Biomedical subjects
A N Howard
Publications and source records attributed to A N Howard.
The lack of evidence for a hypocholesterolaemic factor in milk.
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Lymphocyte thyroid hormone receptors in obesity.
Triiodothyronine (T3)-receptor characteristics of isolated circulating human mononuclear cells have been studied in a group of obese patients who claimed to be unable to lose weight on conventional 4.2 MJ (1000 kcal) diets. The cells of the obese patients exhibited a lower receptor capacity than those of a control group of non-obese subjects but the difference was not significant. There was a significant fall (P less than 0.01) in receptor capacity in the obese patients after 12 weeks in a 1.34 MJ (320 kcal) per d formula diet and this provides a further mechanism whereby a fall in metabolic rate takes place in response to severe dietary restriction. Some patients who also received T3 (60 micrograms/d) in addition to the formula diet showed a further fall in the receptor numbers. These findings may partly account for the previously reported resistance to thyroid hormones in obesity.
Gemfibrozil--the effect of biliary cholesterol saturation of a new lipid-lowering agent and its comparison with clofibrate.
Clofibrate is known to increase cholesterol saturation of bile and the prevalence of gallstones. We studied 10 healthy volunteer subjects to determine the effect of gemfibrozil (a new lipid-lowering agent) on biliary cholesterol saturation and to compare it with that of clofibrate. Biliary cholesterol saturation indices were calculated on fasting duodenal bile samples collected before and after administration of each drug for 4 weeks using a 4-week "washout" period between each preparation. There was a statistically significant rise in the cholesterol saturation index from a control value, taken as the mean of 2 samples, of 1.226 (0.785--1.526), median (range), to 1.547 (0.807--1.781) after clofibrate, P less than 0.05, but the rise to 1.352 (0.840--2.686) after gemfibrozil was not significant. However, direct comparison of the cholesterol saturation indices on clofibrate and gemfibrozil revealed no statistically significant difference. Only prospective clinical trials will establish definitively the risk of cholelithiasis on gemfibrozil but these results suggest that this drug is unlikely to have an advantage over clofibrate in this respect.
The historical development, efficacy and safety of very-low-calorie diets.
The development of very-low-calorie diets (VLCD) over the lats 50 years is described, from the early work of the Pittsburgh group in 1930, using conventional food, to the present day liquid-formula diets containing all essential nutrients. Recent work has been concerned with the protein requirements of obese patients consuming 200-400 kcal (0.8-1.6MJ) VLCD. Independent studies indicate that the protein requirement is about 40-55 g/day without carbohydrate, and about 25-30 g/day when carbohydrate (30-45 g/day) is included. Although some workers use VLCD consisting only of protein, the author prefers those also containing carbohydrate because they prevent excessive ketosis, hyperuricemia, diuresis, electrolyte loss, re-feeding oedema, and may improve muscular endurance. Numerous clinical trials have shown VLCD to be highly effective in about 80 per cent of outpatients and give an average weight loss of 2 kg/week which is comparable to that seen in complete starvation. Clinical studies of up to 16 weeks and longer in numerous medical schools in Europe have demonstrated their safety in patients under medical supervision. Whilst the achievement of a normal body weight in most obese patients is now a reality, the main problem for the future is to achieve permanent weight loss.
Low-dose mianserin as adjuvant therapy in obese patients treated by a very-low-calorie diet.
A double blind trial examined the effects of low doses of the anti-depressant compound mianserin (10 mg nocte, Organon, Oss, Holland) on dietary compliance and weight loss in 45 obese subjects treated by a very-low-calorie diet (VLCD, 320 kcal (1.34 MJ)/day) for 16 weeks. The total mean weight loss of the 25 patients who completed the trial was 15.5 kg +/- 6.1 s.d. There was no significant difference in weight loss between the groups. More patients taking placebo (54 per cent vs 38 per cent) completed the experiment. Three patients stopped mianserin because of drowsiness, but were able to continue on the VLCD alone. Beck rating scores decreased (indicating less depression) in both groups by 50 per cent after eight weeks. With the linear self-rating scale there was no change in the placebo group but the mianserin group reported feeling less depressed (P less than 0.001). No significant changes were observed in ECG and routine clinical and laboratory tests. It is concluded that VLCD can be a safe and acceptable means of achieving substantial weight loss over several months. Patients do not become more depressed during treatment and there is no clinical advantage to be gained by the routine additional use of low doses of mianserin.
Treatment of obesity with triiodothyronine and a very-low-calorie liquid formula diet.
In a double-blind trial physiological doses (60 microgram/day) of triiodothyronine (T3) were compared with placebo in a group of obese patients on a 320 kcal/day (1.34 MJ) liquid formula diet. T3-treated patients had a significantly greater weight-loss by the 12th week. Analysis of serum levels of T3 and thyroxine (T4) showed that those patients in the placebo group whose weight-loss tended to level off at a plateau towards the end of the trial also had the lowest T3 levels and resting metabolic rate (RMR) at that time. Patients in the T3 group had a steady rise in serum T3 levels during the 12 wk period. Those with the highest final T3 levels had the greatest tendency for their weight-loss to level out and, paradoxically, had the least suppression of serum T4 levels and lowest RMR. Some obese patients who do not readily lose weight on conventional low-calorie diets may have an impaired metabolic clearance rate of T3 and a degree of T3 resistance.
Effect of milk products on serum-cholesterol.
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Safety of liquid-protein diets.
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The hypocholesterolemic effect of terbufibrol and other drugs in normal and hypercholesterolemic baboons.
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The effects of ascorbic acid and flavonoids on the occurrence of symptoms normally associated with the common cold.
A controlled study was made of the effects of natural orange juice, synthetic orange juice, and placebo in the prevention of the common cold; both natural and synthetic orange juices contained 80 mg of ascorbic acid daily. Three-hundred sixty-two healthy normal young adult volunteers, ages 17 to 25 years, were studied for 72 days with 97% of participants completing the trial. There was a 14 to 21% reduction in total symptoms due to the common cold in the supplemented groups that was statistically significant (P less than 0.05). Ascorbic acid supplementation also increased the number of "episode-free" subjects. However, the clinical usefulness of the results does not support prophylactic ascorbic acid supplements in the well-nourished adult. The results in this study with both natural and synthetic orange juice of physiological content of ascorbic acid, are similar to those obtained using a "megadose" of ascorbic acid.
Hypocholesterolaemic effect of soya.
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Thyroidal hormone metabolism in obesity during semi-starvation.
Six obese subjects were studied over a period of 12 weeks whilst on a 1260 kJ (300 kcal) formula diet. Weight loss was initially rapid, but later slowed markedly despite good patient compliance. The basal metabolic rate (BMR) fell in all patients during the study. Plasma triiodothyronine fell in all patients, whilst the plasma half-life of thyroxine increased. Plasma thyroxine, reverse triiodothyronine (reverse T3) and the serum prolactin and thyrotropin response to thyroliberin all showed no significant change.
The treatment of obesity with a very-low-calorie liquid-formula diet: an inpatient/outpatient comparison using skimmed-milk protein as the chief protein source.
Fifty obese patients were givena 1.34 MJ (320 kcal) formula diet (containing 44 g/day carbohydrate, milk protein supplying 24--29 g protein/day in a total of 31 g/day, fat 2 g/day and the RDA of minerals and vitamins) for four to 12 weeks, either as inpatients (22) or outpatients (28). This regime was followed by a 3.35 MJ (800 kcal) conventional diet as outpatients. All but six outpatients completed the trial. Substantial weight losses were achieved in all patients with a total mean loss of 8.4 kg at four weeks and 11.0 kg at eight weeks. At four weeks the mean weight loss was 9.6 kg for inpatients and 7.2 kg for outpatients (P less than 0.05). There was no statistical difference in weight between the groups at eight weeks. Patients who continued on the 1.34 MJ formula diet for 12 weeks continued to lose weight but those on the 3.35 MJ conventional diet did not. Nitrogen-balance studies were carried out on the inpatients. During the first four weeks there was a small net loss of nitrogen (56 g, equivalent to 350 g protein) but equilibrium was achieved by the fifth or sixth week. There was no evidence of protein deficiency as judged by unchanged serum total protein, albumin, haemoglobin, RBC and PCV. Equilibrium between intake and excretion of sodium and potassium was also achieved throughout, and serum electrolytes were unchanged. A large number of other routine clinical and laboratory tests showed the treatment was safe. Serum bilirubin was elevated (18--48 per cent) and increased slightly above normal in two outpatients. Serum cholesterol was decreased by 21 per cent and triglycerides by 45 per cent after three weeks. Serum lipids in hyperlipaemic patients were normalised. It is concluded that the very-low-calorie formula diet provides a safe and very effective method of weight reduction, and the advantages of hospital compared with outpatient treatment are small.
Studies on intravenous phosphatidyl choline preparations; their effects on lipolytic enzymes in the normal rabbit.
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Hypocholesterolaemic effect of milk.
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Hypocholesterolaemic effect of milk.
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The baboon as an experimental model in drug testing.
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