48 h when compared to the other two groups (p < 0.04). There was no difference in ease of removal of dressings or the quality of wound healing on day 10 between the three groups. This study demonstrates a significant reduction in post-operative pain in bupivacaine soaked Kaltostat without reducing the beneficial effects of Kaltostat on donor site healing and we recommend its use in clinical practice.

Adult↗