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  • 1.
    Allvin, Renée
    et al.
    Clinical Skills Centre, Faculty of Medicine and Health, School of Medical Sciences, Örebro University, Örebro.
    Berndtzon, Magnus
    Metodikum – Skill Centre of Medical Simulation Region County Jönköping, Jönköping.
    Carlzon, Liisa
    Simulation Centre West, Department of Research, Education and Development, Sahlgrenska University Hospital, Gothenburg.
    Edelbring, Samuel
    Department of Medical and Health Sciences, Faculty of Medicine and Health Sciences, Linköping University, Linköping.
    Hult, Håkan
    Department of Medical and Health Sciences, Faculty of Medicine and Health Sciences, Linköping University, Linköping.
    Hultin, Magnus
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Karlgren, Klas
    Department of Learning, Informatics, Management and Ethics, Karolinska Institutet, Stockholm.
    Masiello, Italo
    Department of Clinical Science and Education, Karolinska Institutet, Södersjukhuset Hospital, Stockholm.
    Södersved Källestedt, Marie-Louise
    Clinical Skills Centre, Centre for Clinical Research, Uppsala University, Västerås.
    Tamás, Éva
    Department of Cardiovascular Diseases, Institute of Medicine and Health, Medical Faculty, University of Linköping, Linköping.
    Confident but not theoretically grounded: experienced simulation educators’ perceptions of their own professional development2017In: Advances in Medical Education and Practice, ISSN 1179-7258, E-ISSN 1179-7258, no 8, p. 99-108Article in journal (Refereed)
    Abstract [en]

    Background: Medical simulation enables the design of learning activities for competency areas (eg, communication and leadership) identi ed as crucial for future health care professionals. Simulation educators and medical teachers follow different career paths, and their education backgrounds and teaching contexts may be very different in a simulation setting. Although they have a key role in facilitating learning, information on the continuing professional development (pedagogical development) of simulation educators is not available in the literature. Objectives: To explore changes in experienced simulation educators’ perceptions of their own teaching skills, practices, and understanding of teaching over time.

    Methods: A qualitative exploratory study. Fourteen experienced simulation educators partici- pated in individual open-ended interviews focusing on their development as simulation educators. Data were analyzed using an inductive thematic analysis. Results: Marked educator development was discerned over time, expressed mainly in an altered way of thinking and acting. Five themes were identi ed: shifting focus, from following to utilizing a structure, setting goals, application of technology, and alignment with profession. Being con dent in the role as an instructor seemed to constitute a foundation for the instructor’s pedagogical development.

    Conclusion: Experienced simulation educators’ pedagogical development was based on self- con dence in the educator role, and not on a deeper theoretical understanding of teaching and learning. This is the rst clue to gain increased understanding regarding educational level and possible education needs among simulation educators, and it might generate several lines of research for further studies. 

  • 2.
    Andersson, Jonas
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Sjöström, Lars-Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Karlsson, Marcus
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Wiklund, Urban
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Hultin, Magnus
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Karpe, Fredrik
    Olsson, Tommy
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Dysregulation of subcutaneous adipose tissue blood flow in overweight postmenopausal women2010In: Menopause: The Journal of the North American Menopause, ISSN 1072-3714, E-ISSN 1530-0374, Vol. 17, no 2, p. 365-371Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE:: A putative link between abdominal obesity and metabolic-vascular complications after menopause may be due to a decreased adipose tissue blood flow (ATBF). The present work aimed to analyze possible changes in ATBF with being overweight and menopausal and its putative link to endothelial dysfunction and autonomic nervous system balance.

    METHODS:: Forty-three healthy women were classified into four groups according to weight and menopause status. The ATBF was measured by xenon washout while fasting and after oral glucose intake. The nitric oxide synthase inhibitor asymmetric dimethylarginine was used as a marker of endothelial function and heart rate variability-estimated autonomic nervous system activity.

    RESULTS:: Fasting ATBF was decreased in both overweight groups (P = 0.044 and P = 0.048) versus normal-weight premenopausal women. Normal-weight and overweight postmenopausal women exhibited lower maximum ATBF compared with normal-weight premenopausal women (P = 0.015 and P = 0.001, respectively), and overweight postmenopausal women exhibited lower maximum ATBF compared with normal-weight postmenopausal women (P = 0.003). A negative correlation was found between fasting ATBF and asymmetric dimethylarginine (P = 0.015), whereas maximum ATBF was negatively associated with sympathetic-parasympathetic nervous system balance (ratio of the power of the low frequency to the power of the high frequency; P = 0.002).

    CONCLUSIONS:: Loss of ATBF flexibility in overweight postmenopausal women may contribute to the metabolic dysfunction seen in this group of women.

  • 3.
    Chevreuil, O
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Hultin, M
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Ostergaard, P
    Olivecrona, T
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Biphasic effects of low-molecular-weight and conventional heparins on chylomicron clearance in rats.1993In: Arteriosclerosis and thrombosis : a journal of vascular biology / American Heart Association, ISSN 1049-8834, Vol. 13, no 10, p. 1397-403Article in journal (Refereed)
    Abstract [en]

    Chylomicrons labeled in vivo with [14C]triglycerides and [3H]retinyl esters were injected in rats at a series of times after administration of conventional unfractionated heparin (UFH), low-molecular-weight heparin (LMWH), or saline. In saline controls the clearance of both chylomicron triglycerides and retinyl esters seemed to follow exponential courses, with half-lives of about 5 and 10 minutes, respectively. Five minutes after administration of LMWH or UFH, the triglyceride clearance rates were dramatically increased and were associated with an increased appearance of the radiolabel in circulating free fatty acids (FFAs). The clearance of [3H]retinol radioactivity, ie, chylomicron particles, was also enhanced 5 minutes after heparin injection. From 75% to 90% disappeared from the circulation within the first 5 minutes. Their continued disappearance was much slower, with a slope similar to that of the saline-treated rats. Hence, it was as if a new, rapid exponent had been added to the disappearance curve that accounted for most of the particle clearance. Injection of chylomicrons 1 hour after the heparins resulted in substantially slower clearance compared with saline-treated controls of both triglyceride and retinol radioactivity in rats given a high dose of LMWH or a low dose of either heparin. Appearance of label in plasma FFAs was also decreased, suggesting that impeded lipolysis was responsible, at least in part, for the impeded chylomicron clearance. Four and 24 hours after heparin injection all studied parameters of chylomicron clearance had returned to normal.(ABSTRACT TRUNCATED AT 250 WORDS)

  • 4.
    Chevreuil, O
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Hultin, M
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Ostergaard, P
    Olivecrona, T
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Depletion of lipoprotein lipase after heparin administration.1993In: Arteriosclerosis and thrombosis : a journal of vascular biology / American Heart Association, ISSN 1049-8834, Vol. 13, no 10, p. 1391-6Article in journal (Refereed)
    Abstract [en]

    Some or most of the turnover of lipoprotein lipase (LPL) occurs by dissociation from vascular endothelial sites in extrahepatic tissues and further degradation in the liver. Heparin greatly enhances this dissociation and delays but does not abolish uptake in the liver, raising the possibility that heparin could lead to accelerated catabolism of functional LPL. To investigate this, we determined time curves for heparin (anti-factor Xa activity) and for LPL and hepatic lipase after injection in rats of two doses of conventional unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH). The high dose (250 U/kg) of both heparins resulted in similar initial levels of LPL activity in plasma, but at 30 minutes the activity with LMWH had declined by more than 80%, whereas with UFH it remained essentially unchanged during this time. In contrast, time curves for heparin activity in blood were similar for the two heparins. The low dose (50 U/kg) led to lower initial levels of LPL activity with LMWH in spite of slower elimination of heparin activity from the blood. These results agree with previous studies that indicate that LMWH has a similar ability as UFH to release LPL, but a lesser ability to delay its removal by the liver. Only slight differences were noted in the time curves for hepatic lipase with the two heparins. To assess the possible depletion of the lipases, we administered a second large dose of conventional heparin. One hour after the first injection, the second injection resulted in lower plasma LPL activities in all four groups.(ABSTRACT TRUNCATED AT 250 WORDS)

  • 5.
    Chevreuil, O
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Hultin, M
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Ostergaard, P
    Olivecrona, T
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Heparin-decasaccharides impair the catabolism of chylomicrons.1996In: Biochemical Journal, ISSN 0264-6021, E-ISSN 1470-8728, Vol. 320 ( Pt 2), p. 437-44Article in journal (Refereed)
    Abstract [en]

    On intravenous injection to rats, decasaccharides gave rise to a short-lived peak of lipoprotein lipase (LPL) activity, whereas octa- and hexasaccharides caused only marginal increases. In isolated hearts perfused by a single pass, decasaccharides released LPL more efficiently than conventional heparin on a mass basis. Octa- and hexasaccharides were much less efficient. Similar results were obtained for hepatic lipase, which was studied both in vivo and by liver perfusion. In the intact rat, the heparin fragments themselves disappeared rapidly from the circulating blood. The decay of hepatic lipase activity after the early peak roughly paralleled the decay of decasaccharide concentration, but for LPL the decay was faster, presumably because the liver extracted this lipase from plasma. To assess the lipase activities remaining in contact with blood a large dose of conventional heparin was injected at a series of times after the decasaccharides. LPL was decreased by 40% after 1 h. At that time, the LPL activity that could be released from isolated hearts by single-pass perfusion with heparin for 2 min ("functional LPL') was decreased by 75%. Chylomicrons labelled in vivo with [14C]oleic acid (primarily in triacylglycerols, providing a tracer for lipolysis) and [3H]retinol (primarily in ester form, providing a tracer for the particles) were injected intravenously to explore the effects of the LPL depletion on lipoprotein metabolism. Triacylglycerol lipolysis and particle clearance was markedly delayed from 30 min to 2 h after injection of decasaccharides. After 1 h the fractional catabolic rate was only one-third of the control value and the catabolism of chylomicron triacylglycerols by perfused hearts was delayed to a similar extent. Thus injection of decasaccharides leads to accelerated turnover of LPL with loss of functional LPL from extrahepatic tissues. This in turn leads to a period of delayed lipolysis and removal of chylomicron particles.

  • 6.
    Claesson, Jonas
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology. Anestesiologi och intensivvård.
    Lehtipalo, Stefan
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology. Anestesiologi och intensivvård.
    Bergstrand, Ulf
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology. Anestesiologi och intensivvård.
    Arnerlöv, Conny
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery. Kirurgi.
    Rocksen, David
    Hultin, Magnus
    Winsö, Ola
    Intestinal circulation, oxygenation and metabolism is not affected by oleic acid lung injury.2005In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 25, no 6, p. 357-363Article in journal (Refereed)
    Abstract [en]

    This study was performed to establish a platform for further studies on effects of ventilatory treatment modalities on the intestines during mechanical ventilation of acute lung injury (ALI). We tested the hypotheses that oleic acid (OA) infusion causes changes in intestinal circulation, oxygenation and metabolism, and that OA is distributed to tissues outside the lung. This was performed as an experimental, prospective and controlled study in an university animal research laboratory. Thirteen juvenile anaesthetized pigs were used in the main study, where seven were given an intravenous infusion of 0.1 ml kg(-1) OA and six served as control (surgery only). In a separate study, four animals were given an intravenous infusion of 0.1 ml kg(-1) (3)H-labelled OA. We measured systemic and mesenteric (portal venous blood flow, jejunal mucosal perfusion) haemodynamic parameters, mesenteric oxygenation (jejunal tissue oxygen tension) and systemic cytokines (tumour necrosis factor-alpha and interleukin-6). We calculated mesenteric lactate flux and mesenteric oxygen delivery, uptake and extraction ratio. In the animals given 3H-OA, we measured 3H-OA in different tissues (lungs, heart, liver, kidney, stomach, jejunum, colon and arterial blood). We found that OA given intravenously is distributed in small amounts to the intestines. This intestinal exposure to OA does not cause intestinal injury when evaluating mesenteric blood flow, metabolism or oxygenation. OA infusion induced a moderate increase in mean pulmonary arterial pressure and a decrease in PaO2/Fraction inspired O2 (P/F) ratio, giving evidence of severe lung injury. Consequently, the OA lung injury model is suitable for studies on intestinal effects of ventilatory treatment modalities during mechanical ventilation of ALI.

  • 7.
    Halliday, T. A.
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology. Anesthesiology and Intensive Care, Sundsvall, Sweden.
    Sundqvist, Jonas
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology. Anesthesiology and Intensive Care, Sundsvall, Sweden.
    Hultin, Magnus
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology. Anesthesiology and Intensive Care, Sundsvall, Sweden.
    Wallden, Jakob
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology. Anesthesiology and Intensive Care, Sundsvall, Sweden.
    Post-operative nausea and vomiting in bariatric surgery patients: an observational study2017In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 61, no 5, p. 471-479Article in journal (Refereed)
    Abstract [en]

    Background: The risk of post-operative nausea and vomiting (PONV) in patients undergoing bariatric surgery is unclear. The aim of the study was to investigate the risk of PONV and the use and effectiveness of PONV prophylaxis.

    Methods: This prospective observational study included 74 patients undergoing bariatric surgery with total intravenous anaesthesia. Patients were given PONV prophylaxis based on published guidelines and a simplified PONV risk score. Perioperative data were collected and a questionnaire was used at 2, 4, 6, 24, 48 and 72 h after the operation to evaluate PONV. Data are presented as risk (%) with the 95% confidence interval.

    Results: Sixty five per cent (54-75) of the patients experienced PONV in the first 24 post-operative hours and the risk increased with the number of risk factors for PONV. PONV occurred in 78% (66-87) of women and 26% (12-49) of men during the first 24 h. In relation to the guidelines, one patient received suboptimal PONV prophylaxis, 23% received optimal prophylaxis and 76% supra-optimal prophylaxis. The risk of PONV was 82% (59-94) with optimal prophylaxis and 59% (46-71) with supra-optimal prophylaxis. Of all patients, 34% (24-45) experienced severe PONV in the first 24 h that limited their activity.

    Conclusions: The incidence of PONV in bariatric surgery patients was high despite a PONV prophylaxis regime following current guidelines. These results cast doubt as to the effectiveness of the usual PONV prophylaxis in this patient group and point to the need for further investigation of PONV prophylaxis and treatment in bariatric surgery patients.

  • 8.
    Hultin, M
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Bengtsson-Olivecrona, G
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Olivecrona, T
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Release of lipoprotein lipase to plasma by triacylglycerol emulsions. Comparison to the effect of heparin.1992In: Biochimica et Biophysica Acta, ISSN 0006-3002, E-ISSN 1878-2434, Vol. 1125, no 1, p. 97-103Article in journal (Refereed)
    Abstract [en]

    It was previously known that lipoprotein lipase (LPL) activity in plasma rises after infusion of a fat emulsion. To explore the mechanism we have compared the release of LPL by emulsion to that by heparin. After bolus injections of a fat emulsion (Intralipid) to rats, plasma LPL activity gradually rose 5-fold to a maximum at 6-8 min. During the same time the concentration of injected triacylglycerols (TG) decreased by about half. Hence, the time-course for plasma LPL activity was quite different from that for plasma TG. The disappearance of injected 125I-labelled bovine LPL from circulation was retarded by emulsion. This effect was more marked 30 min than 3 min after injection of the emulsion. The data indicate that the release of LPL into plasma is not solely due to binding of the lipase to the emulsion particles as such, but involves metabolism of the particles. Emulsion increased the fraction of labelled LPL found in adipose tissue, heart and the red muscle studied, but had no significant effect on the fraction found in liver. The effects of emulsion were quite different from those of heparin, which caused an immediate release of the lipase to plasma, decreased uptake of LPL in most extrahepatic tissues by 60-95%, and increased the fraction taken up in the liver.

  • 9.
    Hultin, M
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Carneheim, C
    Rosenqvist, K
    Olivecrona, T
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Intravenous lipid emulsions: removal mechanisms as compared to chylomicrons.1995In: Journal of Lipid Research, ISSN 0022-2275, E-ISSN 1539-7262, Vol. 36, no 10, p. 2174-84Article in journal (Refereed)
    Abstract [en]

    We have compared the metabolism of chylomicrons and a labeled emulsion, similar to those used for parenteral nutrition. Both were labeled in their triglyceride moieties and by a core label. It is known that chylomicron triglycerides are cleared by two processes: removal of triglycerides from the particles through lipolysis and removal of whole or partly lipolyzed particles. It has been proposed that emulsion droplets are cleared by the same pathways. After intravenous injection to postprandial rats, triglycerides were cleared less rapidly from the emulsion than from the chylomicrons (half-lives of 6.4 and 4.0 min), whereas the core labels were cleared at the same rate (half-lives around 7.5 min). This suggests that there was less lipolysis of the emulsion droplets which was further supported by the finding that less label appeared in the plasma free fatty acids (FFA). In adipose tissue of fed rats given chylomicrons, the ratio between fatty acid and core label was above 6, showing that fatty acids had been taken up after lipoprotein lipase-mediated hydrolysis. In contrast, for rats given emulsion, that ratio was only 1.2 showing that nearly as much emulsion droplets as emulsion-derived fatty acids were present in the tissue. In the liver the ratio was 0.55 after chylomicrons but 0.93 after emulsion. In further support of more lipolysis, fatty acids were oxidized more rapidly from chylomicrons than from emulsion. These data suggest that a large fraction of the emulsion droplets was removed from plasma with little or no preceding lipolysis. A substantial proportion, more than 50%, of this uptake occurred in extrahepatic tissues.

  • 10.
    Hultin, M
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Müllertz, A
    Zundel, M A
    Olivecrona, G
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Hansen, T T
    Deckelbaum, R J
    Carpentier, Y A
    Olivecrona, T
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Metabolism of emulsions containing medium- and long-chain triglycerides or interesterified triglycerides.1994In: Journal of Lipid Research, ISSN 0022-2275, E-ISSN 1539-7262, Vol. 35, no 10, p. 1850-60Article in journal (Refereed)
    Abstract [en]

    This study compares the clearing and metabolism of three different lipid emulsions. They had the same phospholipid emulsifier and similar particle sizes. In one (LLL) the core component was long-chain triglycerides (TG), the second (MMM/LLL) contained equal molar amounts of medium- and long-chain TG, the third (MLM) contained synthetic TG with medium-chain (M) fatty acids in the 1,3-positions and a long-chain (L) fatty acid in the 2-position. In model experiments with bovine lipoprotein lipase, the MMM component was hydrolyzed preferentially in the MMM/LLL emulsion so that the initial products were M fatty acids and M monoglycerides. The MLM emulsion, in contrast, gave M fatty acids and formation of L-MG (monoglyceride) throughout hydrolysis. For in vivo studies [3H]oleic acid was incorporated into the emulsion TG as marker for the long-chain component. After bolus injection to rats, the MMM/LLL and MLM emulsions were cleared more rapidly than the LLL emulsion. This was true at all TG loads studied (4-64 mg for a 200 g rat). The labeled oleic acid was oxidized somewhat more rapidly when administered in the MLM emulsion compared to the MMM/LLL emulsion. There were only slight differences in tissue distribution of label. Hence, differences in in vivo metabolism of the long-chain fatty acids were small compared to the marked differences in TG structure and in patterns of product release during in vitro lipolysis.

  • 11.
    Hultin, M
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Olivecrona, G
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Olivecrona, T
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Effect of protamine on lipoprotein lipase and hepatic lipase in rats.1994In: Biochemical Journal, ISSN 0264-6021, E-ISSN 1470-8728, Vol. 304 ( Pt 3), p. 959-66Article in journal (Refereed)
    Abstract [en]

    The polycation protamine impedes the catabolism of triglyceride-rich lipoproteins and this has been suggested to be due to intravascular inactivation of lipoprotein lipase. We have made intravenous injections of protamine to rats and found that both lipoprotein lipase and hepatic lipase activities were released to plasma. The effect of protamine was more short-lived than that obtained by injection of heparin. The release of hepatic lipase by protamine was as effective as the release by heparin, while the amount of lipoprotein lipase released by protamine was only about one-tenth of that released by heparin. This was not due to inactivation of lipoprotein lipase, since injection of an excess of heparin 10 min after injection of protamine released as much lipoprotein lipase activity to plasma as in controls. The results in vivo differed from those obtained in model experiments in vitro. Protamine was able to almost quantitatively release both lipoprotein lipase and hepatic lipase from columns of heparin-agarose. The displacement was dependent on the total amount of protamine that had passed over the column, indicating that it was due to occupation by protamine of all available binding sites. Our results in vivo showed that the binding sites for lipoprotein lipase were not blocked as efficiently as those for hepatic lipase, indicating that the binding structures were not identical. It was concluded that the impaired turnover of lipoproteins by protamine probably was due to prevention of binding of the lipoproteins to endothelial cell surfaces rather than to impaired lipase function.

  • 12.
    Hultin, M
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Olivecrona, T
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Conversion of chylomicrons into remnants.1998In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 141 Suppl 1, p. S25-9Article in journal (Refereed)
    Abstract [en]

    The turnover of chylomicrons in the blood is the sum of several processes. The native chylomicron is synthesized in the intestine out of available substrates. When the chylomicron enters the circulation exchanges of apolipoproteins with other lipoproteins, it also binds to the vascular endothelium where the chylomicron is lipolyzed by lipoprotein lipase. After a short period in the circulation the chylomicron/chylomicron remnant appears to be available for receptor mediated uptake. In this paper several of the processes involved in generation and clearance of chylomicron remnants are discussed.

  • 13.
    Hultin, M
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Savonen, R
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Olivecrona, T
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Chylomicron metabolism in rats: lipolysis, recirculation of triglyceride-derived fatty acids in plasma FFA, and fate of core lipids as analyzed by compartmental modelling.1996In: Journal of Lipid Research, ISSN 0022-2275, E-ISSN 1539-7262, Vol. 37, no 5, p. 1022-36Article in journal (Refereed)
    Abstract [en]

    Chylomicrons labeled in vivo with [14C]oleic acid (primarily in triglycerides (TG), providing a tracer for lipolysis) and [3H]retinol (primarily in ester form, providing a tracer for the corelipids) were injected into rats. Disappearance of the two labels from plasma and appearance of label in plasma free fatty acids (FFA) were analyzed by compartmental modelling. Both core and TG label distributed into an apparent volume 10-15% larger than the blood volume. Part of this probably represents margination to endothelial-binding-lipolysis sites. An open two-compartmental model for plasma FFA was derived from experiments where unesterified oleic acid complexed to albumin was injected. Applying this model revealed that most of the oleic acid from chylomicron triglycerides mixes with the FFA. The disappearance of chylomicron core label required a model in which the label transfers into a second compartment before it leaves the blood. The rate constant for the transformation was high and predicted that, on average, chylomicron spent less than 2 min in the first compartment. The rate out from the second compartment predicted that about 60% of the core label left blood while, on average, chylomicron retained more than half of its triglyceride molecules, i.e., after rather limited lipolysis. The mechanism by which the core label leaves blood is not clear. Modelling showed that under the assumption that the process is shared by chylomicron triglycerides, about half of them go out by this pathway. Comparing fed and fasted rats, the main differences were in the turnover of FFA and in the extent to which chylomicron TG label reappeared in the FFA. This study indicates that a large fraction of the triglycerides in chylomicrons leave plasma together with the core lipids and that most of the fatty acids from chylomicron triglycerides mix into the same metabolic compartments as do plasma free fatty acids.

  • 14.
    Hultin, Magnus
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Turnover of chylomicrons in the rat1995Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Mechanisms involved in the clearance of chylomicrons and aspects of the interactions at the vascular endothelium were studied in the rat.

    The poly-anion heparin, known to release lipoprotein lipase (LPL) from the vascular endothelium, enhanced the clearance of chylomicrons. Five minutes after heparin injection, the clearance of chylomicron triglycerides and retinyl esters was markedly accelerated. The rapid initial clearance was followed by a slower clearance of heavily lipolyzed chylomicrons. In contrast, one hour after heparin the clearance of both triglycerides and retinyl esters was retarded. This decreased removal of chylomicrons coincided with a decrease in the heparin releasable LPL activity, indicating that the previous release to plasma by heparin had resulted in net loss of functional LPL in the tissues.

    The poly-cation protamine released hepatic lipase and some LPL from their binding sites to plasma. One hour after protamine, plasma triglyceride levels were increased, indicating that chylomicron removal was impeded. It has been speculated that protamine inactivates LPL in vivo, but this was not the case. Ten minutes after injection of protamine normal amounts of LPL could be released by heparin. Thus, the accumulation of plasma triglycerides was not due to a rapid inactivation of LPL by protamine.

    LPL has specificity for sn-1,3-ester bonds. To investigate if this specificity is important in vivo, a lipid emulsion containing medium-chain fatty acids (MCFA) in the sn-1,3-position and long-chain fatty acids (LCFA) in the sn-2-position was synthesized, as well as an emulsion containing MCFA-TG mixed with LCFA-TGs (MMM/LLL). In vitro experiments showed large differences in the hydrolysis of the emulsions, but in vivo there were only small differences in the metabolism.

    To further study if lipid emulsions are cleared by the same mechanisms as chylomicrons, an emulsion was made by the same formulation as Intralipid® with addition of 3H-triolein and ,4C-cholesteryl ester. As measured by the removal of cholesteryl esters, the emulsion was cleared at the same rate as was chylomicrons. The triglyceride label was, however, removed more slowly from the emulsion droplets than from chylomicrons. Together with the lower recirculation of labeled free fatty acids (FFA) in plasma, this suggests that there was less lipolysis of the emulsion. The current view that removal of lipid emulsions in vivo is mainly dependent on LPL-mediated hydrolysis might thus not be correct.

    To further analyze the metabolism of chylomicrons, a compartmental model was developed. In this process, the distribution volume for chylomicrons was shown to be larger than the blood volume, a model for the metabolism of FFA in the rat was validated, and the full tissue distribution of injected chylomicrons was determined. According to the model, about half of the triglyceride label was removed from the circulation together with the core label while for the emulsion this number was about 80 %. In fasted rats all labeled fatty acids appeared to mix with the plasma FFA pool, while in fed rats about one-fifth of the fatty acids did not mix with the FFA but was apparently channeled directly to tissue metabolism.

  • 15.
    Hultin, Magnus
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Hedberg, Hans
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Härgestam, Maria
    Umeå University, Faculty of Medicine, Department of Nursing.
    Söderström, Tor
    Umeå University, Faculty of Social Sciences, Department of Education.
    Thorstensson, Mirko
    Swedish Defense Research Agency (FOI), Linköping, Sweden.
    Brulin, Christine
    Umeå University, Faculty of Medicine, Department of Nursing.
    Has five years of team training in non-technical skills improved trauma team performance in our University Hospital?2011In: Inspire... and be inspired: AMEE 2011 Abstract Book: 29-31 August 2011, Vienna, Austria, Scotland: Association for Medical Education in Europe , 2011, p. 447-447Conference paper (Refereed)
    Abstract [en]

    Background: For five years our emergency ward has trained non-technical skills using trauma scenarios in a simulator environment. Reflection-on-action was accomplished by 60 minutes video-facilitated structured debriefing. The aim of this study was to explore whether teams trained in non-technical skills are more efficient in the management of severely wounded patients.

    Summary of work: The standardized trauma patient scenario started with an ambulance crew being called

    to a location outside the hospital. Patient care was followed from the site of trauma, in the ambulance and

    in the emergency room. When the hand-over was finished, the condition was worsened. All ambulance crew and trauma team communication were recorded, synchronised in F-REX and key events time-logged. Nineteen teams with 144 participants were included in the study.

     

    Summary of results: 56% of the participants had trained non-technical skills. 78% of those with ontechnical

    skills training, and 62% of those without previous simulator based training, estimated themselves to have appropriate training for the task. The time from the induced worsened condition until the trauma team had assessed airways, breathing, circulation and disabilities were 74±39, 104±45, 172±85 and 223±194 s respectively. No significant effect on the medical performance on basis of previous training in non-technical skills could be detected. Further video analysis is required to more deeply understand the links between teamwork and medical performance.

     

    Conclusions: Trauma team training in CRM principles improves the self-confidence in trauma teams, but not the medical performance.

     

    Take-home messages: Improved non-technical skills might be difficult to translate into improvements in technical skills.

  • 16.
    Hultin, Magnus
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Jacobsson, Maritha
    Umeå University, Faculty of Social Sciences, Department of Social Work.
    Brulin, Christine
    Umeå University, Faculty of Medicine, Department of Nursing.
    Härgestam, Maria
    Umeå University, Faculty of Medicine, Department of Nursing. Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Kunskap och kommunikation är en ledares plattform: tvärvetenskaplig studie av traumateamövningar visar betydelsen av verbal och icke-verbal kommunikation2016In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 113, no 39, p. 1-5Article in journal (Refereed)
  • 17.
    Hultin, Magnus
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Magnusson, Erik
    Socialstyrelsen.
    Vi tror provet ger ett bra resultat2017In: Dagens Medicin, no 03-08Article in journal (Other (popular science, discussion, etc.))
    Abstract [sv]

    Vår förhoppning är att det nya systemet ger förutsättningar för fler att få arbeta med det som han eller hon är utbildad för och med det som svensk hälso- och sjukvård så tydligt efter­frågar, skriver Magnus Hultin och Erik Magnusson i ett svar till ett tidigare debattinlägg.

  • 18.
    Hultin, Magnus
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry. Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Savonen, Roger
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Chevreuil, Olivier
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Olivecrona, Thomas
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Chylomicron metabolism in rats: kinetic modeling indicates that the particles remain at endothelial sites for minutes2013In: Journal of Lipid Research, ISSN 0022-2275, E-ISSN 1539-7262, Vol. 54, no 10, p. 2595-2605Article in journal (Refereed)
    Abstract [en]

    Chylomicrons labeled in vivo with (14)C-oleic acid (primarily in triglycerides, providing a tracer for lipolysis) and (3)H-retinol (primarily in ester form, providing a tracer for the core lipids) were injected into rats. Radioactivity in tissues was followed at a series of times up to 40 min and the data were analyzed by compartmental modeling. For heart-like tissues it was necessary to allow the chylomicrons to enter into a compartment where lipolysis is rapid and then transfer to a second compartment where lipolysis is slower. The particles remained in these compartments for minutes and when they returned to blood they had reduced affinity for binding in the tissue. In contrast, the data for liver could readily be fitted with a single compartment for native and lipolyzed chylomicrons in blood, and there was no need for a pathway back to blood. A composite model was built from the individual tissue models. This whole-body model could simultaneously fit all data for both fed and fasted rats and allowed estimation of fluxes and residence times in the four compartments; native and lipolyzed chylomicrons ("remnants") in blood, and particles in the tissue compartments where lipolysis is rapid and slow, respectively.

  • 19.
    Härgestam, Maria
    et al.
    Umeå University, Faculty of Medicine, Department of Nursing. Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Hultin, Magnus
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Brulin, Christine
    Umeå University, Faculty of Medicine, Department of Nursing.
    Jacobsson, Maritha
    Umeå University, Faculty of Social Sciences, Department of Social Work.
    Trauma team leaders' non-verbal communication: video registration during trauma team training2016In: Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine, ISSN 1757-7241, E-ISSN 1757-7241, Vol. 24, article id 37Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: There is widespread consensus on the importance of safe and secure communication in healthcare, especially in trauma care where time is a limiting factor. Although non-verbal communication has an impact on communication between individuals, there is only limited knowledge of how trauma team leaders communicate. The purpose of this study was to investigate how trauma team members are positioned in the emergency room, and how leaders communicate in terms of gaze direction, vocal nuances, and gestures during trauma team training.

    METHODS: Eighteen trauma teams were audio and video recorded during trauma team training in the emergency department of a hospital in northern Sweden. Quantitative content analysis was used to categorize the team members' positions and the leaders' non-verbal communication: gaze direction, vocal nuances, and gestures. The quantitative data were interpreted in relation to the specific context. Time sequences of the leaders' gaze direction, speech time, and gestures were identified separately and registered as time (seconds) and proportions (%) of the total training time.

    RESULTS: The team leaders who gained control over the most important area in the emergency room, the "inner circle", positioned themselves as heads over the team, using gaze direction, gestures, vocal nuances, and verbal commands that solidified their verbal message. Changes in position required both attention and collaboration. Leaders who spoke in a hesitant voice, or were silent, expressed ambiguity in their non-verbal communication: and other team members took over the leader's tasks.

    DISCUSSION:

    In teams where the leader had control over the inner circle, the members seemed to have an awareness of each other's roles and tasks, knowing when in time and where in space these tasks needed to be executed. Deviations in the leaders' communication increased the ambiguity in the communication, which had consequences for the teamwork. Communication cannot be taken for granted; it needs to be practiced regularly just as technical skills need to be trained. Simulation training provides healthcare professionals the opportunity to put both verbal and non-verbal communication in focus, in order to improve patient safety.

    CONCLUSIONS: Non-verbal communication plays a decisive role in the interaction between the trauma team members, and so both verbal and non-verbal communication should be in focus in trauma team training. This is even more important for inexperienced leaders, since vague non-verbal communication reinforces ambiguity and can lead to errors.

  • 20.
    Härgestam, Maria
    et al.
    Umeå University, Faculty of Medicine, Department of Nursing. Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Lindkvist, Marie
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Brulin, Christine
    Umeå University, Faculty of Medicine, Department of Nursing.
    Jacobsson, Maritha
    Umeå University, Faculty of Social Sciences, Department of Social Work.
    Hultin, Magnus
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Communication in interdisciplinary teams: Exploring closed-loop communication during in situ trauma team training2013In: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 3, no 10, article id e003525Article in journal (Refereed)
    Abstract [en]

    Objectives: Investigate the use of call-out (CO) and closed-loop communication (CLC) during a simulated emergency situation, and its relation to profession, age, gender, ethnicity, years in profession, educational experience, work experience and leadership style.

    Design: Exploratory study.

    Setting: In situ simulator-based interdisciplinary team training using trauma cases at an emergency department.

    Participants: The result was based on 16 trauma teams with a total of 96 participants. Each team consisted of two physicians, two registered nurses and two enrolled nurses, identical to a standard trauma team.

    Results: The results in this study showed that the use of CO and CLC in trauma teams was limited, with an average of 20 CO and 2.8 CLC/team. Previous participation in trauma team training did not increase the frequency of use of CLC while ≥2 structured trauma courses correlated with increased use of CLC (risk ratio (RR) 3.17, CI 1.22 to 8.24). All professions in the trauma team were observed to initiate and terminate CLC (except for the enrolled nurse from the operation theatre). The frequency of team members’ use of CLC increased significantly with an egalitarian leadership style (RR 1.14, CI 1.04 to 1.26).

    Conclusions: This study showed that despite focus on the importance of communication in terms of CO and CLC, the difficulty in achieving safe and reliable verbal communication within the interdisciplinary team remained. This finding indicates the need for validated training models combined with further implementation studies.

  • 21.
    Härgestam, Maria
    et al.
    Umeå University, Faculty of Medicine, Department of Nursing. Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Lindkvist, Marie
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health. Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Jacobsson, Maritha
    Umeå University, Faculty of Social Sciences, Department of Social Work.
    Brulin, Christine
    Umeå University, Faculty of Medicine, Department of Nursing.
    Hultin, Magnus
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Trauma teams and time to early management during in situ trauma team training2016In: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 6, no 1, article id e009911Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To investigate the association between the time taken to make a decision to go to surgery and gender, ethnicity, years in profession, experience of trauma team training, experience of structured trauma courses and trauma in the trauma team, as well as use of closed-loop communication and leadership styles during trauma team training.

    DESIGN: In situ trauma team training. The patient simulator was preprogrammed to represent a severely injured patient (injury severity score: 25) suffering from hypovolemia due to external trauma.

    SETTING: An emergency room in an urban Scandinavian level one trauma centre.

    PARTICIPANTS: A total of 96 participants were divided into 16 trauma teams. Each team consisted of six team members: one surgeon/emergency physician (designated team leader), one anaesthesiologist, one registered nurse anaesthetist, one registered nurse from the emergency department, one enrolled nurse from the emergency department and one enrolled nurse from the operating theatre.

    PRIMARY OUTCOME: HRs with CIs (95% CI) for the time taken to make a decision to go to surgery was computed from a Cox proportional hazards model.

    RESULTS: Three variables remained significant in the final model. Closed-loop communication initiated by the team leader increased the chance of a decision to go to surgery (HR: 3.88; CI 1.02 to 14.69). Only 8 of the 16 teams made the decision to go to surgery within the timeframe of the trauma team training. Conversely, call-outs and closed-loop communication initiated by the team members significantly decreased the chance of a decision to go to surgery, (HR: 0.82; CI 0.71 to 0.96, and HR: 0.23; CI 0.08 to 0.71, respectively).

    CONCLUSIONS: Closed-loop communication initiated by the leader appears to be beneficial for teamwork. In contrast, a high number of call-outs and closed-loop communication initiated by team members might lead to a communication overload.

  • 22.
    Jacobsson, Maritha
    et al.
    Umeå University, Faculty of Social Sciences, Department of Social Work.
    Härgestam, Maria
    Umeå University, Faculty of Medicine, Department of Nursing.
    Hultin, Magnus
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Brulin, Christine
    Umeå University, Faculty of Medicine, Department of Nursing.
    Flexible knowledge repertoires: Communication by leaders in trauma teams2012In: Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine, ISSN 1757-7241, E-ISSN 1757-7241, Vol. 20, no 1, p. 44-Article in journal (Refereed)
    Abstract [en]

    Background: In emergency situations, it is important for the trauma team to efficiently communicate their observations and assessments. One common communication strategy is “closed-loop communication”, which can be described as a transmission model in which feedback is of great importance. The role of the leader is to create a shared goal in order to achieve consensus in the work for the safety of the patient. The purpose of this study was to analyze how formal leaders communicate knowledge, create consensus, and position themselves in relation to others in the team.

    Methods: Sixteen trauma teams were audio- and video-recorded during high fidelity training in an emergency department. Each team consisted of six members: one surgeon or emergency physician (the designated team leader), one anaesthesiologist, one nurse anaesthetist, one enrolled nurse from the theatre ward, one registered nurse and one enrolled nurse from the emergency department (ED). The communication was transcribed and analyzed, inspired by discourse psychology and Strauss’ concept of “negotiated order”. The data were organized and coded in NVivo 9.

    Results: The findings suggest that leaders use coercive, educational, discussing and negotiating strategies to work things through. The leaders in this study used different repertoires to convey their knowledge to the team, in order to create a common goal of the priorities of the work. Changes in repertoires were dependent on the urgency of the situation and the interaction between team members. When using these repertoires, the leaders positioned themselves in different ways, either on an authoritarian or a more egalitarian level.

    Conclusion: This study indicates that communication in trauma teams is complex and consists of more than just transferring messages quickly. It also concerns what the leaders express, and even more importantly, how they speak to and involve other team members.

  • 23.
    Karpe, F
    et al.
    Karolinska Institutet.
    Hultin, M
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Endogenous triglyceride-rich lipoproteins accumulate in rat plasma when competing with a chylomicron-like triglyceride emulsion for a common lipolytic pathway.1995In: Journal of Lipid Research, ISSN 0022-2275, E-ISSN 1539-7262, Vol. 36, no 7, p. 1557-66Article in journal (Refereed)
    Abstract [en]

    The rat liver secretes very low density lipoproteins (VLDL) containing either apoB-100 or apoB-48. After oral fat intake, chylomicrons containing apoB-48 and endogenously synthesized VLDL are mixed in the blood and the triglyceride clearance from these triglyceride-rich lipoprotein species compete for the same lipolytic pathway, i.e., lipoprotein lipase. A situation mimicking alimentary lipemia was induced by a short-term intravenous primed infusion of a chylomicron-like triglyceride emulsion to fed and fasted rats. The plasma concentration of apoB-100 and apoB-48 was monitored in triglyceride-rich lipoprotein subfractions after separation with density gradient ultracentrifugation by analytical SDS-PAGE. The net liver secretory output of VLDL was quantified by lipolytic blockade induced by Triton WR 1339. The chylomicron-like triglyceride emulsion induced a linear increase of large VLDL (Sf 60-400 subfraction containing both apoB-100 and apoB-48), almost to the same extent as that induced by Triton. The clearance of postprandial triglyceride-rich lipoproteins and both lipolysis and clearance of intravenously injected labeled rat chylomicrons was efficiently inhibited by the emulsion but not so complete as for fasting VLDL. The linearity of the VLDL increase and the very early response in the Intralipid-treated rats suggest that enhanced synthesis of VLDL is not a major cause for the accumulation. Rather, the present data indicate that a high plasma concentration of a chylomicron-like triglyceride emulsion competes efficiently with liver-derived VLDL for the same lipolytic pathway, which leads to accumulation in plasma of endogenous VLDL in the postprandial state.

  • 24.
    Karpe, F
    et al.
    Karolinska Institutet.
    Olivecrona, T
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Hamsten, A
    Karolinska Institutet.
    Hultin, M
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Chylomicron/chylomicron remnant turnover in humans: evidence for margination of chylomicrons and poor conversion of larger to smaller chylomicron remnants.1997In: Journal of Lipid Research, ISSN 0022-2275, E-ISSN 1539-7262, Vol. 38, no 5, p. 949-61Article in journal (Refereed)
    Abstract [en]

    The size of cholesterol-rich lipoprotein particles is a strong determinant of whether they may be deposited in the arterial wall and by this become potentially atherogenic. This study deals with the in vivo transformation of larger-sized chylomicrons and chylomicron remnants to smaller-sized remnants. Twelve healthy men aged 22 to 45 years were given a fatty meal to which retinyl palmitate (RP) had been added. Plasmapheresis was performed 4 1/2 h after meal intake to isolate approximately 400 ml plasma. The RP-rich plasma was re-injected to the subject 24 h later. The RP content was determined in whole plasma and in Svedberg flotation rate fractions (Sf) > 400, Sf 60-400 and Sf 20-60. A compartmental model was developed for the kinetic analysis. Lipoprotein fractions showed minimal signs of aggregation, thus arguing for well-preserved postprandial lipoproteins. Approximately a fourth [23% (4-68%)] of the RP-containing lipoproteins in the Sf > 400 pool was converted to smaller species (Sf 60-400). Conversion of material from the Sf 60-400 to the Sf 20-60 fraction could not be detected. In a second study a large bolus dose of a triglyceride emulsion (Intralipid) was injected to subjects shortly after the RP-labeled plasma to investigate the endothelial binding of the chylomicron/chylomicron remnants. RP material in the Sf > 400 fraction rapidly returned to plasma, arguing for margination of chylomicrons, whereas the corresponding effect was minimal in the Sf 60-400 and Sf 20-60 fractions. The formation of small chylomicron remnants from the larger chylomicron/chylomicron remnant species is limited and large chylomicron/chylomicron remnants are not evenly distributed in plasma, rather they show signs of being marginated to the vascular endothelium.

  • 25.
    Lindgren, Cecilia
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Hultin, Magnus
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Koskinen, Lars-Owe D
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Lindvall, Peter
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Borota, Ljubisa
    Department of Radiology, Oncology and Radiation Science, Uppsala University, Sweden .
    Naredi, Silvana
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    ADMA levels and arginine/ADMA ratios reflect severity of disease and extent of inflammation after subarachnoid hemorraghe2014In: Neurocritical Care, ISSN 1541-6933, E-ISSN 1556-0961, Vol. 21, no 1, p. 91-101Article in journal (Refereed)
    Abstract [en]

    Background: Subarachnoid hemorrhage (SAH) is characterized by an inflammatory response that might induce endothelial dysfunction. The aim of this study was to evaluate if ADMA and arginine/ADMA ratios after SAH (indicators of endothelial dysfunction) are related to clinical parameters, inflammatory response, and outcome.

    Methods: Prospective observational study. ADMA, arginine, C-reactive protein (CRP), and cytokines were obtained 0–240 h (h) after SAH. Definition of severe clinical condition was Hunt&Hess (H&H) 3–5 and less severe clinical condition H&H 1–2. Impaired cerebral circulation was assessed by clinical examination, transcranial doppler, CT-scan, and angiography. Glasgow outcome scale (GOS) evaluated the outcome.

    Results: Compared to admission, 0–48 h after SAH, the following was observed 49–240 h after SAH; (a) ADMA was significantly increased at 97–240 h (highest 217–240 h), (b) CRP was significantly increased at 49–240 h (highest 73–96 h), (c) interleukin-6 (IL-6) was significantly lower at 97–240 h (highest 49–96 h), p < 0.05. ADMA, CRP, and IL-6 were significantly lower and peak arginine/ADMA ratio was significantly higher in patients with H&H 1–2 compared to patients with H&H 3–5, p < 0.05. The peak ADMA or the nadir arginine/ADMA ratio did not differ significantly between patients with (55 %) or without (45 %) signs of impaired cerebral circulation. The peak ADMA or the nadir arginine/ADMA ratio did not differ significantly between patients with GOS 1–3 and patients with GOS 4–5.

    Conclusions: ADMA increased significantly after SAH, and the increase in ADMA started after the pro-inflammatory markers (CRP and IL-6) had peaked. This might indicate that endothelial dysfunction, with ADMA as a marker, is induced by a systemic inflammation.

  • 26.
    Lindgren, Cecilia
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Hultin, Magnus
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Koskinen, Lars-Owe
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Söderberg, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Edvardsson, Ludwig
    Naredi, Silvana
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology. Göteborgs universitet.
    Long term survivors of subarachnoid haemorrhage have an increased risk of death due to cerebrovascular causesManuscript (preprint) (Other academic)
  • 27.
    Lindgren, Cecilia
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Naredi, Silvana
    Söderberg, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Koskinen, Lars-Owe
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Hultin, Magnus
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Leptin levels after subarachnoid haemorrhage are gender dependent2016In: SpringerPlus, E-ISSN 2193-1801, Vol. 5, article id 667Article in journal (Refereed)
    Abstract [en]

    Background: Subarachnoid hemorrhage (SAH) is a neurological disease where the majority of the patients are critically ill. The adipokine leptin has in cerebral emergencies been related to severity of disease and to adverse outcome. The aim of this study was to examine leptin levels over time after SAH and associations to gender, age, body mass index, severity of disease, parenteral lipids, systemic organ failure and outcome.

    Methods: Prospective observational study in 56 patients. Leptin was obtained 0-240 h after SAH, in 48 h intervals. Severity of disease was assessed with the Hunt and Hess score, organ failure with the sequential organ failure assessment score, and outcome with Glasgow outcome scale. Leptin levels in the SAH group were compared with controls from the same geographical area.

    Results: At admission, Leptin was significantly higher in SAH patients compared to controls, both in female (28.6 +/- 25.6 vs 13.0 +/- 2.3 ng/mL, p = 0.001) and male patients (13.3 +/- 8.4 vs 4.3 +/- 0.7 ng/mL, p = 0.001). Leptin levels remained stable over time. Female patients had significantly higher leptin levels than male patients, and deceased female patients had higher leptin levels than female survivors (85.5 +/- 20.5 vs 50.5 +/- 34.6, n = 4/35, p < 0.05). Leptin levels did not differ between male survivors and non-survivors. Leptin levels were not associated with severity of disease, organ failure or parenteral lipids.

    Conclusion: Leptin levels were significantly higher in both male and female patients compared to controls. Higher leptin levels were related to outcome and organ failure in women but not in men. When analysing leptin levels gender-related differences should be considered.

  • 28.
    Lindgren, Cecilia
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Söderberg, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Koskinen, Lars-Owe
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Hultin, Magnus
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Edvardsson, L.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Naredi, S,
    Anestesiologi, Sahlgrenska Akademin, Göteborg.
    Long-term subarachnoid haemorrhage survivors still die due to cerebrovascular causes2015In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 132, no 6, p. 410-416Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Subarachnoid haemorrhage (SAH) is associated with sympathetic nervous activation and inflammation. SAH could therefore theoretically be a risk factor for development of cardiovascular disease. The aim of this study was to investigate whether long-term (>/=1 year) SAH survivors had an increased risk of death due to cardiovascular causes. MATERIAL & METHODS: SAH patients >/=18 years treated at Umea University Hospital between 1986 and 2006 were eligible for inclusion. Deceased patients were identified in the Swedish population register. Death certificates from long-term SAH survivors and causes of death in the general population were obtained from the National Board of Health and Welfare, Sweden. The prevalence of comorbidities at the time of SAH was compared with the distribution of cardiovascular risk factors in the northern Sweden MONICA (Multinational Monitoring of Trends and Determinants in Cardiovascular Disease) health survey. Analyses were stratified for age and sex. RESULTS: In the SAH patients, the median year of SAH was 1992 and the median year of death was 2001. The MONICA survey in 1994 and the distribution of deaths in the general population in 2001 were used for comparison. Long-term SAH survivors had, compared to the general population, a significantly increased risk for death due to cerebrovascular disease (P < 0.0001), but not for death due to cardiovascular disease. Hypertension was more common in SAH patients compared to survey participants (P < 0.01). CONCLUSION: Cerebrovascular causes of death were significantly more common in long-term survivors after SAH compared to the general population.

  • 29.
    Liu, G
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Hultin, M
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Ostergaard, P
    Olivecrona, T
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Interaction of size-fractionated heparins with lipoprotein lipase and hepatic lipase in the rat.1992In: Biochemical Journal, ISSN 0264-6021, E-ISSN 1470-8728, Vol. 285 ( Pt 3), p. 731-6Article in journal (Refereed)
    Abstract [en]

    Heparin and heparin partially depolymerized by enzymic digestion were separated into six size fractions. Hep 1 (tetrasaccharides), with a mean M(r) of 1200, did not release significant amounts of either lipoprotein lipase (LPL) or hepatic lipase (HL) on intravenous injection into rats. Hep 2 (mainly octa- and deca-saccharides), with a mean M(r) of 2400-3000, released both lipases. To evoke the same plasma activity of LPL and HL required about 10 times more by weight, or about 40 times more molecules, of this heparin than of hep 5 (mean M(r) 12,000, similar to conventional heparin). Hep 5 impeded binding and degradation of 125I-labelled bovine LPL by perfused rat livers. In contrast, hep 2 had no detectable effect on these processes. This demonstrates a difference between the sites in the liver that mediate binding, uptake and degradation of LPL, and the extrahepatic sites that bind functional LPL, and the hepatic sites that bind functional HL. After injection of 3.25 mg of hep 5/kg body weight, plasma LPL activity rapidly rose and then remained high for at least 1 h. With hep 2, plasma LPL also rose rapidly, but then decreased to almost basal by 1 h. When a labelled triacylglycerol emulsion was injected 1 h after the heparins, the fractional catabolic rate was enhanced in the rats that had received conventional heparin, as expected from the high plasma LPL activity, but decreased compared with controls in rats that had received hep 2, indicating that available LPL had been depleted through enhanced transport to and uptake in the liver.

  • 30.
    Lookene, Aivar
    et al.
    Umeå University, Faculty of Medicine, Medical Biosciences, Physiological chemistry.
    Zhang, Liyan
    Umeå University, Faculty of Medicine, Medical Biosciences, Physiological chemistry.
    Hultin, Magnus
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Anesthesiology and Intensive Care.
    Olivecrona, Gunilla
    Umeå University, Faculty of Medicine, Medical Biosciences, Physiological chemistry.
    Rapid subunit exchange in dimeric lipoprotein lipase and properties of the inactive monomer.2004In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 279, no 48, p. 49964-49972Article in journal (Refereed)
  • 31.
    Magnusson, Erik
    et al.
    Socialstyrelsen.
    Hultin, Magnus
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Längre skrivtid och nya chanser i det nya kunskapsprovet för läkare.2017In: Läkartidningen, no 08Article in journal (Other (popular science, discussion, etc.))
    Abstract [sv]

    Socialstyrelsen och Umeå universitet förlänger provtiden till fyra timmar för det teoretiska delprovet i det nya kunskapsprovet för läkare. Dessutom behöver de med underkända resultat vid de första två provtillfällena inte räkna in dem i de maximalt tre försök de har på sig att klara provet. Socialstyrelsen kommer att kontakta berörda.

  • 32.
    Olivecrona, T
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Bengtsson-Olivecrona, G
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Hultin, M
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Peterson, J
    Vilaró, S
    Deckelbaum, R J
    Carpentier, Y A
    Patsch, J
    What factors regulate the action of lipoprotein lipase?1991In: Advances in Experimental Medicine and Biology, ISSN 0065-2598, E-ISSN 2214-8019, Vol. 285, p. 335-9Article in journal (Refereed)
  • 33.
    Olivecrona, T
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Bengtsson-Olivecrona, G
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Ostergaard, P
    Liu, G
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Chevreuil, O
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Hultin, M
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    New aspects on heparin and lipoprotein metabolism.1993In: Haemostasis, ISSN 0301-0147, E-ISSN 1423-0038, Vol. 23 Suppl 1, p. 150-60Article in journal (Refereed)
    Abstract [en]

    Lipoprotein lipase (LPL) and hepatic lipase (HL) are two enzymes which participate in metabolism of plasma lipoproteins. The enzymes are located at vascular surfaces and are released from their binding sites on injection of heparin. In this paper we give a short overview of the structure of the lipases and their role in lipoprotein metabolism. Earlier studies had shown that low molecular weight (LMW) heparin preparations result in lower LPL activities in blood than do corresponding amounts of conventional heparin. Studies with organ perfusion in rats show that the two types of heparin have similar ability to release the lipases from their binding sites in extrahepatic tissues, but that LMW heparin is less effective than conventional heparin in preventing rapid uptake and degradation of LPL by the liver. After injection of heparin the metabolism of triglyceride-rich lipoproteins is initially accelerated, presumably as a result of the high levels of circulating LPL. Then follows a phase when lipoprotein metabolism is slower than normal, perhaps because endothelial LPL has been depleted by accelerated transport to and degradation in the liver.

  • 34.
    Olivecrona, T
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Bergö, M
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Hultin, M
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Olivecrona, G
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Nutritional regulation of lipoprotein lipase.1995In: Canadian Journal of Cardiology, ISSN 0828-282X, E-ISSN 1916-7075, Vol. 11 Suppl G, p. 73G-78GArticle in journal (Refereed)
    Abstract [en]

    Lipoprotein lipase (LPL) is needed for normal catabolism of triglyceride-rich lipoproteins. In some tissues, notably the adipose tissue, the local LPL activity is an important determinant for how much lipid is taken up. There is regulation of gene expression, but the rapid changes that occur in response to the nutritional state are mediated mainly by post-transcriptional mechanisms. In the fed state, the adipose tissue expresses its full potential for LPL production, as set by the mRNA levels and the rate of protein synthesis. During fasting, LPL activity is suppressed by an unknown post-translational mechanism. In heart, regulation is primarily exerted on the equilibrium between LPL at endothelial sites and LPL in blood, with more endothelial LPL in the fasted state. LPL forms complexes with fatty acids which results in shut-down of lipolysis and detachment of both lipase and lipoproteins from the endothelial site. This provides a molecular coupling device between the cellular metabolic state and the rate of lipoprotein catabolism. There is growing evidence that LPL is a ligand for binding of lipoprotein particles such as chylomicron remnants to cell surfaces and receptors.

  • 35.
    Olivecrona, T
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Hultin, M
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Bergö, M
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Olivecrona, G
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Lipoprotein lipase: regulation and role in lipoprotein metabolism.1997In: Proceedings of the Nutrition Society, ISSN 0029-6651, E-ISSN 1475-2719, Vol. 56, no 2, p. 723-9Article in journal (Refereed)
  • 36.
    Olivecrona, Thomas
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Liu, Guoqing
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Hultin, Magnus
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Bengtsson-Olivecrona, Gunilla
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Regulation of lipoprotein lipase1993In: Biochemical Society Transactions, ISSN 0300-5127, E-ISSN 1470-8752, Vol. 21, no 2, p. 509-513Article in journal (Refereed)
  • 37.
    Olofsson, Anders D
    et al.
    Umeå University, Faculty of Social Sciences, Department of Education.
    Pettersson, Fanny
    Umeå University, Faculty of Social Sciences, Department of Education.
    Ljungberg, Christina
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Hand Surgery.
    Hultin, Magnus
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Naredi, Silvana
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    The implementation of distance teaching in the Swedish Regionalized Medical Program - multiple small steps of change for an inert system2013In: Book of Abstracts of the 40th AMEE-conference: Colouring outside the lines / [ed] AMEE, Prague, 2013, p. 329-329Conference paper (Refereed)
    Abstract [en]

    Background: This study examines possibilities and challenges when implementing distance teaching for teaching theoretical content in the Swedish regionalized medical program (RMP). The distance teaching by means of digital technologies and Technology-Enhanced Learning (TEL) is seen as an alternative to the face-to-face teaching in the medical program. Summary of work: A framework built upon the work of Sannino (2008) including the notion of dominant and non-dominant activities, conflicts and transitional actions were used for analysis. Summary of results: In the results a number of conflicts were identified which inhibit medical teachers from adopting especially interactive and communicative elements of distance teaching. Those were for example teachers’ digital literacy, lack of trust in digital teaching tools and willingness to keep to the face-to-face teaching practice. Conclusions: Illustrated by transitional actions it is discussed how the non-dominant distance teaching activity actually functioned as a catalyst for minor but important changes in the medical teachers’ dominant face-to-face teaching practice. Based on the results from this study one can raise the question of what really can be seen as a success or a failure when implementing TEL in medical education. Implementation processes in medical education is a process of interplay between dominant and non-dominant activities. Recognizing such interplay provides possibilities for future educational development. Take-home messages: Implementing distance teaching is not a straightforward process but rather characterized by small steps of change that needs to be continuously supported by the medical program management.

  • 38.
    Rodling Wahlström, Marie
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Olivecrona, Magnus
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Bengtsson, Anders
    The Sahlgrenska Academy, University of Gothenburg.
    Koskinen, Lars-Owe D
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Naredi, Silvana
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Hultin, Magnus
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Effects of prostacyclin on the early inflammatory response in patients with traumatic brain injury: a randomised clinical study2014In: SpringerPlus, E-ISSN 2193-1801, Vol. 3, article id 98Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE AND DESIGN: A prospective, randomised, double-blinded, clinical trial was performed at a level 1 trauma centre to determine if a prostacyclin analogue, epoprostenol (Flolan®), could attenuate systemic inflammatory response in patients with severe traumatic brain injury (TBI).

    SUBJECTS: 46 patients with severe TBI, randomised to epoprostenol (n = 23) or placebo (n = 23).

    TREATMENT: Epoprostenol, 0.5 ng · kg(-1) · min(-1), or placebo (saline) was given intravenously for 72 hours and then tapered off over the next 24 hours.

    METHODS: Interleukin-6 (IL-6), interleukin-8 (IL-8), soluble intracellular adhesion molecule-1 (sICAM-1), C-reactive protein (CRP), and asymmetric dimethylarginine (ADMA) levels were measured over five days. Measurements were made at 24 h intervals ≤24 h after TBI to 97-120 h after TBI.

    RESULTS: A significantly lower CRP level was detected in the epoprostenol group compared to the placebo group within 73-96 h (p = 0.04) and within 97-120 h (p = 0.008) after trauma. IL-6 within 73-96 h after TBI was significantly lower in the epoprostenol group compared to the placebo group (p = 0.04). ADMA was significantly increased within 49-72 h and remained elevated, but there was no effect of epoprostenol on ADMA levels. No significant differences between the epoprostenol and placebo groups were detected for IL-8 or sICAM-1.

    CONCLUSIONS: Administration of the prostacyclin analogue epoprostenol significantly decreased CRP and, to some extent, IL-6 levels in patients with severe TBI compared to placebo. These findings indicate an interesting option for treatment of TBI and warrants future larger studies.

    TRIAL REGISTRATION: ClinicalTrials.gov Identifier, NCT01363583.

  • 39.
    Rodling Wahlström, Marie
    et al.
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Anesthesiology and Intensive Care.
    Olivecrona, Magnus
    Umeå University, Faculty of Medicine, Pharmacology and Clinical Neuroscience, Neurosurgery.
    Koskinen, Lars-Owe
    Umeå University, Faculty of Medicine, Pharmacology and Clinical Neuroscience, Neurosurgery.
    Naredi, Silvana
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Anesthesiology and Intensive Care.
    Hultin, Magnus
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Anesthesiology and Intensive Care.
    Subarachnoid haemorrhage induces a long-lasting increase of asymmetric dimethylarginine, ADMA, in serumArticle in journal (Other academic)
    Abstract [en]

    Background and Purpose: Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase (NOS), inhibiting nitric oxide (NO) production and thus induces vasoconstriction and endothelial dysfunction. ADMA might therefore be involved in the cerebral vasospasm and cardiovascular complications observed after subarachnoid haemorrhage (SAH). The aim of this study was to evaluate whether ADMA was increased in subjects during the acute phase (first week) and non-acute phase (three months later) after SAH.

    Methods: Prospective clinical study of 20 subjects with SAH. ADMA in serum (ADMA/s) at admission was compared to sex and age matched controls. ADMA/s and ADMA in cerebrospinal fluid (ADMA/csf, from subjects with ventriculostomy) were determined by HPLC-based separation and detection.

    Results: There was no significant difference in ADMA/s the day after SAH (day 2) between SAH subjects and controls (0.22±0.10 vs. 0.25±0.12 µmol/L). ADMA/s increased by 68% during the first week after SAH (day 2; 0.22±0.10 vs. day 7; 0.37±0.34 µmol/L, p<0.05) and remained elevated at a three-month follow-up (0.36±0.10 µmol/L). ADMA/csf was significantly lower than ADMA/s throughout the study period.

    Conclusion; ADMA/s in SAH subjects increased significantly during the first week after SAH and remained elevated at a three-month follow-up. This might indicate that reduction of the available NO is involved in long-term effects after SAH.

  • 40.
    Rodling Wahlström, Marie
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Olivecrona, Magnus
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Koskinen, Lars-Owe
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Naredi, Silvana
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Hultin, Magnus
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Subarachnoid haemorrhage induces an inflammatory response followed by a delayed persisting increase in asymmetric dimethylarginine2012In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 72, no 6, p. 484-489Article in journal (Refereed)
    Abstract [en]

    Object: Subarachnoid haemorrhage (SAH) is associated with an inflammatory systemic response and cardiovascular complications. Asymmetric dimethyl arginine (ADMA), an endogenous inhibitor of nitric oxide synthase, mediates vasoconstriction and might contribute to cerebral vasoconstriction and cardiovascular complications after SAH. ADMA is also involved in inflammation and induces endo­thelial dysfunction.

    The aim of this study was to evaluate whether and how CRP (marker for systemic inflammation) and ADMA increased in patients during the acute phase (first week) after SAH. The ADMA level was also assessed in the patients in a non-acute phase (three months), and in healthy controls.

    Methods: Prospective study of 20 patients with aneurysmal SAH. ADMA and CRP were followed daily during the first week after SAH and a follow up sample for ADMA was obtained three months later. A single blood sample for ADMA was collected from age and sex matched healthy controls (n=40, 2 for each case).

    Results: CRP increased significantly from day 2; 16  (Confidence interval (CI) 10-23) mg/L to day 4; 84 (CI 47-120) mg/L, (p<0.01). ADMA increased significantly from day 2; 0.22 (CI 0.17-0.27) µmol/L, to day 7; 0.37 (CI 0.21-0.54) µmol/L, p<0.01. ADMA remained elevated at a three-month follow-up 0.36 (CI 0.31-0.42) µmol/L.

    ADMA in the first sample from the patients (day 1-3); 0.25 (CI 0.19-0.30) µmol/L, was not different from ADMA in matched healthy controls; 0.25 (CI 0.20-0.31), p>0.05.

    Conclusion: After SAH, CRP and ADMA in serum increased significantly during the first week and ADMA remained elevated three months later.

  • 41.
    Ruge, T
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Bergö, M
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Hultin, M
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Olivecrona, G
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Olivecrona, T
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Nutritional regulation of binding sites for lipoprotein lipase in rat heart.2000In: American Journal of Physiology. Endocrinology and Metabolism, ISSN 0193-1849, E-ISSN 1522-1555, Vol. 278, no 2, p. E211-8Article in journal (Refereed)
    Abstract [en]

    Several laboratories have shown that when rats are fasted, the amount of lipoprotein lipase (LPL) at the vascular endothelium in heart (monitored as the amount released by heparin) increases severalfold without corresponding changes in the production of LPL. This suggests that there is a change in endothelial binding of LPL. To study this, (125)I-labeled bovine LPL was injected. The fraction that bound in the heart was more than twice as high in fasted than in fed rats, 4.3% compared with 1.9% of the injected dose. Refeeding reversed this in 5 h. When unlabeled LPL was injected before the tracer, the fraction of (125)I-LPL that bound in heart decreased, indicating that the binding was saturable. When isolated hearts were perfused at 4 degrees C with a single pass of labeled LPL, twice as much bound in hearts of fasted rats. We conclude that fasting causes a change in the vascular endothelium in heart such that its ability to bind LPL increases.

  • 42.
    Savonen, R
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Nordstoga, K
    Christophersen, B
    Lindberg, A
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Shen, Y
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Hultin, M
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Olivecrona, T
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Olivecrona, G
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Chylomicron metabolism in an animal model for hyperlipoproteinemia type I.1999In: Journal of Lipid Research, ISSN 0022-2275, E-ISSN 1539-7262, Vol. 40, no 7, p. 1336-46Article in journal (Refereed)
    Abstract [en]

    Mink homozygous for the mutation Pro214Leu in lipoprotein lipase (LPL) had only traces of LPL activity but amounts of LPL protein in their tissues similar to those of normal mink. In normal mink, lymph chylomicrons from rats given [3H]retinol (incorporated into retinyl esters, providing a core label) and [14C]oleic acid (incorporated mainly in triglycerides (TG)) were rapidly cleared from the circulation. In the homozygous mink, clearance was much retarded. The ratio of TG to core label in plasma did not decrease and much less [14C]oleic acid appeared in plasma. Still, half of the labeled material disappeared from the circulating blood within 30;-40 min and the calculated total turnover of TG in the hypertriglyceridemic mink was almost as large as in normal mink. The core label was distributed to the same tissues in hypertriglyceridemic mink as in normal mink. Half to two-thirds of the cleared core label was in the liver. The large difference was that in the hypertriglyceridemic mink, TG label (about 40% of the total amount removed) followed the core label to the liver and there was no preferential uptake of TG over core label in adipose or muscle tissue. In normal mink, only small amounts of TG label (<10%) appeared in the liver, while most was in adipose and muscle tissues. Apolipoprotein B-48 dominated in the accumulated TG-rich lipoproteins in blood of hypertriglyceridemic mink, even in fasted animals.

  • 43.
    Savonen, Roger
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Hiden, Michaela
    Hultin, Magnus
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Zechner, Rudolf
    Levak-Frank, Sanja
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Olivecrona, Gunilla
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Olivecrona, Thomas
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    The tissue distribution of lipoprotein lipase determines where chylomicrons bind2015In: Journal of Lipid Research, ISSN 0022-2275, E-ISSN 1539-7262, Vol. 56, no 3, p. 588-598Article in journal (Refereed)
    Abstract [en]

    To determine the role of LPL for binding of lipoproteins to the vascular endothelium, and for the distribution of lipids from lipoproteins, four lines of induced mutant mice were used. Rat chylomicrons labeled in vivo with [C-14] oleic acid (primarily in TGs, providing a tracer for lipolysis) and [H-3]retinol (primarily in ester form, providing a tracer for the core lipids) were injected. TG label was cleared more rapidly than core label. There were no differences between the mouse lines in the rate at which core label was cleared. Two minutes after injection, about 5% of the core label, and hence chylomicron particles, were in the heart of WT mice. In mice that expressed LPL only in skeletal muscle, and had much reduced levels of LPL in the heart, binding of chylomicrons was reduced to 1%, whereas in mice that expressed LPL only in the heart, the binding was increased to over 10%. The same patterns of distribution were evident at 20 min when most of the label had been cleared. Thus, the amount of LPL expressed in muscle and heart governed both the binding of chylomicron particles and the assimilation of chylomicron lipids in the tissue.

  • 44.
    Skottova, N
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Savonen, R
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Lookene, A
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Hultin, M
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Olivecrona, G
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Lipoprotein lipase enhances removal of chylomicrons and chylomicron remnants by the perfused rat liver.1995In: Journal of Lipid Research, ISSN 0022-2275, E-ISSN 1539-7262, Vol. 36, no 6, p. 1334-44Article in journal (Refereed)
    Abstract [en]

    Lipoprotein lipase has been found to efficiently mediate binding of lipoproteins to cell surfaces and to the low density lipoprotein (LDL) receptor-related protein (LRP) under cell culture conditions (Beisiegel et al. 1991. Proc. Natl. Acad. Sci. USA. 88: 8242-8346). This supports the previously proposed idea that the lipase could have a role in receptor-mediated uptake of chylomicron remnants in the liver. We have investigated the effects of lipoprotein lipase on the clearance of chylomicrons during perfusions of rat livers. The chylomicrons were doubly labeled in vivo with [14C]retinol (in retinyl esters) and with [3H]oleic acid (in triacylglycerols) and were collected from lymph. In the absence of any lipase the clearance of chylomicron label from the perfusion medium was slow. Addition of lipoprotein lipase caused lipolysis of chylomicron triacylglycerols as evidenced by increased levels of 14C-labeled fatty acids in the perfusate. Simultaneously, the level of [14C]retinyl esters in the perfusate decreased dramatically, indicating core-particle removal. Similar effects were seen with an unrelated lipase from Pseudomonas fluorescens. To discriminate between the effects of lipolysis and a true liganding effect of the lipoprotein lipase protein, the active site inhibitors tetrahydrolipstatinR and hexadecylsulfonylfluoride were used to reduce or totally inhibit the catalytical activity. With lipase covalently inhibited by the latter inhibitor, lipolysis during perfusions was low or absent. Nonetheless, the inhibited enzyme had a clear effect on the removal of chylomicrons by the liver. With 1.2 micrograms of inhibited lipase/ml perfusate, about 70% of the core label had been removed after 15 min as compared to about 20% in perfusions without lipase. With identical amounts of active lipoprotein lipase protein, more than 90% of the label was removed. We conclude that any lipase causing lipolysis of chylomicrons can stimulate their clearance by the liver, but that lipoprotein lipase has an additional effect on the removal, which is not dependent on its catalytic activity.

  • 45.
    Svenmarker, Staffan
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Häggmark, Sören
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Hultin, Magnus
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Holmgren, Anders
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Static blood-flow control during cardiopulmonary bypass is a compromise of oxygen delivery2009In: European Journal of Cardio-Thoracic Surgery, ISSN 1010-7940, E-ISSN 1873-734X, Vol. 37, no 1, p. 218-222Article in journal (Refereed)
    Abstract [en]

    Background: Blood-flow control during cardiopulmonary bypass (CPB) is by tradition based on the patient's body surface area. Emergence of new techniques enables dynamic blood-flow control based on online measurement of venous oxygen saturation and oxygen consumption. Present investigation aimed to compare static versus dynamic blood-flow control with respect to use of oxygen and effects upon organ function. Methods: In this study, 100 coronary-artery-bypass surgical patients were prospectively randomised to static or dynamic hypothermic blood-flow control during CPB. In the static group, pump flow was set to 2.4 (litres per minute) times the patient's body surface area (m(2)) throughout the procedure. Pump flow in the dynamic group was varied according to the reading of the venous oxygen saturation and maintained at >75%. CPB-specific information was collected online. Blood samples were collected for analysis of haemoglobin, lactate, amylase, creatinine and C-reactive protein: pre-CPB, at weaning from CPB and on day 1 postoperatively. Results: Randomisation formed two uniform groups. Choice of static or dynamic blood-flow control during CPB had no significant effects on organ function as judged by lactate, amylase or creatinine levels. On increasing oxygen demand, oxygen balance was maintained by increasing venous oxygen extraction rates in the static flow mode and by increasing the pump flow rate in the dynamic group. Conclusions: Independent of the blood-flow control mode, oxygen balance remained preserved. However, the dynamic mode provided higher oxygen delivery, which may increase margins of safety and protection of organ function.

  • 46.
    Tydén, Jonas
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Herwald, H.
    Hultin, Magnus
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Walldén, Jakob
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Johansson, Joakim
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Heparin-binding protein as a biomarker of acute kidney injury in critical illness2017In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 61, no 7, p. 797-803Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: There is no biomarker with high sensitivity and specificity for the development of acute kidney injury (AKI) in a mixed intensive care unit (ICU) population. Heparin-binding protein (HBP) is released from granulocytes and causes increased vascular permeability which plays a role in the development of AKI in sepsis and ischemia. The aim of this study was to investigate whether plasma levels of HBP on admission can predict the development of AKI in a mixed ICU population and in the subgroup with sepsis. METHODS: Longitudinal observational study with plasma HBP levels from 245 patients taken on admission to ICU. Presence and severity of AKI was scored daily for 1 week. RESULTS: Mean (95% CI) plasma concentrations of log HBP (ng/ml) in the groups developing different stages of AKI were: stage 0 (n = 175), 3.5 (3.4-3.7); stage 1 (n = 33), 3.7 (3.5-4.0), stage 2 (n = 20), 4.4 (3.5-4.8); and stage 3 (n = 17), 4.6 (3.8-5.2). HBP levels were significantly higher in patients developing AKI stage 3 (P < 0.01) compared to AKI stage 0 and 1. The area under the curve (AUC) for HBP to discriminate the group developing AKI stage 2-3 was 0.70 (CI: 0.58-0.82) and in the subgroup with severe sepsis 0.88 (CI: 0.77-0.99). CONCLUSION: Heparin-binding protein levels on admission to ICU are associated with the development of severe kidney injury. The relationship between HBP and AKI needs to be further validated in larger studies.

  • 47.
    Törnell, Siv
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Ekeus, C.
    Hultin, Magnus
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Håkansson, Stellan
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Thunberg, Johan
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Högberg, U.
    Low Apgar score, neonatal encephalopathy and epidural analgesia during labour: a Swedish registry-based study2015In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 59, no 4, p. 486-495Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Maternal intrapartum fever (MF) is associated with neonatal sequelae, and women in labour who receive epidural analgesia (EA) are more likely to develop hyperthermia. The aims of this study were to investigate if EA and/or a diagnosis of MF were associated to adverse neonatal outcomes at a population level. METHODS: Population-based register study with data from the Swedish Birth Register and the Swedish National Patient Register, including all nulliparae (n = 294,329) with singleton pregnancies who gave birth at term in Sweden 1999-2008. Neonatal outcomes analysed were Apgar score (AS) < 7 at 5 min and ICD-10 diagnosis of neonatal encephalopathy (e.g. convulsions or neonatal cerebral ischaemia). Multivariate logistic regression was used to calculate adjusted odds ratios (AOR) with 95% confidence intervals (CI). RESULTS: EA was used in 44% of the deliveries. Low AS or encephalopathy was found in 1.26% and 0.39% of the children in the EA group compared with 0.80% and 0.29% in the control group. In multivariate analysis, EA was associated with increased risk with low AS, AOR 1.27 (95% CI 1.16-1.39), but not with diagnosis of encephalopathy, 1.11 (0.96-1.29). A diagnosis of MF was associated with increased risk for both low AS, 2.27 (1.71-3.02), and of neonatal encephalopathy, 1.97 (1.19-3.26). CONCLUSION: Diagnosis of MF was associated with low AS and neonatal encephalopathy, whereas EA was only associated with low AS and not with neonatal encephalopathy. The found associations might be a result of confounding by indication, which is difficult to assess in a registry-based population study.

  • 48.
    Wallden, Jakob
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology. Anaesthesia and Intensive Care, Sundsvall.
    Flodin, Jesper
    Anaesthesia and Intensive Care, Sunderbyn.
    Hultin, Magnus
    Anaesthesia and Intensive Care, Sunderbyn.
    Validation of a prediction model for post-discharge nausea and vomiting after general anaesthesia in a cohort of Swedish ambulatory surgery patients2016In: European Journal of Anaesthesiology, ISSN 0265-0215, E-ISSN 1365-2346, Vol. 33, no 10, p. 743-749Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: In ambulatory surgery, post-discharge nausea and vomiting (PDNV) has been identified as a significant problem occurring in more than one-third of patients.

    OBJECTIVE: To validate a simplified PDNV score in a Swedish population. DESIGN: Prospective observational study.

    SETTING: Two county hospitals in Sweden: Sundsvall from June 2012 to May 2013 and Sunderbyn from January to October 2014.

    PATIENTS: Adult patients undergoing ambulatory surgery under general anaesthesia.

    MAIN OUTCOME MEASURES: Postoperative outcomes with a focus on nausea and vomiting were collected at 2, 4, and 6 h after surgery and on the first three postoperative days. The simplified PDNV score, calculated before discharge, included the factors: female sex, age less than 50 years, history of postoperative nausea and vomiting, postoperative nausea and opioids given postoperatively. The prediction performance of the simplified PDNV score was evaluated in terms of discrimination (area under receiver-operating characteristics curve) and calibration plots and was compared with that of the original development study.

    RESULTS: A total of 559 patients were asked to participate, of which 431 were included in the final study cohort. The overall risk of postoperative nausea and vomiting and PDNV were 18.8 [95% confidence interval (CI), 15.4-22.8]% and 28.1 (95% CI, 24.0-32.5)%, respectively. The discrimination capacity of the simplified PDNV score in our study was similar to that of the original dataset [area under the curve 0.693 (95% CI, 0.638-0.748) vs. 0.706 (0.681-0.731), absolute difference 0.013]. The slope of the calibration curve was 0.893, with a constant of 0.021 (R-square 0.884).

    CONCLUSION: In a Swedish cohort of patients, the simplified PDNV score performs well in discriminating between patients who will experience post-discharge nausea and/or vomiting after ambulatory surgery. Our results indicate that the simplified PDNV score is as valid in other cohorts as it was in the original development cohort.

  • 49.
    Walldén, Jakob
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Halliday, T. A.
    Hultin, Magnus
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Reply to: Sorbello et al., PONV in bariatric surgery: time for opioid-free anaesthesia2017In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 61, no 7, p. 858-858Article in journal (Refereed)
  • 50.
    Warglo, Zara
    et al.
    Socialstyrelsen.
    Hultin, Magnus
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Kvalitetssäkring av kunskapsprovet är en pågående process2017In: Läkartidningen, Vol. 114:EXFYArticle in journal (Other (popular science, discussion, etc.))
12 1 - 50 of 51
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