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Biomedical subjects

A Holmes

Publications and source records attributed to A Holmes.

At least 181 records · Page 10Linked to original sources
PubMed1982

Concentrations and characteristics of amphibole fibres in the lungs of workers exposed to crocidolite in the British gas-mask factories, and elsewhere, during the second world war.

Concentrations and length distributions of uncoated and coated amphibole fibres in the lungs of 27 workers at the Leyland, Nottingham, and Blackburn gas-mask factories were measured after death with the light microscope using the membrane filter technique. Measurements were also made on a worker exposed to crocidolite at the Chemical Defence Experimental Establishment, Porton, and on three miners from the Wittenoom mine in Western Australia where the crocidolite used in the manufacture of military respirators is reputed to have originated. In selected cases, fibre concentrations and dimensions were also measured with the electron microscope. All but two subjects died with a mesothelial tumour. Fibre concentrations ranged from 7 x 10(4) to almost 10(9) fibres/g dry weight. There appeared to be no relation between latent period and fibre concentration. The significance of the wide range of fibre concentrations which was associated with the development of mesothelial tumours is discussed and also the relation between the relative frequency and dimensions of uncoated and coated fibres.

Aged↗
PubMed1981

Novel synthesis of (S)-1-[5-(benzoylamino)-1,4-dioxo-6-phenylhexyl]-L-proline and analogues: potent angiotensin converting enzyme inhibitors.

A new approach was developed for the synthesis of (S)-1-[5-(benzoylamino)-1,4-dioxo-6-phenylhexyl]-L-proline (1) and 23 analogues. The delta-(acylamino)-gamma-keto acid intermediates were obtained by a modified Dakin--West reaction using 3-carbomethoxypropionyl chloride. Acylation of L-proline and recrystallization of the mixture of diastereomers gave the optically pure title compound in three reaction steps. The in vitro angiotensin converting enzyme (ACE) inhibitory activity of 1 was confirmed. Some of the novel analogues (6, 11, 13, and 17) were also found to be potent inhibitors of ACE in vitro with an IC50 of 1.4-8.8 x 10(-9) M (IC50 for captopril = 0.9 x 10(-8) M). In vivo these compounds (6, 11, 17, and 18) were much less active than captopril, especially by the oral route. Against angiotensin I (AI) challenge in normotensive conscious rats, 1 and 6 produced less than 50% inhibition at 30 mg/kg po but 57 to 82% inhibition at 3 mg/kg iv. Inhibition by both routes lasted less than 1 h. In renal hypertensive rats, 1 and 15 of its analogues failed to produce significant blood pressure lowering effects, in contrast to the marked effects of captopril. Near maximum inhibition of AI was achieved by continuous intravenous infusions of 1 and 20, suggesting that limited oral activity may by due to degradation and/or clearance.

Angiotensin II↗
PubMed1980

Purification of plasma vitamin D metabolites for radioimmunoassay.

The ability of four solvent systems to extract tritiated 25-hydroxy vitamin D3, 24,25-dihydroxy vitamin D3, 25,26-dihydroxy vitamin D3 and 1 alpha, 25-dihydroxy vitamin D3 from plasma was compared. Diethyl ether gave the highest yield of metabolites and lowest yield of "lipid" materials, the dihydroxylated metabolites were more readily extracted than 25-hydroxy vitamin D3. Following extraction with ether the vitamin D metabolites could be separated, without prior purification, on a 6.2 mm X 250 mm Zorbax-Sil high pressure liquid chromatography (HPLC) column, a simplification of previous methods. Plasma 1 alpha, 25-dihydroxy vitamin D levels measured after purification by this method were not significantly different from those obtained by an established, more complex method.

24,25-Dihydroxyvitamin D 3↗
PubMed1980

Concentrations and dimensions of coated and uncoated asbestos fibres in the human lung.

Concentrations and length distributions of uncoated and coated amphibole-type fibres in samples of human lung taken at necropsy were measured by optical microscopy using the membrane filter technique that enables fibres with diameters down to about 0.2 micron to be detected. The subjects included 10 who died with mesothelial tumours, three with lung cancer, and eight of other causes. Measurements of fibre concentrations are compared with those of other workers. It can be deduced from the length distributions that fibres less than 5 microns long are cleared from the lung more efficiently than longer ones. The clearance of short fibres appears to be inhibited in subjects with asbestosis, however. The length distributions of uncoated and coated fibres were dissimilar. In general, few fibres less than 10 microns in length were coated and few greater than 40 microns in length were uncoated. The probability of a fibre of given length, however, becoming coated varied considerably from subject to subject. Possible reasons for this are discussed.

Adult↗
PubMed1979

Axial muscle and myocutaneous flaps: a recent concept in wound closure.

Until the last decade, the greatest advances in reconstructive surgery have been skin grafting and the advent of pedicle flaps. More recently a new understanding of the discrete vascular anatomy of the skin and other composite tissues has enabled the transfer of these tissues with far more reliability, either locally or--using microvascular techniques--to a distance. The axial and random concept of blood supply of flaps will be outlined. A brief historical background of the development of axial flaps is included. A synopsis of the anatomy, uses and limitations of the commonly used and proven muscle and myocutaneous flaps in our experience is reported. In the final discussion, a new and simple classification of wound closure is proposed which encompasses all the recent developments in this field.

Axilla↗
PubMed1979

An improved method for the measurement of red cell survival using non-radioactive chromium.

An improved technique for the measurement of red cell survival is described in which non-radioactive 50Cr is used in patients for whom radioactive labels are not advisable. The 50Cr was measured by neutron activation analysis using a high resolution germanium (lithium) diode gamma-ray spectrometer. In adult controls, the values obtained were in the range accepted as normal for the 51Cr method, and double labelling experiments showed close agreement. The application of this technique to the measurement of red cell survival in pregnant women suspected of having haemolytic anemia is described.

Adolescent↗
PubMed1978

Significance of fibre length in the clearance of asbestos fibres from the lung.

Rats were exposed by inhalation to radioactive anthophyllite asbestos. Animals were then killed serially over a period of 205 days and the fibre content of the lungs measured radiometrically. The lungs were subjected to selective bronchopulmonary lavage and the mean fibre content determined of free cells recovered from the alveolar spaces. The length distributions of fibres recovered from the lungs by lavage, and of those remaining in the lungs following lavage, were measured. Short (less than 5 micrometer) fibres are cleared from the lung via the conducting airways more efficiently than longer fibres and fibres exceeding 50 micrometer in length are not removed from the lungs by this route. Although fibres of about 200 micrometer in length were present in all the lungs examined, the longest which could be recovered by lavage, once fibre deposited in the airways had been cleared, was only about 100 micrometer decreasing to 60-70 micrometer after 205 days. It is suggested that long fibres are more liable than short to penetrate the alveolar wall as they tend to bridge the alveolar ducts and alveoli.

Animals↗
PubMed1977

Retention, distribution, and excretion of lead by the rat after intravenous injection.

The distribution and excretion of lead was studied during a period of about a week after a single intravenous injection of 203Pb as chloride accompanied by less than 1 microng of lead carrier. The peak concentration in venous blood was reached after about an hour when it contained 35 to 40% of the administered activity. The subsequent decline in concentration was much more rapid than is observed in man. The main storage organs were the kidneys and bone. Initially, 20% of the dose could be accounted for in the kidney and the biological half-life was about 100 hours. The level in bone built up rapidly at first and then more slowly. After a week, between 25 and 30% of the dose was present in bone.

Age Factors↗
PubMed1977

The biological effects of magnesium-leached chrysotile asbestos.

Chrysotile asbestos was leached in N hydrochloric acid for varying times to produce a range of magnesium-depleted samples. The protein adsorptive capacity, the haemolytic activity, and the capacity to cause selective release of acid hydrolases from macrophages were measured for the various samples in vitro. The carcinogenicity of the same materials was determined following intrapleural inoculation in rats. The adsorptive capacity for albumin decreased linearly with magnesium removal. The haemolytic activity also declined until about half the magnesium had been removed, after which there was little further change. The selective release of acid hydrolases from macrophages in culture increased up to the point at which half the magnesium had been removed but by 90% depletion had declined rapidly. The carcinogenicity of 50% -depleted chrysotile was similar to that of intact, but at 90% depletion the incidence of mesothelial tumours had fallen considerably. There was no evidence that the leached samples fragmented more than the unleached in vivo.

Adsorption↗
PubMed1976

Computerization of a large antenatal serology service.

A computer scheme for a large antenatal serology service is described. A primary request form (for mother, father or child) has been developed. Standard reports are produced by the computer and are issued with a tear-off slip which should accompany subsequent specimens. Complicated reports are made by special letter. An instruction booklet is issued to all users. Information on patients and clinically significant antibodies is held in a special computer file and is regularly updated. The system provides an efficient and reliable day-to-day service and readily accessible data for retrospective research. A brief note on the computer elements of the system is provided.

Computers↗
PubMed1975

Cardioselective beta-adrenergic blocking agents. 1. 1-((3,4-Dimethoxyphenethyl)amino)-3-aryloxy-2-propanols.

A series of 1-amino-3-aryloxy-2-propanols has been synthesized and examined for cardioselective beta-blockade. The introduction of the (3,4-dimethoxyphenethyl)amino group lead to the most cardioselective agents. Structure-activity relationships are discussed. Of the compounds tested 1-[(3,4-dimethoxyphenethyl)amino]-3-(m-tolyloxy)-2-propanol was selected for clinical trial because of optimal potency and selectivity.

Adrenergic beta-Antagonists↗