liu.seSearch for publications in DiVA
Change search
Refine search result
1 - 37 of 37
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the Create feeds function.
  • 1.
    Andersson-Engels, Stefan
    et al.
    Inst för fysik Lunds Tekniska Högskola.
    Pålsson, S
    Backlund, Erik Olof
    IMT LiU.
    Sturnegk, Patrik
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Neurosurgery. Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurosurgery UHL.
    Lundberg, Peter
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Radiation Physics. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Radiation Physics. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Smedby, Örjan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Medical Radiology. Östergötlands Läns Landsting, Centre for Medical Imaging, Department of Radiology UHL. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Svanberg, K
    Eriksson, Ola
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Wårdell, Karin
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    ALA-PpIX Fluorescence and spectroscopy in connection with stereotactic biopsy of human glioblastomas2005In: European Conference on Biomedical Optics,2005, 2005Conference paper (Refereed)
  • 2.
    Bobinski, L
    et al.
    Neurokirurgisk klinik Rekonstruktionscentrum.
    Boström, Sverre
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Neurosurgery. Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurosurgery UHL.
    Hillman, Jan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Neurosurgery. Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurosurgery UHL.
    Theodorsson, Annette
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurosurgery UHL.
    Postoperative pseudoaneurysm of the superficial temporal artery (S.T.A.) treated with Thrombostat® (thrombin glue) injection2004In: Acta Neurochirurgica, ISSN 0001-6268, E-ISSN 0942-0940, Vol. 146, no 9, p. 1039-1041Article in journal (Refereed)
    Abstract [en]

    Background. Pseudo-aneurysm is a rare complication of craniotomy. Blunt injury to the temporal artery region is the usual cause, but still a rare complication. Clinical presentation. A patient with subarachnoid hemorrhage was successfully treated by aneurysm clipping. The patient developed hydrocephalus, and was admitted for a shunt operation seventeen days later. The craniotomy had healed normally, but a palpable temporal lump was present in the skin incision. Intervention. The pulsating mass proved to be a postoperative aneurysm of the superficial temporal artery (S.T.A.) and was successfully occluded with 500 units Thrombostat® (thrombin glue) which was injected into the aneurysm sac using a 22-gauge needle guided by ultrasound. The permanency of the obliteration was verified by ultrasound examination.

  • 3. Bobinski, L
    et al.
    Boström, Sverre
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Neurosurgery. Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurosurgery UHL.
    Zsigmond, Peter
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Neurosurgery. Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurosurgery UHL.
    Theodorsson, Annette
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurosurgery UHL.
    Leptomeningeal cyst due to vacuum extraction delivery in a twin infant2007In: Acta Neurochirurgica, ISSN 0001-6268, E-ISSN 0942-0940, Vol. 149, no 3, p. 319-323Article in journal (Refereed)
    Abstract [en]

    A rare case of a leptomeningeal cyst is reported in a twin male neonate delivered using a vacuum extractor, who presented a huge, non-pulsating, oedematous mass overlying the frontal fontanelle after birth. The mass was initially diagnosed as a cephalo haematoma. Ultrasonography indicated intracranial bleeding and a subsequent CT scan revealed an intraparenchymal bleeding above the left frontal horn, combined with a thin, left-sided, subdural haematoma and subarachnoid haemorrhage in the left Sylvian fissure. Apart from a bulging soft and round formation (2 × 2 × 3 cm) next to the anterior fontanel growing since birth, the neurological development of the infant was normal. MRI examination at the age of 7 months revealed that it consisted of a cystic mass (leptomeningeal cyst) connected to the left frontal horn, stretching right through the brain and also penetrating the dura mater. No signs of the perinatal haematomas were observed at this time. Surgical treatment, with fenestration of the cyst into the frontal horn and a watertight duraplasty with a periosteal flap and thrombin glue covered by small bone chips, was performed at 9 months of age. Due to a residual skull bone defect a second cranioplasty with autologous skull bone was performed three and half years later. During a follow-up period of 12 years the neurological and psychological development of the boy has been indistinguishable to that of his twin brother, indicating the satisfactory outcome of the treatment. © 2007 Springer-Verlag.

  • 4.
    Boström, Sverre
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Neurosurgery. Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurosurgery UHL.
    Bobinski, Lukas
    Zsigmond, Peter
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Neurosurgery. Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurosurgery UHL.
    Nilsson, Inge
    Theodorsson, Annette
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurosurgery UHL.
    A new scaled microgauge for use in neurosurgery2005In: Acta Neurochirurgica, ISSN 0001-6268, E-ISSN 0942-0940, Vol. 147, no 12, p. 1281-1282Article in journal (Refereed)
    Abstract [en]

    A new scaled microgauge is described for measuring anatomical structures during microsurgery. The instrument has a tip marked in millimetres, which can be positioned in any desired angle enabling measurement in confined areas. © Springer-Verlag 2005.

  • 5.
    Eriksson, Ola
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Backlund, Erik-Olof
    Linköping University, Department of Neuroscience and Locomotion, Neurosurgery. Linköping University, Faculty of Health Sciences.
    Lundberg, Peter
    Linköping University, Department of Medicine and Care, Radiation Physics. Linköping University, Faculty of Health Sciences.
    Lindstam, Håkan
    Linköping University, Department of Medicine and Care, Radiology. Linköping University, Faculty of Health Sciences.
    Lindström, Sivert
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Wårdell, Karin
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Experimental radiofrequency brain lesions: a volumetric study2002In: Neurosurgery, ISSN 0148-396X, E-ISSN 1524-4040, Vol. 51, no 3, p. 781-788Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE : This study describes the production, under strictly standardized and controlled conditions, of radiofrequency lesions with identical neurogenerator settings: in vitro in two different albumin solutions (nongelatinous and gelatinous) and in vivo in the thalamus of the pig.

    METHODS : The radiofrequency lesions were investigated in vitro by the use of a specially designed video system and in vivo by magnetic resonance imaging. Moreover, the size of the in vivo lesions was estimated with the use of histological sectioning. The statistical analysis included the calculation of a correlation coefficient for the length, width, and volume for each lesion estimation.

    RESULTS : A high correlation (R = 0.96, P < 0.005; n = 14) was found between clot sizes in the two albumin solutions. Albumin clots generated in gelatinous albumin showed systematically larger volumes. In the pig, two concentric zones were seen in all magnetic resonance images and all histological preparations. The width correlation of the completely coagulated brain tissue (inner zones) was R = 0.94, P < 0.005, and n = 7. The corresponding correlation between magnetic resonance images and gelatinous albumin was R = 0.93, P < 0.005, and n = 7. As a rule, the in vitro clots were smaller than the outer zone but larger than the inner zone of the magnetic resonance imaging-recorded lesions for all of the electrode and temperature combinations tested. In vivo lesions generated with the same electrode and parameter settings showed high reproducibility.

    CONCLUSION : The value of presurgical electrode tests to validate the electrode function and lesion size in vitro has become evident in this study, which shows a high correlation between the in vitro albumin clots and the in vivo lesions observed on magnetic resonance images.

  • 6.
    Fridriksson, Steen
    et al.
    Linköping University, Department of Neuroscience and Locomotion, Neurosurgery. Linköping University, Faculty of Health Sciences.
    Hillman, Jan
    Linköping University, Department of Neuroscience and Locomotion, Neurosurgery. Linköping University, Faculty of Health Sciences.
    Landtblom, Anne-Marie
    Linköping University, Department of Neuroscience and Locomotion, Neurology. Linköping University, Faculty of Health Sciences.
    Boive, Jörgen
    Linköping University, Department of Neuroscience and Locomotion, Neurology. Linköping University, Faculty of Health Sciences.
    Education of referring doctors about sudden onset headache in subarachnoid hemorrhage2001In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 103, no 4, p. 238-242Article in journal (Refereed)
    Abstract [en]

    Objectives – Forty percent of patients with aneurysmal subarachnoid hemorrhage have prodromal warning episodes and difficulties in identifying these events are repeatedly documented. Modifications of diagnostic and referral patterns through educational programs of local doctors may help to identify such patients before a major devastating rupture occurs.

    Materials and methods– A teaching program about sudden onset headache, targeting referring doctors, was systematically applied and its impact on early misdiagnosis of ruptured aneurysms was prospectively studied.

    Results– Forty percent of all studied patients experienced a warning episode, manifested as apoplectic headache, prior to hospitalization. An initial diagnostic error was evident in 12% of the patients. Diagnostic errors were reduced by 77% as a result of continuous interaction between neurosurgeons and local physicians.

    Conclusion– Misdiagnosed warning episodes cause greater loss of lives and higher morbidity on a population basis than does delayed ischemic complications from vasospasm in aneurysmal SAH. Teaching programs focused on local physicians have a profound impact on outcome at low cost.

  • 7.
    Fridriksson, Steen
    et al.
    Linköping University, Department of Neuroscience and Locomotion, Neurosurgery. Linköping University, Faculty of Health Sciences.
    Kimme, Peter
    Linköping University, Department of Medicine and Care, Anaesthesiology. Linköping University, Faculty of Health Sciences.
    Yu, Zhengquan
    Linköping University, Department of Neuroscience and Locomotion, Neurosurgery. Linköping University, Faculty of Health Sciences.
    Mellergård, Pekka
    Linköping University, Department of Neuroscience and Locomotion, Neurosurgery. Linköping University, Faculty of Health Sciences.
    Hillman, Jan
    Linköping University, Department of Neuroscience and Locomotion, Neurosurgery. Linköping University, Faculty of Health Sciences.
    Routine application of neuroprotection in surgery of intracranial aneurysmsManuscript (preprint) (Other academic)
    Abstract [en]

    To evaluate the value of routine application ofneuroprotection and the use of temporary clips (TCL) in every day aneurysm surgery 203 patients with a total of 236 aneurysms were included in the a perioperative moderate hypothermia (MHT, <34° C) protocol. Poor grade patients (Hunt & Hess IV-V) were excluded fi·om the study. Induction of MHT averaged 0.98+/-0.37 hours and was based on a protocol for administration of cold, intravenous crystalloid fluid and barbiturates. Blood pressure was stable throughout MHT. 40% of the patients needed inotropic support during the first 12 postoperative hours. Cardiac arrhythmia was infrequent and when occurring always of benign character. In 8%, pulmonary problems with central venous congestion and/or poor systemic oxygenation occurred.

    In total, temporary clipping was used in 66 cases (mean occlusion time being 10.5 ±7.3 min), 50% of which had not been expected pre-operatively. Overall, 40 aneurysms (75% 1-12 mm in size) ruptured during dissection - corresponding to 20% of the cases without preplanned use of TCL.

    Excluding biasing confounding factors, TCL did not affect the outcome following aneurismal surgery. The study lends support to the idea that TCL should be considered a routine method for all aneurysm surgery.

  • 8.
    Fridriksson, Steen M.
    Linköping University, Department of Neuroscience and Locomotion, Neurosurgery. Linköping University, Faculty of Health Sciences.
    Changing strategies in the treatment of aneurysmal subarachnoid haemorrhage: challenging the second bleed2004Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Despite considerable advances in the management of aneurysmal subarachnoid haemorrhage (SAH) over the past decades, the overall outcome is still disappointing. Currently, not more than six patients out of every ten with a ruptured aneurysm, reaching hospital alive, will recover to a normal life. Apart from the direct effects of the initial haemorrhage, vasospasm and rebleeding clearly stand out as the leading causes of unfavourable results in this capricious disease, and both of these factors seem potentially amenable to further improvement in therapeutic intervention.

    Ever since the concept of early aneurysm surgery gained wider acceptance, the focus of the neurosurgical community has shifted from re bleeding towards the problem of vasospasm and delayed ischaemic neurological deficits (DIND). During recent years, vasospasm has attracted at least five times more attention than rebleeding in terms of published articles, and huge research efforts have been offered in the pursuit of a medical solution to this problem. Although progress has been made in the treatment of vasospasm during the last decades, DIND continues to contribute significantly to unfavourable outcome in the management of aneurysmal SAH victims. Recent series report an average of 13.5% of patients suffering DIND, leading to unfavourable outcome in 7% of all cases reaching hospital for treatment. Contrary to rebleeding, there is a dominance of morbidity (4.5%) over mortality (2.5%).

    Historically, the efforts aimed at reducing the risk of rebleeding have mostly been related to the controversial question of the timing of surgery. The current performance in many centers, with over 90% of all ruptured aneurysms seen being occluded within 24 hours from the haemorrhage, gives the impression that we have reached the ultimate protection against rebleeding, with little left to improve in that field. However, the term rebleeding, as we are used to defming it, apparently only represents a part of a wider spectrum of recurrent aneurysm ruptures. Index haemorrhages preceeded by warning leaks and intraoperative ruptures occurring after index haemonhages also share the features of devastating impact on clinical condition and on outcome, and from a practical point of view it may be meaningful to consider all these recurrent ruptures as a common entity - the second bleed.

    In the studies presented in this thesis, the second bleed has shown to have a profound impact on management outcome in aneurysmal SAH. It accounts for morbidity and mortality in at least 12% of all patients receiving treatment, which is roughly one-third of all patients with poor management outcome. Evidently, prevention of most recurrent bleeds are within the reach of current management protocols. Modifications of strategies in use are presented, that include new guidelines for the pre-neurosurgical care to ensure detection of warning leaks and to provide protection against ultra-early rebleeds, that cannot be reached by early aneurysm occlusion. In the neurosurgical phase, modifications of the surgical protocol allowing for a routine application of intraoperative neuroprotection and liberal use of temporary clipping are advocated.

    By refocusing the second bleed, identification of it's various forms and modification of treatment protocols for ruptured aneurysms aimed at reducing these recurrent bleeds, many losses can be turned into good outcome, at a cost that is much lower than the cost of pursuing the final solution of vasospasm.

    List of papers
    1. Sudden onset headache: a prospective study of features, incidence and causes
    Open this publication in new window or tab >>Sudden onset headache: a prospective study of features, incidence and causes
    Show others...
    2002 (English)In: Cephalalgia, ISSN 0333-1024, E-ISSN 1468-2982, Vol. 22, no 5, p. 354-360Article in journal (Refereed) Published
    Abstract [en]

    Sudden onset headache is a common condition that sometimes indicates a life- threatening subarachnoid haemorrhage (SAH) but is mostly harmless. We have performed a prospective study of 137 consecutive patients with this kind of headache (thunderclap headache = TCH). The examination included a CT scan, CSF examination and follow-up of patients with no SAH during the period between 2 days and 12 months after the headache attack. The incidence was 43 per 100 000 inhabitants > 18 years of age per year; 11.3% of the patients with TCH had SAH. Findings in other patients indicated cerebral infarction (five), intracerebral haematoma (three), aseptic meningitis (four), cerebral oedema (one) and sinus thrombosis (one). Thus no specific finding indicating the underlying cause of the TCH attack was found in the majority of the patients. A slightly increased prevalence of migraine was found in the non-SAH patients (28%). The attacks occurred in 11 cases (8%) during sexual activity and two of these had an SAH. Nausea, neck stiffness, occipital location and impaired consciousness were significantly more frequent with SAH but did not occur in all cases. Location in the temporal region and pressing headache quality were the only features that were more common in non-SAH patients. Recurrent attacks of TCH occurred in 24% of the non-SAH patients. No SAH occurred later in this group, nor in any of the other patients. It was concluded that attacks caused by a SAH cannot be distinguished from non-SAH attacks on clinical grounds. It is important that patients with their first TCH attack are investigated with CT and CSF examination to exclude SAH, meningitis or cerebral infarction. The results from this and previous studies indicate that it is not necessary to perform angiography in patients with a TCH attack, provided that no symptoms or signs indicate a possible brain lesion and a CT scan and CSF examination have not indicated SAH.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-26956 (URN)10.1046/j.1468-2982.2002.00368.x (DOI)11589 (Local ID)11589 (Archive number)11589 (OAI)
    Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2017-12-13Bibliographically approved
    2. Education of referring doctors about sudden onset headache in subarachnoid hemorrhage
    Open this publication in new window or tab >>Education of referring doctors about sudden onset headache in subarachnoid hemorrhage
    2001 (English)In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 103, no 4, p. 238-242Article in journal (Refereed) Published
    Abstract [en]

    Objectives – Forty percent of patients with aneurysmal subarachnoid hemorrhage have prodromal warning episodes and difficulties in identifying these events are repeatedly documented. Modifications of diagnostic and referral patterns through educational programs of local doctors may help to identify such patients before a major devastating rupture occurs.

    Materials and methods– A teaching program about sudden onset headache, targeting referring doctors, was systematically applied and its impact on early misdiagnosis of ruptured aneurysms was prospectively studied.

    Results– Forty percent of all studied patients experienced a warning episode, manifested as apoplectic headache, prior to hospitalization. An initial diagnostic error was evident in 12% of the patients. Diagnostic errors were reduced by 77% as a result of continuous interaction between neurosurgeons and local physicians.

    Conclusion– Misdiagnosed warning episodes cause greater loss of lives and higher morbidity on a population basis than does delayed ischemic complications from vasospasm in aneurysmal SAH. Teaching programs focused on local physicians have a profound impact on outcome at low cost.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-27678 (URN)10.1034/j.1600-0404.2001.d01-27.x (DOI)12416 (Local ID)12416 (Archive number)12416 (OAI)
    Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2017-12-13Bibliographically approved
    3. Immediate administration of tranexamic acid and reduced incidence of early rebleeding after aneurysmal subarachnoid hemorrhage: a prospective randomized study
    Open this publication in new window or tab >>Immediate administration of tranexamic acid and reduced incidence of early rebleeding after aneurysmal subarachnoid hemorrhage: a prospective randomized study
    Show others...
    2002 (English)In: Journal of Neurosurgery, ISSN 0022-3085, E-ISSN 1933-0693, Vol. 97, no 4, p. 771-778Article in journal (Refereed) Published
    Abstract [en]

    Object. By pursuing a policy of very early aneurysm treatment in neurosurgical centers, in-hospital rebleeds can be virtually eliminated. Nonetheless, as many as 15% of patients with aneurysm rupture suffer ultraearly rebleeding with high mortality rates, and these individuals are beyond the reach of even the most ambitious protocol for diagnosis and referral. Only drugs given immediately after the diagnosis of subarachnoid hemorrhage (SAH) has been established at the local hospital level can, in theory, contribute to the minimization of such ultraearly rebleeding. The object of this randomized, prospective, multicenter study was to assess the efficacy of short-term antifibrinolytic treatment with tranexamic acid in preventing rebleeding.

    Methods. Only patients suffering SAH verified on computerized tomography (CT) scans within 48 hours prior to the first hospital admission were included. A 1-g dose of tranexamic acid was given intravenously as soon as diagnosis of SAH had been verified in the local hospitals (before the patients were transported), followed by doses of 1 g every 6 hours until the aneurysm was occluded; this treatment did not exceed 72 hours. In this study, 254 patients received tranexamic acid and 251 patients were randomized as controls. Age, sex, Hunt and Hess and Fisher grade distributions, as well as aneurysm locations, were congruent between the groups. Outcome was assessed at 6 months post-SAH by using the Glasgow Outcome Scale (GOS). Vasospasm and delayed ischemic neurological deficits were classified according to clinical findings as well as by transcranial Doppler (TCD) studies. All events classified as rebleeding were verified on CT scans or during surgery.

    Conclusions. More than 90% of patients reached the neurosurgical center within 12 hours of their first hospital admission after SAH; 70% of all aneurysms were clipped or coils were inserted within 24 hours of the first hospital admission. Given the protocol, only one rebleed occurred later than 24 hours after the first hospital admission. Despite this strong emphasis on early intervention, however, a cluster of 27 very early rebleeds still occurred in the control group within hours of randomization into the study, and 13 of these patients died. In the tranexamic acid group, six patients rebled and two died. A reduction in the rebleeding rate from 10.8 to 2.4% and an 80% reduction in the mortality rate from early rebleeding with tranexamic acid treatment can therefore be inferred. Favorable outcome according to the GOS increased from 70.5 to 74.8%. According to TCD measurements and clinical findings, there were no indications of increased risk of either ischemic clinical manifestations or vasospasm that could be linked to tranexamic acid treatment. Neurosurgical guidelines for aneurysm rupture should extend also into the preneurosurgical phase to guarantee protection from ultraearly rebleeds. Currently available antifibrinolytic drugs can provide such protection, and at low cost. The number of potentially saved lives exceeds those lost to vasospasm.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-27755 (URN)10.3171/jns.2002.97.4.0771 (DOI)12500 (Local ID)12500 (Archive number)12500 (OAI)
    Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2017-12-13Bibliographically approved
    4. Intraoperative complications in aneurysm surgery: a prospective national study
    Open this publication in new window or tab >>Intraoperative complications in aneurysm surgery: a prospective national study
    Show others...
    2002 (English)In: Journal of Neurosurgery, ISSN 0022-3085, E-ISSN 1933-0693, Vol. 96, no 3, p. 515-522Article in journal (Refereed) Published
    Abstract [en]

    Object. With increasing use of endovascular procedures, the number of aneurysms treated surgically will decline. In this study the authors review complications related to the surgical treatment of aneurysms and address the issue of maintaining quality standards on a national level.

    Methods. A prospective, nonselected amalgamation of every aneurysm case treated in five of six neurosurgical centers in Sweden during 1 calendar year was undertaken (422 patients; 7.4 persons/100,000 population/year). The treatment protocols at these institutions were very similar. Outcome was assessed using clinical end points. In this series, 84.1% of the patients underwent surgery, and intraoperative complications occurred in 30% of these procedures. Poor outcome from technical complications was seen in 7.9% of the surgically treated patients. Intraoperative aneurysm rupture accounted for 60% and branch sacrifice for 12% of all technical difficulties. Although these complications were significantly related to aneurysm base geometry and the competence of the surgeon, problems still occurred apparently at random and also in the best of hands (17%). The temporary mean occlusion time in the patients who suffered intraoperative aneurysm rupture was twice as long as the temporary arrest of blood flow performed to aid dissection.

    Conclusions. The results obtained in this series closely reflect the overall management results of this disease and support the conclusion that surgical complications causing a poor outcome can be estimated on a large population-based scale. Intraoperative aneurysm rupture was the most common and most devastating technical complication that occurred. Support was found for a more liberal use of temporary clips early during dissection, regardless of the experience of the surgeon. Temporary regional interruption of arterial blood flow should be a routine method for aneurysm surgery on an everyday basis. A random occurrence of difficult intraoperative problems was clearly shown, and this factor of unpredictability, which is present in any preoperative assessment of risk, strengthens the case for recommending neuroprotection as a routine adjunct to virtually every aneurysm operation, regardless of the surgeon's experience.

    Keywords
    intracranial aneurysm, intraoperative aneurysm rupture, complication, hypothermia, neuroprotection
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-27754 (URN)10.3171/jns.2002.96.3.0515 (DOI)12499 (Local ID)12499 (Archive number)12499 (OAI)
    Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2017-12-13Bibliographically approved
    5. Routine application of neuroprotection in surgery of intracranial aneurysms
    Open this publication in new window or tab >>Routine application of neuroprotection in surgery of intracranial aneurysms
    Show others...
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    To evaluate the value of routine application ofneuroprotection and the use of temporary clips (TCL) in every day aneurysm surgery 203 patients with a total of 236 aneurysms were included in the a perioperative moderate hypothermia (MHT, <34° C) protocol. Poor grade patients (Hunt & Hess IV-V) were excluded fi·om the study. Induction of MHT averaged 0.98+/-0.37 hours and was based on a protocol for administration of cold, intravenous crystalloid fluid and barbiturates. Blood pressure was stable throughout MHT. 40% of the patients needed inotropic support during the first 12 postoperative hours. Cardiac arrhythmia was infrequent and when occurring always of benign character. In 8%, pulmonary problems with central venous congestion and/or poor systemic oxygenation occurred.

    In total, temporary clipping was used in 66 cases (mean occlusion time being 10.5 ±7.3 min), 50% of which had not been expected pre-operatively. Overall, 40 aneurysms (75% 1-12 mm in size) ruptured during dissection - corresponding to 20% of the cases without preplanned use of TCL.

    Excluding biasing confounding factors, TCL did not affect the outcome following aneurismal surgery. The study lends support to the idea that TCL should be considered a routine method for all aneurysm surgery.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-84851 (URN)
    Available from: 2012-10-24 Created: 2012-10-24 Last updated: 2012-10-24Bibliographically approved
  • 9.
    Fridriksson, Steen
    et al.
    Linköping University, Department of Neuroscience and Locomotion, Neurosurgery. Linköping University, Faculty of Health Sciences.
    Säveland, Hans
    Jakobsson, Karl-Erik
    Edner, Göran
    Zygmunt, Stefan
    Brandt, Lennart
    Hillman, Jan
    Linköping University, Department of Neuroscience and Locomotion, Neurosurgery. Linköping University, Faculty of Health Sciences.
    Intraoperative complications in aneurysm surgery: a prospective national study2002In: Journal of Neurosurgery, ISSN 0022-3085, E-ISSN 1933-0693, Vol. 96, no 3, p. 515-522Article in journal (Refereed)
    Abstract [en]

    Object. With increasing use of endovascular procedures, the number of aneurysms treated surgically will decline. In this study the authors review complications related to the surgical treatment of aneurysms and address the issue of maintaining quality standards on a national level.

    Methods. A prospective, nonselected amalgamation of every aneurysm case treated in five of six neurosurgical centers in Sweden during 1 calendar year was undertaken (422 patients; 7.4 persons/100,000 population/year). The treatment protocols at these institutions were very similar. Outcome was assessed using clinical end points. In this series, 84.1% of the patients underwent surgery, and intraoperative complications occurred in 30% of these procedures. Poor outcome from technical complications was seen in 7.9% of the surgically treated patients. Intraoperative aneurysm rupture accounted for 60% and branch sacrifice for 12% of all technical difficulties. Although these complications were significantly related to aneurysm base geometry and the competence of the surgeon, problems still occurred apparently at random and also in the best of hands (17%). The temporary mean occlusion time in the patients who suffered intraoperative aneurysm rupture was twice as long as the temporary arrest of blood flow performed to aid dissection.

    Conclusions. The results obtained in this series closely reflect the overall management results of this disease and support the conclusion that surgical complications causing a poor outcome can be estimated on a large population-based scale. Intraoperative aneurysm rupture was the most common and most devastating technical complication that occurred. Support was found for a more liberal use of temporary clips early during dissection, regardless of the experience of the surgeon. Temporary regional interruption of arterial blood flow should be a routine method for aneurysm surgery on an everyday basis. A random occurrence of difficult intraoperative problems was clearly shown, and this factor of unpredictability, which is present in any preoperative assessment of risk, strengthens the case for recommending neuroprotection as a routine adjunct to virtually every aneurysm operation, regardless of the surgeon's experience.

  • 10.
    Gunnarsson, Thorsteinn
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Neurosurgery. Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurosurgery UHL.
    Hillman, Jan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Neurosurgery. Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurosurgery UHL.
    Clinical Usefulness of Bedside Intracranial Morphological Monitoring: Mobile Computerized Tomography in the Neurosurgery Intensive Care Unit.2000In: Neurosurgical Focus, ISSN 1092-0684, Vol. 9Article in journal (Refereed)
  • 11.
    Gunnarsson, Thorsteinn
    et al.
    Linköping University, Department of Neuroscience and Locomotion, Neurosurgery. Linköping University, Faculty of Health Sciences.
    Theodorsson, Annette
    Linköping University, Department of Neuroscience and Locomotion, Neurosurgery. Linköping University, Faculty of Health Sciences.
    Karlsson, Per
    Linköping University, Department of Neuroscience and Locomotion, Neurosurgery. Linköping University, Faculty of Health Sciences.
    Fridriksson, Steen
    Linköping University, Department of Neuroscience and Locomotion, Neurosurgery. Linköping University, Faculty of Health Sciences.
    Boström, Sverre
    Linköping University, Department of Neuroscience and Locomotion, Neurosurgery. Linköping University, Faculty of Health Sciences.
    Persliden, Jan
    Linköping University, Department of Medicine and Care, Radio Physics. Linköping University, Faculty of Health Sciences.
    Johansson, Ingegerd
    Hillman, Jan
    Linköping University, Department of Neuroscience and Locomotion, Neurosurgery. Linköping University, Faculty of Health Sciences.
    Mobile computerized tomography scanning in the neurosurgery intensive care unit: increase in patient safety and reduction of staff workload2000In: Journal of Neurosurgery, ISSN 0022-3085, E-ISSN 1933-0693, Vol. 93, no 3, p. 432-436Article in journal (Refereed)
    Abstract [en]

    Object. Transportation of unstable neurosurgical patients involves risks that may lead to further deterioration and secondary brain injury from perturbations in physiological parameters. Mobile computerized tomography (CT) head scanning in the neurosurgery intensive care (NICU) is a new technique that minimizes the need to transport unstable patients. The authors have been using this device since June 1997 and have developed their own method of scanning such patients.

    Methods. The scanning procedure and radiation safety measures are described. The complications that occurred in 89 patients during transportation and conventional head CT scanning at the Department of Radiology were studied prospectively. These complications were compared with the ones that occurred during mobile CT scanning in 50 patients in the NICU. The duration of the procedures was recorded, and an estimation of the staff workload was made. Two patient groups, defined as high- and medium-risk cases, were studied. Medical and/or technical complications occurred during conventional CT scanning in 25% and 20% of the patients in the high- and medium-risk groups, respectively. During mobile CT scanning complications occurred in 4.3% of the high-risk group and 0% of the medium-risk group. Mobile CT scanning also took significantly less time, and the estimated personnel cost was reduced.

    Conclusions. Mobile CT scanning in the NICU is safe. It minimizes the risk of physiological deterioration and technical mishaps linked to intrahospital transport, which may aggravate secondary brain injury. The time that patients have to remain outside the controlled environment of the NICU is minimized, and the staff's workload is decreased.

  • 12.
    Gunnarsson, Tove
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Neurosurgery. Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurosurgery UHL.
    Leszniewski, W
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Neurosurgery. Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurosurgery UHL.
    Bak, Julia
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Molecular and Immunological Pathology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pathology and Clinical Genetics.
    Davidsson, L
    An intradural cervical chordoma mimicking a neurinoma. Case illustration.2001In: Journal of Neurosurgery, ISSN 0022-3085, E-ISSN 1933-0693, Vol. 95, p. 144-144Article in journal (Refereed)
  • 13.
    Gustafsson, Maria
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Neurosurgery. Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurosurgery UHL.
    Lundberg, Peter
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Radio Physics. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Radiation Physics.
    Jaworski, Jacek
    Landtblom, Anne-Marie
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Absolute quantification of metabolites in white matter using MR spectroscopy in patients with MS and normal MRI scans of the brain.2001In: ECTRIMS 2001 Dublin sept 2001,2001, 2001Conference paper (Refereed)
  • 14.
    Hillman, Jan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Neurosurgery. Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurosurgery UHL.
    Population-based analysis of arteriovenous malformation treatment2001In: Journal of Neurosurgery, ISSN 0022-3085, E-ISSN 1933-0693, Vol. 95, no 4, p. 633-637Article in journal (Refereed)
    Abstract [en]

    Object. The author sought to describe overall management data on cerebral arteriovenous malformations (AVMs) and to focus the actuarial need for different treatment modalities on a population-based scale. Such data would seem important in the planning of regional or national multimodality strategies for the treatment of AVMs. This analysis of a nonselected, consecutive series of patients representing every diagnosed case of cerebral AVM in a population of 1,000,000 over one decade may serve to shed some light on these treatment aspects. Methods. During the 11-year period from 1989 to 1999, data from every patient harboring a cerebral AVM that was presented clinically or discovered incidentally in a strictly defined population of 986,000 people were collected prospectively. No patient was lost to follow up. There were 12.4 de novo diagnosed AVMs per 1,000,000 population per year (135 AVMs). Large high-grade AVMs (Spetzler-Martin classification) were rare, and Grade 1 to 3 lesions represented 85% of the caseload. Hemorrhage was the initial manifestation of AVM in 69.6% of the cases. Intracerebral hematoma was the most common hemorrhagic manifestation occurring in 78 patients. There were 4.4 cases per 1,000,000 population per year of hematomas needing expedient surgical evacuation. In the remaining patients who did not require hematoma surgery, small, critically located Grade 3 and Grade 4 lesions amounted to 1.6 cases per 1,000,000 population per year. There were 5.8 cases per 1,000,000 population per year of Grade 1 to 2 and larger noncritically located Grade 3 malformations. There were 0.5 cases per 1,000,000 population per year of Grade 5 AVMs. The overall outcome in 135 patients was classified as good according to the Glasgow Outcome Scale (Score 5) in 61% of the cases, and the overall mortality rate was 9%. Conclusions. In centers with population-based referral, AVM of the brain is predominantly a disease related to intracranial bleeding, and parenchymal clots have a profound impact on overall management outcome. The rupture of an AVM is as devastating as that of an aneurysm. Aneurysm ruptures are more lethal, whereas AVM rupture tends to result in more neurological disability due to the high occurrence of lobar intracerebral hematoma. In an attempt to quantify the need for different modalities of AVM treatment based on a population of 1,000,000 people, figures for surgeries performed range from six to 10 operations per year and embolization as well as gamma knife surgery procedures range from two to seven per year, depending on the strategy at hand. When using nonsurgical approaches to Grade 1 to 3 lesions, the number of patients requiring treatment with more than one method for obliteration increases drastically as does the potential risk for procedure-related complications.

  • 15.
    Hillman, Jan
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Neurosurgery. Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurosurgery UHL.
    Aneman, Oscar
    Anderson, Chris
    Sjögren, Florence
    Säberg, Carina
    Mellergård, Per Erik
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Neurosurgery. Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurosurgery UHL.
    A microdialysis technique for routine measurement of macromolecules in the injured human brain2005In: Neurosurgery, ISSN 0148-396X, E-ISSN 1524-4040, Vol. 56, no 6, p. 1264-1268Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To evaluate a new intracerebral microdialysis catheter with a high-cutoff membrane and its potential for the study of macromolecules in the human brain. METHODS: Paired intracerebral microdialysis catheters were inserted in 10 patients who became comatose after subarachnoid hemorrhage or traumatic brain injury and were then treated in our neurosurgical unit. The only differences from the routine use of microdialysis in our clinic were the length (20 mm) and cutoff properties of the catheter membranes (100 kD) and the perfusion fluids used (standard perfusion fluid, 3.5% albumin, or Ringer-dextran 60). Samples were weighed (for net fluid fluxes) and analyzed at bedside (for routine metabolites) and later in the laboratory (for total protein and interleukin-6). The in vitro recovery of glucose, glutamate, and glycerol were also investigated under different conditions. RESULTS: Even brief perfusion with standard perfusion fluid resulted in a significant loss of volume from the microdialysis system. For albumin and Ringer-dextran 60 fluid, recovery was comparable to standard settings. Interleukin-6 (highest value close to 25,000 pg/ml) was sampled from all catheters, and total protein was analyzed from catheters perfused with Ringer-dextran 60 (average concentration, 234 μg protein/ml). There were detectable patterns of variations in the concentration of interleukin-6, seemingly related to concomitant variations in intracerebral conditions. In the present study, no direct comparison was made with the standard CMA 70 catheter (CMA Microdialysis, Stockholm, Sweden), but in vivo, the measured mean concentrations of glucose, glycerol, lactate, and pyruvate were comparable to those previously reported from standard catheters. In vitro, the recovery of metabolites was better when using Ringer-dextran 60 compared with albumin. CONCLUSION: Microdialysis catheters with high-cutoff membranes can be used in routine clinical practice, allowing for sampling and analysis of cytokines and other macromolecules.

  • 16.
    Hillman, Jan
    et al.
    Linköping University, Department of Neuroscience and Locomotion, Neurosurgery. Linköping University, Faculty of Health Sciences.
    Fridriksson, Steen
    Linköping University, Department of Neuroscience and Locomotion, Neurosurgery. Linköping University, Faculty of Health Sciences.
    Nilsson, Ola
    Neurosurgical Department, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Yu, Zhengquan
    Linköping University, Department of Neuroscience and Locomotion, Neurosurgery. Linköping University, Faculty of Health Sciences.
    Säveland, Hans
    Neurosurgical Department, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Jakobsson, Karl-Erik
    Neurosurgical Department, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Immediate administration of tranexamic acid and reduced incidence of early rebleeding after aneurysmal subarachnoid hemorrhage: a prospective randomized study2002In: Journal of Neurosurgery, ISSN 0022-3085, E-ISSN 1933-0693, Vol. 97, no 4, p. 771-778Article in journal (Refereed)
    Abstract [en]

    Object. By pursuing a policy of very early aneurysm treatment in neurosurgical centers, in-hospital rebleeds can be virtually eliminated. Nonetheless, as many as 15% of patients with aneurysm rupture suffer ultraearly rebleeding with high mortality rates, and these individuals are beyond the reach of even the most ambitious protocol for diagnosis and referral. Only drugs given immediately after the diagnosis of subarachnoid hemorrhage (SAH) has been established at the local hospital level can, in theory, contribute to the minimization of such ultraearly rebleeding. The object of this randomized, prospective, multicenter study was to assess the efficacy of short-term antifibrinolytic treatment with tranexamic acid in preventing rebleeding.

    Methods. Only patients suffering SAH verified on computerized tomography (CT) scans within 48 hours prior to the first hospital admission were included. A 1-g dose of tranexamic acid was given intravenously as soon as diagnosis of SAH had been verified in the local hospitals (before the patients were transported), followed by doses of 1 g every 6 hours until the aneurysm was occluded; this treatment did not exceed 72 hours. In this study, 254 patients received tranexamic acid and 251 patients were randomized as controls. Age, sex, Hunt and Hess and Fisher grade distributions, as well as aneurysm locations, were congruent between the groups. Outcome was assessed at 6 months post-SAH by using the Glasgow Outcome Scale (GOS). Vasospasm and delayed ischemic neurological deficits were classified according to clinical findings as well as by transcranial Doppler (TCD) studies. All events classified as rebleeding were verified on CT scans or during surgery.

    Conclusions. More than 90% of patients reached the neurosurgical center within 12 hours of their first hospital admission after SAH; 70% of all aneurysms were clipped or coils were inserted within 24 hours of the first hospital admission. Given the protocol, only one rebleed occurred later than 24 hours after the first hospital admission. Despite this strong emphasis on early intervention, however, a cluster of 27 very early rebleeds still occurred in the control group within hours of randomization into the study, and 13 of these patients died. In the tranexamic acid group, six patients rebled and two died. A reduction in the rebleeding rate from 10.8 to 2.4% and an 80% reduction in the mortality rate from early rebleeding with tranexamic acid treatment can therefore be inferred. Favorable outcome according to the GOS increased from 70.5 to 74.8%. According to TCD measurements and clinical findings, there were no indications of increased risk of either ischemic clinical manifestations or vasospasm that could be linked to tranexamic acid treatment. Neurosurgical guidelines for aneurysm rupture should extend also into the preneurosurgical phase to guarantee protection from ultraearly rebleeds. Currently available antifibrinolytic drugs can provide such protection, and at low cost. The number of potentially saved lives exceeds those lost to vasospasm.

  • 17.
    Hillman, Jan
    et al.
    Linköping University, Department of Neuroscience and Locomotion, Neurosurgery. Linköping University, Faculty of Health Sciences.
    Milos, Peter
    Linköping University, Department of Neuroscience and Locomotion, Neurosurgery. Linköping University, Faculty of Health Sciences.
    Zhengquan, Yu
    Linköping University, Department of Neuroscience and Locomotion, Neurosurgery. Linköping University, Faculty of Health Sciences.
    Sjögren, Florence
    Linköping University, Department of Biomedicine and Surgery, Dermatology. Linköping University, Faculty of Health Sciences.
    Anderson, Chris
    Linköping University, Department of Biomedicine and Surgery, Dermatology. Linköping University, Faculty of Health Sciences.
    Mellergård, Pekka
    Linköping University, Department of Neuroscience and Locomotion, Neurosurgery. Linköping University, Faculty of Health Sciences.
    Intracerebral microdialysis in neurosurgical intensive care patients utilising catheters with different molecular cut-off (20 and 100 kD)2006In: Acta Neurochirurgica, ISSN 0001-6268, E-ISSN 0942-0940, Vol. 148, no 3, p. 319-324Article in journal (Refereed)
    Abstract [en]

    Objective. To compare the properties of a new intracerebral micro-dialysis catheter with a high cut-off membrane (molecular cut-off 100 kDalton) with a standard catheter (CMA70, molecular cut-off 20 kDalton).

    Methods. Paired intracerebral microdialysis catheters were inserted in fifteen comatose patients treated in a neurosurgical intensive care unit following subarachnoid haemorrhage or traumatic brain injury. The high-cut-off catheter (D100) differed from the CMA 70 catheter by the length (20 mm) and cut-off properties of the catheter membranes (100 kDalton) and the perfusion fluids used (Ringer-Dextran 60). Samples were collected every 4–6 hours, analyzed bedside (for glucose, glutamate, glycerol, lactate, pyruvate and urea) and later in the laboratory (for total protein).

    Results. Fluid recovery was similar for the two types of catheters, but significantly more protein was recovered by the D100 catheter. The recovery of glycerol and pyruvate did not differ, while minor differences in recovery of glutamate and glucose were observed. The recovery of lactate was considerably lower in the D100 catheter (p < 0.01), influencing the lactate/pyruvate-ratio. The patterns of concentration changes over time were consistent for all metabolites, and independent of type of catheter.

    Conclusion. Microdialysis catheters with high cut-off membranes can be used in routine clinical practice in the NSICU, adding the possibility of macro-molecule sampling from the extracellular space during monitoring.

  • 18.
    Hillman, Jan
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Neurosurgery. Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurosurgery UHL.
    Sturnegk, Patrik
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Neurosurgery. Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurosurgery UHL.
    Yonas, H
    Heron, J
    Sandborg, Michael
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Radiation Physics. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Radiation Physics.
    Gunnarsson, Thorsteinn
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Neurosurgery. Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurosurgery UHL.
    Mellergård, Per Erik
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Neurosurgery. Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurosurgery UHL.
    Bedside monitoring of CBF with xenon-CT and a mobile scanner: A novel method in neurointensive care2005In: British Journal of Neurosurgery, ISSN 0268-8697, E-ISSN 1360-046X, Vol. 19, no 5, p. 395-401Article in journal (Refereed)
    Abstract [en]

    Combining previously independently established techniques our objective was to develop and evaluate a method for bedside qualitative assessment of cerebral blood flow in neurointensive care (NICU) patients. The CT-protocol was optimized using phantoms and comparing a mobile CT-scanner (Tomoscan-M, Philips) with two stationary CT scanners. Thirty-two per cent xenon was delivered with standard equipment (Enhancer 3000). Mean cortical flow in volunteers was 48 ml/min/100 g, with the mean vascular territorial flow varying between 45 and 66 ml/min/100 g. The potential clinical usefulness was illustrated in three patients with vasospasm following subarachnoid haemorrhage. Our conclusion is that quantitative bedside measurements of CBF can be repeatedly performed in an easy and safe way in a standard NICU-setting, using xenon-inhalation and a mobile CT-scanner. The method is useful for the decision-making, and is a good example of how the quality of multi-modality monitoring in the NICU can be developed and further diversified. © The Neurosurgical Foundation.

  • 19.
    Hillman, Jan
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Neurosurgery. Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurosurgery UHL.
    Åneman, Oscar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion.
    Persson, Mikael
    Anderson, Chris
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of dermatology and venereology. Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Dabrosin, Charlotta
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Mellergård, Pekka
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Neurosurgery. Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurosurgery UHL.
    Variations in the response of interleukins in neurosurgical intensive care patients monitored using intracerebral microdialysis2007In: Journal of Neurosurgery, ISSN 0022-3085, E-ISSN 1933-0693, Vol. 106, no 5, p. 820-825Article in journal (Refereed)
    Abstract [en]

    Object. The aim of this study was to make a preliminary evaluation of whether microdialysis monitoring of cytokines and other proteins in severely diseased neurosurgical patients has the potential of adding significant information to optimize care, thus broadening the understanding of the function of these molecules in brain injury. Methods. Paired intracerebral microdialysis catheters with high-cutoff membranes were inserted in 14 comatose patients who had been treated in a neurosurgical intensive care unit following subarachnoidal hemorrhage or traumatic brain injury. Samples were collected every 6 hours (for up to 7 days) and were analyzed at bedside for routine metabolites and later in the laboratory for interleukin (IL)-1 and IL-6, in two patients, vascular endothelial growth factor and cathepsin-D were also checked. Aggregated microprobe data gave rough estimations of profound focal cytokine responses related to morphological tissue injury and to anaerobic metabolism that were not evident from the concomitantly collected cerebrospinal fluid data. Data regarding tissue with no macroscopic evidence of injury demonstrated that IL release not only is elicited in severely compromised tissue but also may be a general phenomenon in brains subjected to stress. Macroscopic tissue injury was strongly linked to IL-6 but not IL-1b activation. Furthermore, IL release seems to be stimulated by local ischemia. The basal tissue concentration level of IL-1b was estimated in the range of 10 to 150 pg/ml, for IL-6, the corresponding figure was 1000 to 20,000 pg/ml. Conclusions. Data in the present study indicate that catheters with high-cutoff membranes have the potential of expanding microdialysis to the study of protein chemistry as a routine bedside method in neurointensive care.

  • 20.
    Kimme, Peter
    et al.
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences.
    Fridriksson, Steen
    Linköping University, Department of Neuroscience and Locomotion, Neurosurgery. Linköping University, Faculty of Health Sciences.
    Engdahl, O.
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences.
    Hillman, Jan
    Linköping University, Department of Neuroscience and Locomotion, Neurosurgery. Linköping University, Faculty of Health Sciences.
    Vegfors, Magnus
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences.
    Sjöberg, Folke
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences.
    Moderate hypothermia for 359 operations to clip cerebral aneurysms2004In: British Journal of Anaesthesia, ISSN 0007-0912, E-ISSN 1471-6771, Vol. 93, no 3, p. 343-347Article in journal (Refereed)
    Abstract [en]

    Background. Experimental data have suggested that hypothermia (32–34°C) may improve outcome after cerebral ischaemia, but its efficacy has not yet been established conclusively in humans. In this study we examined the feasibility and safety of deliberate moderate perioperative hypothermia during operations for subarachnoid aneurysms.

    Methods. A total of 359 operations for intracranial cerebral aneurysms were included in this prospective study. By using cold intravenous infusions (4°C) and convective cooling our aim was to reduce the patient's core temperature to more than 34°C within 1 h before operation. The protocol assessed postoperative complications such as infections, prolonged mechanical ventilation, pulmonary complications and coagulopathies.

    Results. During surgery, the body temperature was reduced to a mean of 32.5 (sd 0.4) °C. Cooling was accomplished at a rate of 4.0 (sd 0.4) °C h−1. All patients were normothermic at 5 (sd 2) h postoperatively. Peri/postoperative complications included circulatory instability (n=36, 10%), arrhythmias (n=17, 5%) coagulation abnormalities and blood transfusion (n=169, 47%), infections (n=29, 8%) and pulmonary complications (infiltrate or oedema while on ventilatory support) (n=97, 27%). Eighteen patients died within 30 days (5%). There was no significant correlation between the extent of hypothermia and any of the complications. However, there was a strong correlation between the occurrence of complications and the severity of the underlying neurological disease as assessed by the Hunt and Hess score.

    Conclusion. Moderate hypothermia accomplished within 1 h of induction of anaesthesia and maintained during surgery for subarachnoid aneurysms appears to be a safe method as far as the risks of peri/postoperative complications such as circulatory instability, coagulation abnormalities and infections are concerned.

  • 21.
    Landtblom, Anne-Marie
    et al.
    Linköping University, Department of Neuroscience and Locomotion, Neurology. Linköping University, Faculty of Health Sciences.
    Boivie, Jörgen
    Linköping University, Department of Neuroscience and Locomotion, Neurology. Linköping University, Faculty of Health Sciences.
    Fridriksson, Steen
    Linköping University, Department of Neuroscience and Locomotion, Neurosurgery. Linköping University, Faculty of Health Sciences.
    Hillman, Jan
    Linköping University, Department of Neuroscience and Locomotion, Neurosurgery. Linköping University, Faculty of Health Sciences.
    Johansson, Gunn
    Linköping University, Department of Neuroscience and Locomotion, Neurology. Linköping University, Faculty of Health Sciences.
    Johansson, Ingegerd
    Linköping University, Department of Medicine and Care, Radiology. Linköping University, Faculty of Health Sciences.
    Åskknallshuvudvärk: oftast ett godartat tillstånd2006In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 103, no 37, p. 2632-2637Article in journal (Refereed)
    Abstract [en]

    We have performed a study of 137 consecutive patients with thunderclap headache (TCH), showing that a large majority of the patients do not have a subarachnoidal haemorrhage (SAH). It is concluded that 11% of all TCH is caused by SAH and that history and findings in the clinical neurological examination cannot discriminate safely between an SAH and a more benign cause. All patients should be investigated with a CT scan and an analyses of the cerebrospinal fluid to exclude a SAH if the CT scan did not show an SAH. The 10-year follow-up showed that none of the patients with TH without SAH had a cerebral haemorrhage of any kind. Pathological results on CT and CSF examinations were found in 14 of the patients with non-SAH TCH, including five with cerebral infarction, three with intracerebral haemorrhage, four with aseptic meningitis and one with venous sinus thrombosis.

  • 22.
    Landtblom, Anne-Marie
    et al.
    Linköping University, Department of Neuroscience and Locomotion, Neurology. Linköping University, Faculty of Health Sciences.
    Fridriksson, Steen
    Linköping University, Department of Neuroscience and Locomotion, Neurosurgery. Linköping University, Faculty of Health Sciences.
    Boivie, Jörgen
    Linköping University, Department of Neuroscience and Locomotion, Neurology. Linköping University, Faculty of Health Sciences.
    Hillman, Jan
    Linköping University, Department of Neuroscience and Locomotion, Neurosurgery. Linköping University, Faculty of Health Sciences.
    Johansson, G.
    Linköping University, Department of Neuroscience and Locomotion, Neurology. Linköping University, Faculty of Health Sciences.
    Johansson, Ingegerd
    Linköping University, Department of Medicine and Care, Radiology. Linköping University, Faculty of Health Sciences.
    Sudden onset headache: a prospective study of features, incidence and causes2002In: Cephalalgia, ISSN 0333-1024, E-ISSN 1468-2982, Vol. 22, no 5, p. 354-360Article in journal (Refereed)
    Abstract [en]

    Sudden onset headache is a common condition that sometimes indicates a life- threatening subarachnoid haemorrhage (SAH) but is mostly harmless. We have performed a prospective study of 137 consecutive patients with this kind of headache (thunderclap headache = TCH). The examination included a CT scan, CSF examination and follow-up of patients with no SAH during the period between 2 days and 12 months after the headache attack. The incidence was 43 per 100 000 inhabitants > 18 years of age per year; 11.3% of the patients with TCH had SAH. Findings in other patients indicated cerebral infarction (five), intracerebral haematoma (three), aseptic meningitis (four), cerebral oedema (one) and sinus thrombosis (one). Thus no specific finding indicating the underlying cause of the TCH attack was found in the majority of the patients. A slightly increased prevalence of migraine was found in the non-SAH patients (28%). The attacks occurred in 11 cases (8%) during sexual activity and two of these had an SAH. Nausea, neck stiffness, occipital location and impaired consciousness were significantly more frequent with SAH but did not occur in all cases. Location in the temporal region and pressing headache quality were the only features that were more common in non-SAH patients. Recurrent attacks of TCH occurred in 24% of the non-SAH patients. No SAH occurred later in this group, nor in any of the other patients. It was concluded that attacks caused by a SAH cannot be distinguished from non-SAH attacks on clinical grounds. It is important that patients with their first TCH attack are investigated with CT and CSF examination to exclude SAH, meningitis or cerebral infarction. The results from this and previous studies indicate that it is not necessary to perform angiography in patients with a TCH attack, provided that no symptoms or signs indicate a possible brain lesion and a CT scan and CSF examination have not indicated SAH.

  • 23.
    Persson, Lennart
    et al.
    Linköping University, Department of Neuroscience and Locomotion, Pathology. Linköping University, Department of Medicine and Care, Pulmonary Medicine. Linköping University, Faculty of Health Sciences.
    Yu, Zhengquan
    Linköping University, Department of Neuroscience and Locomotion, Pathology. Linköping University, Department of Neuroscience and Locomotion, Neurosurgery. Linköping University, Faculty of Health Sciences.
    Tirosh, Oren
    Institute of Biochemistry, Food Science and Nutrition, Faculty of Agricultural, Food and Environmental Quality Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel.
    Eaton, John Wallace
    Linköping University, Department of Neuroscience and Locomotion, Pathology. Linköping University, Faculty of Health Sciences.
    Brunk, Ulf
    Linköping University, Department of Neuroscience and Locomotion, Pathology. Linköping University, Faculty of Health Sciences.
    Prevention of oxidant-induced cell death by lysosomotropic iron chelators2003In: Free Radical Biology & Medicine, ISSN 0891-5849, E-ISSN 1873-4596, Vol. 34, no 10, p. 1295-1305Article in journal (Refereed)
    Abstract [en]

    Intralysosomal iron powerfully synergizes oxidant-induced cellular damage. The iron chelator, desferrioxamine (DFO), protects cultured cells against oxidant challenge but pharmacologically effective concentrations of this drug cannot readily be achieved in vivo. DFO localizes almost exclusively within the lysosomes following endocytic uptake, suggesting that truly lysosomotropic chelators might be even more effective. We hypothesized that an amine derivative of α-lipoamide (LM), 5-[1,2] dithiolan-3-yl-pentanoic acid (2-dimethylamino-ethyl)-amide (α-lipoic acid-plus [LAP]; pKa = 8.0), would concentrate via proton trapping within lysosomes, and that the vicinal thiols of the reduced form of this agent would interact with intralysosomal iron, preventing oxidant-mediated cell damage. Using a thiol-reactive fluorochrome, we find that reduced LAP does accumulate within the lysosomes of cultured J774 cells. Furthermore, LAP is approximately 1,000 and 5,000 times more effective than LM and DFO, respectively, in protecting lysosomes against oxidant-induced rupture and in preventing ensuing apoptotic cell death. Suppression of lysosomal accumulation of LAP (by ammonium-mediated lysosomal alkalinization) blocks these protective effects. Electron paramagnetic resonance reveals that the intracellular generation of hydroxyl radical following addition of hydrogen peroxide to J774 cells is totally eliminated by pretreatment with either DFO (1 mM) or LAP (0.2 μM) whereas LM (200 μM) is much less effective.

  • 24.
    Rossitti, Sandro
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Neurosurgery. Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurosurgery UHL.
    Endovascular coiling of intracranial aneurysms using bioactive coils: A single-center study2007In: Acta Radiologica, ISSN 0284-1851, E-ISSN 1600-0455, Vol. 48, no 5, p. 565-576Article in journal (Refereed)
    Abstract [en]

    Background: Some degree of recanalization is reported in up to one-third of intracranial aneurysms treated with endovascular coiling. A technical development potentially effective in avoiding recanalization is the Matrix Detachable Coil (MDC), which is covered with a biodegradable polymeric material that enhances intra-aneurysmal clot organization and fibrosis. Purpose: To report the initial clinical experience of MDC for endovascular aneurysm coiling in a single-center, single-operator, and well-defined population setting. Material and Methods: 118 aneurysms in 104 patients (73 with subarachnoid hemorrhage, SAH) were embolized with MDC alone (n=52) or combined with bare platinum coils (n=66). Results: Initial aneurysm obliteration was class 1 (complete obliteration) in 45 aneurysms (38.1%), class 2 (residual neck) in 44 (37.3%), and class 3 (residual aneurysm) in 29 (24.6%). Procedure-related morbidity was 4.8%, and mortality 0.96%. Clinical follow-up of 61 patients with SAH (mean 5.9 months, range 1-17 months) showed good outcome (Glasgow Outcome Scale, GOS 4-5) in 39 (63.9%), and poor outcome or death (GOS 1-3) in 22 (36.1%). Imaging follow-up of 73 aneurysms (average 6.5 months, range 1-17 months) showed class 1 in 47 (64.4%), class 2 in 18 (24.7%), and class 3 in eight (10.9%). Recanalization occurred in 11 aneurysms (15%), of which four (5.5%) required re-treatment. Conclusion: This study confirms that aneurysm coiling with MDC is feasible, effective, and safe. © 2007 Taylor and Francis.

  • 25.
    Rossitti, Sandro
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Neurosurgery. Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurosurgery UHL.
    Intra-aneurysmal balloon inflation as an aid to endovascular wide-necked cerebral aneurysm coiling [3]2007In: Klinische Neuroradiologie, ISSN 0939-7116, E-ISSN 1615-6706, Vol. 17, no 2, p. 127-129Article in journal (Refereed)
    Abstract [en]

    [No abstract available]

  • 26.
    Rossitti, Sandro
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Neurosurgery. Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurosurgery UHL.
    Preoperative embolization of lower-falx meningiomas with ethylene vinyl alcohol copolymer: Technical and anatomical aspects2007In: Acta Radiologica, ISSN 0284-1851, E-ISSN 1600-0455, Vol. 48, no 3, p. 321-326Article in journal (Refereed)
    Abstract [en]

    Purpose: To report the feasibility of using ethylene vinyl alcohol copolymer (EVAC) for embolization of lower-falx meningiomas. Material and Methods: Three patients were treated. The procedures were done under general anesthesia. A terminal branch of the middle cerebral artery in the proximity of the tumor was catheterized as near as possible or into the pre-falcine arterial anastomotic network around the superior sagittal sinus, and embolization with EVAC was performed with a standard injection technique. Results: This technique resulted in filling of the tumor-supplying dural arteries including all collaterals from both sides, filling of the dural territory of the tumor circulation, and some obliteration of the tumor's pial supply. On later operation, the tumors could be removed from the inside out with minimal brain retraction. Conclusion: Effective preoperative embolization of lower-falx meningiomas using EVAC is feasible. This technique has a sound anatomical basis, and it can be used with benefit even in falx meningiomas with predominantly pial vascular supply. © 2007 Taylor & Francis.

  • 27.
    Rugarn, Olof
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences.
    Hammar, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences.
    Theodorsson, Annette
    Linköping University, Department of Neuroscience and Locomotion, Neurosurgery. Linköping University, Faculty of Health Sciences.
    Theodorsson, Elvar
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Stenfors, Carina
    Department of Laboratory Medicine, Karolinska Hospital, Stockholm, Sweden.
    Sex differences in neuropeptide distribution in the rat brain1999In: Peptides, ISSN 0196-9781, E-ISSN 1873-5169, Vol. 20, no 1, p. 81-86Article in journal (Refereed)
    Abstract [en]

    We have investigated possible sex differences in the regional concentrations of neuropeptides in the rat brain. Immunoreactive neurotensin (NT), neurokinin A (NKA), galanin (GAL), calcitonin gene-related peptide (CGRP), substance P (SP) and neuropeptide Y (NPY) were measured by radioimmunoassay in frontal cortex, occipital cortex, hippocampus, striatum, hypothalamus and pituitary in male and female pre- and postpubertal rats. Sex differences were found for NPY (p < 0.001), NT (p < 0.01) and GAL (p < 0.05), in particular in hippocampus, striatum, hypothalamus and pituitary, but not for CGRP, SP and NKA. Results from analysis of neuropeptides in one sex may not be entirely applicable to the other.

  • 28.
    Rugarn, Olof
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences.
    Theodorsson, Annette
    Linköping University, Department of Neuroscience and Locomotion, Neurosurgery. Linköping University, Faculty of Health Sciences.
    Hammar, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences.
    Theodorsson, Elvar
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Effects of estradiol, progesterone, and norethisterone on regional concentrations of galanin in the rat brain1999In: Peptides, ISSN 0196-9781, E-ISSN 1873-5169, Vol. 20, no 6, p. 743-748Article in journal (Refereed)
    Abstract [en]

    Concentrations of immunoreactive galanin were compared in eight gross brain regions of ovariectomized female rats treated with either estradiol, estradiol + progesterone, estradiol + norethisterone, or placebo. Higher concentrations with estradiol treatment compared with placebo were found in the pituitary (357%), frontal cortex (162%), occipital cortex (174%), hippocampus (170%), and median eminence (202%). A more profound difference with addition of progesterone or norethisterone was seen in the pituitary (529% and 467%, respectively). Sex steroids, particularly estradiol, modulate galanin concentrations not only in reproductive, but also in nonreproductive, brain regions.

  • 29.
    Skau, T.
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Vascular surgery. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Hillman, Jan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Neurosurgery. Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurosurgery UHL.
    Harder, Henrik
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Oto-Rhiono-Laryngology and Head & Neck Surgery. Östergötlands Läns Landsting, RC - Rekonstruktionscentrum, ÖNH - Öron- Näsa- Halskliniken.
    Magnusson, Bengt
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Oto-Rhiono-Laryngology and Head & Neck Surgery. Östergötlands Läns Landsting, RC - Rekonstruktionscentrum, ÖNH - Öron- Näsa- Halskliniken.
    Surgical treatment of distal, extracranial, internal carotid artery aneurysms involving the base of the skull - A multidisciplinary approach2000In: European Journal of Vascular and Endovascular Surgery, ISSN 1078-5884, E-ISSN 1532-2165, Vol. 20, no 3, p. 308-311Article in journal (Refereed)
    Abstract [en]

    [No abstract available]

  • 30.
    Sturnegk, Patrik
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Neurosurgery. Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurosurgery UHL.
    Mellergård, Pekka
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Neurosurgery. Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurosurgery UHL.
    Yonas, H
    Theodorsson, Annette
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurosurgery UHL.
    Hillman, Jan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Neurosurgery. Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurosurgery UHL.
    Potential use of quantitative bedside CBF monitoring (Xe-CT) for decision making in neurosurgical intensive care2007In: British Journal of Neurosurgery, ISSN 0268-8697, E-ISSN 1360-046X, Vol. 21, no 4, p. 332-339Article in journal (Refereed)
    Abstract [en]

    During a 3-year period, mobile xenon-computerized tomography (Xe-CT) for bedside quantitative assessment of cerebral blood flow was used as an integrated tool for decision making during the care of complicated patients in our neurosurgical intensive care units (NSICU), in an attempt to make a preliminary evaluation regarding the usefulness of this method in routine work in the neurosurgical intensive care. With approximately 200 studies involving 75 patients, we identified six different categories where the use of bedside Xe-CT significantly influenced (or, with more experience, could have influenced) the decision making, or facilitated the handling of patients. These categories included identification of problems not apparent from other types of monitoring, avoidance of adverse effects from treatment, titration of standard treatments, evaluation of the vascular resistance reserve, assessment of adequate perfusion pressure and better utilization of resources from access to the bedside cerebral blood flow (CBF) technology. We conclude that quantitative bedside measurements of CBF could be an important addition to the diagnostic and monitoring arsenal of NSICU-tools. © The Neurosurgical Foundation.

  • 31.
    Theodorsson, Annette
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Neurosurgery. Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurosurgery UHL.
    Gunnarsson, Thorsteinn
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Neurosurgery. Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurosurgery UHL.
    Karlsson, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Neurosurgery. Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurosurgery UHL.
    Hillman, Jan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Neurosurgery. Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurosurgery UHL.
    Mobile CT Scanner in the Neurosurgery Intensive Care Unit (NICU): Improving the Bedside Scanning Procedure2001In: Proceedings 12th World Congress of Neurosurgery :: Sydney, Australia September 16 - 20, 2001 World Federation of Neurosurgical SocietiesBook of Proceedings 12th World Congress of Neurosurgery / [ed] Peter Reilly; Glenn McCulloch, Linköping: Linköpings universitet , 2001, p. 400-403Chapter in book (Other academic)
  • 32. Ulfarsson, Elfar
    et al.
    Karström, Alexandra
    Yin, Shucheng
    Girnita, Ada
    Vasilcanu, Daiana
    Thoren, Marja
    Kratz, Gunnar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of surgery. Östergötlands Läns Landsting, Reconstruction Centre, Department of Plastic Surgery, Hand surgery UHL.
    Hillman, Jan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Neurosurgery. Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurosurgery UHL.
    Axelson, Magnus
    Larsson, Olle
    Girnita, Leonard
    Expression and growth dependency of the insulin-like growth factor I receptor in craniopharyngioma cells: A novel therapeutic approach2005In: Clinical Cancer Research, ISSN 1078-0432, E-ISSN 1557-3265, Vol. 11, no 13, p. 4674-4680Article in journal (Refereed)
    Abstract [en]

    Craniopharyngioma is a rare benign intracranial epithelial tumor that, however, often recurs and sometimes kills the affected patients, one-third of which are children. In many cases, the patients acquire growth hormone deficiency and postoperatively need substitution. Generally, growth hormone promotes local release of insulin-like growth factor I (IGF-I), which in turn activates the IGF-I receptor (IGF-IR) if present. Together, these circumstances raise the question whether IGF-IR may be involved in craniopharyngioma growth. To address this issue, we analyzed phenotypically well-characterized primary low-passage craniopharyngioma cell lines from nine different patients for IGF-IR expression and IGF-I dependency. Two of the cell lines showed no/very low expression of the receptor and was independent on IGF-I, whereas five cell lines exhibited a strong expression and was clearly contingent on IGF-I. The two remaining cell lines had low receptor expression and IGF-I dependency. Upon treatment with an IGF-IR inhibitor, cells with high IGF-IR expression responded promptly with decreased Akt phosphorylation followed by growth arrest. These responses were not seen in cells with no/very low receptor expression. Growth of cell lines with tow IGF-IR expression was only slightly affected by IGF-IR inhibition. Taken together, our data suggest that IGF-IR may be involved in the growth of a subset of craniopharyngiomas and points to the possibility of the involvement of IGF-IR inhibitors as a treatment modality to obtain complete tumor-free conditions before growth hormone substitution. © 2005 American Association for Cancer Research.

  • 33.
    Yu, Zhengquan
    Linköping University, Department of Neuroscience and Locomotion, Neurosurgery. Linköping University, Department of Neuroscience and Locomotion, Pathology. Linköping University, Faculty of Health Sciences.
    Proton trapping in the cellular acidic vacuolar compartment: lysosomal mechanisms in apoptosis/necrosis and iron chelation2003Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Under ischemic conditions, a number of cytotoxic metabolic products are formed. Reactive oxygen species are known to be important mediators of progressive ischemic cell injury, and the synergistic damage to cells caused by the combination of such oxygen species and redox-active iron is well appreciated. The acidic interior of lysosome leads to the trapping of substances with high pK4 values. A large variety of molecules, being weak bases, may thus concentrate within this acidic vacuolar compartment, potentially leading to both beneficial and detrimental effects. A major part of the intracellular pool of redoxactive iron is likely to be located in the lysosomal compartment, and iron chelators that are lysosomotropic due to high pK4 values may prove to be important pharmacological tools to protect the brain from oxidative stress. Among a variety of substances formed in the ischemic penumbra zone is the polyamine metabolite, 3-aminopropanal (3-AP), a substance of extreme neurotoxicity. 3-AP is a weak base and may theoretically exert its toxic action through induction of cell death after intralysosomal accumulation.

    On the 1774 mouse histiocytic lymphoma cell line, we used the common lysosomotropic agent NH3 to increase lysosomal pH, the lysosomotropic iron chelator, 5-[1,2] dithiolan-3-yl-pentanoic acid (2-dimethylamino-ethyl)-amide (LAP) and the lysosomotropic iron binder, WR-1065, a metabolite of amifostine, as tools to determine that proton trapping within the lysosomal acidic vacuolar compartment plays an important role in oxidative stress-induced apoptosis. We also used another lysosomotropic agent, 3-AP, on the J774 cell line and on the SH-SY5Y human neuroblastoma cell line. The results indicate that proton trapping of this toxin within the lysosome might explain its toxicity to cells.

    Sulfide-silver cytochemical detection of iron revealed a pronounced decrease in the lysosomal content of redox-active iron following reduced acidity of the lysosome, and electron spin-resonance studies showed that no hydroxyl radicals [OH] were formed from hydrogen peroxide under these conditions. This suggests that lysosomes contain most of the free, redox-active iron. In further support of this idea, the lysosomotropic agents LAP and WR-1065 were found to be 5000 and 2500 times more effective, respectively, in protecting cells from oxidative stress, compared with the well-known iron chelator desferrioxamine [DFO]. Evidence was obtained that LAP and WR-1065 exerted their effect on intralysosomal redox-active iron, and that the effect was linked to the acidity of the lysosome. Being weak bases (LAP, pKa = 8.0; WR-1065, pKa = 9.2), these compounds accumulate intralysosomally by proton trapping. The neurotoxic effect of 3-AP (pKa = 9.3) could be linked to a dose-dependent induction of cell death, most likely based on intralysosomal proton trapping of this molecule followed by lysosomal rupture. The lysosomal rupture seems to induce a chain of intracellular events (including generation of oxidative stress), leading to mitochondrial damage directly or indirectly caused by the release of lysosomal proteases.

    We conclude that the low pH of the lysosome may both serve to attract basic toxins, such as 3-AP, and promote the accumulation of protective agents, such as LAP and WR-1065. Prevention of lysosomal damage from both oxidants and neurotoxins by lysosomotropic agents has great potential therapeutic utility.

    List of papers
    1. Intralysosomal iron: a major determinant of oxidant-induced cell death
    Open this publication in new window or tab >>Intralysosomal iron: a major determinant of oxidant-induced cell death
    2003 (English)In: Free Radical Biology & Medicine, ISSN 0891-5849, E-ISSN 1873-4596, Vol. 34, no 10, p. 1243-1252Article in journal (Refereed) Published
    Abstract [en]

    As a result of continuous digestion of iron-containing metalloproteins, the lysosomes within normal cells contain a pool of labile, redox-active, low-molecular-weight iron, which may make these organelles particularly susceptible to oxidative damage. Oxidant-mediated destabilization of lysosomal membranes with release of hydrolytic enzymes into the cell cytoplasm can lead to a cascade of events eventuating in cell death (either apoptotic or necrotic depending on the magnitude of the insult). To assess the importance of the intralysosomal pool of redox-active iron, we have temporarily blocked lysosomal digestion by exposing cells to the lysosomotropic alkalinizing agent, ammonium chloride (NH4Cl). The consequent increase in lysosomal pH (from ca. 4.5 to > 6) inhibits intralysosomal proteolysis and, hence, the continuous flow of reactive iron into this pool. Preincubation of J774 cells with 10 mM NH4Cl for 4 h dramatically decreased apoptotic death caused by subsequent exposure to H2O2, and the protection was as great as that afforded by the powerful iron chelator, desferrioxamine (which probably localizes predominantly in the lysosomal compartment). Sulfide-silver cytochemical detection of iron revealed a pronounced decrease in lysosomal content of redox-active iron after NH4Cl exposure, probably due to diminished intralysosomal digestion of iron-containing material coupled with continuing iron export from this organelle. Electron paramagnetic resonance experiments revealed that hydroxyl radical formation, readily detectable in control cells following H2O2 addition, was absent in cells preexposed to 10 mM NH4Cl. Thus, the major pool of redox-active, low-molecular-weight iron may be located within the lysosomes. In a number of clinical situations, pharmacologic strategies that minimize the amount or reactivity of intralysosomal iron should be effective in preventing oxidant-induced cell death.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-27102 (URN)10.1016/S0891-5849(03)00109-6 (DOI)11749 (Local ID)11749 (Archive number)11749 (OAI)
    Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2017-12-13Bibliographically approved
    2. Prevention of oxidant-induced cell death by lysosomotropic iron chelators
    Open this publication in new window or tab >>Prevention of oxidant-induced cell death by lysosomotropic iron chelators
    Show others...
    2003 (English)In: Free Radical Biology & Medicine, ISSN 0891-5849, E-ISSN 1873-4596, Vol. 34, no 10, p. 1295-1305Article in journal (Refereed) Published
    Abstract [en]

    Intralysosomal iron powerfully synergizes oxidant-induced cellular damage. The iron chelator, desferrioxamine (DFO), protects cultured cells against oxidant challenge but pharmacologically effective concentrations of this drug cannot readily be achieved in vivo. DFO localizes almost exclusively within the lysosomes following endocytic uptake, suggesting that truly lysosomotropic chelators might be even more effective. We hypothesized that an amine derivative of α-lipoamide (LM), 5-[1,2] dithiolan-3-yl-pentanoic acid (2-dimethylamino-ethyl)-amide (α-lipoic acid-plus [LAP]; pKa = 8.0), would concentrate via proton trapping within lysosomes, and that the vicinal thiols of the reduced form of this agent would interact with intralysosomal iron, preventing oxidant-mediated cell damage. Using a thiol-reactive fluorochrome, we find that reduced LAP does accumulate within the lysosomes of cultured J774 cells. Furthermore, LAP is approximately 1,000 and 5,000 times more effective than LM and DFO, respectively, in protecting lysosomes against oxidant-induced rupture and in preventing ensuing apoptotic cell death. Suppression of lysosomal accumulation of LAP (by ammonium-mediated lysosomal alkalinization) blocks these protective effects. Electron paramagnetic resonance reveals that the intracellular generation of hydroxyl radical following addition of hydrogen peroxide to J774 cells is totally eliminated by pretreatment with either DFO (1 mM) or LAP (0.2 μM) whereas LM (200 μM) is much less effective.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-27105 (URN)10.1016/S0891-5849(03)00106-0 (DOI)11752 (Local ID)11752 (Archive number)11752 (OAI)
    Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2017-12-13Bibliographically approved
    3. The radioprotective agent, amifostine, suppresses the reactivity of intralysosomal iron
    Open this publication in new window or tab >>The radioprotective agent, amifostine, suppresses the reactivity of intralysosomal iron
    2003 (English)In: Redox report, ISSN 1351-0002, E-ISSN 1743-2928, Vol. 8, no 6, p. 347-355Article in journal (Refereed) Published
    Abstract [en]

    Amifostine (2-[(3-aminopropyl)amino]ethane-thiol dihydrogen phosphate ester; WR-2721) is a radioprotective agent used clinically to minimize damage from radiation therapy to adjacent normal tissues. This inorganic thiophosphate requires dephosphorylation to produce the active, cell-permeant thiol metabolite, WR-1065. The activation step is presumably catalyzed by membrane-bound alkaline phosphatase, activity of which is substantially higher in the endothelium of normal tissues. This site-specific delivery may explain the preferential protection of normal versus neoplastic tissues. Although it was developed several decades ago, the mechanisms through which this agent exerts its protective effects remain unknown. Because WR-1065 is a weak base (pKa = 9.2), we hypothesized that the drug should preferentially accumulate (via proton trapping) within the acidic environment of intracellular lysosomes. These organelles contain abundant 'loose' iron and represent a likely initial target for oxidant- and radiation-mediated damage. We further hypothesized that, within the lysosomal compartment, the thiol groups of WR-1065 would interact with this iron, thereby minimizing iron-catalyzed lysosomal damage and ensuing cell death. A similar mechanism of protection via intralysosomal iron chelation has been invoked for the hexadentate iron chelator, desferrioxamine (DFO; although DFO enters the lysosomal compartment by endocytosis, not proton trapping). Using cultured J774 cells as a model system, we found substantial accumulation of WR-1065 within intracellular granules as revealed by reaction with the thiol-binding fluorochrome, BODIPY FL L-cystine. These granules are lysosomes as indicated by co-localization of BODIPY staining with LysoTracker Red. Compared to 1 mM DFO, cells pre-treated with 0.4 ?M WR-1065 are protected from hydrogen peroxide-mediated lysosomal rupture and ensuing cell death. On a molar basis in this experimental system, WR-1065 is approximately 2500 times more effective than DFO in preventing oxidant-induced lysosomal rupture and cell death. This increased effectiveness is most likely due to the preferential concentration of this weak base within the acidic lysosomal apparatus. By electron spin resonance, we found that the generation of hydroxyl radical, which normally occurs following addition of hydrogen peroxide to J774 cells, is totally blocked by pretreatment with either WR-1065 or DFO. These findings suggest a single and plausible explanation for the radioprotective effects of amifostine and may provide a basis for the design of even more effective radio- and chemoprotective drugs.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-27104 (URN)10.1179/135100003225003384 (DOI)11751 (Local ID)11751 (Archive number)11751 (OAI)
    Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2017-12-13Bibliographically approved
    4. 3-Aminopropanal is a lysosomotropic aldehyde that causes oxidative stress and apoptosis by rupturing lysosomes
    Open this publication in new window or tab >>3-Aminopropanal is a lysosomotropic aldehyde that causes oxidative stress and apoptosis by rupturing lysosomes
    2003 (English)In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 111, no 6, p. 643-652Article in journal (Refereed) Published
    Abstract [en]

    During cerebral ischemia and following trauma, potent cytotoxic polyamine-derived aminoaldehydes form, diffuse, and damage adjacent tissues not directly subjected to the initial insult. One such aldehyde is 3-aminopropanal (3-AP). The mechanisms by which such a small aldehydic compound is excessively cytotoxic have been unclear until recently when we showed that 3-AP, having the structure of a weak lysosomotropic base, concentrates within the acidic vacuolar compartment and causes lysosomal rupture that, in turn, induces caspase activation and apoptotic cell death. Here, using cultured J774 cells and 3-AP as a way to selectively burst lysosomes, we show that moderate lysosomal rupture induces a transient wave of oxidative stress. The start of this oxidative stress period is concomitant with a short period of enhanced mitochondrial membrane potential that later fades and is replaced by a decreased potential before the oxidative stress diminishes. The result of the study suggests that oxidative stress, which has often been described during apoptosis induced by agonists other than oxidative stress per se, may be a consequence of lysosomal rupture with direct and/or indirect effects on mitochondrial respiration and electron transport causing a period of passing enhanced formation of reactive oxygen species.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-27708 (URN)10.1034/j.1600-0463.2003.1110607.x (DOI)12446 (Local ID)12446 (Archive number)12446 (OAI)
    Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2017-12-13Bibliographically approved
    5. Human neuroblastoma (SH-SY5Y) cells are highly sensitive to the lysosomotropic aldehyde 3-aminopropanal
    Open this publication in new window or tab >>Human neuroblastoma (SH-SY5Y) cells are highly sensitive to the lysosomotropic aldehyde 3-aminopropanal
    2004 (English)In: Brain Research, ISSN 0006-8993, E-ISSN 1872-6240, Vol. 1016, no 2, p. 163-169Article in journal (Refereed) Published
    Abstract [en]

    3-Aminopropanal (3-AP), a degradation product of polyamines such as spermine, spermidine and putrescine, is a lysosomotropic small aldehyde that causes apoptosis or necrosis of most cells in culture, apparently by inducing moderate or extensive lysosomal rupture, respectively, and secondary mitochondrial changes. Here, using the human neuroblastoma SH-SY5Y cell line, we found simultaneous occurrence of apoptotic and necrotic cell death when cultures were exposed to 3-AP in concentrations that usually are either nontoxic, or only cause apoptosis. At 30 mM, but not at 10 mM, the lysosomotropic base and proton acceptor NH3 completely blocked the toxic effect of 3-AP, proving that 3-AP is lysosomotropic and suggesting that the lysosomal membrane proton pump of neuroblastoma cells is highly effective, creating a lower than normal lysosomal pH and, thus, extensive intralysosomal accumulation of lysosomotropic drugs. A wave of internal oxidative stress, secondary to changes in mitochondrial membrane potential, followed and gave rise to further lysosomal rupture. The preincubation of cells for 24 h with a chain-breaking free radical-scavenger, α-tocopherol, before exposure to 3-AP, significantly delayed both the wave of oxidative stress and the secondary lysosomal rupture, while it did not interfere with the early 3-AP-mediated phase of lysosomal break. Obviously, the reported oxidative stress and apoptosis/necrosis are consequences of lysosomal rupture with ensuing release of lysosomal enzymes resulting in direct/indirect effects on mitochondrial permeability, membrane potential, and electron transport. The induced oxidative stress seems to act as an amplifying loop causing further lysosomal break that can be partially prevented by α-tocopherol. Perhaps secondary brain damage during a critical post injury period can be prevented by the use of drugs that temporarily raise lysosomal pH, inactivate intralysosomal 3-AP, or stabilize lysosomal membranes against oxidative stress.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-23792 (URN)10.1016/j.brainres.2004.04.075 (DOI)3310 (Local ID)3310 (Archive number)3310 (OAI)
    Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13Bibliographically approved
  • 34.
    Yu, Zhengquan
    et al.
    Linköping University, Department of Neuroscience and Locomotion, Pathology. Linköping University, Department of Neuroscience and Locomotion, Neurosurgery. Linköping University, Faculty of Health Sciences.
    Eaton, John Wallace
    James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky, USA.
    Persson, Lennart
    Linköping University, Department of Neuroscience and Locomotion, Pathology. Linköping University, Department of Medicine and Care, Pulmonary Medicine. Linköping University, Faculty of Health Sciences.
    The radioprotective agent, amifostine, suppresses the reactivity of intralysosomal iron2003In: Redox report, ISSN 1351-0002, E-ISSN 1743-2928, Vol. 8, no 6, p. 347-355Article in journal (Refereed)
    Abstract [en]

    Amifostine (2-[(3-aminopropyl)amino]ethane-thiol dihydrogen phosphate ester; WR-2721) is a radioprotective agent used clinically to minimize damage from radiation therapy to adjacent normal tissues. This inorganic thiophosphate requires dephosphorylation to produce the active, cell-permeant thiol metabolite, WR-1065. The activation step is presumably catalyzed by membrane-bound alkaline phosphatase, activity of which is substantially higher in the endothelium of normal tissues. This site-specific delivery may explain the preferential protection of normal versus neoplastic tissues. Although it was developed several decades ago, the mechanisms through which this agent exerts its protective effects remain unknown. Because WR-1065 is a weak base (pKa = 9.2), we hypothesized that the drug should preferentially accumulate (via proton trapping) within the acidic environment of intracellular lysosomes. These organelles contain abundant 'loose' iron and represent a likely initial target for oxidant- and radiation-mediated damage. We further hypothesized that, within the lysosomal compartment, the thiol groups of WR-1065 would interact with this iron, thereby minimizing iron-catalyzed lysosomal damage and ensuing cell death. A similar mechanism of protection via intralysosomal iron chelation has been invoked for the hexadentate iron chelator, desferrioxamine (DFO; although DFO enters the lysosomal compartment by endocytosis, not proton trapping). Using cultured J774 cells as a model system, we found substantial accumulation of WR-1065 within intracellular granules as revealed by reaction with the thiol-binding fluorochrome, BODIPY FL L-cystine. These granules are lysosomes as indicated by co-localization of BODIPY staining with LysoTracker Red. Compared to 1 mM DFO, cells pre-treated with 0.4 ?M WR-1065 are protected from hydrogen peroxide-mediated lysosomal rupture and ensuing cell death. On a molar basis in this experimental system, WR-1065 is approximately 2500 times more effective than DFO in preventing oxidant-induced lysosomal rupture and cell death. This increased effectiveness is most likely due to the preferential concentration of this weak base within the acidic lysosomal apparatus. By electron spin resonance, we found that the generation of hydroxyl radical, which normally occurs following addition of hydrogen peroxide to J774 cells, is totally blocked by pretreatment with either WR-1065 or DFO. These findings suggest a single and plausible explanation for the radioprotective effects of amifostine and may provide a basis for the design of even more effective radio- and chemoprotective drugs.

  • 35.
    Yu, Zhengquan
    et al.
    Linköping University, Department of Neuroscience and Locomotion, Pathology. Linköping University, Department of Neuroscience and Locomotion, Neurosurgery. Linköping University, Faculty of Health Sciences.
    Li, Wei
    Linköping University, Department of Neuroscience and Locomotion, Pathology. Linköping University, Faculty of Health Sciences.
    Brunk, Ulf
    Linköping University, Department of Neuroscience and Locomotion, Pathology. Linköping University, Faculty of Health Sciences.
    3-Aminopropanal is a lysosomotropic aldehyde that causes oxidative stress and apoptosis by rupturing lysosomes2003In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 111, no 6, p. 643-652Article in journal (Refereed)
    Abstract [en]

    During cerebral ischemia and following trauma, potent cytotoxic polyamine-derived aminoaldehydes form, diffuse, and damage adjacent tissues not directly subjected to the initial insult. One such aldehyde is 3-aminopropanal (3-AP). The mechanisms by which such a small aldehydic compound is excessively cytotoxic have been unclear until recently when we showed that 3-AP, having the structure of a weak lysosomotropic base, concentrates within the acidic vacuolar compartment and causes lysosomal rupture that, in turn, induces caspase activation and apoptotic cell death. Here, using cultured J774 cells and 3-AP as a way to selectively burst lysosomes, we show that moderate lysosomal rupture induces a transient wave of oxidative stress. The start of this oxidative stress period is concomitant with a short period of enhanced mitochondrial membrane potential that later fades and is replaced by a decreased potential before the oxidative stress diminishes. The result of the study suggests that oxidative stress, which has often been described during apoptosis induced by agonists other than oxidative stress per se, may be a consequence of lysosomal rupture with direct and/or indirect effects on mitochondrial respiration and electron transport causing a period of passing enhanced formation of reactive oxygen species.

  • 36.
    Yu, Zhengquan
    et al.
    Linköping University, Department of Neuroscience and Locomotion, Pathology. Linköping University, Department of Neuroscience and Locomotion, Neurosurgery. Linköping University, Faculty of Health Sciences.
    Persson, Lennart
    Linköping University, Department of Neuroscience and Locomotion, Pathology. Linköping University, Department of Medicine and Care, Pulmonary Medicine. Linköping University, Faculty of Health Sciences.
    Eaton, John Wallace
    Linköping University, Department of Neuroscience and Locomotion, Pathology. Linköping University, Faculty of Health Sciences.
    Brunk, Ulf
    Linköping University, Department of Neuroscience and Locomotion, Pathology. Linköping University, Faculty of Health Sciences.
    Intralysosomal iron: a major determinant of oxidant-induced cell death2003In: Free Radical Biology & Medicine, ISSN 0891-5849, E-ISSN 1873-4596, Vol. 34, no 10, p. 1243-1252Article in journal (Refereed)
    Abstract [en]

    As a result of continuous digestion of iron-containing metalloproteins, the lysosomes within normal cells contain a pool of labile, redox-active, low-molecular-weight iron, which may make these organelles particularly susceptible to oxidative damage. Oxidant-mediated destabilization of lysosomal membranes with release of hydrolytic enzymes into the cell cytoplasm can lead to a cascade of events eventuating in cell death (either apoptotic or necrotic depending on the magnitude of the insult). To assess the importance of the intralysosomal pool of redox-active iron, we have temporarily blocked lysosomal digestion by exposing cells to the lysosomotropic alkalinizing agent, ammonium chloride (NH4Cl). The consequent increase in lysosomal pH (from ca. 4.5 to > 6) inhibits intralysosomal proteolysis and, hence, the continuous flow of reactive iron into this pool. Preincubation of J774 cells with 10 mM NH4Cl for 4 h dramatically decreased apoptotic death caused by subsequent exposure to H2O2, and the protection was as great as that afforded by the powerful iron chelator, desferrioxamine (which probably localizes predominantly in the lysosomal compartment). Sulfide-silver cytochemical detection of iron revealed a pronounced decrease in lysosomal content of redox-active iron after NH4Cl exposure, probably due to diminished intralysosomal digestion of iron-containing material coupled with continuing iron export from this organelle. Electron paramagnetic resonance experiments revealed that hydroxyl radical formation, readily detectable in control cells following H2O2 addition, was absent in cells preexposed to 10 mM NH4Cl. Thus, the major pool of redox-active, low-molecular-weight iron may be located within the lysosomes. In a number of clinical situations, pharmacologic strategies that minimize the amount or reactivity of intralysosomal iron should be effective in preventing oxidant-induced cell death.

  • 37.
    Zhengquan, Yu
    et al.
    Linköping University, Department of Neuroscience and Locomotion, Pathology. Linköping University, Department of Neuroscience and Locomotion, Neurosurgery. Linköping University, Faculty of Health Sciences.
    Li, Wei
    Linköping University, Department of Neuroscience and Locomotion, Pathology. Linköping University, Faculty of Health Sciences.
    Hillman, Jan
    Linköping University, Department of Neuroscience and Locomotion, Neurosurgery. Linköping University, Faculty of Health Sciences.
    Brunk, Ulf
    Linköping University, Department of Neuroscience and Locomotion, Pathology. Linköping University, Faculty of Health Sciences.
    Human neuroblastoma (SH-SY5Y) cells are highly sensitive to the lysosomotropic aldehyde 3-aminopropanal2004In: Brain Research, ISSN 0006-8993, E-ISSN 1872-6240, Vol. 1016, no 2, p. 163-169Article in journal (Refereed)
    Abstract [en]

    3-Aminopropanal (3-AP), a degradation product of polyamines such as spermine, spermidine and putrescine, is a lysosomotropic small aldehyde that causes apoptosis or necrosis of most cells in culture, apparently by inducing moderate or extensive lysosomal rupture, respectively, and secondary mitochondrial changes. Here, using the human neuroblastoma SH-SY5Y cell line, we found simultaneous occurrence of apoptotic and necrotic cell death when cultures were exposed to 3-AP in concentrations that usually are either nontoxic, or only cause apoptosis. At 30 mM, but not at 10 mM, the lysosomotropic base and proton acceptor NH3 completely blocked the toxic effect of 3-AP, proving that 3-AP is lysosomotropic and suggesting that the lysosomal membrane proton pump of neuroblastoma cells is highly effective, creating a lower than normal lysosomal pH and, thus, extensive intralysosomal accumulation of lysosomotropic drugs. A wave of internal oxidative stress, secondary to changes in mitochondrial membrane potential, followed and gave rise to further lysosomal rupture. The preincubation of cells for 24 h with a chain-breaking free radical-scavenger, α-tocopherol, before exposure to 3-AP, significantly delayed both the wave of oxidative stress and the secondary lysosomal rupture, while it did not interfere with the early 3-AP-mediated phase of lysosomal break. Obviously, the reported oxidative stress and apoptosis/necrosis are consequences of lysosomal rupture with ensuing release of lysosomal enzymes resulting in direct/indirect effects on mitochondrial permeability, membrane potential, and electron transport. The induced oxidative stress seems to act as an amplifying loop causing further lysosomal break that can be partially prevented by α-tocopherol. Perhaps secondary brain damage during a critical post injury period can be prevented by the use of drugs that temporarily raise lysosomal pH, inactivate intralysosomal 3-AP, or stabilize lysosomal membranes against oxidative stress.

1 - 37 of 37
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf