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Biomedical subjects

A N Howard

Publications and source records attributed to A N Howard.

At least 19 recordsLinked to original sources

Do hydroxy-carotenoids prevent coronary heart disease? A comparison between Belfast and Toulouse.

High intakes of antioxidants in fruit, vegetables and wine are thought to protect against coronary heart disease (CHD). Because people in Toulouse have a much lower incidence of CHD compared with Belfast, the plasma concentrations of antioxidant vitamins and carotenoids in the two populations have been compared. The major difference was in some of the plasma carotenoids. Hydroxy-carotenoids were twice as high in Toulouse in both sexes, notably lutein which occurs principally in dark green vegetables and beta-cryptoxanthin which occurs chiefly in citrus fruits. In addition, alpha-carotene was 50% higher in Toulouse, gamma-tocopherol was 50% higher in Belfast. Other plasma vitamins and carotenoids were not significantly different. If antioxidants play a role in preventing CHD, then the hydroxy-carotenoids are major candidates for further investigation.

Aged

Plasma, granulocyte and mononuclear cell copper and zinc in patients with diabetes mellitus.

The concentrations of Cu and Zn were determined in the plasma, granulocytes and mononuclear cells of 26 patients with diabetes mellitus and 26 age and sex-matched controls. In addition, Cu was measured in both washed and unwashed red blood cells, and Cu,Zn-superoxide dismutase (SOD) activity measured in washed red blood cells. Cu and Zn were determined by Zeeman-effect graphite furnace atomic absorption spectrometry following separation of plasma and red blood cells, and the white blood cell fractions (granulocytes and mononuclear cells) by density gradient centrifugation. There were no significant differences in any of the matching factors, or lipid profiles, between the groups. Plasma Zn was reduced by 17% in diabetics, compared with the controls (P = 0.0001). Neither the plasma nor the red blood cell Cu concentrations were significantly different. Of the white blood cell fractions, only mononuclear cell Cu was significantly different (30% lower in diabetics P = 0.0035, The red blood SOD activity was reduced in diabetics by over 12%, but this difference was non-significant (P = 0.0872). There was a significant negative correlation between washed red blood cell Cu and the duration of diabetes (r = -0.613, P = 0.0069). In conclusion, the copper and zinc status of these diabetic patients was reduced, providing further evidence of a role for these antioxidant trace elements in this disease.

Adolescent

Vitamin and mineral nutritional status and other biochemical data assessed in groups of men from Crevalcore and Montegiorgio (Italy).

The vitamin and mineral nutritional status of 34 elderly (mean age 77.6 +/- 4.7 years) and 39 younger subjects (mean age 41.7 +/- 7.5 years) from Crevalcore and Montegiorgio (the two rural areas of The Seven Countries Study) was studied. Comparisons have been made between centres, between age groups, and with data obtained from similar surveys performed in 1960 and 1970. Levels of thiamin and riboflavin nutritional status were higher in 1991 than in 1970. Plasma retinol values were above levels of deficiency, but vitamin E and beta-carotene tended to be low. The zinc status of the populations, as assessed by leucocyte zinc concentrations, was generally low. A decline in copper intake during the past ten years may be responsible for the low leucocyte copper concentration which was more apparent in the younger subjects. Serum cholesterol was above, and HDL cholesterol below, the European Atherosclerosis Society recommendations.

Adult

Effect of changes of water and electrolytes on the validity of conventional methods of measuring fat-free mass.

Fat-free mass was measured by hydrodensitometry, electrical impedance and total body potassium before and after water and electrolyte loss induced by (a) the administration of the diuretic frusemide, and (b) sweat loss. All methods of measuring fat-free mass were shown by pilot experiments to have procedural reliability. The diuretic caused a reduction in apparent fat-free mass of 2.63 kg by the impedance method, of 2.33 kg by hydrodensitometry and of 1.8 kg by total body potassium. Water and electrolyte loss from sweating caused a fat-free loss of 2.3 kg, 2.7 kg and 1.3 kg by the same three procedures. Urinary potassium accounted for about one fifth of the observed 40K fat-free mass loss. Each method was thus clearly sensitive to the induced water loss. These data suggest that in evaluating the composition of weight loss, existing methods of measuring body composition do not distinguish between water and other more critical components of fat-free mass. It is thus essential that stable hydration levels are established for any longitudinal comparison of weight loss by these methods.

Adipose Tissue

Studies in copper status and atherosclerosis.

Findings of this paper indicate that leucocyte copper has a significant link with the level of atherosclerosis found within the groups studied. Therefore copper may be involved in the mechanisms associated with ischaemic heart disease (IHD).

Adult

Metabolic response to low- and very-low-calorie diets.

We compared the metabolic effects of 8-wk caloric restrictions with 330 or 780 kcal/d in two groups of eight obese hospitalized subjects; six control subjects were also studied. Loss of weight but not of adipose tissue was significantly greater on the 330-kcal/d diet. It is likely that dehydration rather than protein catabolism was responsible for additional loss of fat-free mass in the 330-kcal/d group because the nitrogen deficit was not excessive. The thermic response to food was blunted only in the 330-kcal/d group whereas resting oxygen uptake decreased by equal amounts in both groups. There was a decrease in 24-h urinary noradrenaline in the 330-kcal/d group but plasma fT4 was sustained when compared with the 780-kcal/d group; fT3 decreased significantly more quickly in the 330-kcal/d group. There was no correlation between plasma hormone levels and changes in oxygen uptake. Hunger scores were greater on the 780-kcal/d diet.

Adult

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.

Adult

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.

Bile

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.

Body Weight

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.

Adolescent

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.

Basal Metabolism