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Biomedical subjects

J Madsen

Publications and source records attributed to J Madsen.

At least 19 recordsLinked to original sources
PubMed1992

Metabolic changes during treatment with valproate in humans: implication for untoward weight gain.

This study was initiated to elucidate the mechanisms behind valproate-induced weight gain. Eight patients with epilepsy were studied with identical examination programs before and during the end of the first month of treatment with sodium valproate (VPA). The measurements included registration of food intake, indirect calorimetry, and determination of pancreatic and thyroid hormones, catecholamines, albumin, electrolytes, glycerol, and free fatty acids. Measurements were performed both at the basal condition and during a 3-hour oral glucose tolerance test (OGTT). After the start of VPA treatment, the mean levels during the OGTT of plasma glucose and catecholamines were significantly decreased by 7% and 25%, respectively (P less than .05). The mean ratio of insulin to glucagon decreased by 37% (P less than .01). During the glucose load, the decreases in free fatty acids were less pronounced after the start of VPA treatment, whereas the mean levels of glycerol were found to be unchanged. We detected no differences between the two periods with regard to total energy intake or macronutrient selection, energy expenditure, or thyroid hormones. As VPA is known to affect the concentration of carnitine in humans, it is hypothesized that a possible VPA-induced deficiency of the beta-oxidation of fatty acids is important for the development of obesity in epileptic patients in long-term treatment with VPA, but changes in catecholamines or other hormones might also be of importance.

Adult↗
PubMed1992

A 24-h energy expenditure study on reduced-obese and nonobese women: effect of beta-blockade.

Twenty-four-hour energy expenditure (EE) and substrate oxidation rates were studied in a respiration chamber in 15 reduced-obese (BMI = 24.7) and 8 nonobese (BMI = 20.1) women. Two experiments were performed, one in which beta-blockade was introduced by propranolol and one with placebo. When adjusted for differences in fat-free mass, no difference in 24-h EE was found between the reduced-obese and nonobese groups in placebo experiments. Propranolol reduced 24-h EE by 2.7% in the reduced-obese group whereas no reduction was seen in the nonobese group. A positive correlation was found between fasting glycerol concentration and lipid oxidation. During daytime, lipid oxidation was reduced and carbohydrate oxidation increased by propranolol only in the nonobese subjects. Propranolol reduced fasting glycerol and free fatty acid concentrations in both groups. Beta-blockade seems to have little effect on sedentary 24-h EE but may have a suppressing effect on lipid combustion.

Adult↗
PubMed1992

24-hour energy expenditure and sympathetic activity in postobese women consuming a high-carbohydrate diet.

It has been suggested that the energy expenditure (EE) of formerly obese subjects (postobese) is highly susceptible to the dietary carbohydrate content and that a high dietary carbohydrate-to-fat ratio may increase their 24-h EE. We studied eight obese women before and after weight normalization (postobese state) and compared them with eight matched controls. Twenty-four hour EE, substrate oxidations, and 24-h heart rate were measured in respiratory chambers on a fixed physical program, while the postobese and controls were in macronutrient balance on a high-carbohydrate diet. Mean 24-h EE decreased from the obese to the postobese state (P less than 0.01), but it remained higher in the postobese women than in the controls (8,292 +/- 153 vs. 7,646 +/- 190 kJ/day, P = 0.01). The higher EE in the postobese group was entirely covered by a 22% higher carbohydrate oxidation (P = 0.006). The mean 24-h heart rate, as measured by telemetry, was also higher in the postobese group than in the control group (74 vs. 66 beats/min, P less than 0.03). Plasma norepinephrine (NE) concentrations were greater by 50% in the postobese as compared with the controls (P = 0.004), and differences in plasma NE concentrations entirely accounted for the group difference in 24-h EE and heart rate between postobese and controls, as analyzed by stepwise regression analysis. We conclude that postobese women on a high-carbohydrate-low-fat diet have an enhanced sympathetic nervous system activity, which is responsible for the higher 24-h EE and heart rate. These findings may have implications for understanding the pathophysiology and for the treatment of obesity.

Adult↗
PubMed1992

Thermogenic response to epinephrine in the forearm and abdominal subcutaneous adipose tissue.

Whole body energy expenditure, thermogenic and metabolic changes in the forearm, and intercellular glucose concentrations in subcutaneous adipose tissue on the abdomen determined by microdialysis were measured during epinephrine infusion in healthy subjects. After a control period, epinephrine was infused at rates of 0.2 and 0.4 nmol.kg-1 x min-1. Whole body resting energy expenditure was 4.36 +/- 0.56 (SD) kJ/min. Energy expenditure increased to 5.14 +/- 0.74 and 5.46 +/- 0.79 kJ/min, respectively (P < 0.001), during the epinephrine infusions. Respiratory exchange ratio was 0.80 +/- 0.04 in the resting state and did not change. Local forearm oxygen uptake was 3.9 +/- 1.3 mumol.100 g-1 x min-1 in the basal period. During epinephrine infusion, it increased to 5.8 +/- 2.1 (P < 0.03) and 7.5 +/- 2.3 mumol.100 g-1 x min-1 (P < 0.001). Local forearm glucose uptake was 0.160 +/- 0.105 mumol.100 g-1 x min-1 and increased to 0.586 +/- 0.445 and 0.760 +/- 0.534 mumol.100 g-1 x min-1 (P < 0.025). The intercellular glucose concentration in the subcutaneous adipose tissue on the abdomen was equal to the arterial concentration in the basal period but did not increase as much during infusion of epinephrine, indicating glucose uptake in adipose tissue in this condition. If it is assumed that forearm skeletal muscle is representative for the average skeletal muscle, it can be calculated that on average 40% of the enhanced whole body oxygen uptake induced by infusion of epinephrine is taking place in skeletal muscle. It is proposed that adipose tissue may contribute to epinephrine-induced thermogenesis.

Abdomen↗
PubMed1992

Effect of moderate cold exposure on 24-h energy expenditure: similar response in postobese and nonobese women.

Twenty-four-hour energy expenditure (EE) and substrate oxidation rates were measured two times in eight postobese women and eight matched controls. On one occasion the subjects were exposed to a room temperature of 16 degrees C, on the other to 24 degrees C. Cold exposure elicited a 2% increment in 24-h EE (P < 0.05), with similar response in the two groups. The slight increase in EE was entirely covered by an enhanced carbohydrate oxidation rate. Fasting plasma norepinephrine (NE) increased from 0.74 +/- 0.08 to 1.29 +/- 0.21 nmol/l under cold exposure (P < 0.05), with no group difference. The cold-induced increase in 24-h EE was positively correlated to the increase in NE concentration (r2 = 0.41, P = 0.01). Sleeping EE was found to be 5% lower in the postobese women than in the controls (P = 0.04). The postobese group also had higher 24-h nonprotein respiratory quotient than the control group (P = 0.04), which was due to a 26% lower lipid-to-carbohydrate oxidation ratio. The study demonstrates that the thermogenic response to cold is normal in women susceptible to obesity, but it supports previous reports of a slightly lower basal EE and lower lipid-to-carbohydrate oxidation ratio in postobese subjects.

Adult↗
PubMed1992

The contribution of body composition, substrates, and hormones to the variability in energy expenditure and substrate utilization in premenopausal women.

Twenty-four-hour energy expenditure and substrate use were measured by indirect calorimetry in respiration chambers on a fixed physical program and related to body composition and plasma concentrations of various substrates and thermogenic hormones. Fifty premenopausal women with a wide range of body weight were examined in the follicular menstrual phase under weight stable conditions. Most of the variance in the sleeping energy expenditure (82%) was accounted for by two covariates, lean body mass (75%, P less than 0.0001), and fat mass (7%, P less than 0.0001). An additional 6% of the variance in sleeping energy expenditure was accounted for by plasma androstenedione concentration (4%, P = 0.0005) and by free T3 index (2%, P = 0.03). Thus physiological variation among individuals in plasma androstenedione concentration may result in a difference in energy expenditure of 908 kJ/day and the corresponding variation in free T3 index may result in a difference between individuals of 594 kJ/day. Fifty four percent of the variation in carbohydrate oxidation rates was accounted for by 24-h energy balance, and by plasma concentrations of insulin, nonesterified fatty acids, and estradiol. Waist circumference, plasma nonesterified fatty acids, and estradiol concentrations explained 49% of the variance in 24-h lipid oxidation. An obese subgroup of women (n = 27) had significantly higher 24-h energy expenditure, lipid, and carbohydrate oxidation rates than an age-matched normal weight group (n = 16), but the entire group difference in energy expenditure was explained by differences in body composition. We conclude that physiological variations in plasma androstenedione and T3 concentrations contribute to the interindividual variance in energy expenditure of women, and their role is not different in obese women. A positive energy balance and increased insulin action may be mediators of the higher carbohydrate oxidation in obesity, whereas an increased substrate availability seems to bring about the increased lipid oxidation.

Adolescent↗
PubMed1992

The importance of stabilizing the specimen taken at needle localized biopsy of the breast for microcalcifications.

The specimen from a needle localized biopsy of the breast must be compared with its roentgenogram to locate the area of microcalcification within the specimen. Any errors in aligning the specimen to its roentgenogram could result in failure to sample and microscopically examine the area of the microcalcifications. The results of the current study show the importance of maintaining the orientation and position of the specimen from the time the roentgenogram is taken until it is examined by the pathologist. Each of 45 consecutive specimens taken at biopsy were secured to a square of cardboard immediately after excision from the breast to maintain the orientation of the specimen during the process of roentgenography. The histologic findings of this group (group 2) were compared with the preceding 87 biopsies (group 1) in which no effort had been made to immobilize the specimen for a roentgenogram. The presence of microcalcifications was confirmed roentgenographically in all the specimens of each group. Histologic confirmation of the presence of microcalcifications was obtained in 42 of 45 specimens in group 2 and only 71 of 87 in group 1 (p = 0.035). Thirty-one per cent of specimens in group 2 contained a carcinoma compared with 10 per cent in group 1. We conclude that fixing the position of the specimen after excision improves the ability of the pathologist to locate the suspicious area of microcalcifications within the specimen. This may lead to an increase in the yield of these biopsies and the identification of occult carcinomas that might otherwise be missed.

Adult↗
PubMed1991

Thermogenic synergism between ephedrine and caffeine in healthy volunteers: a double-blind, placebo-controlled study.

Animal and human studies have suggested a thermogenic synergism between ephedrine (E), a beta-agonist, and caffeine (C), an adenosine antagonist, which may be suitable for the treatment of obesity. To study this phenomenon, the thermogenic effect of single doses of oral placebo, E 10 mg, E 20 mg, C 100 mg, and C 200 mg were compared with the effects of three different combinations of E + C, 10 mg/200 mg, 20 mg/100 mg, and 20 mg/200 mg, measured by indirect calorimetry in six healthy, lean subjects. The thermogenic effect after E + C 20 mg/200 mg was larger than that of any of the other combinations. In this dose ratio, ephedrine and caffeine exerted a supra-additive synergism, whereas the thermogenic effects of the other two combinations were only additive. The 3-hour postintake increase in systolic blood pressure after all three combinations averaged 5 to 7 mm Hg more than placebo (P less than .01), which exceeded the predicted additive effect fivefold to sevenfold. Diastolic blood pressure was not increased by E + C 20 mg/200 mg, whereas the other two combinations increased it by approximately 4 mm Hg more than placebo. E + C 20 mg/100 mg and 20 mg/200 mg increased heart rate more than placebo, while E + C 10 mg/200 mg had no effect on heart rate. As expected, all combinations increased plasma glucose, insulin, and C-peptide from their ephedrine content. No significant effects of the combinations were found on plasma lactate, glycerol, nonesterified fatty acids (NEFA), triglyceride, potassium, or sodium.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Clearance of xenon-133 from bone marrow in patients with small-cell lung cancer.

The aim of this study was to estimate bone-marrow blood flow (BMBF) in man and to correlate this with myelosuppression induced by cytostatic treatment dosed as a function of surface area. Twenty-four patients suffering from small-cell lung cancer participated in the study. Blood flow was measured with the xenon-133 washout technique. The 133Xe clearance measurement took place in conjunction with the pre-treatment bone-marrow staging procedure (ad modern Radner). Tissue samples were taken for microscopy and for the determination of the blood-to-tissue partition coefficient lambda. After the bone-marrow aspiration, 0.1-0.2 ml of 133Xe in saline was injected into the bone marrow and the cannula was removed. Following a hyperaemic phase of 12 min (7-16 min), monoexponential washouts were demonstrated. The median washout rate constant was 0.0063 min-1 (0.0038-0.0098 min-1). Lambda values of 0.3-3.5 ml g were found, but microscopy of the bone marrow showed a fairly large admixture of peripheral blood. Therefore, the lambda values should be taken with caution and absolute blood-flow values were not calculated. The results demonstrated no correlation between 133Xe clearance from crista iliaca and leucocyte or platelet suppression.

Aged↗
PubMed1991

Electrical potential difference across the stomach wall and gastric morphology in anaesthetized pigs after intravenous administration of cytotoxic drugs.

Nausea and vomiting are frequent side-effects of cancer chemotherapy. To investigate whether such therapy has an acute toxic effect on the gastric mucosa, cyclophosphamide, epirubicin and fluorouracil were administered intravenously to anaesthetized pigs. Gastric mucosal function was evaluated by continuous measurements of the gastric transmucosal electrical potential difference (PD) and the intragastric pH by using a newly developed microelectrode principle. After sacrifice, gastric histology was examined. During chemotherapy a significant decline in gastric PD was observed two hours after drug infusion, indicating a hampered gastric mucosal function. Apart from a slight hyperemia, gastric histology was normal. In this animal model a change in gastric mucosal function developed at the same time after chemotherapy as the gastric side-effects in humans.

Anesthesia↗
PubMed1990

Impaired glucose-induced thermogenesis and arterial norepinephrine response persist after weight reduction in obese humans.

A reduced thermic response and an impaired activation of the sympathetic nervous system (SNS) has been reported after oral glucose in human obesity. It is, however, not known whether the reduced SNS activity returns to normal along with weight reduction. The thermic effect of glucose was lower in eight obese patients than in matched control subjects (1.7% vs 9.2%, p less than 0.002). The increase in arterial norepinephrine after glucose was also blunted in the obese patients. After a 30-kg weight loss their glucose and lipid profiles were markedly improved but the thermic effect of glucose was still lower than that of the control subjects (4.2%, p less than 0.001). The glucose-induced arterial norepinephrine response remained diminished in the reduced obese patients whereas the changes in plasma epinephrine were similar in all three groups. The results suggest that a defective SNS may be a cause in the development of obesity.

Adult↗
PubMed1990

Caffeine: a double-blind, placebo-controlled study of its thermogenic, metabolic, and cardiovascular effects in healthy volunteers.

In humans caffeine stimulates thermogenesis by unknown mechanisms and its effect on body weight has not been studies. The effect of placebo and 100, 200, and 400 mg oral caffeine on energy expenditure, plasma concentrations of substrates and hormones, blood pressure, and heart rate was investigated in a double-blind study in healthy subjects who had a moderate habitual caffeine consumption. Caffeine increased energy expenditure dose dependently and the thermogenic response was positively correlated with the response in plasma caffeine (r = 0.52; p less than 0.018), plasma lactate (r = 0.79; p less than 0.000001), and plasma triglyceride (r = 0.53; p less than 0.02). Stepwise regression analysis with the thermogenic response as the dependent variable excluded plasma caffeine and yielded the following equation: thermic effect (kcal/3 h) = -0.00459 X heart rate + 0.30315 X (triglyceride) + 0.53114 X (lactate) + 15.34 (r = 0.86; p = 0.0001). The results suggest that lactate and triglyceride production and increased vascular smooth muscle tone may be responsible for the major part of the thermogenic effect of caffeine.

Adult↗
PubMed1990

Gastric mucosal electrical potential difference, pH, blood flow, and morphology during hypoxia and selective gastric ischaemia with and without allopurinol pretreatment in anaesthetized dogs.

Ischaemia has been implicated in the pathogenesis of gastric mucosal disorders. The aim of this investigation was to study the gastric mucosal electrical potential difference (PD), pH, blood flow and morphology during hypoxia, gastric ischaemia, and gastric ischaemia following inhibition of free radical formation with allopurinol. PD and pH were measured simultaneously with an intragastric microelectrode, and the PD values were corrected for the liquid junction potentials created by the intragastric pH variation. Blood flow was measured by the radiolabelled microsphere technique in 18 anaesthetized dogs. Short general hypoxia and short ischaemia caused reversible declines in PD, increases in pH, and no morphological damage. Ischaemia for 1 h caused a significant decline in PD persistent after reperfusion, an increase in pH, and morphological PD, but after reperfusion PD was normalized. Gross morphology was normal, and histology showed only minor damage. The results therefore support the hypothesis that oxygen-derived free radicals are involved in gastric mucosal injury occurring during ischaemia and reperfusion.

Allopurinol↗
PubMed1990

Diet-induced changes in subcutaneous adipose tissue blood flow in man: effect of beta-adrenoceptor inhibition.

The effect of a carbohydrate-rich meal on subcutaneous adipose tissue blood flow was studied with and without continuous i.v. infusion of propranolol in healthy volunteers. The subcutaneous adipose tissue blood flow was measured with the 133Xe washout method in three different locations: the forearm, the thigh and the abdomen. The subjects were given a meal consisting of white bread, jam, honey and apple juice (about 2300 kJ). The meal induced a twofold increase in blood flow in the examined tissues. Propranolol abolished the flow increase in the thigh and the abdomen and reduced it in the forearm. This indicates that the mechanism for the flow increase is elicited by a stimulation of vascular beta-adrenoceptors in the subcutaneous adipose tissue, since the beta-adrenoceptor inhibition did not affect the overall metabolic and hormonal responses to the meal.

Adipose Tissue↗
PubMed1990

Reversibility of the effects on local circulation of high lipid concentrations in blood.

Regional perfusion and vascular resistance were examined in different tissues with the radioactive microsphere technique in Göttingen minipigs before, during and after treatment with Intralipid and heparin. This treatment led to an increase in the free fatty acid/albumin molar ratio from 0.39 +/- 0.23 to 3.43 +/- 1.37. Concomitantly a decrease in regional perfusion and an increase in regional vascular resistance was found in skin, adipose tissue, skeletal muscle, kidney, the gastro-intestinal tract, the thyroid and pancreas, while heart and liver showed vasodilatation. The vascular effects were fully reversible when the free fatty acid/albumin molar ratio had normalized. This vascular effect of lipid emulsions has to be considered when patients are treated with parenteral nutrition.

Adipose Tissue↗
PubMed1990

Decreased blood perfusion in canine tibial diaphysis after filling with acrylic bone cement compared with inert bone wax.

Sixteen dogs had one tibia filled with acrylic PMMA bone cement and the opposite, control tibia filled with inert bone wax. After 1, 4, and 12 weeks, the blood perfusion in diaphyses was measured with Sc-46 labeled microspheres. The blood flow rates increased from 1 to 4 weeks and dropped to about the 1-week level after 12 weeks on both sides, with the acrylic side lower than the control side. On both sides, Disulphine Blue staining of the bones showed severe endosteal avascularity after 1 and 4 weeks and massive periosteal apposition after 4 and 12 weeks. The initial increase in blood flow is considered due to periosteal apposition, and the differences in blood flow rates are attributed to avascularity caused by the polymerization heat and toxicity of the acrylic cement.

Animals↗
PubMed1989

Epinephrine mediates facultative carbohydrate-induced thermogenesis in human skeletal muscle.

The thermic effect of carbohydrate has a component mediated by the sympathoadrenal system but of unknown anatomical localization. We have studied the contribution of skeletal muscle to the thermic effect of a carbohydrate-rich natural meal (115 g of carbohydrate, approximately 80% of energy) by means of the forearm technique on two occasions, with and without intravenous beta-blockade with propranolol. The meal-induced thermogenesis was reduced from 9.6 to 7.1% by beta-blockade (P less than 0.04), the major difference was found 90 to 240 min after the meal. The postprandial increments in plasma glucose and lactate did not change by beta-blockade, but there was a trend toward a decreased insulin response (P = 0.06). The carbohydrate-induced increase in forearm oxygen consumption was reduced by 23% after beta-blockade (P less than 0.05), the entire difference being present 90-180 min postprandially and coinciding with the peak in arterial epinephrine. The present study provides evidence of a facultative thermogenic component in skeletal muscle, mediated by epinephrine via beta 2-adrenoreceptors. However, it also points to a nonmuscle component mediated through beta 1-adrenoceptors by norepinephrine released from the sympathetic nervous system. Consequently, the sympathoadrenal system seems to play a physiological role in the daily energy balance.

Adult↗