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Biomedical subjects

C J Roberts

Publications and source records attributed to C J Roberts.

At least 199 records · Page 11Linked to original sources

The production of chromosome aberrations in Chinese hamster fibroblasts by gamma and neutron radiation.

Chromosomal aberrations were scored in V79/4 Chinese hamster fibroblasts exposed to 60Co gamma-rays and to fast neutrons produced from the 9Be(d,n)10B reaction. In oder to avoid problems with the variation of aberration induction with the phase of the cell cycle, the cells were irradiated in stationary phase, where they are concentrated in the G1 phase of the cycle. The r.b.e. for the production of dicentrics was 2.7 +/- 0.2 at a neutron dose of 2.0 Cy; the r.b.e. of the 'one-hit' component of response was 6.4 +/- 1.1. These r.b.e. values are much lower than those reported for primary human lymphocytes. Graphs of the proportion of cells without a dicentric, centric-ring or acentric fragment, as a function of dose, corresponded closely to the survival curves of the cells, which had been obtained previously, for both radiations.

Animals↗

The short term effects of propranolol, atenolol and labetalol on antipyrine kinetics in normal subjects.

1 The effects of three day courses of propranolol 40 mg three times daily, atenolol 100 mg twice daily and labetalol 100 mg three times daily on antipyrine kinetics were examined in 13 normal subjects. 2 The mean antipyrine clearance initially was 41.3 +/- 12.4 ml/min (mean +/- s.d.) and fell to 35.0 +/- 12.1 ml/min following propranolol (P less than 0.025), 34.5 +/- 9.5 ml/min following atenolol (P less than 0.01), and 35.2 +/- 8.6 ml/min following labetalol (P less than 0.05). 3 The prolongation in antipyrine half-life was significant only following atenolol. Propranolol only caused a significant reduction in the volume of distribution of antipyrine. 4 These adrenoceptor antagonists appear to decrease antipyrine clearance in normal subjects. The reduction in antipyrine clearance was similar with all three drugs and appeared to be independent of the differing lipid solubilities and pharmacological profiles of the adrenoceptor antagonists examined.

Adult↗

The influence of food on the oral and intravenous pharmacokinetics of a high clearance drug: a study with labetalol.

1 The effects of food on the pharmacokinetics of orally and intravenously administered labetalol were assessed in six healthy volunteers. 2 Food caused a 38% increase in the mean systemic bioavailability of labetalol: from 0.26 +/- 0.03 (mean +/- s.e. mean) to 0.36 +/- 0.05 (P less than 0.05). 3 Food caused 20% increases in the volume of distribution of labetalol: (from 567 +/- 63 to 685 +/- 76) and in plasma clearance (from 1923 +/- 417 to 2344 +/- 566 ml/min. These changes did not reach statistical significance. Food did not alter the plasma half-life of labetalol after oral or intravenous dosing. 4 Food appears to increase labetalol bioavailability by decreasing its first pass metabolism. It is suggested that this change results from transient alteration of hepatic blood flow. The drug should therefore be taken at a standard time in relation to meals to minimise intraindividual variation in bioavailability.

Administration, Oral↗

A study of the inhibitory effects of SCH 28080 on gastric secretion in man.

1 SCH 28080 (2-methyl-8-(phenyl methoxy) imidazo-(1-2-a) pyrine-3-acetonitrile) is a novel drug unrelated to existing anti-ulcer agents. 2 The effect of placebo and increasing doses of the drug on gastric acid output and peptic activity was examined in four healthy men, in the resting state and following pentagastrin stimulation. 3 Significant inhibition of gastric acid secretion and peptic activity occurred with the 50 mg dose in both the stimulated and unstimulated states. Approximately 90% inhibition of acid output was achieved with the 200 mg dose. 4 Antisecretory activity of SCH 28080 is confirmed in man. This drug or an analogue may have potential in anti-ulcer therapy.

Adult↗

Disposition of oral metronidazole in hepatic cirrhosis and in hepatosplenic schistosomiasis.

The pharmacokinetics of metronidazole 500 mg orally were determined in patients with hepatosplenic schistosomiasis and normal controls in the Sudan, and in cirrhotics and normal controls in Bristol. Plasma metronidazole levels were above the minimum inhibitory concentration of most susceptible anaerobic bacteria for four to six hours post-dose in all groups. Liver disease did not markedly influence the disposition of single oral doses of metronidazole. Cirrhotics showed some prolongation of metronidazole half-life, and somewhat greater metronidazole concentrations 24 hours after the dose. Concentrations of the oxidative metabolite of metronidazole were lower in Sudanese patients and normal controls than in normal British subjects. In chronic liver disease adjustment of metronidazole dosage is probably not required provided renal function is unimpaired.

Administration, Oral↗

Effects of cirrhosis and ageing on the elimination and bioavailability of ranitidine.

The plasma concentrations of ranitidine after oral and intravenous administration have been measured in 10 healthy young adults, nine cirrhotic patients, and eight healthy elderly people. In the first of these bioavailability was 51 +/- 4% and half life 161 +/- 11 minutes after oral and 124 +/- 5 minutes after intravenous administration. In the cirrhotics bioavailability was increased to 70 +/- 7%, clearance was reduced, and there was a modest increase in half life. In the elderly bioavailability was similar to that in young adults, clearance was markedly reduced, and half life was prolonged to 241 +/- 7 minutes after oral and 194 +/- 11 minutes after intravenous administration. It is predicted that blood levels in cirrhotics and the elderly would be 50 to 60% higher than in healthy young adults after repeated oral administration of similar doses.

Administration, Oral↗

Termination of twin gestation by blastocyst crush in the broodmare.

Manual crushing of one blastocyst performed on 181 bicornuate twin pregnancies between Days 24 and 45 has shown that the uncrushed blastocyst can either survive and develop normally to full term or may be rejected and resorbed like its crushed twin, depending mainly on the stage of pregnancy. Crushing, which causes rupture of fetal membranes, results in a rapid fall in the survival rate of the uncrushed blastocyst when performed after Day 31. In some mares rupture is not possible after Day 35 even if extreme pressure is used. Crushed, but unruptured, blastocysts mainly between Days 35 and 45 may (a) resorb as does the uncrushed twin (60%) (b) resorb without loss of the uncrushed twin (20%) or (c) survive, as does the uncrushed twin, even when several attempts on alternate days are made to destroy the blastocyst (20%). At no stage of pregnancy is the uncrushed embryo resorbed unless the crushed twin is destroyed. The rejection and resorption of the uncrushed twin is not due to transference of pressure, but presumably to physiological processes involving prostaglandin. Mefenamic acid appears to increase survival rates especially when crushing is performed after 31 days, although the twin of apparently successful crushings at this stage may be lost between Days 50 and 70.

Abortion, Induced↗

A fat mobilisation syndrome in dairy cows in early lactation.

High yielding dairy cows undergo a period of energy deficit in early lactation and mobilise body reserves for milk production. In this period a high proportion of cows develop moderate or severe fatty liver. Fat is deposited in other tissues at the same time, particularly skeletal muscle. The relationship between measurements of fat mobilisation and fat deposition in liver and muscle has been investigated in a group of 19 cows in the post calving period. Cows with higher levels of indices of mobilisation, namely plasma free fatty acid and D(--) -3- hydroxybutyrate concentration and subcutaneous adipose tissue loss, had higher indices of fat deposition in liver and skeletal muscle. Statistical analysis of the data indicated that fatty liver was part of a more general fat mobilisation syndrome which was not specific to any one organ or tissue.

Adipose Tissue↗

Dose-response studies of indenolol, a beta adrenoceptor blocker.

Two studies were conducted on indenolol, a new beta-adrenoceptor blocker. In the first, nine healthy men received indenolol 40, 80, 160, and 320 mg and placebo orally. Two hours later a standard exercise test was performed, and systolic blood pressure, heart rate, and peak expiratory flow rate were recorded. Indenolol induced attenuation of exercise-induced rise in systolic blood pressure and tachycardia. In the second study, seven healthy men received indenolol 40, 80, 160, and 320 mg and propranolol 40, 80, 160, and 320 mg in randomized order. Dose-response curves for both drugs revealed that maximum attenuation of exercise tachycardia and systolic blood pressure were in the same range but suggested that indenolol induced a greater response in the lower doses. Neither drug had any effect on the exercise-induced rise in peak expiratory flow rate. Indenolol was well tolerated.

Adrenergic beta-Antagonists↗

Physiological and pharmacological variability in estimated hepatic blood flow in man.

1 Changes in hepatic blood flow have been estimated by measurement of single-dose indocyanine green kinetics in groups of healthy individuals. 2 The effects of change in posture, exercise and ingestion of milk on estimated hepatic blood flow have been assessed. 3 The erect posture and exercise significantly decreased ICG clearance. However, no consistent change was noted after ingestion of milk. 4 The effects of the adrenoceptor blocking drugs phenoxybenzamine, propranolol and labetalol on hepatic blood flow were also assessed. 5 Propranolol and labetalol caused a significant fall in ICG clearance in the supine position. Phenoxybenzamine did not show a consistent change. 6 Posture, exercise and adrenoceptor blockade appear to be important variables affecting hepatic blood flow. They should be considered when kinetics of high-clearance drugs are measured, and may provide a useful model for the assessment of the effects of alterations in hepatic blood flow on the clearance of drugs.

Adrenergic alpha-Antagonists↗