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Biomedical subjects

K Ekberg

Publications and source records attributed to K Ekberg.

At least 55 records · Page 3Linked to original sources

Glucose production and gluconeogenesis in adults with uncomplicated falciparum malaria.

Although glucose production is increased in severe malaria, the influence of uncomplicated malaria on glucose production is unknown. Therefore, we measured in eight adult Vietnamese patients with uncomplicated falciparum malaria and eight healthy Vietnamese controls glucose production (by infusion of [6,6-2H2]glucose) and the fractional contribution of gluconeogenesis (by oral ingestion of 2H2O); glycogenolysis was calculated as the difference between the two. After 20 h of fasting, plasma glucose was 4.7 +/- 0.2 mmol/l in the patients and 4.3 +/- 0.2 mmol/l in the controls (not significant). Glucose production was approximately 25% higher in the patients (16.9 +/- 1.3 vs. 13.4 +/- 0.3 mumol.kg-1.min-1, P = 0.01). Fractional and absolute gluconeogenesis were increased in the patients (approximately 87 vs. approximately 59%, P < 0.001; and 14.6 +/- 1.3 vs. 7.9 +/- 0.2 mumol.kg-1.min-1, P < 0.001, respectively). The contribution of glycogenolysis to total glucose production was decreased in the patients: 2.3 +/- 0.5 vs. 5.5 +/- 0.4 mumol.kg-1.min-1 (P < 0.002). In conclusion, in adult patients with uncomplicated falciparum malaria, glucose production is increased by approximately 25% due to an increased rate of gluconeogenesis, whereas glycogenolysis is decreased. The mechanism by which these changes occur is uncertain. However, counterregulatory hormone and cytokine concentrations were increased in the patients.

Adult↗

Quantifying gluconeogenesis during fasting.

The use of 2H2O in estimating gluconeogenesis' contribution to glucose production (%GNG) was examined during progressive fasting in three groups of healthy subjects. One group (n = 3) ingested 2H2O to a body water enrichment of approximately 0.35% 5 h into the fast. %GNG was determined at 2-h intervals from the ratio of the enrichments of the hydrogens at C-5 and C-2 of blood glucose, assayed in hexamethylenetetramine. %GNG increased from 40 +/- 8% at 10 h to 93 +/- 6% at 42 h. Another group ingested 2H2O over 2.25 h, beginning at 11 h (n = 7) and 19 h (n = 7) to achieve approximately 0.5% water enrichment. Enrichment in plasma water and at C-2 reached steady state approximately 1 h after completion of 2H2O ingestion. The C-5-to-C-2 ratio reached steady state by the completion of 2H2O ingestion. %GNG was 54 +/- 2% at 14 h and 64 +/- 2% at 22 h. A 3-h [6,6-2H2]glucose infusion was also begun to estimate glucose production from enrichments at C-6, again in hexamethylenetetramine. Glucose produced by gluconeogenesis was 0.99 +/- 0.06 mg.kg-1.min-1 at both 14 and 22 h. In a third group (n = 3) %GNG reached steady state approximately 2 h after 2H2O ingestion to only approximately 0.25% enrichment. In conclusion, %GNG by 2 h after 2H2O ingestion and glucose production using [6,6-2H2]glucose infusion, begun together, can be determined from hydrogen enrichments at blood glucose C-2, C-5, and C-6. %GNG increases gradually from the postabsorptive state to 42 h of fasting, without apparent change in the quantity of glucose produced by gluconeogenesis at 14 and 22 h.

Adult↗

Influence of circulating epinephrine and norepinephrine on insulin-like growth factor binding protein-1 in humans.

The aim of the present study was to investigate the influence of circulating epinephrine (Epi) and norepinephrine (Norepi) on serum insulin-like growth factor binding protein-1 (IGFBP-1) concentrations. Healthy men received 0.3 nmol.kg.min Epi iv (n = 6), 0.5 nmol.kg.min Norepi iv (n = 7), or saline (n = 5) during 30 min. Arterial blood samples were obtained before, during, and 120 min after infusion. During the catecholamine infusion arterial Epi and Norepi plasma concentrations reached 6.35 +/- 0.53 and 15.65 +/- 2.71 nmol/L, respectively, which resulted in significant increases in glucose concentrations. When Epi was infused, IGFBP-1 increased from 45 +/- 6 micrograms/L to 76 +/- 10 micrograms/L (P < 0.05) 60 min after the infusion. Epi was also followed by increases in insulin, C-peptide, and glucagon. Norepi resulted in a slight increase in circulating IGFBP-1 (43 +/- 6 to 54 +/- 8 nmol/L, NS). The findings suggest that Epi, at plasma concentrations similar to those reached during physical stress, stimulates the production of IGFBP-1 in humans.

Adult↗

Are deficits in the equilibrium system relevant to the clinical investigation of solvent-induced neurotoxicity?

OBJECTIVES: The diagnosis of solvent-induced chronic toxic encephalopathy is commonly based on case histories of exposure to solvents, symptoms, and deficits on psychometric tests. It has previously been demonstrated that long-term solvent-exposed workers have disturbances of the equilibrium system. The correlation between these disturbances and the diagnosis of chronic toxic encephalopathy has been analyzed in the present study. MATERIAL AND METHODS: Sixty men, consecutively admitted due to the suspicion of this syndrome, were investigated and classified into 3 groups--solvent-induced chronic toxic encephalopathy, incipient chronic toxic encephalopathy and nonchronic toxic encephalopathy. They were all examined using an otoneurological test battery, including analysis of saccades, smooth pursuit, visual suppression of the vestibular ocular reflex, and dynamic posturography. RESULTS: Compared with healthy referents several of the subjects, even in the nonchronic toxic encephalopathy group, showed a reduced visual suppression ability, a prolonged latency of saccades, and pathological posturographic results. Some otoneurological tests correlated with the duration of exposure and the results of psychometric tests representing memory and perceptual skills. Nevertheless, there was no significant group correlation between the otoneurological findings and the diagnosis of chronic toxic encephalopathy. CONCLUSION: Disturbances revealed by an otoneurological investigation have so far not been considered in the diagnosis of chronic toxic encephalopathy. Our results indicate that an otoneurological test battery adds worthwhile information about lesions within the brainstem-cerebellar complex not revealed by a psychometric investigation.

Adult↗

Contributions of gluconeogenesis to glucose production in the fasted state.

Healthy subjects ingested 2H2O and after 14, 22, and 42 h of fasting the enrichments of deuterium in the hydrogens bound to carbons 2, 5, and 6 of blood glucose and in body water were determined. The hydrogens bound to the carbons were isolated in formaldehyde which was converted to hexamethylenetetramine for assay. Enrichment of the deuterium bound to carbon 5 of glucose to that in water or to carbon 2 directly equals the fraction of glucose formed by gluconeogenesis. The contribution of gluconeogenesis to glucose production was 47 +/- 49% after 14 h, 67 +/- 41% after 22 h, and 93 +/- 2% after 42 h of fasting. Glycerol's conversion to glucose is included in estimates using the enrichment at carbon 5, but not carbon 6. Equilibrations with water of the hydrogens bound to carbon 3 of pyruvate that become those bound to carbon 6 of glucose and of the hydrogen at carbon 2 of glucose produced via glycogenolysis are estimated from the enrichments to be approximately 80% complete. Thus, rates of gluconeogenesis can be determined without corrections required in other tracer methodologies. After an overnight fast gluconeogenesis accounts for approximately 50% and after 42 h of fasting for almost all of glucose production in healthy subjects.

Adult↗

Assembly work in Indonesia and in Sweden--ergonomics, health and satisfaction.

Work conditions in industrial production vary substantially between different cultures. In the present study the aims were to identify differences between Swedish and Indonesian assembly industry workers regarding work environment factors, health and job satisfaction, and to find associations between work environment factors, and the health measures. Data were collected by a questionnaire from 326 Swedish and 136 Indonesian assembly industry workers, interviews and from company documents. The prevalence of musculoskeletal symptoms was high in both groups. Stress and psychosomatic symptoms had higher prevalences in the Swedish group, which also rated their work conditions as worse in most respects. Work tasks were physically heavier in Indonesia, but less monotonous and with lower demands on productivity. The Indonesians were more satisfied with their jobs. Physical job demands were associated with musculoskeletal symptoms. Competence development was associated with increased job satisfaction. Conflicts and harassments at work were associated with stress and psychosomatic symptoms. Job pressure, especially deficient planning of the jobs was associated with lower job satisfaction, psychosomatic and stress symptoms in the Swedish group. Implications for job design in the two cultures are presented.

Cross-Cultural Comparison↗

Anaesthesia for day-care arthroscopy. A comparison between desflurane and isoflurane.

A study was undertaken to compare desflurane- and isoflurane-based anaesthesia in patients undergoing day-care arthroscopic surgery. Anaesthesia was induced with propofol 2-3 mg.kg-1 and a laryngeal mask airway was inserted after loss of the eyelash reflex. Patients were then randomly divided into two groups to receive maintenance anaesthesia with either isoflurane or desflurane delivered in oxygen and nitrous oxide. Alfentanil was used as the analgesic during the operation. Early recovery was assessed by measurement of the times to eye opening, extubation and ability to give a date of birth. Psychomotor recovery was assessed by performance on the finger tapping and perceptive accuracy tests. Mood was evaluated using visual analogue mood scores and the mood adjective checklist. Discharge times were also measured. Early recovery was significantly quicker following desflurane anaesthesia but no differences between the groups were found in psychomotor tests. The mood adjective checklist showed that patients in the isoflurane group had a greater total mood score and were more calm than those in the desflurane group; this was particularly evident 2 h after anaesthesia. The discharge times were similar for the two groups. Desflurane is a satisfactory alternative to isoflurane for day care anaesthesia.

Adult↗

Glycerol production and utilization in humans: sites and quantitation.

Liver is assumed to be the major site of glycerol uptake and fatty acid reesterification. [U-13C]glycerol was infused into ten 60 h-fasted healthy subjects. Measured were 1) blood glycerol concentrations and 13C enrichments in brachial and pulmonary arteries and in hepatic, renal, superficial, and deep forearm veins; 2) glycerol appearance rates in systemic circulation; and 3) splanchnic bed and kidney glycerol uptakes with use of balance and tracer methodology. Glycerol concentrations were one-fifth in hepatic, one-half in renal, 40% more in superficial, and the same in deep vein and pulmonary artery as in brachial artery blood. Glycerol enrichments were one-fifth in hepatic, two-thirds to three-quarters in renal and superficial veins, and the same in pulmonary as in brachial artery blood. Splanchnic glycerol uptake was 29% and kidney glycerol uptake was 17% of glycerol's rate of appearance, 5.11 mumol.min-1.kg-1. Splanchnic fatty acid uptake was 25% of calculated fatty acid release. Glycerol contributed 15% to glucose production. Most of the [13C]glycerol uptake by splanchnic bed and kidneys was incorporated into glucose. Thus, in 60 h-fasted individuals, most glycerol uptake does not occur in liver, and the extent of fatty acid reesterification in liver is in doubt.

Adult↗

Long-term sickness absence due to musculoskeletal disorders: the necessary intervention of work conditions.

To make rehabilitation of musculoskeletal disorders effective it is crucial to identify circumstances that tend to support the persistence of sickness absence. A total of 93 patients with recently developed disorders in the neck and shoulders were followed for one year after rehabilitation, in order to identify factors associated with recovery and chronicity, respectively. Health status was evaluated before rehabilitation and after 12 months in terms of sickness absence, pain ratings and self-rated quality of life, the Sickness Impact Profile. The study group was divided into tertiles based on their number of days of sickness absence during the follow-up period (short: < 25 days, medium: 25-101 days, long: > 101 days). Those with long-term sickness absence perceived higher physical and mental load in their jobs. There was also a higher proportion of persons who were not born in Sweden in this group and on average they had more sick-leave days the preceding year. Other background characteristics and personality ratings were similar between the groups. Long-term sickness absence was associated with worse ratings in quality of life after one year, and pain did not diminish during the follow-up year. Multiple regression analysis indicated that long-term sickness absence was largely associated with work conditions rather than with individual characteristics. Therefore, the results underscore the importance not only of treating the individual with musculoskeletal disorders, but in particular of improving his or her work conditions.

Adult↗

Gluconeogenesis and glucuronidation in liver in vivo and the heterogeneity of hepatocyte function.

In order to examine metabolic zonation in human liver, [2-14C]glycerol, which labels carbons 2 and 5 of glucose-6-P, and [1-14C]lactate, which labels carbons 3 and 4 of glucose-6-P, in the process of gluconeogenesis, were infused intravenously into healthy subjects who ingested acetaminophen and had fasted 36 h. Distributions of 14C were determined in glucose in blood and in the glucuronic acid moiety of acetaminophen glucuronide excreted in urine. Ratios of 14C in carbons 2 and 5 to 14C in carbons 3 and 4 were significantly higher in blood glucose than in glucuronide. Since glucose and glucuronic acid are formed from glucose-6-P in liver without randomization of carbon, the differences in the ratios indicate that the pool of glucose-6-P in liver is not homogeneous. The glucuronide sampled glucose-6-P with more label from lactate than glycerol compared to the glucose-6-P sampled by the glucose. The apparent explanation is the greater decrease in glycerol compared with lactate concentration as blood streams from the periportal to the perivenous zones of the liver lobule. Glucuronidation is then expressed in humans relatively more in the perivenous than periportal zones and gluconeogenesis from glycerol more in the periportal than perivenous zones.

Acetaminophen↗

Estimates of Krebs cycle activity and contributions of gluconeogenesis to hepatic glucose production in fasting healthy subjects and IDDM patients.

Normal subjects, fasted 60 h, and patients with insulin-dependent diabetes mellitus (IDDM), withdrawn from insulin and fasted overnight, were given phenylacetate orally and intravenously infused with [3-14C]lactate and 13C-bicarbonate. Rates of hepatic gluconeogenesis relative to Krebs cycle rates were estimated from the 14C distribution in glutamate from urinary phenylacetylglutamine. Assuming the 13C enrichment of breath CO2 was that of the CO2 fixed by pyruvate, the enrichment to be expected in blood glucose, if all hepatic glucose production had been by gluconeogenesis, was then estimated. That estimate was compared with the actual enrichment in blood glucose, yielding the fraction of glucose production due to gluconeogenesis. Relative rates were similar in the 60-h fasted healthy subjects and the diabetic patients. Conversion of oxaloacetate to phosphoenolpyruvate was two to eight times Krebs cycle flux and decarboxylation of pyruvate to acetyl-CoA, oxidized in the cycle, was less than one-30th the fixation by pyruvate of CO2. Thus, in estimating the contribution of a gluconeogenic substrate to glucose production by measuring the incorporation of label from the labelled substrate into glucose, dilution of label at the level of oxaloacetate is relatively small. Pyruvate cycling was as much as one-half the rate of conversion of pyruvate to oxaloacetate. Glucose and glutamate carbons were derived from oxaloacetate formed by similar pathways if not from a common pool. In the 60-h fasted subjects, over 80% of glucose production was via gluconeogenesis. In the diabetic subjects the percentages averaged about 45%.

Adult↗

Cross-sectional study of risk factors for symptoms in the neck and shoulder area.

This study was performed in order to evaluate how individual characteristics, as well as ergonomic, organizational and psychosocial factors in the work situation are associated with early symptoms in the neck and shoulder area. Nine hundred randomly drawn subjects of the working population in a semi-rural community in Sweden were mailed a questionnaire comprising the Nordic questionnaire on musculoskeletal symptoms, questions on ergonomic, organizational and psychosocial work conditions, life style factors, and background factors. The total response rate was 73% (n = 637). Questions on ergonomic work conditions and on organizational and psychosocial work conditions provided the measures of exposure. Prevalence ratios (PR) were calculated for symptoms in the neck and shoulder area as reported by 303 subjects. Significant determinants for early symptoms were being a female and being an immigrant, as were repetitive movements demanding precision. High work pace, low work content and work role ambiguity were significant organizational risk factors while life style characteristics did not appear as risk factors. The results suggest that symptoms are signals not only of ergonomic deficiencies in the work situation, but in particular of work organizational conditions. Special attention should be given to the work conditions of women and immigrants in preventive interventions.

Adolescent↗

Assessment of recovery following day-case arthroscopy. A comparison between propofol and isoflurane-based anaesthesia.

Fifty healthy patients, aged 15-45 years, undergoing day-case arthroscopy, participated in a study to assess aspects of recovery and mood. Psychomotor tests, including the p-deletion test and the Trieger dot test, were performed pre-operatively and mood was measured using the mood adjective checklist. Anaesthesia in all patients was induced with propofol and a laryngeal mask airway was inserted immediately. All patients received alfentanil as the intra-operative analgesic. The patients were randomly allocated to receive one of two different regimens for maintenance of anaesthesia: propofol group--maintenance with an infusion of propofol 10 mg.kg-1.h-1 for 15 min followed by 6 mg.kg-1.h-1 and nitrous oxide and oxygen (bolus doses of propofol were given if anaesthesia was deemed to be light); isoflurane group--maintenance with isoflurane (inspired concentration 0.5-2.0%) in nitrous oxide and oxygen. Postoperatively, psychomotor tests were repeated every 30 min and mood was measured after 2 h and 24 h. Psychomotor recovery was quicker in the isoflurane group than the propofol group and had returned to baseline values in the isoflurane group by 60 min. The time to discharge was similar in both groups as was the incidence of side effects. There was no difference in mood scores between the groups either at the time of discharge or at 24 h. We conclude that psychomotor recovery is somewhat quicker when isoflurane-based anaesthesia is used for day-case arthroscopy, but other factors, including time to awakening, mood and time to discharge are similar for both techniques.

Adolescent↗

A limitation in the use of mass isotopomer distributions to measure gluconeogenesis in fasting humans.

The use of distributions of mass isotopomers in glucose from [U-13C]glycerol to estimate fractional rates of gluconeogenesis was examined. [U-13C]glycerol was infused into normal subjects who ingested acetaminophen and fasted for 60 h. Isotopomer distributions were measured by mass spectrometry in blood glucose and in glucuronic acid from urinary acetaminophen glucuronide. The distributions are incompatible with glucose production solely via gluconeogenesis from a single pool of triose phosphates. Rather, with the assumption of a single enriched triose phosphate pool, the distributions indicate, despite the 60 h of fasting, about as much glucose formation from an unlabeled glucose source as from that pool. Therefore the data indicate cellular heterogeneity in glycerol's metabolism, so that two or more pools with significantly different enrichments were the source of the glucose and glucuronic acid. This heterogeneity is related to much greater concentrations of glycerol in periportal than in pericentral zones of the liver lobule. Beyond evidence for heterogeneity, the findings emphasize a limitation in applying analyses of mass isotopomer distributions to measure polymer biosynthesis in the presence of heterogeneity in the precursor pool.

Acetaminophen↗

Use of 2H2O for estimating rates of gluconeogenesis. Application to the fasted state.

A method is introduced for estimating the contribution of gluconeogenesis to glucose production. 2H2O is administered orally to achieve 0.5% deuterium enrichment in body water. Enrichments are determined in the hydrogens bound to carbons 2 and 6 of blood glucose and in urinary water. Enrichment at carbon 6 of glucose is assayed in hexamethylenetetramine, formed from formaldehyde produced by periodate oxidation of the glucose. Enrichment at carbon 2 is assayed in lactate formed by enzymatic transfer of the hydrogen from glucose via sorbitol to pyruvate. The fraction gluconeogenesis contributes to glucose production equals the ratio of the enrichment at carbon 6 to that at carbon 2 or in urinary water. Applying the method, the contribution of gluconeogenesis in healthy subjects was 23-42% after fasting 14 h, increasing to 59-84% after fasting 42 h. Enrichment at carbon 2 to that in urinary water was 1.12 +/- 0.13. Therefore, the assumption that hydrogen equilibrated during hexose-6-P isomerization was fulfilled. The 3H/14C ratio in glucose formed from [3-3H,3-14C]lactate given to healthy subjects was 0.1 to 0.2 of that in the lactate. Therefore equilibration during gluconeogenesis of the hydrogen bound to carbon 6 with that in body water was 80-90% complete, so that gluconeogenesis is underestimated by 10-20%. Glycerol's contribution to gluconeogenesis is not included in these estimates. The method is applicable to studies in humans of gluconeogenesis at safe doses of 2H2O.

Adult↗

Protein dynamics in whole body and in splanchnic and leg tissues in type I diabetic patients.

To elucidate the mechanism of insulin's anticatabolic effect in humans, protein dynamics were evaluated in the whole-body, splanchnic, and leg tissues in six C-peptide-negative type I diabetic male patients in the insulin-deprived and insulin-treated states using two separate amino acid models (leucine and phenylalanine). L-(1-13C,15N)leucine, L-(ring-2H5)phenylalanine, and L-(ring-2H2) tyrosine were infused intravenously, and isotopic enrichments of [1-13C,15N]-leucine, (13C)leucine, (13C)ketoisocaproate, (2H5)phenylalanine, [2H4]tyrosine, (2H2)tyrosine, and 13CO2 were measured in arterial, hepatic vein, and femoral vein samples. Whole-body leucine flux, phenylalanine flux, and tyrosine flux were decreased (< 0.01) by insulin treatment, indicating an inhibition of protein breakdown. Moreover, insulin decreased (< 0.05) the rates of leucine oxidation and leucine transamination (P < 0.01), but the percent rate of ketoisocaproate oxidation was increased by insulin (P < 0.01). Insulin also reduced (< 0.01) whole-body protein synthesis estimated from both the leucine model (nonoxidative leucine disposal) and the phenylalanine model (disposal of phenylalanine not accounted by its conversion to tyrosine). Regional studies demonstrated that changes in whole body protein breakdown are accounted for by changes in both splanchnic and leg tissues. The changes in whole-body protein synthesis were not associated with changes in skeletal muscle (leg) protein synthesis but could be accounted for by the splanchnic region. We conclude that though insulin decreases whole-body protein breakdown in patients with type I diabetes by inhibition of protein breakdown in splanchnic and leg tissues, it selectively decreases protein synthesis in splanchnic tissues, which accounted for the observed decrease in whole-body protein synthesis. Insulin also augmented anabolism by decreasing leucine transamination.

Adult↗