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Sjögren, Florence
Publications (10 of 22) Show all publications
Sjögren, F., Davidsson, K., Sjöström, M. & Anderson, C. (2012). Cutaneous Microdialysis: Cytokine Evidence for Altered Innate Reactivity in the Skin of Psoriasis Patients?. AAPS Journal, 14(2), 187-195
Open this publication in new window or tab >>Cutaneous Microdialysis: Cytokine Evidence for Altered Innate Reactivity in the Skin of Psoriasis Patients?
2012 (English)In: AAPS Journal, ISSN 1550-7416, E-ISSN 1550-7416, Vol. 14, no 2, p. 187-195Article in journal (Refereed) Published
Abstract [en]

Cutaneous microdialysis demonstrates cytokine production in living human skin. In the present study, microdialysis samples taken from uninvolved and lesional skin in three test subjects with psoriasis over 24 h have been investigated for cytokine content with a bead-based multiplex immunoassay from Luminex. Concentration curves for a set of Th1/Th2 and pro-inflammatory cytokines measured differed from a reference group of ten subjects without psoriasis. The time to return to near baseline values after innate insertion reactivity is between 9 and 16 h. Post-equilibration levels (17-24 h) for the three main cytokines elevated in the reference group were differentially elevated outside the range of the reference group for interleukin-1 beta (IL1 beta) and IL8 but not so for IL6. Two further cytokines, granulocyte-macrophage colony-stimulating factor and tumor necrosis factor-alpha not generally elevated in the reference group, showed elevated values in the test subjects. Multivariate time series analysis (chemometry) showed that cytokine patterns for the individual test subjects often fell outside the 99% confidence intervals of a model generated from the reference group. In a clinical research situation, cutaneous microdialysis is feasible, gives generally higher cytokine levels than in the blood and generates interpretable data on an individuals reactivity compared with a reference group. This may well prove useful in delineation of pathogenetic issues, selection of appropriate therapy and monitoring of subsequent response in inflammatory dermatoses such as psoriasis.

Place, publisher, year, edition, pages
American Association of Pharmaceutical Scientists, 2012
Keywords
cytokines, dermis, human, microdialysis, multivariate time series analysis
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-77319 (URN)10.1208/s12248-012-9331-z (DOI)000302814900005 ()
Note
Funding Agencies|Swedish Psoriasis Foundation||Welander Foundation||Available from: 2012-05-11 Created: 2012-05-11 Last updated: 2017-12-07
Seifert, O., Matussek, A., Sjögren, F., Geffers, R. & Anderson, C. (2012). Gene expression profiling of macrophages: implications for an immunosuppressive effect of dissolucytotic gold ions. Journal of Inflammation, 9(43)
Open this publication in new window or tab >>Gene expression profiling of macrophages: implications for an immunosuppressive effect of dissolucytotic gold ions
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2012 (English)In: Journal of Inflammation, ISSN 1476-9255, E-ISSN 1476-9255, Vol. 9, no 43Article in journal (Refereed) Published
Abstract [en]

Background: Gold salts has previously been used in the treatment of rheumatoid arthritis but have been replaced by biologicals such as TNF-alpha inhibitors. The mechanisms behind the anti-inflammatory effect of metallic gold ions are still unknown, however, recent data showed that charged gold atoms are released from pure metallic gold implants by macrophages via a dissolucytosis membrane, and that gold ions are taken up by local macrophages, mast cells and to some extent fibroblasts. These findings open the question of possible immunomodulatory effects of metallic gold and motivate efforts on a deeper understanding of the effect of metallic gold on key inflammatory cells as macrophages. less thanbrgreater than less thanbrgreater thanMethods: Human macrophage cells (cell line THP-1) were grown on gold foils and intracellular uptake was analysed by autometallography. The impact of phagocytised gold ions on viability of THP-1 cells was investigated by trypan blue staining and TUNEL assay. The global gene expression profile of THP-1 cells after incorporation of gold ions was studied using microarray analysis comprising approximately 20,000 genes. The gene expression data was confirmed by measurement of secreted proteins. less thanbrgreater than less thanbrgreater thanResults: Autometallography showed intracellular uptake of gold ions into THP-1 cells. No significant effect on viability of THP-1 cells was demonstrated. Our data revealed a unique gene expression signature of dissolucytotic THP-1 cells that had taken up gold ions. A large number of regulated genes were functionally related to immunomodulation. Gold ion uptake induced downregulation of genes involved in rheumatoid arthritis such as hepatocyte growth factor, tenascin-C, inhibitor of DNA binding 1 and 3 and matrix metalloproteinase 13. less thanbrgreater than less thanbrgreater thanConclusion: The data obtained in this study offer new insights into the mode of action of gold ions and suggest for the investigation of effects on other key cells and a possible future role of metallic gold as implants in rheumatoid arthritis or other inflammatory conditions.

Place, publisher, year, edition, pages
BioMed Central, 2012
Keywords
Gold, Macrophages, Inflammation, Rheumatoid arthritis
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-87469 (URN)10.1186/1476-9255-9-43 (DOI)000312597100001 ()
Available from: 2013-01-18 Created: 2013-01-18 Last updated: 2017-12-06
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
Sjöwall, J., Fryland, L., Nordberg, M., Sjögren, F., Garpmo, U., Jansson, C., . . . Ekerfelt, C. (2011). Decreased Th1-Type Inflammatory Cytokine Expression in the Skin Is Associated with Persisting Symptoms after Treatment of Erythema Migrans. PLOS ONE, 6(3), 0018220
Open this publication in new window or tab >>Decreased Th1-Type Inflammatory Cytokine Expression in the Skin Is Associated with Persisting Symptoms after Treatment of Erythema Migrans
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2011 (English)In: PLOS ONE, ISSN 1932-6203, Vol. 6, no 3, p. 0018220-Article in journal (Refereed) Published
Abstract [en]

Background: Despite the good prognosis of erythema migrans (EM), some patients have persisting symptoms of various character and duration post-treatment. Several factors may affect the clinical outcome of EM, e. g. the early interaction between Borrelia (B.) burgdorferi and the host immune response, the B. burgdorferi genotype, antibiotic treatment as well as other clinical circumstances. Our study was designed to determine whether early cytokine expression in the skin and in peripheral blood in patients with EM is associated with the clinical outcome. Methods: A prospective follow-up study of 109 patients with EM was conducted at the A land Islands, Finland. Symptoms were evaluated at 3, 6, 12 and 24 months post-treatment. Skin biopsies from the EM and healthy skin were immunohistochemically analysed for expression of interleukin (IL)-4, IL-10, IL-12p70 and interferon (IFN)-gamma, as well as for B. burgdorferi DNA. Blood samples were analysed for B. burgdorferi antibodies, allergic predisposition and levels of systemic cytokines. Findings: None of the patients developed late manifestations of Lyme borreliosis. However, at the 6-month follow-up, 7 of 88 patients reported persisting symptoms of diverse character. Compared to asymptomatic patients, these 7 patients showed decreased expression of the Th1-associated cytokine IFN-gamma in the EM biopsies (p = 0.003). B. afzelii DNA was found in 48%, B. garinii in 15% and B. burgdorferi sensu stricto in 1% of the EM biopsies, and species distribution was the same in patients with and without post-treatment symptoms. The two groups did not differ regarding baseline patient characteristics, B. burgdorferi antibodies, allergic predisposition or systemic cytokine levels. Conclusion: Patients with persisting symptoms following an EM show a decreased Th1-type inflammatory response in infected skin early during the infection, which might reflect a dysregulation of the early immune response. This finding supports the importance of an early, local Th1-type response for optimal resolution of LB.

Place, publisher, year, edition, pages
Public Library of Science (PLoS), 2011
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-67829 (URN)10.1371/journal.pone.0018220 (DOI)000289057200045 ()
Note
Original Publication: Johanna Sjöwall, Linda Fryland, Marika Nordberg, Florence Sjögren, Ulf Garpmo, Christian Jansson, Sten-Anders Carlsson, Sven Bergstrom, Jan Ernerudh, Dag Nyman, Pia Forsberg and Christina Ekerfelt, Decreased Th1-Type Inflammatory Cytokine Expression in the Skin Is Associated with Persisting Symptoms after Treatment of Erythema Migrans, 2011, PLOS ONE, (6), 3, 0018220. http://dx.doi.org/10.1371/journal.pone.0018220 Copyright: Public Library of Science (PLoS) http://www.plos.org/Available from: 2011-04-29 Created: 2011-04-29 Last updated: 2013-08-29
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
Johansson, J., Sjögren, F., Bodelsson, M. & Sjöberg, F. (2011). Dynamics of leukocyte receptors after severe burns: An exploratory study. BURNS, 37(2), 227-233
Open this publication in new window or tab >>Dynamics of leukocyte receptors after severe burns: An exploratory study
2011 (English)In: BURNS, ISSN 0305-4179, Vol. 37, no 2, p. 227-233Article in journal (Refereed) Published
Abstract [en]

Background: Patients with burns are susceptible to organ failure, and there is indirect evidence that leukocytes may contribute to this process. They may change the expression of cell-surface receptors after certain stimuli, for example, the burn. We therefore aimed to assess the changes induced by the burn in the expression of leukocyte cell-surface receptors CD11b, CD14, CD16, and CD62L on the surface of PMNs and monocytes. We also wanted to examine the dynamics of this activation during the first week after the burn, and to relate it to the size of the injury. Methods: Ten patients with burns of andgt;15% (TBSA) were included in the study. Blood samples were collected on arrival and every consecutive morning during the first week. Healthy volunteers acted as controls. Results: PMN CD11b expression was increased. The extent of PMN CD11b expression correlated negatively to the size of the full thickness burn. Monocyte CD14 expression increased initially but there was no relation to the size of the burn. PMN CD16 expression decreased initially during the first days and the decrease was related to burn size. CD62L did not vary depending on the burn in either PMN or monocytes during the first week after the burn. Conclusion: This study showed that specific receptors on the surface of leukocytes (PMN CD11b, monocyte CD14 and PMN CD16) are affected by the burn. Expression of PMN CD11b and CD16 are related to burn size. Burn-induced effects on the expression of PMN receptors, such as PMN CD11b and CD16, may contribute to burn-induced infection susceptibility.

Place, publisher, year, edition, pages
Elsevier Science B.V., Amsterdam., 2011
Keywords
Burn, CD11, CD14, CD16, CD62, Granulocyte, Integrin, Monocyte, PMN, Trauma
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-67169 (URN)10.1016/j.burns.2010.08.015 (DOI)000288410900007 ()
Note
Original Publication: Joakim Johansson, Florence Sjögren, Mikael Bodelsson and Folke Sjöberg, Dynamics of leukocyte receptors after severe burns: An exploratory study, 2011, BURNS, (37), 2, 227-233. http://dx.doi.org/10.1016/j.burns.2010.08.015 Copyright: Elsevier Science B.V., Amsterdam. http://www.elsevier.com/Available from: 2011-04-01 Created: 2011-04-01 Last updated: 2013-06-25
Sjögren, F. & Anderson, C. D. (2010). Are cutaneous microdialysis cytokine findings supported by end-point biopsy immunohistochemistry findings?. AAPS Journal, 12(4), 741-749
Open this publication in new window or tab >>Are cutaneous microdialysis cytokine findings supported by end-point biopsy immunohistochemistry findings?
2010 (English)In: AAPS Journal, ISSN 1550-7416, E-ISSN 1550-7416, Vol. 12, no 4, p. 741-749Article in journal (Refereed) Published
Abstract [en]

Insertion of a cutaneous microdialysis catheter into normal dermis has been shown to induce the production of IL1b, IL6 and IL8 in an innate response to minimal trauma. In the present study, skin biopsy for immunohistochemistry has been performed at the site of the microdialysis catheter to compare the findings with that of the microdialysis findings 24 h after insertion. Of the three named cytokines, concordance between the two investigated technologies was highest for IL8 (100%) followed by IL6 (70%) and IL1b (50%). For seven other pro-inflammatory and T cell-relevant cytokines studied, concordance ranged between 50% and 80%. The total number of positive (microdialysis or immunofluorescence) findings was similar between the two methodologies. Technical and biological phenomenon can explain the differences. We conclude that both methodologies illustrate important features of tissue biology and that a combination of the two methods in clinical research can provide the chronology of soluble mediator participation and the more classic, but also more invasive, biopsy-based methodology at a point which constitutes the end of the observation period. We conclude further that at the 24-h time period here studied, microdialysis catheters are still functional and thus capable of producing relevant data which can be corroborated and extended by the “end point biopsy”.

Keywords
cutaneous microdialysis, cytokines, human, immunostaining, innate
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-66928 (URN)10.1208/s12248-010-9235-8 (DOI)000288426100028 ()
Available from: 2011-03-22 Created: 2011-03-22 Last updated: 2017-12-11
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
Farnebo, S., Karlander, L.-E., Steinwall, I., Sjögren, F. & Sjöberg, F. (2009). Continuous assessment of concentrations of cytokines in experimental injuries of the extremity. International Journal of Clinical and Experimental Medicine, 2(4), 354-362
Open this publication in new window or tab >>Continuous assessment of concentrations of cytokines in experimental injuries of the extremity
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2009 (English)In: International Journal of Clinical and Experimental Medicine, ISSN 1940-5901, Vol. 2, no 4, p. 354-362Article in journal (Refereed) Published
Abstract [en]

Background. Inflammation plays an important part in the healing process. Little is known about the extent local inflammatory trauma response interacts with the central circulation and inflammation produced by central organs. The aim of the present study was to examine whether high cut-off microdialysis catheters offer potential to in real time assess interstitial cytokines variations in conjunction to markers of metabolism distal to a blunt vascular contusion. Methods. In a standardised contusion trauma model, microdialysis catheters (high MW (100kDa)) were inserted in the gracilis muscle distal to the trauma for the local assessment of IL-6, IL-8, TNF-a, total protein and the metabolic mediators (glycerol, puruvate and lactate). The contra lateral uninjured leg served as control of the centrally mediated inflammation propagated to the extremities. Results. The trauma led to a significant and quantitatively large (8-10 fold) increase in inflammatory cytokines (IL6 and 8) as measured both in the injured and control legs. There was only a minor, and not significant increase in concentrations of cytokines in the injured leg compared to the control leg.. There were no signs of ischemia in either leg. Conclusion. The new finding in this study is that both central, and local, inflammatory responses as well as metabolic mediators may be assessed continuously in skeletal muscle tissue distal to a major injury in an animal model. The findings suggest that the large trauma elicits a generalised inflammatory response to trauma rather than propagating a local one distal to the trauma.

Place, publisher, year, edition, pages
e-Century Publishing Corporation, 2009
Keywords
Blunt trauma; Inflammation; Microcirculation; Microdialysis; Rat
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-57062 (URN)20057979 (PubMedID)
Available from: 2010-06-11 Created: 2010-06-09 Last updated: 2010-12-28
Sjögren, F. & Anderson, C. (2009). Sterile trauma to normal human dermis invariably induces IL1beta, IL6 and IL8 in an innate response to "danger".. Acta Dermato-Venereologica, 89(5), 459-465
Open this publication in new window or tab >>Sterile trauma to normal human dermis invariably induces IL1beta, IL6 and IL8 in an innate response to "danger".
2009 (English)In: Acta Dermato-Venereologica, ISSN 0001-5555, E-ISSN 1651-2057, Vol. 89, no 5, p. 459-465Article in journal (Refereed) Published
Abstract [en]

Microdialysis allows the study of the local production and temporal resolution of cytokines in living skin. Samples were taken from the normal skin of 10 healthy subjects for 24-28 h after insertion of a concentric microdialysis catheter, and analysed with a Luminex bead-based assay. Interleukin-1 beta (IL1b), IL6 and IL8 were seen in all subjects at all time-points after the first hour. Levels peaked at 5-8 h, equilibrating to lower levels at 24 h. Immunohistological double staining for human leukocyte antigen (HLA)-DR and intracellular cytokines on biopsies taken after catheter removal showed many stained cells in the dermis, in contrast to the few cells stained in the epidermis. This study demonstrates the reactive capability of the dermis when provoked separately from the epidermis. The production of IL1b, IL6 and IL8 occurs invariably in what can be termed an innate, dermal response to "danger"; in this case in the form of sterile needle trauma.

Keywords
microdialysis; human; dermis; cytokines; chronology; innate immunity; bead immunoassay
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-21339 (URN)10.2340/00015555-0683 (DOI)19734969 (PubMedID)
Available from: 2009-10-01 Created: 2009-10-01 Last updated: 2017-12-13
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