PubMed Health⌕ Search

Biomedical subjects

L Simonsen

Publications and source records attributed to L Simonsen.

At least 73 records · Page 4Linked to original sources
PubMed1994

Inter-relationships between single carbon units' metabolism and resting energy expenditure in weight-losing patients with small cell lung cancer. Effects of methionine supply and chemotherapy.

The one-carbon unit metabolism was investigated in 8 weight-losing patients with small cell carcinoma of the lung (SCLC). At diagnosis, 6 of the 8 patients had elevated formiminoglutamic acid (FIGLU) excretion after a histidine load, suggesting a lack of one-carbon units. In accordance, a significant decrease of FIGLU excretion was observed in the patients after oral administration of DL-methionine for 4 days. The elevated FIGLU excretion was positively correlated to weight loss prior to diagnosis and negatively correlated to serum albumin at time of diagnosis. After 3 months of combination chemotherapy, FIGLU excretion was reduced in all patients except 1, who had progressive disease. Despite the elevated FIGLU excretions, all patients had normal blood folate levels. The resting energy expenditure (REE) was recorded in 7 patients, and a significant, positive correlation was observed between pretreatment FIGLU excretion and REE, although the REE measured in this group of patients was within the normal range. These data demonstrate an increased demand of "active" one-carbon units in energy consumption in a group of weight-losing cancer patients. The one-carbon unit deficit was reconditioned by oral administration of the one-carbon unit donor DL-methionine.

Aged↗
PubMed1994

Glucose-induced thermogenesis in patients with small cell lung carcinoma. The effect of acute beta-adrenergic inhibition.

Seven patients with histologically verified small cell lung carcinoma were given an oral glucose load of 75 g on two occasions to examine the effect of glucose on whole body and forearm thermogenesis with and without acute beta-adrenergic inhibition with propranolol. Whole body energy expenditure was measured by the open circuit ventilated hood system. Forearm blood flow was measured by venous occlusion strain-gauge plethysmography. The uptake of oxygen in the forearm was calculated as the product of the forearm blood flow and the difference in arteriovenous oxygen concentration. The glucose-induced thermogenesis in the 120 min following the glucose load was significantly reduced by beta-adrenergic inhibition with approximately 50% from 63.9 +/- 5.8 kJ 120 min-1 (mean +/- SE) to 27.8 +/- 9.8 kJ 120 min-1 (P < 0.01). Almost the entire reduction took place from 60 to 120 min (P < 0.005). The integrated glucose-induced forearm oxygen uptake in the period 60-120 min following the glucose load was significantly reduced after beta-adrenergic inhibition from 103 +/- 28 mumol 100 g-1 60 min-1 to 29 +/- 29 mumol 100 g-1 60 min-1 (P < 0.05). The noreadrenaline concentration in the arterial blood was not increased in the baseline period compared to healthy elderly; it increased following the glucose load while there was no demonstrable increase in adrenaline concentration in the two experiments. It is suggested that these patients have increased sensitivity of the beta-adrenergic receptors and an early facultative component of the glucose-induced thermogenesis in part takes place in the forearm.

Aged↗
PubMed1994

Adipose tissue metabolism in humans determined by vein catheterization and microdialysis techniques.

A technique for catheterization of a vein draining abdominal subcutaneous tissue and a microdialysis technique that allows measurements of intercellular water concentrations in adipose tissue in humans have recently been described. In the present study, we compare the two techniques during an oral glucose load. In addition a technique using microdialysis for measurement of tissue oxygen and carbon dioxide tensions is described. Microdialysis and vein catheterization were performed in the same region on the abdomen, and the subcutaneous adipose tissue blood flow was measured by the local 133Xe washout method. The results show that subcutaneous adipose tissue gas tensions are on level with gas tensions measured in abdominal venous blood. Comparison of metabolite concentrations measured in the venous blood and venous blood concentrations calculated from microdialysis data shows that there is good agreement between the concentrations obtained by the two techniques with respect to glucose and glycerol, whereas lactate concentrations are very different. With regard to substrate fluxes calculated by Fick's principle, the catheterization technique is probably the most reliable, considering the numerous assumptions on which calculations of venous concentrations from microdialysis data are based. Advantages and disadvantages of the two techniques are discussed.

Abdomen↗
PubMed1994

Methodological approach to the evaluation of neurotoxicity data and the classification of neurotoxic chemicals.

This text is the result of the authors' involvement in a working group on criteria for the identification and classification of neurotoxic chemicals. (The work of the group does not necessarily represent the official stand of the affiliated institutes.) A definition of neurotoxicity and criteria for evaluating studies dealing with neurotoxicology are presented. The evaluation is a stepwise process that ends with assigning the chemicals to groups depending on the available evidence for neurotoxicity (ie, neurotoxic, probably neurotoxic, possibly neurotoxic, probably not neurotoxic, or not classifiable). Finally, the description of the potency of neurotoxic chemicals is briefly discussed. The model has been tested by evaluating selected research papers on the following 10 chemicals: manganese, aluminum, tetrahydrofuran, cyclohexanone, dichlorvos, trichloroethylene, formaldehyde, tri-ortho-cresyl phosphate, n-hexane, and vinyl chloride. There was sufficient evidence for classifying five of the ten chemicals (aluminum, manganese, n-hexane, trichloroethylene, tri-ortho-cresyl phosphate) as definitely neurotoxic to humans, and three were considered to be possibly neurotoxic to humans (dichlorvos, tetrahydrofuran, vinyl chloride). Cyclohexanone and formaldehyde were not classifiable according to the model.

Animals↗
PubMed1993

Sensory-evoked potentials as indices of neurotoxicity in the rat: effect of 4-tert-butyltoluene.

The use of evoked potentials to measure neurotoxicity was evaluated using 4-tert-butyltoluene (TBT) as a test compound. Male Wistar rats were habituated to the recordings of auditory- and flash-evoked potentials until the combined waveform of the evoked potentials reached a steady state. The rats were then divided into three groups and exposed to 0, 50 and 150 ppm TBT for 6 h, and the auditory- and flash-evoked potentials were measured for up to 288 h after exposure. Event-related potentials specifically associated with the temporal pairing of auditory and visual stimuli were not apparent in the recordings. The peak-to-peak values of selected components, integrated amplitude and power spectra of the waveforms in exposed rats were significantly different from control values for at least 288 h in the group exposed to 150 ppm TBT and for 120 h in the group exposed to 50 ppm TBT. It is concluded that evoked potentials may be used for detection and characterization of minor neurofunctional changes due to low-dose exposure to chemicals.

Acoustic Stimulation↗
PubMed1993

Glucose-induced thermogenesis in patients with small cell lung carcinoma. Before and after inhibition of tumour growth by chemotherapy.

Seven weight-losing patients with histologically verified small cell lung carcinoma were given an oral glucose load of 75 g before and at least 3 weeks after the end of chemotherapy to examine the effect of glucose on whole body and skeletal muscle thermogenesis before and after reduction of tumour. Whole body energy expenditure was measured by the open circuit ventilated hood system. Forearm blood flow was measured by venous-occlusion strain-gauge plethysmography. The uptake of oxygen in skeletal muscle was calculated as the product of the forearm blood flow and the difference in a-v oxygen concentration. Whole body resting energy expenditure (REE) did not increase, it was 4.4 +/- 0.3 kJ min-1 (mean +/- SE) before chemotherapy and 4.4 +/- 0.2 kJ min-1 after chemotherapy. The glucose-induced thermogenesis in the 180 min following the glucose load was 93.6 +/- 9.9 kJ 180 min-1 before chemotherapy. This is significantly increased compared to that found in a healthy control group (74.7 +/- 4.8 kJ 180 min-1, P < 0.02). The glucose-induced thermogenesis was significantly reduced to 47.7 +/- 10.2 kJ 180 min-1 (P < 0.05) after chemotherapy. The oxygen uptake in resting skeletal muscles was 6.9 +/- 0.3 mumol 100 g-1 min-1 before chemotherapy and 7.0 +/- 0.7 mumol 100 g-1 min-1 after chemotherapy. This did not increase during the first 90 min following the glucose load in either investigations. In the period 90-180 min following the glucose load, the oxygen uptake was significantly increased before chemotherapy as compared to after chemotherapy, which suggests that the reduced whole body thermogenesis after chemotherapy in part was due to reduced skeletal muscle thermogenesis.

Adult↗
PubMed1993

Local forearm and whole-body respiratory quotient in humans after an oral glucose load: methodological problems.

The effects of an oral glucose load of 75 g on the local forearm and whole-body energy thermogenesis were measured in normal subjects during the 4 h after the glucose intake. Simultaneous assessment of substrate metabolism in the forearm was performed. Energy expenditure (EE) increased after the glucose load and had not returned to baseline level at the end of the experiment. Whole-body respiratory quotient (RQ) was, on average, 0.80 (SD 0.05) in the baseline condition and increased to a maximum of 0.91 (0.03) and then decreased to baseline level at the end of the experiment. The local forearm oxygen uptake increased 30 min after the glucose intake and remained elevated during the rest of the experiment. The carbon dioxide output from the forearm did not increase before 90 min after the glucose load. Consequently the local forearm RQ decreased significantly from a baseline value of 0.86 (0.17) to 0.63 (0.17) 30 min after the glucose load (P < 0.05). Ninety min after the glucose load RQ increased to a maximum level at 0.95 (0.22) and decreased then gradually to baseline level. The experiments emphasize several methodological problems in the measurement of local forearm RQ. The whole-body RQ and local forearm RQ are not significantly different in the fasting state. The finding of a decrease in local forearm RQ below 0.70 30 min after the glucose load probably indicates a non-steady state in the carbon dioxide exchange. Thus, indirect calorimetry cannot be applied locally during short time periods.

Adult↗
PubMed1993

Aerosolized pentamidine for primary prophylaxis of Pneumocystis carinii pneumonia: a controlled, randomized trial.

The objective was to assess the efficacy of a biweekly dose of 60 mg aerosolized pentamidine (AP) for primary prophylaxis (PP) of Pneumocystis carinii pneumonia (PCP) and the impact of prophylaxis on survival in HIV-infected patients. Participants were AIDS patients with no history of PCP, patients with a CD4 count < or = 0.200 x 10(9)/L, or patients belonging to the CDC group IVC2, irrespective of CD4 count. It was an open, randomized, controlled trial. Patients were assigned to receive AP, 60 mg biweekly via a System 22 nebulizer, or to a control group not receiving any prophylaxis. Incidence curves for PCP and survival were generated using the Kaplan-Meier method, stratified by treatment group, and compared using the log-rank test. Data were analyzed according to intention to treat. There were 15 cases of PCP among 105 patients in the AP group and 32 cases among 104 patients in the control group. The cumulative incidence of PCP by 18 months was 13% (95% CI 5-21%) in the AP group and 30% (95% CI 18-41%) in the control group, (p = 0.002). During the study period 19 patients (18%) in the AP group died and 24 patients (23%) in the control group (NS; p = 0.28). We conclude that a biweekly dose of 60 mg AP is efficient as primary PCP prophylaxis when a System 22 nebulizer is used. There was, however, no difference in survival between the groups, suggesting that AP has an impact on morbidity only.

AIDS-Related Opportunistic Infections↗
PubMed1993

Contribution of skeletal muscle and adipose tissue to adrenaline-induced thermogenesis in man.

Elevated plasma adrenaline is known to increase whole body energy expenditure. We studied the thermogenic effect and the effects on substrate utilization in man during infusion of adrenaline. Two series were performed: in one series skeletal muscle metabolism was investigated and in another series subcutaneous adipose tissue metabolism was investigated. In both series Fick's principle was applied. Intravenous infusion increased blood flow, glucose uptake and oxygen uptake in both skeletal muscle and adipose tissue. It is concluded that skeletal muscle contributes about 40% and adipose tissue about 5% of the whole body adrenaline-induced thermogenesis.

Adipose Tissue↗
PubMed1992

A strategy for delineating risks due to exposure to neurotoxic chemicals.

A method for delineating the risks due to exposure to neurotoxic chemicals based upon the linkage of four national computer-based registers is described. The four registers are: the Danish Product Register database, PROBAS; Register of air pollution measurements in Danish workplaces, ATABAS; Register of notified occupational diseases; and Register of work force. Based on the information from the four registers, risk profiles for neurotoxic chemicals in 69 industrial groups were generated. The risk profiles describe the number of neurotoxic chemicals, their potency, the number of exposure measurements exceeding the occupational exposure limit (OEL), and the total and relative number of diseases caused by the chemicals in each group. Based on this linkage, twelve industries are noted to be potentially at high risk due to exposure to neurotoxic chemicals; therein, 18 chemicals are identified as "risk chemicals," primarily used in 8 main groups of products. The goal of the evaluation is to develop a tool for priority setting of preventive measures. The evaluation may also serve as a tool for assessing improvements and selecting areas for further epidemiological studies.

Denmark↗
PubMed1992

Effect on hemodynamics of a liquid meal alone and in combination with propranolol in cirrhosis.

Thirteen patients with alcoholic cirrhosis had splanchnic and systemic hemodynamics assessed before and after ingestion of a standard liquid meal of 700 kcal (consisting of isocaloric proteins, lipids, and carbohydrates). Half of the patients (n = 6) were randomized to a treatment group receiving intravenous infusion of propranolol in combination with the meal. No significant effects were observed on systemic hemodynamics after the meal alone. Heart rate (-14%; P less than 0.01) and cardiac index (-24%; P less than 0.01) decreased after meal in combination with propranolol. The mean hepatic venous pressure gradient increased significantly after ingestion of the meal alone with a maximal effect after 30 minutes (+13%; P less than 0.05) and returned to baseline values after 2 hours. Meal in combination with propranolol had no significant effect on the hepatic venous pressure gradient. Hepatic blood flow increased substantially after the meal alone with a maximal effect after 30 minutes (+28%; P less than 0.01), whereas no significant effect was observed after meal in combination with propranolol. Azygos blood flow increased significantly after the meal alone (+36%; P less than 0.05), whereas this effect was abolished in combination with propranolol. In conclusion, ingestion of a peroral mixed meal in cirrhotic patients has, contrary to what is observed in normal controls, no effects on systemic hemodynamics. Substantial changes in splanchnic hemodynamics were observed, and these effects were all abolished when the meal was administered in combination with propranolol.

Analysis of Variance↗
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↗
PubMed1991

[Observer variation and accuracy in the clinical diagnosis of ascites].

Seventeen observers participated in an observer variation study of the clinical evaluation of ascites. In a blinded design, eight patients with diagnoses of liver disease were examined. Fourteen observers examined the patients twice in order also to estimate the intra-observer variation. The accuracy of the observers' statements was compared with ultrasound findings, by which mean ascites was demonstrated in two patients. Poor correspondance between the observers' gradings and volume estimations, and poor accuracy of the gradings, make qualitative and quantitative ascites estimations useless. The inter-observer agreement was found to be low although the intra-observer agreement was good. The observers' subjective certainty of correctness of their own findings, marked as certain/uncertain, did not reflect the chance of making a correct statement on each particular occasion. The individual patient's general ability of inducing certainty did relate the chance of forming a correct diagnosis. Ultrasonic investigation of the abdomen is recommended in all situations in which demonstration of ascites is essential to diagnosis or therapy.

Ascites↗
PubMed1990

Effects of nutrient intake on sympathoadrenal activity and thermogenic mechanisms.

Ingestion of carbohydrate results in a diphasic activation of the sympathoadrenal system. One component is an insulin-mediated activation of the sympathetic nervous system (SNS). This activation is partly a haemodynamic reflex, but it may cause a weak thermogenic effect via beta 1-adrenoceptors in white adipose tissue, the liver and the heart. The second thermogenic component of carbohydrate occurs later when the blood glucose concentration decreases towards baseline levels. This elicits an increased secretion of adrenaline from the adrenal medulla, and the circulating level exceeds the physiological threshold for thermogenic effect. The target is mainly skeletal muscle where thermogenesis is stimulated via beta 2-adrenoceptors. Also the basal metabolic rate and the thermogenic responses to cold and heat exposure, mental stress and exercise, have facultative components. Inhibition of facultative thermogenesis by beta-blockers such as propranolol, diminishes the daily energy expenditure and promotes weight gain and obesity. Although thermogenesis mediated by the sympathoadrenal system accounts for only a small part of the daily energy expenditure, it is sufficient to explain the positive energy balance and weight gain reported in patients receiving treatment with beta-adrenoceptor blocking agents.

Adrenal Glands↗
PubMed1990

Estimating the rate of plasmid transfer: an end-point method.

We describe a method for determining the rate parameter of conjugative plasmid transfer that is based on single estimates of donor, recipient and transconjugant densities and the growth rate in exponential phase of the mating culture. The formula for estimating the plasmid transfer rate, gamma, was derived from a mathematical model describing cell growth and plasmid transfer in batch culture. Computer simulations were used to explore the sensitivity of this method to the realities of bacterial life, such as growth rate differences, plasmid segregation and transitory derepression of pilus synthesis. As predicted by the theory, mating experiments with the plasmid R1 in Escherichia coli K12 demonstrated that the estimate gamma is unaffected by cell density, donor:recipient ratio and mating time. Unlike previous techniques, our method allows us to investigate the effect of environmental factors on plasmid transfer rates when these factors also influence population growth rates. To illustrate this, we examined the effect of temperature on the rate of plasmid transfer.

Computer Simulation↗
PubMed1990

Dynamics of plasmid transfer on surfaces.

A protocol was developed to study the dynamics of growth and plasmid transfer in surface populations of bacteria. This method allows for quantitative estimates of cell population densities over time, as well as microscopic observations of colony growth and interactions. Using this 'surface slide system' (SSS), the dynamics of the plasmid R1 and its permanently derepressed mutant R1drd19 in surface cultures of Escherichia coli K12 was examined. In surface culture, the stationary-phase cell densities were constant over a wide range of initial cell density (= colony density) and comparable to those obtained in liquid culture. For high initial cell densities, where the cells formed a confluent layer at stationary phase, the kinetics of growth and plasmid transfer was similar to that obtained in liquid culture, and the relative yields of R1drd19 and R1 transconjugants were similar in the two habitats. In surface culture, however, R1drd19 transconjugant yield was profoundly affected, and R1 transfer to a lesser extent, by colony density. In contrast, liquid matings were virtually unaffected by initial cell density. The transfer advantage of the permanently depressed over the repressed plasmid was much less apparent for lower colony densities. I propose a hypothesis for plasmid transfer between colonies that explains these observations as a consequence of the geometry of the surface habitat and the effect of transitory derepression of the synthesis of pili.

Colony Count, Microbial↗