[Dexfenfluramine--a new anorexic agent].
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Biomedical subjects
Publications and source records attributed to F Quaade.
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Horizontal and vertical banded gastroplasty (GP) were compared as to their effectiveness and side-effects in patients pre-treated for morbid obesity with a very-low-calorie formula diet (VLCD). The pre-treatment served to select the compliant patients, to minimize the surgical hazard, and to optimize the total weight reduction. Seventy-four consecutive patients (median age 34 years, median body weight 125.1 kg, and median overweight 93 per cent) were included according to the criteria for entry. The median weight loss on VLCD was 25.7 kg (range, 5.8-92.6 kg) and the median overweight reduction reached 46 per cent of the initial overweight (range, 9-83 per cent). Only few and mild side-effects were observed. Sixty-nine per cent of the patients fulfilled our criterion for surgery by reducing their initial overweight by at least 40 per cent. Of these, 23 and 22 patients were assigned respectively to either vertical banded or to horizontal GP. Patients and dietitians were not informed of the assignment. A significant weight loss occurred in both groups. Three months after surgery weight loss after vertical banded GP proved to be the larger (P less than 0.001). The difference became even more pronounced due to an earlier regain among patients treated with the horizontal GP. Thus, at 12 months, the net weight loss after surgery was 9.7 kg (range, -28.2-28.7 kg) in the vertical banded GP group and -1.0 kg (range, -15.0-36.5 kg) in patients treated with horizontal GP (P less than 0.0005). At this time, the total weight loss in the groups was 48.5 kg (range, 6.4-104.0 kg) and 32.6 (range, 3.7-125.1 kg) respectively (P less than 0.02), and the total reduction of overweight was greater in the group treated with vertical banded GP (80 per cent (range, 10-96) versus 56 per cent (range, 8-92), P less than 0.005). There were no deaths, and side-effects to VLCD as well as to GP were generally mild. It is concluded that vertical banded GP is more effective than horizontal GP and that the former operation adds a significant weight loss to that obtained by VLCD. The combined treatments offer a weight reduction comparable to that observed after jejunoileal bypass. However, some regain within 1 year makes it questionable if the vertical banded GP is sufficient to prevent weight regain.
From a 7-day food recording in 29 morbidly obese patients two groups of six patients each were selected: a high-energy-intake group (HEI) and a low-energy-intake group (LEI). The groups were otherwise comparable. Five lean subjects served as controls for some observations. Oral glucose tolerance tests showed that all patients in the HEI group and the lean controls had normal glucose tolerance, whereas it was abnormal in all subjects in the LEI group. The fasting metabolic rate did not differ between the obese groups but was significantly lower in the lean group. The glucose-induced thermogenesis during 180 min expressed as a percentage of the energy content of the glucose load was lower in both obese groups compared with the lean controls (lean: +11.5 per cent, HEI: +5.3 per cent and LEI: -4.2 per cent, HEI vs lean: P = 0.04 and LEI vs lean: P = 0.005), and lower in the LEI group compared with the HEI group (P = 0.02). The integrated increase in leg oxygen consumption after glucose was also smaller in the LEI group than in the HEI group (15 +/- 269 vs 987 +/- 356 ml, P less than 0.05). The arterial noradrenaline response to glucose was significantly diminished in both obese groups compared with the lean controls. Glucose induced a similar increase in leg noradrenaline release in both obese groups, whereas the arterial adrenaline level was lower in the LEI group compared with the HEI group and with the lean controls (P = 0.04). Among the obese subjects the degree of glucose intolerance was inversely correlated with the post-glucose arterial adrenaline level (r = -0.55, and P = 0.04), and positively correlated with the fractional leg adrenaline extraction (r = 0.71, and P = 0.003). The results suggest that patients who are obese in spite of a fairly low energy intake have a reduced glucose-induced facultative thermogenesis, and that the defect is at least in part located in skeletal muscle. Since the sympathetic nervous system is partly responsible for the glucose-induced thermogenesis, the reduced thermogenic response in the obese patients may be due to an impaired activation of the sympathetic nervous system. It is hypothesized that the reduced arterial adrenaline level in the LEI group is caused by hyperglycaemic suppression of the adrenomedullary secretion and further that this may be a link connecting deterioration of glucose tolerance and a thermogenic defect in obesity.
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In addition to the obligatory thermogenesis due to processing and storage, carbohydrate ingestion is accompanied by a facultative thermogenesis mediated by catecholamines via beta-adrenoceptors. The anatomical origin of facultative thermogenesis has hitherto not been determined. The possible involvement of skeletal muscle was examined in lean, healthy subjects by measuring the response in forearm oxygen consumption to an oral glucose load. The study demonstrates an early component of skeletal muscle thermogenesis coinciding with the local glucose uptake, followed by a late facultative thermogenesis. The arterial epinephrine concentration increased to a maximum of 200% above base-line values 4 h after glucose. This value greatly exceeds the physiological threshold for the thermogenic action of epinephrine. In forearm venous blood the corresponding increase in epinephrine was only approximately 50% due to enhanced peripheral extraction, which accompanies an increase in arterial epinephrine levels. Due to venous sampling previous studies have overlooked the magnitude of the late postglucose increase in arterial epinephrine, and its potential thermogenic effect has been disregarded. The facultative thermogenesis in skeletal muscle may be of importance for the regulation of body weight in humans.
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We compared the weight-reducing effect of diet and gastroplasty with that of diet alone in a randomized trial in 60 morbidly obese patients followed for two years. Initial median body weight was 120 kg in patients randomly assigned to gastroplasty plus diet and 115 kg in those assigned to diet alone. Maximum weight losses did not differ significantly between the groups (26.1 kg in the gastroplasty group and 22.0 kg in the group treated with diet alone, P greater than 0.05). The risk of a Type II error with a true difference larger than 9.5 kg was less than 5 per cent. However, the group treated with diet alone regained significantly more weight after maximum weight loss had been achieved, so that the gastroplasty group had a more favorable net outcome at two years (P less than 0.05).
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To evaluate the effect of the popular use of formula diets in the treatment of moderate obesity two regimens have been standardized: (1) formula diet replacing three of five daily meals (partial meal replacement (PMR, 1000 kcal (4.19 MJ] and (2) formula diet taken as five pre-meals (pre-meal satiation, PMS greater than or equal to 565 kcal (greater than or equal to 2.37 MJ]. Weight loss and compliance have been evaluated in a prospective 12 weeks randomized clinical trial with allocation to one of the two regimens or to a control group treated with a 1000 kcal (4.19 MJ) conventional diet (CD). CD and PMR were supported by diethylpropion (Dobesin) individually dosaged by the patient. No anorexic drugs was given to the PMS-group. Of 136 consecutively admitted patients 120 were included. After 12 weeks the median weight loss was 7.0, 8.4 and 6.1 kg in the CD-, PMR- and PMS-group, respectively (no significant differences between the groups (P much greater than 0.02]. Thirteen percent dropped out. Consumption of diethylpropion was significantly lower in the PMR-group compared with the CD-group (median 0.15 and 0.60 tablets of 25 mg per d, respectively). Even among selected sub-groups only few subjects obtained a relevant weight loss through continued treatment after the initial 12 weeks. No serious side-effects to the treatments were observed.
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Blood pressure (BP) was followed simultaneously with body weight in 134 morbidly obese patients randomized to either jejunoileal bypass (101 patients) or dietary treatment (33 patients). After a median observation time of 24 months (range 12-48 months) body weight fell significantly from a median of 124.0 kg to 81.2 kg in the jejunoileal bypass patients whilst median BP decreased significantly from 140/85 mmHg to 120/80 mmHg. In the patients treated with diet, body weight decreased significantly from a median of 129.0 kg to 119.0 kg after a median observation time of 18 months (range 9-36 months) whereas the median BP of 140/90 mmHg was unaffected. The fall in BP after weight loss was significantly positively correlated with the height of BP before the weight loss. The correlation could not be explained by a greater weight loss in the patients with initially high BP. Furthermore, a significantly positive correlation between BP changes and body weight changes was demonstrated, but this correlation was lesser than the above-mentioned. The study shows that the beneficial effect of a weight loss upon BP in obese patients is greater the higher the initial BP is, but also that a normal BP is only little affected and explained mainly by cuff artifact.
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