SwePub
Sök i SwePub databas

  Extended search

Träfflista för sökning "WFRF:(Bentzer Peter) "

Search: WFRF:(Bentzer Peter)

  • Result 1-50 of 88
Sort/group result
   
EnumerationReferenceCoverFind
1.
  • Bansch, Peter, et al. (author)
  • A Model for Evaluating the Effects of Blunt Skeletal Muscle Trauma on Microvascular Permeability and Plasma Volume in the Rat
  • 2010
  • In: Shock. - 1540-0514. ; 33:4, s. 399-404
  • Journal article (peer-reviewed)abstract
    • The objective of the present study was to develop an experimental model suitable for studying the effects of a nonhemorrhagic soft tissue trauma on plasma volume (PV) and microvascular permeability. Anesthetized Sprague-Dawley rats were exposed to a sham procedure or a laparotomy followed by a standardized trauma to the abdominal rectus muscle. We evaluated the effects of trauma on transcapillary escape rate and on PV (3 h after trauma) using I-125-albumin as tracer and on edema formation in the traumatized muscle with a wet- versus dry- weight method. The effects of the trauma on the cytokines IFN-gamma, IL-4, IL-6, IL-10, and TNF-alpha were investigated 1 and 3 h after trauma in a separate group. Transcapillary escape rate was 13.9% per hour in the sham animals compared with 18.5% per hour in the traumatized animals (P < 0.05). Because arterial and venous blood pressures were not altered by the trauma, the change in transcapillary escape rate most likely reflects a change in microvascular permeability. Plasma volume decreased from 42 mL/kg at baseline to 31 mL/kg at the end of the experiments (P < 0.05) in the trauma group, whereas PV remained unchanged in the sham group. Only 15% of the PV loss could be referred to edema in the traumatized muscle. Trauma induced a significant increase in IL-6 and IL-10 after 1 h. We conclude that the present nonhemorrhagic trauma induces an increase in microvascular permeability in the traumatized tissue and in other parts of the body, resulting in hypovolemia. The model may be used for the evaluation of different therapeutic interventions aimed at the correction of hypovolemia.
  •  
2.
  • Bansch, Peter, et al. (author)
  • Changes in the sublingual microcirculation during major abdominal surgery and post-operative morbidity.
  • 2014
  • In: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172. ; 58:1, s. 89-97
  • Journal article (peer-reviewed)abstract
    • Little is known about perioperative microcirculatory changes during major abdominal surgery, and the main objectives of this study were to evaluate perioperative microcirculatory alterations in this setting, and if changes in microcirculatory parameters are associated with post-operative morbidity and/or with changes in parameters reflecting oxygen delivery.
  •  
3.
  • Bansch, Peter, et al. (author)
  • Effect of charge on microvascular permeability in early experimental sepsis in the rat.
  • 2011
  • In: Microvascular Research. - : Elsevier BV. - 1095-9319 .- 0026-2862. ; 82, s. 339-345
  • Journal article (peer-reviewed)abstract
    • A key feature of sepsis is hypovolemia due to increased microvascular permeability. It has been suggested that the negative charge of albumin and of the endothelial glycocalyx is important for maintenance of the normally low permeability for albumin. Here we tested the hypothesis that charge effects contribute to the increased permeability in sepsis. Transcapillary escape rate (TER) and initial distribution volume for (125)I-labeled bovine serum albumin (BSA, isoelectric point pH 4.6) and for (131)I-labeled charge modified BSA (cBSA, average isoelectric point, pH 7.1) was measured 3h after sepsis was induced by cecal ligation and incision (CLI) (n=11) and in control animals (n=12). The importance of charge for permeability in sepsis was estimated by comparing the ratio between TER for cBSA and TER for BSA during control conditions to that after CLI. Plasma concentration of the glycocalyx component glycosaminoglycans (GAGs) was measured in separate control and CLI animals. The initial distribution volume for BSA and cBSA in control animals was 38±3ml/kg and 47±4mL/kg and decreased by 17% and 19%, respectively, following CLI. TER for BSA increased from 16.7±4.1% in the controls to 20.1±1.9% following CLI. Corresponding values for cBSA were 26.7±5.6% and 29.8±3.5%, respectively. The ratio between TER for cBSA and TER for BSA was 1.62±0.1 in the control group and 1.49±0.1 following CLI (p<0.05). Plasma GAG concentrations were higher in CLI animals than in the control group. We conclude that CLI induce hypovolemia secondary to increased microvascular permeability. Negative charge contributes to the normally low permeability of albumin and the importance of charge is decreased in early experimental sepsis. The observed charge effects are associated with CLI-induced breakdown of the glycocalyx.
  •  
4.
  •  
5.
  •  
6.
  • Bansch, Peter, et al. (author)
  • Prostacyclin reduces plasma volume loss after skeletal muscle trauma in the rat.
  • 2012
  • In: Journal of Trauma and Acute Care Surgery. - 2163-0755.
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Trauma induces transcapillary leakage of fluid and proteins because of increased microvascular permeability. Based on studies showing that prostacyclin (PGI2) has permeability-reducing properties, in the present study, we investigated whether PGI2 reduces plasma volume (PV) loss after a nonhemorrhagic trauma. METHODS: The study was performed on anesthetized Sprague-Dawley rats exposed to a controlled standardized blunt trauma to the abdominal rectus muscle. Thereafter, the animals were randomized to treatment with either PGI2 (2 ng/kg per minute) or 0.9% NaCl. PV was estimated before and 3 hours after the trauma using I-albumin as tracer. In separate experiments, the transcapillary escape rate of I-albumin was calculated and plasma concentrations of cytokines were measured after both treatments. RESULTS: Average PV at baseline was 41.6 mL/kg ± 2.5 mL/kg and 42.3 mL/kg ± 1.7 mL/kg in the PGI2 and NaCl animals, respectively. PV was decreased by 22% ± 8% in the NaCl animals and by 11% ± 9% in the PGI2 animals 3 hours after the trauma (p < 0.05). Trauma induced a decrease in mean arterial blood pressure and an increase in hematocrit in both groups. There were no differences in urine production and mean arterial blood pressure between the PGI2 and NaCl animals. The transcapillary escape rate for albumin was calculated for one hour starting 30 minutes after the trauma and was 15.1% ± 2.4% per hour in the PGI2 animals and 17.4% ± 3.3% per hour in the NaCl animals (p = 0.09). Interleukin 6 concentration 3 hours after the trauma was lower in the PGI2 animals than in the NaCl animals (p < 0.05). CONCLUSION: We conclude that PGI2 attenuates PV loss after blunt muscle trauma. The vascular effects of PGI2 are associated with a modulation of the trauma-induced inflammatory response.
  •  
7.
  • Jungner, Mårten, et al. (author)
  • Blood-brain barrier permeability following traumatic brain injury.
  • 2016
  • In: Minerva Anestesiologica. - 1827-1596. ; 82:5, s. 525-533
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Brain edema and intracranial hypertension is deleterious after traumatic brain injury (TBI), but the underlying pathophysiology is complex and poorly understood. One major subject of controversy is the time course and extent of blood-brain barrier (BBB) dysfunction following trauma, and previous studies in humans have only provided semi-quantitative data. The objective of the present study was therefore to quantify changes in BBB-permeability in the early course of TBI, when brain edema is still evolving. METHODS: Sixteen non-consecutive brain trauma patients and two controls were included. Following i.v. injection of iohexol and CT perfusion scans, patients were scanned eight times from 4 to 25 minutes. Blood to brain transfer constant (Ki) for iohexol (molecular weight 821 D), reflecting permeability and available area for diffusion, was calculated offline by Patlak plot analysis of the enhancement curves of intracerebral large venous vessels and pericontusional brain parenchyma. RESULTS : In non-ischemic tissue surrounding contusions and hematomas Ki was increased 2-to 10-fold compared to normal tissue, reaching maximal values of 0.5 mL/min/100 g. In non-injured areas and in controls Ki was about 0.06 mL/min/100 g. The increase was more pronounced in the most severely injured patients, and was detectable within 24 hours after trauma and up to five days after. CONCLUSIONS: Our results suggest that traumatic brain injury is associated with early focal increases in small molecular BBB-permeability. The results indicate that in the injured brain, capillary hydrostatic and oncotic pressures may influence edema formation.
  •  
8.
  • Kamal, Nadia, et al. (author)
  • The mosaic oat genome gives insights into a uniquely healthy cereal crop
  • 2022
  • In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 606:7912, s. 113-119
  • Journal article (peer-reviewed)abstract
    • Cultivated oat (Avena sativa L.) is an allohexaploid (AACCDD, 2n = 6x = 42) thought to have been domesticated more than 3,000 years ago while growing as a weed in wheat, emmer and barley fields in Anatolia1,2. Oat has a low carbon footprint, substantial health benefits and the potential to replace animal-based food products. However, the lack of a fully annotated reference genome has hampered efforts to deconvolute its complex evolutionary history and functional gene dynamics. Here we present a high-quality reference genome of A. sativa and close relatives of its diploid (Avena longiglumis, AA, 2n = 14) and tetraploid (Avena insularis, CCDD, 2n = 4x = 28) progenitors. We reveal the mosaic structure of the oat genome, trace large-scale genomic reorganizations in the polyploidization history of oat and illustrate a breeding barrier associated with the genome architecture of oat. We showcase detailed analyses of gene families implicated in human health and nutrition, which adds to the evidence supporting oat safety in gluten-free diets, and we perform mapping-by-sequencing of an agronomic trait related to water-use efficiency. This resource for the Avena genus will help to leverage knowledge from other cereal genomes, improve understanding of basic oat biology and accelerate genomics-assisted breeding and reanalysis of quantitative trait studies.
  •  
9.
  • Mohanty, Tirthankar, et al. (author)
  • Neutrophil extracellular traps in the central nervous system hinder bacterial clearance during pneumococcal meningitis
  • 2019
  • In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 1667-1667
  • Journal article (peer-reviewed)abstract
    • Neutrophils are crucial mediators of host defense that are recruited to the central nervous system (CNS) in large numbers during acute bacterial meningitis caused by Streptococcus pneumoniae. Neutrophils release neutrophil extracellular traps (NETs) during infections to trap and kill bacteria. Intact NETs are fibrous structures composed of decondensed DNA and neutrophil-derived antimicrobial proteins. Here we show NETs in the cerebrospinal fluid (CSF) of patients with pneumococcal meningitis, and their absence in other forms of meningitis with neutrophil influx into the CSF caused by viruses, Borrelia and subarachnoid hemorrhage. In a rat model of meningitis, a clinical strain of pneumococci induced NET formation in the CSF. Disrupting NETs using DNase I significantly reduces bacterial load, demonstrating that NETs contribute to pneumococcal meningitis pathogenesis in vivo. We conclude that NETs in the CNS reduce bacterial clearance and degrading NETs using DNase I may have significant therapeutic implications.
  •  
10.
  • Adrian, Maria, et al. (author)
  • Mechanical complications after central venous catheterisation in the ultrasound-guided era : a prospective multicentre cohort study
  • 2022
  • In: British Journal of Anaesthesia. - : Elsevier BV. - 1471-6771 .- 0007-0912. ; 129:6, s. 843-850
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Limited data are available on the incidence of mechanical complications after ultrasound-guided central venous catheterisation. We aimed to determine the incidence of mechanical complications in hospitals where real-time ultrasound guidance is clinical practice for central venous access and to identify variables associated with mechanical complications.METHODS: All central venous catheter insertions in patients ≥16 yr at four emergency care hospitals in Sweden from March 2, 2019 to December 31, 2020 were eligible for inclusion. Every insertion was monitored for complete documentation and occurrence of mechanical complications within 24 h after catheterisation. Multivariable logistic regression analyses were used to determine associations between predefined variables and mechanical complications.RESULTS: In total, 12 667 catheter insertions in 8586 patients were included. The incidence (95% confidence interval [CI]) of mechanical complications was 7.7% (7.3-8.2%), of which 0.4% (0.3-0.5%) were major complications. The multivariable analyses showed that patient BMI <20 kg m -2 (odds ratio 2.69 [95% CI: 1.17-5.62]), male operator gender (3.33 [1.60-7.38]), limited operator experience (3.11 [1.64-5.77]), and increasing number of skin punctures (2.18 [1.59-2.88]) were associated with major mechanical complication. Subclavian vein catheterisation was associated with pneumothorax (5.91 [2.13-17.26]). CONCLUSIONS: The incidence of major mechanical complications is low in hospitals where real-time ultrasound guidance is the standard of care for central venous access. Several variables independently associated with mechanical complications can be used for risk stratification before catheterisation procedures, which might further reduce complication rates.CLINICAL TRIAL REGISTRATION: NCT03782324.
  •  
11.
  • Adrian, Maria, et al. (author)
  • Research protocol for mechanical complications after central venous catheterisation : a prospective controlled multicentre observational study to determine incidence and risk factors of mechanical complications within 24 hours after cannulation
  • 2019
  • In: BMJ Open. - : BMJ. - 2044-6055. ; 9:10, s. 029301-029301
  • Journal article (peer-reviewed)abstract
    • INTRODUCTION: Central venous catheterisation is a common procedure in intensive care therapy and the use of central venous catheters is essential for treatment of many medical disorders. Although rare, central venous catheterisation is associated with mechanical complications that can be life-threatening if untreated. Real-time ultrasound guidance reduces the incidence of mechanical complications when compared with the anatomic landmark method. The purpose of this study is to determine the incidence of and potential risk factors associated with early mechanical complications of central venous catheterisation in an era where real-time ultrasound guidance has become clinical practice. METHODS AND ANALYSIS: This is a prospective, controlled, multicentre, observational study. All participating hospitals follow the same clinical guidelines for central venous catheterisation. Each central venous catheter insertion will be recorded in the common electronic chart system according to a recently revised template. An automated script-based search will identify all recorded central venous catheter insertion templates during the study period and relevant variables will be extracted. Outcome measures and independent variables are pre-defined in this study protocol. Multivariable and univariable logistic regression analysis will be used to determine associations and risk factors of mechanical complications. ETHICS AND DISSEMINATION: The Regional Ethical Review Board in Lund, Sweden has approved this study. The results will be submitted for publication in peer-reviewed medical journals and presented at national and international scientific meetings. TRIAL REGISTRATION NUMBER: NCT03782324.
  •  
12.
  • Bentzer, Peter, et al. (author)
  • Advances in Sepsis Research.
  • 2015
  • In: Clinics in Chest Medicine. - : Elsevier BV. - 1557-8216 .- 0272-5231. ; 36:3, s. 521-530
  • Research review (peer-reviewed)abstract
    • Recent research has identified promising targets for therapeutic interventions aimed at modulating the inflammatory response in sepsis. Herein, the authors describe mechanisms involved in the clearance of pathogen toxin from the circulation and potential interventions aimed at enhancing clearance mechanisms. The authors also describe advances in the understanding of the innate immune response as potential therapeutic targets. Finally, novel potential treatment strategies aimed at decreasing vascular leak are discussed.
  •  
13.
  • Bentzer, Peter, et al. (author)
  • Capillary filtration coefficient is independent of number of perfused capillaries in cat skeletal muscle
  • 2001
  • In: American Journal of Physiology: Heart and Circulatory Physiology. - 1522-1539. ; 280:6, s. 2697-2706
  • Journal article (peer-reviewed)abstract
    • The capillary filtration coefficient (CFC) is assumed to reflect both microvascular hydraulic conductivity and the number of perfused capillaries at a given moment (precapillary sphincter activity). Estimation of hydraulic conductivity in vivo with the CFC method has therefore been performed under conditions of unchanged vascular tone and metabolic influence. There are studies, however, that did not show any change in CFC after changes in vascular tone and metabolic influence, and these studies indicate that CFC may not be influenced by alteration in the number of perfused capillaries. The present study reexamined to what extent CFC in a pressure-controlled preparation depends on the vascular tone and number of perfused capillaries by analyzing how CFC is influenced by 1) vasoconstriction, 2) increase in metabolic influence by decrease in arterial blood pressure, and 3) occlusion of precapillary microvessels by arterial infusion of microspheres. CFC was calculated from the filtration rate induced by a fixed decrease in tissue pressure. Vascular tone was increased in two steps by norepinephrine (n = 7) or angiotensin II (n = 6), causing a blood flow reduction from 7.2 +/- 0.8 to at most 2.7 +/- 0.2 ml . min(-1) . 100 g(-1) (P< 0.05). The decrease in arterial pressure reduced blood flow from 4.8 +/- 0.4 to 1.40 +/- 0.1 ml . min(-1) . 100 g(-1) (n = 6). Vascular resistance increased to 990 +/- 260% of control after the infusion of microspheres (n = 6). CFC was not significantly altered from control after any of the experimental interventions. We conclude that CFC under these conditions is independent of the vascular tone and number of perfused capillaries and that variation in CFC reflects variation in microvascular hydraulic conductivity.
  •  
14.
  • Bentzer, Peter, et al. (author)
  • Effect of dextran-70 on outcome in severe sepsis; A propensity-score matching study
  • 2017
  • In: Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine. - : Springer Science and Business Media LLC. - 1757-7241. ; 25:1
  • Journal article (peer-reviewed)abstract
    • Background: Albumin may be beneficial in patients with septic shock but availability is limited and cost is high. The objective of the present study was to investigate if the use of dextran-70 in addition to albumin and crystalloids influences organ failure or mortality in patients with severe sepsis or septic shock. Methods: Patients with severe sepsis or septic shock (n = 778) admitted to a university hospital intensive care unit (ICU) between 2007 and 2015 that received dextran-70 during resuscitation were propensity score matched to controls at a 1 to 1 ratio. Outcomes were highest acute kidney injury network (AKIN) score the first 10 days in the ICU, use of renal replacement therapy, days alive and free of organ support the first 28 days after admission to ICU, mortality and events of severe bleeding. Outcomes were assessed using paired hypothesis testing. Results: Propensity score matching resulted in two groups of patients with 245 patients in each group. The dextran group received a median volume of 1483 ml (interquartile range, 1000-2000 ml) of dextran-70 during the ICU stay. Highest AKIN score did not differ between the control- and dextran groups (1 (0-3) versus 2 (0-3), p = 0.06). Incidence of renal replacement therapy in the control- and dextran groups was similar (19% versus 22%, p = 0.42, absolute risk reduction -2.9% [95% CI: -9.9 to 4.2]). Days alive and free of renal replacement, vasopressors and mechanical ventilation did not differ between the control- and dextran groups. The 180-day mortality was 50.2% in the control group and 41.6% in the dextran group (p = 0.046, absolute risk reduction 8.6% [-0.2 to 17.4]). Fraction of patients experiencing a severe bleeding in the first 10 days in the ICU did not differ between the control and dextran groups (14% versus 18%, p = 0.21). Discussion: There is a paucity of high quality data regarding effects of dextran solutions on outcome in sepsis. In the present study, propensity score matching was used in attempt to reduce bias. Conclusion: No evidence to support a detrimental effect of dextran-70 on mortality or on organ failures in patients with severe sepsis or septic shock could be detected.
  •  
15.
  • Bentzer, Peter, et al. (author)
  • Endothelin-1 Reduces Microvascular Fluid Permeability through Secondary Release of Prostacyclin in Cat Skeletal Muscle.
  • 2002
  • In: Microvascular Research. - : Elsevier BV. - 1095-9319 .- 0026-2862. ; 63:1, s. 50-60
  • Journal article (peer-reviewed)abstract
    • The aim of the study was to analyze effects of various plasma concentrations of the vasoconstrictor endothelin-1 on microvascular fluid permeability and on transcapillary fluid exchange. We also analyzed whether the permeability-reducing substance prostacyclin is involved in the permeability effects of endothelin-1, as prostacylin is suggested to be released via ET(B) receptor stimulation. The study was performed on an autoperfused cat calf muscle preparation, and a capillary filtration coefficient (CFC) technique was used to estimate variations in microvascular fluid permeability (conductivity). Intraarterial infusion of endothelin-1 in low doses (5 and 10 ng/min/100 g muscle) caused transcapillary absorption, whereas higher doses (20-40 ng/min/100 g) induced filtration despite further vasoconstriction. Low-dose endothelin-1 had no significant effect on CFC, while CFC was reduced to at most 55% of baseline at higher doses (P < 0.01). Simultaneous local intraarterial infusion of the prostacyclin synthesis inhibitor tranylcypromine restored CFC to 114% of baseline (P < 0.01) and further increased vascular resistance. A low, nonvasodilator dose of prostacyclin given intravenously counteracted the tranylcypromine effect on CFC. The decreased CFC induced by a high dose of endothelin-1 was counteracted by the ET(B) receptor antagonist BQ-788 with no change in vascular resistance (P < 0.05). We conclude that the decreased CFC following high doses of endothelin-1 can be attributed to a decrease in microvascular hydraulic conductivity, mediated by secondary release of prostacylin via stimulation of the ET(B) receptor. Endothelin-1 may induce edema through postcapillary vasoconstriction. (c)2001 Elsevier Science.
  •  
16.
  • Bentzer, Peter, et al. (author)
  • Evaluation of capillary perfusion - Reply
  • 2002
  • In: American Journal of Physiology: Heart and Circulatory Physiology. - 1522-1539. ; 282:3, s. 1172-1173
  • Journal article (other academic/artistic)
  •  
17.
  • Bentzer, Peter, et al. (author)
  • Heparin-binding protein is important for vascular leak in sepsis
  • 2016
  • In: Intensive Care Medicine Experimental. - : Springer Science and Business Media LLC. - 2197-425X. ; 4:1
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Elevated plasma levels of heparin-binding protein (HBP) are associated with risk of organ dysfunction and mortality in sepsis, but little is known about causality and mechanisms of action of HBP. The objective of the present study was to test the hypothesis that HBP is a key mediator of the increased endothelial permeability observed in sepsis and to test potential treatments that inhibit HBP-induced increases in permeability.METHODS: Association between HBP at admission with clinical signs of increased permeability was investigated in 341 patients with septic shock. Mechanisms of action and potential treatment strategies were investigated in cultured human endothelial cells and in mice.RESULTS: Following adjustment for comorbidities and Acute Physiology and Chronic Health Evaluation (APACHE) II, plasma HBP concentrations were weakly associated with fluid overload during the first 4 days of septic shock and the degree of hypoxemia (PaO2/FiO2) as measures of increased systemic and lung permeability, respectively. In mice, intravenous injection of recombinant human HBP induced a lung injury similar to that observed after lipopolysaccharide injection. HBP increased permeability of vascular endothelial cell monolayers in vitro, and enzymatic removal of luminal cell surface glycosaminoglycans (GAGs) using heparinase III and chondroitinase ABC abolished this effect. Similarly, unfractionated heparins and low molecular weight heparins counteracted permeability increased by HBP in vitro. Intracellular, selective inhibition of protein kinase C (PKC) and Rho-kinase pathways reversed HBP-mediated permeability effects.CONCLUSIONS: HBP is a potential mediator of sepsis-induced acute lung injury through enhanced endothelial permeability. HBP increases permeability through an interaction with luminal GAGs and activation of the PKC and Rho-kinase pathways. Heparins are potential inhibitors of HBP-induced increases in permeability.
  •  
18.
  • Bentzer, Peter, et al. (author)
  • Infusion of prostacyclin following experimental brain injury in the rat reduces cortical lesion volume
  • 2001
  • In: Journal of Neurotrauma. - : Mary Ann Liebert Inc. - 1557-9042 .- 0897-7151. ; 18:3, s. 275-285
  • Journal article (peer-reviewed)abstract
    • Endothelial-derived prostacyclin is an important regulator of microvascular function, and its main actions are inhibition of platelet/leukocyte aggregation and adhesion, and vasodilation. Disturbances in endothelial integrity following traumatic brain injury (TBI) may result in insufficient prostacyclin production and participate in the pathophysiological sequelae of brain injury. The objective of this study was to evaluate the potential therapeutic effects of a low-dose prostacyclin infusion on cortical lesion volume, CA3 neuron survival and functional outcome following TBI in the rat. Anesthetized animals (sodium pentobarbital, 60 mg/kg, i.p.) were subjected to a lateral fluid percussion brain injury (2.5 atm) or sham injury. Following TBI, animals were randomized to receive a constant infusion of either prostacyclin (1 ng/kg x min(-1) i.v.) or vehicle over 48 h. All sham animals received vehicle (n = 6). Evaluation of neuromotor function, lesion volume, and CA3 neuronal loss was performed blindly. By 7 days postinjury, cortical lesion volume was significantly reduced by 43% in the prostacyclin-treated group as compared to the vehicle treated group (p < 0.01; n = 12 prostacyclin, n = 12 vehicle). No differences were observed in neuromotor function (48 h and 7 days following TBI), or in hippocampal cell loss (7 days following TBI) between the prostacyclin- and vehicle-treated groups. We conclude that prostacyclin in a low dose reduces loss of neocortical neurons following TBI and may be a potential clinical therapeutic agent to reduce neuronal cell death associated with brain trauma.
  •  
19.
  • Bentzer, Peter, et al. (author)
  • Isolated Brain Trauma in Cats Triggers Rapid Onset of Hypovolemia
  • 2017
  • In: Neurocritical Care. - : Springer Science and Business Media LLC. - 1541-6933 .- 1556-0961. ; 26:3, s. 450-456
  • Journal article (peer-reviewed)abstract
    • Background: Hemodynamic instability responsive to fluid resuscitation is common after a traumatic brain injury (TBI), also in the absence of systemic hemorrhage. The present study tests if an isolated severe TBI induces a decrease in plasma volume (PV). Methods: The study was performed in three groups of anesthetized and tracheostomized male cats (n = 21). In one group (n = 8), the cats were prepared with a cranial borehole (10 mm i.d) used to expose the brain to a fluid percussion brain injury (FPI) (1.90–2.20 bar), and two smaller cranial boreholes (4 mm i.d) for insertion of an intracranial pressure (ICP) and a microdialysis catheter. To differentiate the effect of FPI from that of the surgical preparation, a sham group was exposed to the same surgical preparation but no FPI trauma (n = 8). A control group had no brain trauma and no surgical preparation (n = 5). PV was determined by a 125I-albumin dilution technique. PV, electrolytes, pH, BE (base excess), hematocrit (Hct), PaO2, and PaCO2 were measured at baseline and after 3 h. Mean arterial pressure (MAP) was measured continuously. ICP was measured in the FPI and the sham group. Results: In the FPI group, PV decreased by 11.2 mL/kg from 31.7 mL/kg (p < 0.01) with a simultaneous increase in Hct and decrease in pH. In the sham group, PV decreased by 5.7 mL/kg from 32.7 mL/kg (p < 0.01). The control group showed no PV reduction. Conclusions: The results support that an isolated severe head trauma triggers a significant and rapid reduction in PV, most likely due to vascular leak.
  •  
20.
  • Bentzer, Peter, et al. (author)
  • Low-Dose Prostacyclin Improves Cortical Perfusion following Experimental Brain Injury in the Rat.
  • 2003
  • In: Journal of Neurotrauma. - : Mary Ann Liebert Inc. - 1557-9042 .- 0897-7151. ; 20:5, s. 447-461
  • Journal article (peer-reviewed)abstract
    • It was recently shown that prostacyclin at a low dose reduces cortical cell death following brain trauma in the rat. Conceivably, prostacyclin with its vasodilatory, anti-aggregatory, anti-adhesive and permeability-reducing properties improved a compromised perfusion caused by post-traumatic vasoconstriction, microthrombosis and increased microvascular permeability. The objective of the present study was therefore to investigate the hemodynamic effects of low-dose prostacyclin in the traumatized rat cortex. Following a fluid percussion brain injury or a sham procedure, animals were treated with a continuous intravenous infusion of prostacyclin of 1 or 2 ng x kg(-1) x min(-1), or vehicle. Blood flow ([(14)C]-iodoantipyrine), the permeability-surface area product (PS) for [(51)Cr]-EDTA, and brain water content were measured after 3 or 48 h of treatment. Blood flow values in the injured cortex were transiently reduced to 0.42 +/- 0.2 mL x min(-1) in the vehicle group 3 h following trauma from a corresponding value of about 1.6 mL x min(-1) in the sham group, with recovery of blood flow after 48 h. Prostacyclin treatment caused a dose-dependent increase in blood flow which reached statistical significance 48 h following trauma. Brain water content and PS increased in the injured cortex post trauma and the higher dose of prostacyclin increased these parameters further at 48 h compared to the vehicle group (p < 0.05). The latter effects of prostacyclin cannot be attributed to an increase in permeability, as prostacyclin did not influence PS or brain water content following sham trauma. In fact prostacyclin has been shown to have permeability-decreasing properties. We conclude that prostacyclin improves cortical perfusion following brain trauma. The simultaneous aggravation of brain edema can be explained by an increased surface area, perhaps in combination with increased capillary hydrostatic pressure.
  •  
21.
  •  
22.
  • Bentzer, Peter, et al. (author)
  • Microdialysis-based long-term measurements of energy-related metabolites in the rat brain following a fluid percussion trauma
  • 2000
  • In: Journal of Neurotrauma. - 1557-9042. ; 17:5, s. 441-447
  • Journal article (peer-reviewed)abstract
    • The aim of the study was to evaluate an experimental approach based on a fluid percussion rat trauma model in combination with the microdialysis technique for the analysis of cerebral interstitial biochemical alterations following head trauma, and to test the hypothesis that the previously observed acute accumulation of lactate and increase in the lactate pyruvate ratio may persist for several days following trauma. We analyzed how lactate, pyruvate, and glucose were altered in the cortex adjacent to the contusion and in the contralateral side of the brain following a traumatic brain injury. The results were compared with those from sham-operated animals. The lactate concentration in the cortex adjacent to the contusion was 0.73 +/- 0.13 mmol/L and 0.71 +/- 0.08 mmol/L 24 and 48 h posttrauma, respectively, and 0.42 +/- 0.07 mmol/L in the sham group (p < 0.05). The lactate/pyruvate ratio of 18.3 +/- 2.3 in the cortex adjacent to the contusion 24 h posttrauma was higher than corresponding value of 10.3 +/- 1.5 in the sham group (p < 0.05). The lactate/pyruvate ratio 48 h posttrauma did not differ from that in the sham group. Interstitial glucose in the cortex adjacent to the contusion and the sham group were similar. Microdialysis measurements from the contralateral side did not differ from those in the sham group. We conclude that the previously observed acute alterations in brain metabolism persist for at least 48 h posttrauma. Further, the measured parameters from the contralateral side can be used as controls since they did not differ from the sham group. Combining microdialysis with a fluid percussion trauma model may be a tool to explore secondary brain injury mechanisms and evaluate new therapies for the treatment of traumatic brain injury.
  •  
23.
  • Bentzer, Peter, et al. (author)
  • Plasma cytokine levels predict response to corticosteroids in septic shock
  • 2016
  • In: Intensive Care Medicine. - : Springer Science and Business Media LLC. - 0342-4642 .- 1432-1238. ; 42:12, s. 1970-1979
  • Journal article (peer-reviewed)abstract
    • Purpose: To investigate if plasma cytokine concentrations predict a beneficial response to corticosteroid treatment in septic shock patients. Methods: A cohort of septic shock patients in whom a panel of 39 cytokines had been measured at baseline (n = 363) was included. Patients who received corticosteroids were propensity score matched to non-corticosteroid-treated patients. An optimal threshold to identify responders to corticosteroid treatment for each cytokine was defined as the concentration above which the odds ratio for 28-day survival between corticosteroid- and non-corticosteroid-treated patients was highest. Results: Propensity score matching partitioned 165 patients into 61 sets; each set contained matched corticosteroid- and non-corticosteroid-treated patients. For 13 plasma cytokines threshold concentrations were found where the odds ratio for survival between corticosteroid- and non-corticosteroid-treated patients was significant (P <0.05). CD40 ligand was associated with the highest odds ratio and identified 21 % of the patients in the propensity score matched cohort as responders to corticosteroid treatment. Combinations of triplets of cytokines with a significant odds ratio, using the thresholds identified above, were tested to find a higher proportion of responders. IL3, IL6, and CCL4 identified 50 % of the patients in the propensity score matched cohort as responders to corticosteroid treatment. The odds ratio for 28-day survival was 19 (95 % CI 3.5–140, P = 0.02) with a concentration above threshold for a least one of these cytokines. Conclusion: Plasma concentration of selected cytokines is a potential predictive biomarker to identify septic shock patients that may benefit from treatment with corticosteroids.
  •  
24.
  • Bentzer, Peter, et al. (author)
  • Prostacyclin reduces microvascular fluid conductivity in cat skeletal muscle through opening of ATP-dependent potassium channels
  • 1999
  • In: Journal of Vascular Research. - 1423-0135. ; 36:6, s. 516-523
  • Journal article (peer-reviewed)abstract
    • Prostacyclin is suggested to reduce microvascular permeability, but the cellular mechanisms mediating this response in the microvascular endothelial cells are still unknown. Considering that prostacyclin relaxes vascular smooth muscle cells via opening of ATP-dependent potassium channels, and opening of ATP-dependent potassium channels in the endothelial cells is suggested to influence microvascular permeability, this study was designed to test (1) if ATP-dependent potassium channels are involved in the regulation of microvascular hydraulic permeability, (2) if the permeability-reducing effect of prostacyclin is mediated through opening of ATP-dependent potassium channels, and (3) if cAMP is involved in this process. An autoperfused cat calf hindlimb was used as experimental model, and microvascular hydraulic permeability (conductivity) was estimated by a capillary filtration coefficient (CFC) technique. The potassium channel opener PCO-400 (0.5 microg x min(-1) per 100 g muscle, intra-arterially), prostacyclin (1 ng x min(-1) per kg body weight, intravenously) and the cAMP analogue dibutyryl-cAMP (24 microg x min(-1) per 100 g muscle, intra-arterially), decreased CFC to 77, 72 and 69% compared to control, respectively (p < 0.01). The decrease in CFC obtained by these substances was completely restituted after the start of a simultaneous infusion of the ATP-dependent potassium channel blocker glibenclamide (6 microg x min(-1) per 100 g muscle, intra-arterially; p < 0.01). Infusion of glibenclamide alone increased CFC to 107% of control (p < 0.05). In conclusion, the ATP-dependent potassium channels contribute to the regulation of microvascular hydraulic conductivity, and the prostacyclin permeability-reducing effect may act through this mechanism via increase in intracellular cAMP.
  •  
25.
  • Bentzer, Peter, et al. (author)
  • Supersensitivity in rat micro-arteries after short-term denervation
  • 1997
  • In: Acta Physiologica Scandinavica. - 0001-6772. ; 161:2, s. 125-133
  • Journal article (peer-reviewed)abstract
    • Contractile responses to phenylephrine and high-K+ were investigated in vitro in microvascular preparations from the rat medial plantar artery, a branch from the saphenous artery, obtained after short-term denervation in vivo. Two groups of animals were studied: (1) animals undergoing surgical resection of the saphenous nerve, and (2) animals undergoing surgical resection of both the sciatic and saphenous nerves. The animals were operated on one side only. Microvascular preparations (diameter about 325 microns) were obtained 10 days after surgery. Vessels from the non-operated side served as controls. Immunocytochemistry showed a decreased number of both neuropeptide Y (NPY) and calcitonin gene-related peptide (CGRP) immunoreactive nerve fibres in vessels after resection of the saphenous nerve only. Resection of both the saphenous and the sciatic nerve caused a complete loss of immunoreactive nerve fibres. Mechanical measurements were performed using a wire myograph. In vessels subjected to resection of the saphenous nerve the sensitivity to phenylephrine was similar to controls. Vessels denervated by resection of both the saphenous and sciatic nerves showed significant increases in phenylephrine and potassium sensitivity. When depolarized in high-K+ solution the denervated vessels showed an increased sensitivity to extracellular Ca2+. The results show that complete short-term denervation of the rat medial plantar artery in vivo causes a pronounced supersensitivity in the vascular smooth muscle. The supersensitivity appears not to be restricted to the sympathetic alpha-receptors but also associated with changes in the cellular excitation-contraction coupling. Such altered reactivity of the vascular smooth muscle may contribute to vascular disturbances observed in vivo after nerve damage or surgical denervation.
  •  
26.
  •  
27.
  • Bentzer, Peter, et al. (author)
  • The volume-expanding effects of autologous liquid stored plasma following hemorrhage.
  • 2012
  • In: Scandinavian Journal of Clinical and Laboratory Investigation. - : Informa UK Limited. - 1502-7686 .- 0036-5513. ; 72:6, s. 490-494
  • Journal article (peer-reviewed)abstract
    • Background: Plasma use has increased since studies have suggested that early treatment with blood components in trauma with severe hemorrhage may improve outcome. Plasma is also commonly used to correct coagulation disturbances in non-bleeding patients. Little is known about the effects of plasma transfusion on plasma volume. We report a prospective interventional study in which the plasma volume-expanding effect of autologous plasma was investigated after a controlled hemorrhage. Methods: Plasma obtained by plasmapheresis from nine healthy regular blood donors was stored at 2-6°C. Five weeks after donation the subjects were bled of 600 ml and then transfused with 600 ml of autologous plasma. Plasma volume was estimated using (125)I-albumin before and after bleeding, and immediately after plasma transfusion. Plasma volume changes were then estimated by measuring changes in hematocrit during the following 3-h period. Results: Estimated plasma volume after bleeding was 3170 ± 320 ml and 3690 ± 380 ml (mean ± standard deviation) immediately following the transfusion of plasma (p 0.05). This increase in plasma volume corresponds to 86 ± 13% of the infused volume. Three hours after transfusion, plasma volume was still 3680 ± 410 ml. Conclusions: Stored liquid plasma has a plasma volume expanding effect up to 86% of its infused volume with a duration of at least 3 h.
  •  
28.
  • Bentzer, Peter (author)
  • Vascular effects of prostacyclin in cat skeletal muscle and in the traumatised rat brain
  • 2001
  • Doctoral thesis (other academic/artistic)abstract
    • Disturbances in microvascular function may be important for tissue damage in many disease states. Prostacyclin, a substance produced by endothelial cells, is important for the maintenance of normal vascular homeostasis and is a potential drug for treatment of microvascular dysfunction, but indications and optimal dosage remains to be established. In the present thesis we evaluated the capillary filtration coefficient (CFC)-method as a tool to investigate changes in microvascular permeability in vivo. In contrast to previous studies we found that CFC is not significantly influenced by alterations in precapillary sphincter activity and concluded that changes in CFC reflect changes in fluid permeability in cat skeletal muscle. Using the CFC-method we investigated effects of prostacyclin on microvascular fluid permeability and found that prostacyclin may decrease fluid permeability through opening of ATP-dependent potassium channels. We also found that prostacyclin may be released and decrease fluid permeability following increases in plasma concentrations of endothelin-1. We also investigated effects of prostacyclin in a low dose, which is clinically applicable without side effects such as hypotension, on macromolecular permeability in cat skeletal muscle and found that such a treatment could counteract an increase in macromolecular permeability. In order to evaluate potentially beneficial effects on microvascular perfusion following a brain trauma, prostacyclin in a low dose was administered following traumatic brain injury in rats. Prostacyclin reduced cell death simultaneously with an increase in cerebral blood flow and an increase in the number of perfused capillaries in the injured part of the brain. The results presented in the present thesis suggest that treatment with prostacyclin in low doses may be beneficial in disease states characterised by an impaired microvascular perfusion and increased vascular permeability such as following a brain trauma.
  •  
29.
  • Bentzer, Peter, et al. (author)
  • Will this hemodynamically unstable patient respond to a bolus of intravenous fluids?
  • 2016
  • In: JAMA: The Journal of the American Medical Association. - : American Medical Association (AMA). - 0098-7484. ; 316:12, s. 1298-1309
  • Journal article (peer-reviewed)abstract
    • IMPORTANCE Fluid overload occurring as a consequence of overly aggressive fluid resuscitation may adversely affect outcome in hemodynamically unstable critically ill patients. Therefore, following the initial fluid resuscitation, it is important to identify which patients will benefit from further fluid administration. OBJECTIVE To identify predictors of fluid responsiveness in hemodynamically unstable patients with signs of inadequate organ perfusion. DATA SOURCES AND STUDY SELECTION Search of MEDLINE and EMBASE (1966 to June 2016) and reference lists from retrieved articles, previous reviews, and physical examination textbooks for studies that evaluated the diagnostic accuracy of tests to predict fluid responsiveness in hemodynamically unstable adult patients who were defined as having refractory hypotension, signs of organ hypoperfusion, or both. Fluid responsiveness was defined as an increase in cardiac output following intravenous fluid administration. DATA EXTRACTION Two authors independently abstracted data (sensitivity, specificity, and likelihood ratios [LRs]) and assessed methodological quality. A bivariate mixed-effects binary regression model was used to pool the sensitivities, specificities, and LRs across studies. RESULTS A total of 50 studies (N = 2260 patients) were analyzed. In all studies, indices were measured before assessment of fluid responsiveness. The mean prevalence of fluid responsiveness was 50% (95%CI, 42%-56%). Findings on physical examination were not predictive of fluid responsiveness with LRs and 95%CIs for each finding crossing 1.0. A low central venous pressure (CVP) (mean threshold 8mmHg) was associated with fluid responsiveness (positive LR, 2.6 [95%CI, 1.4-4.6]; pooled specificity, 76%), but a CVP greater than the threshold made fluid responsiveness less likely (negative LR, 0.50 [95%CI, 0.39-0.65]; pooled sensitivity, 62%). Respiratory variation in vena cava diameter measured by ultrasound (distensibility index >15%) predicted fluid responsiveness in a subgroup of patients without spontaneous respiratory efforts (positive LR, 5.3 [95%CI, 1.1-27]; pooled specificity, 85%). Patients with less vena cava distensibility were not as likely to be fluid responsive (negative LR, 0.27 [95%CI, 0.08-0.87]; pooled sensitivity, 77%). Augmentation of cardiac output or related parameters following passive leg raising predicted fluid responsiveness (positive LR, 11 [95%CI, 7.6-17]; pooled specificity, 92%). Conversely, the lack of an increase in cardiac output with passive leg raising identified patients unlikely to be fluid responsive (negative LR, 0.13 [95%CI, 0.07-0.22]; pooled sensitivity, 88%). CONCLUSIONS AND RELEVANCE Passive leg raising followed by measurement of cardiac output or related parameters may be the most useful test for predicting fluid responsiveness in hemodynamically unstable adults. The usefulness of respiratory variation in the vena cava requires confirmatory studies.
  •  
30.
  • Björkander, Malin, et al. (author)
  • Mechanical complications of central venous catheter insertions : A retrospective multicenter study of incidence and risks
  • 2019
  • In: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172. ; 63:1, s. 61-68
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Incidence and risk factors for complications after insertion of central venous catheters have previously been reported for smaller cohorts. The aim of this observational multicenter study was to study risk factors for mechanical complications in a large, recently collected cohort of patients.METHODS: Records of central venous catheter insertions from 8 hospitals in southern Sweden from 2013 to 2016 were collected from the regional chart system. Data on blood coagulation tests, use of ultrasonography, central venous catheter location, bore size, number of needle passes, arterial puncture, the chronological order of the central venous catheter insertion, and mechanical complications were extracted. Only one insertion/patient was included using worst-case selection criteria. Predefined primary outcome was mechanical complications defined as bleeding, pneumothorax, nerve injury, or malignant arrhythmia. Severe mechanical complications were defined as bleeding requiring intervention or transfusion, pneumothorax, persistent nerve injury, or non-self-limiting arrhythmias.RESULTS: We included 10 949 insertions and identified 118 (1.1%) incidents of mechanical complication, of which 85 (0.8%) were bleedings, 21 (0.2%) were pneumothoraces, 7 (0.06%) were transient nerve injuries, and 5 (0.05%) were self-limiting arrhythmias. Severe mechanical complications occurred in 23 (0.2%) cases.CONCLUSIONS: In this retrospective, multicenter observational study on 10 949 central venous catheter insertions, mechanical complications were rare. Preprocedural coagulopathy, number of needle passes, and arterial puncture were associated with grade 2-4 bleeding. Subclavian vein insertions, arterial puncture, and chronological order of the central venous catheter insertion were associated with pneumothorax.
  •  
31.
  • Boberg, Linn, et al. (author)
  • Environmental impact of single-use, reusable, and mixed trocar systems used for laparoscopic cholecystectomies
  • 2022
  • In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 17:7
  • Journal article (peer-reviewed)abstract
    • INTRODUCTION: Climate change is one of the 21st century's biggest public health issues and health care contributes up to 10% of the emissions of greenhouse gases in developed countries. About 15 million laparoscopic procedures are performed annually worldwide and single-use medical equipment is increasingly used during these procedures. Little is known about costs and environmental footprint of this change in practice.METHODS: We employed Life Cycle Assessment method to evaluate and compare the environmental impacts of single-use, reusable, and mixed trocar systems used for laparoscopic cholecystectomies at three hospitals in southern Sweden. The environmental impacts were calculated using the IMPACT 2002+ method and a functional unit of 500 procedures. Monte Carlo simulations were used to estimate differences between trocar systems. Data are presented as medians and 2.5th to 97.5th percentiles. Financial costs were calculated using Life Cycle Costing.RESULTS: The single-use system had a 182% higher impact on resources than the reusable system [difference: 5160 MJ primary (4400-5770)]. The single-use system had a 379% higher impact on climate change than the reusable system [difference: 446 kg CO2eq (413-483)]. The single-use system had an 83% higher impact than the reusable system on ecosystem quality [difference: 79 PDF*m2*yr (24-112)] and a 240% higher impact on human health [difference: 2.4x10-4 DALY/person/yr (2.2x10-4-2.6x10-4)]. The mixed and single-use systems had a similar environmental impact. Differences between single-use and reusable trocars with regard to resource use and ecosystem quality were found to be sensitive to lower filling of machines in the sterilization process. For ecosystem quality the difference between the two were further sensitive to a 50% decrease in number of reuses, and to using a fossil fuel intensive electricity mix. Differences regarding effects on climate change and human health were robust in the sensitivity analyses. The reusable and mixed trocar systems were approximately half as expensive as the single-use systems (17360 € and 18560 € versus 37600 €, respectively).CONCLUSION: In the Swedish healthcare system the reusable trocar system offers a robust opportunity to reduce both the environmental impact and financial costs for laparoscopic surgery.
  •  
32.
  • Damén, Tor, et al. (author)
  • Effects of different mean arterial pressure targets on plasma volume, ANP and glycocalyx-A randomized trial.
  • 2021
  • In: Acta anaesthesiologica Scandinavica. - : Wiley. - 1399-6576 .- 0001-5172. ; 65:2, s. 220-227
  • Journal article (peer-reviewed)abstract
    • Arterial haematocrit (Hct) has been shown to decrease after anaesthesia induction, most probably because of an increased plasma volume (PV). The primary objective was to quantify change in PV if mean arterial pressure (MAP) was kept at baseline level or allowed to decrease to 60mm Hg. Our secondary objective was to evaluate underlying mechanisms of this response.Twenty-four coronary artery bypass patients were randomized to a higher (90mm Hg, intervention group) or lower (60mm Hg, control group) MAP by titration of norepinephrine. During the experimental procedure, no fluids were administered. Baseline PV was measured by 125 I-albumin and the change in PV was calculated from the change in Hct. Changes in MAP, plasma 125 I-albumin, colloid osmotic pressure, albumin, Mid Regional-pro Atrial Natriuretic Peptide (MR-proANP) and endothelial glycocalyx components were measured from baseline to 50minutes after anaesthesia induction.The MAP during the trial was 93±9mm Hg in the intervention group and 62±5mm Hg in the control group. PV increased with up to 420±180mL in the control group and 45±130mL in the intervention group (P<.001). Albumin and colloid osmotic pressure decreased significantly more in the control group. MR-proANP increased in the control group but no shedding of the glycocalyx layer was detected in either of the groups.Allowing mean arterial pressure to fall to 60mm Hg during anaesthesia induction, increases the plasma volume due to reabsorption of interstitial water, with no ANP-induced degradation of the endothelial glycocalyx.
  •  
33.
  • Dauti, Fredrik, et al. (author)
  • Perioperative changes in PIVKA-II
  • 2015
  • In: Scandinavian Journal of Clinical & Laboratory Investigation. - : Informa UK Limited. - 1502-7686 .- 0036-5513. ; 75:7, s. 562-567
  • Journal article (peer-reviewed)abstract
    • Background and aims. Proteins induced by vitamin K absence for factor II (PIVKA-II) is an enzyme-linked immunosorbent assay that monitors uncarboxylated prothrombin and responds to vitamin K deficits prior to changes in the prothrombin test. The aim of this project was to study perioperative PIVKA-II changes during various types of surgery in a prospective observational study. Methods. Patients undergoing abdominal or orthopaedic surgery were included. Blood was sampled on the day of surgery (preoperatively) and up to 5 days after surgery. The activated partial thromboplastin time, Quick and Owren prothrombin times were analyzed, together with PIVKA-II. Results. Thirty-nine patients were included, 27 male and 12 female. All but 7 patients had elevated PIVKA-II levels preoperatively. PIVKA-II levels had already increased significantly (p < 0.017) on day 1 after surgery as compared to presurgery plasma levels. The median PIVKA-II was highest on day 5. Routine tests were mostly normal. No significant difference in PIVKA-II was seen when comparing patients undergoing abdominal versus orthopaedic surgeries. There was no significant correlation between PIVKA-II and routine coagulation tests. Patients with anterior resection, emergency laparotomy and emergency hip fractures had higher postoperative increases, which could be linked to increased gastrointestinal recovery times, paralytic ileus, peritonitis and comorbidities. Conclusions. PIVKA-II levels increase during the perioperative period, despite mostly normal routine coagulation tests. Pre- and perioperative vitamin K supplementation in patients with elevated PIVKA-II levels should be studied, and its clinical significance be defined in future studies.
  •  
34.
  • Dolinina, Julia, et al. (author)
  • Glomerular hyperpermeability after acute unilateral ureteral obstruction : Effects of Tempol, NOS, RhoA, and Rac-1 inhibition
  • 2018
  • In: American Journal of Physiology - Renal Physiology. - : American Physiological Society. - 1522-1466 .- 1931-857X. ; 315:3, s. 445-453
  • Journal article (peer-reviewed)abstract
    • It is well known that proteinuria following urinary tract obstruction is mainly of a tubular nature. However, it is unknown whether there are also changes in glomerular permeability. In this study, we compared glomerular sieving coefficients (θ) of polydisperse fluorescein isothiocyanate (FITC)-Ficoll 70/400 following a 120-or 180-min unilateral ureteral obstruction (UUO) in anesthetized Sprague-Dawley rats. Samples were collected from the obstructed kidney at 5, 15, and 30 min postrelease and analyzed by means of high-pressure size-exclusion chromatography. After 120-min UUO, mean θ for Ficoll70Å was increased (P < 0.01) from 2.2 ± 0.5 × 10−5 (baseline) to 10.6 ± 10 × 10−5 15 min postrelease (highest value). After 180-min UUO, mean θ for Ficoll70Å was further increased (P < 0.001) from 1.4 ± 0.5 × 10−5 (baseline) to 40 ± 10 × 10−5 at 5 min postrelease (highest value). Administration of a reactive oxygen species (ROS) scavenger (Tempol; 1 mg·kg−1·min−1) partly abrogated the permeability effects following 120-min UUO but not after 180 min. Moreover, administration of the RhoA kinase inhibitor Y-27632, the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester, or Rac-1 inhibition did not ameliorate glomerular hyperpermeability following 180-min UUO. We show, for the first time, that acute UUO results in marked elevations in glomerular permeability. In addition, our data suggest a time-dependent pathophysiology of UUO-induced hyperpermeability, where reactive oxygen species generation may play an important role in the early stages.
  •  
35.
  • Fisher, Jane, et al. (author)
  • A functional observational battery for evaluation of neurological outcomes in a rat model of acute bacterial meningitis
  • 2020
  • In: Intensive Care Medicine Experimental. - : Springer Science and Business Media LLC. - 2197-425X. ; 8
  • Journal article (peer-reviewed)abstract
    • Background Acute bacterial meningitis is a disease with a high mortality and a high incidence of neurological sequelae in survivors. There is an acute need to develop new adjuvant therapies. To ensure that new therapies evaluated in animal models are translatable to humans, studies must evaluate clinically relevant and patient-important outcomes, including neurological symptoms and sequelae. Methods We developed and tested a functional observational battery to quantify the severity of a variety of relevant neurological and clinical symptoms in a rat model of bacterial meningitis. The functional observational battery included symptoms relating to general clinical signs, gait and posture abnormalities, involuntary motor movements, focal neurological signs, and neuromotor abnormalities which were scored according to severity and summed to obtain a combined clinical and neurological score. To test the functional observational battery, adult Sprague-Dawley rats were infected by intracisternal injection of a clinical isolate of Streptococcus pneumoniae. Rats were evaluated for 6 days following the infection. Results Pneumococcal meningitis was not lethal in this model; however, it induced severe neurological symptoms. Most common symptoms were hearing loss (75% of infected vs 0% of control rats; p = 0.0003), involuntary motor movements (75% of infected vs 0% of control rats; p = 0.0003), and gait and posture abnormality (67% of infected vs 0% of control rats; p = 0.0013). Infected rats had a higher combined score when determined by the functional observational battery than control rats at all time points (24 h 12.7 ± 4.0 vs 4.0 ± 2.0; 48 h 17.3 ± 7.1 vs 3.4 ± 1.8; 6 days 17.8 ± 7.4 vs 1.7 ± 2.4; p < 0.0001 for all). Conclusions The functional observational battery described here detects clinically relevant neurological sequelae of bacterial meningitis and could be a useful tool when testing new therapeutics in rat models of meningitis.
  •  
36.
  • Fisher, Jane, et al. (author)
  • Elevated plasma glypicans are associated with organ failure in patients with infection
  • 2019
  • In: Intensive Care Medicine Experimental. - : Springer Science and Business Media LLC. - 2197-425X. ; 7
  • Journal article (peer-reviewed)abstract
    • Background Increased vascular permeability is a key feature in the pathophysiology of sepsis and the development of organ failure. Shedding of the endothelial glycocalyx is increasingly being recognized as an important pathophysiological mechanism but at present it is unclear if glypicans contribute to this response. We hypothesized that plasma levels of glypicans (GPC) are elevated in patients with sepsis. Methods Plasma GPC 1–6 levels were measured by ELISA in 10 patients with sepsis and 10 healthy controls as an initial screening. Plasma GPC 1, 3, and 4 were further measured in a cohort of 184 patients with a clinically confirmed infection. Patients were divided into groups of those who had sepsis and those who had an infection without organ failure. To determine whether plasma glypicans could predict the development of organ failure, patients were further subdivided to those who had organ failure at enrolment and those who developed it after enrollment. The association of plasma GPC 1, 3, and 4 with organ failure and with various markers of inflammation, disease severity, and glycocalyx shedding was investigated. Results In the pilot study, only GPC 1, 3, and 4 were detectable in the plasma of sepsis patients. In the larger cohort, GPC 1, 3, and 4 levels were significantly higher (p < 0.001) in patients with sepsis than in those with infection without organ failure. GPC 1, 3, and 4 were significantly positively correlated with plasma levels of the disease severity markers C-reactive protein, lactate, procalcitonin, and heparin binding protein, and with the marker of glycocalyx degradation syndecan 1. They were significantly negatively correlated with plasma levels of the glycocalyx-protective factors apolipoprotein M and sphingosine-1-phosphate. Conclusions We show that GPC 1, 3, and 4 are elevated in plasma of patients with sepsis and correlate with markers of disease severity, systemic inflammation, and glycocalyx damage.
  •  
37.
  • Fisher, Jane, et al. (author)
  • Heparin-Binding Protein (HBP) : A Causative Marker and Potential Target for Heparin Treatment of Human Sepsis-Induced Acute Kidney Injury
  • 2017
  • In: Shock. - 1540-0514. ; 48:3, s. 313-320
  • Journal article (peer-reviewed)abstract
    • RATIONALE: Sepsis-induced acute kidney injury (AKI) is a common condition with high morbidity and mortality. Neutrophil-derived heparin-binding protein (HBP) induces vascular leakage and is a promising biomarker of sepsis-induced organ dysfunction. It remains unknown if HBP is prognostic of AKI in septic shock and if HBP could play a role in the pathophysiology of sepsis-induced AKI.OBJECTIVES: To determine the association of plasma HBP levels with development of AKI, investigate the role of HBP in the pathophysiology of sepsis-induced AKI, and test the effect of blocking HBP using heparin derivatives.METHODS: In 296 septic shock patients from the randomized multicenter Vasopressin and Septic Shock Trial (VASST) plasma HBP levels were associated with development of AKI and need for renal replacement therapy (RRT). Human renal tubular cells were exposed to recombinant HBP to evaluate inflammation and heparin derivatives were used to abrogate these effects. Finally, mice were exposed to HBP with and without heparin derivatives and the kidneys examined for signs of inflammation.FINDINGS: Plasma HBP levels were significantly higher in patients with AKI and those requiring RRT. HBP levels identified patients with moderate AKI with an area under curve (AUC) of 0.85. HBP increased IL-6 production in renal tubular epithelial cells. Different heparin derivatives abrogated the HBP-induced increased inflammatory response in vitro and in vivo.CONCLUSION: Elevated plasma HBP is associated with development of sepsis-induced AKI and HBP is involved in its pathophysiology. Our studies suggest that heparin(s) could be tested for efficacy and safety of prevention of sepsis-induced AKI.
  •  
38.
  • Fisher, Jane, et al. (author)
  • Is heparin-binding protein inhibition a mechanism of albumin's efficacy in human septic shock?
  • 2018
  • In: Critical Care Medicine. - 0090-3493. ; 46:5, s. 364-374
  • Journal article (peer-reviewed)abstract
    • Objectives: Our objectives were to determine first whether albumin prevents heparin-binding protein-induced increased endothelial cell permeability and renal cell inflammation and second, whether a plasma heparin-binding protein-to-albumin ratio predicts risk of acute kidney injury, fluid balance, and plasma cytokine levels in septic shock. Design: In vitro human endothelial and renal cell model and observation cohort of septic shock. Settings: Research laboratory and multicenter clinical trial (Vasopressin and Septic Shock Trial). Patients: Adult septic shock (norepinephrine dose > 5 μg/min for > 6 hr). Interventions: In vitro: heparin-binding protein (or thrombin) was added with or without albumin to 1) human endothelial cell monolayers to assess permeability and 2) to human renal tubular epithelial cells to assess inflammation. Measurements and Main Results: Transendothelial electrical resistance - a marker of permeability - of human endothelial cells was measured using a voltohmmeter. We measured plasma heparin-binding protein-to-albumin ratio and a panel of cytokines in septic shock patients (n = 330) to define an heparin-binding protein-to-albumin ratio that predicts risk of acute kidney injury. Albumin inhibited heparin-binding protein (and thrombin-induced) increased endothelial cell permeability at a threshold concentration of 20-30 g/L but increased renal tubular cell interleukin-6 release. Patients who developed or had worsened acute kidney injury had significantly higher heparin-binding protein-to-albumin ratio (1.6 vs 0.89; p < 0.001) and heparin-binding protein (38.2 vs 20.8 ng/mL; p < 0.001) than patients without acute kidney injury. The highest heparin-binding protein-to-albumin ratio (> 3.05), heparin-binding protein quartiles (> 69.8), and heparin-binding protein > 30 ng/mL were significantly associated with development or worsening of acute kidney injury (p < 0.001) in unadjusted and adjusted analyses and were robust to sensitivity analyses for death as a competing outcome. Heparin-binding protein and heparin-binding protein-to-albumin ratio were directly associated with positive fluid balance (p < 0.001) and with key inflammatory cytokines. Increasing quartiles of heparin-binding protein-to-albumin ratio and heparin-binding protein (but not albumin) were highly significantly associated with days alive and free of acute kidney injury and renal replacement therapy (p < 0.001), vasopressors (p < 0.001), ventilation (p < 0.001), and with 28-day mortality. Conclusions: Albumin inhibits heparin-binding protein-induced increased human endothelial cell permeability and heparin-binding protein greater than 30 ng/mL and heparin-binding protein-to-albumin ratio greater than 3.01 - but not serum albumin - identified patients at increased risk for acute kidney injury in septic shock.
  •  
39.
  • Fisher, Jane, et al. (author)
  • Non-corticosteroid adjuvant therapies for acute bacterial meningitis
  • 2021
  • In: Cochrane Database of Systematic Reviews. - 1465-1858. ; 2021:11
  • Research review (peer-reviewed)abstract
    • Background: Acute bacterial meningitis is a bacterial infection of the membranes that surround and protect the brain, known as the meninges. The primary therapy for bacterial meningitis is antibiotics and corticosteroids. Although these therapies significantly improve outcomes, bacterial meningitis still has a high risk of death and a high risk of neurological sequelae in survivors. New adjuvant therapies are needed to further reduce the risk of death and neurological sequelae in bacterial meningitis. Objectives: To assess the effects of non-corticosteroid adjuvant pharmacological therapies for mortality, hearing loss, and other neurological sequelae in people with acute bacterial meningitis. Search methods: We searched CENTRAL, MEDLINE, Embase, CINAHL, and LILACS databases and ClinicalTrials.gov and WHO ICTRP trials registers up to 30 September 2021, together with reference checking, citation searching, and contact with study authors to identify additional studies. Selection criteria: We included randomised controlled trials (RCTs) of any pharmacological adjuvant therapy for acute bacterial meningitis. Data collection and analysis: Two review authors independently assessed and extracted data on methods, participants, interventions, and outcomes. We assessed risk of bias of studies with the Cochrane risk of bias tool and the certainty of the evidence using the GRADE approach. We presented results using risk ratios (RR) and 95% confidence intervals (CI) when meta-analysis was possible. All other results are presented in a narrative synthesis. Main results: We found that five different adjuvant therapies have been tested in RCTs for bacterial meningitis. These include paracetamol (3 studies, 1274 participants who were children); immunoglobulins (2 studies, 49 participants; one study included children, and the other adults); heparin (1 study, 15 participants who were adults); pentoxifylline (1 study, 57 participants who were children); and a mixture of succinic acid, inosine, nicotinamide, and riboflavin mononucleotide (1 study, 30 participants who were children). Paracetamol may make little or no difference to mortality (paracetamol 35.2% versus placebo 37.4%, 95% CI 30.3% to 40.8%; RR 0.94, 95% CI 0.81 to 1.09; 3 studies, 1274 participants; I² = 0%; low certainty evidence); hearing loss (RR 1.04, 95% CI 0.80 to 1.34; 2 studies, 901 participants; I² = 0%; low certainty evidence); neurological sequelae other than hearing loss (RR 1.56, 95% CI 0.98 to 2.50; 3 studies, 1274 participants; I² = 60%; low certainty evidence); and severe hearing loss (RR 0.96, 95% CI 0.67 to 1.36; 2 studies, 901 participants; I² = 0%; low certainty evidence). Paracetamol may lead to slightly more short-term neurological sequelae other than hearing loss (RR 1.99, 95% CI 1.40 to 2.81; 2 studies, 1096 participants; I² = 0%; low certainty evidence) and slightly more long-term neurological sequelae other than hearing loss (RR 2.32, 95% CI 1.34 to 4.04; 2 studies, 901 participants; I² = 0%; low certainty evidence). No adverse events were reported in either group in any of the paracetamol studies (very low certainty evidence). Two paracetamol studies had a low risk of bias in most domains, and one had low or unclear risk of bias in all domains. We judged the certainty of evidence to be low for mortality due to limitations in study design (unclear risk of bias in at least one domain and imprecision (high level of uncertainty in absolute effects), and low for all other outcomes due to limitations in study design (unclear risk of bias in at least one domain), and imprecision (low sample size and few events) or inconsistency in effect estimates (heterogeneity). We were not able to perform meta-analysis for any of the other adjuvant therapies due to the limited number of included studies. It is uncertain whether immunoglobulins, heparin, or pentoxifylline improves mortality outcomes due to the very low certainty of the evidence. Zero adverse events were reported for immunoglobulins (very low certainty evidence), and allergic reactions occurred at a rate of 3.3% in participants receiving a mixture of succinic acid, inosine, nicotinamide, and riboflavin mononucleotide (intervention group) (very low certainty evidence). None of our other outcomes (hearing loss, neurological sequelae other than hearing loss, severe hearing loss, and short-term or long-term neurological sequelae other than hearing loss) were reported in these studies, and all of these studies were judged to have a high risk of bias. All reported outcomes for all included adjuvant therapies, other than paracetamol, were graded as very low certainty of evidence due to limitations in study design (unclear or high risk of bias in at least four domains) and imprecision (extremely low sample size and few events). Authors' conclusions: Few adjuvant therapies for bacterial meningitis have been tested in RCTs. Paracetamol may make little or no difference to mortality, with a high level of uncertainty in the absolute effects (low certainty evidence). Paracetamol may make little or no difference to hearing loss, neurological sequelae other than hearing loss, and severe hearing loss (all low certainty evidence). Paracetamol may lead to slightly more short-term and long-term neurological sequelae other than hearing loss (both outcomes low certainty evidence). There is insufficient evidence to determine whether any of the adjuvant therapies included in this review (paracetamol, immunoglobulins, heparin, pentoxifylline, or a mixture of succinic acid, inosine, nicotinamide, and riboflavin mononucleotide) are beneficial or detrimental in acute bacterial meningitis.
  •  
40.
  • Fisher, Jane, et al. (author)
  • The Dynamics of Circulating Heparin-Binding Protein : Implications for Its Use as a Biomarker
  • 2022
  • In: Journal of Innate Immunity. - : S. Karger AG. - 1662-811X .- 1662-8128. ; 14:5, s. 447-460
  • Journal article (peer-reviewed)abstract
    • Heparin-binding protein (HBP) is a promising biomarker for the development and severity of sepsis. To guide its use, it is important to understand the factors that could lead to false-positive or negative results, such as inappropriate release and inadequate clearance of HBP. HBP is presumably released only by neutrophils, and the organs responsible for its elimination are unknown. In this study, we aimed to determine whether non-neutrophil cells can be a source of circulating HBP and which organs are responsible for its removal. We found that in two cohorts of neutropenic patients, 12% and 19% of patients in each cohort, respectively, had detectable plasma HBP levels. In vitro, three leukemia-derived monocytic cell lines and healthy CD14+ monocytes constitutively released detectable levels of HBP. When HBP was injected intravenously in rats, we found that plasma levels of HBP decreased rapidly, with a distribution half-life below 10 min and an elimination half-life of 1-2 h. We measured HBP levels in the liver, spleen, kidneys, lungs, and urine using both ELISA and immunofluorescence quantitation, and found that the majority of HBP was present in the liver, and a small amount was present in the spleen. Immunofluorescence imaging indicated that HBP is associated mainly with hepatocytes in the liver and monocytes/macrophages in the spleen. The impact of hematologic malignancies and liver diseases on plasma HBP levels should be explored further in clinical studies.
  •  
41.
  •  
42.
  • Gelberg, Jan, et al. (author)
  • Subparalyzing Doses of Rocuronium Reduce Muscular Endurance without Detectable Effect on Single Twitch Height in Awake Subjects
  • 2019
  • In: Anesthesiology Research and Practice. - : Hindawi Limited. - 1687-6962 .- 1687-6970. ; 2019
  • Journal article (peer-reviewed)abstract
    • Purpose. To test the hypothesis that a low-dose rocuronium acts mainly by means of reducing muscular endurance rather than by reducing momentary force. Methods. In a randomized placebo-controlled double-blinded study, eight healthy volunteers were studied in two sets of experiments. In the first set, the subjects made a sustained maximum effort with the dominant hand for 80 seconds while squeezing an electronic handgrip dynamometer at three minutes after intravenous administration of placebo, 0.04 or 0.08 mg/kg rocuronium. Handgrip force at initiation of testing (maximum handgrip force) and after 60 seconds was evaluated. In the second set, the ulnar nerve of the subjects was electrically stimulated every tenth second for at least 10 and a maximum of 30 minutes following the administration of placebo and 0.08 mg/kg rocuronium. Single twitch height of the adductor pollicis muscle was recorded. Results. There was no significant difference in the effect on maximum handgrip force at time 0 between the three different doses of rocuronium. As compared with placebo, handgrip force after 0.08 mg/kg rocuronium was reduced to approximately a third at 60 seconds (214 N (120-278) vs. 69 (30-166); p=0.008), whereas only a slight reduction was seen after 0.04 mg/kg (187 (124-256); p=0.016). Based on these results, the sustained handgrip force after 0.2 mg/kg at 60 seconds was calculated to be 1.27% (95% CI [0.40, 4.03]) of the maximum force of placebo. No effect on single twitch height after 0.08 mg/kg rocuronium at four minutes after drug administration could be detected. Conclusions. Subparalyzing doses of rocuronium show a distinct effect on muscular endurance as opposed to momentary force. The findings support the hypothesis that low doses of rocuronium act mainly by reducing muscular endurance, thereby facilitating, for example, tracheal intubation.
  •  
43.
  • Genét, Gustav Folmer, et al. (author)
  • Effects of propranolol and clonidine on brain edema, blood-brain barrier permeability, and endothelial glycocalyx disruption after fluid percussion brain injury in the rat
  • 2018
  • In: Journal of Trauma and Acute Care Surgery. - 2163-0755. ; 84:1, s. 89-96
  • Journal article (peer-reviewed)abstract
    • BACKGROUND Traumatic brain injury causes a disruption of the vascular endothelial glycocalyx layer that is associated with an overactivation of the sympathoadrenal system. We hypothesized that early and unselective beta-blockade with propranolol alone or in combination with the alfa2-agonist clonidine would decrease brain edema, blood-brain barrier permeability, and glycocalyx disruption at 24 hours after trauma. METHODS We subjected 53 adult male Sprague-Dawley rats to lateral fluid percussion brain injury and randomized infusion with propranolol (n = 16), propranolol + clonidine (n = 16), vehicle (n = 16), or sham (n = 5) for 24 hours. Primary outcome was brain water content at 24 hours. Secondary outcomes were blood-brain barrier permeability and plasma levels of syndecan-1 (glycocalyx disruption), cell damage (histone-complexed DNA fragments), epinephrine, norepinephrine, and animal motor function. RESULTS We found no difference in brain water content (mean ± SD) between propranolol (80.8 ± 0.3%; 95% confidence interval [CI], 80.7-81.0) and vehicle (81.1 ± 0.6%; 95% CI, 80.8-81.4) (p = 0.668) or between propranolol/clonidine (80.8 ± 0.3%; 95% CI, 80.7-81.0) and vehicle (p = 0.555). We found no effect of propranolol and propranolol/clonidine on blood-brain barrier permeability and animal motor scores. Unexpectedly, propranolol and propranolol/clonidine caused an increase in epinephrine and syndecan-1 levels. CONCLUSION This study does not provide any support for unselective beta-blockade with propranolol or the combination of propranolol and the alfa2-agonist clonidine on brain water content. The novel finding of an increase in plasma concentrations of epinephrine and syndecan-1 after propranolol treatment in traumatic brain injury is of unclear significance and should be investigated further.
  •  
44.
  • Genét, Gustav Folmer, et al. (author)
  • Resuscitation with Pooled and Pathogen-Reduced Plasma Attenuates the Increase in Brain Water Content following Traumatic Brain Injury and Hemorrhagic Shock in Rats
  • 2017
  • In: Journal of Neurotrauma. - : Mary Ann Liebert Inc. - 0897-7151 .- 1557-9042. ; 34:5, s. 1054-1062
  • Journal article (peer-reviewed)abstract
    • Traumatic brain injury and hemorrhagic shock is associated with blood-brain barrier (BBB) breakdown and edema formation. Recent animal studies have shown that fresh frozen plasma (FFP) resuscitation reduces brain swelling and improves endothelial function compared to isotonic NaCl (NS). The aim of this study was to investigate whether pooled and pathogen-reduced plasma (OctaplasLG® [OCTA]; Octapharma, Stockholm, Sweden) was comparable to FFP with regard to effects on brain water content, BBB permeability, and plasma biomarkers of endothelial glycocalyx shedding and cell damage. After fluid percussion brain injury, hemorrhage (20 mL/kg), and 90-min shock, 48 male Sprague-Dawley rats were randomized to resuscitation with OCTA, FFP, or NS (n = 16/group). Brain water content (wet/dry weight) and BBB permeability (transfer constant for 51Cr-EDTA) were measured at 24 h. Plasma osmolality, oncotic pressure, and biomarkers of systemic glycocalyx shedding (syndecan-1) and cell damage (histone-complexed DNA) were measured at 0 and 23 h. At 24 h, brain water content was 80.44 ± 0.39%, 80.82 ± 0.82%, and 81.15 ± 0.86% in the OCTA, FFP, and NS groups (lower in OCTA vs. NS; p = 0.026), with no difference in BBB permeability. Plasma osmolality and oncotic pressures were highest in FFP and OCTA resuscitated, and osmolality was further highest in OCTA versus FFP (p = 0.027). In addition, syndecan-1 was highest in FFP and OCTA resuscitated (p = 0.010). These results suggest that pooled solvent-detergent (SD)-treated plasma attenuates the post-traumatic increase in brain water content, and that this effect may, in part, be explained by a high crystalloid and colloid osmotic pressure in SD-treated plasma.
  •  
45.
  •  
46.
  •  
47.
  • H Jonsson, Magnus, et al. (author)
  • Markers of renal function at admission and mortality in hip fracture patients-a single center prospective observational study
  • 2021
  • In: Scandinavian Journal of Clinical and Laboratory Investigation. - : Taylor & Francis. - 0036-5513 .- 1502-7686. ; 81:3, s. 201-207
  • Journal article (peer-reviewed)abstract
    • Plasma cystatin C and shrunken pore syndrome (SPS) are associated with increased mortality in older adults. The objective was to assess the association between these markers of kidney function at admission and mortality in hip fracture patients. Hip fracture patients presenting at Lund University Hospital were eligible for inclusion. Cox regression was used to assess association between plasma cystatin C, creatinine, cystatin C- or creatinine-based estimations of glomerular filtration rate (eGFR(CYS) and eGFR(CREA)), or SPS (defined as eGFR(CYS)/eGFR(CREA) < 0.7) and mortality during one year follow up. Improvement in discrimination relative to the Nottingham Hip fracture score was assessed by Receiver Operational Characteristics (ROC) analysis and calculation of Net Reclassification Index (NRI). 996 patients were included in the study. Cystatin C, creatinine, eGFR(CYS) and eGFR(CREA) were associated with one-year mortality in both unadjusted and adjusted analyses. The association with mortality was stronger for cystatin C and for eGFR(CYS) than for creatinine and eGFR(CREA). Patients with SPS had doubled mortality compared with patients without SPS (43.7 and 20.2%, respectively, p < .001). Hazard ratio for SPS in the adjusted analysis was 1.66 (95%CI; 1.16-2.39, p = .006). None of the markers improved discrimination compared to the Nottingham Hip Fracture Score using ROC analysis whereas eGFR(CYS) and eGFR(CREA) improved NRI. Our conclusion is that plasma concentrations of creatinine or cystatin C, eGFR(CYS) or eGFR(CREA) or SPS at admission in hip fracture patients are associated with mortality when known risk factors are accounted for. Identification of high risk patients may be improved by eGFR(CYS) or eGFR(CREA).
  •  
48.
  •  
49.
  • Holbeck, Staffan, et al. (author)
  • Dextran, gelatin, and hydroxyethyl starch do not affect permeability for albumin in cat skeletal muscle
  • 2001
  • In: Critical Care Medicine. - 1530-0293. ; 29:1, s. 123-128
  • Journal article (peer-reviewed)abstract
    • OBJECTIVE: To evaluate the effects of the three commercially available colloid solutions, 6% dextran 70, 6% hydroxyethyl starch (HES) 200/0.5, and 3.5% urea-linked gelatin on permeability for human albumin in a skeletal muscle in vivo model by evaluating their effects on the reflection coefficient for albumin. DESIGN: Controlled laboratory study. SETTING: University research laboratory. SUBJECTS: Eighteen adult cats. INTERVENTIONS: The autoperfused and denervated calf muscles of the cat hindlimb were placed in a plethysmograph. The transvascular fluid absorption induced by an increase in the colloid osmotic pressure following a fixed intravenous bolus of human albumin was analyzed, first before start of, and then during an intra-arterial infusion to, the muscle preparation of the synthetic colloid to be analyzed. Capillary filtration coefficient as a measure of microvascular fluid permeability (conductance) was analyzed before and after start of the synthetic colloid. MEASUREMENTS AND MAIN RESULTS: Arterial blood flow, arterial and venous blood pressures, total vascular resistance, tissue volume changes, capillary filtration coefficient, and plasma volume were measured before and during the colloid infusion. According to the Starling fluid equilibrium, the ratio between the reflection coefficients for albumin on two occasions (before and after infusion of the synthetic colloid) can be calculated from the maximum osmotic absorption rates induced by a fixed intravenous bolus infusion of albumin and from the capillary filtration coefficients. Obtained data were adjusted for different plasma volume at the two occasions. We found that none of the three synthetic colloids analyzed had any significant effect on the reflection coefficient for albumin. CONCLUSION: An effect on albumin microvascular permeability of the synthetic colloids dextran 70, HES 200/0.5, and urea-linked gelatin could not be shown by a method analyzing their effect on the reflection coefficient for albumin.
  •  
50.
  • Holbeck, Staffan, et al. (author)
  • Effects of hypertonic saline, mannitol, and urea with regard to absorption and rebound filtration in cat skeletal muscle.
  • 2002
  • In: Critical Care Medicine. - 1530-0293. ; 30:1, s. 212-217
  • Journal article (peer-reviewed)abstract
    • OBJECTIVE: To study the effects of the hypertonic solutions 15% mannitol, 3% and 7.5% saline, and 30% urea at clinically relevant plasma concentrations with regard to absorption and rebound effects on tissue volume in skeletal muscle. DESIGN: A prospective, experimental study. SETTING: University laboratory. SUBJECTS: Twenty-eight anesthetized cats. INTERVENTIONS: The study was performed on an autoperfused and denervated cat calf muscle placed in a fluid-filled plethysmograph. Muscle volume changes and capillary filtration coefficient (reflecting capillary fluid conductivity) were measured before, during, and after intra-arterial infusion (4 mL/hr) of the hypertonic solutions. Mannitol and 3% saline have the same osmolality and were compared specifically in an attempt to distinguish osmotic effects from those specific to the compound. MEASUREMENTS AND MAIN RESULTS: All solutions reduced muscle volume during the infusion (p < .05). The maximum volume reduction persisted after 2 hrs of infusion for 3% and 7.5% saline, whereas there was a tendency for volume recovery during the urea infusion and a complete recovery back to control for mannitol. After discontinuation of the infusions, the muscle volume increased for all four solutions, stabilizing at the initial control for 3% and 7.5% saline, whereas it increased to levels above control for mannitol and urea (p < .05). Capillary filtration coefficient was increased by hypertonic saline (p < .05) but was unaffected by mannitol and urea. CONCLUSIONS: The effectiveness of a hypertonic solution in reducing tissue volume and its tendency to cause a rebound volume increase depends not only on the osmolality of the solution. Hypertonic saline may in the long run be superior to mannitol and urea to increase plasma volume or decrease tissue volume of an organ, because it lacks rebound effects. Alterations in capillary filtration coefficient (fluid conductivity) may reflect volume changes of the capillary endothelial cell and thereby differences in cell membrane permeability for the hypertonic solutions, also consistent with the obtained differences in tissue volume effects.
  •  
Skapa referenser, mejla, bekava och länka
  • Result 1-50 of 88
Type of publication
journal article (77)
research review (5)
conference paper (4)
doctoral thesis (2)
Type of content
peer-reviewed (83)
other academic/artistic (5)
Author/Editor
Bentzer, Peter (86)
Grände, Per-Olof (25)
Linder, Adam (12)
Fisher, Jane (12)
Kander, Thomas (10)
Lundblad, Cornelia (10)
show more...
Schött, Ulf (8)
Jungner, Mårten (8)
Nielsen, Niklas (7)
Statkevicius, Svajun ... (7)
Bansch, Peter (6)
Russell, James A (5)
Walley, Keith R (5)
Linné, Erik (4)
Spångfors, Martin (4)
Gluud, Christian (4)
Holbeck, Staffan (4)
Boyd, John (4)
Bonnevier, Johan (4)
Thabane, Lehana (4)
Adrian, Maria (3)
Hommel, Ami (3)
Öberg, Carl M. (3)
Nelson, Axel (3)
Lundgaard, Iben (3)
Åkesson, Anna (3)
Jakobsen, Janus Chri ... (3)
Venturoli, Daniele (2)
Mörgelin, Matthias (2)
Grubb, Anders (2)
Larsson, Erik (2)
Melander, Olle (2)
Borgquist, Ola (2)
Åkeson, Jonas (2)
Holmström, Anders (2)
Linnér, Rikard (2)
Undén, Johan (2)
Tingstedt, Bobby (2)
Kannisto, Päivi (2)
Nilson, Bo (2)
Reinstrup, Peter (2)
Kong, HyeJin Julia (2)
Boyd, John H. (2)
Mattiasson, Gustav (2)
Hemberg, Linn (2)
Johansson, Pär I (2)
Johansson, Pär Ingem ... (2)
Gelberg, Jan (2)
Holgersson, Johan (2)
Grubb, David (2)
show less...
University
Lund University (87)
Malmö University (3)
University of Gothenburg (2)
Uppsala University (1)
Linköping University (1)
Language
English (87)
Swedish (1)
Research subject (UKÄ/SCB)
Medical and Health Sciences (87)
Engineering and Technology (1)
Agricultural Sciences (1)

Year

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

 
pil uppåt Close

Copy and save the link in order to return to this view