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  • 1.
    Appelqvist, Hanna
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Experimental Pathology. Linköping University, Faculty of Health Sciences.
    Sandin, Linnea
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Björnström, Karin
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Intensive Care.
    Saftig, Paul
    Biochemical Institute, Christian-Albrechts-University Kiel, Kiel, Germany.
    Garner, Brett
    Illawarra Health and Medical Research Institute, University of Wollongong, Australia.
    Öllinger, Karin
    Linköping University, Department of Clinical and Experimental Medicine, Experimental Pathology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pathology and Clinical Genetics.
    Kågedal, Katarina
    Linköping University, Department of Neuroscience and Locomotion, Pathology. Linköping University, Faculty of Health Sciences.
    Sensitivity to Lysosome-Dependent Cell Death is Directly Regulated by Lysosomal Cholesterol Content2012In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, no 11Article in journal (Refereed)
    Abstract [en]

    Alterations in lipid homeostasis are implicated in several neurodegenerative diseases, although the mechanisms responsible are poorly understood. We evaluated the impact of cholesterol accumulation, induced by U18666A, quinacrine or mutations in the cholesterol transporting Niemann-Pick disease type C1 (NPC1) protein, on lysosomal stability and sensitivity to lysosome-mediated cell death. We found that neurons with lysosomal cholesterol accumulation were protected from oxidative stress-induced apoptosis. In addition, human fibroblasts with cholesterol-loaded lysosomes showed higher lysosomal membrane stability than controls. Previous studies have shown that cholesterol accumulation is accompanied by the storage of lipids such as sphingomyelin, glycosphingolipids and sphingosine and an up regulation of lysosomal associated membrane protein-2 (LAMP-2), which may also influence lysosomal stability. However, in this study the use of myriocin and LAMP deficient fibroblasts excluded these factors as responsible for the rescuing effect and instead suggested that primarily lysosomal cholesterol content determined the cellular sensitivity to toxic insults. Further strengthening this concept, depletion of cholesterol using methyl-β-cyclodextrin or 25-hydroxycholesterol decreased the stability of lysosomes and cells became more prone to undergo apoptosis. In conclusion, cholesterol content regulated lysosomal membrane permeabilization and thereby influenced cell death sensitivity. Our data suggests that lysosomal cholesterol modulation might be used as a therapeutic strategy for conditions associated with accelerated or repressed apoptosis.

  • 2.
    Farnebo, Simon
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Plastic Surgery, Hand surgery UHL.
    Winbladh, Anders
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Zettersten, Erik
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Sandström, Per
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Gullstrand, P
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Anaesthesiology and Surgery UHL.
    Samuelsson, Anders
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Intensive Care UHL.
    Theodorsson, Elvar
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Burn Center. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Plastic Surgery, Hand surgery UHL. Östergötlands Läns Landsting, Sinnescentrum, Department of Anaesthesiology and Surgery UHL.
    Urea Clearance: A New Technique Based on Microdialysis to Assess Liver Blood Flow Studied in a Pig Model of Ischemia/Reperfusion2010In: EUROPEAN SURGICAL RESEARCH, ISSN 0014-312X, Vol. 45, no 2, p. 105-112Article in journal (Refereed)
    Abstract [en]

    Delayed detection of ischemia is one of the most feared postoperative complications. Early detection of impaired blood flow and close monitoring of the organ-specific metabolic status may therefore be critical for the surgical outcome. Urea clearance is a new technique for continuous monitoring of alterations in blood flow and metabolic markers with acceptable temporal characteristics. We compare this new microdialysis technique with the established microdialysis ethanol technique to assess hepatic blood flow. Six pigs were used in a liver ischemia/reperfusion injury model. Microdialysis catheters were placed in liver segment IV and all circulation was stopped for 80 min, followed by reperfusion for 220 min. Urea and ethanol clearance was calculated from the dialysate and correlated with metabolic changes. A laser Doppler probe was used as reference of restoration of blood flow. Both urea and ethanol clearance reproducibly depicted changes in liver blood flow in relation to metabolic changes and laser Doppler measurements. The two techniques highly correlated both overall and during the reperfusion phase (r = 0.8) and the changes were paralleled by altered perfusion as recorded by laser Doppler.

  • 3.
    Farnebo, Simon
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Plastic Surgery, Hand Surgery and Burns. Linköping University, Faculty of Health Sciences.
    Zettersten, Erik
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Samuelsson, Anders
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Intensive Care UHL. Östergötlands Läns Landsting, Sinnescentrum, Department of Anaesthesiology and Surgery UHL.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Burn Center. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Plastic Surgery, Hand surgery UHL. Östergötlands Läns Landsting, Sinnescentrum, Department of Anaesthesiology and Surgery UHL.
    Assessment of blood flow changes in human skin by microdialysis urea clearance2011In: Microcirculation, ISSN 1073-9688, E-ISSN 1549-8719, Vol. 18, no 3, p. 198-204Article, review/survey (Refereed)
    Abstract [en]

    Objective: The aim of this study was to evaluate the urea clearance technique for the measurement of drug-induced blood flow changes in human skin, and compare it with two non-invasive techniques: polarization light spectroscopy and laser Doppler perfusion imaging.

    Methods: Fifteen microdialysis catheters were placed intracutaneously on the volar aspect of the forearms of healthy human subjects, and were perfused with nitroglycerine, noradrenaline, and again nitroglycerine, to induce local tissue hyperaemia, hypoperfusion, and hyperaemia, respectively.

    Results: Urea clearance, but not the other techniques, detected the changes in blood flow during all three periods of altered flow.  The last hyperaemic response was detected by all three methods.

    Conclusion: Urea clearance can be used as a relatively simple method to estimate blood flow changes during microdialysis of vasoactive substances, in particular when the tissue is preconditioned in order to enhance the contrast between baseline and the responses to the provocations. Our results support that, in the model described, urea clearance was superior to the optical methods as it detected both the increases and decrease in blood flow, and the returns to baseline between these periods.

  • 4.
    Folkesson, Tchou
    et al.
    Pharmaceutical Biosciences, Faculty of Pharmacy, Uppsala University, Uppsala, Sweden,.
    Samuelsson, Anders
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Intensive Care UHL. Östergötlands Läns Landsting, Sinnescentrum, Department of Anaesthesiology and Surgery UHL.
    Tesselaar, Erik
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Dahlström, B.
    Berzelius Clinical Research Center, Linköping, Sweden.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Burn Center. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Plastic Surgery, Hand surgery UHL. Östergötlands Läns Landsting, Sinnescentrum, Department of Anaesthesiology and Surgery UHL.
    A human vascular model based on microdialysis for the assessment of the vasoconstrictive dose-response effects of noradrenaline and vasopressin in skin: in JOURNAL OF VASCULAR RESEARCH, vol 48, pp 320-3202011In: JOURNAL OF VASCULAR RESEARCH, Karger , 2011, p. 320-320Conference paper (Refereed)
    Abstract [en]

    Microdialysis is a well-established technique for continuous sampling of small, water-soluble molecules within the extracellular fluid space in vivo. It also allows the use of microdoses of drugs, and the simultaneous evaluation of their related effects at the site of action. The present study was an experimental, randomized microdose trial to develop a human vascular model of dose response. We aimed to evaluate a microdialysis dosing method using urea clearance as a marker of druginduced changes in dermal blood flow and metabolism (glucose and lactate) in 12 healthy volunteers. We found that asymptomatic vasoconstriction can be detected by continuous microdialysis measurements of urea clearance in dermal tissue. More importantly, dose-effect relations using the Emax model could be constructed using the corresponding data on drug doses and both the urea clearance-based flow estimates and the changes in concentrations of tissue metabolites. This in vivo human experimental skin model offers an interesting tool with which both the dose-response effects on blood flow and concentrations of tissue metabolites of potent vasoactive substances can be evaluated.

  • 5.
    Gupta, Anil
    et al.
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Anaesthesiology and Surgery UHL.
    Bjornsson, A.
    Department Anaesthesiol and Intens Care, Orebro.
    Fredriksson, M.
    Hallböök, Olof
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Östergötland.
    Eintrei, Christina
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Intensive Care UHL.
    Reduction in mortality after epidural anaesthesia and analgesia in patients undergoing rectal but not colonic cancer surgery: a retrospective analysis of data from 655 patients in Central Sweden2011In: British Journal of Anaesthesia, ISSN 0007-0912, E-ISSN 1471-6771, Vol. 107, no 2, p. 164-170Article in journal (Refereed)
    Abstract [en]

    Background. There is some evidence that epidural analgesia (EDA) reduces tumour recurrence after breast and prostatic cancer surgery. We assessed whether EDA reduces long-term mortality after colorectal cancer surgery. Methods. All patients having colorectal cancer surgery between January 2004 and January 2008 at Linkoping and Orebro were included. Exclusion criteria were: emergency operations, laparoscopic-assisted colorectal resection, and stage 4 cancer. Statistical information was obtained from the Swedish National Register for Deaths. Patients were analysed in two groups: EDA group or patient-controlled analgesia (PCA group) as the primary method of analgesia. Results. A total of 655 patients could be included. All-cause mortality for colorectal cancer (stages 1-3) was 22.7% (colon: 20%, rectal: 26%) after 1-5 yr of surgery. Multivariate regression analysis identified the following statistically significant factors for death after colon cancer (Pless than0.05): age (greater than72 yr) and cancer stage 3 (compared with stage 1). A similar model for rectal cancer found that age (greater than72 yr) and the use of PCA rather than EDA and cancer stages 2 and 3 (compared with stage 1) were associated with a higher risk for death. No significant risk of death was found for colon cancer when comparing EDA with PCA (P=0.23), but a significantly increased risk of death was seen after rectal cancer when PCA was used compared with EDA (P=0.049) [hazards ratio: 0.52 (0.27-1.00)]. Conclusions. We found a reduction in all-cause mortality after rectal but not colon cancer in patients having EDA compared with PCA technique.

  • 6.
    Orwelius, L
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Intensive Care. 3Svenska Intensivvårdsregistret.
    Åkerman, E
    3Svenska Intensivvårdsregistret.
    Wickerts, C-J
    3Svenska Intensivvårdsregistret.
    Walther, Sten M.
    Linköping University, Department of Medical and Health Sciences. 3Svenska Intensivvårdsregistret.
    Hälsorelaterad livskvalitet upp till 12 mpnader efter intensivvård: rikstäckange lärdomar från SIR2015Conference paper (Refereed)
  • 7.
    Orwelius, Lotti
    et al.
    Linköping University, Department of Medical and Health Sciences, Nursing Science. Linköping University, Faculty of Health Sciences.
    Bäckman, Carl
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Work and Environmental Science.
    Fredrikson, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Simonsson, Eva
    Ryhov Hospital.
    Nordlund, Peter
    Ryhov Hospital.
    Samuelsson, Anders
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Intensive Care UHL. Östergötlands Läns Landsting, Sinnescentrum, Department of Anaesthesiology and Surgery UHL.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Burn Center. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Plastic Surgery, Hand surgery UHL. Östergötlands Läns Landsting, Sinnescentrum, Department of Anaesthesiology and Surgery UHL.
    Social integration: an important factor for health-related quality of life after critical illness2011In: INTENSIVE CARE MEDICINE, ISSN 0342-4642, Vol. 37, no 5, p. 831-838Article in journal (Refereed)
    Abstract [en]

    To examine to what extent availability of social integration affects health-related quality of life (HRQoL) in former intensive care unit (ICU) patients and how it relates to corresponding findings in a general reference group. Controlled, multicenter, prospective, explorative study. HRQoL data (SF-36) were collected from three combined medical and surgical ICUs in the south-east of Sweden. Social integration was assessed by the Availability of Social Integration (AVSI) instrument (seven questions related to the social interaction of the patient). As reference group, a random sample (n = 6,093) of people from the uptake area of the hospitals was used. Social integration (AVSI), HRQoL (SF-36), and comorbidity were examined also in the reference group. None. The level of social integration significantly affected HRQoL for the former ICU patients, whereas no such effect was seen for the general reference group. For the ICU patients, social integration affected HRQoL to a larger extent than age, sex, and the ICU-related factors examined, but to a lower extent than the pre-existing diseases. For a comprehensive assessment of HRQoL in former ICU patients, it is mandatory to include the effect of social integration.

  • 8.
    Orwelius, Lotti
    et al.
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Anaesthesiology and Surgery UHL.
    Nordlund, Anders
    TFS Trial Form Support AB, Lund.
    Nordlund, Peter
    Department of Anaesthesia and Intensive Care, Ryhov Hospital, Jönköping, Sweden.
    Simonsson, Eva
    Department of Anaesthesia and Intensive Care, Ryhov Hospital, Jönköping, Sweden.
    Bäckman, Carl
    Department of Anaesthesia and Intensive Care, Vrinnevi Hospital, Norrköping, Sweden.
    Samuelsson, Anders
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Intensive Care UHL.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Burn Center. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Plastic Surgery, Hand surgery UHL. Östergötlands Läns Landsting, Sinnescentrum, Department of Anaesthesiology and Surgery UHL.
    Pre-existing disease: the most important factor for health related quality of life long-term after critical illness: a prospective, longitudinal, multicentre trial2010In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 14, no 2Article in journal (Refereed)
    Abstract [en]

    Introduction

    The aim of the present multicenter study was to assess long term (36 months) health related quality of life in patients after critical illness, compare ICU survivors health related quality of life to that of the general population and examine the impact of pre-existing disease and factors related to ICU care on health related quality of life.

    Methods

    Prospective, longitudinal, multicentre trial in three combined medical and surgical intensive care units of one university and two general hospitals in Sweden. By mailed questionnaires, health related quality of life was assessed at 6, 12, 24 and 36 months after the stay in ICU by EQ-5D and SF-36, and information of pre-existing disease was collected at the 6 months measure. ICU related factors were obtained from the local ICU database. Comorbidity and health related quality of life (EQ-5D; SF-36) was examined in the reference group. Among the 5306 patients admitted, 1663 were considered eligible (>24 hrs in the intensive care unit, and age ≥ 18 yrs, and alive 6 months after discharge). At the 6 month measure 980 (59%) patients answered the questionnaire. Of these 739 (75%) also answered at 12 month, 595 (61%) at 24 month, and 478 (47%) answered at the 36 month measure. As reference group, a random sample (n = 6093) of people from the uptake area of the hospitals were used in which concurrent disease was assessed and adjusted for.

    Results

    Only small improvements were recorded in health related quality of life up to 36 months after ICU admission. The majority of the reduction in health related quality of life after care in the ICU was related to the health related quality of life effects of pre-existing diseases. No significant effect on the long-term health related quality of life by any of the ICU-related factors was discernible.

    Conclusions

    A large proportion of the reduction in the health related quality of life after being in the ICU is attributable to pre-existing disease. The importance of the effect of pre-existing disease is further supported by the small, long term increment in the health related quality of life after treatment in the ICU. The reliability of the conclusions is supported by the size of the study populations and the long follow-up period.

     

  • 9.
    Orwelius, Lotti
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Intensive Care. Linköping University, Faculty of Medicine and Health Sciences. The Swedish Intensive Care Registry, Karlstad, Sweden .
    Åkerman, E
    Swedish Intensive Care Registry, Karlstad, Sweden /Clinic of Intensive Care and Perioperative Medicine, Skåne University Hospital (Malmö), Malmö, Sweden.
    Wickerts, C-J
    The Swedish Intensive Care Registry, Karlstad, Sweden .
    Walther, Sten
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery. The Swedish Intensive Care Registry, Karlstad, Sweden .
    Health-related quality of life at 2, 6 and 12 months after critical illness - lessons learnt from a nationwide follow-up of 4,500 ICU admissions2015Conference paper (Refereed)
    Abstract [en]

    Introduction

    The development of intensive care medicine has led to improved survival of patients with complex illnesses and extensive injuries. Survivors are at risk of acquiring physical and functional deficits that may have negative effects on health-related quality of life (HRQoL). The significance of measuring HRQoL has been underlined by critical care researchers since poor HRQoL is associated with an adverse prognosis.

    Objective

    The aim of this work was to examine the development of HRQoL at 2, 6 and 12 months after ICU discharge in a mixed ICU patient population with an ICU-stay > 96 hrs.

    Methods

    We analysed admissions during 2008-2014 to 49 ICUs that submitted follow-up data to the Swedish Intensive Care Registry (SIR, http://www.icuregswe.org). HRQoL was measured using the Short Form 36 (SF36) questionnaire at 2, 6, and 12 months after discharge from ICU. SF36 domains, age, gender, illness severity on admission (SAPS3 probabilities) and length of ICU-stay were analysed for the entire cohort and for important diagnostic groups. SF36 scores were compared to an age- and gender-adjusted Swedish normal population. Differences in SF36 domains were analysed using non-parametric methods. Medians and interquartile ranges are presented.

    Results

    Complete SF36 responses were analysed for 4453, 4019 and 2515 admissions at 2, 6 and 12 months, respectively. HRQoL at 2 months in patients that subsequently were lost to follow-up was generally similar to those with follow-up, but they were younger, less ill and had shorter ICU-stay. Full longitudinal data with complete SF36 responses were obtained in 1438 patients [Age: 66 yrs. (57-73 yrs.), female gender: 37.2%, SAPS3 prob: 0.36 (0.19-0.55), ICU-stay: 7.0 days (4.9-11.5 days)]. SF36 improved over time in all domains (P < 0.001, Table), although some domains remained stable from 6 to 12 months. Patterns of recovery differed between important diagnostic groups (i.e. sepsis, out-of-hospital cardiac arrest, COPD, ARDS). A large proportion of patients (10-25% depending on SF36 domain) had HRQoL scores at 12 months which was below 2 standard deviations of the age- and gender-adjusted Swedish norm. The cardiac arrest group were among those with best, and the COPD group were among those with worst HRQoL at 12 months.

    Conclusions

    HRQoL recovered over 12 months in critically ill patients with a prolonged ICU stay. Recovery varied between diagnostic groups and a large proportion of patients had markedly depressed HRQoL. These findings may have important implications for follow-up and care after critical illness.

  • 10.
    Oscarsson, Anna
    et al.
    Östergötlands Läns Landsting, Sinnescentrum, Department of Intensive Care UHL.
    Oster, Susanne
    Östergötlands Läns Landsting, Sinnescentrum, Department of Intensive Care UHL.
    Fredrikson, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Lindahl, Tomas
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Chemistry.
    Eintrei, Christina
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Intensive Care UHL.
    Platelet function assessed by whole-blood aggregometry in patients undergoing non-cardiac surgery2011In: EUROPEAN JOURNAL OF ANAESTHESIOLOGY, ISSN 0265-0215, Vol. 28, no 5, p. 363-369Article in journal (Refereed)
    Abstract [en]

    Background The risk/benefit of continuing low-dose acetylsalicylic acid (aspirin) for secondary prevention in the perioperative period is still debated. The primary aim of this study was to determine the effect of acetylsalicylic acid compared with placebo on platelet function in the perioperative period. Methods This is a subgroup analysis of a randomised, double-blind, placebo-controlled multicentre study. High-risk patients undergoing major non-cardiac surgery were randomised to 75 mg acetylsalicylic acid or placebo 7 days preoperatively, until the third postoperative day. In 36 patients, platelet function in response to arachidonic acid was assessed by whole-blood impedance aggregometry using a multiplate analyser 1 h before surgery, directly after surgery and 48 h postoperatively. Results The platelet function was significantly reduced in patients treated with acetylsalicylic acid compared with placebo in the preoperative period [200 aggregation units (AU) min (interquartile range [IQR] 133-261 AU min(-1)) vs. 860 AU min (IQR 800-1010 AU min), P andlt; 0.001] as well as postoperatively [198 AU min (IQR 138-270 AU min) vs. 605 AU min (IQR 434-836 AU min), Pandlt;0.001]. The platelet response was significantly reduced postoperatively compared with preoperatively in patients receiving placebo [860 AU min (IQR 800-1010 AU min) vs. 605 AU min (IQR 434-861 AU min), P=0.0009]. No significant differences were found between pre- and postoperative platelet function in patients on acetylsalicylic acid [200 AU min (IQR 133-261 AU min) vs. 198 AU min (133-270 AU min), P=0.21]. Conclusion Multiplate whole-blood impedance aggregometry demonstrates acetylsalicylic affect in preoperative as well as postoperative samples derived from patients undergoing non-cardiac surgery.

  • 11.
    Oscarsson Tibblin, Anna
    et al.
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Anaesthesiology and Intensive Care VHN.
    Gupta, Anil
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Anaesthesiology and Surgery UHL.
    Fredrikson, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Järhult, Johannes
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Nyström, Matti
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Anaesthesiology and Intensive Care VHN.
    Pettersson, Eva
    Östergötlands Läns Landsting, Anaesthesiology and Surgical Centre, Department of Anaesthesiology and Intensive Care VHN.
    Darvish, Bijan
    Department of Anaesthesia & Intensive Care University Hospital, Örebro, Sweden.
    Krook, Helena
    Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Swahn, Eva
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Eintrei, Christina
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Intensive Care UHL.
    To continue or discontinue aspirin in the perioperative period: a randomized, controlled clinical trial2010In: British Journal of Anaesthesia, ISSN 0007-0912, E-ISSN 1471-6771, Vol. 104, no 3, p. 305-312Article in journal (Refereed)
    Abstract [en]

    Background: Major adverse cardiac events (MACEs) are a common cause of deathafter non-cardiac surgery. Despite evidence for the benefitof aspirin for secondary prevention, it is often discontinuedin the perioperative period due to the risk of bleeding.

    Methods: We conducted a randomized, double-blind, placebo-controlledtrial in order to compare the effect of low-dose aspirin withthat of placebo on myocardial damage, cardiovascular, and bleedingcomplications in high-risk patients undergoing non-cardiac surgery.Aspirin (75 mg) or placebo was given 7 days before surgery andcontinued until the third postoperative day. Patients were followedup for 30 days after surgery.

    Results: A total of 220 patients were enrolled, 109 patients receivedaspirin and 111 received placebo. Four patients (3.7%) in theaspirin group and 10 patients (9.0%) in the placebo group hadelevated troponin T levels in the postoperative period (P=0.10).Twelve patients (5.4%) had an MACE during the first 30 postoperativedays. Two of these patients (1.8%) were in the aspirin groupand 10 patients (9.0%) were in the placebo group (P=0.02). Treatmentwith aspirin resulted in a 7.2% absolute risk reduction [95%confidence interval (CI), 1.3–13%] for postoperative MACE.The relative risk reduction was 80% (95% CI, 9.2–95%).Numbers needed to treat were 14 (95% CI, 7.6–78). No significantdifferences in bleeding complications were seen between thetwo groups.

    Conclusions: In high-risk patients undergoing non-cardiac surgery, perioperativeaspirin reduced the risk of MACE without increasing bleedingcomplications. However, the study was not powered to evaluatebleeding complications.

     

  • 12.
    Samuelsson, Anders
    et al.
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Intensive Care UHL.
    Farnebo, Simon
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Plastic Surgery, Hand surgery UHL.
    Magnusson, Beatrice
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Anderson, Chris
    Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Dermatology and Venerology in Östergötland.
    Tesselaar, Erik
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Zettersten, Erik
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Burn Center. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Plastic Surgery, Hand surgery UHL. Östergötlands Läns Landsting, Sinnescentrum, Department of Anaesthesiology and Surgery UHL.
    Implications for burn shock resuscitation of a new in vivo human vascular microdosing technique (microdialysis) for dermal administration of noradrenaline2012In: Burns, ISSN 0305-4179, E-ISSN 1879-1409, Vol. 38, no 7, p. 975-983Article in journal (Refereed)
    Abstract [en]

    Introduction: Skin has a large dynamic capacity for alterations in blood flow, and is therefore often used for recruitment of blood during states of hypoperfusion such as during burn shock resuscitation. However, little is known about the blood flow and metabolic consequences seen in the dermis secondary to the use vasoactive drugs (i.e. noradrenaline) for circulatory support. The aims of this study were therefore: to develop an in vivo, human microdosing model based on dermal microdialysis; and in this model to investigate effects on blood flow and metabolism by local application of noradrenaline and nitroglycerin by the microdialysis system simulating drug induced circulatory support. less thanbrgreater than less thanbrgreater thanMethod: Nine healthy volunteers had microdialysis catheters placed intradermally in the volar surface of the lower arm. The catheters were perfused with noradrenaline 3 or 30 mmol/L and after an equilibrium period all catheters were perfused with nitroglycerine (2.2 mmol/L). Dermal blood flow was measured by the urea clearance technique and by laser Doppler imaging. Simultaneously changes in dermal glucose, lactate, and pyruvate concentrations were recorded. less thanbrgreater than less thanbrgreater thanResults: Noradrenaline and nitroglycerine delivered to the dermis by the microdialysis probes induced large time- and dose-dependent changes in all variables. We particularly noted that tissue glucose concentrations responded rapidly to hypoperfusion but remained higher than zero. Furthermore, vasoconstriction remained after the noradrenaline administration implicating vasospasm and an attenuated dermal autoregulatory capacity. The changes in glucose and lactate by vasoconstriction (noradrenaline) remained until vasodilatation was actively induced by nitroglycerine. less thanbrgreater than less thanbrgreater thanConclusion: These findings, i.e., compromised dermal blood flow and metabolism are particularly interesting from the burn shock resuscitation perspective where noradrenaline is commonly used for circulatory support. The importance and clinical value of the results obtained in this in vivo dermal model in healthy volunteers needs to be further explored in burn-injured patients.

  • 13.
    Sjöberg, Folke
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Burn Center. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Plastic Surgery, Hand surgery UHL. Östergötlands Läns Landsting, Sinnescentrum, Department of Intensive Care UHL.
    Iredahl, Fredrik
    Linköping University, Department of Clinical and Experimental Medicine, Burn Center. Linköping University, Faculty of Health Sciences.
    Larsen, Robert
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Plastic Surgery, Hand surgery UHL. Östergötlands Läns Landsting, Sinnescentrum, Department of Intensive Care UHL.
    Samuelsson, Anders
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Plastic Surgery, Hand surgery UHL. Östergötlands Läns Landsting, Sinnescentrum, Department of Intensive Care UHL.
    Thorfinn, Johan
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Plastic Surgery, Hand surgery UHL.
    Bak, Zoltan
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Plastic Surgery, Hand surgery UHL. Östergötlands Läns Landsting, Sinnescentrum, Department of Intensive Care UHL.
    Huss, Fredrik
    Akademiska sjukhuset, Uppsala, Sweden.
    Rousseau, Andreas
    Linköping University, Department of Clinical and Experimental Medicine, Psychiatry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    Data visar att hyperbar syrgasbehandling kan vara skadlig2011In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 108, no 32-33, p. 1506-1506Article, review/survey (Other (popular science, discussion, etc.))
  • 14.
    Sjöberg, Folke
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Burn Center. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Plastic Surgery, Hand surgery UHL. Östergötlands Läns Landsting, Sinnescentrum, Department of Anaesthesiology and Surgery UHL.
    Larsen, Robert
    Linköping University, Department of Clinical and Experimental Medicine, Burn Center. Linköping University, Faculty of Health Sciences.
    Bak, Zoltan
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Östergötland. Östergötlands Läns Landsting, Sinnescentrum, Department of Anaesthesiology and Surgery UHL.
    Samuelsson, Anders
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Intensive Care UHL. Östergötlands Läns Landsting, Sinnescentrum, Department of Anaesthesiology and Surgery UHL.
    Iredahl, Fredrik
    Linköping University, Department of Clinical and Experimental Medicine, Burn Center. Linköping University, Faculty of Health Sciences.
    Thorfinn, Johan
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Plastic Surgery, Hand surgery UHL.
    Huss, Fredrik
    Brännskadecentrum, Akademiska sjukhuset, Uppsala.
    Rousseau, Andreas
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Psychiatry. Östergötlands Läns Landsting, Sinnescentrum, Department of Anaesthesiology and Surgery UHL.
    Hyperbar syrgasbehandling kan vara skadlig vid kolmonoxidförgiftning2011In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 108, no 32-33, p. 1506-Article in journal (Refereed)
  • 15.
    Sondergaard, S
    et al.
    Sahlgrens University Hospital.
    Tesselaar, Erik
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Samuelsson, Anders
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Intensive Care UHL.
    Fagerberg, A
    Sahlgrens University Hospital.
    Orman, J
    Östergötlands Läns Landsting, Anaesthesiology and Surgical Centre, Department of Intensive Care UHL.
    Viksten, J L
    Östergötlands Läns Landsting, Sinnescentrum, Department of Intensive Care UHL.
    Hallen, K
    Sahlgrens University Hospital.
    Einarsson, H
    Sahlgrens University Hospital.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Burn Center. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Plastic Surgery, Hand surgery UHL. Östergötlands Läns Landsting, Sinnescentrum, Department of Anaesthesiology and Surgery UHL.
    Aneman, A
    Sahlgrens University Hospital.
    ORIGIN OF IMPEDANCE CHANGES RELATED TO LUNG PERFUSION IN ELECTRICAL IMPEDANCE TOMOGRAPHY in INTENSIVE CARE MEDICINE, vol 36, issue , pp S95-S952010In: INTENSIVE CARE MEDICINE, Springer Science Business Media , 2010, Vol. 36, p. S95-S95Conference paper (Refereed)
    Abstract [en]

    n/a

  • 16.
    Steinvall, Ingrid
    et al.
    Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Plastic Surgery, Hand surgery UHL. Linköping University, Department of Clinical and Experimental Medicine, Plastic Surgery, Hand Surgery and Burns.
    Fredrikson, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Bak, Zoltan
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery UHL. Östergötlands Läns Landsting, Sinnescentrum, Department of Intensive Care UHL.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Burn Center. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Plastic Surgery, Hand surgery UHL. Östergötlands Läns Landsting, Sinnescentrum, Department of Anaesthesiology and Surgery UHL.
    Incidence of early burn-induced effects on liver functionas reflected by the plasma disappearance rate of indocyanine green: a prospective descriptive cohort study2012In: Burns, ISSN 0305-4179, E-ISSN 1879-1409, Vol. 38, no 2, p. 214-224Article in journal (Refereed)
    Abstract [en]

    Organ dysfunction and failure are important for burned patients as they increase morbidity and mortality. Recent evidence has suggested that organ injuries are occurring earlier after burns, and are more common, than previously thought. In this study we have assessed the extent to which liver function, assessed by the plasma disappearance rate of indocyanine green (PDRICG), is affected in patients with severe burns. This is a prospective, descriptive exploratory study at a national burn centre. Consecutive adult patients with a total burned body surface area (TBSA%) of 20% or more, were examined prospectively by dynamic (PDRICG) and static liver function tests (plasma: bilirubin concentration, prothrombin complex, and alanine aminotransferase and alkaline phosphatase activities). Early liver dysfunction was common, as assessed by both dynamic (7 of 17) and static liver function tests (6-17 of 17). A regression model showed that changes in PDRICG were associated with age, TBSA%, plasma bilirubin concentration, plasma C-reactive protein concentration, and cardiac index. Persistent and advanced hepatic dysfunction was associated with mortality. The PDRICG seems to give a comprehensive assessment of liver function after major burns. Hepatic dysfunction seems to be as common as dysfunction in other organs. We interpret the recorded effects on liver function as part of a multiple organ dysfunction syndrome, primarily induced by the burn itself. However, this needs to be further investigated.

  • 17.
    Tchou Folkesson, Kim
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Samuelsson, Anders
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Intensive Care UHL.
    Tesselaar, Erik
    Linköping University, Department of Clinical and Experimental Medicine, Burn Center. Linköping University, Faculty of Health Sciences.
    Dahlström, Bengt
    AB Biopharmacon, Uppsala.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Burn Center. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Plastic Surgery, Hand surgery UHL. Östergötlands Läns Landsting, Sinnescentrum, Department of Anaesthesiology and Surgery UHL.
    A Human Vascular Model Based on Microdialysis for the Assessment of the Vasoconstrictive Dose-Response Effects of Norepinephrine and Vasopressin in Skin2012In: Microcirculation, ISSN 1073-9688, E-ISSN 1549-8719, Vol. 19, no 4, p. 352-359Article in journal (Refereed)
    Abstract [en]

    Abstract Objective: Microdialysis enables drug delivery in the skin and simultaneous measurement of their effects. The present study aimed to evaluate dose-dependent changes in blood flow and metabolism during microdialysis of norepinephrine and vasopressin. Methods: We investigated whether increasing concentrations of norepinephrine (NE, 1.859 mu mol/L) and vasopressin (VP, 1100 nmol/L), delivered sequentially in one catheter or simultaneously through four catheters, yield dose-dependent changes in blood flow (as measured using urea clearance) and metabolism (glucose and lactate). Results: We found a significant dose-dependent vasoconstriction with both drugs. Responses were characterized by a sigmoid dose response model. Urea in the dialysate increased from a baseline of 7.9 +/- 1.7 to 10.9 +/- 0.9 mmol/L for the highest concentration of NE (p andlt; 0.001) and from 8.1 +/- 1.4 to 10.0 +/- 1.7 mmol/L for the highest concentration of VP (p = 0.037). Glucose decreased from 2.3 +/- 0.7 to 0.41 +/- 0.18 mmol/L for NE (p = 0.001) and from 2.7 +/- 0.6 to 1.3 +/- 0.5 mmol/L for VP (p andlt; 0.001). Lactate increased from 1.1 +/- 0.4 to 2.6 +/- 0.5 mmol/L for NE (p = 0.005) and from 1.1 +/- 0.4 to 2.6 +/- 0.5 mmol/L for VP (p = 0.008). There were no significant differences between responses from a single catheter and from those obtained simultaneously using multiple catheters. Conclusions: Microdialysis in the skin, either with a single catheter or using multiple catheters, offers a useful tool for studying dose response effects of vasoactive drugs on local blood flow and metabolism without inducing any systemic effects.

  • 18.
    Turina, Dean
    et al.
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Anaesthesiology and Surgery UHL.
    Björnström-Karlsson, Karin
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Anaesthesiology and Surgery UHL.
    Sundqvist, Tommy
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Eintrei, Christina
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Intensive Care UHL.
    Propofol alters vesicular transport in rat cortical neuronalcultures2011In: Journal of Physiology and Pharmacology, ISSN 0867-5910, E-ISSN 1899-1505, Vol. 62, no 1, p. 119-124Article in journal (Refereed)
    Abstract [en]

    Neuronal intracellular transport is performed by motor proteins, which deliver vesicles, organelles and proteins along cytoskeletal tracks inside the neuron. We have previously shown that the anesthetic propofol causes dose- and time-dependent, reversible retraction of neuronal neurites. We hypothesize that propofol alters the vesicular transport of cortical neurons due to this neurite retraction. Primary cultures of co-cultivated rat cortical neurons and glial cells were exposed to either 2 mu M propofol, control medium or the lipid vehicle, in time-response experiments. Reversibility was tested by washing propofol off the cells. The role of the GABA(A) receptor (GABA(A)R) was assessed with the GABA(A)R antagonist gabazine. Vesicles were tracked using differential interference contrast video microscopy. Propofol caused a retrograde movement in 83.4 +/- 5.2% (mean +/- S.E.M.) of vesicles, which accelerated over the observed time course (0.025 +/- 0.012 mu m.s(-1)). In control medium, vesicles moved predominantly anterograde (84.6 +/- 11.1%) with lower velocity (0.011 +/- 0.004 mu m.s(-1)). Cells exposed to the lipid vehicle showed the same dynamic characteristics as cells in control medium. The propofol-induced effect on vesicle transport was reversible and blocked by the GABA(A)R antagonist gabazine in low concentration. Our results show that propofol causes a reversible, accelerating vesicle movement toward the neuronal cell body that is mediated via synaptic GABA(A)R. We have previously reported that propofol initiates neurite retraction, and we propose that propofol causes vesicle movement by retrograde flow of cytoplasm from the narrowed neurite.

  • 19.
    Turina, Dean
    et al.
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences.
    Karin, Björnström Karlsson
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences.
    Sundqvist, Tommy
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Eintrei, Christina
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Intensive Care UHL.
    Orexin A inhibits propofol-induced neurite retraction by a PLD-dependent mechanism in neuronsManuscript (preprint) (Other academic)
    Abstract [en]

    Background: Propofol retracts neurites and reverses the transport of vesicles in rat cortical neurons in a γ-aminobutyric acid type A (GABAA) receptor dependent manner. Orexin A (OA) is an endogenous peptide regulating wakefulness, and is known to interact with anaesthetics. We aim to investigate whether OA inhibits propofol-induced neurite retraction and elucidate the intracellular signalling involved.

    Methods: In primary cortical cell cultures from newborn rat brains, live cell light microscopy was used to measure neurite retraction after propofol (2 μM) with or without OA (10 nM) application after preincubation with the Rhokinase inhibitor (HA-1077), phospholipase D (PLD) inhibitor [5-fluoro-2- indolyl des-chlorohalopemide (FIPI)], protein kinase C (PKC) inhibitor (staurosporine) or PKC activator phorbol 12-myristate 13-acetate (PMA).

    Results: The neurite retraction induced by propofol is blocked by HA-1077 and PMA. OA blocks neurite retraction induced by propofol, and this inhibitory effect could be prevented by FIPI, as well as staurosporine.

    Conclusions: Rho-kinase is essential for propofol-induced neurite retraction in cortical neuronal cells. Activation of PKC plays an inhibitive role during neurite retraction caused by propofol. OA blocks propofol-induced neurite retraction by a PLD/PKC-mediated pathway.

  • 20.
    Zdolsek, Joachim
    et al.
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Anaesthesiology and Surgery UHL. Östergötlands Läns Landsting, Sinnescentrum, Department of Intensive Care UHL.
    Vegfors, Magnus
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Anaesthesiology and Intensive Care VHN.
    Lindahl, Tomas
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Chemistry.
    Tornquist, T.
    Regional Hospital Motala.
    Bortnik, P.
    Regional Hospital Motala.
    Hahn, Robert
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Anaesthesiology and Surgery UHL.
    Hydroxyethyl starches and dextran during hip replacement surgery: effects on blood volume and coagulation2011In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 55, no 6, p. 677-685Article in journal (Refereed)
    Abstract [en]

    Background: Colloid fluids influence the coagulation system by diluting the plasma and, potentially, by exerting other effects that are unique for each fluid product. We hypothesised that changes in the coagulation measured at the end of surgery would be mainly governed by differences in half-life between the colloid fluids. Methods: Eighty-four patients were randomised to receive one of four colloids: HES 130/0.42/6 : 1 (Venofundin (R)), 130/0.4/9 : 1 (Voluven (R)), 200/0.5/5 : 1 (Haes-steril (R)) and 6% dextran 70 (Macrodex (R)). Blood samples were taken just before and after a preoperative 500ml bolus, and also after subsequent elective hip replacement surgery. Volume expansion was estimated from the blood dilution and coagulation assessed by ROTEM, activated partial thromboplastin time, prothrombin international normalised ratio (PT-INR), D-dimer and thrombin-antithrombin complex (TAT). Results: The blood volume expansion amounted to approximately 600 ml for all four colloids directly after infusion. Voluven (R) and Haes-steril (R) prolonged the aPT time and Venofundin (R) increased TAT. Although all colloids increased PT-INR and D-dimer, the ROTEM analyses showed that they consistently shortened the clotting time and weakened the clot strength. These effects were mainly unchanged after surgery, during which the haemorrhage averaged 500-600 ml. Macrodex (R) produced a stronger volume support at the end of the surgery (91% of infused volume; Pless than0.001) than the three starch solutions (42-60%). Conclusions: All tested colloid fluids induced a mild hypercoagulable state with faster clotting, but with weaker clot strength. The additive influence of surgery was relatively small, and postoperative changes in coagulation were mainly due to differences in the half-life of each colloid.

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