Biomedical subjects
R W Stout
Publications and source records attributed to R W Stout.
Lipoproteins, insulin and glycaemic control in diabetes.
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Dibutyryl cyclic AMP inhibits LDL binding in cultured fibroblasts and arterial smooth muscle cells.
The interaction of low density lipoproteins (LDL) with cell membrane receptors is regulated by certain hormones. To test whether LDL receptor activity is influenced by cyclic AMP, the effect of dibutyryl cyclic AMP on LDL binding uptake and degradation was studied in cultured human skin fibroblasts and in rat and human arterial smooth muscle cells. Dibutyryl cyclic AMP in concentrations of 10(-3) to 10(-7)M inhibited LDL binding and degradation in fibroblasts and rat arterial smooth muscle cells, and degradation in human arterial smooth muscle cells. Inhibition of LDL receptor activity by dibutyryl cyclic AMP did not appear to be due to a non-specific toxic effect of the nucleotide. It appeared to be mediated on the affinity of the receptor for LDL rather than receptor number.
The significance of cardiac arrhythmias in the aged.
Twenty-four-hour ambulatory electrocardiography was performed in 25 young and 29 active elderly subjects. Sinus bradycardia and sinus arrhythmia were common in the young but uncommon in the elderly. Ventricular and supraventricular premature beats and brief runs of supraventricular tachycardia were common in the elderly but uncommon in the young. Complex ventricular arrhythmias only occurred in the elderly but brief episodes of nocturnal Wenckebach AV block were quite common in young and old alike. No significant difference in arrhythmia frequency was found between elderly subjects with heart disease and those without heart disease or between elderly subjects without symptoms and those with non-episodic symptoms such as dizziness. None of the arrhythmias in the young or elderly subjects was associated with symptoms. In follow-up at 30 months, only one elderly subject was deceased (from pneumonia) and none had suffered a stroke or heart attack. It is concluded that transient cardiac arrhythmias are commoner in the elderly than in the young. However, their long-term significance remains unknown, but it is likely that they are relatively benign.
The effect of age and sex on the response of enteropancreatic polypeptides to oral glucose.
Enteropancreatic polypeptide responses during a 50 g oral glucose tolerance test were studied in 10 young men, 10 young women, 10 elderly men and 10 elderly women. Elderly females had higher gastric inhibitory polypeptide (GIP) responses to oral glucose than elderly males. Elderly males and females had higher fasting and post-glucose human pancreatic polypeptide (HPP) levels than young males and females. N-Glucagon-like immunoreactivity (N-GLI) responses differed between the young and elderly. In the young, N-GLI levels fell after oral glucose but in the elderly they rose. Post-glucose C-glucagon-like immunoreactivity (C-GLI) responses were higher in elderly females than in young females. The significance of the higher plasma levels of GIP, N-GLI and C-GLI following oral glucose in elderly females compared to elderly males is unclear.
Cardiac arrhythmias and femoral neck fracture.
Nineteen of 45 consecutive patients admitted to hospital with fracture of the neck of femur had ambulatory electrocardiography performed on the fourteenth post-operative day. The frequency of cardiac arrhythmias was compared with control subjects who had undergone total hip replacement operations. No significant difference was found. None of the cardiac arrhythmias in the fracture or control subjects was associated with symptoms. Two fracture patients and three control subjects suffered an acute myocardial infarct peri-operatively and were excluded from the study. Fracture patients on drug therapy for heart disease had an increased six-month mortality rate compared with those not on such therapy. Episodic cardiac arrhythmias do not appear to be an important contributory factor to fracture of the neck of femur in the elderly.
Is ambulatory electrocardiography a useful investigation in elderly people with 'funny turns'?
Episodic diffuse cerebral symptoms and unexpected falls were investigated by ambulatory electrocardiography in nine men and 19 women aged 65 years or more. Eight subjects with episodic dizziness or syncope had cardiac arrhythmias which are known to be capable of causing these symptoms and four of these had symptoms at the time of the arrhythmia. However, only one was detected by ambulatory electrocardiography alone. No significant arrhythmias were found in any of the remaining subjects. When 17 symptomatic subjects were compared with 17 age- and sex-matched asymptomatic controls, cardiac arrhythmias known to be capable of causing symptoms were commoner in the symptomatic group, but the differences were not statistically significant. Ambulatory electrocardiography is of no more value than standard electrocardiography in the detection of arrhythmias associated with diffuse cerebral symptoms in elderly people.
Are cardiac arrhythmias important in stroke?
Ambulatory electrocardiography was performed on 21 consecutive acute stroke patients on the day of admission and 14 and 42 days later. There was no statistically significant difference in cardiac arrhythmias between stroke patients and a group of age- and sex-matched controls. There was considerable variation in the frequency of cardiac arrhythmias on each day but none of the arrhythmias was associated with a sudden deterioration in the condition of the patients and no arrhythmias produced symptoms in either the stroke or the control groups. Fourteen per cent of stroke patients had an associated acute myocardial infarction and 57% had a history of previous heart disease. While a history of previous heart disease or the occurrence of major ventricular arrhythmias were associated with an increased six-week mortality rate, routine continuous monitoring of cardiac rhythm would not appear to be of value in acute stroke.
Teaching geriatric medicine at the Queen's University of Belfast.
Undergraduate teaching at the Queen's University, Belfast, takes place in the fourth year of a five year curriculum. It lasts three weeks and this is divided into two parts. First, held within the university department, is topic-based teaching including seminars, discussions, case histories and visits. The second phase of two weeks consists of attachment of two to four students to geriatric medical units both in and outside Belfast. The whole of this module is situated within a combined course involving community medicine, general practice, geriatric medicine and mental health lasting 12 weeks and involving one-third of the year of 150 students each time. In addition to the three weeks teaching in geriatrics, joint discussion groups are held.
Cyclic AMP: a potent inhibitor of DNA synthesis in cultured arterial endothelial and smooth muscle cells.
The effect of dibutyryl cyclic AMP on DNA synthesis was studied in cultured human umbilical endothelial cells and rat aortic smooth muscle cells. Dibutyryl cyclic AMP (2 X 10(-4) mol/l) inhibited DNA synthesis in both arterial cell types when they were grown in medium supplemented with whole serum or with platelet poor serum, but had no effect in the absence of serum. An effect was seen one hour after the addition of the nucleotide, and the threshold concentration was between 2 X 10(-6) and 2 X 10(-5) mol/l. These results may have relevance to the interaction of platelets and insulin with the arterial wall in the development of atherosclerosis in diabetes.
Glucose inhibits replication of cultured human endothelial cells.
Diabetes is an important risk factor for atherosclerosis but the mechanism of the risk is unknown. As endothelial injury is considered to be an early event in the development of atherosclerosis, the effect of glucose on endothelial cell replication was studied. Concentrations of glucose of 11.2, 16.8 and 22.4 mmol/l inhibited DNA synthesis in cultured human umbilical venous endothelial cells by 8.1 +/- 10.8, 24.3 +/- 8.8 and 30.9 +/- 7.4%, respectively. Glucose also inhibited the proliferative response of endothelial cells to experimental wounds in the cell layer. Sorbitol (22.4 mmol/l) inhibited endothelial cell DNA synthesis by 50 +/- 13.6%, but mannitol (22.4 mmol/l) inhibited DNA synthesis by only 3 +/- 24.3%. It is suggested that in diabetic subjects, high blood glucose levels may cause endothelial injury, or inhibit its repair, and hence allow the exposure of the arterial media to plasma and its constituents.
Glucose tolerance in the elderly: the role of insulin and its receptor.
Oral glucose tolerance tests were performed in young and elderly subjects with minimal risk factors for diabetes mellitus. Compared to the normal glucose tolerance in the young there was a 45% rate of impaired tolerance in the elderly. Fasting insulin levels were significantly lower in the elderly but post-glucose insulin responses in the first hour were similar in young and elderly subjects. Peripheral insulin action was assessed in terms of the 125 monoiodoinsulin binding to specific insulin receptor sites on circulating lymphocytes in the young, the elderly and a group of age and sex matched obese maturity-onset diabetics. Specific insulin binding was not significantly different in the elderly than in the young but was significantly lower in the diabetics than the young and the elderly. The results suggest that neither defective insulin binding are major causative factors in the reduced glucose tolerance of the elderly.
Integrated medical student teaching. A combined course in community medicine, general practice, geriatric medicine and mental health.
In order to provide "horizontal" integration of related clinical subjects, a combined teaching course in community medicine, general practice, geriatric medicine and mental health has been devised. The course lasts 12 weeks and is divided between joint teaching of topics of common interest and clinical clerkships in individual disciplines. A joint assessment takes place at the end of the course. The course was popular with students who all felt that it covered topics not encountered in other parts of the medical curriculum. A course of this type leads to a better integration of clinical subjects and avoids repetition or omission of topics which are not clearly the responsibility of any individual department.
Hyperinsulinaemia as an independent risk factor for atherosclerosis.
There is both epidemiological evidence that elevated insulin levels are associated with clinical atherosclerosis and experimental evidence that insulin has actions on the arterial wall which may be relevant to the development of atheromatous lesions. This paper reviews the evidence and puts forward the hypothesis that insulin may have a role in the pathogenesis of atherosclerosis. If this hypothesis is correct, measures to reduce insulin levels, including weigh reduction, exercise and improved methods for treating diabetes, may contribute to the prevention of atherosclerosis.
Effect of a low dose estrogen-progestogen oral contraceptive on lipids and lipoproteins.
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The role of insulin in atherosclerosis in diabetics and nondiabetics: a review.
Disease of coronary, cerebral, and peripheral arteries is associated with exaggerated insulin responses to oral glucose. In three populations, high fasting or post-glucose insulin levels have a predictive value in the incidence of ischemic heart disease and in cardiac mortality. Diabetics who are obese or who have received treatment with insulin have elevated insulin levels and, as a group, have an increased incidence of cardiovascular disease. Insulin, in small concentrations, has effects on arterial tissue including stimulation of smooth muscle cell proliferation and of glucose incorporation into lipid. It is suggested that insulin has a role in the development of atherosclerosis.
Sex hormone levels in younger male stroke survivors.
Increased plasma oestrogen levels have been reported in men with myocardial infarction. To establish whether similar findings occur in stroke, plasma oestradiol and testosterone levels were measured in 26 male survivors of stroke and 27 healthy male controls. There was no difference in oestradiol or testosterone levels between the two groups and the oestradiol : testosterone ratio was also identical. The result of this study does not support the suggestion that hyperoestrogenaemia is a risk factor for atherosclerosis in general.
Control of DNA synthesis in cultured vascular endothelial and smooth muscle cells--response to serum, platelet-deficient serum, lipid-free serum, insulin and oestrogens.
Endothelial and smooth muscle cell proliferation has an important role in the pathogenesis of atherosclerosis. To study the effect of serum and some of its putative growth factors on DNA synthesis, the incorporation of thymidine into DNA was studied in cultured human umbilical endothelial and rat aortic smooth muscle cells. DNA synthesis in endothelial cells was progressively stimulated by increasing concentrations of human serum, maximum stimulation occurring with 20% serum. Foetal calf serum had a much lesser effect on DNA synthesis in endothelial cells. Smooth muscle cells responded equally to human and foetal calf serum. Exposure to serum prepared to exclude the platelet-derived growth factor resulted in reduced DNA synthesis in smooth muscle cells. However, endothelial cells increased DNA synthesis in platelet-poor serum. Serum from which lipid had been extracted stimulated DNA synthesis less well than whole serum in both endothelial and smooth muscle cells. Insulin stimulated DNA synthesis in smooth muscle cells but not in endothelial cells, while ethinylestradiol, estrone and estriol had no effect on DNA synthesis in either type of cell. Thus cultured endothelial and smooth muscle cells differ in their requirements for human serum and in their response to platelet factor and to insulin.