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Hillman, Jan
Publications (10 of 32) Show all publications
Tobieson, L., Rossitti, S., Zsigmond, P., Hillman, J. & Marklund, N. (2018). Persistent Metabolic Disturbance in the Perihemorrhagic Zone Despite a Normalized Cerebral Blood Flow Following Surgery for Intracerebral Hemorrhage.. Neurosurgery
Open this publication in new window or tab >>Persistent Metabolic Disturbance in the Perihemorrhagic Zone Despite a Normalized Cerebral Blood Flow Following Surgery for Intracerebral Hemorrhage.
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2018 (English)In: Neurosurgery, ISSN 0148-396X, E-ISSN 1524-4040Article in journal (Refereed) Epub ahead of print
Abstract [en]

BACKGROUND: We hypothesized that reduced cerebral blood flow (CBF) and/or energy metabolic disturbances exist in the tissue surrounding a surgically evacuated intracerebral hemorrhage (ICH). If present, such CBF and/or metabolic impairments may contribute to ongoing tissue injury and the modest clinical efficacy of ICH surgery.

OBJECTIVE: To conduct an observational study of CBF and the energy metabolic state in the perihemorrhagic zone (PHZ) tissue and in seemingly normal cortex (SNX) by microdialysis (MD) following surgical ICH evacuation.

METHODS: We evaluated 12 patients (median age 64; range 26-71 yr) for changes in CBF and energy metabolism following surgical ICH evacuation using Xenon-enhanced computed tomography (n = 10) or computed tomography perfusion (n = 2) for CBF and dual MD catheters, placed in the PHZ and the SNX at ICH surgery.

RESULTS: CBF was evaluated at a mean of 21 and 58 h postsurgery. In the hemisphere ipsilateral to the ICH, CBF improved between the investigations (36.6 ± 20 vs 40.6 ± 20 mL/100 g/min; P < .05). In total, 1026 MD samples were analyzed for energy metabolic alterations including glucose and the lactate/pyruvate ratio (LPR). The LPR was persistently elevated in the PHZ compared to the SNX region (P < .05). LPR elevations in the PHZ were predominately type II (pyruvate normal-high; indicating mitochondrial dysfunction) as opposed to type I (pyruvate low; indicating ischemia) at 4 to 48 h (70% vs 30%) and at 49 to 84 h (79% vs 21%; P < .05) postsurgery.

CONCLUSION: Despite normalization of CBF following ICH evacuation, an energy metabolic disturbance suggestive of mitochondrial dysfunction persists in the perihemorrhagic zone.

Place, publisher, year, edition, pages
Oxford University Press, 2018
National Category
Neurology
Identifiers
urn:nbn:se:liu:diva-150994 (URN)10.1093/neuros/nyy179 (DOI)29788388 (PubMedID)
Available from: 2018-09-10 Created: 2018-09-10 Last updated: 2018-09-10
Haj-Hosseini, N., Richter, J., Olivecrona, M., Hillman, J., Hallbeck, M. & Wårdell, K. (2013). Fluorescence guided spectroscopy versus fluorescence microscopy for brain tumor resection. In: : . Paper presented at 64th meeting of the Scandinavian Neurosurgical Society, Harpa Reykjavík, Iceland, 5–8 June 2013.
Open this publication in new window or tab >>Fluorescence guided spectroscopy versus fluorescence microscopy for brain tumor resection
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2013 (English)Conference paper, Oral presentation with published abstract (Other academic)
National Category
Medical Engineering
Identifiers
urn:nbn:se:liu:diva-92387 (URN)
Conference
64th meeting of the Scandinavian Neurosurgical Society, Harpa Reykjavík, Iceland, 5–8 June 2013
Available from: 2013-05-10 Created: 2013-05-10 Last updated: 2017-02-14Bibliographically approved
Rejmstad, P., Åkesson, G., Hillman, J. & Wårdell, K. (2012). A laser Doppler system for monitoring of intracerebral microcirculation. Conf Proc IEEE Eng Med Biol Soc., 1988-1991
Open this publication in new window or tab >>A laser Doppler system for monitoring of intracerebral microcirculation
2012 (English)In: Conf Proc IEEE Eng Med Biol Soc., ISSN 1557-170X, p. 1988-1991Article in journal (Refereed) Published
Abstract [en]

A two-channel standard laser Doppler perfusion monitor has been adapted for intracerebral measurements. Software developed in Labview makes it possible to present the microvascular perfusion, total light intensity (TLI), heart rate and trend curves in real-time during surgery. A custom-made optical probe was designed in order to enable easy fixation during brain surgery. The constructed brain probe was evaluated and compared to a standard probe. Both probes presented similar feasibility when used for the skin recordings. In addition, evaluation was done in one patient in relation to tumor resection. Stable perfusion and TLI signals were immediately recorded when the probe was positioned in cerebral tissue. Movement artifacts were clearly seen when the probe was moved to a new site. Recordings in cortex and tumor border showed higher perfusion and lower TLI compared to measurements in subcortical white matter. The calculated heart rate estimate agreed well with the noted value from the electrocardiographic patient monitoring system.                                                                                                                                                      

Place, publisher, year, edition, pages
IEEE, 2012
National Category
Medical Engineering
Identifiers
urn:nbn:se:liu:diva-86150 (URN)10.1109/EMBC.2012.6346346 (DOI)000313296502058 ()23366307 (PubMedID)978-1-4244-4119-8 (ISBN)e-978-1-4244-4120-4 (ISBN)978-1-4577-1787-1 (ISBN)
Funder
Swedish Research Council
Available from: 2012-12-07 Created: 2012-12-07 Last updated: 2017-02-03Bibliographically approved
Rejmstad, P., Åkesson, G., Hillman, J. & Wårdell, K. (2012). Intracerebral perfusion monitoring by laser Doppler flowmetry, Medicinteknikdagarna. In: : . Paper presented at Medicinteknikdagarns (MTD). Lund
Open this publication in new window or tab >>Intracerebral perfusion monitoring by laser Doppler flowmetry, Medicinteknikdagarna
2012 (English)Conference paper, Published paper (Other academic)
Place, publisher, year, edition, pages
Lund: , 2012
National Category
Medical Engineering
Identifiers
urn:nbn:se:liu:diva-81378 (URN)
Conference
Medicinteknikdagarns (MTD)
Available from: 2012-09-12 Created: 2012-09-12 Last updated: 2017-02-03Bibliographically approved
Mellergard, P., Sjögren, F. & Hillman, J. (2012). The Cerebral Extracellular Release of Glycerol, Glutamate, and FGF2 Is Increased in Older Patients following Severe Traumatic Brain Injury. Journal of Neurotrauma, 29(1), 112-118
Open this publication in new window or tab >>The Cerebral Extracellular Release of Glycerol, Glutamate, and FGF2 Is Increased in Older Patients following Severe Traumatic Brain Injury
2012 (English)In: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 29, no 1, p. 112-118Article in journal (Refereed) Published
Abstract [en]

Old age is associated with a poor recovery from traumatic brain injury (TBI). In a retrospective study we investigated if the biochemical response following TBI is age dependent. Extracellular fluids were continuously sampled by microdialysis in 69 patients admitted to our NSICU following severe TBI. The concentrations of glycerol, glutamate, lactate, pyruvate, and eight different cytokines (IL-1 beta, IL-6, IL-10, IL-8, MIP-1 beta, RANTES, FGF2, and VEGF) were determined by fluorescence multiplex bead technology. Patients in the oldest age group (andgt;= 65 years) had significantly higher microdialysate concentrations of glycerol and glutamate compared to younger patients: the mean microdialysate concentration of glycerol increased from 55.9 mu mol/L (25-44 year) to 252 mu mol/L (andgt;= 65 years; p andlt; 0.0001); similarly glutamate increased from 15.8 mmol/L to 92.2 mmol/L (p andlt; 0.0001). The lactate-pyruvate ratio was also significantly higher in the patients andgt;= 65 years of age (63.9) compared with all the other age groups. The patterns of cytokine responses varied. For some cytokines (IL-1b, IL-10, and IL-8) there were no differences between age groups, while for others (MIP-1b, RANTES, VEGF, and IL-6) some differences were observed, but with no clear correlation with increasing age. For FGF2 the mean microdialysate concentration was 43 pg/mL in patients andgt;= 65 years old, significantly higher compared to all other age groups (p andlt; 0.0001). Increased concentrations of glycerol and glutamate would indicate more extensive damaging processes in the elderly. An increase in concentration of FGF2 could serve a protective function, but could also be related to a dysregulation of the timing in the cellular response in elderly patients.

Place, publisher, year, edition, pages
Mary Ann Liebert, 2012
Keywords
cytokines, FGF2, glutamate, glycerol, microdialysis, monitoring, traumatic brain injury
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-75116 (URN)10.1089/neu.2010.1732 (DOI)000299317300013 ()
Available from: 2012-02-21 Created: 2012-02-17 Last updated: 2017-12-07
Mellergård, P., Åneman, O., Sjögren, F., Säberg, C. & Hillman, J. (2011). Differences in Cerebral Extracellular Response of Interleukin-1 beta, Interleukin-6, and Interleukin-10 After Subarachnoid Hemorrhage or Severe Head Trauma in Humans. NEUROSURGERY, 68(1), 12-19
Open this publication in new window or tab >>Differences in Cerebral Extracellular Response of Interleukin-1 beta, Interleukin-6, and Interleukin-10 After Subarachnoid Hemorrhage or Severe Head Trauma in Humans
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2011 (English)In: NEUROSURGERY, ISSN 0148-396X, Vol. 68, no 1, p. 12-19Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Microdialysis has become a routine method for biochemical surveillance of patients in neurosurgical intensive care units. OBJECTIVE: To analyze the intracerebral extracellular levels of 3 interleukins (ILs) during the 7 days after major subarachnoid hemorrhage or traumatic brain injury). METHODS: Microdialysate from 145 severely injured neurosurgical intensive care unit patients (88 with subarachnoid hemorrhage, 57 with traumatic brain injury) was collected every 6 hours for 7 days. The concentrations of IL-1 beta and IL-6 were determined by fluorescence multiplex bead technology, and IL-10 was determined by enzyme-linked immunosorbent assay. RESULTS: Presented are the response patterns of 3 ILs during the first week after 2 different types of major brain injury. These patterns are different for each IL and also differ with respect to the kind of pathological impact. For both IL-1 beta and IL-6, the initial peaks (mean values for all patients at day 2 being 26.9 +/- 4.5 and 4399 +/- 848 pg/mL, respectively) were followed by a gradual decline, with IL-6 values remaining 100-fold higher compared with IL-1 beta. Female patients showed a stronger and more sustained response. The response of IL-10 was different, with mean values less than 23 pg/mL and with no significant variation between any of the postimpact days. For all 3 ILs, the responses were stronger in subarachnoid hemorrhage patients. The study also indicates that under normal conditions, IL-1 beta, IL-6, and IL-10 are present only at very low concentrations or not at all in the extracellular space of the human brain. CONCLUSION: This is the first report presenting in some detail the human cerebral response of IL-1 beta, IL-6, and IL-10 after subarachnoid hemorrhage and traumatic brain injury. The 3 ILs have different reaction patterns, with the response of IL-1 beta and IL-6 being related to the type of cerebral damage sustained, whereas the IL-10 response was less varied.

Place, publisher, year, edition, pages
Williams and Wilkins, 2011
Keywords
Interleukins, Interleukin-1, Interleukin-6, Interleukin-10, Microdialysis, Subarachnoid hemorrhage, Traumatic brain injury
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-64237 (URN)10.1227/NEU.0b013e3181ef2a40 (DOI)000285288200018 ()
Available from: 2011-01-17 Created: 2011-01-17 Last updated: 2012-04-02
Mellergard, P., Sjögren, F. & Hillman, J. (2010). Release of VEGF and FGF in the extracellular space following severe subarachnoidal haemorrhage or traumatic head injury in humans. British Journal of Neurosurgery, 24(3), 261-267
Open this publication in new window or tab >>Release of VEGF and FGF in the extracellular space following severe subarachnoidal haemorrhage or traumatic head injury in humans
2010 (English)In: British Journal of Neurosurgery, ISSN 0268-8697, E-ISSN 1360-046X, Vol. 24, no 3, p. 261-267Article in journal (Refereed) Published
Abstract [en]

Microdialysate fluid from 145 severely injured NSICU-patients, 88 with subarachnoidal haemorrage (SAH), and 57 with traumatic brain injury (TBI), was collected by microdialysis during the first 7 days following impact, and levels of the neurotrophins fibroblast growth factor-2 (FGF2) and vascular endothelial growth factor (VEGF) were analysed. The study illustrates both similarities and differences in the reaction patterns of the 2 inflammatory proteins. The highest concentrations of both FGF2 and VEGF were measured on Day 2 (mean (+/- SE) values being 47.1 +/- 15.33 and 116.9 +/- 41.85 pg/ml, respectively, in the pooled patient material). The VEGF concentration was significantly higher in TBI-patients, while the FGF2 showed a tendency to be higher in SAH-patients. This is the first report presenting in some detail the human cerebral response of FGF2 and VEGF following SAH and TBI. Apart from increasing the understanding of the post-impact inflammatory response of the human brain, the study identifies potential threshold values for these chemokines that may serve as monitoring indicators in the NSICU.

Place, publisher, year, edition, pages
Informa Healthcare, 2010
Keywords
Intensive care; microdialysis; monitoring; VEGF; FGF2; subarachnoidal hemorrhage; traumatic brain injury
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-58200 (URN)10.3109/02688690903521605 (DOI)000279905200007 ()
Available from: 2010-08-11 Created: 2010-08-09 Last updated: 2017-12-12
Rossitti, S., Radzinska, R., Vigren, P. & Hillman, J. (2009). Letter: Postoperative Ophthalmic Artery Pseudoaneurysm Presenting as Monocular Blindness Successful Endovascular Treatment [Letter to the editor]. Klinische Neuroradiologie, 19(3), 230-234
Open this publication in new window or tab >>Letter: Postoperative Ophthalmic Artery Pseudoaneurysm Presenting as Monocular Blindness Successful Endovascular Treatment
2009 (English)In: Klinische Neuroradiologie, ISSN 0939-7116, E-ISSN 1615-6706, Vol. 19, no 3, p. 230-234Article in journal, Letter (Other academic) Published
Abstract [en]

n/a

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-20615 (URN)10.1007/s00062-009-9003-2 (DOI)
Available from: 2009-09-16 Created: 2009-09-15 Last updated: 2017-12-13Bibliographically approved
Mellergård, P., Åneman, O., Sjögren, F., Pettersson, P. & Hillman, J. (2008). Changes in Extracellular Concentrations of Some Cytokines, Chemokines, and Neurotrophic Factors After Insertion of Intracerebral Microdialysis Catheters in Neurosurgical Patients. Neurosurgery, 62(1), 151-157
Open this publication in new window or tab >>Changes in Extracellular Concentrations of Some Cytokines, Chemokines, and Neurotrophic Factors After Insertion of Intracerebral Microdialysis Catheters in Neurosurgical Patients
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2008 (English)In: Neurosurgery, ISSN 0148-396X, E-ISSN 1524-4040, Vol. 62, no 1, p. 151-157Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: The extracellular levels of eight different inflammatory agents were analyzed during the initial 36 hours after insertion of microdialysis catheters in patients. METHODS: Cerebral extracellular fluid from 38 patients who were treated in a neurosurgical intensive care unit for severe brain injury was collected every 6 hours for 36 hours. The concentration of interleukin (IL)-1ß, IL-6, IL-8, macrophage inflammatory protein-1ß, regulated on activation, normal T-cell expressed and secreted (RANTES), fibroblast growth factor-2, and vascular endothelial growth factor was determined by a multiplex assay, and IL-10 was determined by enzyme-linked immunosorbent assay. RESULTS: This is the first report regarding the presence of IL-10, IL-8, macrophage inflammatory protein-1ß, regulated on activation, T-cell expressed and secreted, vascular endothelial growth factor, and fibroblast growth factor-2 in the tissue level proper of the living human brain. The study also provides new information regarding the response of IL-1ß and IL-6 after insertion of a microdialysis catheter. The study confirms that the intriguing patterns of interplay between different components of the inflammatory response studied in laboratory settings are present in the human brain. This was most clearly observed in the variations in response between the three different chemokines investigated, as well as in the rapid and transient response of fibroblast growth factor-2. CONCLUSION: The data presented illustrate the opportunity to monitor biochemical events of possible importance in the human brain and indicate the potential of such monitoring in neurosurgical intensive care. The study also underlines that any analysis of events in the brain involving mechanical invasiveness needs to take into account biochemical changes that are directly related to the manipulation of brain tissue.

Keywords
Chemokine, Cytokine, Head trauma, Intensive care, Microdialysis, Monitoring, Neurotrophic factor, Subarachnoidal hemorrhage
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-47988 (URN)10.1227/01.NEU.0000311072.33615.3A (DOI)
Available from: 2009-10-11 Created: 2009-10-11 Last updated: 2017-12-13
Wårdell, K., Hariz, M., Dizdar Segrell, N., Hillman, J. & Andersson-Engels, S. (2008). Neuro-engineering for navigation, Intervention and Implementation in Neurosurgery. In: Medicinteknikdagarna 2008,2008: . Paper presented at Medicinteknikdagarna, Göteborg, 14-15 Oktober, 2008 (pp. 122-122).
Open this publication in new window or tab >>Neuro-engineering for navigation, Intervention and Implementation in Neurosurgery
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2008 (English)In: Medicinteknikdagarna 2008,2008, 2008, p. 122-122Conference paper, Published paper (Other academic)
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-44319 (URN)76310 (Local ID)76310 (Archive number)76310 (OAI)
Conference
Medicinteknikdagarna, Göteborg, 14-15 Oktober, 2008
Available from: 2009-10-10 Created: 2009-10-10 Last updated: 2018-01-12Bibliographically approved
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