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Biomedical subjects

J R Mitchell

Publications and source records attributed to J R Mitchell.

At least 181 records · Page 10Linked to original sources
PubMed1980

Changes in blood lipids and blood pressure during adolescence.

A total of 625 adolescents from three general practices participated in a cross-sectional study of cardiovascular disease risk factors. The girls had higher serum total and high density lipoprotein (HDL) cholesterol concentrations than the boys, while the boys had higher serum triglyceride concentrations. Smoking (equally prevalent in both sexes) was associated with lower HDL cholesterol concentrations, particularly in boys, while in girls use of oral contraceptives was associated with higher total cholesterol and lower HDL cholesterol concentrations showed striking associations with age, height, and sexual maturation in boys, but not in girls. Triglyceride concentrations were associated with age in boys. Systolic blood pressure and serum urate concentrations were higher in boys and rose steeply with age, but no age association was seen for urate concentrations or systolic blood pressure in girls or for diastolic pressures in either sex. Girls, however, had higher diastolic pressures. There was a strong association between urate concentration and the other cardiovascular disease risk factors, especially HDL cholesterol. Adolescence is associated with considerable changes in cardiovascular disease risk factors, and there are striking sex differences in these changes.

Adolescent↗
PubMed1980

Randomised trial comparing propranolol with atenolol in immediate treatment of suspected myocardial infarction.

The value of beta-blockade for suspected acute myocardial infarction was assessed by determining the six-week and one-year mortality rates in patients started on propranolol, atenolol, or placebo immediately on entry to a coronary care unit. A total of 388 patients entered this double-blind, randomised study, and when analysed on the basis of the initial, intention-to-treat categories there was no significant difference between the three groups in respect of the mortality rate at one year. There was, however, a high withdrawal rate from the trial; the reasons for this illustrate problems of physician compliance and interpretation of data, which are common to all early-entry trials of haemodynamically active agents in acute myocardial infarction.

Adult↗
PubMed1980

Platelet-release reaction in myocardial infarction.

A study was made of the platelet-release reaction in heparinised platelet-rich plasma taken from 26 patients, of whom 22 had sustained a definite and four a possible myocardial infarction, and from 54 age-matched controls. No significant differences in reaction were observed between the two groups. Signficant differences were seen, however, between eight patients who died within a year after infarction and the controls (P less than 0.01) and the remaining 18 patients who survived (P = 0.02). These differences were abolished when sodium citrate was included in the experimental procedure. Poor prognosis was thus related to an increased platelet-release reaction after infarction.

Adenosine Diphosphate↗
PubMed1980

Isoniazid hepatoxicity: the relationship between covalent binding and metabolism in vivo.

The relationship between the hepatotoxicity and metabolism of isoniazid and its metabolites, acetylisoniazid and acetylhydrazine, has been investigated. Toxic doses of acetylisoniazid and acetylhydrazine, radiolabeled in the acetyl group, were found to bind covalently to liver protein in vivo. This binding was mediated by the microsomal enzyme system as indicated by the effects of pretreatments altering the activity of these enzymes. Metabolic studies revealed that the pretreatments increased the metabolism of the acetylhydrazine moiety of acetyl-labeled acetylisoniazid and of acetylhydrazine itself by the microsomal enzyme system. Pretreatment with the acyl amidase inhibitor, bis-p-nitrophenyl phosphate, inhibited the hydrolysis of acetylisoniazid to isonicotinic acid plus acetylhydrazine and concomitantly decreased the covalent binding of acetyl-labeled acetylisoniazid. The changes in the metabolism of isoniazid, acetylisoniazid and acetylhydrazine effected by various pretreatments paralleled changes in the severity of the hepatic necrosis caused by the compounds. These results strongly suggest that acetylhydrazine is the metabolite responsible for the hepatic necrosis caused by isoniazid and that mirosomal metabolism of acetylhydrazine in vivo leads to the production of a reactive acylating species capable of reacting covalently with tissue macromolecules.

Acetylation↗
PubMed1980

The effects of age and glutathione depletion on hepatic glutathione turnover in vivo determined by acetaminophen probe analysis.

We have validated a method to assess hepatic glutathione turnover in individual animals in vivo. This method would be applicable to man by collection of bile samples via nasoduodenal intubation. The rate of glutathione turnover was calculated from the time course of the specific activity of the glutathione-acetaminophen adduct in bile after the administration of a radiolabeled glutathione precursor and a small dose of acetaminophen. Identical results were obtained with radiolabeled glutathione or with radiolabeled cysteine, glutamic acid or glycine as the precursors. The small dose of acetaminophen administered to trap glutathione as an excretable adduct did not stimulate glutathione turnover, which reflects glutathione synthesis under steady-state conditions. No evidence for two pools of glutathione with different half-lives was found; previous reports of two glutathione pools may have failed to account for hepatic protein turnover with subsequent release of radiolabeled amino acids for glutathione synthesis. In male rats, the rate of glutathione turnover decreased from 0.52 per hr at 6 weeks of age to 0.12 per hr at 24 weeks of age. After acute depletion of glutathione by diethylmaleate, the rate of glutathione turnover promptly doubled in all age groups. Similar increases in the rate of glutathione synthesis and in the ability to stimulate glutathione production in response to acute depletion in children might explain their decreased susceptibility to acetaminophen hepatotoxicity.

Acetaminophen↗
PubMed1979

The effect of agents which modify platelet behaviour and of magnesium ions on thrombus formation in vivo.

The ability of potential anti-thrombotic agents to modify platelet-thrombus formation in injured cerebral arteries in the rabbit was tested. Low doses of heparin were without effect, while higher doses produced variable suppression of white body formation but at the expense of bleeding. Aspirin did not inhibit white body formation but another non-steroid anti-inflammatory agent, flurbiprofen was able to do so, as was the anti-gout agent, sulphinpyrazone. Magnesium salts both topically and parenterally, suppressed thrombus formation and increased the concentration of ADP which was required to initiate thrombus production at minor injury sites.

Animals↗
PubMed1979

Acute pulmonary injury in rats by nitrofurantoin and modification by vitamin E, dietary fat, and oxygen.

The subcutaneous administration of nitrofurantoin to rats caused severe pulmonary damage, characterized by edema, congestion, and hemorrhage. The acute lethality of the drug was greater in rats fed vitamin E-deficient diets high in polyunsaturated fats as compared to rats fed the NIH open-formula diet. The survival times of vitamin E-deficient rats were increased if such animals were fed diets supplemented with vitamin E and/or diets containing saturated fat (lard) for 3 weeks before administration of nitrofurantoin. The toxicity of nitrofurantoin was enhanced in both the rats deficient in vitamin E and in those given vitamin E supplements and exposed to O2-enriched atmospheres. These results, in conjunction with previous metabolic studies in vitro showing redox cycling and O2 activation in rat lung microsomes in the presence of nitrofurantoin, illustrate certain similarities with the lung-toxic herbicide, paraquat, and raise the question of whether the 2 agents may be capable of damaging lungs by a common mechanism.

Animals↗