| 1. |
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| 2. |
- Amer-Wåhlin, Isis, et al.
(author)
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Fetal cerebral energy metabolism and electrocardiogram during experimental umbilical cord occlusion and resuscitation.
- 2010
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In: Journal of Maternal-Fetal & Neonatal Medicine. - : Informa UK Limited. - 1476-7058 .- 1476-4954. ; 23:2, s. 158-166
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Journal article (peer-reviewed)abstract
- Objective. The purpose of this experimental study was to elucidate alterations in fetal energy metabolism in relation to ECG changes during extreme fetal asphyxia, postnatal resuscitation and the immediate post-resuscitatory phase. Study design. Five near-term fetal sheep were subjected to umbilical cord occlusion until cardiac arrest followed by delivery, resuscitation and postnatal pressure-controlled ventilation. Four sheep served as sham controls and were delivered immediately after ligation of the umbilical cord. Fetal ECG was analysed online for changes of the ST segment. Fetal metabolism was monitored by intracerebral and subcutaneous microdialysis catheters. Results. Fetal ECG reacted on cord occlusion with an increase in the T-wave height followed by changes in intracerebral levels of oxidative parameters. Cerebral lactate/pyruvate ratio and glutamate increased to median (range) of 240 (200-744) and 34.0 (22.6-60.5) mmol/l, respectively; both parameters returned to baseline after resuscitation. Cerebral glucose decreased to 0.1 (0.08-0.12) mmol/l after occlusion and increased above baseline upon resuscitation. In subcutaneous tissue as well as blood the increase in lactate occurred with a delay compared to cerebral levels. Conclusion. The fetal ECG changes related to asphyxia preceded the increase in excitotoxicity as determined by increase in cerebral glutamate during asphyxia. Cerebral lactate increase was superior to subcutaneous lactate increase.
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| 3. |
- Andersson, Kent, 1967-, et al.
(author)
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Introduktion till Operationsanalys : En antologi med essäer av studerande i militärteknik 2011
- 2012
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Other publication (other academic/artistic)abstract
- I ämnesplanen definieras militärteknik som ”den vetenskap som beskriver och förklarar hur tekniken inverkar på militär verksamhet på alla nivåer, strategisk, operativ och taktisk, samt hur officersprofessionen påverkar och påverkas av tekniken.”[1] En militärteknikers uppgift brukar, utgående från definitionen, uttryckas som att beskriva och förklara den militära nyttan med tekniken. För att kunna göra detta behövs verktyg. Och många av dem kommer från den vetenskapliga disciplinen Operationsanalys.Syftet med den här antologin är att introducera studerande i militärteknik på Försvarshögskolan till två av de mest refererade boktitlarna i operationsanalys – Methods for conducting military operational analysis editerad av Andrew G. Loerch och Larry B. Rainey samt Military Operations Research, quantitative decision making av N.K. Jaiswal.Kapitlen utgörs av essäer skrivna av studerande på den högre stabsofficersutbildningen med teknisk inriktning, som examinationsuppgift i en fördjupningskurs. Essäerna är till del referat av kapitel i de två böckerna ovan, men kryddade med exempel satta i svenskt sammanhang och med de studerandes egen värdering av metodernas användbarhet.[1]Försvarshögskolan, Ämnesplan militärteknik, 2007.
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| 4. |
- Bellander, B M, et al.
(author)
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Consensus meeting on microdialysis in neurointensive care
- 2004
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In: Intensive Care Medicine. - : Springer Science and Business Media LLC. - 0342-4642 .- 1432-1238. ; 30, s. 2166-2169
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Journal article (peer-reviewed)abstract
- Background: Microdialysis is used in many European neurointensive care units to monitor brain chemistry in patients suffering subarachnoid hemorrhage (SAH) or traumatic brain injury (TBI). Discussion: We present a consensus agreement achieved at a meeting in Stockholm by a group of experienced users of microdialysis in neurointensive care, defining the use of microdialysis, placement of catheters, unreliable values, chemical markers, and clinical use in SAH and in TBI. Conclusions: As microdialysis is maturing into a clinically useful technique for early detection of cerebral ischemia and secondary brain damage, there is a need to following such definition regarding when and how to use microdialysis after SAH and TBI.
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| 5. |
- Bengtsson, Jörgen, et al.
(author)
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The influence of age on the distribution of morphine and morphine-3-glucuronide across the blood-brain barrier in sheep
- 2009
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In: British Journal of Pharmacology. - : Wiley. - 0007-1188 .- 1476-5381. ; 157:6, s. 1085-1096
-
Journal article (peer-reviewed)abstract
- Background and purpose The effect of age on the distribution of morphine and morphine-3-glucuronide (M3G) across the blood-brain barrier (BBB) was studied in a sheep model utilizing intracerebral microdialysis. The effect of neonatal asphyxia on brain drug distribution was also studied. Experimental approach Microdialysis probes were inserted into the cortex, striatum and blood of 11 lambs (127 gestation days) and six ewes. Morphine, 1 mg.kg(-1), was intravenously administered as a 10 min constant infusion. Microdialysis and blood samples were collected for up to 360 min and analysed using liquid chromatography-tandem mass spectrometry. The half-life, clearance, volume of distribution, unbound drug brain : blood distribution ratio (K(p,uu)) and unbound drug volume of distribution in brain (V(u,brain)) were estimated. Key results Morphine K(p,uu) was 1.19 and 1.89 for the sheep and premature lambs, respectively, indicating that active influx into the brain decreases with age. Induced asphyxia did not affect transport of morphine or M3G across the BBB. Morphine V(u,brain) measurements were higher in sheep than in premature lambs. The M3G K(p,uu) values were 0.27 and 0.17 in sheep and premature lambs, indicating a net efflux from the brain in both groups. Conclusions and implications The morphine K(p,uu) was above unity, indicating active transport into the brain; influx was significantly higher in premature lambs than in adult sheep. These results in sheep differ from those in humans, rats, mice and pigs where a net efflux of morphine from the brain is observed.
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| 6. |
- Boström, Gustaf, et al.
(author)
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Effects of a high-intensity functional exercise program on depressive symptoms among people with dementia in residential care : a randomized controlled trial
- 2016
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In: International Journal of Geriatric Psychiatry. - : Wiley. - 0885-6230 .- 1099-1166. ; 31:8, s. 868-878
-
Journal article (peer-reviewed)abstract
- OBJECTIVES: The aim of this study is to evaluate the effect of a high-intensity functional exercise program on depressive symptoms among older care facility residents with dementia.METHODS: Residents (n = 186) with a diagnosis of dementia, age ≥ 65 years, Mini-Mental State Examination score ≥ 10, and dependence in activities of daily living were included. Participants were randomized to a high-intensity functional exercise program or a non-exercise control activity conducted 45 min every other weekday for 4 months. The 15-item Geriatric Depression Scale (GDS) and the Montgomery-Åsberg Depression Rating Scale (MADRS) were administered by blinded assessors at baseline, 4, and 7 months.RESULTS: No difference between the exercise and control activity was found in GDS or MADRS score at 4 or 7 months. Among participants with GDS scores ≥ 5, reductions in GDS score were observed in the exercise and control groups at 4 months (-1.58, P = 0.001 and -1.54, P = 0.004) and 7 months (-1.25, P = 0.01 and -1.45, P = 0.007). Among participants with MADRS scores ≥ 7, a reduction in MADRS score was observed at 4 months in the control group (-2.80, P = 0.009) and at 7 months in the exercise and control groups (-3.17, P = 0.003 and -3.34, P = 0.002).CONCLUSIONS: A 4-month high-intensity functional exercise program has no superior effect on depressive symptoms relative to a control activity among older people with dementia living in residential care facilities. Exercise and non-exercise group activities may reduce high levels of depressive symptoms.
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| 7. |
- Bouw, R., et al.
(author)
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Increased blood-brain barrier permeability of morphine in a patient with severe brain lesions as determined by microdialysis
- 2001
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In: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172. ; 45, s. 390-
-
Journal article (peer-reviewed)abstract
- Intracerebral microdialysis was utilised to obtain information regarding how morphine is transported across the blood-brain barrier (BBB). In a patient with a severe brain injury, we measured simultaneously unbound extracellular fluid (ECF) concentrations of morphine in human brain and in subcutaneous fat tissue, which were compared to morphine levels in arterial blood. This report shows an increase in morphine levels near the trauma site in the brain compared to uninjured brain tissue. The half-life of morphine in uninjured and injured brain tissue of 178 min and 169 min, respectively, were comparable but were longer than in blood (64 min) and adipose tissue (63 min). This indicates that morphine is retained in brain tissue for a longer time than what could be expected from the blood concentration-time profile. These results show the potential of the microdialysis technique in providing new information regarding the pharmacokinetics of drug in the human brain close to the trauma site and in macroscopically intact tissue.
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| 8. |
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| 9. |
- Chaurasia, Chandra S., et al.
(author)
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AAPS-FDA workshop white paper : microdialysis principles, application and regulatory perspectives
- 2007
-
In: Pharmaceutical research. - : Springer Science and Business Media LLC. - 0724-8741 .- 1573-904X. ; 24:5, s. 1014-1025
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Journal article (peer-reviewed)abstract
- Many decisions in drug development and medical practice are based on measuring blood concentrations of endogenous and exogenous molecules. Yet most biochemical and pharmacological events take place in the tissues. Also, most drugs with few notable exceptions exert their effects not within the bloodstream, but in defined target tissues into which drugs have to distribute from the central compartment. Assessing tissue drug chemistry has, thus, for long been viewed as a more rational way to provide clinically meaningful data rather than gaining information from blood samples. More specifically, it is often the extracellular (interstitial) tissue space that is most closely related to the site of action (biophase) of the drug. Currently microdialysis (microD) is the only tool available that explicitly provides data on the extracellular space. Although microD as a preclinical and clinical tool has been available for two decades, there is still uncertainty about the use of microD in drug research and development, both from a methodological and a regulatory point of view. In an attempt to reduce this uncertainty and to provide an overview of the principles and applications of microD in preclinical and clinical settings, an AAPS-FDA workshop took place in November 2005 in Nashville, TN, USA. Stakeholders from academia, industry and regulatory agencies presented their views on microD as a tool in drug research and development.
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| 10. |
- Chaurasia, Chandra S., et al.
(author)
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AAPS-FDA Workshop White Paper : microdialysis principles, application, and regulatory perspectives
- 2007
-
In: Journal of clinical pharmacology. - : Wiley. - 0091-2700 .- 1552-4604. ; 47:5, s. 589-603
-
Journal article (peer-reviewed)abstract
- Many decisions in drug development and medical practice are based on measuring blood concentrations of endogenous and exogenous molecules. Yet most biochemical and pharmacological events take place in the tissues. Also, most drugs with few notable exceptions exert their effects not within the bloodstream, but in defined target tissues into which drugs have to distribute from the central compartment. Assessing tissue drug chemistry has, thus, for long been viewed as a more rational way to provide clinically meaningful data rather than gaining information from blood samples. More specifically, it is often the extracellular (interstitial) tissue space that is most closely related to the site of action (biophase) of the drug. Currently microdialysis (μD) is the only tool available that explicitly provides data on the extracellular space. Although μD as a preclinical and clinical tool has been available for two decades, there is still uncertainty about the use of μD in drug research and development, both from a methodological and a regulatory point of view. In an attempt to reduce this uncertainty and to provide an overview of the principles and applications of μD in preclinical and clinical settings, an AAPS-FDA workshop took place in November 2005 in Nashville, TN, USA. Stakeholders from academia, industry and regulatory agencies presented their views on μD as a tool in drug research and development.
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| 11. |
- Diaz-Parejo, P, et al.
(author)
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Cerebral energy metabolism during transient hyperglycemia in patients with severe brain trauma
- 2003
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In: Intensive Care Medicine. - : Springer Science and Business Media LLC. - 0342-4642 .- 1432-1238. ; 29:4, s. 544-550
-
Journal article (peer-reviewed)abstract
- Objective: To study whether transient hyperglycemia adversely affects cerebral energy metabolism in patients with severe traumatic brain lesions. Design and setting: Prospective, nonrandomized study in the neurosurgical intensive care unit of a university hospital. Patients: 108 patients treated for severe traumatic brain lesions. Interventions: All patients were treated according to neurosurgical intensive care routine including monitoring of, intracranial pressure. One microdialysis catheter was inserted via a burr hole frontally to that used for the intraventricular catheter ("better" position). In patients with focal lesions one or more catheters were inserted into cerebral cortex surrounding an evacuated focal contusion or underlying an evacuated hematoma ("worse" position). Perfusion rate was 0.3 mul/min and samples were taken every. 30 or 60 min. The levels of glucose, pyruvate, lactate, glutamate, and glycerol were analyzed and displayed bedside. Measurements and results: There were 18 episodes of moderate (12-15 mmol/1) and 6 episodes of pronounced (>15 mmol/1) hyperglycemia. Moderate hyperglycemia did not change intracerebral levels of lactate, pyruvate, glutamate, glycerol, or lactate/pyruvate ratio. Lactate concentrations increased during pronounced hyperglycemia. Pronounced cerebral lactic acidosis and a moderate increase in interstitial glycerol concentration indicating cell membrane degradation was observed in a single patient with pronounced, long-lasting hyperglycemia. Conclusions: Cerebral energy metabolism was affected by transient hyperglycemia only at blood glucose concentration above 15 mmol/l as shown by a moderate increase in interstitial lactate level.
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| 12. |
- Dienel, Gerald A., et al.
(author)
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Microdialysate concentration changes do not provide sufficient information to evaluate metabolic effects of lactate supplementation in brain-injured patients
- 2016
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In: Journal of Cerebral Blood Flow and Metabolism. - 0271-678X. ; 36:11, s. 1844-1864
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Journal article (peer-reviewed)abstract
- Cerebral microdialysis is a widely used clinical tool for monitoring extracellular concentrations of selected metabolites after brain injury and to guide neurocritical care. Extracellular glucose levels and lactate/pyruvate ratios have high diagnostic value because they can detect hypoglycemia and deficits in oxidative metabolism, respectively. In addition, patterns of metabolite concentrations can distinguish between ischemia and mitochondrial dysfunction, and are helpful to choose and evaluate therapy. Increased intracranial pressure can be life-threatening after brain injury, and hypertonic solutions are commonly used for pressure reduction. Recent reports have advocated use of hypertonic sodium lactate, based on claims that it is glucose sparing and provides an oxidative fuel for injured brain. However, changes in extracellular concentrations in microdialysate are not evidence that a rise in extracellular glucose level is beneficial or that lactate is metabolized and improves neuroenergetics. The increase in glucose concentration may reflect inhibition of glycolysis, glycogenolysis, and pentose phosphate shunt pathway fluxes by lactate flooding in patients with mitochondrial dysfunction. In such cases, lactate will not be metabolizable and lactate flooding may be harmful. More rigorous approaches are required to evaluate metabolic and physiological effects of administration of hypertonic sodium lactate to brain-injured patients.
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| 13. |
- Ederoth, Per, et al.
(author)
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Blood-brain barrier transport of morphine in patients with severe brain trauma
- 2004
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In: British Journal of Clinical Pharmacology. - : Wiley. - 0306-5251 .- 1365-2125. ; 57:4, s. 427-435
-
Journal article (peer-reviewed)abstract
- AIMS: In experimental studies, morphine pharmacokinetics is different in the brain compared with other tissues due to the properties of the blood-brain barrier, including action of efflux pumps. It was hypothesized in this clinical study that active efflux of morphine occurs also in human brain, and that brain injury would alter cerebral morphine pharmacokinetics. METHODS: Patients with traumatic brain injury, equipped with one to three microdialysis catheters in the brain and one in abdominal subcutaneous fat for metabolic monitoring, were studied. The cerebral catheter locations were classified as 'better' and 'worse' brain tissue, referring to the degree of injury. Morphine (10 mg) was infused intravenously over a 10-min period in seven patients in the intensive care setting. Tissue and plasma morphine concentrations were obtained during the subsequent 3-h period with microdialysis and regular blood sampling. RESULTS: The area under the concentration-time curve (AUC) ratio of unbound morphine in brain tissue to plasma was 0.64 (95% confidence interval 0.40, 0.87) in 'better' brain tissue (P < 0.05 vs. the subcutaneous fat/plasma ratio), 0.78 (0.49, 1.07) in 'worse' brain tissue and 1.00 (0.86, 1.13) in subcutaneous fat. The terminal half-life and T(max) were longer in the brain vs. plasma and fat, respectively. The relative recovery for morphine was higher in 'better' than in 'worse' brain tissue. The T(max) value tended to be shorter in 'worse' brain tissue. CONCLUSIONS: The unbound AUC ratio below unity in the 'better' human brain tissue demonstrates an active efflux of morphine across the blood-brain barrier. The 'worse' brain tissue shows a decrease in relative recovery for morphine and in some cases also an increase in permeability for morphine over the blood-brain barrier.
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| 14. |
- Ederoth, Per, et al.
(author)
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Experimental pancreatitis causes acute perturbation of energy metabolism in the intestinal wall
- 2002
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In: Pancreas. - 0885-3177. ; 25:3, s. 270-276
-
Journal article (peer-reviewed)abstract
- Introduction: The systemic inflammatory response syndrome (SIRS) may be initiated by a number of underlying conditions such as acute pancreatitis. The association between the local inflammatory reaction, the systemic response, and potential concomitant dysfunction of remote organs is not quite clear. Aim: To evaluate whether severe acute pancreatitis in the rat affects energy metabolism in the pancreas and whether the focal inflammation also causes biochemical deterioration in remote organs such as the liver and intestine. Methodology: With the patient under general anesthesia, microdialysis probes were inserted in the pancreas, liver, and small intestine. Two groups of eight rats each were studied: the sham (control) group and the pancreatitis group. Acute pancreatitis was induced by intraductal injection of 5% sodium taurodeoxycholate, and the animals were studied for 3 hours thereafter. The microdialysis fluid was analyzed for glucose, lactate, and pyruvate. Results: In the pancreatitis group we found significant increases in glucose concentration in the pancreas and lactate levels in the pancreas and intestinal wall, and the lactate/pyruvate ratio was significantly higher in the intestine than in the sham group. Conclusion: Induction of severe acute pancreatitis results in immediate metabolic alterations in the pancreas. In the intestinal wall a severe perturbation of energy metabolism is observed after only 1 hour. This implies a rapid onset of metabolic disturbances, not only in the local, challenged organ (pancreas) but also in remote organs.
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| 15. |
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| 16. |
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| 17. |
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| 18. |
- Gardenfors, F, et al.
(author)
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Adverse biochemical and physiological effects of prostacyclin in experimental brain oedema
- 2004
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In: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 48:10, s. 1316-1321
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Journal article (peer-reviewed)abstract
- Background: Prostacyclin (PGI(2)) and its stable analogues are known to reduce capillary hydraulic permeability. This study explores the biochemical and physiological effects of i.v. infusion of low-dose PGI(2) in an experimental model of vasogenic brain oedema. Methods: Twenty-seven anaesthetized and mechanically ventilated piglets with brain oedema induced by intrathecal injection of lipopolysaccharide (LPS) were used. Five of the animals received a continuous infusion of PGI(2) (1 ng kg(-1) min(-1)) i.v. Four microdialysis catheters were placed in the brain to measure interstitial concentrations of glucose, lactate, and glycerol. Mean arterial pressure (MAP), intracranial pressure (ICP) and temperature were monitored continuously. Low-dose infusion of PGI(2) started 1 h before the LPS injection and was constant during the study period. Results: Intracranial pressure increased significantly in animals treated with PGI(2). The increase in ICP was associated with significant cerebral biochemical changes: decrease in glucose, increase in lactate, increase in lactate/glucose ratio and increase in glycerol. Conclusion: In LPS-induced brain oedema i.v. infusion of low-dose PGI(2) caused a further increase in ICP and a perturbation of energy metabolism, indicating cerebral ischemia and degradation of cellular membranes.
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| 19. |
- Grände, Per-Olof, et al.
(author)
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Lund strikes again - Reply
- 2002
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In: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172. ; 46:10, s. 1281-1283
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Journal article (other academic/artistic)
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| 20. |
- Grände, Per-Olof, et al.
(author)
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Treatment of intracranial hypertension and aspects on lumbar dural puncture in severe bacterial meningitis.
- 2002
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In: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172. ; 46:3, s. 264-270
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Brain stem herniation due to raised intracranial pressure (ICP) is a common cause of mortality in severe bacterial meningitis, but continuous measurements of ICP and the effects of ICP-reducing therapy in these patients have, to our knowledge, not been described. METHODS: During a four-year period, an ICP-monitoring device was implanted in patients admitted to our hospital with severe bacterial meningitis and suspected intracranial hypertension. ICP above 20 mmHg was treated using the Lund Concept, which includes antihypertensive therapy (beta1-antagonist,alpha2-agonist), normalization of the plasma colloid osmotic pressure and the blood volume, and antistress therapy. RESULTS: ICP above 20 mmHg was found in all 12 patients studied. It was effectively reduced in all but two patients, who died. Both patients had a low cerebral perfusion pressure (<10 mmHg), dilated pupils at start of therapy and were beyond recovery. Radiological signs of brain swelling were present in only five patients. Seven patients recovered fully, while mild audiological impairment was observed in two and minor neurological sequelae in one patient. Eight patients showed signs suggesting imminent brain stem herniation before start of ICP-reducing treatment, seven of whom had been subjected to diagnostic lumbar dural puncture shortly before development of the brain stem symptoms. These symptoms gradually regressed after initiation of therapy, and in one patient reversal of brain stem herniation was documented by MRI. CONCLUSIONS: Severe bacterial meningitis can be associated with increased ICP, which can be reduced using the Lund Concept. The high survival rate, the low frequency of sequelae and the reversal of signs of imminent brain stem herniation in these high-risk patients indicated beneficial effects of the intervention. The study confirms earlier observations that lumbar dural puncture is potentially hazardous in patients with intracranial hypertension, because it may trigger brain stem herniation. A normal CT brain scan does not rule out intracranial hypertension.
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| 21. |
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| 22. |
- Grände, Per-Olof, et al.
(author)
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Volume-targeted therapy of increased intracranial pressure: the Lund concept unifies surgical and non-surgical treatments
- 2002
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In: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172. ; 46:8, s. 929-941
-
Research review (peer-reviewed)abstract
- Opinions differ widely on the various treatment protocols for sustained increase in intracranial pressure (ICP). This review focuses on the physiological volume regulation of the intracranial compartments. Based on these mechanisms we describe a protocol called 'volume-targeted' ('Lund concept') for treatment of increased ICP. The driving force for transcapillary fluid exchange is determined by the balance between effective transcapillary hydrostatic and osmotic pressures. Fluid exchange across the intact blood-brain barrier (BBB) is counteracted by the low permeability to crystalloids (mainly Na+ and Cl-) combined with the high osmotic pressure (5500 mmHg) on both sides of the BBB. This contrasts to most other capillary regions where the osmotic pressure is mainly derived from the plasma proteins (approximately 25 mmHg). Accordingly, the level of the cerebral perfusion pressure (CPP) is of less importance under physiological conditions. In addition cerebral intracapillary hydrostatic pressure (and cerebral blood flow) is physiologically tightly autoregulated, and variations in systemic blood pressure are generally not transmitted to these capillaries. If the BBB is disrupted, transcapillary water transport will be determined by the differences in hydrostatic and colloid osmotic pressure between the intra- and extracapillary compartments. Under these pathological conditions, pressure autoregulation of cerebral blood flow is likely to be impaired and intracapillary hydrostatic pressure will depend on variations in systemic blood pressure. The volume-targeted 'Lund concept' can be summarized under four headings: (1) Reduction of stress response and cerebral energy metabolism; (2) reduction of capillary hydrostatic pressure; (3) maintenance of colloid osmotic pressure and control of fluid balance; and (4) reduction of cerebral blood volume. The efficacy of the protocol has been evaluated in experimental and clinical studies regarding the physiological and biochemical (utilizing intracerebral microdialysis) effects, and the clinical experiences have been favorable.
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| 23. |
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| 24. |
- Hansen-Schwartz, Jacob, et al.
(author)
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Human endothelin subtype a receptor enhancement during tissue culture via de novo transcription
- 2002
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In: Neurosurgery. - 0148-396X. ; 50:1, s. 127-133
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Journal article (peer-reviewed)abstract
- OBJECTIVE: Endothelin (ET) has, since its discovery, increasingly been considered a key player in the pathophysiological processes of cerebral vasospasm in the course of subarachnoid hemorrhage, although it remains unclear how ET is involved. We present data that indicate an inherent capacity of human cerebral arteries to change their sensitivity to ET. METHODS: Human cerebral arteries were obtained from patients undergoing intracranial tumor surgery. The vessels were divided into segments and subjected to organ culture for 48 hours. The vessels were then examined by using in vitro pharmacological methods and molecular biological techniques. RESULTS: After organ culture of the cerebral arteries, both the sensitivity to and potency of ET were enhanced (maximal response, 152 +/- 9%; -log (50% effective concentration), 10.3 +/- 0.3), in comparison with data for fresh cerebral arteries. Contractions were inhibited by both FR139317 (a specific ETA receptor antagonist) and bosentan (a mixed ETA and ETB receptor antagonist), in a manner indicating the sole presence of contractile ETA receptors. An inconsistent dilative response to the selective ETB receptor agonist sarafotoxin 6c was observed; the response was preserved in some segments and abolished in others, and potentiation of the precontraction was observed in yet other segments. No isolated contractile response to sarafotoxin 6c was observed, however. In reverse transcription-polymerase chain reaction assays, both ETA and ETB receptor messenger ribonucleic acid was detected. CONCLUSION: These results demonstrate that human cerebral arteries are capable of enhancing the function of ETA receptors.
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| 25. |
- Holmer, Helene, et al.
(author)
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Hypothalamic involvement predicts cardiovascular risk in adults with childhood onset craniopharyngioma on long-term GH therapy.
- 2009
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In: European Journal of Endocrinology. - 0804-4643 .- 1479-683X. ; 16, s. 671-679
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Journal article (peer-reviewed)abstract
- Context: Craniopharyngioma patients without GH therapy are at an increased cardiovascular disease (CVD) risk and particularly concerning women. No previous study on long-term GH therapy in adults with childhood onset (CO) craniopharyngioma was identified. Objective: To investigate CVD risk in adults with CO craniopharyngioma on complete hormone replacement, including long-term GH therapy, and to investigate the impact of disease-related factors on CVD risk. Design and participants: In a cross-sectional study of operated CO craniopharyngiomas (1958–2000) from a defined area of Sweden (2.5 million), we enrolled 42 patients (20 women) with a median age of 28 years (range 17–57) and assessed CVD risk of 20 (4–40) years after first operation. Comparisons were made with matched controls and between patients with tumor growth into the third ventricle (TGTV) versus non-TGTV. GH therapy was 10–12 years in women and men. Results: In comparison with controls, both male and female patients had increased body mass index, fat mass, insulin, and leptin levels. Overall, while not significantly increased in male patients, 55–60% of female patients had a medium–high CVD risk, compared with 10–20% in controls. An increased CVD risk (all P<0.05) and higher levels of fat mass and insulin were recorded in the TGTV group versus the non-TGTV group. Late puberty induction and lack of androgens were shown in female patients. Conclusions: Adult patients with CO craniopharyngioma, especially those with TGTV, have persistently increased CVD risk. Conventional hormone substitution, including GH, is insufficient to normalize CVD risk, suggesting an important role for irreversible hypothalamic dysfunction.
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| 26. |
- Hutchinson, Peter J, et al.
(author)
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Consensus statement from the 2014 International Microdialysis Forum
- 2015
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In: Intensive Care Medicine. - : Springer Science and Business Media LLC. - 0342-4642 .- 1432-1238. ; 41:9, s. 1517-1528
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Journal article (peer-reviewed)abstract
- Microdialysis enables the chemistry of the extracellular interstitial space to be monitored. Use of this technique in patients with acute brain injury has increased our understanding of the pathophysiology of several acute neurological disorders. In 2004, a consensus document on the clinical application of cerebral microdialysis was published. Since then, there have been significant advances in the clinical use of microdialysis in neurocritical care. The objective of this review is to report on the International Microdialysis Forum held in Cambridge, UK, in April 2014 and to produce a revised and updated consensus statement about its clinical use including technique, data interpretation, relationship with outcome, role in guiding therapy in neurocritical care and research applications.
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| 27. |
- Jakobsen, Rasmus Peter, et al.
(author)
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Effects of norepinephrine infusion on cerebral energy metabolism during experimental haemorrhagic shock
- 2022
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In: Intensive Care Medicine Experimental. - : Springer Science and Business Media LLC. - 2197-425X. ; 10:1
-
Journal article (peer-reviewed)abstract
- Background: The use of norepinephrine in the case of life-threatening haemorrhagic shock is well established but widely discussed. The present study was designed to compare the effects of early norepinephrine treatment vs. no treatment on cerebral energy metabolism during haemorrhagic shock. Methods: Twelve pigs were subjected to haemorrhagic shock, 4 in the control group and 8 in the norepinephrine (NE) group. Following a 60 min baseline period haemorrhagic shock was achieved by bleeding all animals to a pre-defined mean arterial blood pressure (MAP) of approximately 40 mm Hg. When mean arterial pressure had decreased to 40 mmHg NE infusion started in the treatment group. After 90 min, NE infusion stopped, and all pigs were resuscitated with autologous blood and observed for 2.5 h. During the experiment cerebral tissue oxygenation (PbtO2) was monitored continuously and variables reflecting cerebral energy metabolism (glucose, lactate, pyruvate, glutamate, glycerol) were measured by utilizing intracerebral microdialysis. Results: All 12 pigs completed the protocol. NE infusion resulted in significantly higher MAP (p < 0.001). During the shock period lactate/pyruvate (LP) ratio group increased from 20 (15–29) to 66 (38–82) (median (IQR)) in the control group but remained within normal limits in the NE group. The significant increase in LP ratio in the control group remained after resuscitation. After induction of shock PbtO2 decreased markedly in the control group and was significantly lower than in the NE group during the resuscitation phase. Conclusion: NE infusion during haemorrhagic shock improved cerebral energy metabolism compared with no treatment.
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| 28. |
- Jansson, Kjell, 1958-
(author)
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Intraperitoneal microdialysis : technique and results
- 2004
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Doctoral thesis (other academic/artistic)abstract
- Microdialysis has recently developed from a laboratory research method of animals to a useful clinical tool to evaluate parameters suggesting tissue ischemia. It is now used in neurosurgery, plastic surgery and liver transplantation.Shock and multiple organ failure after surgery are rare but serious complications with a high mortality rate and splanchnic ischemia is an early and important step in this development. Splanchnic ischemia is leading to increased permeability of the intestinal mucosa and to activation of macrophages. Subsequent release of inflammatory mediators like cytokines initiates shock, which may result in multiple organ failure and death. The importance of splanchnic hypoxia/ischemia is investigated in these five studies in relation to activation of cytokines (intraperitoneal and systemic) during a normal recovery and in case of surgical complications after major gastrointestinal surgery.Postoperatively the metabolic substances, glucose, pyruvate, lactate and glycerol were analysed and the LP ratio was calculated using microdialysis intraperitoneally and subcutaneously. Two studies are focused on the activation of the immunologic system by measurement of the cytokines TNF-, IL-6 and IL-10 and the relationship between LP ratio and the cytokines. Three studies are describing the performance of intraperitoneal microdialysis, different responses depending on the site of measurement, the difference between intraperitoneal and subcutaneous measurements and normal values in postoperative gastrointestinal surgery. Patients with clinical complications are described separately.No adverse effects of the intraperitoneal measurement technique were seen. An increase of the intraperitoneal LP ratio and decrease of glucose were in several cases preceding clinical complications. Intraperitoneal LP ratio, glucose and cytokines were higher in the abdominal cavity compared to subcutaneous and systemic measurements in a normal postoperative recovery. An intraperitoneal correlation between TNF-a and the LP ratio was found. Intraperitoneal concentrations of the cytokines and the LP ratio were decreasing in parallel during a normal postoperative recovery.The intraperitoneal inflammatory response is higher, during a normal postoperative recovery as well as in patients suffering from complications, compared to systemic findings, emphazising the importance of the gastrointestinal tract as the source of early immunological reactions postoperatively. IPM enables safe and sensitive analysis of glucose, pyruvate, lactate and glycerol from the intraperitoneal organs measured in the intraperitoneal fluid.Measurement of the LP ratio with microdialysis seems to detect early splanchnic hypoxia/ischemia that correlates to the intraperitoneal inflammation. IPM may have a future as an important clinical tool for monitoring patients at risk of developing postoperative surgical complications.
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| 29. |
- Kelsen, Jesper, et al.
(author)
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Copenhagen Head Injury Ciclosporin Study : A Phase IIa Safety, Pharmacokinetics, and Biomarker Study of Ciclosporin in Severe Traumatic Brain Injury Patients
- 2019
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In: Journal of Neurotrauma. - : Mary Ann Liebert Inc. - 0897-7151 .- 1557-9042. ; 36:23, s. 3253-3263
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Journal article (peer-reviewed)abstract
- Traumatic brain injury (TBI) contributes to almost one third of all trauma-related deaths, and those that survive often suffer from long-term physical and cognitive deficits. Ciclosporin (cyclosporine, cyclosporin A) has shown promising neuroprotective properties in pre-clinical TBI models. The Copenhagen Head Injury Ciclosporin (CHIC) study was initiated to establish the safety profile and pharmacokinetics of ciclosporin in patients with severe TBI, using a novel parenteral lipid emulsion formulation. Exploratory pharmacodynamic study measures included microdialysis in brain parenchyma and protein biomarkers of brain injury in the cerebrospinal fluid (CSF). Sixteen adult patients with severe TBI (Glasgow Coma Scale 4-8) were included, and all patients received an initial loading dose of 2.5 mg/kg followed by a continuous infusion for 5 days. The first 10 patients received an infusion dosage of 5 mg/kg/day whereas the subsequent 6 patients received 10 mg/kg/day. No mortality was registered within the study duration, and the distribution of adverse events was similar between the two treatment groups. Pharmacokinetic analysis of CSF confirmed dose-dependent brain exposure. Between- and within-patient variability in blood concentrations was limited, whereas CSF concentrations were more variable. The four biomarkers, glial fibrillary acidic protein, neurofilament light, tau, and ubiquitin carboxy-terminal hydrolase L1, showed consistent trends to decrease during the 5-day treatment period, whereas the samples taken on the days after the treatment period showed higher values in the majority of patients. In conclusion, ciclosporin, as administered in this study, is safe and well tolerated. The study confirmed that ciclosporin is able to pass the blood-brain barrier in a TBI population and provided an initial biomarker-based signal of efficacy.
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| 30. |
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| 31. |
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| 32. |
- Lourido, J, et al.
(author)
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Correlation between blood glucose concentration and glucose concentration in subcutaneous adipose tissue evaluated with microdialysis during intensive care
- 2002
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In: Scandinavian Journal of Clinical & Laboratory Investigation. - : Informa UK Limited. - 1502-7686 .- 0036-5513. ; 62:4, s. 285-292
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Journal article (peer-reviewed)abstract
- Background: Hyper- as well as hypoglycemia may be detrimental for brain energy metabolism and even a moderate increase in blood glucose concentration can affect outcome adversely. During physiological conditions, glucose concentration obtained from microdialysis of subcutaneous adipose tissue adequately reflects plasma glucose concentration. This study examines whether this correlation is also obtained during intensive care in patients with severe injuries. Methods.. The study included 62 patients with severe traumatic brain injuries. All patients received one 30 mm microdialysis catheter (CMA 60, CMA Microdialysis) inserted into periumbilical subcutaneous adipose tissue. The probe was perfused (0.3 mul/min) with a Ringer solution from a microinfusion Pump and analyzed for glucose, lactate, and glycerol. The Study included 2.434 simultaneous analyses of glucose concentration in arterial blood and subcutaneous adipose tissue. Results.' The correlation coefficient for glucose concentration in blood and interstitial fluid was 0.743 for the whole material. The cot-relation was relatively poor for 1-6h after insertion of the probes, During this period. a continuous increase in the Subcutaneous level Of glucose and decreases in lactate and glycerol were noted. Conclusions: The correlation between blood glucose concentration and glucose Concentration in subcutaneous adipose tissue was not as good during intensive care as in normal humans. The poor correlation during the first 6h probably reflects a stress reaction (and possibly local vasoconstriction). Microdialysis of subcutaneous adipose tissue permits frequent bedside analyses of the biochemical composition of the extracellular fluid and may be of value during routine intensive care provided the methodological limitations are recognized.
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| 33. |
- Malm, J., et al.
(author)
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The Swedish Malignant Middle cerebral artery Infarction Study : long-term results from a prospective study of hemicraniectomy combined with standardized neurointensive care
- 2006
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In: Acta Neurologica Scandinavica. - Copenhagen : Munksgaard. - 0001-6314 .- 1600-0404. ; 113:1, s. 25-30
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Journal article (peer-reviewed)abstract
- Objectives: Hemicraniectomy in patients with malignant middle cerebral artery (mMCA) infarct may be life-saving. The long-term prognosis is unknown.Methods: Patients with mMCA infarct treated with hemicraniectomy between 1998 and 2002 at three hospitals were included. The criterion for surgical intervention was if the patients deteriorated from awake to being responding to painful stimuli only. All patients were followed for at least 1 year. Outcome was defined as alive/dead, walkers/non-walkers or modified Rankin Scale (mRS) score ≤2.Results: Thirty patients were included (median age at stroke onset 49 years, range 17–67 years). Fourteen patients had mMCA infarct on the left side and 16 patients on the right side. Fourteen patients had pupil dilatation before surgery. Hemicraniectomy was performed at a median of 52 h (range 13–235 h) after stroke onset. Nine patients died within 1 month after surgery because of cerebral herniation (n = 6), myocardial infarction (n = 1) or intensive care complications (n = 2). No further deaths occurred during follow-up, which was at median 3.4 years after surgery. Status for the 21 survivors at the last follow-up was: mRS 2 or less (n = 6) and mRS 3–5 (n = 15). The oldest patient with mRS 2 or less was 53 years at stroke onset. Thirteen patients (43%) could walk without substantial aid.Conclusion: The long-term survival after mMCA infarction treated with hemicraniectomy seems to be favourable if the patient survives the acute phase. The outcome as measured with mRS may be better among younger patients.
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| 34. |
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| 35. |
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| 36. |
- Nilsson, F, et al.
(author)
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A porcine model for evaluation of cerebral haemodynamics and metabolism during increased intracranial pressure
- 1995
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In: Acta Anaesthesiologica Scandinavica. - 0001-5172. ; 39:6, s. 827-834
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Journal article (peer-reviewed)abstract
- In patients with severe head injuries raised intracranial pressure (ICP) constitutes the most important cause of mortality. Several new therapies for increased ICP have recently been suggested and it is of importance to study the physiological effects of these treatments in animal experiments during steady state conditions. A porcine model for evaluation of cerebral haemodynamics and metabolism during increased ICP is presented. Intracranial hypertension was induced by inflation of two tonometric gastric balloons placed extradurally covering a major part of the parietooccipital region bilaterally. The distribution of the blood flow supplied by the carotid artery used for the cerebral blood flow (CBF) measurements was studied by intraarterial (i.a.) injection of 99mTc-HMPAO. The measurements showed that following ligation of the external carotid and the occipital artery no accumulation of tracer substance occurred in extracranial tissues during normal or increased ICP. Cerebral physiological variables (CBF, Cavo2, and ICP) were measured 5, 20 and 60 min after induction of intracranial hypertension. The results confirm that the experimental situation gives a reproducible increase in ICP (25-28 mm Hg) and that the physiological variables remain stable during the period of intracranial hypertension. We conclude that the model simulates the effects of an acute intracranial focal mass and is well suited for the evaluation of different pharmacological therapies of increased ICP.
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| 37. |
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| 38. |
- Nilsson, Petra, et al.
(author)
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Tumefactive demyelinating disease treated with decompressive craniectomy.
- 2009
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In: European Journal of Neurology. - : Wiley. - 1351-5101 .- 1468-1331. ; 16, s. 639-642
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Journal article (peer-reviewed)abstract
- Background: Tumefactive demyelinating disease (TDD) is a rare primary demyelinating disease with diagnostic and therapeutic challenges. Methods and results: We report a 50-year old woman with TDD successfully treated with decompressive craniectomy and corticosteroids. The patient presented with seizures, subacute progressive hemispheric syndrome, and a tumourlike abnormality on MRI. Demyelinating disease was initially considered unlikely. Due to a rapidly evolving herniation syndrome hemicraniectomy was performed. Outcome was favourable with only very mild neurological deficits 6 weeks later. Conclusion: TDD should be considered as a differential diagnosis in tumour-like presentations, and appears to have distinctive neuroimaging features. In the advent of treatement failure from high dose corticosteroids and plasmapheresis and development of severe mass effect, decompressive hemicraniectomy is an important treatment option.
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| 39. |
- Nordström, Carl-Henrik, et al.
(author)
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Aspects on the Physiological and Biochemical Foundations of Neurocritical Care
- 2017
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In: Frontiers in Neurology. - : Frontiers Media S.A.. - 1664-2295. ; 8
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Research review (peer-reviewed)abstract
- Neurocritical care (NCC) is a branch of intensive care medicine characterized by specific physiological and biochemical monitoring techniques necessary for identifying cerebral adverse events and for evaluating specific therapies. Information is primarily obtained from physiological variables related to intracranial pressure (ICP) and cerebral blood flow (CBF) and from physiological and biochemical variables related to cerebral energy metabolism. Non-surgical therapies developed for treating increased ICP are based on knowledge regarding transport of water across the intact and injured blood-brain barrier (BBB) and the regulation of CBF. Brain volume is strictly controlled as the BBB permeability to crystalloids is very low restricting net transport of water across the capillary wall. Cerebral pressure autoregulation prevents changes in intracranial blood volume and intracapillary hydrostatic pressure at variations in arterial blood pressure. Information regarding cerebral oxidative metabolism is obtained from measurements of brain tissue oxygen tension (PbtO2) and biochemical data obtained from intracerebral microdialysis. As interstitial lactate/pyruvate (LP) ratio instantaneously reflects shifts in intracellular cytoplasmatic redox state, it is an important indicator of compromised cerebral oxidative metabolism. The combined information obtained from PbtO2, LP ratio, and the pattern of biochemical variables reveals whether impaired oxidative metabolism is due to insufficient perfusion (ischemia) or mitochondrial dysfunction. Intracerebral microdialysis and PbtO2 give information from a very small volume of tissue. Accordingly, clinical interpretation of the data must be based on information of the probe location in relation to focal brain damage. Attempts to evaluate global cerebral energy state from microdialysis of intraventricular fluid and from the LP ratio of the draining venous blood have recently been presented. To be of clinical relevance, the information from all monitoring techniques should be presented bedside online. Accordingly, in the future, the chemical variables obtained from microdialysis will probably be analyzed by biochemical sensors.
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| 40. |
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| 41. |
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| 42. |
- Nordström, Carl Henrik, et al.
(author)
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Biochemical indications of cerebral ischaemia and mitochondrial dysfunction in severe brain trauma analysed with regard to type of lesion
- 2016
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In: Acta Neurochirurgica. - : Springer Science and Business Media LLC. - 0001-6268 .- 0942-0940. ; 158:7, s. 1231-1240
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Journal article (peer-reviewed)abstract
- Background: The study focuses on three questions related to the clinical usefulness of microdialysis in severe brain trauma: (1) How frequently is disturbed cerebral energy metabolism observed in various types of lesions? (2) How often does the biochemical pattern indicate cerebral ischaemia and mitochondrial dysfunction? (3) How do these patterns relate to mortality? Method: The study includes 213 consecutive patients with severe brain trauma (342 intracerebral microdialysis catheters). The patients were classified into four groups according to the type of lesion: extradural haematoma (EDH), acute subdural haematoma (SDH), cerebral haemorrhagic contusion (CHC) and no mass lesion (NML). Altogether about 150,000 biochemical analyses were performed during the initial 96 h after trauma. Results: Compromised aerobic metabolism occurred during 38 % of the study period. The biochemical pattern indicating mitochondrial dysfunction was more common than that of ischaemia. In EDH and NML aerobic metabolism was generally close to normal. In SDH or CHC it was often severely compromised. Mortality was increased in SDH with impaired aerobic metabolism, while CHC did not exhibit a similar relation. Conclusions: Compromised energy metabolism is most frequent in patients with SDH and CHC (32 % and 49 % of the study period, respectively). The biochemical pattern of mitochondrial dysfunction is more common than that of ischaemia (32 % and 6 % of the study period, respectively). A correlation between mortality and biochemical data is obtained provided the microdialysis catheter is placed in an area where energy metabolism reflects tissue outcome in a large part of the brain.
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| 43. |
- Nordström, Carl-Henrik
(author)
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Cerebral energy metabolism and microdialysis in neurocritical care.
- 2010
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In: Child's Nervous System. - : Springer Science and Business Media LLC. - 1433-0350 .- 0256-7040. ; 26, s. 465-472
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Journal article (peer-reviewed)abstract
- It is of obvious clinical importance to monitor cerebral metabolism-in particular, cerebral energy metabolism and indicators of cellular damage-online at the bedside. The technique of cerebral microdialysis provides the opportunity for continuous monitoring of metabolic changes in the tissue before they are reflected in peripheral blood chemistry or in systemic physiological parameters. The basic idea of microdialysis is to mimic the function of a blood capillary by positioning a thin dialysis tube in the tissue and to be used to analyze the chemical composition of the interstitial fluid. The biochemical variables used during routine monitoring were chosen to cover important aspects of cerebral energy metabolism (glucose, pyruvate and lactate), to indicate excessive interstitial levels of excitatory transmitter substance (glutamate) and to give indications of degradation of cellular membranes (glycerol). Furthermore, pharmokinetic studies can be conducted using microdialysis. This article discusses technical and physiological aspects of microdialysis, and its clinical applications in brain injury.
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| 44. |
- Nordström, Carl-Henrik
(author)
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Cerebral metabolism
- 2004
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In: Journal of Neurosurgery. - 0022-3085. ; 100:3, s. 575-576
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Journal article (other academic/artistic)
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| 45. |
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| 46. |
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| 47. |
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| 48. |
- Nordström, Carl-Henrik
(author)
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Insulin, intracerebral glucose and bedside biochemical monitoring utilizing microdialysis.
- 2008
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In: Critical Care. - : Springer Science and Business Media LLC. - 1364-8535. ; 12:2
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Journal article (peer-reviewed)abstract
- ABSTRACT: Following subarachnoid hemorrhage, hyperglycemia is strongly associated with complications and with impaired neurological recovery. Targeted insulin therapy for glycemic control might, on the contrary, have harmful effects by causing too low cerebral glucose levels. The study published by Schlenk and colleagues in the previous issue of Critical Care shows that insulin caused a significant decrease in the interstitial cerebral glucose concentration although the blood glucose level remained unaffected. Since several studies utilizing various analytical techniques have shown that cerebral blood flow and cerebral glucose uptake and metabolism are insulin-independent processes, the observation remains unexplained.
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| 49. |
- Nordström, Carl-Henrik
(author)
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Intracerebral microdialysis during routine neuro intensive care
- 2004
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In: Microdialysis – Monitoring Tissue Chemistry in Intensive Care Medicine. Experimental Results and Clinical Application of Biochemical Tissue Monitoring in Critical Illness. - 3899671244 ; , s. 23-34
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Conference paper (peer-reviewed)
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| 50. |
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