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Biomedical subjects

M D Rawlins

Publications and source records attributed to M D Rawlins.

At least 91 records · Page 5Linked to original sources
PubMed1988

The effect of age upon the affinity of microsomal mono-oxygenase enzymes for substrate in human liver.

Although the clearance of many oxidized drugs falls with age, a corresponding fall in the maximal activities of drug metabolizing enzymes has not been noted. The possibility of a fall in enzyme affinity for substrate with age, which could account for the observed changes, has not previously been investigated in human liver. We have studied the kinetics of the microsomal mono-oxygenase 7-ethoxycoumarin-O-de-ethylase in 17 human liver biopsy specimens. No correlation was observed between age and microsomal protein recovery, maximal enzyme activity or apparent enzyme affinity. Since microsomal mono-oxygenase activities and affinities appear not to change in human liver, other factors such as a fall in liver volume or blood flow must be responsible for the decline in clearance of many oxidized drugs which occurs with ageing.

7-Alkoxycoumarin O-Dealkylase↗
PubMed1988

Reversal of histamine-induced bronchoconstriction by the H1-receptor antagonist levocabastine: a potential model for efficacy in anaphylaxis.

1. The rate of onset and magnitude of the effect of levocabastine, a potent H1-receptor antagonist, in reversing histamine-induced bronchoconstriction were determined in a double-blind cross-over trial against saline placebo. Histamine was administered by nebuliser so that forced expiratory volume in 1 second (FEV1) was reduced to 80-75% of baseline FEV1 in 10 men with mildly or moderately responsive airways and the effects of intravenous injection of saline or saline + 200 micrograms levocabastine were studied. 2. The maximum rate of recovery of FEV1 was 7[2-10]% min-1 (median [range]) in the first 5 min after levocabastine injection, but only 4[1-7]% min-1 after saline alone (P less than 0.05). 3. The median area under the recovery curve of FEV1 from 0 to 30 min after injection was 405 [228-498]% basal FEV1 X min after levocabastine and 301[98-502]% basal FEV1 X min after saline alone (P less than 0.002). 4. FEV1 returned to 90% of baseline within 30 min in all subjects after levocabastine, but not after saline alone (P less than 0.002). 5. Histamine-induced bronchoconstriction was relieved more quickly by levocabastine than saline alone. This model may have application to the study of drugs used in the treatment of anaphylaxis.

Adult↗
PubMed1988

Review of yellow cards (1986): report to the Committee on the Safety of Medicines.

1. In 1986 the CSM received 15,527 yellow cards. This was the highest number received in any one year since the scheme started in 1964. Much of the increase was due to the use by doctors of the yellow cards now included in the British National Formulary and NHS prescription pads. 2. The overall profile of reports of serious reaction, in 1986, was broadly similar to that of the previous years. The most commonly reported serious suspected adverse reactions involved the gastro-intestinal tract (801 reports), the skin (539 reports), the central nervous system (535 reports), and the blood (505 reports). 3. Of the drugs introduced between 1984 and 1986 appreciable numbers of reports of serious reactions were received in association with the use of diltiazem (33 reports), mitozantrone (30 reports), enalapril (173 reports) and etodolac (27 reports).

Drug-Related Side Effects and Adverse Reactions↗
PubMed1988

Impaired beta-cell responses improve when fasting blood glucose concentration is reduced in non-insulin-dependent diabetes.

Pancreatic beta-cell responses to a controlled intravenous glucose stimulus in 18 untreated non-insulin-dependent diabetic patients were compared with those in seven healthy control subjects. The patients' first-and second-phase responses were only 10 to 20 per cent of those of the normal subjects. However, when normal subjects had been hyperglycaemic for two hours, their first-phase responses were similar to those of the patients. Six patients were subsequently treated by diet alone, six by diet and tolbutamide and six by diet and metformin. There was no improvement in first-phase responses after treatment, but second-phase responses doubled. Improved responses were seen with all treatments, and correlated with the fall in fasting blood glucose concentration during treatment. This study supports the view that hyperglycaemia impairs beta-cell function and suggests that first-phase responses are more sensitive to hyperglycaemia than second-phase responses.

Adult↗
PubMed1987

Effects of intradermal bradykinin after inhibition of angiotensin converting enzyme.

Inhibitors of angiotensin converting enzyme may cause angio-oedema. To see if this might be due to potentiation of the tissue effects of bradykinin the thickness of weals raised by intradermal injection of saline or 1, 3, or 10 micrograms bradykinin was measured before and three times after single doses of captopril, enalapril, or placebo. The mean thickness increased with increasing doses of bradykinin. It did not change with time after the administration of placebo or captopril but increased from 0.61 mm before enalapril to 1.12 mm two and a half hours and 1.06 mm five hours after enalapril was given. Five subjects flushed when given bradykinin after captopril and four after enalapril, but none flushed when given bradykinin after placebo. It is concluded that angiotensin converting enzyme inhibitors potentiate the effects of intradermal bradykinin in vivo and that this may partially explain why they cause angio-oedema in susceptible patients.

Adult↗
PubMed1987

Plasma esterase activity in patients with aspirin-sensitive asthma or urticaria.

Plasma aspirin esterase activity and cholinesterase activity were reduced in patients with aspirin sensitive asthma and aspirin sensitive urticaria compared to asthmatic and dermatological controls. Phenylacetate (non specific) esterase activities, were however unaltered in these patients. The reason for the lower activity is uncertain but it does not appear to be due to genetically determined lower cholinesterase or due to the avoidance of aspirin by sensitive patients. A low aspirin esterase activity may be a contributory factor in precipitating these aspirin sensitive reactions.

Aspirin↗
PubMed1987

7-Ethoxyresorufin deethylase (EROD) in human liver--the effect of alcoholic liver disease.

We have investigated the effect of alcoholic liver disease (ALD) on the metabolism of 7-ethoxycoumarin 0-deethylase in human liver microsomes. EROD activity was significantly reduced in tissue from ALD patients who smoked, compared to smoking controls. A similar trend was seen in non-smokers. These results have implications for the metabolism of environmental carcinogens.

Adult↗
PubMed1987

The effect of age on mono-oxygenase enzyme kinetics in rat liver microsomes.

The clearance of many oxidized drugs falls with age. Whilst factors such as reduced liver size, blood flow and specific enzyme activity may be important, the possibility that reduced enzyme affinity for substrate contributes to this fall has not hitherto been investigated. Using liver microsomes from 12 young adult and 12 elderly male Norwegian Brown rats we defined the kinetics of ethoxyresorufin-O-de-ethylation and aldrin epoxidation, specific substrates for the 3-methylcholanthrene inducible and phenobarbitone inducible forms of cytochrome P450, respectively. Our results show a marked fall in the maximal activity of both enzymes in advanced age whether expressed in terms of microsomal protein or unit of cytochrome P450, but with no change in apparent enzyme affinity (Km). Since Km is unchanged, we feel that qualitative age-related changes in cytochrome P450 are unlikely. Reduced metabolism may be due to age-related alterations in coenzymes or smooth endoplasmic reticulum lipid membranes.

Aging↗
PubMed1987

Age and self-poisoning: the epidemiology in Newcastle upon Tyne in the 1980s.

The epidemiology of 737 consecutive self-poisoning admissions to Freeman Hospital, Newcastle upon Tyne, has been investigated with reference to age in young (less than 35), mid-aged (35-64) and elderly (greater than or equal to 65 year) patients. The most important differences were increased formal psychiatric illness in the elderly, demonstrated by increased likelihood of admission to psychiatric units; less likelihood of overdose with multiple agents in the elderly, and less use of alcohol. There were also differences in the types of drugs used. The youngest patients took more paracetamol and less psychoactive drugs and more of their drugs were prescribed for a relative than the other two groups. The elderly were much less likely to receive gastric lavage or emesis and more likely to receive supportive treatment only than younger patients. This difference may, in part, be explained by the more frequent occurrence of benzodiazepine poisoning in those over 65 years.

Adolescent↗