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Biomedical subjects

G Edwards

Publications and source records attributed to G Edwards.

At least 145 records · Page 8Linked to original sources

Tissue ablation by a free-electron laser tuned to the amide II band.

Efforts to ablate soft tissue with conventional lasers have been limited by collateral damage and by concern over potential photochemical effects. Motivated by the thermal-confinement model, past infrared investigations targeted the OH-stretch mode of water with fast pulses from lasers emitting near 3,000 nm (refs 1, 7-9). What does a free-electron laser offer for the investigation of tissue ablation? Operating at non-photochemical single-photon energies, these infrared sources can produce trains of picosecond pulses tunable to the vibrational modes of proteins, lipids and/or water. We report here that targeting free-electron laser radiation to the amide II band of proteins leads to tissue ablation characterized by minimal collateral damage while maintaining a substantial ablation rate. To account for these observations we propose a novel ablation mechanism based on compromising tissue through resonant denaturation of structural proteins.

Amides↗

Ferriprotoporphyrin catalysed decomposition of artemether: analytical and pharmacological implications.

The ability of the products of erythrocytic haemolysis and ferriprotoporphyrin (FP-IX)-containing substances of facilitate the decomposition of the antimalarial drug artemether has been evaluated in vitro. The products of haemolysis accelerate the degradation of artemether to unidentified compounds which are undetectable by currently available HPLC methods. This decomposition is temperature dependent and occurs after relatively brief artemether (ARM)-catalyst contact. Using radiolabelled [16-14C]ARM, we have demonstrated that the extractability of total radioactivity into the organic phase diminishes with increasing FP-IX concentration with an appreciable reduction in the organic extractability as ARM in the presence of FP-IX and associated increase in water solubility of radioactivity when the concentration of FP-IX increases from 0 to 7.7 mM. This effect appears to be temperature dependent for incubations with haematin. Characterisation of the organically extractable radioactivity from incubations of [16-14C]ARM with FP-IX has shown a loss of ARM and the formation of two radioactive products which occurs in proportion to the concentration of FP-IX. We believe these findings are of particular relevance to the determination of plasma concentrations of ARM and dihydroartemisinin (DHA) in malaria patients where extensive haemolysis and the presence of breakdown products of haemoglobin may contribute to a reduction in the circulating concentration of these substances. In these circumstances, measurement of ARM and DHA by conventional methods may be meaningless.

Antimalarials↗

Treatment with coumarin to prevent or delay recurrence of malignant melanoma.

Both coumarin (1,2-benzopyrone) and warfarin (4-hydroxycoumarin) have been shown to prevent the recurrence of malignant melanoma. Their action is macrophage-dependent and the dosage is critical. In 1984 a multicentre, prospective, randomised, double-blind trial of coumarin, given as a daily 50-mg dose for 2 years after surgery in patients with high-risk melanoma, was started. the patients had lesions greater than 1.70 mm thick and TNM stage IB or stage II disease. To date there are 4 recurrences in the coumarin-treated group of 13 patients, and 10 recurrences in the placebo-treated group of 14 patients (P < 0.01). There were no toxic effects.

Chemotherapy, Adjuvant↗

Measurement of artemisinin and its derivatives in biological fluids.

The development of selective analytical methods for the determination of artemisinin and its analogues and metabolites in biological fluids poses challenging problems. All are thermally labile, lack ultraviolet (u.v.) absorbent or fluorescent chromophores and do not possess functional groups for derivatization. Two chemical approaches have been used; acid (or alkali) catalysed decomposition to u.v. absorbing compounds followed by high-performance liquid chromatography (HPLC) of the decomposition products, and HPLC with reductive electrochemical detection. Each has its difficulties. The first, although sensitive, may lack specificity if drug metabolities are also converted to identical products, but a recently developed method surmounts this problem. The second, while providing good sensitivity and specificity, requires rigorous deoxygenation of the sample and mobile phase and an electrochemical detector, which is expensive, and may prove difficult to operate under field conditions. As an alternative to a chemical method, a bioassay may be suitable for plasma level monitoring in such circumstances. However its lack of selectivity means it is of questionable value in the determination of the pharmacokinetic parameters for individual drug-related species.

Antimalarials↗

D.L. Davies and 'Normal drinking in recovered alcohol addicts': the genesis of a paper.

This paper explores the genesis of D.L. Davie's 1962 paper on 'Normal drinking in recovered alcohol addicts' in terms of the background and training of its author and the institutional context within which he worked. Davies was born in 1911 and died in 1982. Alter a brilliant undergraduate medical career and war service in command of a military hospital, Davies joined the staff of the Maudsley Hospital in 1946 and was exposed to the intellectual influence of Aubrey Lewis. The research tradition to which he was introduced emphasised case description. The 1962 paper radically challenged perceived wisdom by purporting to describe 7 'alcohol addicts' who had achieved sustained, controlled drinking over a 7-11 year period. A subsequent follow-up of these cases suggested that Davies had been substantially mislead, and the paradox exists that a widely influential paper which did much to stimulate new thinking was based on faulty data. Some possible explanations for the occurrence of such a scientific accident are considered and the relevance of this story for the present day.

Alcohol Drinking↗

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↗

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↗