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Biomedical subjects

R Hughes

Publications and source records attributed to R Hughes.

At least 181 records · Page 10Linked to original sources

Some direct and reflex cardiovascular actions of prostacyclin (PGI2) and prostaglandin E2 in anaesthetized dogs.

1 The aim of the study was to determine the mechanism of the hypotension and bradycardia produced by prostacyclin (PGI2). 2 Haemodynamic studies were carried out in nineteen open-chest beagle dogs anaesthetized with chloralose. PGI2 was infused intravenously or into the left atrium. 3 Infusions of PGI2 either intravenously or into the left atrium equally reduced arterial pressure and total peripheral resistance but bradycardia was greater after infusion into the left atrium. 4 Comparison of effects of PGI2 with those of prostaglandin E2 (PGE2) showed that although left atrial infusions both reduced aortic pressure and total peripheral resistance, PGE2 always increased heart rate, cardiac output and maximum acceleration. 5 Similar effects were observed with sodium nitroprusside except that it always caused tachycardia and reduced stroke volume. 6 Atropine (0.05 or 1 mg/kg i.v.) reduced or reversed the bradycardia induced by PGI2 but its hypotensive effects were reduced only after 1 mg/kg atropine. After vagotomy changes in cardiac output, stroke volume and maximum acceleration were increased, the hypotensive effects of PGI2 were reduced and the bradycardia was reversed; effects induced by PGE2 were not significantly altered. 7 The hypotension induced by prostacyclin is due to two components, a direct relaxation of vascular smooth muscle and a reflex, non-cholinergic vasodilatation. The bradycardia is reflex in nature and is partially mediated by the vagus pathway.

Anesthesia↗

Neuropathy in thoracic scoliosis.

The erector spinae muscles of 20 normal humans were evaluated at C7, T3, T11, and L5 vertebral body levels bilaterally. At each level, the mean potential duration of the motor unit action potential was calculated. This control group was compared with a group of patients with C7 and L5 radiculopathy and with a group of patients with thoracic scoliosis. The mean potential durations of the radiculopathy group at the C7 and L5 levels were prolonged as were those values at the convex thoracic levels in the scoliotic group. Muscle biopsy of the erector spinae in the scoliotic group revealed grouped atrophy and changes consistent with a neuropathic process. A radiculopathic process was associated with idiopathic thoracic scoliosis and involved the convex side. It was maximal near the apex of the curve.

Action Potentials↗

A comparison of the turnover and metabolism cholesterol in normal and atherosclerotic monkey aortas.

Rhesus monkeys were fed high cholesterol and cholesterol-free diets for 21-24 months. The animals were then given isotopic cholesterol intravenously and autopsied from 1 to 51 weeks later. The plasma and aortic cholesterol contents were 633 +/- 130 mg/dl and 35.6 +/- 11.4 mg/g dried tissue (45.5% in ester form) for atherosclerotic monkeys and 135 +/- 25 mg/dl and 9.9 +/- 3.6 mg/g (15.0% in ester form) for control monkeys, respectively. The minimal influx rate of cholesterol from plasma into the aorta was much greater for atherosclerotic animals, 0.470 +/- 0.20 mg/g per day versus 0.088 +/- 0.031 for control monkeys. There was a rapid turnover of both free and esterified cholesterol in the atherosclerotic aortas, greater than for normal aortas. These studies of cholesteryl ester metabolism indicated a likely origin of aortic cholesteryl ester from the plasma cholesteryl esters. Our data indicated a dynamic cholesterol metabolism and turnover in the aorta during atherogenesis.

Animals↗

On the pathogenesis of mitochondrial myopathies. An experimental study.

The intra-arterial injection of 2-4 dinitrophenol, an uncoupler of oxidative phosphorylation, resulted in the production of ragged red fibers. The ultrastructure of these fibers showed intramitochondrial paracrystalline inclusions, laminar and fingerprint bodies. Antimycin A and oligomycin injection (which inhibit mitochondrial respiration) only caused swelling and disruption of the mitochondria. An increase in muscle lactic acid, decrease in ATP, glycogen and phosphocreatine was observed after the injection of all these agents. This indicates that lactic acidosis has no significant role in the pathogenesis of mitochondrial pathology. It is concluded that mitochondrial changes are a morphological expression of uncoupled but intact mitochondrial respiration.

Animals↗

Interaction of halothane with non-depolarizing neuromuscular blocking drugs in man.

1 Tetanic and single twitch contractions of the adductor pollicis muscles, in response to indirect stimulation of each ulnar nerve, were recorded in patients anaesthetized with thiopentone and nitrous oxide in oxygen. 2 Concentrations of 1 and 2% halothane were administered for 10 min during recovery from neuromuscular paralysis by tubocurarine, dimethyl tubocurarine and gallamine. 3 During exposure to halothane, the peak contraction of the tetanic response was reduced and tetanic fade was increased whereas the single twitch was unaffected. 4 The effects of halothane on the tetanic responses were readily antagonized by intravenous neostigmine preceded by atropine. 5 Halothane could act post-synaptically by a non-depolarizing block or by desensitizing the post-synaptic receptors, but a pre-synaptic action seems more likely since neuromuscular block was only evident when tetanic stimulation was applied. Such an effect could be caused by impairment of the release of acetylcholine.

Anesthesia↗

Albumin-coated Amberlite XAD-7 resin for hemoperfusion in acute liver failure. Part II: in vivo evaluation.

Albumin-coated Amberlite XAD-7 has been previously shown to be blood compatible in in vitro hemoperfusion experiments whith human blood. In this study, the preliminary results are reported on single hemoperfusions with albumin-coated XAD-7 resin in four patients with acute liver failure. The mean platelet count was 116+/-SE 16.3% of the initial arterial value and the mean white cell count was 96+/-SE 6.5% of initial at the end of four hours of hemoperfusion. Removal of bilirubin, phenols and substances in the middle molecular weight range by the resin was demonstrated. These preliminary results suggest albumin-coated Amberlite XAD-7 resin to be blood compatible and capable of removing protein-bound and middle molecular weight substances from patients with acute liver failure. Further clinical evaluation of repeated resin hemoperfusion is required to determine whether this treatment will be beneficial to patient survival.

Acrylic Resins↗

Prostacyclin (PGI2) induces coronary vasodilatation in anaesthetised dogs.

Prostacyclin (PGI2), the predominant metabolite of arachidonic acid in isolated hearts, relaxes strips of bovine coronary artery and is a potent vasodilator in isolated perfused hearts. We have examined the actions of prostacyclin on coronary blood flow in open chest dogs anaesthetised with chloralose. An electromagnetic flow probe was fitted to the left circumflex artery and phasic coronary flow, mean coronary flow (a measure of coronary volume flow over 4 s intervals), and coronary vascular resistance were recorded together with aortic pressure and heart rate. Intravenous infusion of prostacyclin (0.05 to 1.0 microgram.kg.1.min.1), reduced coronary vascular resistance and aortic pressure according to dose, but had only small effects on phasic coronary flow or mean coronary flow. Both tachycardia and bradycardia occurred during infusion of prostacyclin, but 6-oxo-prostaglandin F1alpha (infused at 10 micrograms.kg-1.min-1), the stable degradation produce of prostacyclin, had no cardiovascular effects. The coronary vasodilator effects of prostacyclin were clear when it was injected into the left circumflex artery via a fine catheter distal to the flow probe. Prostacyclin (0.05 to 0.5 microgram) increased phasic coronary flow and mean coronary flow up to 3 fold and reduced coronary vascular resistance without affecting aortic pressure or heart rate, although higher doses had systemic effects. Prostaglandin E1 (0.1 to 0.5 microgram), which also dilated the coronary vessels, had a longer lasting effect and was 1 to 4 times more potent than prostacyclin. Prostaglandin E2, (0.5 to 4 microgram) was less potent than prostacyclin. In four dogs prostacyclin (20 to 500 micrograms) applied epicardially to the left ventricle caused marked and prolonged coronary vasodilatation. Epicardial application of prostacyclin (10 to 25 micrograms) to the right ventricle increased coronary sinus oxygen content with minimal changes in blood pressure. The endoperoxide prostaglandin H2 was a coronary vasodilator of similar potency to prostacyclin, but its analogue U46619 is a vasoconstrictor. Inhibition of cyclo-oxygenase with indomethacin (5 mg.kg-1 i.v.) or sodium meclofenamate (2 mg.kg-1 i.v.) potentiated the coronary dilator effects of prostacyclin given intravenously or into the coronary artery. Cyclo-oxygenase inhibition did not alter the hypotensive effects and increased the coronary vasodilator potency of prostacyclin relative to prostaglandin E2. Thus the sensitivity of the coronary vascular bed to prostacyclin is enhanced when endogenous biosynthesis of prostaglandin-like substances is inhibited. Although the importance of arachidonic acid metabolites in the coronary circulation still requires validation in vivo, it is clear that prostacyclin, and not prostaglandin E2, is the prostaglandin most likely to be involved.

Animals↗

Studies on replacement and suppressive dosages of 1-thyroxine.

Serum thyrotropin (TSH) levels were studied in 55 hypothyroid patients in order to determine adequate replacement and suppression dosages of 1-thyroxine (T4). In accordance with previous reports it was found that most patients had normal TSH levels and were clinically euthyroid at daily doses of 0.10-0.15 mg T4. None of the patients required a dose exceeding 0.20 mg. When the TSH levels normalized, serum thyroxine and serum triiodothyronine also fell to levels within their normal ranges. The effectiveness of various doses of T4 in suppressing the temporary rise in serum TSH concentration normally induced by thyrotropin-releasing hormone was examined in 57 patients treated with T4 for atoxic goitre or after subtotal surgical removal of such a goitre. The rise in TSH was not usually inhibited by a T4 dose of less than 0.20 mg, a finding which at least theoretically has implications for the adequate suppressive dose of T4.

Female↗

Transient changes in plasma digoxin concentration and the development of cardiotoxicity.

1. Eight dogs were given two infusions of digoxin 0.1 mg/kg, one over 9 min and the other one over 90 min in a randomized sequence, allowing at least 12 days between each experiment. 2. Digoxin plasma profiles reflected the rate of digoxin infusion, the peak concentration of drug attained at the end of each infusion being considerably higher but more transient after the 9 min than after the 90 min transfusion. 3. Digoxin reduced the amount of acetylstrophanthidin required to produce electrocardiographic evidence of cardiotoxicity. This increase in cardiac sensitivity at 150 and at 360 min after the start of the digoxin infusion was independent of rate of infusion. 4. These results suggest that the development of cardiotoxicity is dependent upon the quantity of digoxin delivered into the systemic circulation regardless of the plasma concentration. 5. By inference, cardiotoxicity is related solely to the amount and not the rate of absorption from a given dose of digoxin.

Animals↗

A study of swine dysentery by immunofluorescence and histology.

Twenty-six specific-pathogen-free pigs were fed pure cultures of Treponema hyodysenteriae. Five untreated pigs were controls. Distribution of this large spirochete in pigs with swine dysentery was shown by the indirect fluorescent antibody technique. Findings by this method were compared with those from dark-field examination of colonic mucosal scrapings and from tissue sections. The cultures caused mucohemorrhagic colitis which by 10 days after inoculation was indistinguishable from the colitis of swine dysentery. Control pigs remained normal. Pigs killed when spirochetes were first seen in the feces had normal colonic mucosa with only a few spirochetes. At the first sign of diarrhea, however, the colonic mucosa was thicker than normal and had many spirochetes. T. hyodysenteriae was confined to regions of hypertrophy and exudation of the large intestine mucosa throughout the course of disease.

Animals↗

The usefulness and reliability of a drug severity scale.

This paper reports on the interrater reliability of a previously developed method for measuring severity of multidrug use. This method is based on interviewer's ratings of the number of different drugs used, the frequency of use, and the length of use of each drug. The results show that relatively unsophisticated raters in comparison with trained and experienced raters are able to utilize the drug severity form with a minimum of error.

Humans↗