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Biomedical subjects

G Edwards

Publications and source records attributed to G Edwards.

At least 19 recordsLinked to original sources
PubMed2006

The efficiency of an air filtration system in the hospital ward.

A study was conducted to ascertain the efficiency and effectiveness of an air filtration system (Electromedia Model 100C, Clean Air UK, UK) in the hospital ward. The sampling was conducted using a portable Surface Air Sampler (Cherwell Laboratories, Bicester, UK) in conjunction with settle plates. Samples were taken two days before and two days following activation of the filtration system and results compared. A clear, demonstrable, statistically significant reduction in microbial organisms following the activation of the filtration systems is evident (81% settle plates; 24% Surface Air Sampler). This study has implications for the improved health and welfare of patients and healthcare workers who may benefit through the implementation of such a system.

Air Microbiology↗
PubMed2004

Functional evidence of a role for two-pore domain potassium channels in rat mesenteric and pulmonary arteries.

1. Experiments were performed to elucidate the mechanism by which alterations of extracellular pH (pH(o)) change membrane potential (E(M)) in rat mesenteric and pulmonary arteries. 2. Changing pH(o) from 7.4 to 6.4 or 8.4 produced a depolarisation or hyperpolarisation, respectively, in mesenteric and pulmonary arteries. Anandamide (10 microm) or bupivacaine (100 microm) reversed the hyperpolarisation associated with alkaline pH(o), shifting the E(M) of both vessels to levels comparable to that at pH 6.4. In pulmonary arteries, clofilium (100 microm) caused a significant reversal of hyperpolarisation seen at pH 8.4 but was without effect at pH 7.4. 3. K(+) channel blockade by 4-aminopyridine (4-AP) (5 mm), tetraethylammonium (TEA) (10 mm), Ba(2+) (30 microm) and glibenclamide (10 microm) depolarised the pulmonary artery. However, shifts in E(M) with changes in pH(o) remained and were sensitive to anandamide (10 microm), bupivacaine (100 microm) or Zn(2+) (200 microm). 4. Anandamide (0.3-60 microm) or bupivacaine (0.3-300 microm) caused a concentration-dependent increase in basal tone in pulmonary arteries. 5. RT-PCR demonstrated the expression of TASK-1, TASK-2, THIK-1, TRAAK, TREK-1, TWIK-1 and TWIK-2 in mesenteric arteries and TASK-1, TASK-2, THIK-1, TREK-2 and TWIK-2 in pulmonary arteries. TASK-1, TASK-2, TREK-1 and TWIK-2 protein was demonstrated in both arteries by immunostaining. 6. These experiments provide evidence for the presence of two-pore domain K(+) channels in rat mesenteric and pulmonary arteries. Collectively, they strongly suggest that modulation of TASK-1 channels is most likely to have mediated the pH-induced changes in membrane potential observed in these vessels, and that blockade of these channels by anandamide or bupivacaine generates a small increase in pulmonary artery tone.

Animals↗
PubMed2004

Postsynthesis stabilization of free-standing mesoporous silica films.

Mixed ammonia-water vapor postsynthesis treatment provides a simple and convenient method for stabilizing mesostructured silica films. X-ray diffraction, transmission electron microscopy, nitrogen adsorption/desorption, and solid-state NMR (13C, 29Si) were applied to study the effects of mixed ammonia-water vapor at 90 degrees C on the mesostructure of the films. An increased cross-linking of the silica network was observed. Subsequent calcination of the silica films was seen to cause a bimodal pore-size distribution, with an accompanying increase in the volume and surface area ratios of the primary (d = 3 nm) to secondary (d = 5-30 nm) pores. Additionally, mixed ammonia-water treatment was observed to cause a narrowing of the primary pore-size distribution. These findings have implications for thin film based applications and devices, such as sensors, membranes, or surfaces for heterogeneous catalysis.

Adsorption↗
PubMed2004

Pharmacokinetic and pharmacodynamic issues in the treatment of parasitic infections.

Despite increases in the incidence of many parasitic infections in recent years, the number of studies designed to improve the treatment of these infections has failed to keep pace with their huge impact on public health. Unfortunately, research and development in this field is not an economically attractive proposition for the pharmaceutical industry, and this neglect is exacerbated by the fact that many parasitic diseases have negligible profiles in countries that have the funds to research them. An absence of effective vaccines means that, for the foreseeable future, chemotherapy is likely to be the mainstay of disease management. This review describes the advances gained in our understanding of the relationship between pharmacokinetics and pharmacodynamics, with the aim of improving the way in which we use antiparasitic agents while at the same time highlighting those areas where there is an urgent need for further investigation. Unsurprisingly, much of our success has been in the chemotherapy of malaria, where the link between drug concentration and response is reasonably well characterised. For many other diseases, however, this link is poorly understood, in some cases because the mechanism of action of the drug has not been fully elucidated, or in other cases because a true pharmacodynamic endpoint may be unavailable. Overcoming these problems is critical if the clinician is to have the information necessary to enable optimal treatment of patients who may be severely ill and in need of immediate, life-saving attention.

Administration, Oral↗
PubMed2004

Marker-evaluated selection in rice: shifts in allele frequency among bulks selected in contrasting agricultural environments identify genomic regions of importance to rice adaptation and breeding.

Conventional methods for quantitative trait locus (QTL) mapping require the selection of particular traits to be measured based on assumptions as to their importance. We have tested an alternative approach for the location of QTLs-marker-evaluated selection-that makes no prior assumptions as to which traits are important. The results of phenotype selection were evaluated in the products of modified bulk-population breeding that was replicated across a range of rice ecosystems. Selection was carried out in close collaboration with farmers in bulk populations that were all derived from a cross between an Indian upland variety (Kalinga III) and a high-yielding semi-dwarf variety (IR64).Twenty-seven diverse bulks were produced that were screened with molecular markers in order to determine whether shifts could be detected in marker allele frequency as a result of selection and if such changes varied by genomic region across ecosystems. Marker loci linked to important traits for adaptation to specific environments were identified without making any prior assumptions about which traits might be important. Genomic regions from Kalinga III were strongly selected in the upland environments and regions from IR64 in the lowland ones.However, exceptions occurred where the upland parent contributed positively to lowland adaptation and vice versa. The results can be used as a basis for the development of second-cycle varieties, using marker-assisted selection to produce genotypic ideotypes for specific target environments. The very strong selection for genomic regions from the adapted parents of the wide(upland x lowland) cross indicates that, in non-marker-assisted breeding, where genetically distant parents have been used, modified backcross breeding should be efficient. A single backcross to the adapted parent for aspecific ecosystem will result in a higher frequency of segregants with the desired high genetic contribution from the adapted parent.

Acclimatization↗
PubMed2004

Effects of pioglitazone on the components of diabetic dyslipidaemia: results of double-blind, multicentre, randomised studies.

A total of 3,713 patients with poorly controlled type 2 diabetes were enroled into four multicentre, double-blind studies and randomised to receive pioglitazone, sulphonylurea, metformin or a combination of two of these agents for up to 52 weeks. Data from patients with a lipid evaluation, at week 52, were pooled, and treatment groups were compared using analysis of covariance. Pioglitazone, alone or combined with metformin or sulphonylurea, resulted in mean decreases in triglycerides (-9 to -11%), total/HDL cholesterol ratio (-9 to -10%) and free fatty acid (-0.051 to -0.123 mmol/l) and mean increases in HDL cholesterol (17 to 20%). The sustained, favourable effects of pioglitazone on important components of diabetic dyslipidaemia may contribute to reduced cardiovascular disease risk, among patients with type 2 diabetes.

Adult↗
PubMed2004

Cardiovascular effects of treatment of type 2 diabetes with pioglitazone, metformin and gliclazide.

Cardiovascular mortality and morbidity are increased in patients with type 2 diabetes. However, there are few data from clinical trials comparing cardiovascular effects of alternative oral anti-diabetic agents. Major cardiovascular outcomes during four one-year, double-blind trials in over 3700 patients with type 2 diabetes randomised to either a thiazolidinedione, pioglitazone, metformin or a sulphonylurea, gliclazide treatment have been combined. Mean blood pressure was slightly reduced by all treatments, with pioglitazone treatment resulting in the largest falls (approximately 1.5 mmHg). Hospitalisations for cardiac or cerebrovascular events were similar with the different treatments. Overall mortality was seven of 1857 for pioglitazone and 10 of 1856 for non-pioglitazone treatments, of which three and six were cardiac deaths, respectively. The incidence of congestive cardiac failure was similar with pioglitazone (12/1857) and non-pioglitazone (10/1856) treatments. The results show similar cardiovascular outcome for the three different treatments over a one-year period, but demonstrate interesting differences, which will require longer-term formal outcome studies to determine their significance.

Blood Pressure↗
PubMed2004

An investigation of persistent microfilaridermias despite multiple treatments with ivermectin, in two onchocerciasis-endemic foci in Ghana.

If ivermectin-based programmes for the control of human onchocerciasis are to be successful, the drug must remain effective for as long as necessary. In an open, case-control study, an attempt was made to determine if the persistent, significant, Onchocerca volvulus microfilaridermias seen in some individuals who had received at least nine treatments with ivermectin were the result of the development of drug resistance in the parasite. Twenty-one of these 'sub-optimal' responders (cases) were matched, by age, weight, number of treatments, locality and skin microfilarial counts, with seven amicrofilaridermic responders and 14 ivermectin-naive subjects. The number of treatments taken, any potential drug interactions and significant underlying disease were determined from detailed clinical and laboratory studies. Each subject was treated with ivermectin during the study, so that plasma concentrations of the drug could be determined for 72 h from the time of dosage. The microfilarial and adult-worm responses to this treatment were assessed from skin microfilarial counts (obtained before the treatment and at days 8, 90 and 365 post-treatment), day-90 embryogrammes, and the results of fly-feeding experiments. Parasite-sensitivity criteria for various time-points were derived from earlier data on skin microfilaridermias and the effects of ivermectin on the adult worms. The results indicate that the significant microfilaridermias that persist despite multiple treatments with ivermectin are mainly attributable to the non-response of the adult female worms and not to inadequate drug exposure or other factors. The possibility that some adult female worms have developed resistance to ivermectin cannot be excluded. These results justify the routine monitoring of treatment efficacy in any ivermectin-based programme of disease control.

Adolescent↗
PubMed2004

Thirty-month follow-up of sub-optimal responders to multiple treatments with ivermectin, in two onchocerciasis-endemic foci in Ghana.

The pathogenesis of the sub-optimal response of Onchocerca volvulus to ivermectin was investigated in a 30-month follow-up of 28 individuals who, in a previous study, had been found to show a sub-optimal (N = 15) or adequate response (N = 13) to multiple treatments with the drug. Verbal informed consent was obtained before each subject was given a general clinical and ocular examination. Skin snips were taken from both iliac crests and both calves. Seventeen nodule carriers were hospitalized for nodulectomy. Adult worms were harvested, embryogrammes were constructed and all developmental stages were counted; degenerate, stretched microfilariae were noted separately. All the subjects were in good general health and all except one had received at least one additional treatment with ivermectin since the earlier study. A large proportion of the adult female worms in 10 out of the 11 sub-optimal responders who were nodule carriers were in full embryonic production but most of the stretched microfilariae they carried were degenerate. This picture is similar to that found in adult worms exposed to the first dose of ivermectin. In one subject who had no viable worms in his nodules, the existence of occult but actively reproductive worms was inferred from the high level of microfilaridermia observed less than 12 months after treatment. These observations confirm the existence of populations of adult female O. volvulus that respond poorly to repeated doses of ivermectin. The use of suramin in the treatment of the sub-optimal responders is discussed.

Adult↗
PubMed2004

The safety, tolerability and pharmacokinetics of levamisole alone, levamisole plus ivermectin, and levamisole plus albendazole, and their efficacy against Onchocerca volvulus.

Two randomized, double-blind, placebo-controlled trials, in which levamisole (2.5 mg/kg) was given alone or co-administered with ivermectin (200 microg/kg) or albendazole (400 mg), were conducted. In Trial 1, safety and drug-drug interaction were explored in 42 healthy male volunteers. During Trial 2, the safety of the same treatment regimens and their efficacy against the adult worms and microfilariae of Onchocerca volvulus were investigated in 66 infected subjects of both sexes. Safety was determined from the results of detailed clinical and laboratory examinations before treatment, during hospitalization and on day 30. The pharmacokinetic parameters for levamisole alone and the combinations were determined in Trial 1 and then compared with historical data for ivermectin and albendazole, given as single agents, to determine if drug-drug interaction had occurred. The level of efficacy against the adult worms was determined by the examination of histology sections of nodules excised 6 months posttreatment and from the changes seen in the levels of microfilaridermia within a year of treatment. Microfilaricidal efficacy was estimated from the reductions in the levels of microfilaridermia between day 0 (1 day pre-treatment) and day 30. Although the regimens were generally well tolerated, there were unexpected adverse effects in both healthy volunteers and infected subjects. Clinically significant drug-drug interactions resulted in an increase in the bio-availability of ivermectin but a reduction in that of albendazole when these drugs were co-administered with levamisole. Levamisole given alone or with albendazole had little effect on O. volvulus. The combination of levamisole with ivermectin was neither macrofilaricidal nor more effective against the microfilariae and the adult worms than ivermectin alone. The pathogenesis of the adverse events and the drug-drug interactions are discussed.

Adolescent↗
PubMed2003

Trends in antimicrobial drug resistance in Salmonella enterica serotypes Typhi and Paratyphi A isolated in Europe, 1999-2001.

Results of antimicrobial sensitivity tests for strains of Salmonella enterica serotypes Typhi and Paratyphi A isolated from patients in ten European countries between 1999 and 2001 have been transferred electronically to the Enter-net surveillance hub. For Typhi between 22 and 29% of isolates were multiresistant (to four drugs or more) with decreased susceptibility to ciprofloxacin (MIC 0.25-1.0 mg/l) increasing from 20% in 1999 to 26% in 2001. Nineteen of 169 (11%) strains with decreased ciprofloxacin susceptibility were sensitive to nalidixic acid. For Paratyphi A multiple resistance increased from 9% in 1999 to 25% in 2001 and decreased ciprofloxacin susceptibility from 6 to 17%. Clinicians should be aware of the possibility of treatment failures when fluoroquinolones are used as the first-line drug for infections with Typhi and Paratyphi A, particularly for patients recently returning from areas where drug-resistant strains are endemic.

Anti-Bacterial Agents↗
PubMed2003

The co-administration of ivermectin and albendazole--safety, pharmacokinetics and efficacy against Onchocerca volvulus.

A randomized, double-blind, placebo-controlled trial was conducted, to determine whether the co-administration of ivermectin with albendazole is safe and more effective against Onchocerca volvulus than ivermectin alone, and whether a significant pharmacokinetic interaction occurs. Forty-two male onchocerciasis patients received ivermectin (200 mug/kg) alone, albendazole (400 mg) alone or the combination. Safety was determined from the results of detailed clinical and laboratory examinations before treatment, during hospitalization and on day 30. Microfilaricidal efficacy was estimated from the reductions in skin counts between day 0 (pretreatment) and day 30. To determine efficacy against the adult worms, two independent observers examined histology slides prepared from nodules excised on day 180; changes in the skin counts of skin microfilariae between days 30 and 365 provided additional indicators of the level of adulticidal activity. Pharmacokinetic parameters for ivermectin and albendazole sulphoxide were defined over 72 h post-treatment. The co-administration of ivermectin with albendazole did not produce more severe adverse effects than ivermectin alone. Both nodule examiners found that the combination was not macrofilaricidal and that it was not clearly superior to ivermectin alone in the effects on reproductive activity; this was supported by the similar efficacy of the two regimens in the suppression of skin microfilariae. There was no significant pharmacokinetic interaction. Although the co-administration of ivermectin with albendazole appears safe, it offers no advantage over ivermectin alone in the control of onchocerciasis. The combination does not require an alteration in the dosage of either component.

Administration, Oral↗
PubMed2003

Antimicrobial drug resistance in isolates of Salmonella enterica from cases of salmonellosis in humans in Europe in 2000: results of international multi-centre surveillance.

The Enter-net surveillance system received results of antimicrobial sensitivity tests for isolates from over 27 000 cases of human salmonellosis in 2000 in 10 European countries. Almost 40% of isolates were resistant to at least one antimicrobial, with 18% multiresistant. Resistance to ampicillin, streptomycin, sulphonamides and tetracyclines was common, with over 20% of isolates resistant to at least one of these antimicrobials. Clinical resistance to ciprofloxacin was rare, with only 0.5% of isolates exhibiting such resistance (MIC >1.0 mg/l). Resistance to nalidixic acid coupled with a decreased susceptibility to ciprofloxacin (MIC 0.25-1.0 mg/l) was more common, with 14% of isolates showing these properties. Resistance to third-generation cephalosporins was rare with only 0.6% of isolates resistant to cefotaxime. In all countries multiple resistance was most common in Salmonella enterica serotype Typhimurium, with 51% of isolates multiresistant in total. In England and Wales multiple resistance was also prevalent in S. Virchow and S. Hadar, whereas in other countries multiple resistance was common in serotypes such as S. Blockley.

Anti-Bacterial Agents↗