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  • 1.
    Andersson, Nina
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Grip, Helena
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Physiotherapy.
    Lindvall, Peter
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Koskinen, Lars-Owe D
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Brändström, Helge
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Air transport of patients with intracranial air: computer model of pressure effects2003In: Aviation, Space and Environmental Medicine, ISSN 0095-6562, E-ISSN 1943-4448, Vol. 74, no 2, p. 138-144Article in journal (Refereed)
  • 2.
    Arnell, Kai
    et al.
    Department of Paediatric Surgery, University Hospital, Uppsala.
    Koskinen, Lars-Owe D
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology.
    Eklund, Anders
    Evaluation of Strata NSC and Codman Hakim adjustable cerebrospinal fluid shunts and their corresponding antisiphon devices: laboratory investigation2009In: Journal of Neurosurgery: Pediatrics, ISSN 1933-0707, E-ISSN 1933-0715, Vol. 3, no 3, p. 166-172Article in journal (Refereed)
    Abstract [en]

    OBJECT: The authors investigated and compared the in vitro characteristics of 2 CSF shunts, the Strata NSC and the Codman Hakim, and their corresponding antisiphon devices (ASDs).

    METHODS: Six new CSF shunts and the corresponding ASDs for each model were tested in an automated, computerized experimental setup based on pressure regulation. Opening pressure accuracy, resistance, sensitivity to abdominal pressure, antisiphon effect, and the influence of different ASD positions were determined.

    RESULTS: In general the shunts performed according to the manufacturers' specifications. However, at the lowest setting, the opening pressure of the Strata NSC was close to 0, and in the Codman Hakim shunt, it was higher than specified. The resistance in the Codman Hakim shunt (5.4 mm Hg/ml/min) was much higher than that in the Strata NSC (3.6 mm Hg/ml/min). Abdominal pressure affected opening pressure in both valves. Positioning the Strata ASD above or below the ventricular catheter tip resulted in higher and lower opening pressures, respectively, than when it was placed in line with the catheter. The positioning of the Codman Hakim ASD did not influence the opening pressure.

    CONCLUSIONS: Both CSF shunts work properly, but at the lowest setting the opening pressure of the Strata NSC was near 0 and in the Codman Hakim it was twice the manufacturer's specifications. The resistance in the Strata NSC was below the normal physiological range, and in the Codman Hakim device it was in the lower range of normal. The ASD did not change the shunt characteristics in the lying position and therefore might not do so in children. If this is the case, then a shunt system with an integrated ASD could be implanted at the first shunt insertion, thus avoiding a second operation and the possibility of infection.

  • 3.
    Behrens, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology.
    Lenfeldt, Niklas
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology.
    Ambarki, Khalid
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Koskinen, Lars-Owe
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Transcranial Doppler pulsatility index: not an accurate method to assess intracranial pressure.2010In: Neurosurgery, ISSN 0148-396X, E-ISSN 1524-4040, Vol. 66, no 6, p. 1050-1057Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Transcranial Doppler sonography (TCD) assessment of intracranial blood flow velocity has been suggested to accurately determine intracranial pressure (ICP). OBJECTIVE: We attempted to validate this method in patients with communicating cerebrospinal fluid systems using predetermined pressure levels. METHODS: Ten patients underwent a lumbar infusion test, applying 4 to 5 preset ICP levels. On each level, the pulsatility index (PI) in the middle cerebral artery was determined by measuring the blood flow velocity using TCD. ICP was simultaneously measured with an intraparenchymal sensor. ICP and PI were compared using correlation analysis. For further understanding of the ICP-PI relationship, a mathematical model of the intracranial dynamics was simulated using a computer. RESULTS: The ICP-PI regression equation was based on data from 8 patients. For 2 patients, no audible Doppler signal was obtained. The equation was ICP = 23*PI + 14 (R = 0.22, P < .01, N = 35). The 95% confidence interval for a mean ICP of 20 mm Hg was -3.8 to 43.8 mm Hg. Individually, the regression coefficients varied from 42 to 90 and the offsets from -32 to +3. The mathematical simulations suggest that variations in vessel compliance, autoregulation, and arterial pressure have a serious effect on the ICP-PI relationship. CONCLUSIONS: The in vivo results show that PI is not a reliable predictor of ICP. Mathematical simulations indicate that this is caused by variations in physiological parameters.

  • 4.
    Behrens, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Lenfeldt, Niklas
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Ambarki, Khalid
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Koskinen, Lars-Owe D
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Intracranial Pressure and Pulsatility Index:  2011In: Neurosurgery, ISSN 0148-396X, E-ISSN 1524-4040, Vol. 69, no 4, p. E1033-E1034Article in journal (Refereed)
  • 5.
    Behrens, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Lenfeldt, Niklas
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Qvarlander, Sara
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Koskinen, Lars-Owe
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Are intracranial pressure wave amplitudes measurable through lumbar puncture?2013In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 127, no 4, p. 233-241Article in journal (Refereed)
    Abstract [en]

     Objective The aim of this study was to investigate whether pulsations measured in the brain correspond to those measured in lumbar space, and subsequently whether lumbar punctures could replace invasive recordings. Methods In ten patients with normal pressure hydrocephalus, simultaneous recordings of the intracranial pressure (ICP; intraparenchymal) and lumbar pressure (LP; cerebrospinal fluid pressure) were performed. During registration, pressure was altered between resting pressure and 45mmHg using an infusion test. Data were analyzed regarding pulsations (i.e., amplitudes). Also, the pressure sensors were compared in a bench test. Results The correlation between intracranial and lumbar amplitudes was 0.98. At resting pressure, and moderately elevated ICP, intracranial pulse amplitudes exceeded that of lumbar space with about 0.9mmHg. At the highest ICP, the difference changed to 0.2mmHg. The bench test showed that the agreement of sensor readings was good at resting pressure, but reduced at higher amplitudes. Conclusions Compared to intracranial registrations, amplitudes measured through lumbar puncture were slightly attenuated. The bench test showed that differences were not attributable to dissimilarities of the sensor systems. A lumbar pressure amplitude measurement is an alternative to ICP recording, but the thresholds for what should be interpreted as elevated amplitudes need to be adjusted.

  • 6. Björkman, Sven
    et al.
    Lewander, Tommy
    Karlsson, Jan-Anders
    Koskinen, Lars-Owe D.
    Psychiatric Research Center, Ulleråker Hospital, University of Uppsala, S‐750 17 Uppsala, Sweden.
    Zetterström, Tyra
    Thermic and tremorogenic effects of thyroliberin (TRH) in reserpine-treated mice--the non-involvement of GABA-ergic mechanisms.1981In: Journal of Pharmacy and Pharmacology (JPP), ISSN 0022-3573, E-ISSN 2042-7158, Vol. 33, no 9, p. 580-585Article in journal (Refereed)
    Abstract [en]

    Administration of thyroliberin (TRH) to reserpinized mice causes tremor and counteracts the hypothermia in a dose-dependent fashion. The thyroliberin response is inhibited by gamma-hydroxybutyric acid (GHB) and baclofen, but not by other, more specific GABA-ergic agents, such as THIP, gamma-acetylenic GABA, and sodium valproate. Picrotoxin neither potentiates nor inhibits the thyroliberin actions. Nor are the thyroliberin effects dependent on cholinergic, monoaminergic or histaminergic mechanisms. The results repudiate a current hypothesis, that the peptide actions may be mediated by GABA-ergic pathways in the brain.

  • 7.
    Blomstedt, Patric
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Hariz, Gun-Marie
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Occupational Therapy.
    Hariz, Marwan I
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Koskinen, Lars-Owe D
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Thalamic deep brain stimulation in the treatment of essential tremor: a long-term follow-up2007In: British Journal of Neurosurgery, ISSN 0268-8697, E-ISSN 1360-046X, Vol. 21, no 5, p. 504-509Article in journal (Refereed)
    Abstract [en]

    Deep brain stimulation (DBS) of the nucleus ventralis intermedius thalami (Vim) in the treatment of essential tremor (ET) is well documented concerning the acute effects. Reports of the long-term effects are, however, few and the aim of the present study was to analyse the long-term efficacy of this treatment. Nineteen patients operated with unilateral Vim-DBS were evaluated with the Essential Tremor Rating Scale (ETRS) before surgery, and after a mean time of 1 and 7 years after surgery. The ETRS score for tremor of the contralateral hand was reduced from 6.8 at baseline to 1.2 and 2.7, respectively, on stimulation at follow-up. For hand function (item 11 – 14) the score was reduced from 12.7 to 4.1 and 8.2, respectively. Vim-DBS is an efficient treatment for ET, also after many years of treatment. There is, however, a decreasing effect over time, most noticeable concerning tremor of action.

    Read More: http://informahealthcare.com/doi/abs/10.1080/02688690701552278

  • 8.
    Blomstedt, Patric
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Jabre, Mazen
    Bejjani, Boulos-Paul
    Koskinen, Lars-Owe
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Electromagnetic environmental influences on implanted deep brain stimulators2006In: Neuromodulation (Malden, Mass.), ISSN 1094-7159, E-ISSN 1525-1403, Vol. 9, no 4, p. 262-269Article in journal (Refereed)
    Abstract [en]

    Objective.  The objective of this study was to report our observations on the external electromagnetic field influences on deep brain stimulation (DBS) in our patient population and how these influences affected our patients’ lives and other healthcare-related conditions.

    Materials and Methods.  We have retrospectively analyzed data concerning the effects of external electromagnetic fields on 172 of our patients implanted with DBS.

    Results.  Identifiable electromagnetic sources turned the implantable pulse generator (IPG) off in 20 patients. In two patients, these episodes necessitated replacement of the Itrel II IPG (Medtronic Inc., Minneapolis, MN, USA) with the magnetically shielded Kinetra IPG (Medtronic Inc.). Six patients received cardiac pacemakers, leading, in two patients, to interference between the systems. Our experience concerning magnetic resonance imaging, electrocardiogram (ECG), heart defibrillation, electro-cautery, and other sources of electromagnetic interference also is described.

    Conclusions.  External electromagnetic interference may, in rare cases, constitute a severe threat to the well-being of the patient implanted with a DBS system. Also, malfunction of a DBS system may constitute a medical emergency. Nevertheless, in spite of these external electromagnetic influences, we consider DBS to be a safe method, provided safety protocols are followed, and provided that provider awareness about potential hazards is present.

  • 9.
    Blomstedt, Patric
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Sandvik, Ulrika
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Hariz, Marwan
    UCL Insitute of Neurology, Queen Square, London, Uk.
    Fytagoridis, Anders
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Forsgren, Lars
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Hariz, Gun-Marie
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Occupational Therapy.
    Koskinen, Lars-Owe
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Influence of age, gender and severity of tremor on outcome after thalamic and subthalamic DBS for essential tremor2011In: Parkinsonism & Related Disorders, ISSN 1353-8020, E-ISSN 1873-5126, Vol. 17, no 8, p. 617-620Article in journal (Refereed)
    Abstract [en]

    Deep brain stimulation (DBS) is an established treatment for essential tremor (ET). The nucleus ventralis intermedius thalami (Vim) is the target of choice, but promising results have been presented regarding DBS in the posterior subthalamic area (PSA). The aim of this study was to evaluate the possible influence of gender, age and severity of disease on the outcome of these procedures. Sixty eight patients (34 Vim, 34 PSA) with ET were included in this non-randomised study. Evaluation using the Essential Tremor Rating Scale (ETRS) was performed before, and one year after surgery concerning PSA DBS, and at a mean of 28 ± 24 months concerning Vim DBS. Items 5/6 and 11-14 (hand tremor and hand function) were selected for analysis of tremor outcome. The efficacy of DBS on essential tremor was not related to age or gender. Nor was it associated with the severity of tremor when the percentual reduction of tremor on stimulation was taken into account. However, patients with a more severe tremor at baseline had a higher degree of residual tremor on stimulation. Tremor in the treated hand and hand function were improved with 70% in the Vim group and 89% in the PSA group.

  • 10.
    Bobinski, Lukas
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Koskinen, Lars-Owe D.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Lindvall, Peter
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Complications following cranioplasty using autologous bone or polymethylmethacrylate-Retrospective experience from a single center2013In: Clinical neurology and neurosurgery (Dutch-Flemish ed. Print), ISSN 0303-8467, E-ISSN 1872-6968, Vol. 115, no 9, p. 1788-1791Article in journal (Refereed)
    Abstract [en]

    Objective: A decompressive hemicraniectomy is a potentially life-saving intervention following head trauma. Once performed patients are obliged to undergo a second procedure with cranioplasty. Two of the most commonly used materials are autologous bone and polymethylmethacrylate (PMMA). We have now evaluated complications following a cranioplasty using these materials. Materials and methods: During a 7-year period (2002-2008) 49 patients were operated with a decompressive craniectomy following head trauma. Patients received a cranioplasty consisting of autologous bone (30 patients, 61.2%) or PMMA (19 patients, 38.8%) and were followed at least 24 months. Patient data were collected retrospectively. Results: Twenty patients (20/49, 40.8%) experienced a complication that prompted a re-operation. There was a significantly higher rate of complications leading to a re-operation (53.3% vs. 21.1%, p = 0.03) and a shorter survival time of the cranioplasty (mean 48.1 +/- 7.8 vs. 79.5 +/- 9.0 months, p = 0.035) in patients with autologous bone compared to PMMA. Bone resorption and the presence of postoperative hematomas were significantly more common in patients with autologous bone. The material used for cranioplasty was the only variable that significantly correlated to the rate of complications. Conclusions: In our series we had a high percentage of patients needing re-operation due to complications following a cranioplasty. Though generally considered a straightforward procedure, complications and associated morbidity in patients undergoing cranioplasty should not be underestimated. 

  • 11.
    Bobinski, Lukas
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Olivecrona, Magnus
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Koskinen, Lars-Owe D.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Dynamics of brain tissue changes induced by traumatic brain injury assessed with the Marshall, Morris-Marshall, and the Rotterdam classifications and its impact on outcome in a prostacyclin placebo-controlled study2012In: Acta Neurochirurgica, ISSN 0001-6268, E-ISSN 0942-0940, Vol. 154, no 6, p. 1069-1079Article in journal (Refereed)
    Abstract [en]

    The present study evaluates the types and dynamics of intracranial pathological changes in patients with severe traumatic brain injury (sTBI) who participated in a prospective, randomized, double-blinded study of add-on treatment with prostacyclin. Further, the changes of brain CT scan and their correlation to Glasgow Coma Scale score (GCS), maximal intracranial pressure (ICPmax), minimal cerebral perfusion pressure (CPPmin), and Glasgow Outcome Score (GOS) at 3, 6, and 12 months were studied. Forty-eight subjects with severe traumatic brain injury were treated according to an ICP-targeted therapy protocol based on the Lund concept with the addition of prostacyclin or placebo. The first available CT scans (CTi) and follow-up scans nearest to 24 h (CT24) were evaluated using the Marshall, Rotterdam, and Morris-Marshall classifications. There was a significant correlation of the initial Marshall, Rotterdam, Morris-Marshall classifications and GOS at 3 and 12 months. The CT24 Marshall classification did not significantly correlate to GOS while the Rotterdam and the Morris-Marshall classification did. The CTi Rotterdam classification predicted outcome evaluated as GOS at 3 and 12 months. Prostacyclin treatment did not influence the dynamic of tissue changes. The Rotterdam classification seems to be appropriate for describing the evolution of the injuries on the CT scans and contributes in predicting of outcome in patients treated with an ICP-targeted therapy. The Morris-Marshall classification can also be used for prognostication of outcome but it describes only the impact of traumatic subarachnoid hemorrhage (tSAH).

  • 12.
    Bobinski, Lukas
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Olivecrona, Magnus
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Koskinen, Lars-Owe D.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Rotterdam score, ICP, CPP, S-100B, NSE and their association with Decompressive Craniectomy in severe Traumatic Brain InjuryArticle in journal (Other academic)
  • 13.
    Brorsson, Camilla
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Rodling-Wahlström, Marie
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Olivecrona, Magnus
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Koskinen, Lars-Owe
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Naredi, Silvana
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Severe traumatic brain injury: consequences of early adverse events2011In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 55, no 8, p. 944-951Article in journal (Refereed)
    Abstract [en]

    Background: Several factors associated with an unfavourable outcome after severe traumatic brain injury (TBI) have been described: prolonged pre-hospital time, secondary referral to a level 1 trauma centre, the occurrence of secondary insults such as hypoxia, hypotension or low end-tidal carbon dioxide (ETCO(2)). To determine whether adverse events were linked to outcome, patients with severe TBI were studied before arrival at a level 1 trauma centre.

    Methods: Prospective, observational study design. Patients with severe TBI (n = 48), admitted to Umea University Hospital between January 2002 to December 2005 were included. All medical records from the site of the accident to arrival at the level 1 trauma centre were collected and evaluated.

    Results: A pre-hospital time of >60 min, secondary referral to a level 1 trauma centre, documented hypoxia (oxygen saturation <95%), hypotension (systolic blood pressure <90 mmHg), hyperventilation (ETCO(2) <4.5 kPa) or tachycardia (heart rate >100 beats/min) at any time before arrival at a level 1 trauma centre were not significantly related to an unfavourable outcome (Glasgow Outcome Scale 1-3).

    Conclusion: Early adverse events before arrival at a level 1 trauma centre were without significance for outcome after severe TBI in the trauma system studied.

  • 14.
    Brändström, Helge
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Sundelin, Anna
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Hoseason, Daniela
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Sundström, Nina
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Birgander, Richard
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Johansson, Göran
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Winsö, Ola
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Koskinen, Lars-Owe
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Haney, Michael
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Risk for intracranial pressure increase related to enclosed air in post-craniotomy patients during air ambulance transport: a retrospective cohort study with simulation2017In: Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine, ISSN 1757-7241, E-ISSN 1757-7241, Vol. 25, article id 50Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Post-craniotomy intracranial air can be present in patients scheduled for air ambulance transport to their home hospital. We aimed to assess risk for in-flight intracranial pressure (ICP) increases related to observed intracranial air volumes, hypothetical sea level pre-transport ICP, and different potential flight levels and cabin pressures. METHODS: A cohort of consecutive subdural hematoma evacuation patients from one University Medical Centre was assessed with post-operative intracranial air volume measurements by computed tomography. Intracranial pressure changes related to estimated intracranial air volume effects of changing atmospheric pressure (simulating flight and cabin pressure changes up to 8000 ft) were simulated using an established model for intracranial pressure and volume relations. RESULTS: Approximately one third of the cohort had post-operative intracranial air. Of these, approximately one third had intracranial air volumes less than 11 ml. The simulation estimated that the expected changes in intracranial pressure during 'flight' would not result in intracranial hypertension. For intracranial air volumes above 11 ml, the simulation suggested that it was possible that intracranial hypertension could develop 'inflight' related to cabin pressure drop. Depending on the pre-flight intracranial pressure and air volume, this could occur quite early during the assent phase in the flight profile. DISCUSSION: These findings support the idea that there should be radiographic verification of the presence or absence of intracranial air after craniotomy for patients planned for long distance air transport. CONCLUSIONS: Very small amounts of air are clinically inconsequential. Otherwise, air transport with maintained ground-level cabin pressure should be a priority for these patients.

  • 15. Cnossen, Maryse C
    et al.
    Huijben, Jilske A
    van der Jagt, Mathieu
    Volovici, Victor
    van Essen, Thomas
    Polinder, Suzanne
    Nelson, David
    Ercole, Ari
    Stocchetti, Nino
    Citerio, Giuseppe
    Peul, Wilco C
    Maas, Andrew I R
    Menon, David
    Steyerberg, Ewout W
    Lingsma, Hester F
    Variation in monitoring and treatment policies for intracranial hypertension in traumatic brain injury: a survey in 66 neurotrauma centers participating in the CENTER-TBI study2017In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 21, no 1, article id 233Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: No definitive evidence exists on how intracranial hypertension should be treated in patients with traumatic brain injury (TBI). It is therefore likely that centers and practitioners individually balance potential benefits and risks of different intracranial pressure (ICP) management strategies, resulting in practice variation. The aim of this study was to examine variation in monitoring and treatment policies for intracranial hypertension in patients with TBI.

    METHODS: A 29-item survey on ICP monitoring and treatment was developed on the basis of literature and expert opinion, and it was pilot-tested in 16 centers. The questionnaire was sent to 68 neurotrauma centers participating in the Collaborative European Neurotrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study.

    RESULTS: The survey was completed by 66 centers (97% response rate). Centers were mainly academic hospitals (n = 60, 91%) and designated level I trauma centers (n = 44, 67%). The Brain Trauma Foundation guidelines were used in 49 (74%) centers. Approximately 90% of the participants (n = 58) indicated placing an ICP monitor in patients with severe TBI and computed tomographic abnormalities. There was no consensus on other indications or on peri-insertion precautions. We found wide variation in the use of first- and second-tier treatments for elevated ICP. Approximately half of the centers were classified as using a relatively aggressive approach to ICP monitoring and treatment (n = 32, 48%), whereas the others were considered more conservative (n = 34, 52%).

    CONCLUSIONS: Substantial variation was found regarding monitoring and treatment policies in patients with TBI and intracranial hypertension. The results of this survey indicate a lack of consensus between European neurotrauma centers and provide an opportunity and necessity for comparative effectiveness research.

  • 16. Cnossen, Maryse C.
    et al.
    Lingsma, Hester F.
    Tenovuo, Olli
    Maas, Andrew I. R.
    Menon, David
    Steyerberg, Ewout W.
    Ribbers, Gerard M.
    Polinder, Suzanne
    Rehabilitation after traumatic brain injury: A survey in 70 European neurotrauma centres participating in the CENTER-TBI study.2017In: Journal of Rehabilitation Medicine, ISSN 1650-1977, E-ISSN 1651-2081, Vol. 49, no 5, p. 395-401Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To describe variation in structural and process characteristics of acute in-hospital rehabilitation and referral to post-acute care for patients with traumatic brain injury across Europe.

    DESIGN: Survey study, of neurotrauma centres.

    METHODS: A 14-item survey about in-hospital rehabilitation and referral to post-acute care was sent to 71 neurotrauma centres participating in a European multicentre study (CENTER-TBI). The questionnaire was developed based on literature and expert opinion and was pilot-tested before sending out to the centres.

    RESULTS: Seventy (99%) centres in 20 countries completed the survey. The included centres were predominately academic level I trauma centres. Among the 70 centres, a multidisciplinary rehabilitation team can be consulted at 41% (n = 29) of the intensive care units and 49% (n = 34) of the wards. Only 13 (19%) centres used rehabilitation guidelines in patients with traumatic brain injury. Age was reported as a major determinant of referral decisions in 32 (46%) centres, with younger patients usually referred to specialized rehabilitation centres, and patients ≥ 65 years also referred to nursing homes or local hospitals.

    CONCLUSION: Substantial variation exists in structural and process characteristics of in-hospital acute rehabilitation and referral to post-acute rehabilitation facilities among neurotrauma centres across Europe.

  • 17. Cnossen, Maryse C.
    et al.
    Polinder, Suzanne
    Lingsma, Hester F.
    Maas, Andrew I. R.
    Menon, David
    Steyerberg, Ewout W.
    Variation in Structure and Process of Care in Traumatic Brain Injury: Provider Profiles of European Neurotrauma Centers Participating in the CENTER-TBI Study2016In: PLoS ONE, E-ISSN 1932-6203, Vol. 11, no 8, article id e0161367Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: The strength of evidence underpinning care and treatment recommendations in traumatic brain injury (TBI) is low. Comparative effectiveness research (CER) has been proposed as a framework to provide evidence for optimal care for TBI patients. The first step in CER is to map the existing variation. The aim of current study is to quantify variation in general structural and process characteristics among centers participating in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study.

    METHODS: We designed a set of 11 provider profiling questionnaires with 321 questions about various aspects of TBI care, chosen based on literature and expert opinion. After pilot testing, questionnaires were disseminated to 71 centers from 20 countries participating in the CENTER-TBI study. Reliability of questionnaires was estimated by calculating a concordance rate among 5% duplicate questions.

    RESULTS: All 71 centers completed the questionnaires. Median concordance rate among duplicate questions was 0.85. The majority of centers were academic hospitals (n = 65, 92%), designated as a level I trauma center (n = 48, 68%) and situated in an urban location (n = 70, 99%). The availability of facilities for neuro-trauma care varied across centers; e.g. 40 (57%) had a dedicated neuro-intensive care unit (ICU), 36 (51%) had an in-hospital rehabilitation unit and the organization of the ICU was closed in 64% (n = 45) of the centers. In addition, we found wide variation in processes of care, such as the ICU admission policy and intracranial pressure monitoring policy among centers.

    CONCLUSION: Even among high-volume, specialized neurotrauma centers there is substantial variation in structures and processes of TBI care. This variation provides an opportunity to study effectiveness of specific aspects of TBI care and to identify best practices with CER approaches.

  • 18. Cnossen, Maryse C.
    et al.
    van der Brande, Ruben
    Lingsma, Hester F.
    Polinder, Suzanne
    Lecky, Fiona
    Maas, Andrew I. R.
    Prehospital Trauma Care among 68 European Neurotrauma Centers: Results of the CENTER-TBI Provider Profiling Questionnaires2018In: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 36, no 1, p. 176-181Article in journal (Refereed)
    Abstract [en]

    The first hour following traumatic brain injury (TBI) is considered crucial to prevent death and disability. It is, however, not established yet how the prehospital care should be organized to optimize recovery during the first hour. The objective of the current study was to examine variation in prehospital trauma care across Europe aiming to inform comparative effectiveness analyses on care for neurotrauma patients. A survey on prehospital trauma care was sent to 68 neurotrauma centers from 20 European countries participating in the Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI) study. The survey was developed using literature review and expert opinion and was pilot tested in 16 centers. All participants completed the questionnaire. Advanced life support was used in half of the centers (n = 35; 52%), whereas the other centers used mainly basic life support (n = 26; 38%). A mobile medical team (MMT) could be dispatched 24/7 in most centers (n = 66; 97%). Helicopters were used in approximately half of the centers to transport the MMT to the scene (n = 39; 57%) and the patient to the hospital (n = 31, 46%). Half of the centers used a stay-and-play approach at the scene (n = 37; 55%), while the others used a scoop-and-run approach or another policy. We found wide variation in prehospital trauma care across Europe. This may reflect differences in socio-economic situations, geographic differences, and a general lack of strong evidence for some aspects of prehospital care. The current variation provides the opportunity to study the effectiveness of prehospital interventions and systems of care in comparative effectiveness research.

  • 19.
    Dahlqvist, Per
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Koskinen, Lars-Owe D
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Brännström, Thomas
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Hägg, Erik
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Testicular enlargement in a patient with a FSH-secreting pituitary adenoma2010In: Endocrine (Basingstoke), ISSN 1355-008X, E-ISSN 1559-0100, Vol. 37, no 2, p. 289-293Article in journal (Refereed)
    Abstract [en]

    Clinically non-functional pituitary adenomas are often derived from gonadotropin producing cells. However, gonadotropinomas causing elevated serum levels of follicle-stimulating hormone (FSH) and clinical signs of FSH hypersecretion are very rarely described. Our patient, a 56-year-old man, was referred to our clinic with signs of hypogonadism. Magnetic resonance imaging (MRI) and biochemical examinations showed a large pituitary adenoma and excessive levels of serum FSH. Clinical examination and ultrasound measurement revealed bilaterally enlarged testes. After pituitary surgery, serum FSH levels normalized and there was a decrease in testicular volume. This case suggests that supraphysiological levels of FSH from a gonadotropinoma can cause a clinically observable effect, i.e. testicular enlargement. This is in line with experimental studies showing biological effect of FSH from pituitary adenomas and previous occasional reports of ovarian hyperstimulation and testicular enlargement in patients with FSH-secreting gonadotropinomas.

  • 20.
    Eklund, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Jóhannesson, Gauti
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Johansson, Elias
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Holmlund, Petter
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Qvarlander, Sara
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Ambarki, Khalid
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Wåhlin, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Koskinen, Lars-Owe D.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    The Pressure Difference between Eye and Brain Changes with Posture2016In: Annals of Neurology, ISSN 0364-5134, E-ISSN 1531-8249, Vol. 80, no 2, p. 269-276Article in journal (Refereed)
    Abstract [en]

    Objective: The discovery of a posture-dependent effect on the difference between intraocular pressure (IOP) and intracranial pressure (ICP) at the level of lamina cribrosa could have important implications for understanding glaucoma and idiopathic intracranial hypertension and could help explain visual impairments in astronauts exposed to microgravity. The aim of this study was to determine the postural influence on the difference between simultaneously measured ICP and IOP.

    Methods: Eleven healthy adult volunteers (age = 46 ± 10 years) were investigated with simultaneous ICP, assessed through lumbar puncture, and IOP measurements when supine, sitting, and in 9° head-down tilt (HDT). The trans–lamina cribrosa pressure difference (TLCPD) was calculated as the difference between the IOP and ICP. To estimate the pressures at the lamina cribrosa, geometrical distances were estimated from magnetic resonance imaging and used to adjust for hydrostatic effects.

    Results: The TLCPD (in millimeters of mercury) between IOP and ICP was 12.3 ± 2.2 for supine, 19.8 ± 4.6 for sitting, and 6.6 ± 2.5 for HDT. The expected 24-hour average TLCPD on earth—assuming 8 hours supine and 16 hours upright—was estimated to be 17.3mmHg. By removing the hydrostatic effects on pressure, a corresponding 24-hour average TLCPD in microgravity environment was simulated to be 6.7mmHg.

    Interpretation: We provide a possible physiological explanation for how microgravity can cause symptoms similar to those seen in patients with elevated ICP. The observed posture dependency of TLCPD also implies that assessment of the difference between IOP and ICP in upright position may offer new understanding of the pathophysiology of idiopathic intracranial hypertension and glaucoma. 

  • 21.
    Eklund, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Koskinen, Lars-Owe D
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Williams, Michael A
    Luciano, Mark G
    Dombrowski, Stephen M
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Hydrodynamics of the CertasTM programmable valve for the treatment of hydrocephalus2012In: Fluids and barriers of the CNS, ISSN 2045-8118, Vol. 9, no 1, p. 12-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The new CertasTM shunt for the treatment of hydrocephalus has seven standard pressure settings that according to the manufacturer range from 36 to 238 mmH2O, and an additional "Virtual Off" setting with an opening pressure >400 mmH2O. Information on actual pressure response and reliability of shunt performance is important in clinical application, especially the "Virtual Off" setting as a non-surgical replacement for shunt ligation. The objective of this study was to evaluate the in-vitro hydrodynamic performance of the CertasTM shunt.

    METHODS: Six new CertasTM shunts with proximal and distal catheters were tested with an automated, computerized test system that raised the pressure from zero to a maximum pressure and back to zero at each valve setting. Opening pressure and flow resistance were determined.

    RESULTS: For settings 1-7 the measured opening pressure range was 26 to 247 mmH2O, and the mean change in opening pressure for a one-step adjustment was between 33 and 38 mmH2O. For setting 8 ("Virtual Off") the measured mean opening pressure was 494 +/- 34 mmH2O (range 451 to 556 mmH2O). The mean outflow resistance was 7.0 mmHg/ml/min (outflow conductance 17.9 ul/s/kPa).

    CONCLUSIONS: The six shunts had similar characteristics and closely matched the manufacturer's specifications for opening pressure at settings 1-7. The opening pressure for the "Virtual Off" setting was nearly 500 mmH2O, which is 100 mmH2O higher than the manufacturer's specification of ">400" and should be functionally off for most patients with communicating hydrocephalus. Clinical studies are needed to evaluate if the CSF dynamic profile persists after implantation in patients.

  • 22. Foks, Kelly A.
    et al.
    Cnossen, Maryse C.
    Dippel, Diederik W. J.
    Maas, Andrew I.R.
    Menon, David
    van der Naalt, Joukje
    Steyerberg, Ewout W.
    Lingsma, Hester F.
    Polinder, Suzanne
    Koskinen, Lars-Owe
    Management of mild traumatic brain injury at the emergency department and hospital admission in Europe: A survey of 71 neurotrauma centers participating in the CENTER-TBI study2017In: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 34, no 17, p. 2529-2535Article in journal (Refereed)
    Abstract [en]

    Previous studies have indicated that there is no consensus about management of mild traumatic brain injury (mTBI) at the emergency department (ED) and during hospital admission. We aim to study variability between management policies for TBI patients at the ED and hospital ward across Europe. Centers participating in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study received questionnaires about different phases of TBI care. These questionnaires included 71 questions about TBI management at the ED and at the hospital ward. We found differences in how centers defined mTBI. For example, 40 centers (59%) defined mTBI as a Glasgow Coma Scale (GCS) score between 13-15 and 26 (38%) as a GCS score between 14-15. At the ED various guidelines for the use of head CT in mTBI patients were used; 32 centers (49%) used national guidelines, 10 centers (15%) local guidelines and 14 centers (21%) used no guidelines at all. Also differences in indication for admission between centers were found. After ED discharge, 7 centers (10%) scheduled a routine follow-up appointment, while 38 (54%) did so only after ward admission. In conclusion, large between-center variation exists in policies for diagnostics, admission and discharge decisions in patients with mTBI at the ED and in hospital. Guidelines are not always operational in centers, and reported policies systematically diverge from what is recommended in those guidelines. The results of this study may be useful in the understanding of mTBI care in Europe and show the need for further studies on the effectiveness of different policies on outcome.

  • 23.
    Gasslander, Johan
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience. Departments of Cardiology and Health, Medicine and Caring Services, Linkoping University, Vrinnevi General Hospital Norrköping.
    Sundström, Nina
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Koskinen, Lars-Owe D.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Risk factors for developing subdural hematoma: a registry-based study in 1457 patients with shunted idiopathic normal pressure hydrocephalus2020In: Journal of Neurosurgery, ISSN 0022-3085, E-ISSN 1933-0693, p. 1-10Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Subdural hematomas and hygromas (SDHs) are common complications in idiopathic normal pressure hydrocephalus (iNPH) patients with shunts. In this registry-based study, patients with shunted iNPH were screened nationwide to identify perioperative variables that may increase the risk of SDH.

    METHODS: The Swedish Hydrocephalus Quality Registry was reviewed for iNPH patients who had undergone shunt surgery in Sweden in 2004-2014. Potential risk factors for SDH were recorded preoperatively and 3 months after surgery. Drug prescriptions were identified from a national pharmacy database. Patients who developed SDHs were compared with those without SDHs.

    RESULTS: The study population consisted of 1457 patients, 152 (10.4%) of whom developed an SDH. Men developed an SDH more often than women (OR 2.084, 95% CI 1.421-3.058, p < 0.001). Patients on platelet aggregation inhibitors developed an SDH more often than those who were not (OR 1.733, 95% CI 1.236-2.431, p = 0.001). At surgery, shunt opening pressures had been set 5.9 mm H2O lower in the SDH group than in the no-SDH group (109.6 ± 24.1 vs 115.5 ± 25.4 mm H2O, respectively, p = 0.009). Antisiphoning devices (ASDs) were used in 892 patients but did not prevent SDH. Mean opening pressures at surgery and the follow-up were lower with shunts with an ASD, without causing more SDHs. No other differences were seen between the groups.

    CONCLUSIONS: iNPH patients in this study were diagnosed and operated on in routine practice; thus, the results represent everyday care. Male sex, antiplatelet medication, and a lower opening pressure at surgery were risk factors for SDH. Physical status and comorbidity were not. ASD did not prevent SDH, but a shunt with an ASD allowed a lower opening pressure without causing more SDHs.

  • 24. Gravesteijn, B. Y.
    et al.
    Sewalt, C. A.
    Ercole, A.
    Lecky, F.
    Menon, D.
    Steyerberg, E. W.
    Maas, A. I. R.
    Lingsma, H. F.
    Klimek, M.
    Variation in the practice of tracheal intubation in Europe after traumatic brain injury: a prospective cohort study2020In: Anaesthesia, ISSN 0003-2409, E-ISSN 1365-2044, Vol. 75, no 1, p. 45-53Article in journal (Refereed)
    Abstract [en]

    Traumatic brain injury patients frequently undergo tracheal intubation. We aimed to assess current intubation practice in Europe and identify variation in practice. We analysed data from patients with traumatic brain injury included in the prospective cohort study collaborative European neurotrauma effectiveness research in traumatic brain injury (CENTER-TBI) in 45 centres in 16 European countries. We included patients who were transported to hospital by emergency medical services. We used mixed-effects multinomial regression to quantify the effects on pre-hospital or in-hospital tracheal intubation of the following: patient characteristics; injury characteristics; centre; and trauma system characteristics. A total of 3843 patients were included. Of these, 1322 (34%) had their tracheas intubated; 839 (22%) pre-hospital and 483 (13%) in-hospital. The fit of the model with only patient characteristics predicting intubation was good (Nagelkerke R2 64%). The probability of tracheal intubation increased with the following: younger age; lower pre-hospital or emergency department GCS; higher abbreviated injury scale scores (head and neck, thorax and chest, face or abdomen abbreviated injury score); and one or more unreactive pupils. The adjusted median odds ratio for intubation between two randomly chosen centres was 3.1 (95%CI 2.1-4.3) for pre-hospital intubation, and 2.7 (95%CI 1.9-3.5) for in-hospital intubation. Furthermore, the presence of an anaesthetist was independently associated with more pre-hospital intubation (OR 2.9, 95%CI 1.3-6.6), in contrast to the presence of ambulance personnel who are allowed to intubate (OR 0.5, 95%CI 0.3-0.8). In conclusion, patient and injury characteristics are key drivers of tracheal intubation. Between-centre differences were also substantial. Further studies are needed to improve the evidence base supporting recommendations for tracheal intubation.

  • 25. Grenander, A.
    et al.
    Bredbacka, S.
    Rydvall, A.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Aroch, R.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Edner, G.
    Koskinen, Lars-Owe D.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Olivecrona, M.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Antithrombin treatment in patients with traumatic brain injury: a pilot study2001In: J Neurosurg Anesthesiol, Vol. 13, no 1, p. 49-56Article in journal (Refereed)
    Abstract [en]

    This study will determine if early administration of antithrombin concentrate to patients with traumatic brain injury (TBI) can inhibit or significantly shorten the time of coagulopathy. The progress of brain injury monitored by computed tomographic scan (CT) was also assessed, as was the time needed for intensive care and outcome related to Glasgow outcome scale (GOS). Twenty-eight patients with isolated brain trauma verified with CT were included in either of two parallel groups. The Glasgow coma score (GCS) was mean 7.5, and median 7.0; signifying a moderate to severe traumatic brain injury but with a mortality of only 3.5%. The patients randomized to antithrombin treatment received a total of 100 U/kg BW during 24 hours. To measure hypercoagulability, soluble fibrin (SF), D-dimer (D-d), and thrombin-antithrombin complex (TAT) were assessed together with antithrombin (AT) and routine coagulation tests. Before treatment, SF, D-d, and TAT were markedly increased in both groups. Soluble fibrin and D-dimer (measured after treatment began) appeared to decrease faster in the AT group, and there was a statistically significant difference between the groups at 36 hours for SF and at 36 hours, 48 hours, and at Day 3 for D-d. Thrombin-antithrombin complex levels were very high in both groups but, surprisingly, showed no significant difference between the groups. The authors conclude that antithrombin concentrate administered to patients with severe TBI resulted in a marginal reduction of hypercoagulation. We could not detect any obvious influence by antithrombin on brain injury progress, on CT, or on outcome or time needed for intensive care.

  • 26. Grände, P-O
    et al.
    Koskinen, L-O
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Naredi, S
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Reinstrup, P
    Romner, B
    Conventional treatments for severe head injury: are they effective, ineffective, or even harmful?2007In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 51, no 10, p. 1294-1296Article in journal (Other academic)
  • 27.
    Hariz, Gun-Marie
    et al.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Occupational Therapy. Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Blomstedt, Patric
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Koskinen, Lars-Owe D
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Long-term effect of deep brain stimulation for essential tremor on activities of daily living and health-related quality of life2008In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 118, no 6, p. 387-394Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To report long-term effects of thalamic deep brain stimulation (DBS) on activities of daily living (ADL) and health-related quality of life (HRQoL) in patients with essential tremor (ET).

    MATERIALS AND METHODS: Nineteen consecutive patients were evaluated at baseline, at a mean of 1 year, then at a mean of 7 years after DBS using Tremor Rating Scale, Mini Mental Test, ADL Taxonomy, Nottingham Health Profile, Life Satisfaction Checklist, Visual Analogue Scale and interview.

    RESULTS: There was a decrease of DBS efficacy on tremor between 1 and 7 years post-operatively. The marked improvement in ADL at 1 year was no longer sustained at long-term, except for the ability to eat. Social life remained improved.

    CONCLUSION: Although there is a decrease of DBS effect on tremor at 7 years, and even though further ageing and co-morbidities may impact on the well-being of patients, there is still relevant benefit of DBS on few aspects of ADL and HRQoL in patients with ET.

  • 28.
    Holmlund, Petter
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Koskinen, Lars-Owe D.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Johansson, Elias
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Sundström, Nina
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Qvarlander, Sara
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Venous collapse regulates intracranial pressure in upright body positions2018In: American Journal of Physiology. Regulatory Integrative and Comparative Physiology, ISSN 0363-6119, E-ISSN 1522-1490, Vol. 314, no 3, p. R377-R385Article in journal (Refereed)
    Abstract [en]

    Recent interest in intracranial pressure (ICP) in the upright posture has revealed that the mechanisms regulating postural changes in ICP are not fully understood. We have suggested an explanatory model where the postural changes in ICP depend on well-established hydrostatic effects in the venous system and where these effects are interrupted by collapse of the internal jugular veins (IJVs) in more upright positions. The aim of this study was to investigate this relationship by simultaneous invasive measurements of ICP, venous pressure and IJV collapse in healthy volunteers. ICP (monitored via the lumbar route), central venous pressure (PICC-line) and IJV cross-sectional area (ultrasound) were measured in 11 healthy volunteers (47±10 years) in seven positions, from supine to sitting (0°-69°). Venous pressure and anatomical distances were used to predict ICP in accordance with the explanatory model, and IJV area was used to assess IJV collapse. The hypothesis was tested by comparing measured ICP to predicted ICP. Our model accurately described the general behavior of the observed postural ICP changes (mean difference: -0.03±2.7 mmHg). No difference was found between predicted and measured ICP for any tilt-angle (p-values: 0.65 - 0.94). The results support the hypothesis that postural ICP changes are governed by hydrostatic effects in the venous system and IJV collapse. This improved understanding of the postural ICP regulation may have important implications for the development of better treatments for neurological and neurosurgical conditions affecting ICP.

  • 29.
    Holmlund, Petter
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Johansson, Elias
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Qvarlander, Sara
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Wåhlin, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Ambarki, Khalid
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Koskinen, Lars-Owe D.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Human jugular vein collapse in the upright posture: implications for postural intracranial pressure regulation2017In: Fluids and Barriers of the CNS, ISSN 2045-8118, E-ISSN 2045-8118, Vol. 14, article id 17Article in journal (Refereed)
    Abstract [en]

    Background: Intracranial pressure (ICP) is directly related to cranial dural venous pressure (P-dural). In the upright posture, P-dural is affected by the collapse of the internal jugular veins (IJVs) but this regulation of the venous pressure has not been fully understood. A potential biomechanical description of this regulation involves a transmission of surrounding atmospheric pressure to the internal venous pressure of the collapsed IJVs. This can be accomplished if hydrostatic effects are cancelled by the viscous losses in these collapsed veins, resulting in specific IJV cross-sectional areas that can be predicted from flow velocity and vessel inclination. Methods: We evaluated this potential mechanism in vivo by comparing predicted area to measured IJV area in healthy subjects. Seventeen healthy volunteers (age 45 +/- 9 years) were examined using ultrasound to assess IJV area and flow velocity. Ultrasound measurements were performed in supine and sitting positions. Results: IJV area was 94.5 mm(2) in supine and decreased to 6.5 +/- 5.1 mm(2) in sitting position, which agreed with the predicted IJV area of 8.7 +/- 5.2 mm(2) (equivalence limit +/- 5 mm(2), one-sided t tests, p = 0.03, 33 IJVs). Conclusions: The agreement between predicted and measured IJV area in sitting supports the occurrence of a hydrostatic-viscous pressure balance in the IJVs, which would result in a constant pressure segment in these collapsed veins, corresponding to a zero transmural pressure. This balance could thus serve as the mechanism by which collapse of the IJVs regulates P-dural and consequently ICP in the upright posture.

  • 30.
    Holmlund, Petter
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Johansson, Elias
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Qvarlander, Sara
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Wåhlin, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Ambarki, Khalid
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Koskinen, Lars-Owe D.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Jugular vein collapse in upright and its relation to intracranial pressure regulation2017In: Journal of Cerebral Blood Flow and Metabolism, ISSN 0271-678X, E-ISSN 1559-7016, Vol. 37, p. 297-297Article in journal (Refereed)
  • 31. Huijben, Jilske A.
    et al.
    van der Jagt, Mathieu
    Cnossen, Maryse C.
    Kruip, Marieke J. H. A.
    Haitsma, Iain K.
    Stocchetti, Nino
    Maas, Andrew I. R.
    Menon, David K.
    Ercole, Ari
    Maegele, Marc
    Stanworth, Simon J.
    Citerio, Giuseppe
    Polinder, Suzanne
    Steyerberg, Ewout W.
    Lingsma, Hester F.
    Variation in Blood Transfusion and Coagulation Management in Traumatic Brain Injury at the Intensive Care Unit: A Survey in 66 Neurotrauma Centers Participating in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury Study2017In: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 35, no 2, p. 323-332Article in journal (Refereed)
    Abstract [en]

    Our aim was to describe current approaches and to quantify variability between European intensive care units (ICUs) in patients with traumatic brain injury (TBI). Therefore, we conducted a provider profiling survey as part of the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. The ICU Questionnaire was sent to 68 centers from 20 countries across Europe and Israel. For this study, we used ICU questions focused on 1) hemoglobin target level (Hb-TL), 2) coagulation management, and 3) deep venous thromboembolism (DVT) prophylaxis. Seventy-eight participants, mostly intensivists and neurosurgeons of 66 centers, completed the ICU questionnaire. For ICU-patients, half of the centers (N = 34; 52%) had a defined Hb-TL in their protocol. For patients with TBI, 26 centers (41%) indicated an Hb-TL between 70 and 90 g/L and 38 centers (59%) above 90 g/L. To treat trauma-related hemostatic abnormalities, the use of fresh frozen plasma (N = 48; 73%) or platelets (N = 34; 52%) was most often reported, followed by the supplementation of vitamin K (N = 26; 39%). Most centers reported using DVT prophylaxis with anticoagulants frequently or always (N = 62; 94%). In the absence of hemorrhagic brain lesions, 14 centers (21%) delayed DVT prophylaxis until 72 h after trauma. If hemorrhagic brain lesions were present, the number of centers delaying DVT prophylaxis for 72 h increased to 29 (46%). Overall, a lack of consensus exists between European ICUs on blood transfusion and coagulation management. The results provide a baseline for the CENTER-TBI study, and the large between-center variation indicates multiple opportunities for comparative effectiveness research.

  • 32. Huijben, Jilske A
    et al.
    Volovici, Victor
    Cnossen, Maryse C
    Haitsma, Iain K
    Stocchetti, Nino
    Maas, Andrew I R
    Menon, David K
    Ercole, Ari
    Citerio, Giuseppe
    Nelson, David
    Polinder, Suzanne
    Steyerberg, Ewout W
    Lingsma, Hester F
    van der Jagt, Mathieu
    Variation in general supportive and preventive intensive care management of traumatic brain injury: a survey in 66 neurotrauma centers participating in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study2018In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 22, no 1, article id 90Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: General supportive and preventive measures in the intensive care management of traumatic brain injury (TBI) aim to prevent or limit secondary brain injury and optimize recovery. The aim of this survey was to assess and quantify variation in perceptions on intensive care unit (ICU) management of patients with TBI in European neurotrauma centers.

    METHODS: We performed a survey as part of the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. We analyzed 23 questions focused on: 1) circulatory and respiratory management; 2) fever control; 3) use of corticosteroids; 4) nutrition and glucose management; and 5) seizure prophylaxis and treatment.

    RESULTS: The survey was completed predominantly by intensivists (n = 33, 50%) and neurosurgeons (n = 23, 35%) from 66 centers (97% response rate). The most common cerebral perfusion pressure (CPP) target was > 60 mmHg (n = 39, 60%) and/or an individualized target (n = 25, 38%). To support CPP, crystalloid fluid loading (n = 60, 91%) was generally preferred over albumin (n = 15, 23%), and vasopressors (n = 63, 96%) over inotropes (n = 29, 44%). The most commonly reported target of partial pressure of carbon dioxide in arterial blood (PaCO2) was 36-40 mmHg (4.8-5.3 kPa) in case of controlled intracranial pressure (ICP) < 20 mmHg (n = 45, 69%) and PaCO2 target of 30-35 mmHg (4-4.7 kPa) in case of raised ICP (n = 40, 62%). Almost all respondents indicated to generally treat fever (n = 65, 98%) with paracetamol (n = 61, 92%) and/or external cooling (n = 49, 74%). Conventional glucose management (n = 43, 66%) was preferred over tight glycemic control (n = 18, 28%). More than half of the respondents indicated to aim for full caloric replacement within 7 days (n = 43, 66%) using enteral nutrition (n = 60, 92%). Indications for and duration of seizure prophylaxis varied, and levetiracetam was mostly reported as the agent of choice for both seizure prophylaxis (n = 32, 49%) and treatment (n = 40, 61%).

    CONCLUSIONS: Practice preferences vary substantially regarding general supportive and preventive measures in TBI patients at ICUs of European neurotrauma centers. These results provide an opportunity for future comparative effectiveness research, since a more evidence-based uniformity in good practices in general ICU management could have a major impact on TBI outcome.

  • 33. Huijben, Jilske A.
    et al.
    Wiegers, Eveline J. A.
    de Keizer, Nicolette F.
    Maas, Andrew I. R.
    Menon, David
    Ercole, Ari
    Citerio, Giuseppe
    Lecky, Fiona
    Wilson, Lindsay
    Cnossen, Maryse C.
    Polinder, Suzanne
    Steyerberg, Ewout W.
    van der Jagt, Mathieu
    Lingsma, Hester F.
    Aries, Marcel
    Badenes, Rafael
    Beishuizen, Albertus
    Bilotta, Federico
    Chieregato, Arturo
    Cingolani, Emiliano
    Cnossen, Maryse
    Coburn, Mark
    Coles, Jonathan P.
    Delargy, Mark
    Depreitere, Bart
    Flaatten, Hans
    Golyk, Volodymyr
    Grauwmeijer, Erik
    Haitsma, Iain
    Helbok, Raimund
    Hoedemaekers, Cornelia
    Jacobs, Bram
    Jellema, Korne
    Koskinen, Lars-Owe D.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Maegele, Marc
    Martin Delgado, Maria Cruz
    Moller, Kirsten
    Moreno, Rui
    Nelson, David
    Oldenbeuving, Annemarie W.
    Payen, Jean-Francois
    Pejakovic, Jasmina
    Ribbbers, Gerard M.
    Rossaint, Rolf
    Schoonman, Guus Geurt
    Steiner, Luzius A.
    Stocchetti, Nino
    Silvio, Fabio
    Takala, Riikka
    Tenovuo, Olli
    Valeinis, Eglis
    van den Bergh, Walter M.
    van Essen, Thomas
    van Leeuwen, Nikki
    Verhofstad, Michael H. J.
    Vos, Pieter E.
    Development of a quality indicator set to measure and improve quality of ICU care for patients with traumatic brain injury2019In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 23, article id 95Article in journal (Refereed)
    Abstract [en]

    Background: We aimed to develop a set of quality indicators for patients with traumatic brain injury (TBI) in intensive care units (ICUs) across Europe and to explore barriers and facilitators for implementation of these quality indicators.

    Methods: A preliminary list of 66 quality indicators was developed, based on current guidelines, existing practice variation, and clinical expertise in TBI management at the ICU. Eight TBI experts of the Advisory Committee preselected the quality indicators during a first Delphi round. A larger Europe-wide expert panel was recruited for the next two Delphi rounds. Quality indicator definitions were evaluated on four criteria: validity (better performance on the indicator reflects better processes of care and leads to better patient outcome), feasibility (data are available or easy to obtain), discriminability (variability in clinical practice), and actionability (professionals can act based on the indicator). Experts scored indicators on a 5-point Likert scale delivered by an electronic survey tool.

    Results. The expert panel consisted of 50 experts from 18 countries across Europe, mostly intensivists (N=24, 48%) and neurosurgeons (N=7, 14%). Experts agreed on a final set of 42 indicators to assess quality of ICU care: 17 structure indicators, 16 process indicators, and 9 outcome indicators. Experts are motivated to implement this finally proposed set (N=49, 98%) and indicated routine measurement in registries (N=41, 82%), benchmarking (N=42, 84%), and quality improvement programs (N=41, 82%) as future steps. Administrative burden was indicated as the most important barrier for implementation of the indicator set (N=48, 98%).

    Conclusions: This Delphi consensus study gives insight in which quality indicators have the potential to improve quality of TBI care at European ICUs. The proposed quality indicator set is recommended to be used across Europe for registry purposes to gain insight in current ICU practices and outcomes of patients with TBI. This indicator set may become an important tool to support benchmarking and quality improvement programs for patients with TBI in the future.

  • 34.
    Johansson, M.
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Henriksson, R.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Bergenheim, A .T.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Koskinen, Lars-Owe D.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Interleukin-2 and histamine in combination inhibit tumour growth and angiogenesis in malignant glioma2000In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 83, no 6, p. 826-832Article in journal (Refereed)
    Abstract [en]

    Biotherapy including interleukin-2 (IL-2) treatment seems to be more effective outside the central nervous system when compared to the effects obtained when the same tumour is located intracerebrally. Recently published studies suggest that reduced activity of NK cells in tumour tissue can be increased by histamine. The present study was designed to determine whether IL-2 and histamine, alone or in combination, can induce anti-tumour effects in an orthotopic rat glioma model. One group of rats was treated with histamine alone (4 mg kg(-1)s.c. as daily injections from day 6 after intracranial tumour implantation), another group with IL-2 alone as a continuous subcutaneous infusion and a third group with both histamine and IL-2. The animals were sacrificed at day 24 after tumour implantation. IL-2 and histamine in combination significantly reduced tumour growth. The microvessel density was significantly reduced, an effect mainly affecting the small vessels. No obvious alteration in the pattern of VEGF mRNA expression was evident and no significant changes in apoptosis were observed. Neither IL-2 nor histamine alone caused any detectable effects on tumour growth. Histamine caused an early and pronounced decline in tumour blood flow compared to normal brain. The results indicate that the novel combination of IL-2 and histamine can be of value in reducing intracerebral tumour growth and, thus, it might be of interest to re-evaluate the therapeutic potential of biotherapy in malignant glioma.

  • 35.
    Johansson, Mikael
    et al.
    Departments of Oncology, University Hospital, Umeå, Sweden.
    Bergenheim, A. Tommy
    Departments of Oncology, University Hospital, Umea, Sweden. Neurosurgery, University Hospital, Umeå, Sweden.
    Henriksson, Roger
    Departments of Oncology, University Hospital, Umea, Sweden.
    Koskinen, Lars-Owe D.
    Neurosurgery, University Hospital, Umeå, Sweden.
    Vallbo, Christina
    Departments of Oncology, University Hospital, Umea, Sweden.
    Widmark, Anders
    Departments of Oncology, University Hospital, Umea, Sweden.
    Tumor blood flow and the cytotoxic effects of estramustine and its constituents in a rat glioma model.1997In: Neurosurgery, ISSN 0148-396X, E-ISSN 1524-4040, Vol. 41, no 1, p. 237-244Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Estramustine (EaM) is a conjugate of nor-nitrogen mustard (NNM) and 17 beta-estradiol (E2) that has cytotoxic and radiosensitizing effects on experimental malignant glioma. Its mechanism of action is only partly understood. To further investigate the mechanism in vivo, the effects on tumor blood flow (TBF) and tumor growth were analyzed.

    METHODS: TBF was measured by radioactive microspheres, and tumor growth was measured by weight. Apoptosis was evaluated by in situ end labeling and gel electrophoresis. The effects of the constituents NNM and E2 were also evaluated.

    RESULTS: EaM increased TBF to 153.8 ml/100 g/min after 3 days and to 153.9 ml/100 g/min after 10 days of treatment, compared with 94.0 ml/100 g/min in untreated controls. Cerebral blood flow did not change after EaM treatment. NNM increased TBF but also showed a tendency to increase cerebral blood flow. E2 increased TBF, whereas cerebral blood flow was unchanged. EaM resulted in a rapid reduction in tumor weight from 230 mg in untreated animals to 146 mg after 3 days of treatment. EaM induced an early transient fragmentation of deoxyribonucleic acid in glioma but not in the normal brain. Neither NNM nor E2 affected tumor weight.

    CONCLUSION: EaM increases TBF in the BT4C rat glioma model with a concomitant rapid antitumoral effect. The increase in TBF could partially be induced by an estrogen-like action of EaM, but the rapid cytotoxic effect of the drug is obviously attributed to the intact EaM compound. This cytotoxic effect might be attributable to the induction of programmed cell death.

  • 36. Karlsson, Britt M.
    et al.
    Koch, Mona
    Koskinen, Lars-Owe D.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Nimodipine affects the microcirculation and modulates the vascular effects of acetylcholinesterase inhibition2003In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 108, no 2, p. 141-149Article in journal (Refereed)
    Abstract [en]

    The present investigation was undertaken in order to study whether microvascular effects of the calcium antagonist nimodipine induces changes that can explain an increased detoxification of the highly toxic cholinesterase inhibitor soman. Anaesthetised, tracheotomised and artificially ventilated rats were treated intra-peritoneally (ip) with nimodipine, 10 mg kg(-1) or vehicle followed one hour later by the exposure to 45 microg kg(-1) soman (iv). Nimodipine per se induced a vasodilation in the intestine, myocardium and other muscles. In the abdominal skin soman elicited a significant vasoconstriction that was turned into an increased blood flow after nimodipine pre-treatment. A slight vasoconstriction in diaphragm of soman intoxicated rats was turned into a significant vasodilation by nimodipine pre-treatment. In the intestinal parts no effect of soman was detected. However, in nimodipine pretreated animals soman induced a significant vasoconstriction. The capacity of soman detoxifying processes, i.e. enzymatic hydrolysis and covalent binding to different esterases, is unequally distributed throughout the body. Together with the knowledge of the detoxifying processes of cholinesterase inhibition the results support our theory, that nimodipine alters the peripheral blood flow in a beneficial way resulting in improved detoxification ability.

  • 37.
    Karlsson, Britt M.
    et al.
    Defence Research Establishment, Division of NBC Defence, 5‐907 82 Umeå, Sweden.
    Waara, Lena M.
    Defence Research Establishment, Division of NBC Defence, 5‐907 82 Umeå, Sweden.
    Fredriksson, Sten-Åke
    Koskinen, Lars-Owe D.
    Department of Neurosurgery, University Hospital of Umeå, S‐901 85 Umeå, Sweden.
    The effect of the calcium antagonist nimodipine on the detoxification of soman in anaesthetized rabbits.1997In: Journal of Pharmacy and Pharmacology (JPP), ISSN 0022-3573, E-ISSN 2042-7158, Vol. 49, no 3, p. 296-300Article in journal (Refereed)
    Abstract [en]

    The effect of nimodipine, a vasoactive calcium antagonist, on the disappearance of soman from blood was studied in anaesthetized rabbits intoxicated with soman (10.8 micrograms kg-1 i.v.). Blood samples from the left heart ventricle and femoral artery were used to investigate soman detoxification. The concentrations of the soman isomers C+P- and C-P- in blood samples were determined by gas chromatography coupled with high-resolution mass spectrometry. During the sampling, 15-300 s after soman injection, the soman concentration in control animals decreased from 50 to 0.029 ng mL-1; in animals pre-treated with nimodipine (10 mg kg-1) it decreased from 15 to 0.033 ng mL-1. In animals pre-treated with nimodipine the soman concentration was significantly reduced during the first minute of sampling. No differences were detected between soman concentrations in samples from the heart and femoral artery. Acetylcholinesterase inhibition was also used as an indicator of soman activity; there was no difference between the activity of this enzyme in different peripheral organs of control and nimodipine-treated animals. Nimodipine reduces the initial concentration of soman in the blood, which might be of significance in the treatment of soman intoxication.

  • 38. Koch, Bo L.
    et al.
    Edvinsson, Åsa A.
    Koskinen, Lars-Owe D.
    University Hospital of Northern Sweden, Department of Neurosurgery, SE‐901 85 Umeå, Sweden.
    Inhalation of substance P and thiorphan: acute toxicity and effects on respiration in conscious guinea pigs.1999In: Journal of Applied Toxicology, ISSN 0260-437X, E-ISSN 1099-1263, Vol. 19, no 1, p. 19-23Article in journal (Refereed)
    Abstract [en]

    Substance P is a tachykinin and a biologically active neuropeptide. The peptide produces salivation, neuronal excitation, vasodilatation, increased vascular permeability and contraction of smooth muscles in the respiratory tract. The study was designed to evaluate the acute effects in guinea pigs of inhaled aerosolized Substance P (SP). Apart from the acute toxic effect of the peptide, the distribution in different organs was also investigated. The acute inhalation toxicity of SP (LC50, 15 min) when co-administrated with the neutral endopeptidase inhibitor thiorphan was 368 microg m(-3). The peptide caused an increase in respiratory rate proceeding a decrease in tidal volume. As the exposure proceeded, a decrease in both respiratory rate and further decreases in tidal volume were observed until either the animal died or the exposure was terminated. The decreases in respiratory rate and tidal volume were probably due to bronchoconstriction caused by SP. Eighteen per cent of the inhaled amount of radioactive SP was retained in the body, and the highest concentrations of radioactivity were found in the kidney, lung and liver. Substance P in combination with thiorphan administered as an aerosol is extremely toxic and highly potent. Exposure to the substance at extremely low air concentrations may result in incapacitation in humans.

  • 39. Koskinen, L O
    et al.
    Koch, M L
    Svedberg, J
    Cerebrovascular effects of the TRH analogues pGlu-3-methyl-His-Pro amide and pGlu-Glu-Pro amide: a comparison with TRH.2000In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 105, no 1, p. 73-83Article in journal (Refereed)
    Abstract [en]

    The goal of the study was to assess whether TRH analogues possess cerebrovascular effects similar to the native peptide. The neuropeptide thyrotropin releasing hormone (TRH) elicits cerebrovasodilation in several species under various conditions. The laser-Doppler method was employed to study the effects of TRH and the analogues pGlu-3-methyl-His-Pro amid (M-TRH) and pGlu-Glu-Pro amide. Intravenous (i.v.) injection of 300 microg kg(-1) of TRH elicited cerebrovasodilation and a 62% increase in blood flow within 1 minute. M-TRH, in a dose of 300 microg kg(-1) i.v., elicited a 80% increase in cerebral blood flow. Even a minute dose of M-TRH (625 ng kg(-1)) caused an increase in cerebral blood flow. No clear difference in effects on the cerebral blood flow was observed between spontaneously and mechanically ventilated animals, pGlu-Glu-Pro amide had no cerebrovascular effect.

  • 40.
    Koskinen, L. O.
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery. Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Olivecrona, M.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Rodling-Wahlstrom, M.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Naredi, S.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Prostacyclin treatment normalises the MCA flow velocity in nimodipine-resistant cerebral vasospasm after aneurysmal subarachnoid haemorrhage: a pilot study2009In: Acta Neurochir (Wien), Vol. 151, no 6, p. 595-9; discussion 599Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Cerebral vasospasm triggered by subarachnoid haemorrhage is one of the major causes of post-haemorrhage morbidity and mortality. Several treatment modalities have been proposed, and none of them are fully effective. METHODS: In this study we treated five patients with prostacyclin suffering vasospasm after a ruptured aneurysm not responding to high i.v. doses of nimodipine. All patients were severely ill, unconscious and in need of intensive care. FINDINGS: A low dose of prostacyclin i.v. infusion for 72 h reversed the vasospasm as measured by transcranial Doppler technique. The mean MCA blood flow velocity decreased from 199 +/- 31 cm/s to 92 +/- 6 cm/s within 72 h after the start of the prostacyclin infusion. CONCLUSIONS: We suggest that low-dose prostacyclin treatment, an old treatment strategy, can be a treatment option in patients with vasospasm not responding to ordinary measures.

  • 41.
    Koskinen, Lars-Owe D.
    Department of Physiology and Medical Biophysics, Biomedical Centre University of Uppsala, Box 572, S-75123 Uppsala, Sweden.
    Cerebral and peripheral blood flow effects of TRH in the rat: a role of vagal nerves1989In: Peptides, ISSN 0196-9781, E-ISSN 1873-5169, Vol. 10, no 5, p. 933-938Article in journal (Refereed)
    Abstract [en]

    The cardiovascular effects of the IV infusion of TRH were studied in the rat. TRH tended to increase the MAP and markedly increased the CBF(tot) in the control group, in vagotomized animals and in methylatropine-pretreated rats. A marked vasodilation was noted in the pancreas, gastric mucosa, duodenum and cardiac muscle. This effect was turned to vasoconstriction, the heart excluded, in vagotomized animals. Muscarinic blockade attenuated the vasodilating effect of TRH in the duodenum and gastric mucosa. The results indicate that TRH elicits cerebral vasodilation and a partly nonmuscarinic parasympathetically mediated vasodilation in several gastrointestinal organs in parallel with a vasoconstriction which is unmasked by vagotomy.

  • 42.
    Koskinen, Lars-Owe D.
    Department of Physiology and Medical Biophysics, Biomedical Centre, University of Uppsala, Uppsala, Sweden.
    Effect of low intravenous doses of TRH, acid-TRH and cyclo(His-Pro) on cerebral and peripheral blood flows.1986In: British Journal of Pharmacology, ISSN 0007-1188, E-ISSN 1476-5381, Vol. 87, no 3, p. 509-519Article in journal (Refereed)
    Abstract [en]

    Local cerebral and peripheral blood flow in conscious and anaesthetized rabbits were investigated with the microsphere method, before and after the i.v. administration of 25 or 50 micrograms kg-1 thyrotropin-releasing hormone (TRH). Before the experiment, the cervical sympathetic chain was sectioned on one side in order to evaluate the possible effect of the sympathetic nerves on cranial and extracranial blood flows. Blood flow was also determined in anaesthetized rabbits before and after the administration of the TRH metabolites cyclo(His-Pro) and acid-TRH and after subsequent administration of 50 micrograms kg-1 TRH. TRH caused an increase in mean arterial blood pressure (MAP) of about 1 to 2 kPa whereas cyclo(His-Pro) and acid-TRH had no effect on MAP. In the anaesthetized animal an increase in total cerebral blood flow (CBFtot), from 71 +/- 7 to 107 +/- 12 g min-1 100 g-1 (P less than 0.05) was observed on the sympathetic intact side after 25 micrograms kg-1 TRH and a further increase to 130 +/- 9 g min-1 100g-1 (P less than 0.01) after 50 micrograms kg-1 TRH. A similar effect was observed on the sympathotomized side. An effect on CBF in the conscious animal was not detected. The control CBFtot (104 +/- 8 g min-1 100g-1) was higher in these animals than in the anaesthetized animals (P less than 0.02). Neither cyclo(His-Pro) nor acid-TRH mimicked the effect of TRH on CBF. In several peripheral tissues, e.g. skin, pancreas and gastric mucosa, a reduction in blood flow was noted after the administration of TRH in both anaesthetized and conscious rabbits. It was concluded that TRH can induce cerebral vasodilatation in animals with a depressed CBF, whereas the vasoconstrictor effect of TRH in peripheral organs is not markedly affected by the state of consciousness.

  • 43.
    Koskinen, Lars-Owe D.
    Department of Physiology and Medical Biophysics, Biomedical Centre, University of Uppsala, Uppsala, Sweden..
    Effects of raised intracranial pressure on regional cerebral blood flow: a comparison of effects of naloxone and TRH on the microcirculation in partial cerebral ischaemia.1985In: British Journal of Pharmacology, ISSN 0007-1188, E-ISSN 1476-5381, Vol. 85, no 2, p. 489-497Article in journal (Refereed)
    Abstract [en]

    The effects on regional cerebral blood flow (rCBF) of raised intracranial pressure (ICP) and of naloxone and thyrotropin releasing hormone (TRH) during this condition were studied in anaesthetized rabbits. The ICP was elevated until a central ischaemic response was observed. The regional blood flow was determined with the microsphere technique before and during elevation of the ICP (ICPe) and after drug treatment. Total CBF was reduced by about 70% during ICPe while the uveal blood flow increased slightly and some other peripheral tissue blood flows remained unaffected. The administration of TRH caused an increase in mean arterial blood pressure (MAP) from 11.9 +/- 0.6 to 14.6 +/- 0.7 kPa and a normalization of the rCBF. In some peripheral tissues, e.g. gastric mucosa and spleen, TRH reduced the blood flow by 53% and 76%, respectively. In blood pressure stabilized animals no effect on rCBF was seen after TRH. Naloxone had no consistent effect on MAP or local blood flow. It was concluded that in the range of cerebral perfusion pressure studied there was a passive relationship between cerebral blood flow and perfusion pressure. The lack of effect of naloxone and the marked effect of TRH during cerebral ischaemia are consistent with a mechanism of action of TRH not related to a 'physiological' antagonism of opioids.

  • 44.
    Koskinen, Lars-Owe D.
    Department of Physiology and Medical Biophysics Biomedical Center University of Uppsala S‐751 23 Uppsala, Sweden.
    Effects of TRH on blood flow and the microcirculation.1989In: Annals of the New York Academy of Sciences, ISSN 0077-8923, E-ISSN 1749-6632, Vol. 553, p. 353-69Article in journal (Refereed)
  • 45.
    Koskinen, Lars-Owe D.
    Department of Physiology and Medical Biophysics, Biomedical Centre, University of Uppsala, Sweden.
    Effects of TRH on cerebral and peripheral blood flows; role of submesencephalic brain stem centres.1986In: Acta Physiologica Scandinavica, ISSN 0001-6772, E-ISSN 1365-201X, Vol. 128, no 2, p. 277-288Article in journal (Refereed)
    Abstract [en]

    The localization of the origin of the cardiovascular effects elicited by thyrotropin-releasing hormone (TRH) was attempted in this study. The radioactively labelled microsphere method was employed for measurement of regional cerebral (rCBF) and peripheral blood flow in albino rabbits anaesthetized with urethane. The effect of 50 micrograms and 2 mg kg-1 TRH (administered i.v.) on rCBF and peripheral blood flow was evaluated in animals with the brain stem sectioned (BSS) at the level of pons-mesencephalon. The cerebral vasodilating effect of TRH was abolished or attenuated, while the peripheral vasoconstriction and increase in mean arterial blood pressure (MAP) was unaffected. Cordotomy at the CI level caused a marked fall in MAP and abolished the pressor response to TRH. In animals infused with angiotensin II, in order to normalize the decreased MAP after cordotomy, TRH caused a marked increase in rCBF. Administration of 50 ng and 5 micrograms TRH into the fourth ventricle caused a marked peripheral vasoconstriction and pressor response. The same amounts of TRH administered into the mesencephalic aqueduct caused a marked increase in rCBF and peripheral vasoconstriction. The results indicate that TRH elicits the pressor and peripheral vasoconstrictor responses from a submesencephalic brain stem region. The increase in rCBF caused by TRH is probably mediated by a somewhat higher submesencephalic level.

  • 46.
    Koskinen, Lars-Owe D.
    Department of Neurosurgery, University Hospital, S-90185 Umeå, Sweden; Department of Physiology and Medical Biophysics, Biomedical Center University of Uppsala, Box 572, S-75123 Uppsala, Sweden.
    Naloxone and TRH affect regional blood flows in the anesthetized rabbit.1991In: Peptides, ISSN 0196-9781, E-ISSN 1873-5169, Vol. 12, no 6, p. 1273-1277Article in journal (Refereed)
    Abstract [en]

    The cardiovascular effects of IV naloxone and a subsequent administration of TRH IV were studied in the rabbit. Naloxone caused a vasodilation in the myocardium and adrenal glands. Naloxone elicited an increment in cerebral blood flow in several regions which attenuated the cerebrovasodilating effect of TRH in a few regions. The blockade of endogenous opioids with naloxone did not modify the peripheral vasoconstricting effect of TRH or affect the vascular effects of TRH mediated by the peripheral sympathetic nerves. The results indicate that naloxone has a vasodilating effect in the myocardium and CNS in anesthetized rabbits. The major part of the cardiovascular effect of TRH is not dependent on mechanisms sensitive to naloxone.

  • 47.
    Koskinen, Lars-Owe D.
    Department of Physiology and Medical Biophysics, Biomedical Centre, University of Uppsala, Uppsala, Sweden.
    The influence of bilateral electrical preganglionic sympathetic stimulation on intra- and extracranial blood flow.1987In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 92, no 2, p. 185-192Article in journal (Refereed)
    Abstract [en]

    The effects of bilateral electrical stimulation (SS) of the cervical sympathetic chain on intra- and extra cerebral blood flows were studied with the labelled microsphere method in the rabbit. Control blood flow was determined before the SS was started. The stimulation frequency was 7 Hz, the impulse duration 2 ms, the intensity 7 V and the stimulation time varied between 1 to 5 minutes before the second blood flow determination. Arterial blood gas values and blood pressure were unaffected by the stimulation. Due to the SS there were blood flow decrements in the extracranial tissues between 60-96%. The blood flow in the eyes, the dura, pineal gland and choroid plexa was markedly reduced during the SS. No obvious effect was elicited by the SS in the regional or total cerebral blood flow. The stimulation to control blood flow ratio ranged between 0.92 +/- 0.08 to 1.13 +/- 0.09 in different parts of the brain. The conclusions are that SS elicits vasoconstriction in several extra- and intracranial nonneuronal tissues and in the eye. Cerebral blood flow is not influenced by the SS.

  • 48.
    Koskinen, Lars-Owe D.
    Department of Physiology and Medical Biophysics, Biomedical Centre, University of Uppsala; Department of Neurosurgery, University Hospital, Umeå; Department of Biomedicine, National Defence Research Establishment, Umeå, Sweden.
    The influence of muscarinic and prostaglandic mechanisms on regional cerebral and peripheral blood flows and on the vascular effects of thyrotropin releasing hormone (TRH).1994In: Acta Physiologica Scandinavica, ISSN 0001-6772, E-ISSN 1365-201X, Vol. 152, no 4, p. 399-406Article in journal (Refereed)
    Abstract [en]

    TRH has pronounced vascular effects. The final transmitter mechanisms of these effects are not fully understood. The present study was conducted in order to elucidate whether these effects are mediated by prostaglandic or muscarinic mechanisms. Muscarinic blockade augmented the vasoconstricting- and pressor effect of TRH; vasodilation in the brain was attenuated only in the caudate nucleus. Indomethacin provoked a decrease in regional cerebral blood flow and in the gastric mucosal blood flow. No effect of indomethacin was observed on the vascular effects of TRH. It is concluded that the cerebral vasodilating and peripheral vasoconstricting effects of TRH are not mediated by prostaglandins. Muscarinic mechanisms are involved in the vasodilating effect of TRH only in the caudate nucleus.

  • 49.
    Koskinen, Lars-Owe D.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Vasodilation: Vascular smooth muscle, Peptides, Autonomic Nerves and Endothelium: Thyrotropin-releasing hormone and cerebral blood flow.1988Book (Refereed)
  • 50. Koskinen, Lars-Owe D.
    et al.
    Algers, Göran
    Missvisande om patienter med handsvett (kor)1995In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 92, no 40, p. 3661-3661Article in journal (Refereed)
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