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  • 1.
    Biermann, Olivia
    et al.
    Karolinska Institute, Sweden.
    Eckhardt, Martin
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Emergency Medicine. Linköping University, Department of Medical and Health Sciences, Division of Community Medicine.
    Carlfjord, Siw
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Primary Health Care in Central County.
    Falk, Magnus
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in West Östergötland, Research & Development Unit in Local Health Care.
    Forsberg, Birger C.
    Karolinska Institute, Sweden.
    Collaboration between non-governmental organizations and public services in health - a qualitative case study from rural Ecuador2016In: Global Health Action, ISSN 1654-9716, E-ISSN 1654-9880, Vol. 9, article id 32237Article in journal (Refereed)
    Abstract [en]

    Background: Non-governmental organizations (NGOs) have a key role in improving health in low-and middle-income countries. Their work needs to be synergistic, complementary to public services, and rooted in community mobilization and collective action. The study explores how an NGO and its health services are perceived by the population that it serves, and how it can contribute to reducing barriers to care. Design: A qualitative exploratory study was conducted in remote Ecuador, characterized by its widespread poverty and lack of official governance. An international NGO collaborated closely with the public services to deliver preventative and curative health services. Data were collected using focus group discussions and semistructured interviews with purposively sampled community members, healthcare personnel, and community health workers based on their links to the health services. Conventional qualitative content analysis was used, focusing on manifest content. Results: Emerging themes relate to the public private partnership (PPP), the NGO and its services, and community participation. The population perceives the NGO positively, linking it to healthcare improvements. Their priority is to get services, irrespective of the providers structure. The presence of an NGO in the operation may contribute to unrealistic expectations of health services, affecting perceptions of the latter negatively. Conclusions: To avoid unrealistic expectations and dissatisfaction, and to increase and sustain the populations trust in the organization, an NGO should operate in a manner that is as integrated as possible within the existing structure. The NGO should work close to the population it serves, with services anchored in the community. PPP parties should develop a common platform with joint messages to the target population on the providers structure, and regarding partners roles and responsibilities. Interaction between the population and the providers on service content and their expectations is key to positive outcomes of PPP operations.

  • 2.
    Brito, H. O.
    et al.
    University of Federal Parana, Brazil.
    Radulski, D. R.
    University of Federal Parana, Brazil.
    Björk Wilhelms, Daniel
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Emergency Medicine.
    Stojakovic, Andrea
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Brito, L. M. O.
    University of Federal Maranhao, Brazil.
    Engblom, David
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Franco, C. R. C.
    University of Federal Parana, Brazil.
    Zampronio, A. R.
    University of Federal Parana, Brazil.
    Female Sex Hormones Influence the Febrile Response Induced by Lipopolysaccharide, Cytokines and Prostaglandins but not by Interleukin-1 beta in Rats2016In: Journal of neuroendocrinology (Print), ISSN 0953-8194, E-ISSN 1365-2826, Vol. 28, no 10Article in journal (Refereed)
    Abstract [en]

    There are differences in the immune response, and particularly fever, between males and females. In the present study, we investigated how the febrile responses induced by lipopolysaccharide (LPS) and different endogenous pyrogens were affected by female gonadal hormones. The febrile response to i.p. injection of LPS (50g/kg) was 40% lower in female rats compared to male or ovariectomised (OVX) female rats. Accordingly, oestrogen replacement in OVX animals reduced LPS-induced fever. Treatment with the prostaglandin synthesis inhibitor indomethacin (2mg/kg, i.p. 30min before) reduced the febrile response induced by LPS in both OVX (88%) and sham-operated (71%) rats. In line with the enhanced fever in OVX rats, there was increased expression of cyclooxygenase-2 (COX-2) in the hypothalamus and elevated levels of prostaglandin E-2 (PGE(2)). In addition, OVX rats were hyper-responsive to PGE(2) injected i.c.v. By contrast to the enhanced fever in response to LPS and PGE(2), the febrile response induced by i.c.v. injection of interleukin (IL)-1 was unaffected by ovariectomy, whereas the responses induced by tumour necrosis factor (TNF)- and macrophage inflammatory protein (MIP)-1 were completely abrogated. These results suggest that the mediators involved in the febrile response in females are similar to males, although the reduction of female hormones may decrease the responsiveness of some mediators such as TNF- and MIP-1. Compensatory mechanisms may be activated in females after ovariectomy such as an augmented synthesis of COX-2 and PGE(2).

  • 3.
    Carlfjord, Siw
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Primary Health Care in Central County.
    Öhrn, Annica
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Medicine and Health Sciences.
    Gunnarsson, Anna
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Emergency Medicine.
    Experiences from ten years of incident reporting in health care: a qualitative study among department managers and coordinators2018In: BMC Health Services Research, ISSN 1472-6963, E-ISSN 1472-6963, Vol. 18, article id 113Article in journal (Refereed)
    Abstract [en]

    Background: Incident reporting (IR) in health care has been advocated as a means to improve patient safety. The purpose of IR is to identify safety hazards and develop interventions to mitigate these hazards in order to reduce harm in health care. Using qualitative methods is a way to reveal how IR is used and perceived in health care practice. The aim of the present study was to explore the experiences of IR from two different perspectives, including heads of departments and IR coordinators, to better understand how they value the practice and their thoughts regarding future application. Methods: Data collection was performed in Ostergotland County, Sweden, where an electronic IR system was implemented in 2004, and the authorities explicitly have advocated IR from that date. A purposive sample of nine heads of departments from three hospitals were interviewed, and two focus group discussions with IR coordinators took place. Data were analysed using qualitative content analysis. Results: Two main themes emerged from the data: "Incident reporting has come to stay" building on the categories entitled perceived advantages, observed changes and value of the IR system, and "Remaining challenges in incident reporting" including the categories entitled need for action, encouraged learning, continuous culture improvement, IR system development and proper use of IR. Conclusions: After 10 years, the practice of IR is widely accepted in the selected setting. IR has helped to put patient safety on the agenda, and a cultural change towards no blame has been observed. The informants suggest an increased focus on action, and further development of the tools for reporting and handling incidents.

  • 4.
    Eckhardt, Martin
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Emergency Medicine.
    The Bumpy Road to Universal Health Coverage: Access to Primary and Emergency Care in Rural Tropical Ecuador2018Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background: By the turn of the new millennium 84% of families in rural coastal Ecuador had difficulties to access health services. A health reform some years earlier to improve this situation had not been implemented. In 2001, the non-governmental organization (NGO) Foundation Human Nature together with a rural population established a primary health care center in North-Western Ecuador. A public private partnership with the Ministry of Public Health was formed. Services depended on out-of-pocket payments, restricting the poor’s access to care. In order to increase access to primary and emergency care, Foundation Human Nature planned to establish a community-based health insurance. In the meantime, a major health reform was initiated by a new government in 2008. It aimed at universal health coverage, providing qualitative services for all based on primary health care, while ensuring protection from financial hardship. The aims of this thesis were to appraise the feasibility of community- based health insurance in Ecuador; to study how rural stakeholders perceived the 2008 reform and its effects on rural health services; to explore the local population’s perception of the NGO in service delivery; and to measure the scope and describe the nature of perceived emergencies, the related health care seeking behavior and health expenditure.

    Methods: Quantitative and qualitative methods were applied to tackle the research objectives. Data collection for the health insurance study and the study of perceived emergencies was carried out through cross-sectional household surveys. For each of the studies 210 households were sampled with two-stage cluster sampling. Structured questionnaires were used with on the spot household interviews. Focus group discussions with local stakeholders were performed to explore their perceived effects of the 2008 health reform. The population’s perception of the NGO was also studied through focus group discussions, which were complemented by key-informant interviews with local stakeholders. Inductive qualitative content analysis, focusing on the manifest content was applied.

    Results: 69% of interviewees were willing to join the presented community-based health insurance scheme for 30 US$ per household and year. Attitudes towards the scheme were positive and 92% of interviewees stated they would increase their health service utilization with affiliation. The implementation of the 2008 health reform was perceived as top-down, lacking communication. However, the reform’s effects were mainly perceived as positive with free medical attendance and drugs. Increased service utilization was described as leading to a relative shortage of drugs and appointments. Access problems for remote dwellers were found, who were described of having to seek private care, also in emergencies. The NGO and its services were perceived positively by the population due to health care improvements in the region. The structure of the public private partnership was unclear, leading to dissatisfaction. Community participation was found to be rather weak. Perceived emergencies occurred to at least 90/1,000 inhabitants in the past year. Fever, traumatic injury and abdominal pain were the most frequent chief complaints. The first contacted providers in 57% of all cases were private for-profit providers, including traditional healers. Public health services treated one third of all cases. Health expenditure was found to be high and catastrophic health expenditure occurred in 24% of all cases.

    Conclusions: Prior to the 2008 reform community-based health insurance was found to be feasible in the study region. This financing instrument may have a role in the post-reform system, to cover services that the government does not yet sufficiently provide. The effects of the 2008 reform were mainly perceived positively, but an adjustment of the system is needed to improve the relative lack of drugs and appointments, especially for remote dwellers. Free health services may not be sufficient to reach universal health coverage for patients with perceived emergencies. Changes in public emergency departments and improved financial protection for emergency patients may improve the situation. The NGO’s role was perceived positively by the population. A lack of communication about the public private partnership and relatively weak community participation restricted the NGO’s full potential and should be improved.

    List of papers
    1. Feasibility of community-based health insurance in rural tropical Ecuador
    Open this publication in new window or tab >>Feasibility of community-based health insurance in rural tropical Ecuador
    2011 (English)In: REVISTA PANAMERICANA DE SALUD PUBLICA-PAN AMERICAN JOURNAL OF PUBLIC HEALTH, ISSN 1020-4989, Vol. 29, no 3, p. 177-184Article in journal (Refereed) Published
    Abstract [en]

    Objective. The main objective of this study was to assess peoples willingness to join a community-based health insurance (CHI) model in El Paramo, a rural area in Ecuador, and to determine factors influencing this willingness. A second objective was to identify peoples understanding and attitudes toward the presented CHI model. Methods. A cross-sectional survey was carried out using a structured questionnaire. Of an estimated 829 households, 210 were randomly selected by two-stage cluster sampling. Attitudes toward the scheme were assessed. Information on factors possibly influencing willingness to join was collected and related to the willingness to join. To gain an insight into a respondents possible ability to pay, health care expenditure on the last illness episode was assessed. Feasibility was defined as at least 50% of household heads willing to join the scheme. Results. Willingness to join the CHI model for US$30 per year was 69.3%. With affiliation, 92.2% of interviewees stated that they would visit the local health facility more often. Willingness to join was found to be negatively associated with education. Other variables showed no significant association with willingness to join. The study showed a positive attitude toward the CHI scheme. Substantial health care expenditures on the last illness episode were documented. Conclusions. The investigation concludes that CHI in the study region is feasible. However, enrollments are likely to be lower than the stated willingness to join. Still, a CHI scheme should present an interesting financing alternative in rural areas where services are scarce and difficult to sustain.

    Place, publisher, year, edition, pages
    Organizacion Panamericana de la Salud, 2011
    Keywords
    Health insurance, feasibility studies, primary health care, Ecuador
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-68013 (URN)000289364100005 ()
    Available from: 2011-05-06 Created: 2011-05-06 Last updated: 2018-07-26
    2. Collaboration between non-governmental organizations and public services in health - a qualitative case study from rural Ecuador
    Open this publication in new window or tab >>Collaboration between non-governmental organizations and public services in health - a qualitative case study from rural Ecuador
    Show others...
    2016 (English)In: Global Health Action, ISSN 1654-9716, E-ISSN 1654-9880, Vol. 9, article id 32237Article in journal (Refereed) Published
    Abstract [en]

    Background: Non-governmental organizations (NGOs) have a key role in improving health in low-and middle-income countries. Their work needs to be synergistic, complementary to public services, and rooted in community mobilization and collective action. The study explores how an NGO and its health services are perceived by the population that it serves, and how it can contribute to reducing barriers to care. Design: A qualitative exploratory study was conducted in remote Ecuador, characterized by its widespread poverty and lack of official governance. An international NGO collaborated closely with the public services to deliver preventative and curative health services. Data were collected using focus group discussions and semistructured interviews with purposively sampled community members, healthcare personnel, and community health workers based on their links to the health services. Conventional qualitative content analysis was used, focusing on manifest content. Results: Emerging themes relate to the public private partnership (PPP), the NGO and its services, and community participation. The population perceives the NGO positively, linking it to healthcare improvements. Their priority is to get services, irrespective of the providers structure. The presence of an NGO in the operation may contribute to unrealistic expectations of health services, affecting perceptions of the latter negatively. Conclusions: To avoid unrealistic expectations and dissatisfaction, and to increase and sustain the populations trust in the organization, an NGO should operate in a manner that is as integrated as possible within the existing structure. The NGO should work close to the population it serves, with services anchored in the community. PPP parties should develop a common platform with joint messages to the target population on the providers structure, and regarding partners roles and responsibilities. Interaction between the population and the providers on service content and their expectations is key to positive outcomes of PPP operations.

    Place, publisher, year, edition, pages
    CO-ACTION PUBLISHING, 2016
    Keywords
    community participation; healthcare services; perception; primary healthcare; public private partnership
    National Category
    Health Care Service and Management, Health Policy and Services and Health Economy
    Identifiers
    urn:nbn:se:liu:diva-134110 (URN)10.3402/gha.v9.32237 (DOI)000390858600001 ()27852423 (PubMedID)
    Note

    Funding Agencies|Karolinska Institutet; Linkoping University; Ecuador

    Available from: 2017-01-22 Created: 2017-01-22 Last updated: 2018-07-26
  • 5.
    Eckhardt, Martin
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Emergency Medicine.
    Santillán, Dimitri
    Universidad Central del Ecuador, Facultad de Ciencias Médicas, Quito, Ecuador.
    Faresjö, Tomas
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Forsberg, Birger C.
    Karolinska Institute, Department of Public Health Sciences, Stockholm, Sweden.
    Falk, Magnus
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Primary Care Center, Primary Health Care Center Kärna, Linköping.
    Universal Health Coverage in Rural Ecuador: A Cross-sectional Study of Perceived Emergencies2018In: Western Journal of Emergency Medicine, ISSN 1936-900X, E-ISSN 1936-9018, Vol. 19, no 5, p. 889-900Article in journal (Refereed)
    Abstract [en]

    Introduction: In many low- and middle-income countries emergency care is provided anywhere in the health system; however, no studies to date have looked at which providers are chosen by patients with perceived emergencies. Ecuador has universal health coverage that includes emergency care. However, earlier research indicates that patients with emergencies tend to seek private care. Our primary research questions were these: What is the scope of perceived emergencies?; What is their nature?; and What is the related healthcare-seeking behavior? Secondary objectives were to study determinants of healthcare-seeking behavior, compare health expenditure with expenditure from the past ordinary illness, and measure the prevalence of catastrophic health expenditure related to perceived emergencies. 

    Methods: We conducted a cross-sectional survey of 210 households in a rural region of northwestern Ecuador. The households were sampled with two-stage cluster sampling and represent an estimated 20% of the households in the region. We used two structured, pretested questionnaires. The first questionnaire collected demographic and economic household data, expenditure data on the past ordinary illness, and presented our definition of perceived emergency. The second recorded the number of emergency events, symptoms, further case description, healthcare-seeking behavior, and health expenditure, which was defined as being catastrophic when it exceeded 40% of a household´s ability to pay.

    Results: The response rate was 85% with a total of 74 reported emergency events during the past year (90/1,000 inhabitants). We further analyzed the most recent event in each household (n=54). Private, for-profit providers, including traditional healers, were chosen by 57.4% (95% confidence interval [CI] [44-71%]). Public providers treated one third of the cases. The mean health expenditure per event was $305.30 United States dollars (USD), compared to $135.80 USD for the past ordinary illnesses. Catastrophic health expenditure was found in 24.4% of households. 

    Conclusion: Our findings suggest that the provision of free health services may not be sufficient to reach universal health coverage for patients with perceived emergencies. Changes in the organization of public emergency departments and improved financial protection for emergency patients may improve the situation.

  • 6.
    Fritz, Michael
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Klawonn, Anna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Nilsson, Anna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Kumar Singh, Anand
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Zajdel, Joanna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Wilhelms, Daniel
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Emergency Medicine.
    Lazarus, Michael
    University of Tsukuba, Japan.
    Löfberg, Andreas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Jaarola, Maarit
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Örtegren Kugelberg, Unn
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Billiar, Timothy R.
    University of Pittsburgh, PA USA.
    Hackam, David J.
    Johns Hopkins University, MD USA.
    Sodhi, Chhinder P.
    Johns Hopkins University, MD USA.
    Breyer, Matthew D.
    Lilly Research Labs, IN USA.
    Jakobsson, Johan
    Lund University, Sweden; Lund University, Sweden.
    Schwaninger, Markus
    University of Lubeck, Germany.
    Schuetz, Gunther
    German Cancer Research Centre, Germany.
    Rodriguez Parkitna, Jan
    Polish Academic Science, Poland.
    Saper, Clifford B.
    Beth Israel Deaconess Medical Centre, MA 02215 USA; Harvard University, MA USA.
    Blomqvist, Anders
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Engblom, David
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Prostaglandin-dependent modulation of dopaminergic neurotransmission elicits inflammation-induced aversion in mice2016In: Journal of Clinical Investigation, ISSN 0021-9738, E-ISSN 1558-8238, Vol. 126, no 2, p. 695-705Article in journal (Refereed)
    Abstract [en]

    Systemic inflammation causes malaise and general feelings of discomfort. This fundamental aspect of the sickness response reduces the quality of life for people suffering from chronic inflammatory diseases and is a nuisance during mild infections like common colds or the flu. To investigate how inflammation is perceived as unpleasant and causes negative affect, we used a behavioral test in which mice avoid an environment that they have learned to associate with inflammation-induced discomfort. Using a combination of cell-type-specific gene deletions, pharmacology, and chemogenetics, we found that systemic inflammation triggered aversion through MyD88-dependent activation of the brain endothelium followed by COX1-mediated cerebral prostaglandin E-2 (PGE(2)) synthesis. Further, we showed that inflammation-induced PGE(2) targeted EP1 receptors on striatal dopamine D1 receptor-expressing neurons and that this signaling sequence induced aversion through GABA-mediated inhibition of dopaminergic cells. Finally, we demonstrated that inflammation-induced aversion was not an indirect consequence of fever or anorexia but that it constituted an independent inflammatory symptom triggered by a unique molecular mechanism. Collectively, these findings demonstrate that PGE(2)-mediated modulation of the dopaminergic motivational circuitry is a key mechanism underlying the negative affect induced by inflammation.

  • 7.
    Henricson, Joakim
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology.
    Toll John, Rani
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Anderson, Chris
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology.
    Björk Wilhelms, Daniel
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Emergency Medicine.
    Diffuse Reflectance Spectroscopy: Getting the Capillary Refill Test Under Ones Thumb2017In: Journal of Visualized Experiments, ISSN 1940-087X, E-ISSN 1940-087X, no 130, article id e56737Article in journal (Refereed)
    Abstract [en]

    The capillary refill test was introduced in 1947 to help estimate circulatory status in critically ill patients. Guidelines commonly state that refill should occur within 2 s after releasing 5 s of firm pressure (e.g., by the physicians finger) in the normal healthy supine patient. A slower refill time indicates poor skin perfusion, which can be caused by conditions including sepsis, blood loss, hypoperfusion, and hypothermia. Since its introduction, the clinical usefulness of the test has been debated. Advocates point out its feasibility and simplicity and claim that it can indicate changes in vascular status earlier than changes in vital signs such as heart rate. Critics, on the other hand, stress that the lack of standardization in how the test is performed and the highly subjective nature of the naked eye assessment, as well as the tests susceptibility to ambient factors, markedly lowers the clinical value. The aim of the present work is to describe in detail the course of the refill event and to suggest potentially more objective and exact endpoint values for the capillary refill test using diffuse polarization spectroscopy.

    The full text will be freely available from 2019-12-02 09:45
  • 8.
    Klawonn, Anna
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Stanford Univ, CA 94305 USA.
    Wilhelms, Daniel
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Emergency Medicine.
    Lindström, Sarah
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Singh, Anand Kumar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Baylor Coll Med, TX 77030 USA.
    Jaarola, Maarit
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Wess, Jurgen
    NIH, MD 20892 USA.
    Fritz, Michael
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Stanford Univ, CA 94305 USA.
    Engblom, David
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Muscarinic M4 Receptors on Cholinergic and Dopamine D1 Receptor-Expressing Neurons Have Opposing Functionality for Positive Reinforcement and Influence Impulsivity2018In: Frontiers in Molecular Neuroscience, ISSN 1662-5099, Vol. 11, article id 139Article in journal (Refereed)
    Abstract [en]

    The neurotransmitter acetylcholine has been implicated in reward learning and drug addiction. However, the roles of the various cholinergic receptor subtypes on different neuron populations remain elusive. Here we study the function of muscarinic M4 receptors (M4Rs) in dopamine D1 receptor (D1R) expressing neurons and cholinergic neurons (expressing choline acetyltransferase; ChAT), during various reward-enforced behaviors and in a "waiting"-impulsivity test. We applied cell-type-specific gene deletions targeting M4Rs in D1RCre or ChATCre mice. Mice lacking M4Rs in D1R-neurons displayed greater cocaine seeking and drug-primed reinstatement than their littermate controls in a Pavlovian conditioned place preference (CPP) paradigm. Furthermore, the M4R-D1RCre mice initiated significantly more premature responses (PRs) in the 5-choice-serial-reaction-time-task (5CSRTT) than their littermate controls, indicating impaired waiting impulse control. In contrast, mice lacking M4Rs in cholinergic neurons did not acquire cocaine Pavlovian conditioning. The M4R-ChATCre mice were also unable to learn positive reinforcement to either natural reward or cocaine in an operant runway paradigm. Immediate early gene (IEG) expression (cFos and FosB) induced by repeated cocaine injections was significantly increased in the forebrain of M4R-D1RCre mice, whereas it remained normal in the M4R-ChATCre mice. Our study illustrates that muscarinic M4Rs on specific neural populations, either cholinergic or D1R-expressing, are pivotal for learning processes related to both natural reward and drugs of abuse, with opposing functionality. Furthermore, we found that neurons expressing both M4Rs and D1Rs are important for signaling impulse control.

  • 9.
    Källman, Ulrika
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences. Södra Älvsborgs Sjukhus, Sweden.
    Bergstrand, Sara
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Science & Engineering.
    Ek, Anna-Christina
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Emergency Medicine.
    Engström, Maria
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Lindgren, Margareta
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Medical and Health Sciences, Division of Nursing Science.
    Blood flow responses over sacrum in nursing home residents during one hour bed rest2016In: Microcirculation, ISSN 1073-9688, E-ISSN 1549-8719, Vol. 23, no 7, p. 530-539Article in journal (Refereed)
    Abstract [en]

    ObjectivesTo describe individual BF responses in a nursing home resident population for one-hour periods of bed rest. MethodsBF was measured for one hour over the sacrum in 0 degrees supine position and 30 degrees supine tilt position in 25 individuals aged 65 y or older while lying on a pressure-redistributing mattress. Measurements were made at three tissue depths (1, 2, and 10 mm) using the noninvasive optical techniques, LDF and PPG. ResultsEleven participants had a PIV response at 1mm depth in both positions and seven participants had a lack of this response at this depth and positions. The BF response at 1mm depth appeared immediately and remained over, or below, baseline for the entire 60min of loading in both positions. These BF patterns were also seen in deeper tissue layers. ConclusionsThe cutaneous BF response among the nursing home residents was distinct, appeared early, and remained during the one hour of loading.

  • 10.
    Källman, Ulrika
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Health Sciences.
    Bergstrand, Sara
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Ek, Anna-Christina
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Emergency Medicine.
    Engström, Maria
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Lindgren, Margareta
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Health Sciences.
    Nursing staff induced repositionings and immobile patients' spontaneous movements in nursing care.2016In: International Wound Journal, ISSN 1742-4801, E-ISSN 1742-481X, Vol. 13, no 6, p. 1168-1175Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to investigate nursing staff induced repositionings and the patients' spontaneous movements during the day and night among older immobile patients in nursing care. Furthermore, the aim was to identify factors associated with the nursing staff induced repositionings and the patients' spontaneous movement frequency. An observational cross-sectional design was used. Spontaneous movements among patients (n = 52) were registered continuously using the MovinSense monitoring system. The nursing staff documented each time they repositioned the patient. Patients spontaneous movements were compared with nursing staff induced repositionings. There were large variations in the patients' spontaneous repositioning frequency during both days and nights, which shows that, although immobilised, some patients frequently reposition themselves. Analgesics were positively related to the movement frequency and psycholeptics were negatively related. The nursing staff more often repositioned the patients who were assessed as high risk than those assessed as low risk, but the patients' spontaneous movement frequency was not correlated to the risk score. This may be important when planning repositioning schedules. A monitoring system may be useful in decision making with regard to planning repositioning and positions used in the prevention of pressure ulcers among elderly immobile patients.

  • 11.
    Källman, Ulrika
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Health Sciences.
    Bergstrand, Sara
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Ek, Anna-Christina
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Acute Health Care in Linköping.
    Engström, Maria
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Lindgren, Margareta
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Health Sciences.
    Sacral pressure-induced blood flow responses at different tissue depths during one hour supine bedrest in nursing home residents2015Manuscript (preprint) (Other academic)
    Abstract [en]

    Background. Pressure induced vasodilation (PIV) protects the skin from pressure induced ischemia. PIV responses at individual level during a long-term measurement period have not previously been described in an elderly population in a clinically relevant situation.

    Aim. To describe individual PIV responses in a nursing home resident population for 1-hour periods of bed rest.

    Method. From May 2011 to August 2012, blood flow at three tissue depths was measured for one hour over the sacrum in 0° supine position and 30° supine tilt position in 25 individuals aged 65 years or older while lying on a pressure redistributing mattress. Measurements were made using the non-invasive optical techniques Laser Doppler Flowmetry (LDF) and photoplethysmography. The individuals were divided into a PIV group and a non-PIV group based upon the LDF data.

    Results. In the PIV group, the blood flow in almost all cases increased immediately and remained over baseline for the entire 60 minutes of loading in both positions, while the blood flow decreased immediately and remained below baseline in the non-PIV group. These blood flow patterns were also seen in deeper tissue layers although a PIV response was most common in the underlying tissue in both groups.

    Conclusion. The cutaneous blood flow response among the nursing home residents was distinct, appeared early and remained during the one hour of loading in both the PIV and non-PIV group. The non-PIV group may be more vulnerable to pressure and thus may be at risk for pressure ulcer development. More research is needed in order to verify the results.

  • 12.
    Linder, Adam
    et al.
    Lund University, Sweden.
    Arnold, Ryan
    Christiana Care Health Syst, DE USA; Christiana Care Health Syst, DE USA.
    Boyd, John H.
    University of British Columbia, Canada.
    Zindovic, Marko
    Lund University, Sweden.
    Zindovic, Igor
    Lund University, Sweden.
    Lange, Anna
    Örebro University Hospital, Sweden.
    Paulsson, Magnus
    Lund University, Sweden.
    Nyberg, Patrik
    Region Östergötland, Local Health Care Services in Central Östergötland, Department of Emergency Medicine. Linköping University.
    Russell, James A.
    University of British Columbia, Canada.
    Pritchard, David
    Axis Shield Diagnost, Scotland.
    Christensson, Bertil
    Lund University, Sweden.
    Akesson, Per
    Lund University, Sweden.
    Heparin-Binding Protein Measurement Improves the Prediction of Severe Infection With Organ Dysfunction in the Emergency Department2015In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 43, no 11, p. 2378-2386Article in journal (Refereed)
    Abstract [en]

    Objectives: Early identification of patients with infection and at risk of developing severe disease with organ dysfunction remains a difficult challenge. We aimed to evaluate and validate the heparin-binding protein, a neutrophil-derived mediator of vascular leakage, as a prognostic biomarker for risk of progression to severe sepsis with circulatory failure in a multicenter setting. Design: A prospective international multicenter cohort study. Setting: Seven different emergency departments in Sweden, Canada, and the United States. Patients: Adult patients with a suspected infection and at least one of three clinical systemic inflammatory response syndrome criteria (excluding leukocyte count). Intervention: None. Measurements and Main Results: Plasma levels of heparin-binding protein, procalcitonin, C-reactive protein, lactate, and leukocyte count were determined at admission and 12-24 hours after admission in 759 emergency department patients with suspected infection. Patients were defined depending on the presence of infection and organ dysfunction. Plasma samples from 104 emergency department patients with suspected sepsis collected at an independent center were used to validate the results. Of the 674 patients diagnosed with an infection, 487 did not have organ dysfunction at enrollment. Of these 487 patients, 141 (29%) developed organ dysfunction within the 72-hour study period; 78.0% of the latter patients had an elevated plasma heparin-binding protein level (greater than 30 ng/mL) prior to development of organ dysfunction (median, 10.5 hr). Compared with other biomarkers, heparin-binding protein was the best predictor of progression to organ dysfunction (area under the receiver operating characteristic curve = 0.80). The performance of heparin-binding protein was confirmed in the validation cohort. Conclusion: In patients presenting at the emergency department, heparin-binding protein is an early indicator of infection-related organ dysfunction and a strong predictor of disease progression to severe sepsis within 72 hours.

  • 13.
    Nilsson, Anna
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Wilhelms, Daniel
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Emergency Medicine.
    Mirrasekhian, Elahe
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Jaarola, Maarit
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Blomqvist, Anders
    Linköping University, Department of Clinical and Experimental Medicine, Divison of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences.
    Engblom, David
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Inflammation-induced anorexia and fever are elicited by distinct prostaglandin dependent mechanisms, whereas conditioned taste aversion is prostaglandin independent.2017In: Brain, behavior, and immunity, ISSN 0889-1591, E-ISSN 1090-2139, Vol. 61, p. 236-243, article id S0889-1591(16)30549-9Article in journal (Refereed)
    Abstract [en]

    Systemic inflammation evokes an array of brain-mediated responses including fever, anorexia and taste aversion. Both fever and anorexia are prostaglandin dependent but it has been unclear if the cell-type that synthesizes the critical prostaglandins is the same. Here we show that pharmacological inhibition or genetic deletion of cyclooxygenase (COX)-2, but not of COX-1, attenuates inflammation-induced anorexia. Mice with deletions of COX-2 selectively in brain endothelial cells displayed attenuated fever, as demonstrated previously, but intact anorexia in response to peripherally injected lipopolysaccharide (10μg/kg). Whereas intracerebroventricular injection of a cyclooxygenase inhibitor markedly reduced anorexia, deletion of COX-2 selectively in neural cells, in myeloid cells or in both brain endothelial and neural cells had no effect on LPS-induced anorexia. In addition, COX-2 in myeloid and neural cells was dispensable for the fever response. Inflammation-induced conditioned taste aversion did not involve prostaglandin signaling at all. These findings collectively show that anorexia, fever and taste aversion are triggered by distinct routes of immune-to-brain signaling.

  • 14.
    Simona Chisalita, Ioana
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology.
    Chong, Lee Ti
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Wajda, Maciej
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Emergency Medicine.
    Adolfsson, Lars
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Woisetschläger, Mischa
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Spångeus, Anna
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology.
    Association of Insulin-like Growth Factor-1, Bone Mass and Inflammation to Low-energy Distal Radius Fractures and Fracture Healing in Elderly Women Attending Emergency Care2017In: ORTHOPAEDIC SURGERY, ISSN 1757-7853, Vol. 9, no 4, p. 380-385Article in journal (Refereed)
    Abstract [en]

    Objective

    Elderly patients suffer fractures through low-energy mechanisms. The distal radius is the most frequent fracture localization. Insulin-like growth factor-1 (IGF1) plays an important role in the maintenance of bone mass and its levels decline with advancing age and in states of malnutrition. Our aim was to investigate the association of IGF1 levels, bone mass, nutritional status, and inflammation to low-energy distal radius fractures and also study if fracture healing is influenced by IGF1, nutritional status, and inflammation.

    Methods

    Postmenopausal women, 55 years or older, with low-energy distal radius fractures occurring due to falling on slippery ground, indoors or outdoors, were recruited in the emergency department (ED) and followed 1 and 5 weeks after the initial trauma with biomarkers for nutritional status and inflammation. Fractures were diagnosed according to standard procedure by physical examination and X-ray. All patients were conservatively treated with plaster casts in the ED. Patients who needed interventions were excluded from our study. Fracture healing was evaluated from radiographs. Fracture healing assessment was made with a five-point scale where the radiological assessment included callus formation, fracture line, and stage of union. Blood samples were taken within 24 h after fracture and analyzed in the routine laboratory. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry (DXA).

    Results

    Thirty-eight Caucasian women, aged 70.5 8.9 years (mean +/- SD) old, were recruited. Nutritional status, as evaluated by albumin (40.3 +/- 3.1 g/L), IGF1 (125.3 +/- 39.9 g/L), body mass index (26.9 +/- 3.6 kg/m(2)), arm diameter (28.9 +/- 8.9 cm), and arm skinfold (2.5 +/- 0.7 cm), was normal. A positive correlation was found between IGF1 at visit 1 and the lowest BMD for hip, spine, or radius (r = 0.39, P = 0.04). High sensitive C-reactive protein (hsCRP) and leukocytes were higher at the fracture event compared to 5 weeks later (P = 0.07 and P amp;lt; 0.001, respectively). Fracture healing parameters (i.e. callus formation, fracture line, and stage of union) were positively correlated with the initial leukocyte count and to difference in thrombocyte count between visit 1 and 3.

    Conclusions

    In elderly women with low-energy distal radius fractures, an association between IGF1 and lowest measures of BMD was found, indicating that low IGF1 could be an indirect risk factor for fractures. Fracture healing was associated with initial leukocytosis and a lower thrombocyte count, suggesting that inflammation and thrombocytes are important components in fracture healing.

  • 15.
    Toll John, Rani
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Emergency Medicine.
    Henricson, Joakim
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Emergency Medicine. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology.
    Junker, Johan
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Disaster Medicine and Traumatology.
    Jonson, Carl-Oscar
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Disaster Medicine and Traumatology.
    Nilsson, Gert
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology. WheelsBridge AB, Linköping, Sweden.
    Björk Wilhelms, Daniel
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Emergency Medicine.
    Anderson, Chris D
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology.
    A cool response: the influence of ambient temperature on capillary refill time2018In: Journal of Biophotonics, ISSN 1864-063X, E-ISSN 1864-0648, Vol. 11, no 6Article in journal (Refereed)
    Abstract [en]

    Objective

    To describe the effect of low ambient temperature on skin temperature and capillary refill (CR) time in forehead, sternum and finger pulp.

    Methods

    An observational, nonrandomized experimental study on 15 healthy subjects (6 females) in a cold room (8°C). Outcome measures were skin temperature and quantified CR test after application of a standardized blanching pressure (9 N/cm2) using digital photographic polarization spectroscopy to generate CR times.

    Results

    The finger pulp showed marked temperature fall and prolonged CR times (>10 seconds). The CR registrations of the forehead and sternum were more comparable to curves observed in a control material at room temperature, and skin temperature falls were less marked. CR times were not prolonged in forehead measurements. At the sternum, some individuals showed CR times beyond guideline recommendations despite only a marginal reduction in skin temperature.

    Conclusions

    Low ambient temperature is a strong independent factor for CR time at peripheral sites. Reservation about sternum as a site of measurement is warranted since cold provocation produced prolonged CR times in some individuals. We found that the forehead is the most thermostable of the 3 sites and thus the preferred site to avoid ambient temperature artifact in measuring CR time.

  • 16.
    Toll John, Rani
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Emergency Medicine.
    Henricson, Joakim
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology.
    Nilsson, Gert E.
    WheelsBridge AB, Linköping, Sweden.
    Wilhelms, Daniel
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Emergency Medicine.
    Anderson, Chris
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology.
    Reflectance spectroscopy: to shed new light on the capillary refill test2018In: Journal of Biophotonics, ISSN 1864-063X, E-ISSN 1864-0648, Vol. 11, no 1, article id e201700043Article in journal (Refereed)
    Abstract [en]

    To use Bioengineering methodology is used to achieve, at five anatomical sites, a detailed, quantitative assessment of the return of blood content to the blanched area, during the Capillary Refill (CR) test. An observational, non-randomized, experimental study on 23 healthy subjects (14 females) was performed in our climate controlled skin physiology laboratory. Our main outcome measures were based on the chronological assessment and quantification of red blood cell concentration (RBC) after the release of blanching pressure in the CR test, using Tissue Viability Imaging (TiVi), a digital photographic technique based on polarisation spectroscopy. TiVi enabled collection of detailed data on skin RBC concentration during the CR test. The results were shown as curves with skin blood concentration (TiVi-value) on the y-axis and the time on the x-axis. Quantitative CR responses showed site and temperature variability. We also suggest possible objective endpoint values from the capillary refill curve. Detailed data on skin RBC concentration during the CR test is easily obtained and allows objective determination of end points not possible to achieve by naked eye assessment. These findings have the potential to place the utility of the CR test in a clinical setting in a new light. Picture: Regular photograph and TiVi Image showing CR test and corresponding graph for the CR response. [GRAPHICS] .

  • 17.
    Tornell, Elena
    Region Östergötland, Local Health Care Services in Central Östergötland, Department of Emergency Medicine.
    Jobba i England – Hur coolt var det?2017In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 114, no 12Article in journal (Refereed)
  • 18.
    Van dijk, Peter R
    et al.
    Isala, Diabetes Centre, Zwolle, The Netherlands.
    Logtenberg, Susan J J
    University Medical Center Groningen, The Netherlands.
    Chisalita, Ioana Simona
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Emergency Medicine.
    Hedman, Christina A.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology.
    Groenier, Klaas H
    University Medical Center Groningen, The Netherlands.
    Gans, Reinold O B
    University Medical Center Groningen, The Netherlands.
    Kleefstra, Nanne
    University Medical Center Groningen, The Netherlands.
    Arnqvist, Hans J.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology.
    Bilo, Henk J G
    University Medical Center Groningen, The Netherlands.
    After 6years of intraperitoneal insulin administration IGF-I concentrations in T1DM patients are at low-normal level.2015In: Growth Hormone & IGF Research, ISSN 1096-6374, E-ISSN 1532-2238, Vol. 25, no 6, p. 316-319Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Low concentrations of insulin-like growth factor-I (IGFI) have been reported in type 1 diabetes mellitus (T1DM), suggested to be due to low insulin concentrations in the portal vein. The aim was to describe the long-term course of IGFI concentrations among T1DM subjects treated with continuous intraperitoneal (IP) insulin infusion (CIPII).

    DESIGN: Nineteen patients that participated in a randomized cross-over trial comparing CIPII and subcutaneous (SC) insulin therapy in 2006 were followed until 2012. IGF-I measurements were performed at the start of the 2006 study, after the 6month SC- and CIPII treatment phase in 2006 and during CIPII therapy in 2012. Z-scores were calculated to compare the IGF-I concentrations with age-specific normative range values of a non-DM reference population.

    RESULTS: In 2012, IGF-I Z-scores (-0.7; 95% confidence interval -1.3, -0.2) were significantly higher than at the start of the 2006 study (-2.5; -3.3, -1.8), the end of the SC (-2.0; -2.6, -1.5) and CIPII (-1.6; -2.1, -1.0) treatment phase with a mean difference of: 1.8 (0.9, 2.7), 1.3 (0.5, 2.1) and 0.8 (0.1, 1.6), respectively.

    CONCLUSION: After 6years of treatment with CIPII, IGF-I concentrations among T1DM patients increased to a level that is higher than during prior SC insulin treatment and is in the lower normal range compared to a non-DM reference population. The results of this study suggest that long-term IP insulin administration influences the IGF system in T1DM.

  • 19.
    van Dijk, Peter R.
    et al.
    Isala, Netherlands.
    Logtenberg, Susan J. J.
    Isala, Netherlands; Diakonessen Hospital, Netherlands.
    Chisalita, Ioana Simona
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Emergency Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Hedman, Christina
    Region Östergötland, Heart and Medicine Center, Department of Endocrinology. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine.
    Groenier, Klaas H.
    Isala, Netherlands; University of Groningen, Netherlands.
    Gans, Reinold O. B.
    University of Groningen, Netherlands.
    Kleefstra, Nanne
    Isala, Netherlands; University of Groningen, Netherlands; Langerhans Medical Research Grp, Netherlands.
    Arnqvist, Hans
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology.
    Bilo, Henk J. G.
    Isala, Netherlands; Isala, Netherlands; University of Groningen, Netherlands.
    Different Effects of Intraperitoneal and Subcutaneous Insulin Administration on the GH-IGF-1 Axis in Type 1 Diabetes2016In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 101, no 6, p. 2493-2501Article in journal (Refereed)
    Abstract [en]

    Context: In type 1 diabetes mellitus, low levels of insulin-like growth factor -1 (IGF-1) and IGF binding protein-3 (IGFBP-3) and high levels of GH and IGFBP-1 are present, probably due to portal vein insulinopenia. Objective: To test the hypothesis that continuous ip insulin infusion (CIPII) has a more pronounced effect than sc insulin therapy on regulation of the GH-IGF-1 axis. Design: This was a prospective, observational case-control study. Measurements were performed twice at a 26-week interval. Setting: Two secondary care hospitals in the Netherlands participated in the study. Patients: There were a total of 184 patients, age-and gender-matched, of which 39 used CIPII and 145 sc insulin therapy for the past 4 years. Outcomes: Primary endpoint included differences in IGF-1. Secondary outcomes were differences in GH, IGFBP-1, and IGFBP-3. Results: IGF-1 was higher with CIPII as compared to SC insulin therapy: 124 mu g/liter (95% confidence interval [CI], 111-138) vs 108 mu g/liter (95% CI 102-115) (P = .035). Additionally, IGFBP-3 concentrations were higher and IGFBP-1 and GH concentrations were lower with CIPII as compared to SC insulin therapy: 3.78 mg/liter (95% CI, 3.49 - 4.10) vs 3.31 mg/liter (95% CI, 3.173.47) for IGFBP-3, 50.9 mu g/liter (95% CI, 37.9 - 68.2) vs 102.6 mu g/liter (95% CI, 87.8 - 119.8) for IGFBP-1 and 0.68 mu g/liter (95% CI, 0.44 - 1.06) vs 1.21 mu g/liter (95% CI, 0.95-1.54) for GH, respectively. In multivariate analysis, IGF-1 had no significant association with HbA1c. Conclusions: The GH-IGF-1 axis may be affected by the route of insulin administration with CIPII counteracting dysregulation of the GH-IGF1 axis present during sc insulin therapy.

  • 20.
    Wilhelms, Daniel
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Clinical and Experimental Medicine. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Emergency Medicine.
    Mirrasekhian, Elahe
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Zajdel, Joanna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Singh, Anand Kumar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Engblom, David
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Cyclooxygenase Isoform Exchange Blocks Brain-Mediated Inflammatory Symptoms2016In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 11, article id e0166153Article in journal (Refereed)
    Abstract [en]

    Cyclooxygenase-2 (COX-2) is the main source of inducible prostaglandin E-2 production and mediates inflammatory symptoms including fever, loss of appetite and hyperalgesia. COX-1 is dispensable for fever, anorexia and hyperalgesia but is important for several other functions both under basal conditions and during inflammation. The differential functionality of the COX isoforms could be due to differences in the regulatory regions of the genes, leading to different expression patterns, or to differences in the coding sequence, resulting in distinct functional properties of the proteins. To study the molecular underpinnings of the functional differences between the two isoforms in the context of inflammatory symptoms, we used mice in which the coding sequence of COX-2 was replaced by the corresponding sequence of COX-1. In these mice, COX-1 mRNA was induced by inflammation but COX-1 protein expression did not fully mimic inflammation-induced COX-2 expression. Just like mice globally lacking COX-2, these mice showed a complete lack of fever and inflammation-induced anorexia as well as an impaired response to inflammatory pain. However, as previously reported, they displayed close to normal survival rates, which contrasts to the high fetal mortality in COX-2 knockout mice. This shows that the COX activity generated from the hybrid gene was strong enough to allow survival but not strong enough to mediate the inflammatory symptoms studied, making the line an interesting alternative to COX-2 knockouts for the study of inflammation. Our results also show that the functional differences between COX-1 and COX-2 in the context of inflammatory symptoms are not only dependent on the features of the promoter regions. Instead they indicate that there are fundamental differences between the isoforms at translational or posttranslational levels.

  • 21.
    Wilhelms, Daniel
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Emergency Medicine.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Chew, Michelle
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Linköping.
    Emergency medicine is about collaboration, not monopolisation2018In: European Journal of Anaesthesiology, ISSN 0265-0215, E-ISSN 1365-2346, Vol. 35, no 3, p. 231-232Article in journal (Other academic)
    Abstract [en]

    n/a

1 - 21 of 21
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