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  • 101.
    Abioye, Ajibola I.
    et al.
    Brown Univ, RI 02912 USA.
    McDonald, Emily A.
    Brown Univ, RI 02912 USA.
    Park, Sangshin
    Brown Univ, RI 02912 USA; Univ Seoul, South Korea.
    Joshi, Ayush
    Brown Univ, RI 02912 USA.
    Kurtis, Jonathan D.
    Brown Univ, RI 02912 USA.
    Wu, Hannah
    Brown Univ, RI 02912 USA.
    Pond-Tor, Sunthorn
    Brown Univ, RI 02912 USA.
    Sharma, Surendra
    Brown Univ, RI 02912 USA; Women and Infants Hosp Rhode Isl, RI 02908 USA.
    Ernerudh, Jan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin.
    Baltazar, Palmera
    Remedios Trinidad Romualdez Hosp, Philippines.
    Acosta, Luz P.
    Res Inst Trop Med, Philippines.
    Olveda, Remigio M.
    Res Inst Trop Med, Philippines.
    Tallo, Veronica
    Res Inst Trop Med, Philippines.
    Friedman, Jennifer F.
    Brown Univ, RI 02912 USA.
    Maternal, placental and cord blood cytokines and the risk of adverse birth outcomes among pregnant women infected with Schistosoma japonicum in the Philippines2019Inngår i: PLoS Neglected Tropical Diseases, ISSN 1935-2727, E-ISSN 1935-2735, Vol. 13, nr 6, artikkel-id e0007371Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background The objectives of this study were to 1) evaluate the influence of treatment with praziquantel on the inflammatory milieu in maternal, placental, and cord blood, 2) assess the extent to which proinflammatory signatures in placental and cord blood impacts birth outcomes, and 3) evaluate the impact of other helminths on the inflammatory micro environment. Methods/Findings This was a secondary analysis of samples from 369 mother-infant pairs participating in a randomized controlled trial of praziquantel given at 12-16 weeks gestation. We performed regression analysis to address our study objectives. In maternal peripheral blood, the concentrations of CXCL8, and TNF receptor I and II decreased from 12 to 32 weeks gestation, while IL-13 increased. Praziquantel treatment did not significantly alter the trajectory of the concentration of any of the cytokines examined. Hookworm infection was associated with elevated placental IL-1, CXCL8 and IFN-gamma. The risk of small-for-gestational age increased with elevated IL-6, IL-10, and CXCL8 in cord blood. The risk of prematurity was increased when cord blood sTNFRI and placental IL-5 were elevated. Conclusions Our study suggests that fetal cytokines, which may be related to infectious disease exposures, contribute to poor intrauterine growth. Additionally, hookworm infection influences cytokine concentrations at the maternal-fetal interface. Clinical Trial Registry number and website ClinicalTrials.gov (NCT00486863). Author summary Schistosomiasis is one of the most prevalent parasitic tropical diseases, and it is primarily treated with the drug praziquantel. This study examined the effects of praziquantel treatment for schistosomiasis and the presence of geohelminth infections during pregnancy on cytokines in maternal, placental, and cord blood, and examined the effects of pro-inflammatory signatures at the maternal-fetal interface on perinatal outcomes. We analyzed the data of 369 mother-infant pairs obtained from a randomized controlled trial of praziquantel given at 12-16 weeks gestation. Praziquantel treatment did not significantly alter the trajectory of the concentration of any of the cytokines examined. Elevated levels of both Th1 and Th2 cytokines were associated with the risk of adverse perinatal outcomes (small-for-gestational age and prematurity). Hookworm coinfection at 12 weeks gestation was, however, related to elevated levels of certain cytokines in the placenta (IL-1, IL-5, CXCL8 and IFN-gamma).

    Fulltekst (pdf)
    fulltext
  • 102.
    Abioye, Ajibola I.
    et al.
    Brown Univ, RI 02912 USA; Rhode Isl Hosp, RI USA; Rhode Isl Hosp, RI USA.
    Park, Sangshin
    Brown Univ, RI 02912 USA; Rhode Isl Hosp, RI USA; Rhode Isl Hosp, RI USA.
    Ripp, Kelsey
    Brown Univ, RI 02912 USA.
    McDonald, Emily A.
    Brown Univ, RI 02912 USA; Rhode Isl Hosp, RI USA; Rhode Isl Hosp, RI USA.
    Kurtis, Jonathan D.
    Brown Univ, RI 02912 USA; Rhode Isl Hosp, RI USA; Rhode Isl Hosp, RI USA.
    Wu, Hannah
    Brown Univ, RI 02912 USA; Rhode Isl Hosp, RI USA; Rhode Isl Hosp, RI USA.
    Pond-Tor, Sunthorn
    Rhode Isl Hosp, RI USA.
    Sharma, Surendra
    Brown Univ, RI 02912 USA; Women and Infants Hosp Rhode Isl, RI 02908 USA.
    Ernerudh, Jan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin.
    Baltazar, Palmera
    Res Inst Trop Med, Philippines; Remedios Trinidad Romualdez Hosp, Philippines.
    Acosta, Luz P.
    Res Inst Trop Med, Philippines.
    Olveda, Remigio M.
    Res Inst Trop Med, Philippines.
    Tallo, Veronica
    Res Inst Trop Med, Philippines.
    Friedman, Jennifer F.
    Brown Univ, RI 02912 USA; Rhode Isl Hosp, RI USA; Rhode Isl Hosp, RI USA.
    Anemia of Inflammation during Human Pregnancy Does Not Affect Newborn Iron Endowment2018Inngår i: Journal of Nutrition, ISSN 0022-3166, E-ISSN 1541-6100, Vol. 148, nr 3, s. 427-436Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: To our knowledge, no studies have addressed whether maternal anemia of inflammation (AI) affects newborn iron status, and few have addressed risk factors for specific etiologies of maternal anemia. Objectives: The study aims were to evaluate 1) the contribution of AI and iron deficiency anemia (IDA) to newborn iron endowment, 2) hepcidin as a biomarker to distinguish AI from IDA among pregnant women, and 3) risk factors for specific etiologies of maternal anemia. Methods: We measured hematologic biomarkers in maternal blood at 12 and 32 wk of gestation and in cord blood from a randomized trial of praziquantel in 358 pregnant women with Schistosoma japonicum in The Philippines. IDA was defined as anemia with serum ferritin amp;lt; 30 ng/mL and non-IDA (NIDA), largely due to AI, as anemia with ferritin amp;gt;= 30 ng/mL. We identified cutoffs for biomarkers to distinguish IDA from NIDA by using area under the curve (AUC) analyses and examined the impact of different causes of anemia on newborn iron status (primary outcome) by using multivariate regression modeling. Results: Of the 358 mothers, 38% (n = 136) had IDA and 9% (n = 32) had NIDA at 32 wk of gestation. At 32 wk of gestation, serum hepcidin performed better than soluble transferrin receptor (sTfR) in identifying women with NIDA compared with the rest of the cohort (AUCs: 0.75 and 0.70, respectively) and in identifying women with NIDA among women with anemia (0.73 and 0.72, respectively). The cutoff that optimally distinguished women with NIDA from women with IDA in our cohort was 6.1 mu g/L. Maternal IDA, but not NIDA, was associated with significantly lower newborn ferritin (114.4 ng/mL compared with 148.4 mu g/L; P = 0.042). Conclusions: Hepcidin performed better than sTfR in identifying pregnant women with NIDA, but its cost may limit its use. Maternal IDA, but not NIDA, is associated with decreased newborn iron stores, emphasizing the need to identify this cause and provide iron therapy.

  • 103.
    Aboelnaga, Ahmed
    et al.
    Plastic Surgery Unit, Surgery Department, Suez Canal University, Egypt.
    Elmasry, Moustafa
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Hand- och plastikkirurgiska kliniken US. Plastic Surgery Unit, Surgery Department, Suez Canal University, Egypt.
    Adly, Osama A.
    Plastic Surgery Unit, Surgery Department, Suez Canal University, Egypt.
    Elbadawy, Mohamed A.
    Plastic Surgery Unit, Surgery Department, Suez Canal University, Egypt.
    Abbas, Ashraf H.
    Plastic Surgery Unit, Surgery Department, Suez Canal University, Egypt.
    Abdelrahman, Islam
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Hand- och plastikkirurgiska kliniken US. Plastic Surgery Unit, Surgery Department, Suez Canal University, Egypt.
    Salah, Omar
    Plastic Surgery Unit, Surgery Department, Suez Canal University, Egypt.
    Steinvall, Ingrid
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Hand- och plastikkirurgiska kliniken US.
    Microbial cellulose dressing compared with silver sulphadiazine for the treatment of partial thickness burns: A prospective, randomised, clinical trial2018Inngår i: Burns, ISSN 0305-4179, E-ISSN 1879-1409, Vol. 44, nr 8, s. 1982-1988Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background

    The current treatment for partial thickness burns at the trial site is silver sulphadiazine, as it minimises bacterial colonisation of wounds. Its deleterious effect on wound healing, together with the need for repeated, often painful, procedures, has brought about the search for a better treatment. Microbial cellulose has shown promising results that avoid these disadvantages. The aim of this study was therefore to compare microbial cellulose with silver sulphadiazine as a dressing for partial thickness burns.

    Method

    All patients who presented with partial thickness (superficial and deep dermal) burns from October 2014 to October 2016 were screened for this randomised clinical trial. Twenty patients were included in each group: the cellulose group was treated with microbial cellulose sheets and the control group with silver sulphadiazine cream 10 mg/g. The wound was evaluated every third day. Pain was assessed using the Face, Legs, Activity, Cry, Consolability (FLACC) scale during and after each procedure. Other variables recorded were age, sex, percentage total body surface area burned (TBSA%), clinical signs of infection, time for epithelialisation and hospital stay. Linear multivariable regression was used to analyse the significance of differences between the treatment groups by adjusting for the size and depth of the burn, and the patient’s age.

    Results

    Median TBSA% was 9% (IQR 5.5–12.5). The median number of dressing changes was 1 (IQR 1–2) in the cellulose group, which was lower than that in the control group (median 9.5, IQR 6–16) (p < 0.001). Multivariable regression analysis showed that the group treated with microbial cellulose spent 6.3 (95% CI 0.2–12.5) fewer days in hospital (p = 0.04), had a mean score that was 3.4 (95% CI 2.5–4.3) points lower during wound care (p < 0.001), and 2.2 (95% CI 1.6–2.7) afterwards (p < 0.001). Epithelialisation was quicker, but not significantly so.

    Conclusion

    These results suggest that the microbial cellulose dressing is a better first choice for treatment of partial thickness burns than silver sulphadiazine cream. Fewer dressings of the wound were done and, combined with the low pain scores, this is good for both the patients and the health care system. The differences in randomisation of the area of burns is, however, a concern that needs to be included in the interpretation of the results.

  • 104.
    Abong'o, Deborah
    et al.
    University of Nairobi, Kenya.
    Wandiga, Shem
    University of Nairobi, Kenya.
    Jumba, Isaac
    University of Nairobi, Kenya.
    Madadi, Vincent
    University of Nairobi, Kenya.
    Kylin, Henrik
    Linköpings universitet, Institutionen för tema, Tema vatten i natur och samhälle. Linköpings universitet, Filosofiska fakulteten.
    Impacts of pesticides on human health and environment in the River Nyando catchment, Kenya2014Inngår i: International Journal of Humanities, Arts, Medicine and Sciences, ISSN 2348-0521, Vol. 2, nr 3, s. 1-14Artikkel i tidsskrift (Annet vitenskapelig)
    Abstract [en]

    The population of the River Nyando catchment largely relies on rain fed agriculture for their subsistence.

    Important crops grown include cereals, cash crops fruits and vegetables. Farming is one of the contributors of pollution to Lake Victoria. Organophosphates and other banned organochlorine pesticides such as lindane, aldrin and dieldrin were used by farmers. The pesticides transport was by storm water run-off and air drift into the lake. Environmental risk assessment background information was collected through questionnaire and interviews of farmers to determine knowledge and safe use of pesticides. Fourteen pesticides were identified as commonly used of which four are toxic to bees and five to birds. The farmers identified declines in the number of pollinating insects, the disappearance of Red-billed Oxpecker (Buphagus erythrorthynchus) and wild bird’s fatalities. The general knowledge among farmers about chemicals risks, safety, and chronic illnesses was low. Activities that increases environmental awareness and safety of pesticides should be initiated by the agrochemical firms and government.

    Fulltekst (pdf)
    River Nyando catchment 1
  • 105. Bestill onlineKjøp publikasjonen >>
    Aboulaich, Nabila
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Expanding role of caveolae in control of adipocyte metabolism: proteomics of caveolae2006Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    The primary function of adipose tissue is to store energy in the form of triacylglycerol, which is hydrolyzed to fatty acids to supply other tissues with energy. While insulin promotes the storage of triacylglycerol, catecholamines stimulate its hydrolysis. The development of type II diabetes is strongly associated with obesity, indicating a role of triacylglycerol metabolism in the pathogenesis of diabetes. Caveolae are plasma membrane invaginations found in most cells but are highly abundant in adipocytes. Insulin receptors are localized in caveolae and their function depends on intact caveolae structures. In the present thesis work, mass spectrometry-based methodology allowed identification of a number of new proteins and their posttranslational modifications in caveolae of human adipocytes. Variable N-terminal acetylation and phosphorylation of caveolin-1α and caveolin-1β were identified, which might regulate the function of caveolae. The transcription regulator protein PTRF was identified as the major caveolae associated protein. Specific proteolytic modifications of PTRF at the cytosolic surface of caveolae and phosphorylation on nine serine and one threonine residues were identified. Moreover, insulin induced translocation of PTRF from the plasma membrane to the nucleus. PTRF was previously shown to regulate the activity of both RNA polymerase I and polymerase II, thus a role of PTRF in mediating the anabolic action of insulin on protein synthesis and gene transcription is proposed.

    PTRF was also involved in an extranuclear function in the hormonal regulation of triacylglycerol metabolism in caveolae. PTRF was colocalized with the triacylglycerol regulator proteins perilipin and hormone-sensitive lipase (HSL) in the triacylglycerol-synthesizing caveolae subclass. We showed that, while perilipin was translocated to the plasma membrane, both PTRF and HSL were translocated from the plasma membrane to the cytosol as a complex in response to insulin. The perilipin recruited to the plasma membrane was highly threonine phosphorylated. By mass spectrometry, three phosphorylated threonine residues were identified and were located in an acidic domain in the lipid droplet targeting domain of perilipin. The insulin-induced recruitment of perilipin to the plasma membrane might, therefore be phosphorylation-dependent. Isoproterenol, which stimulates hydrolysis of triacylglycerol, induced a complete depletion of perilipin B from the plasma membrane, suggesting a function of perilipin B to protect newly synthesized triacylglycerol in caveolae from being hydrolyzed by HSL. The location of PTRF and HSL was not affected by isoproterenol, indicating that insulin is acting against a default presence of PTRF and HSL in caveolae.

    Taken together, this thesis expands our knowledge about caveolae and provided valuable information about their involvement in novel roles, particularly in the hormonal regulation of triacylglycerol metabolism.

    Delarbeid
    1. Vectorial proteomics reveal targeting, phosphorylation and specific fragmentation of polymerase I and transcript release factor (PTRF) at the surface of caveolae in human adipocytes
    Åpne denne publikasjonen i ny fane eller vindu >>Vectorial proteomics reveal targeting, phosphorylation and specific fragmentation of polymerase I and transcript release factor (PTRF) at the surface of caveolae in human adipocytes
    2004 (engelsk)Inngår i: The Biochemical journal, ISSN 1470-8728, Vol. 383, nr Pt 2, s. 237-248Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Caveolae, the specialized invaginations of plasma membranes, formed sealed vesicles with outwards-orientated cytosolic surface after isolation from primary human adipocytes. This morphology allowed differential, vectorial identification of proteins at the opposite membrane surfaces by proteolysis and MS. Extracellular-exposed caveolae-specific proteins CD36 and copper-containing amine oxidase were concealed inside the vesicles and resisted trypsin treatment. The cytosol-orientated caveolins were efficiently digested by trypsin, producing peptides amenable to direct MS sequencing. Isolation of peripheral proteins associated with the cytosolic surface of caveolae revealed a set of proteins that contained nuclear localization signals, leucine-zipper domains and PEST (amino acid sequence enriched in proline, glutamic acid, serine and threonine) domains implicated in regulation by proteolysis. In particular, PTRF (polymerase I and transcript release factor) was found as a major caveolae-associated protein and its co-localization with caveolin was confirmed by immunofluorescence confocal microscopy. PTRF was present at the surface of caveolae in the intact form and in five different truncated forms. Peptides (44 and 45 amino acids long) comprising both the PEST domains were sequenced by nanospray-quadrupole-time-of-flight MS from the full-length PTRF, but were not found in the truncated forms of the protein. Two endogenous cleavage sites corresponding to calpain specificity were identified in PTRF; one of them was in a PEST domain. Both cleavage sites were flanked by mono- or diphosphorylated sequences. The phosphorylation sites were localized to Ser-36, Ser-40, Ser-365 and Ser-366 in PTRF. Caveolae of human adipocytes are proposed to function in targeting, relocation and proteolytic control of PTRF and other PEST-domain-containing signalling proteins.

    Emneord
    Caveolae, human adipocyte, MS, PEST sequence, polymerase I and transcript release factor (PTRF), proteolysis
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-19145 (URN)10.1042/BJ20040647 (DOI)15242332 (PubMedID)
    Tilgjengelig fra: 2009-06-12 Laget: 2009-06-12 Sist oppdatert: 2009-06-12bibliografisk kontrollert
    2. N-terminal processing and modifications of caveolin-1 in caveolae from human adipocytes
    Åpne denne publikasjonen i ny fane eller vindu >>N-terminal processing and modifications of caveolin-1 in caveolae from human adipocytes
    Vise andre…
    2004 (engelsk)Inngår i: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 320, nr 2, s. 480-486Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Caveolin, the principal structural protein of caveolae membrane domains, has a cytosol-exposed N-terminal part that was cleaved off by trypsin treatment of caveolae vesicles isolated from primary human adipocytes. Sequencing of the released tryptic peptides by nanospray quadrupole time-of-flight mass spectrometry revealed that both caveolin-1alpha and caveolin-1beta were processed by excision of the starting methionines. The N-terminus of the mature caveolin-1alpha was acetylated, while caveolin-1beta was found in acetylated as well as in non-acetylated forms. Fractional phosphorylation of serine-36 in the mature caveolin-1alpha and of the homologous serine-5 in caveolin-1beta was identified. This is the first experimental evidence for in vivo phosphorylation of caveolin-1 at the consensus site for phosphorylation by protein kinase C. The phosphorylation was found in both the acetylated and non-acetylated variants of caveolin-1beta. This variability in modifications is consistent with critical involvement of the N-terminal domain of caveolin in the regulation of caveolae.

    Emneord
    Human adipocyte, Caveolin-1; Caveolae, Protein phosphorylation, N-terminal acetylation, Mass spectrometry
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-19146 (URN)10.1016/j.bbrc.2004.05.196 (DOI)15219854 (PubMedID)
    Tilgjengelig fra: 2009-06-12 Laget: 2009-06-12 Sist oppdatert: 2017-12-13bibliografisk kontrollert
    3. Hormonal control of reversible translocation of perilipin B to the plasma membrane in primary human adipocytes
    Åpne denne publikasjonen i ny fane eller vindu >>Hormonal control of reversible translocation of perilipin B to the plasma membrane in primary human adipocytes
    2006 (engelsk)Inngår i: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 281, nr 17, s. 11446-11449Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    In adipocytes, perilipin coats and protects the central lipid droplet, which stores triacylglycerol. Alternative mRNA splicing gives rise to perilipin A and B. Hormones such as catecholamines and insulin regulate triacylglycerol metabolism through reversible serine phosphorylation of perilipin A. It was recently shown that perilipin was also located in triacylglycerol-synthesizing caveolae of the plasma membrane. We now report that perilipin at the plasma membrane of primary human adipocytes was phosphorylated on a cluster of threonine residues (299, 301, and 306) within an acidic domain that forms part of the lipid targeting domain. Perilipin B comprised <10% of total perilipin but was the major isoform associated with the plasma membrane of human adipocytes. This association was controlled by insulin and catecholamine: perilipin B was specifically depleted from the plasma membrane in response to the catecholamine isoproterenol, while insulin increased the amount of threonine phosphorylated perilipin at the plasma membrane. The reversible translocation of perilipin B to and from the plasma membrane in response to insulin and isoproterenol, respectively, suggests a specific function for perilipin B to protect newly synthesized triacylglycerol in the plasma membrane.

    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-19147 (URN)10.1074/jbc.C500461200 (DOI)16527823 (PubMedID)
    Tilgjengelig fra: 2009-06-12 Laget: 2009-06-12 Sist oppdatert: 2017-12-13bibliografisk kontrollert
    4. Association and insulin regulated translocation of hormone-sensitive lipase with PTRF
    Åpne denne publikasjonen i ny fane eller vindu >>Association and insulin regulated translocation of hormone-sensitive lipase with PTRF
    2006 (engelsk)Inngår i: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 350, nr 3, s. 657-661Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Polymerase I and transcript release factor (PTRF) is in human adipocytes mainly localized at the plasma membrane. This localization was under control of insulin, which translocated PTRF to the cytosol and nucleus, indicating a novel role for PTRF in insulin transcriptional control. In the plasma membrane PTRF was specifically bound to a triacylglycerol-metabolizing subclass of caveolae containing hormone-sensitive lipase (HSL). In response to insulin PTRF was translocated to the cytosol in parallel with HSL. PTRF and HSL were quantitatively immunoprecipitated from the cytosol by antibodies against either PTRF or HSL. The findings indicate also a novel extranuclear function for PTRF in the control of lipolysis.

    Emneord
    Hormone-sensitive lipase, Polymerase I and transcript release factor, Adipocyte, Human, Insulin, Translocation, Protein complex, Caveolae, Lipid metabolism, Transcriptional control
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-19148 (URN)10.1016/j.bbrc.2006.09.094 (DOI)17026959 (PubMedID)
    Tilgjengelig fra: 2009-06-12 Laget: 2009-06-12 Sist oppdatert: 2017-12-13bibliografisk kontrollert
    Fulltekst (pdf)
    Expanding Role of Caveolae in Control of Adipocyte Metabolism
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  • 106.
    Aboulaich, Nabila
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Ortegren, Unn
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Vener, Alexander V
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Strålfors, Peter
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Association and insulin regulated translocation of hormone-sensitive lipase with PTRF2006Inngår i: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 350, nr 3, s. 657-661Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Polymerase I and transcript release factor (PTRF) is in human adipocytes mainly localized at the plasma membrane. This localization was under control of insulin, which translocated PTRF to the cytosol and nucleus, indicating a novel role for PTRF in insulin transcriptional control. In the plasma membrane PTRF was specifically bound to a triacylglycerol-metabolizing subclass of caveolae containing hormone-sensitive lipase (HSL). In response to insulin PTRF was translocated to the cytosol in parallel with HSL. PTRF and HSL were quantitatively immunoprecipitated from the cytosol by antibodies against either PTRF or HSL. The findings indicate also a novel extranuclear function for PTRF in the control of lipolysis.

  • 107.
    Aboulaich, Nabila
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Vainonen, Julia P
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Strålfors, Peter
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Vener, Alexander V
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Vectorial proteomics reveal targeting, phosphorylation and specific fragmentation of polymerase I and transcript release factor (PTRF) at the surface of caveolae in human adipocytes2004Inngår i: The Biochemical journal, ISSN 1470-8728, Vol. 383, nr Pt 2, s. 237-248Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Caveolae, the specialized invaginations of plasma membranes, formed sealed vesicles with outwards-orientated cytosolic surface after isolation from primary human adipocytes. This morphology allowed differential, vectorial identification of proteins at the opposite membrane surfaces by proteolysis and MS. Extracellular-exposed caveolae-specific proteins CD36 and copper-containing amine oxidase were concealed inside the vesicles and resisted trypsin treatment. The cytosol-orientated caveolins were efficiently digested by trypsin, producing peptides amenable to direct MS sequencing. Isolation of peripheral proteins associated with the cytosolic surface of caveolae revealed a set of proteins that contained nuclear localization signals, leucine-zipper domains and PEST (amino acid sequence enriched in proline, glutamic acid, serine and threonine) domains implicated in regulation by proteolysis. In particular, PTRF (polymerase I and transcript release factor) was found as a major caveolae-associated protein and its co-localization with caveolin was confirmed by immunofluorescence confocal microscopy. PTRF was present at the surface of caveolae in the intact form and in five different truncated forms. Peptides (44 and 45 amino acids long) comprising both the PEST domains were sequenced by nanospray-quadrupole-time-of-flight MS from the full-length PTRF, but were not found in the truncated forms of the protein. Two endogenous cleavage sites corresponding to calpain specificity were identified in PTRF; one of them was in a PEST domain. Both cleavage sites were flanked by mono- or diphosphorylated sequences. The phosphorylation sites were localized to Ser-36, Ser-40, Ser-365 and Ser-366 in PTRF. Caveolae of human adipocytes are proposed to function in targeting, relocation and proteolytic control of PTRF and other PEST-domain-containing signalling proteins.

  • 108.
    Aboulaich, Nabila
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Vener, Alexander V
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Strålfors, Peter
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Hormonal control of reversible translocation of perilipin B to the plasma membrane in primary human adipocytes2006Inngår i: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 281, nr 17, s. 11446-11449Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    In adipocytes, perilipin coats and protects the central lipid droplet, which stores triacylglycerol. Alternative mRNA splicing gives rise to perilipin A and B. Hormones such as catecholamines and insulin regulate triacylglycerol metabolism through reversible serine phosphorylation of perilipin A. It was recently shown that perilipin was also located in triacylglycerol-synthesizing caveolae of the plasma membrane. We now report that perilipin at the plasma membrane of primary human adipocytes was phosphorylated on a cluster of threonine residues (299, 301, and 306) within an acidic domain that forms part of the lipid targeting domain. Perilipin B comprised <10% of total perilipin but was the major isoform associated with the plasma membrane of human adipocytes. This association was controlled by insulin and catecholamine: perilipin B was specifically depleted from the plasma membrane in response to the catecholamine isoproterenol, while insulin increased the amount of threonine phosphorylated perilipin at the plasma membrane. The reversible translocation of perilipin B to and from the plasma membrane in response to insulin and isoproterenol, respectively, suggests a specific function for perilipin B to protect newly synthesized triacylglycerol in the plasma membrane.

  • 109.
    Aboyans, Victor
    et al.
    Dupuytren University Hospital.
    Criqui, Michael
    University of California, USA.
    Abraham, Pierre
    University Hospital of Angers, France.
    Allison, Matthew
    University of California, USA.
    Creager, Mark
    Brigham and Women’s Hospital, USA.
    Diehm, Curt
    Karlsbad Clinic/University of Heidelberg, Germany.
    Fowkes, Gerry
    University of Edinburgh, UK.
    Hiatt, William
    University of Colorado, USA.
    Jönsson, Björn
    Linköpings universitet, Institutionen för medicin och hälsa, Thoraxkirurgi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Thorax-kärlkliniken i Östergötland.
    Lacroix, Philippe
    Limoges University, France.
    Marin, Benoit
    Limoges Teaching Hospital, France.
    McDermott, Mary
    Northwestern University,USA.
    Norgren, Lars
    University Hospital, Örebro, Sweden.
    Pande, Reena
    Brigham and Women’s Hospital, USA.
    Preux, Pierre-Marie
    University of Limoges, France.
    Stoffers, H.E.
    Maastricht University, Netherlands.
    Treat-Jacobsson, Diane
    University of Minnesota, USA.
    Measurement and interpretation of the ankle-brachial index: a scientific statement from the Ammerican Heart Association2012Inngår i: Circulation, ISSN 0009-7322, E-ISSN 1524-4539Artikkel i tidsskrift (Fagfellevurdert)
  • 110.
    Abrahams, M
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Anestesiologi.
    Eriksson, H
    Björnström, Karin
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Anestesiologi. Östergötlands Läns Landsting, MKC - Medicin och kirurgicentrum, Anestesi.
    Eintrei, Christina
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Anestesiologi. Östergötlands Läns Landsting, MKC - Medicin och kirurgicentrum, Anestesi.
    Effects of propofol on extracellular acidification rates in primary cortical cell cultures: application of silicon microphysiometry to anaesthesia.1999Inngår i: British Journal of Anaesthesia, ISSN 0007-0912, E-ISSN 1471-6771, Vol. 83, s. 567-569Artikkel i tidsskrift (Fagfellevurdert)
  • 111.
    Abrahams, M
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Anestesiologi. Östergötlands Läns Landsting, MKC - Medicin och kirurgicentrum, Anestesi.
    Sjöberg, Folke
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Hand och plastikkirurgi. Östergötlands Läns Landsting, Rekonstruktionscentrum, Hand- och plastikkirurgiska kliniken US.
    Oscarsson, Anna
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Anestesiologi. Östergötlands Läns Landsting, MKC - Medicin och kirurgicentrum, Anestesi.
    Sundqvist, Tommy
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Medicinsk mikrobiologi.
    The effects of human burn injury on urinary nitrate excretion. 1999Inngår i: Burns, ISSN 0305-4179, E-ISSN 1879-1409, Vol. 25, s. 29-33Artikkel i tidsskrift (Fagfellevurdert)
  • 112.
    Abrahamsson, Annelie
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Capodanno, Alessandra
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Rzepecka, Anna
    Linköpings universitet, Institutionen för medicin och hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Röntgenkliniken i Linköping.
    Dabrosin, Charlotta
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Downregulation of tumor suppressive microRNAs in vivo in dense breast tissue of postmenopausal women2017Inngår i: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 8, nr 54, s. 92134-92142Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Women with dense breast tissue on mammography are at higher risk of developing breast cancer but the underlying mechanisms are not well understood. De-regulation of microRNAs (miRNAs) has been associated with the onset of breast cancer. miRNAs in the extracellular space participate in the regulation of the local tissue microenvironment. Here, we recruited 39 healthy postmenopausal women attending their mammography-screen that were assessed having extreme dense or entirely fatty breasts (nondense). Microdialysis was performed in breast tissue and a reference catheter was inserted in abdominal subcutaneous fat for local sampling of extracellular compounds. Three miRNAs, associated with tumor suppression, miR-193b, miR-365a, and miR-452 were significantly down-regulated in dense breast tissue compared with nondense breast tissue. In addition, miR-452 exhibited significant negative correlations with several pro-inflammatory cytokines in vivo, which was confirmed in vitro by overexpression of miR-452 in breast cancer cells. No differences were found of miR-21, -29a, -30c, 146a, -148a, -203, or -451 in breast tissue and no miRs were different in plasma. Extracellular miRNAs may be among factors that should be included in studies of novel prevention strategies for breast cancer.

    Fulltekst (pdf)
    fulltext
  • 113.
    Abrahamsson, Annelie
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten.
    Dabrosin, Charlotta
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Tissue specific expression of extracellular microRNA in human breast cancers and normal human breast tissue in vivo2015Inngår i: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 6, nr 26, s. 22959-22969Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Extracellular circulating microRNAs (miRNAs) have been suggested to be biomarkers for disease monitoring but data are inconsistent, one reason being that blood miRNA is of heterogeneous origin. Here, we sampled extracellular microRNAs locally in situ using microdialysis. Three different cohorts of women were included; postmenopausal women with ongoing breast cancer investigated within the cancer and in normal adjacent breast tissue, postmenopausal women investigated in their normal healthy breast and subcutaneous fat before and after six weeks of tamoxifen therapy, premenopausal women during the menstrual cycle. Samples were initially screened using TaqMan array cards with subsequently absolute quantification. 124 miRNA were expressed in microdialysates. After absolute quantifications extracellular miRNA-21 was found to be significantly increased in breast cancer. In addition, the levels were significantly higher in pre-menopausal breast tissue compared with postmenopausal. In breast tissue of pre-menopausal women miRNA-21 exhibited a cyclic variation during the menstrual cycle and in postmenopausal women six weeks of tamoxifen treatment decreased miRNA-21 suggesting that this miRNA may be important for breast carcinogenesis. None of these changes were found in plasma or microdialysates from subcutaneous fat. Our data revealed tissue specific changes of extracellular circulating miRNAs that would be otherwise unraveled using blood samples.

    Fulltekst (pdf)
    fulltext
  • 114.
    Abrahamsson, Annelie
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet.
    Morad, Vivian
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Saarinen, Niina M
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet.
    Dabrosin, Charlotta
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Estradiol, Tamoxifen, and Flaxseed Alter IL-1 beta and IL-1Ra Levels in Normal Human Breast Tissue in Vivo2012Inngår i: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 97, nr 11, s. E2044-E2054Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Introduction: Sex steroid exposure increases the risk of breast cancer by unclear mechanisms. Diet modifications may be one breast cancer prevention strategy. The proinflammatory cytokine family of IL-1 is implicated in cancer progression. IL-1Ra is an endogenous inhibitor of the proinflammatory IL-1 alpha and IL-1 beta. less thanbrgreater than less thanbrgreater thanObjective: The objective of this study was to elucidate whether estrogen, tamoxifen, and/or diet modification altered IL-1 levels in normal human breast tissue. less thanbrgreater than less thanbrgreater thanDesign and Methods: Microdialysis was performed in healthy women under various hormone exposures, tamoxifen therapy, and diet modifications and in breast cancers of women before surgery. Breast tissue biopsies from reduction mammoplasties were cultured. less thanbrgreater than less thanbrgreater thanResults: We show a significant positive correlation between estradiol and in vivo levels of IL-1 beta in breast tissue and abdominal sc fat, whereas IL-1Ra exhibited a significant negative correlation with estradiol in breast tissue. Tamoxifen or a dietary addition of 25 g flaxseed per day resulted in significantly increased levels of IL-1Ra in the breast. These results were confirmed in ex vivo culture of breast biopsies. Immunohistochemistry of the biopsies did not reveal any changes in cellular content of the IL-1s, suggesting that mainly the secreted levels were affected. In breast cancer patients, intratumoral levels of IL-1 beta were significantly higher compared with normal adjacent breast tissue. less thanbrgreater than less thanbrgreater thanConclusion: IL-1 may be under the control of estrogen in vivo and may be attenuated by antiestrogen therapy and diet modifications. The increased IL-1 beta in breast cancers of women strongly suggests IL-1 as a potential therapeutic target in breast cancer treatment and prevention.

  • 115.
    Abrahamsson, Annelie
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Rzepecka, Anna
    Linköpings universitet, Institutionen för medicin och hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Röntgenkliniken i Linköping.
    Dabrosin, Charlotta
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Equal Pro-inflammatory Profiles of CCLs, CXCLs, and Matrix Metalloproteinases in the Extracellular Microenvironment In Vivo in Human Dense Breast Tissue and Breast Cancer2018Inngår i: Frontiers in Immunology, ISSN 1664-3224, E-ISSN 1664-3224, Vol. 8, artikkel-id 1994Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The inflammatory microenvironment affects breast cancer progression. Proteins that govern the inflammatory response are secreted into the extracellular space, but this compartment still needs to be characterized in human breast tissues in vivo. Dense breast tissue is a major risk factor for breast cancer by yet unknown mechanisms and no non-toxic prevention for these patients exists. Here, we used the minimal invasive technique of microdialysis for sampling of extracellular proteins in live tissues in situ in breast cancers of women before surgery and in healthy women having dense or non-dense breast tissue on mammography. Proteins were profiled using a proximity extension assay. Out of the 32 proteins assessed, 26 exhibited similar profiles in breast cancers and dense breast tissues; CCL-4, -7, -8, -11, -15, -16, -22, -23, and -25, CXCL-5, -8, -9, -16 as well as sIL-6R, IL-18, vascular endothelial growth factor, TGF-a, fibroblast growth factor 19, matrix metalloproteinase (MMP)-1, -2, -3, and urokinase-type plasminogen activator were all increased, whereas CCL-3, CX3CL1, hepatocyte growth factor, and MMP-9 were unaltered in the two tissues. CCL-19 and -24, CXCL-1 and -10, and IL-6 were increased in dense breast tissue only, whereas IL-18BP was increased in breast cancer only. Our results provide novel insights in the inflammatory microenvironment in human breast cancer in situ and define potential novel therapeutic targets. Additionally, we show previously unrecognized similarities of the pro-inflammatory microenvironment in dense breast tissue and breast cancer in vivo suggesting that anti-inflammatory breast cancer prevention trials for women with dense breast tissue may be feasible.

    Fulltekst (pdf)
    fulltext
  • 116.
    Abrahamsson, Annelie
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Rzepecka, Anna
    Region Östergötland, Diagnostikcentrum, Röntgenkliniken i Linköping. Linköpings universitet, Institutionen för medicin och hälsa. Linköpings universitet, Medicinska fakulteten.
    Dabrosin, Charlotta
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Increased nutrient availability in dense breast tissue of postmenopausal women in vivo2017Inngår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, artikkel-id 42733Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Metabolic reprogramming is a hallmark of cancer. Nutrient availability in the tissue microenvironment determines cellular events and may play a role in breast carcinogenesis. High mammographic density is an independent risk factor for breast cancer. Whether nutrient availability differs in normal breast tissues with various densities is unknown. Therefore we investigated whether breast tissues with various densities exhibited differences in nutrient availability. Healthy postmenopausal women from the regular mammographic screening program who had either predominantly fatty breast tissue (nondense), n = 18, or extremely dense breast tissue (dense), n = 20, were included. Microdialysis was performed for the in vivo sampling of amino acids (AAs), analyzed by ultra-high performance liquid chromatography with tandem mass spectroscopy, glucose, lactate and vascular endothelial growth factor (VEGF) in breast tissues and, as a control, in abdominal subcutaneous (s.c.) fat. We found that dense breast tissue exhibited significantly increased levels of 20 proteinogenic AAs and that 18 of these AAs correlated significantly with VEGF. No differences were found in the s.c. fat, except for one AA, suggesting tissue-specific alterations in the breast. Glucose and lactate were unaltered. Our findings provide novel insights into the biology of dense breast tissue that may be explored for breast cancer prevention strategies.

    Fulltekst (pdf)
    fulltext
  • 117.
    Abrahamsson, Annelie
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Rzepecka, Anna
    Region Östergötland, Diagnostikcentrum, Röntgenkliniken i Linköping.
    Romu, Thobias
    Linköpings universitet, Institutionen för medicinsk teknik, Medicinsk informatik. Linköpings universitet, Tekniska fakulteten. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV.
    Borga, Magnus
    Linköpings universitet, Institutionen för medicinsk teknik, Medicinsk informatik. Linköpings universitet, Tekniska fakulteten. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV.
    Dahlqvist Leinhard, Olof
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för radiologiska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Radiofysikavdelningen US. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV.
    Lundberg, Peter
    Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Radiofysikavdelningen US. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för radiologiska vetenskaper. Linköpings universitet, Medicinska fakulteten.
    Kihlberg, Johan
    Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för radiologiska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Röntgenkliniken i Linköping.
    Dabrosin, Charlotta
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Dense breast tissue in postmenopausal women is associated with a pro-inflammatory microenvironment in vivo2016Inngår i: Oncoimmunology, ISSN 2162-4011, E-ISSN 2162-402X, Vol. 5, nr 10, artikkel-id e1229723Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Inflammation is one of the hallmarks of carcinogenesis. High mammographic density has been associated with increased risk of breast cancer but the mechanisms behind are poorly understood. We evaluated whether breasts with different mammographic densities exhibited differences in the inflammatory microenvironment.Postmenopausal women attending the mammography-screening program were assessed having extreme dense, n = 20, or entirely fatty breasts (nondense), n = 19, on their regular mammograms. Thereafter, the women were invited for magnetic resonance imaging (MRI), microdialysis for the collection of extracellular molecules in situ and a core tissue biopsy for research purposes. On the MRI, lean tissue fraction (LTF) was calculated for a continuous measurement of breast density. LTF confirmed the selection from the mammograms and gave a continuous measurement of breast density. Microdialysis revealed significantly increased extracellular in vivo levels of IL-6, IL-8, vascular endothelial growth factor, and CCL5 in dense breast tissue as compared with nondense breasts. Moreover, the ratio IL-1Ra/IL-1 was decreased in dense breasts. No differences were found in levels of IL-1, IL-1Ra, CCL2, leptin, adiponectin, or leptin:adiponectin ratio between the two breast tissue types. Significant positive correlations between LTF and the pro-inflammatory cytokines as well as between the cytokines were detected. Stainings of the core biopsies exhibited increased levels of immune cells in dense breast tissue.Our data show that dense breast tissue in postmenopausal women is associated with a pro-inflammatory microenvironment and, if confirmed in a larger cohort, suggests novel targets for prevention therapies for women with dense breast tissue.

  • 118. Bestill onlineKjøp publikasjonen >>
    Abrahamsson, Thomas
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomsmedicinska kliniken US.
    Can Lactobacillus Reuteri Prevent Allergic Disease in Early Childhood?2009Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Background: An altered microbial exposure may be partly responsible for the increase of allergic diseases in populations with a western lifestyle. Activation of the immune system by microbes early in life is probably required for an accurate maturation of the immune system. Probiotics, live bacteria which are considered to confer health when ingested, have been suggested to prevent eczema and sensitisation infants.

    Aim: The general aim of this thesis was to assess the effect of oral supplementation with the probiotic bacterium Lactobacillus reuteri (L. reuteri) in infancy on the development of allergic disease and sensitisation during the first 2 years of life and to examine mechanisms possibly underlying eventual effects on allergic manifestations.

    Subjects: The thesis is based on results obtained from a prospective double-blind placebo-controlled multicenter trial, comprising 232 families with allergic disease, of whom 188 completed the study.

    Methods: The families were recruited at the antenatal clinic, and the mothers received L. reuteri ATCC 55730 (1 x 108 colony forming units) or placebo daily from gestational week 36 until delivery. Their babies then continued with the same study product from birth until 12 months of age and were followed up for another year. The primary outcomes were allergic disease, with or without positive skin prick test or circulating IgE to food allergens. Bacterial counts and prevalence were assessed in maternal breast milk and faeces and infant faeces, employing conventional cultivation methods. Cytokines and IgA antibodies were analysed in colostrum and mature milk from the mothers with ELISA, and Na/K- ratio in breast milk with ion selective electrodes. Circulating Th1/Th2-associated chemokines were analysed in cord and peripheral blood in the infants with Luminex or ELISA technique.

    Results: The incidence of eczema was similar, 36% in the treated versus 34% in the placebo group. The L. reuteri group had a lower cumulative incidence of IgE-associated allergic disease, 20% versus 35% (p=0.04), and less IgE-associated eczema during the second year, 8% versus 20% (p=0.02). The prevalence of L. reuteri was higher during the first year of life in stool samples from infants, as well as in colostrum, in the active as compared to the placebo treated group. Colostrum from L. reuteri supplemented mothers had lower levels of TGF-β2, and low levels of this cytokine were associated with less sensitisation. Low Th1- and high Th2-associated chemokine levels preceded allergic disease. The presence of L. reuteri in stool was associated with lower levels of the Th2-associated chemokines CCL17 and CCL22 and higher levels of the Th1-associated CXCL11.

    Conclusion: Although a preventive effect of probiotics on infant eczema was not confirmed, the L. reuteri treated infants had lower incidence of IgE-associated allergic disease at two years of age, and therefore possibly run a reduced risk to develop later respiratory allergic disease. The mechanisms underlying this effect require further elucidation.

    Delarbeid
    1. Probiotics in prevention of IgE-associated eczema: a double-blind, randomized, placebo-controlled trial
    Åpne denne publikasjonen i ny fane eller vindu >>Probiotics in prevention of IgE-associated eczema: a double-blind, randomized, placebo-controlled trial
    Vise andre…
    2007 (engelsk)Inngår i: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 119, nr 5, s. 1174-1180Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    BACKGROUND: An altered microbial exposure may underlie the increase of allergic diseases in affluent societies. Probiotics may alleviate and even prevent eczema in infants.

    OBJECTIVE: To prevent eczema and sensitization in infants with a family history of allergic disease by oral supplementation with the probiotic Lactobacillus reuteri.

    METHODS: Double-blind, randomized, placebo-controlled trial, which comprised 232 families with allergic disease, of whom 188 completed the study. The mothers received L reuteri ATCC 55730 (1 x 10(8) colony forming units) daily from gestational week 36 until delivery. Their babies then continued with the same product from birth until 12 months of age and were followed up for another year. Primary outcome was allergic disease, with or without positive skin prick test or circulating IgE to food allergens.

    RESULTS: The cumulative incidence of eczema was similar, 36% in the treated versus 34% in the placebo group. The L reuteri group had less IgE-associated eczema during the second year, 8% versus 20% (P = .02), however. Skin prick test reactivity was also less common in the treated than in the placebo group, significantly so for infants with mothers with allergies, 14% versus 31% (P = .02). Wheeze and other potentially allergic diseases were not affected.

    CONCLUSION: Although a preventive effect of probiotics on infant eczema was not confirmed, the treated infants had less IgE-associated eczema at 2 years of age and therefore possibly run a reduced risk to develop later respiratory allergic disease. CLINICAL IMPLICATION: Probiotics may reduce the incidence of IgE-associated eczema in infancy.

    Emneord
    Children, eczema, IgE, Lactobacillus, prevention, probiotics, sensitization, skin prick test
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-20580 (URN)10.1016/j.jaci.2007.01.007 (DOI)17349686 (PubMedID)
    Tilgjengelig fra: 2009-09-15 Laget: 2009-09-15 Sist oppdatert: 2017-12-13bibliografisk kontrollert
    2. Probiotic lactobacilli in breast milk and infant stool in relation to oral intake during the first year of life
    Åpne denne publikasjonen i ny fane eller vindu >>Probiotic lactobacilli in breast milk and infant stool in relation to oral intake during the first year of life
    Vise andre…
    2009 (engelsk)Inngår i: Journal of pediatric gastroenterology and nutrition, ISSN 1536-4801, Vol. 49, nr 3, s. 349-354Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    OBJECTIVES: This is to identify factors affecting the prevalence of Lactobacillus reuteri in maternal faeces and breast milk and infant faeces after oral supplementation with L reuteri and to assess the influence on microbial ecology, particularly Clostridium difficile and Bifidobacterium colonization.

    MATERIALS AND METHODS: In this double-blind trial, 232 mothers with a family history of atopic disease were randomized to a daily intake of either L reuteri American-type culture collection (ATCC) 55730 (1 x 10 colony-forming units [CFU]) or placebo for the last 4 weeks of pregnancy. Their babies then continued with the same study product daily from birth until 12 months of age. Bacterial counts and prevalence were assessed in maternal breast milk and faeces and infant faeces, using conventional cultivation methods.

    RESULTS: The prevalence of L reuteri was higher during the first year of life in the stool samples from infants in the active as compared with the placebo-treated group. The highest prevalence was recorded at 5 to 6 days of age (82% in the treated vs 20% in the placebo group, P < 0.001). Lactobacillus reuteri was isolated from 12% and 2%, respectively, in the colostrum samples (P < 0.05). Breast-feeding seemed to reduce faecal L reuteri counts, although antibiotics did not influence the levels of L reuteri. The administration of L reuteri did not affect bifidobacteria or C difficile colonization.

    CONCLUSION: Lactobacillus reuteri may be detected in breast milk after oral supplementation to the mother and in almost all infants after oral supplementation during the first year of life, as well as occasionally in many untreated infants.

    Emneord
    Bifidobacteria, Clostridium, Faeces, Probiotics, Lactobacillus reuteri
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-20622 (URN)10.1097/MPG.0b013e31818f091b (DOI)19525871 (PubMedID)
    Tilgjengelig fra: 2009-09-15 Laget: 2009-09-15 Sist oppdatert: 2009-09-27bibliografisk kontrollert
    3. Low breast milk TGF-beta2 is induced by Lactobacillus reuteri supplementation and associates with reduced risk of sensitization during infancy
    Åpne denne publikasjonen i ny fane eller vindu >>Low breast milk TGF-beta2 is induced by Lactobacillus reuteri supplementation and associates with reduced risk of sensitization during infancy
    Vise andre…
    2008 (engelsk)Inngår i: Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology, ISSN 1399-3038, Vol. 19, nr 6, s. 497-504Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    The immunological composition of breast milk differs between mothers. The reasons for these differences and the consequences for the breast-fed infants are poorly understood. The aim of this study was to evaluate the effect of probiotic Lactobacillus reuteri supplementation on the immunological composition of breast milk in relation to sensitization and eczema in the babies. Total IgA, secretory IgA (SIgA), TGF-beta1, TGF-beta2, IL-10, TNF, soluble CD14 (sCD14), and Na/K ratios were analyzed in colostrum and mature milk obtained from women treated with L. reuteri (n = 54) or placebo (n = 55) from gestational week 36 until delivery. Bacteriological analyses of L. reuteri were performed in faecal samples of the mothers. The infants were followed prospectively for 2 yr regarding development of eczema and sensitization as defined by a positive skin prick test and/or circulating allergen-specific IgE antibodies at 6, 12, and 24 months of age. Supplementation of L. reuteri during pregnancy was associated with low levels of TGF-beta2 and slightly increased levels of IL-10 in colostrum. For TGF-beta2, this association was most pronounced in mothers with detectable L. reuteri in faeces. Infants receiving breast milk with low levels of TGF-beta2 were less likely to become sensitized during their first 2 yr of life. A similar trend was observed for development of IgE-associated eczema. The levels of total IgA, SIgA, TGF-beta1, TNF, sCD14, and Na/K ratios in breast milk were not affected by the intake of L. reuteri. None of these parameters correlated with sensitization or development of eczema in the infant, except for high Na/K ratios that associated with increased risk of sensitization. Supplementation with L. reuteri during late pregnancy reduces breast milk levels of TGF-beta2, and low levels of this cytokine are associated with less sensitization and possibly less IgE-associated eczema in breast-fed infants.

    Emneord
    Lactobacilli, breast milk, TGF-b, sensitization, infancy
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-20623 (URN)10.1111/j.1399-3038.2007.00687.x (DOI)18221472 (PubMedID)
    Tilgjengelig fra: 2009-09-15 Laget: 2009-09-15 Sist oppdatert: 2009-09-27bibliografisk kontrollert
    4. A Th1/Th2-associated chemokine imbalance preceding allergic disease is influenced by birth size, breastfeeding, daycare and probiotics
    Åpne denne publikasjonen i ny fane eller vindu >>A Th1/Th2-associated chemokine imbalance preceding allergic disease is influenced by birth size, breastfeeding, daycare and probiotics
    Vise andre…
    2009 (engelsk)Inngår i: in Allergy, vol 64, 2009, Vol. 64, s. 56-56Konferansepaper, Publicerat paper (Fagfellevurdert)
    Abstract [en]

    Background: Analyses of circulating chemokines offer novel tools to investigate the Th1/Th2 imbalance in allergic disease in vivo and explore the influence of pre- and postnatal factors in infancy.

    Objective: To relate circulating Th1- and Th2-associated chemokines to the development of allergic disease, pre- and postnatal factors and probiotic supplementation in infancy.

    Methods: Circulating levels of Th1-associated CXC-chemokine ligand (CXCL)9, CXCL10 and CXCL11 and Th2-associated CC-chemokine ligand (CCL)17, CCL18 and CCL22 were assessed with Luminex and ELISA at birth (n=109), 6 (n=104), 12 (n=116) and 24 months (n=123) in 179 infants completing a double-blind placebo-controlled allergy prevention trial with Lactobacillus reuteri during the last month of gestation and through the first year of life. The infants were followed regarding development of allergic disease and sensitization until two years of age.

    Results: The Th2-associated chemokines were as highest at birth and then decreased, whereas the Th1-associated chemokines increased with age. Low Th1- and high Th2-associated chemokine levels were observed in children developing allergic disease. Sensitization was preceded by elevated CCL22 and reduced CXCL11 levels. High Th2-associated chemokine46 levels were associated with increased birth length and weight and long duration of breastfeeding, and high Th1-associated chemokine levels with day-care attendance. Presence of L. reuteri in stool the first week of life was associated with low CCL17 and CCL22 and high CXCL11 levels at 6 months.

    Conclusion: Allergic disease in infancy was associated with low circulating Th1- and high Th2-associated chemokine levels during the first year of life. The chemokine levels were affected by both pre and –postnatal factors.

    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-19153 (URN)
    Tilgjengelig fra: 2009-06-12 Laget: 2009-06-12 Sist oppdatert: 2009-09-15bibliografisk kontrollert
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    Can Lactobacillus Reuteri Prevent Allergic Disease in Early Childhood?
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  • 119.
    Abrahamsson, Thomas
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Editorial Material: Not all probiotic strains prevent necrotising enterocolitis in premature infants in LANCET, vol 387, issue 10019, pp 624-6252016Inngår i: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 387, nr 10019, s. 624-625Artikkel i tidsskrift (Annet vitenskapelig)
    Abstract [en]

    n/a

  • 120.
    Abrahamsson, Thomas
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Using probiotics to prevent necrotising enterocolitis2017Inngår i: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 106, nr 11, s. 1718-1719Artikkel i tidsskrift (Annet vitenskapelig)
    Abstract [en]

    n/a

  • 121.
    Abrahamsson, Thomas
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Jakobsson, H.E.
    Karolinska Institute, Stockholm, Sweden.
    Andersson, A.F.
    KTH Royal Institute of Technology, Stockholm, Sweden.
    Björksten, B.
    Karolinska Institute, Stockholm, Sweden; Örebro University, Sweden .
    Engstrand, L.
    Karolinska Institute, Stockholm, Sweden; KTH Royal Institute of Technology, Stockholm, Sweden.
    Jenmalm, Maria
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för inflammationsmedicin. Linköpings universitet, Hälsouniversitetet.
    Low gut microbiota diversity in early infancy precedes asthma at school age2014Inngår i: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 44, nr 6, s. 842-850Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND:

    Low total diversity of the gut microbiota during the first year of life is associated with allergic diseases in infancy, but little is known how early microbial diversity is related to allergic disease later in school age.

    OBJECTIVE:

    To assess microbial diversity and characterize the dominant bacteria in stool during the first year of life in relation to the prevalence of different allergic diseases in school age, such as asthma, allergic rhinoconjunctivitis (ARC) and eczema.

    METHODS:

    The microbial diversity and composition was analysed with barcoded 16S rDNA 454 pyrosequencing in stool samples at 1 week, 1 month and 12 months of age in 47 infants which were subsequently assessed for allergic disease and skin prick test reactivity at 7 years of age (ClinicalTrials.gov ID NCT01285830).

    RESULTS:

    Children developing asthma (n = 8) had a lower diversity of the total microbiota than non-asthmatic children at 1 week (P = 0.04) and 1 month (P = 0.003) of age, whereas allergic rhinoconjunctivitis (n = 13), eczema (n = 12) and positive skin prick reactivity (n = 14) at 7 years of age did not associate with the gut microbiota diversity. Neither was asthma associated with the microbiota composition later in infancy (at 12 months). Children having IgE-associated eczema in infancy and subsequently developing asthma had lower microbial diversity than those that did not. There were no significant differences, however, in relative abundance of bacterial phyla and genera between children with or without allergic disease.

    CONCLUSION AND CLINICAL RELEVANCE:

    Low total diversity of the gut microbiota during the first month of life was associated with asthma but not ARC in children at 7 years of age. Measures affecting microbial colonization of the infant during the first month of life may impact asthma development in childhood.

    Fulltekst (pdf)
    fulltext
  • 122.
    Abrahamsson, Thomas
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Jakobsson, Hedvig E.
    Karolinska Institute, Sweden .
    Andersson, Anders F.
    KTH Royal Institute Technology, Sweden .
    Bjorksten, Bengt
    University of Örebro, Sweden .
    Engstrand, Lars
    KTH Royal Institute Technology, Sweden .
    Jenmalm, Maria
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Reply: Gut microbiota diversity and atopic disease: Does breast-feeding play a role?2013Inngår i: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 131, nr 1, s. 248-249Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    n/a

    Fulltekst (pdf)
    fulltext
  • 123.
    Abrahamsson, Thomas
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Jakobsson, Hedvig E
    Department of Preparedness, Swedish Institute for Communicable Disease Control, Solna, Sweden.
    Andersson, Anders F
    Science for Life Laboratory, School of Biotechnology, KTH Royal Institute of Technology, Stockholm, Sweden.
    Björksten, Bengt
    Institute of Environmental Medicine, Karolinska Institutet, Stockholm, and the School of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Engstrand, Lars
    Department of Preparedness, Swedish Institute for Communicable Disease Control, Solna, Sweden.
    Jenmalm, Maria
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Low diversity of the gut microbiota in infants with atopic eczema2012Inngår i: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 129, nr 2, s. 434-440Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background

    It is debated whether a low total diversity of the gut microbiota in early childhood is more important than an altered prevalence of particular bacterial species for the increasing incidence of allergic disease. The advent of powerful, cultivation-free molecular methods makes it possible to characterize the total microbiome down to the genus level in large cohorts.

    Objective

    We sought to assess microbial diversity and characterize the dominant bacteria in stool during the first year of life in relation to atopic eczema development.

    Methods

    Microbial diversity and composition were analyzed with barcoded 16S rDNA 454-pyrosequencing in stool samples at 1 week, 1 month, and 12 months of age in 20 infants with IgE-associated eczema and 20 infants without any allergic manifestation until 2 years of age (ClinicalTrials.gov ID NCT01285830).

    Results

    Infants with IgE-associated eczema had a lower diversity of the total microbiota at 1 month (P = .004) and a lower diversity of the bacterial phylum Bacteroidetes and the genus Bacteroides at 1 month (P = .02 and P = .01) and the phylum Proteobacteria at 12 months of age (P = .02). The microbiota was less uniform at 1 month than at 12 months of age, with a high interindividual variability. At 12 months, when the microbiota had stabilized, Proteobacteria, comprising gram-negative organisms, were more abundant in infants without allergic manifestation (Empirical Analysis of Digital Gene Expression in R [edgeR] test: P = .008, q = 0.02).

    Conclusion

    Low intestinal microbial diversity during the first month of life was associated with subsequent atopic eczema.

    Fulltekst (pdf)
    fulltext
  • 124.
    Abrahamsson, Thomas
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Jakobsson, Ted
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Björksten, Bengt
    Karolinska Institute, Sweden.
    Oldaeus, Göran
    County Hospital Ryhov, Sweden.
    Jenmalm, Maria
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för inflammationsmedicin. Linköpings universitet, Hälsouniversitetet.
    No effect of probiotics on respiratory allergies: a seven-year follow-up of a randomized controlled trial in infancy2013Inngår i: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 24, nr 6, s. 556-561Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background

    Supplementation with the probiotic Lactobacillus reuteri reduced the incidence of IgE-associated allergic disease in infancy. This treatment might therefore also reduce the risk of asthma and allergic rhinoconjunctivitis in school age.

    Objective

    To evaluate whether perinatal and infant supplementation with L. reuteri reduced the prevalence of respiratory allergic disease in school age and to explore whether this supplementation was associated with any long-term side effects.

    Methods

    A randomized, placebo-controlled trial with oral supplementation with Lreuteri ATCC 55730 (1 × 108 CFU) during the last month of gestation and through the first year of life comprising 232 families with allergic disease, of whom 184 completed a 7-yr follow-up. The primary outcomes at 7 yr of age were allergic disease and skin prick test reactivity (ClinicalTrials.gov ID NCT01285830).

    Results

    The prevalence of asthma (15% in the probiotic vs. 16% in placebo group), allergic rhinoconjunctivitis (27% vs. 20%), eczema (21% vs. 19%) and skin prick test reactivity (29% vs. 26%) was similar in the probiotic and placebo group. Growth indices and gastrointestinal symptoms were similar in the two groups. No severe adverse events were reported.

    Conclusion

    The effect of L. reuteri on sensitization and IgE-associated eczema in infancy did not lead to a lower prevalence of respiratory allergic disease in school age. Thus, the effect of L. reuteri on the immune system seems to be transient. Administration of L. reuteri during the last weeks of gestation and in infancy was not associated with any long-term side effects.

    Fulltekst (pdf)
    fulltext
  • 125.
    Abrahamsson, Thomas R
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomsmedicinska kliniken US.
    Jakobsson, Ted
    Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomsmedicinska kliniken US.
    Böttcher, Malin Fagerås
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Fredrikson, Mats
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Yrkes- och miljömedicin. Linköpings universitet, Hälsouniversitetet.
    Jenmalm, Maria C
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Björkstén, Bengt
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomsmedicinska kliniken US.
    Oldaeus, Göran
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Probiotics in prevention of IgE-associated eczema: a double-blind, randomized, placebo-controlled trial2007Inngår i: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 119, nr 5, s. 1174-1180Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: An altered microbial exposure may underlie the increase of allergic diseases in affluent societies. Probiotics may alleviate and even prevent eczema in infants.

    OBJECTIVE: To prevent eczema and sensitization in infants with a family history of allergic disease by oral supplementation with the probiotic Lactobacillus reuteri.

    METHODS: Double-blind, randomized, placebo-controlled trial, which comprised 232 families with allergic disease, of whom 188 completed the study. The mothers received L reuteri ATCC 55730 (1 x 10(8) colony forming units) daily from gestational week 36 until delivery. Their babies then continued with the same product from birth until 12 months of age and were followed up for another year. Primary outcome was allergic disease, with or without positive skin prick test or circulating IgE to food allergens.

    RESULTS: The cumulative incidence of eczema was similar, 36% in the treated versus 34% in the placebo group. The L reuteri group had less IgE-associated eczema during the second year, 8% versus 20% (P = .02), however. Skin prick test reactivity was also less common in the treated than in the placebo group, significantly so for infants with mothers with allergies, 14% versus 31% (P = .02). Wheeze and other potentially allergic diseases were not affected.

    CONCLUSION: Although a preventive effect of probiotics on infant eczema was not confirmed, the treated infants had less IgE-associated eczema at 2 years of age and therefore possibly run a reduced risk to develop later respiratory allergic disease. CLINICAL IMPLICATION: Probiotics may reduce the incidence of IgE-associated eczema in infancy.

  • 126.
    Abrahamsson, Thomas R
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomsmedicinska kliniken US.
    Sinkiewicz, Gabriela
    Department of Biomedical Lab Science, Malmö University, Malmö, Sweden.
    Jakobsson, Ted
    Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomsmedicinska kliniken US.
    Fredrikson, Mats
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Yrkes- och miljömedicin. Linköpings universitet, Hälsouniversitetet.
    Björkstén, Bengt
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomsmedicinska kliniken US.
    Probiotic lactobacilli in breast milk and infant stool in relation to oral intake during the first year of life2009Inngår i: Journal of pediatric gastroenterology and nutrition, ISSN 1536-4801, Vol. 49, nr 3, s. 349-354Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVES: This is to identify factors affecting the prevalence of Lactobacillus reuteri in maternal faeces and breast milk and infant faeces after oral supplementation with L reuteri and to assess the influence on microbial ecology, particularly Clostridium difficile and Bifidobacterium colonization.

    MATERIALS AND METHODS: In this double-blind trial, 232 mothers with a family history of atopic disease were randomized to a daily intake of either L reuteri American-type culture collection (ATCC) 55730 (1 x 10 colony-forming units [CFU]) or placebo for the last 4 weeks of pregnancy. Their babies then continued with the same study product daily from birth until 12 months of age. Bacterial counts and prevalence were assessed in maternal breast milk and faeces and infant faeces, using conventional cultivation methods.

    RESULTS: The prevalence of L reuteri was higher during the first year of life in the stool samples from infants in the active as compared with the placebo-treated group. The highest prevalence was recorded at 5 to 6 days of age (82% in the treated vs 20% in the placebo group, P < 0.001). Lactobacillus reuteri was isolated from 12% and 2%, respectively, in the colostrum samples (P < 0.05). Breast-feeding seemed to reduce faecal L reuteri counts, although antibiotics did not influence the levels of L reuteri. The administration of L reuteri did not affect bifidobacteria or C difficile colonization.

    CONCLUSION: Lactobacillus reuteri may be detected in breast milk after oral supplementation to the mother and in almost all infants after oral supplementation during the first year of life, as well as occasionally in many untreated infants.

  • 127.
    Abrahamsson, Thomas
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Rautava, Samuli
    University of Turku, Finland; Turku University Hospital, Finland.
    Moore, Aideen M.
    University of Toronto, Canada.
    Neu, Josef
    University of Florida, FL USA.
    Sherman, Philip M.
    University of Toronto, Canada.
    Editorial Material: The Time for a Confirmative Necrotizing Enterocolitis Probiotics Prevention Trial in the Extremely Low Birth Weight Infant in North America Is Now! in JOURNAL OF PEDIATRICS, vol 165, issue 2, pp 389-3942014Inngår i: Journal of Pediatrics, ISSN 0022-3476, E-ISSN 1097-6833, Vol. 165, nr 2, s. 389-394Artikkel i tidsskrift (Annet vitenskapelig)
    Abstract [en]

    n/a

  • 128.
    Abrahamsson, Thomas
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Sandberg, Martina
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Forsberg, Anna
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik.
    Bjorksten, B
    Karolinska Institute.
    Jenmalm, Maria
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    A Th1/Th2-associated chemokine imbalance during infancy in children developing eczema, wheeze and sensitization2011Inngår i: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 41, nr 12, s. 1729-1739Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background Analyses of circulating chemokines offer novel tools to investigate the T helper (Th)1/Th2 imbalance in allergic disease in vivo. less thanbrgreater than less thanbrgreater thanObjective To relate circulating Th1- and Th2-associated chemokines in infancy to allergic disease, sensitization and probiotic supplementation. less thanbrgreater than less thanbrgreater thanMethods Circulating levels of Th1-associated CXC-chemokine ligand (CXCL) 9, CXCL10 and CXCL11 and Th2-associated CC-chemokine ligand (CCL)17 and CCL22 were assessed with Luminex and CCL18 with enzyme-linked immunosorbent assay at birth (n = 109), 6 (n = 104), 12 (n = 116) and 24 months (n = 123) in 161 infants completing a double-blind placebo-controlled allergy prevention trial with Lactobacillus reuteri during the last month of gestation and through the first year of life. The infants were followed regarding the development of allergic disease and sensitization until 2 years of age. less thanbrgreater than less thanbrgreater thanResults The Th2-associated chemokines CCL17 and CCL22 were the highest at birth and then decreased, whereas CCL18 and the Th1-associated chemokines increased with age. High Th2-associated chemokine levels were observed in children developing allergic disease. Sensitization was preceded by elevated levels of the Th2-associated CCL22 and reduced levels of the Th1-associated CXCL11 already at birth. The Th2-associated CCL17 was also elevated at birth in infants developing recurrent wheeze. A high Th2/Th1 ratio (CCL22/CXCL10) at birth associated with both sensitization and eczema development. The presence of L. reuteri in stool in the first week of life was associated with low CCL17 and CCL22 and high CXCL11 levels at 6 months of age. High Th1-associated chemokine levels were associated with day-care. less thanbrgreater than less thanbrgreater thanConclusion and Clinical Relevance Allergic disease and sensitization in infancy was associated with low circulating Th1- and high Th2-associated chemokine levels already from birth. Circulating chemokines are useful for investigating the Th1/Th2 imbalance in allergic disease in vivo. Elucidation of the role of chemokines in allergic diseases may lead to future treatments.

    Fulltekst (pdf)
    fulltext
  • 129.
    Abrahamsson, Thomas
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Sandberg, Martina
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Forsberg, Anna
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Bjorksten, B
    Karolinska Institute.
    Jenmalm, Maria
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    A Th1/Th2-associated chemokine imbalance preceding allergic disease is influenced by birth size, breastfeeding, daycare and probiotics2009Inngår i: in Allergy, vol 64, 2009, Vol. 64, s. 56-56Konferansepaper (Fagfellevurdert)
    Abstract [en]

    Background: Analyses of circulating chemokines offer novel tools to investigate the Th1/Th2 imbalance in allergic disease in vivo and explore the influence of pre- and postnatal factors in infancy.

    Objective: To relate circulating Th1- and Th2-associated chemokines to the development of allergic disease, pre- and postnatal factors and probiotic supplementation in infancy.

    Methods: Circulating levels of Th1-associated CXC-chemokine ligand (CXCL)9, CXCL10 and CXCL11 and Th2-associated CC-chemokine ligand (CCL)17, CCL18 and CCL22 were assessed with Luminex and ELISA at birth (n=109), 6 (n=104), 12 (n=116) and 24 months (n=123) in 179 infants completing a double-blind placebo-controlled allergy prevention trial with Lactobacillus reuteri during the last month of gestation and through the first year of life. The infants were followed regarding development of allergic disease and sensitization until two years of age.

    Results: The Th2-associated chemokines were as highest at birth and then decreased, whereas the Th1-associated chemokines increased with age. Low Th1- and high Th2-associated chemokine levels were observed in children developing allergic disease. Sensitization was preceded by elevated CCL22 and reduced CXCL11 levels. High Th2-associated chemokine46 levels were associated with increased birth length and weight and long duration of breastfeeding, and high Th1-associated chemokine levels with day-care attendance. Presence of L. reuteri in stool the first week of life was associated with low CCL17 and CCL22 and high CXCL11 levels at 6 months.

    Conclusion: Allergic disease in infancy was associated with low circulating Th1- and high Th2-associated chemokine levels during the first year of life. The chemokine levels were affected by both pre and –postnatal factors.

  • 130.
    Abrahamsson, Thomas
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Sherman, Philip M.
    University of Toronto, Canada .
    Editorial Material: Multifaceted Effects of Human Milk Oligosaccharides2014Inngår i: Journal of Infectious Diseases, ISSN 0022-1899, E-ISSN 1537-6613, Vol. 209, nr 3, s. 323-324Artikkel i tidsskrift (Annet vitenskapelig)
    Abstract [en]

    n/a

  • 131.
    Abrahamsson, Thomas
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Wu, Richard Y.
    University of Toronto, Canada.
    Sherman, Philip M.
    University of Toronto, Canada.
    Microbiota in Functional Gastrointestinal Disorders in Infancy: Implications for Management2017Inngår i: INTESTINAL MICROBIOME: FUNCTIONAL ASPECTS IN HEALTH AND DISEASE, KARGER , 2017, Vol. 88, s. 107-115Konferansepaper (Fagfellevurdert)
    Abstract [en]

    The complex and diverse intestinal microbiome is recognized as important in promoting human health. An altered gut microflora, referred to as dysbiosis, is increasingly recognized as having an etiologic role in a variety of conditions, including functional gastrointestinal disorders: colic in infants and irritable bowel syndrome in older children. Probiotics are defined as live microorganisms that, if ingested in sufficient amounts, restore microbial homeostasis and have a benefit on health. Randomized controlled trials indicate that probiotics can be effective in a variety of intestinal conditions, including colic and irritable bowel syndrome. Probiotics may promote gut microbial diversity, but timing of the intervention appears crucial. Strain-specific effects on colonization resistance, epithelial barrier integrity, modulation of signal transduction, impacts on innate and adaptive immune responses, and effects on visceral hyperalgesia likely explain the observed variability in various probiotic strains. In the future, probiotics are likely to be chosen for use in a defined clinical setting based on underlying mechanism(s) of action. The precise component of the probiotic agent mediating observed effects is the subject of current research. Unresolved issues relate to optimal dosages, timing of ingestion, single versus combination formulations, maintenance of viability in storage, and the merits of employing probiotic- derived products. (C) 2017 Nestec Ltd., Vevey/S. Karger AG, Basel

  • 132.
    Abrahamsson, Thomas
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping. University of Toronto, Canada.
    You Wu, Richard
    University of Toronto, Canada.
    Jenmalm, Maria
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Gut microbiota and allergy: the importance of the pregnancy period2015Inngår i: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 77, nr 1, s. 214-219Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Limited microbial exposure is suggested to underlie the increase of allergic diseases in affluent countries, and bacterial diversity seems to be more important than specific bacteria taxa. Prospective studies indicate that the gut microbiota composition during the first months of life influences allergy development, and support the theory that factors influencing the early maturation of the immune system might be important for subsequent allergic disease. However, recent research indicates that microbial exposure during pregnancy may be even more important for the preventative effects against allergic disease. This review gives a background of the epidemiology, immunology, and microbiology literature in this field. It focuses on possible underlying mechanisms such as immune-regulated epigenetic imprinting and bacterial translocation during pregnancy, potentially providing the offspring with a pioneer microbiome. We suggest that a possible reason for the initial exposure of bacterial molecular patterns to the fetus in utero is to prime the immune system and/or the epithelium to respond appropriately to pathogens and commensals after birth.

    Fulltekst (pdf)
    fulltext
  • 133.
    Abramsson, Marianne
    Linköpings universitet, Institutionen för samhälls- och välfärdsstudier, Avdelningen Åldrande och social förändring. Linköpings universitet, Filosofiska fakulteten.
    The housing situation of older people – Issues of investigations2017Inngår i: Book of abstracts, 2017, s. 51-51Konferansepaper (Annet vitenskapelig)
    Abstract [en]

    The housing situation of older people has been on the Swedish political agenda for some time. An increasing ageing population implies a demand for housing in correspodence to their needs. Assisted living facilities decreased with 30 000 places between 2002 and 2016, as a result, the majority of older people age in a dwelling in the ordinary housing market. In 2008 and 2015 respectively two government investigations on older people’s housing were presented. The investigations focused on the need for housing to bridge the gap between ordinary housing and assisted living facilities and issues of affordability and social community but also the lack of accessible housing in particular geographic areas. This paper aims to investigate the origins of the two investigations and relate them to changes in the housing market affecting older people, arguing that the strong emphasis on ageing in place has shifted the responsibility of having a good place to live from general welfare to older individuals themselves.

  • 134.
    Abrandt Dahlgren, Madeleine
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Medicinska fakulteten.
    I takt med framtiden: Utveckling av ett nytt interprofessionellt curriculum vid Hälsouniversitetet i Linköping2015Rapport (Annet vitenskapelig)
    Abstract [sv]

    Hälso- och sjukvårdsutbildningarnas ansvar att utbilda professionella som kan samarbetaoch förstå varandras kompetens, för att utföra och utveckla patientsäker vård, betonas alltmer i den globala debatten om framtidens hälso- och sjukvård. Modern professionsutbildning inom hälso- och sjukvården måste idag därför innehålla moment av god kvalitet där studenter lär med, av och om varandra för att utveckla interprofessionell kompetens. Hälsouniversitetet i Linköping är pionjär, både nationellt och internationellt, när det gäller interprofessionellt lärande tack vare satsningen på integrerade utbildningsmoment som funnits med sedan från starten 1986. Den här rapporten är en sammanställning av den interna process som har genomförts för att initiera ett pedagogiskt utvecklingsprojekt med avsikt att revidera och utveckla dessa gemensamma utbildningsmoment inriktade mot interprofessionellt lärande. Texten är upplagd kronologiskt och inleds med det direktiv som fakultetsledningen gav för att en utvald grupp lärare skulle kunna utarbeta ett förslag på hur de interprofessionella lärandemomenten vid Hälsouniversitetet skulle kunna förbättras. Härefter följer den rapport som utredningsgruppen lämnade, och som sedan skickades på remiss till olika intressenter. Rapporten följs av en sammanställning och bearbetning av de inkomna remissvaren och till sist följer fakultetsstyrelsens beslut om hur curriculum för interprofessionell utbildning inom Hälsouniversitetet ska utvecklas eller förändras. Det är vår förhoppning att dokumentationen av processen för att förnya fakultetens interprofessionella utbildning ska ge inspiration för fortsatt förändrings- och utvecklingsarbete både inom och utom Linköpings universitet.

    Fulltekst (pdf)
    fulltext
  • 135.
    Abrandt Dahlgren, Madeleine
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Medicinska fakulteten.
    Rystedt, HansDepartment of Education, Communication and Learning, University of Gothenburg, Gothenburg, Sweden.Felländer-Tsai, LiDepartment of Clinical Science, Intervention and Technology (CLINTEC) Division of Orthopedics and Biotechnology, Karolinska Institutet, Stockholm, Sweden.Nyström, SofiaLinköpings universitet, Institutionen för beteendevetenskap och lärande, Pedagogik och vuxnas lärande. Linköpings universitet, Utbildningsvetenskap. Region Östergötland, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin.
    Simulation in Health Care: Materiality, Embodiment, Interaction2019Collection/Antologi (Fagfellevurdert)
    Abstract [en]

    Series editors abstract:

    A key goal of this book series is to contribute to discussions about and processes for improving the enactment of occupational capacities through professional practice- based experiences. A related goal is associated with understanding and enhancing the contributions that different kinds of experiences can make to the formation and continuity of those occupational practices. The volumes in this series have contrib- uted a range of perspectives, approaches and outcomes to these discussions. This volume continues that tradition through considerations of how simulation-based activities can contribute to enhancing occupational practices in which working and learning progresses inter- and intra-professionally within healthcare settings. The procedural concern here is to enhance patient safety through improving the quality of collaborative working and learning by healthcare workers. The conceptual concern here is to understand how such working and learning can be understood more fully as a process of interdependence amongst practitioners, and how such co- working and learning progresses, in what ways and for what outcomes. Added here are the ways in which technology comes to mediate and support that process. Perhaps only through such considerations, focused empirical work and detailed analysis will our understanding of human capacities, their enactment and evaluation transcend from either wholly individualised or wholly socialised accounts.

    The sections comprising this book are drawn from a large collaborative study hosted by three institutions that have longer and solid traditions of making contribu- tions to understanding the development of professional capacities through interpro- fessional practices (i.e. Linkoping), dedicated focuses on improving healthcare practices (Karolinska) and the use of technology in working and learning (Gothenburg). These collaborations have been informed and enriched by contribu- tors from other institutions who bring explanatory concepts. The attempt to utilise, accommodate and optimise these different contributions is exercised within the organisation of the sections of the book and chapters within it, highlighted by a process of dual considerations and separate commentaries. Each of these sections provides an overview, statements about procedural matters (e.g. how to conduct inquiries or how to analyse data), proposing and advancing particular explanatory accounts, and also offering perspectives on how educational or work practice might be enhanced. This structuring is particularly helpful as it provides focused consid- erations of particular phenomena (e.g. team-based approaches to simulation, use of video recordings, doing simulations) through description, analysis and commentary.

    In these ways, this volume offers contributions to discussions about the goals for, processes of and outcomes of professional and practice-based learning in a manner that is highly consistent with the ambitions of this book series.

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    presentationsbild
  • 136.
    Abrate, Alberto
    et al.
    IRCCS Osped San Raffaele, Italy.
    Buono, Roberta
    IRCCS Osped San Raffaele, Italy.
    Canu, Tamara
    IRCCS Osped San Raffaele, Italy.
    Esposito, Antonio
    IRCCS Osped San Raffaele, Italy.
    Del Maschio, Alessandro
    IRCCS Osped San Raffaele, Italy.
    Luciano, Roberta
    IRCCS Osped San Raffaele, Italy; IRCCS Osped San Raffaele, Italy.
    Bettiga, Arianna
    IRCCS Osped San Raffaele, Italy.
    Colciago, Giorgia
    IRCCS Osped San Raffaele, Italy.
    Guazzoni, Giorgio
    IRCCS Osped San Raffaele, Italy.
    Benigni, Fabio
    IRCCS Osped San Raffaele, Italy.
    Hedlund, Petter
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk farmakologi. IRCCS Osped San Raffaele, Italy.
    Altaner, Cestmir
    Slovak Academic Science, Slovakia; St Elisabeth Cancer Institute, Slovakia.
    Montorsi, Francesco
    IRCCS Osped San Raffaele, Italy.
    Cavarretta, Ilaria T. R.
    IRCCS Osped San Raffaele, Italy.
    Mesenchymal stem cells expressing therapeutic genes induce autochthonous prostate tumour regression2014Inngår i: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 50, nr 14, s. 2478-2488Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Mesenchymal stem cells (MSC) as vehicles of therapeutic genes represent a unique tool to activate drugs within a neoplastic mass due to their property to home and engraft into tumours. In particular, MSC expressing the cytosine deaminase:: uracil phosphoribosyltransferase (CD-MSC) have been previously demonstrated to inhibit growth of subcutaneous prostate cancer xenografts thanks to their ability to convert the non-toxic 5-fluorocytosine into the antineoplastic 5-fluorouracil. Since both the immune system and the tumour microenvironment play a crucial role in directing cancer progression, in order to advance towards clinical applications, we tested the therapeutic potential of this approach on animal models that develop autochthonous prostate cancer and preserve an intact immune system. As cell vectors, we employed adipose-tissue and bone-marrow MSC. CD-MSC toxicity on murine prostate cancer cells and tumour tropism were verified in vitro and ex-vivo before starting the preclinical studies. Magnetic Resonance Imaging was utilised to follow orthotopic tumour progression. We demonstrated that intravenous injections of CD-MSC cells, followed by intraperitoneal administration of 5-fluorocytosine, caused tumour regression in the transgenic adenocarcinoma of the mouse prostate (TRAMP) model, which develops aggressive and spontaneous prostate cancer. These results add new insights to the therapeutic potential of specifically engineered MSC in prostate cancer disease.

  • 137. Bestill onlineKjøp publikasjonen >>
    Abtahi, Jahan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Ortopedi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Sinnescentrum, Käkkliniken US.
    Bisphosphonates and implants in the jaw bone2013Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Insertion of metal implants in bone is one of the commonest of all surgical procedures. The success of these operations is dependent on the fixation of the implants, which, in turn, depends on the strength of the bone that holds them. If the quality of the bone holding the implant could be improved locally, surgical procedures would become simpler and rehabilitation would become faster. Bisphosphonates are anti-resorptive drugs that act specifically on osteoclasts, thereby maintaining bone density and strength. Once released from the surface of a coated implant, bisphosphonates reduce osteoclast activity, thereby changing the balance of bone turnover in favor of bone formation, leading to a net gain in local bone density. During the last decades, the effects of bisphosphonate treatment on the stability of implants have been tested in several clinical and animal studies, but not in human jaws. This may be because it has been suggested that there is a link between the use of bisphosphonates (especially those given intravenously) and a condition called osteonecrosis of the jaw (ONJ). The pathophysiology and treatment of ONJ is controversial. The difficulty in treating ONJ has highlighted the importance of prevention.

    The overall aim of the present thesis was to evaluate the effect of local and systemic use of bisphosphonates on bone tissue. Could a thin, bisphosphonate-eluting fibrinogen coating improve the fixation of metal implants in the human jaw? Would it be possible to reproduce ONJ and prevent the development of this condition in an animal model?

    In two clinical studies, a total number of 96 implants were inserted in 21 patients. In a randomized trial with a paired design, one implant in each pair was coated with a thin fibrinogen layer containing two bisphosphonates (pamidronate and ibandronate). The bisphosphonate-coated implants showed better stability as measured by resonancefrequency analysis. Radiographic intraoral films also showed less bone loss. Three animal models were developed. In a study comparing local and systemic effects of bisphosphonates, zoledronate-coated screws inserted in rats showed better fixation in spite of a drug treatment that is known to induce ONJ-like lesions when given systemically. In another rat model, ONJ-like lesions were reproducibly induced at sites of tooth extraction whereas there were no signs of bone cell death in uninjured sites. Finally, rat experiments showed that the development of ONJ-like lesions after tooth extraction could be prevented by early mucoperiosteal coverage.

    In conclusion, a thin, bisphosphonate-eluting fibrinogen coating can improve the fixation of dental implants in human bone. This may lead to new possibilities in orthopaedic surgery and dentistry. The pathophysiology of ONJ is strongly linked to bone exposure in combination with drugs that reduce resorption.

    Delarbeid
    1. Bisphosphonate coating might improve fixation of dental implants in the maxilla: A pilot study
    Åpne denne publikasjonen i ny fane eller vindu >>Bisphosphonate coating might improve fixation of dental implants in the maxilla: A pilot study
    2010 (engelsk)Inngår i: International Journal of Oral and Maxillofacial Surgery, ISSN 0901-5027, E-ISSN 1399-0020, Vol. 39, nr 7, s. 673-677Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    This pilot study evaluates the clinical stability of bisphosphonate-coated dental implants placed using a two-stage surgical procedure in five patients. Each patient received seven regular Branemark implants, one of which was coated with bisphosphonate in a fibrinogen matrix. The coated implant was inserted where the bone was expected to have the least favourable quality. The level of the marginal bone around each implant was measured by intraoral periapical radiographs and implant stability was recorded using resonance frequency measurements. Frequency values (ISQ) were obtained peroperatively before flap closure and after 6 months at abutment connection. At abutment connection the bisphosphonate-coated implants were removed en bloc in two patients for histological examination. An animal experiment had previously confirmed that gamma-sterilization did not reduce bioactivity of the bisphosphonate coating. In each patient, the bisphosphonate-coated implant showed the largest improvement in ISQ level of all implants. Their values at the start tended to be lower, and the absolute value at 6 months did not differ. No complications occurred with the coated implants. Histology showed no abnormalities. Improvement in ISQ values was an expected effect of the bisphosphonate coating, but could be due to the choice of insertion site. This finding warrants a randomized blinded study.

    sted, utgiver, år, opplag, sider
    Elsevier Science B.V., Amsterdam, 2010
    Emneord
    bisphosphonate coating; dental implants; fixation
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-58193 (URN)10.1016/j.ijom.2010.04.002 (DOI)000279972500007 ()
    Tilgjengelig fra: 2010-08-11 Laget: 2010-08-09 Sist oppdatert: 2018-01-12
    2. A bisphosphonate-coating improves the fixation of metal implants in human bone. A randomized trial of dental implants
    Åpne denne publikasjonen i ny fane eller vindu >>A bisphosphonate-coating improves the fixation of metal implants in human bone. A randomized trial of dental implants
    2012 (engelsk)Inngår i: Bone, ISSN 8756-3282, E-ISSN 1873-2763, Vol. 50, nr 5, s. 1148-1151Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Many surgical procedures use metal implants in bone. The clinical results depend on the strength of the bone holding these implants. Our objective was to show that a drug released from the implant surface can improve parameters reflecting the quality or amount of this bone. Sixteen patients received paired dental titanium implants in the maxilla, in a randomized, double-blinded fashion. One implant in each pair was coated with a thin fibrinogen layer containing 2 bisphosphonates. The other implant was untreated. Fixation was evaluated by measurement of resonance frequency (implant stability quotient; ISQ) serving as a proxy for stiffness of the implant-bone construct. Increase in ISQ at 6 months of follow-up was the primary variable. None of the patients had any complications. The resonance frequency increased 6.9 ISQ units more for the coated implants (p = 0.0001; Cohens d = 1.3). The average difference in increase in ISQ and the effect size, suggested a clinically relevant improvement. X-ray showed less bone resorption at the margin of the implant both at 2 months (p = 0.012) and at 6 months (p = 0.012). In conclusion, a thin, bisphosphonate-eluting fibrinogen coating might improve the fixation of metal implants in human bone. This might lead to new possibilities for orthopedic surgery in osteoporotic bone and for dental implants.

    sted, utgiver, år, opplag, sider
    Elsevier, 2012
    Emneord
    Bone healing, Dental implant, Drug delivery, Mechanical test, Osseointegration bisphosphonates
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-77527 (URN)10.1016/j.bone.2012.02.001 (DOI)000303274400018 ()
    Merknad

    Funding Agencies|Swedish Research Council|VR 2009-6725|

    Tilgjengelig fra: 2012-05-28 Laget: 2012-05-22 Sist oppdatert: 2017-12-07
    3. Bisphosphonate-induced osteonecrosis of the jaw in a rat model arises first after the bone has become exposed. No primary necrosis in unexposed bone
    Åpne denne publikasjonen i ny fane eller vindu >>Bisphosphonate-induced osteonecrosis of the jaw in a rat model arises first after the bone has become exposed. No primary necrosis in unexposed bone
    2012 (engelsk)Inngår i: Journal of Oral Pathology & Medicine, ISSN 0904-2512, E-ISSN 1600-0714, Vol. 41, nr 6, s. 494-499Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    J Oral Pathol Med (2012) 41: 494499 Background: Bisphosphonate-related osteonecrosis of the jaw was first described to start with sterile osteocyte death, similar to osteonecrosis in other parts of the skeleton. The typical chronic osteomyelitis was thought to develop when the dead bone was exposed to the oral cavity. An alternative explanation would be that the chronic osteomyelitis is a result of a bisphosphonate-related inability of infected bony lesions to heal. We tested the hypothesis that primary osteocyte death is not necessary for the development of jaw osteonecrosis. Material and methods: Forty rats were randomly allocated to four groups of 10. All animals underwent unilateral molar extraction and received the following drug treatments: Group I, controls with no drug treatment; Group II, 200 mu g/kg per day alendronate; Groups III and IV, 200 mu g/kg per day alendronate and 1 mg/kg of dexamethasone. All rats were euthanized after 14 days. Presence of osteonecrosis was determined by clinical and histological observations for groups IIII. For group IV, osteocyte viability at the contralateral uninjured site was examined using lactate dehydrogenase histochemistry (LDH). Results: All animals in the alendronate plus dexamethasone groups developed large ONJ-like lesions. Lactate dehydrogenase staining showed viable osteocytes in the contralateral jaw with no tooth extraction. No signs of osteonecosis were seen in the other groups. Conclusion: Bisphosphonates and dexamethasone caused no osteocyte death in uninjured bone, but large ONJ-like lesions after tooth extraction. Osteonecrosis of the jaw appears to arise first after the bone has been exposed. Possibly, bisphosphonates hamper the necessary resorption of bone that has become altered because of infection.

    sted, utgiver, år, opplag, sider
    John Wiley and Sons, 2012
    Emneord
    bisphosphonates; bisphosphonate associated osteonecrosis of the jaw; osteonecrosis; rat
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-79679 (URN)10.1111/j.1600-0714.2011.01125.x (DOI)000305961100010 ()
    Tilgjengelig fra: 2012-08-14 Laget: 2012-08-13 Sist oppdatert: 2017-12-07
    4. Effect of Local vs. Systemic Bisphosphonate Delivery on Dental Implant Fixation in a Model of Osteonecrosis of the Jaw
    Åpne denne publikasjonen i ny fane eller vindu >>Effect of Local vs. Systemic Bisphosphonate Delivery on Dental Implant Fixation in a Model of Osteonecrosis of the Jaw
    2013 (engelsk)Inngår i: Journal of Dental Research, ISSN 0022-0345, E-ISSN 1544-0591, Vol. 92, nr 3, s. 279-283Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Locally applied bisphosphonates may improve the fixation of metal implants in bone. However, systemic bisphosphonate treatment is associated with a risk of osteonecrosis of the jaw (ONJ). We hypothesized that local delivery of bisphosphonate from the implant surface improves the fixation of dental implants without complications in a setting where systemic treatment induces ONJ. Forty rats were randomly allocated to 4 groups of 10. All groups received a titanium implant inserted in an extraction socket. Group I received the implants only. Group II received dexamethasone (0.5 mg/kg). Group III received dexamethasone as above plus alendronate (200 µg/kg). Group IV received zoledronate-coated implants and dexamethasone as above. The animals were sacrificed 2 weeks after tooth extraction. All 10 animals with systemic alendronate treatment developed large ONJ-like changes, while all with local treatment were completely healed. Implant removal torque was higher for the bisphosphonate-coated implants compared with the other groups (p < 0.03 for each comparison). Micro-computed tomography of the maxilla showed more bone loss in the systemic alendronate group compared with groups receiving local treatment (p = 0.001). Local bisphosphonate treatment appears to improve implant fixation in a setting where systemic treatment caused ONJ.

    sted, utgiver, år, opplag, sider
    Sage Publications, 2013
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-89667 (URN)10.1177/0022034512472335 (DOI)000314914100013 ()23264610 (PubMedID)
    Tilgjengelig fra: 2013-03-01 Laget: 2013-03-01 Sist oppdatert: 2017-12-06bibliografisk kontrollert
    5. Prevention of osteonecrosis of the jaw by mucoperiosteal coverage in a rat model
    Åpne denne publikasjonen i ny fane eller vindu >>Prevention of osteonecrosis of the jaw by mucoperiosteal coverage in a rat model
    2013 (engelsk)Inngår i: International Journal of Oral and Maxillofacial Surgery, ISSN 0901-5027, E-ISSN 1399-0020, Vol. 42, nr 5, s. 632-636Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    There is evidence for a link between the use of systemic bisphosphonates and osteonecrosis of the jaw (ONJ). This condition has the appearance of chronic osteomyelitis, and antibiotics prevent the development of ONJ in animal models. Clinically, ONJ can sometimes be successfully treated by mucoperiosteal coverage. If ONJ is indeed primarily caused by bacterial infection, immediate coverage of the extraction alveolus might reduce the risk of ONJ development in risk patients. Therefore, we studied whether immediate mucoperiosteal coverage after tooth extraction could prevent ONJ development in a rat model. Thirty rats were randomly allocated to three groups of 10. Group I (controls): extraction, no drug treatment; Group II (non-coverage): extraction, dexamethasone plus alendronate; Group III (coverage): dexamethasone plus alendronate, plus coverage by a mucoperiosteal flap. Rats were examined for macroscopic ONJ-like wounds after 2 weeks. All animals in the non-coverage group developed large ONJ-like changes. The coverage and control groups showed an intact overlying mucosa in all rats. Findings were confirmed with histology. Bisphosphonates and dexamethasone caused ONJ-like lesions after tooth extraction in a rat model. This was prevented by immediate mucoperiosteal coverage. The risk of ONJ in patients using bisphosphonates might be reduced by mucoperiosteal coverage after tooth extraction.

    Emneord
    Bisphosphonates, osteonecrosis, jaw, rat, mucoperiosteal flap, antibiotics
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-89668 (URN)10.1016/j.ijom.2013.02.007 (DOI)000318132600014 ()
    Tilgjengelig fra: 2013-03-01 Laget: 2013-03-01 Sist oppdatert: 2017-12-06bibliografisk kontrollert
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    Bisphosphonates and implants in the jaw bone
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  • 138.
    Abtahi, Jahan
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Ortopedi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Sinnescentrum, Käkkliniken US.
    Agholme, Fredrik
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Ortopedi. Linköpings universitet, Hälsouniversitetet.
    Aspenberg, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Ortopedi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping.
    Prevention of osteonecrosis of the jaw by mucoperiosteal coverage in a rat model2013Inngår i: International Journal of Oral and Maxillofacial Surgery, ISSN 0901-5027, E-ISSN 1399-0020, Vol. 42, nr 5, s. 632-636Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    There is evidence for a link between the use of systemic bisphosphonates and osteonecrosis of the jaw (ONJ). This condition has the appearance of chronic osteomyelitis, and antibiotics prevent the development of ONJ in animal models. Clinically, ONJ can sometimes be successfully treated by mucoperiosteal coverage. If ONJ is indeed primarily caused by bacterial infection, immediate coverage of the extraction alveolus might reduce the risk of ONJ development in risk patients. Therefore, we studied whether immediate mucoperiosteal coverage after tooth extraction could prevent ONJ development in a rat model. Thirty rats were randomly allocated to three groups of 10. Group I (controls): extraction, no drug treatment; Group II (non-coverage): extraction, dexamethasone plus alendronate; Group III (coverage): dexamethasone plus alendronate, plus coverage by a mucoperiosteal flap. Rats were examined for macroscopic ONJ-like wounds after 2 weeks. All animals in the non-coverage group developed large ONJ-like changes. The coverage and control groups showed an intact overlying mucosa in all rats. Findings were confirmed with histology. Bisphosphonates and dexamethasone caused ONJ-like lesions after tooth extraction in a rat model. This was prevented by immediate mucoperiosteal coverage. The risk of ONJ in patients using bisphosphonates might be reduced by mucoperiosteal coverage after tooth extraction.

  • 139.
    Abtahi, Jahan
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Ortopedi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Sinnescentrum, Käkkliniken US.
    Agholme, Fredrik
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Ortopedi. Linköpings universitet, Hälsouniversitetet.
    Sandberg, Olof
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Aspenberg, Per
    Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Ortopedi. Linköpings universitet, Hälsouniversitetet.
    Bisphosphonate-induced osteonecrosis of the jaw in a rat model arises first after the bone has become exposed. No primary necrosis in unexposed bone2012Inngår i: Journal of Oral Pathology & Medicine, ISSN 0904-2512, E-ISSN 1600-0714, Vol. 41, nr 6, s. 494-499Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    J Oral Pathol Med (2012) 41: 494499 Background: Bisphosphonate-related osteonecrosis of the jaw was first described to start with sterile osteocyte death, similar to osteonecrosis in other parts of the skeleton. The typical chronic osteomyelitis was thought to develop when the dead bone was exposed to the oral cavity. An alternative explanation would be that the chronic osteomyelitis is a result of a bisphosphonate-related inability of infected bony lesions to heal. We tested the hypothesis that primary osteocyte death is not necessary for the development of jaw osteonecrosis. Material and methods: Forty rats were randomly allocated to four groups of 10. All animals underwent unilateral molar extraction and received the following drug treatments: Group I, controls with no drug treatment; Group II, 200 mu g/kg per day alendronate; Groups III and IV, 200 mu g/kg per day alendronate and 1 mg/kg of dexamethasone. All rats were euthanized after 14 days. Presence of osteonecrosis was determined by clinical and histological observations for groups IIII. For group IV, osteocyte viability at the contralateral uninjured site was examined using lactate dehydrogenase histochemistry (LDH). Results: All animals in the alendronate plus dexamethasone groups developed large ONJ-like lesions. Lactate dehydrogenase staining showed viable osteocytes in the contralateral jaw with no tooth extraction. No signs of osteonecosis were seen in the other groups. Conclusion: Bisphosphonates and dexamethasone caused no osteocyte death in uninjured bone, but large ONJ-like lesions after tooth extraction. Osteonecrosis of the jaw appears to arise first after the bone has been exposed. Possibly, bisphosphonates hamper the necessary resorption of bone that has become altered because of infection.

  • 140.
    Abtahi, Jahan
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Ortopedi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Sinnescentrum, Käkkliniken US.
    Agholme, Fredrik
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Ortopedi. Linköpings universitet, Hälsouniversitetet.
    Sandberg, Olof
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Ortopedi. Linköpings universitet, Hälsouniversitetet.
    Aspenberg, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Ortopedi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping.
    Effect of Local vs. Systemic Bisphosphonate Delivery on Dental Implant Fixation in a Model of Osteonecrosis of the Jaw2013Inngår i: Journal of Dental Research, ISSN 0022-0345, E-ISSN 1544-0591, Vol. 92, nr 3, s. 279-283Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Locally applied bisphosphonates may improve the fixation of metal implants in bone. However, systemic bisphosphonate treatment is associated with a risk of osteonecrosis of the jaw (ONJ). We hypothesized that local delivery of bisphosphonate from the implant surface improves the fixation of dental implants without complications in a setting where systemic treatment induces ONJ. Forty rats were randomly allocated to 4 groups of 10. All groups received a titanium implant inserted in an extraction socket. Group I received the implants only. Group II received dexamethasone (0.5 mg/kg). Group III received dexamethasone as above plus alendronate (200 µg/kg). Group IV received zoledronate-coated implants and dexamethasone as above. The animals were sacrificed 2 weeks after tooth extraction. All 10 animals with systemic alendronate treatment developed large ONJ-like changes, while all with local treatment were completely healed. Implant removal torque was higher for the bisphosphonate-coated implants compared with the other groups (p < 0.03 for each comparison). Micro-computed tomography of the maxilla showed more bone loss in the systemic alendronate group compared with groups receiving local treatment (p = 0.001). Local bisphosphonate treatment appears to improve implant fixation in a setting where systemic treatment caused ONJ.

  • 141.
    Abtahi, Jahan
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Käkkliniken US.
    Ajan, Aida
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Käkkliniken US.
    Malignant Transformation of Ossifying Fibroma into Parosteal Osteosarcoma with High-grade Component: Presentation of an Unusual Case and Review of the Literature2018Inngår i: The Open Dentistry Journal, E-ISSN 1874-2106, Vol. 12, s. 1059-1068Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Parosteal Osteosarcoma of the Jaw (POSJ) is a rare entity that is associated with a high survival rate. Several case reports and case series of POSJ have been published in the literature, but few authors have described development of this tumor by possible transformation from a fibro-osseous neoplasm. Objective: We present a rare occurrence of parosteal osteosarcoma with involvement of the posterior maxilla, orbit floor, and infra-temporal fossa in a 20-year-old man. Furthermore, we performed a literature review regarding clinical, radiological, and histological features; treatment strategies; and etiology/pathophysiology. Methods: A PubMed search yielded a total of 74 articles and the articles were sorted according to their corresponding key area of focus. Results: This was a case of POSJ with high-grade component in the maxillofacial region of a 20-year old male. Co-expression of MDM2 and CDK4 was confirmed. At 2.5-year follow-up, the patient had died. The literature review revealed 18 articles including 20 cases of POSJ. Four cases represent the possible development of this tumor by transformation from a fibro-osseous neoplasm: Two cases of fibrous dysplasia, one case of cemento-ossifying fibroma, and the case of Ossifying Fibroma (OF) in the present study. Conclusion: In conclusion, we found an unusual case of POSJ of the midface in a patient with a previous diagnosis of OF in the same region. To our knowledge, there have been no previous reports of development of POSJ in OF. Furthermore, this is the first described case of high-grade surface osteosarcoma in the craniofacial region.

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  • 142.
    Abtahi, Jahan
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Käkkliniken US.
    Henefalk, G.
    Region Östergötland, Sinnescentrum, Käkkliniken US.
    Aspenberg, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping.
    Randomised trial of bisphosphonate-coated dental implants: Radiographic follow-up after five years of loading2016Inngår i: International Journal of Oral and Maxillofacial Surgery, ISSN 0901-5027, E-ISSN 1399-0020, Vol. 45, nr 12, s. 1564-1569Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The results of a randomised trial with bisphosphonate-coated dental implants have been reported previously. Each patient received one coated and one uncoated implant in a double-blind split-mouth design study. After 6 months of osseointegration, resonance frequency analysis indicated better fixation of the coated implants. Reduced marginal bone resorption was also shown. However, it was not known whether the advantage of the bisphosphonate coating would persist over time. The radiographic results at 5 years after implant installation are reported herein. A blinded investigator measured marginal resorption on fresh radiographs obtained for 14 of the 16 patients (two had died) and compared these with the post-implantation images. Non-parametric statistics were used. All implants functioned well. The median marginal bone loss for control implants was found to be 0.70 mm, which is less than usually reported in the literature. The bisphosphonate-coated implants showed even less resorption (median 0.20 mm). The median difference within each pair of implants after 5 years of use was 0.34 mm (95% confidence interval 0.00-0.75 mm; P = 0.04). The present data suggest that bisphosphonate-coated implants enable prolonged preservation of the marginal bone.

  • 143.
    Abtahi, Jahan
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Käkkliniken US.
    Henefalk, Gustav
    Region Östergötland, Sinnescentrum, Käkkliniken US.
    Aspenberg, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping.
    Impact of a zoledronate coating on early post-surgical implant stability and marginal bone resorption in the maxilla-A split-mouth randomized clinical trial.2019Inngår i: Clinical Oral Implants Research, ISSN 0905-7161, E-ISSN 1600-0501, Vol. 30, nr 1, s. 49-58Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVES: The objective of this clinical study was to evaluate the effect of a bisphosphonate coating on a titanium implant on the implant stability quotient (ISQ) and the radiographic marginal bone levels at implants during early healing (2-8 weeks).

    MATERIALS AND METHODS: In a randomized double-blind trial with internal controls, 16 patients received a dental implant coated with zoledronate and one uncoated implant as a control. The coated and uncoated implants which were visually indistinguishable were bone level titanium implants with a moderately rough surface and a microthreaded neck. ISQ values were obtained at insertion and at 2, 4, 6, and 8 weeks. Radiographs were obtained at insertion and at 8 weeks. The primary outcome was the difference in ISQ values between the coated implants and the control implants at 4 and 6 weeks, corrected for insertion values. The secondary outcome was loss of marginal bone level from insertion to 8 weeks.

    RESULTS: Implant stability quotient values remained largely constant over the 8 weeks, and there was no significant difference between coated and uncoated implants at any time point. There was 0.12 (SD 0.10) mm marginal bone loss at the control implants and 0.04 (SD 0.08) mm at the coated implants. The difference was 0.17 mm; SD 0.14; p < 0.006). On blind qualitative scoring, 13 of the 15 control implants and two of 15 coated implants showed small marginal bone defects (p = 0.003).

    CONCLUSIONS: There were no statistically significant differences observed in ISQ values between the coated and uncoated implants during the early healing. There was less marginal bone loss at the coated implants.

  • 144.
    Abtahi, Jahan
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Käkkliniken US.
    Malakuti, Iman
    Region Östergötland, Sinnescentrum, Käkkliniken US.
    Ajan, Aida
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Käkkliniken US.
    Surgical Management of Granular Cell Tumor of the Orbit: Case Report and Literature Review2019Inngår i: Open Dentistry Journal, ISSN 1874-2106, E-ISSN 1874-2106, Vol. 13, s. 33-40Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Introduction: Granular Cell Tumors (GCTs) of the orbit are rare-entity soft-tissue tumors, and few reports have been published in the literature. The treatment of the choice is total excision. Early diagnosis prior to surgery is valuable for the distinction of malignant from benign tumor.

    Case presentation: We report a case of a 55-year-old woman with a solitary slow-growing mass in the right orbit with the involvement of the rectus inferior muscle, and present a review of the recent literature. The lesion had a diameter of 1 cm and was noticed 2 years before the examination. Excisional biopsy confirmed the diagnosis of GCT. The tumor was resected through a retroseptal transconjunctival approach. The final histological examination revealed findings characteristic of GCT, including positive reaction for protein S-100, SOX10, and calcitonin and negative reaction for desmin, myogenin, Smooth Muscle Antigen (SMA), Melan-A, and HMB-45. There were no signs of malignancy in this sample. Disturbance of motility was not noted by the patient after surgery.

    Conclusion: GCT should be included in the differential diagnosis of intraorbital lesions, particularly those that involve the orbit muscles. A biopsy is recommended before surgical resection, to exclude malignancy and prevent radical resection.

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  • 145.
    Abtahi, Jahan
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Ortopedi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Sinnescentrum, Käkkliniken US.
    Tengvall, Pentti
    Gothenburg University.
    Aspenberg, Per
    Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Ortopedi. Linköpings universitet, Hälsouniversitetet.
    A bisphosphonate-coating improves the fixation of metal implants in human bone. A randomized trial of dental implants2012Inngår i: Bone, ISSN 8756-3282, E-ISSN 1873-2763, Vol. 50, nr 5, s. 1148-1151Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Many surgical procedures use metal implants in bone. The clinical results depend on the strength of the bone holding these implants. Our objective was to show that a drug released from the implant surface can improve parameters reflecting the quality or amount of this bone. Sixteen patients received paired dental titanium implants in the maxilla, in a randomized, double-blinded fashion. One implant in each pair was coated with a thin fibrinogen layer containing 2 bisphosphonates. The other implant was untreated. Fixation was evaluated by measurement of resonance frequency (implant stability quotient; ISQ) serving as a proxy for stiffness of the implant-bone construct. Increase in ISQ at 6 months of follow-up was the primary variable. None of the patients had any complications. The resonance frequency increased 6.9 ISQ units more for the coated implants (p = 0.0001; Cohens d = 1.3). The average difference in increase in ISQ and the effect size, suggested a clinically relevant improvement. X-ray showed less bone resorption at the margin of the implant both at 2 months (p = 0.012) and at 6 months (p = 0.012). In conclusion, a thin, bisphosphonate-eluting fibrinogen coating might improve the fixation of metal implants in human bone. This might lead to new possibilities for orthopedic surgery in osteoporotic bone and for dental implants.

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  • 146.
    Abtahi, Jahan
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Ortopedi och idrottsmedicin. Linköpings universitet, Hälsouniversitetet.
    Tengvall, Pentti
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Tillämpad Fysik. Linköpings universitet, Tekniska högskolan. Department of Biomaterials, Institute of Clinical Sciences, Sahlgrenska Academy, Gothenburg, Sweden.
    Aspenberg, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Ortopedi och idrottsmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Ortopedicentrum, Ortopedkliniken Linköping.
    Bisphosphonate coating might improve fixation of dental implants in the maxilla: A pilot study2010Inngår i: International Journal of Oral and Maxillofacial Surgery, ISSN 0901-5027, E-ISSN 1399-0020, Vol. 39, nr 7, s. 673-677Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    This pilot study evaluates the clinical stability of bisphosphonate-coated dental implants placed using a two-stage surgical procedure in five patients. Each patient received seven regular Branemark implants, one of which was coated with bisphosphonate in a fibrinogen matrix. The coated implant was inserted where the bone was expected to have the least favourable quality. The level of the marginal bone around each implant was measured by intraoral periapical radiographs and implant stability was recorded using resonance frequency measurements. Frequency values (ISQ) were obtained peroperatively before flap closure and after 6 months at abutment connection. At abutment connection the bisphosphonate-coated implants were removed en bloc in two patients for histological examination. An animal experiment had previously confirmed that gamma-sterilization did not reduce bioactivity of the bisphosphonate coating. In each patient, the bisphosphonate-coated implant showed the largest improvement in ISQ level of all implants. Their values at the start tended to be lower, and the absolute value at 6 months did not differ. No complications occurred with the coated implants. Histology showed no abnormalities. Improvement in ISQ values was an expected effect of the bisphosphonate coating, but could be due to the choice of insertion site. This finding warrants a randomized blinded study.

  • 147. Abu-Elyazeed, R R
    et al.
    Heineman, T
    Dubin, G
    Fourneau, M
    Leroux-Roels, I
    Leroux-Roels, G
    Richardus, J H
    Ostergaard, L
    Diez-Domingo, J
    Poder, A
    Van Damme, P
    Romanowski, B
    Blatter, M
    Silfverdal, S A
    Berglund, J
    Josefsson, Ann
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Cunningham, A L
    Flodmark, C E
    Tragiannidis, A
    Dobson, S
    Olafsson, J
    Puig-Barbera, J
    Mendez, M
    Barton, S
    Bernstein, D
    Mares, J
    Ratner, P
    Safety and immunogenicity of a glycoprotein D genital herpes vaccine in healthy girls 10-17 years of age: results from a randomised, controlled, double-blind trial.2013Inngår i: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 31, nr 51, s. 6136-6043Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE: The investigational AS04-adjuvanted herpes simplex virus type 2 (HSV-2) glycoprotein D (gD2) subunit prophylactic vaccine ('HSV vaccine'; GlaxoSmithKline Vaccines) has been shown to be well tolerated in adults, but limited data exist for pre-teen and adolescent girls, a likely target population. The primary objective of this study was to compare the occurrence of serious adverse events (SAEs) over 12 months between HSV vaccine recipients and saline recipients (placebo control group) in pre-teen and adolescent girls. The immunogenicity of the HSV vaccine was also assessed.

    METHODS: Healthy girls aged 10-17 years, stratified by age (10-15 years; 16-17 years), were randomised 2:1:1 to receive the HSV vaccine, a hepatitis A vaccine (Havrix™; HAV control) or placebo (saline) according to a 0-, 1-, 6-month schedule. Participants and study personnel not involved in the preparation or administration of vaccines were blinded to treatment. Safety and immunogenicity analyses were performed overall and by age (10-15 years; 16-17 years) and HSV serostatus.

    RESULTS: No statistically significant difference in the percentage of subjects with SAEs was observed between the HSV and saline group, or between the HSV and pooled control (HAV and saline) groups. The HSV vaccine was well tolerated, although a higher incidence of solicited local symptoms was observed in the HSV group than in the control group. Neither age nor HSV serostatus at the time of study entry had an impact on the safety profile of this vaccine. The HSV vaccine was immunogenic regardless of pre-vaccination HSV serostatus. Higher anti-gD geometric mean concentrations were observed in HSV-1 seropositive participants than in HSV-1 seronegative participants.

    CONCLUSION: The HSV vaccine had an acceptable safety profile, and was well tolerated and immunogenic when administered to girls aged 10-17 years regardless of age or HSV pre-vaccination serostatus.

  • 148.
    Abuzeid, Nadir
    et al.
    Medical and Aromat Plants Research Institute, Sudan; Omdurman Islamic University, Sudan.
    Kalsum, Sadaf
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Hälsouniversitetet.
    Koshy, Richin John
    Larsson, Marie C
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Hälsouniversitetet.
    Glader, Mikaela
    Andersson, Henrik
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Hälsouniversitetet.
    Raffetseder, Johanna
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Hälsouniversitetet.
    Pienaar, Elsje
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Hälsouniversitetet.
    Eklund, Daniel
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för inflammationsmedicin. Linköpings universitet, Hälsouniversitetet.
    Alhassan, Muddathir S.
    Medical and Aromat Plants Research Institute, Sudan.
    AlGadir, Haidar A.
    Medical and Aromat Plants Research Institute, Sudan.
    Koko, Waleed S.
    Medical and Aromat Plants Research Institute, Sudan.
    Schon, Thomas
    Kalmar County Hospital, Sweden.
    Ahmed Mesaik, M.
    University of Kebangsaan Malaysia, Malaysia; University of Karachi, Pakistan.
    Abdalla, Omer M.
    University of Karachi, Pakistan.
    Khalid, Asaad
    Medical and Aromat Plants Research Institute, Sudan.
    Lerm, Maria
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Hälsouniversitetet.
    Antimycobacterial activity of selected medicinal plants traditionally used in Sudan to treat infectious diseases2014Inngår i: Journal of Ethnopharmacology, ISSN 0378-8741, E-ISSN 1872-7573, Vol. 157, s. 134-139Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Ethnopharmacological relevance: The emergence of multidrug-resistant strains of Mycobacterium tuberculosis underscores the need for continuous development of new and efficient methods to determine the susceptibility of isolates of Mycobacterium tuberculosis in the search for novel antimycobacterial agents. Natural products constitute an important source of new drugs, and design and implementation of antimycobacterial susceptibility testing methods are necessary to evaluate the different extracts and compounds. In this study we have explored the antimycobacterial properties of 50 ethanolic extracts from different parts of 46 selected medicinal plants traditionally used in Sudan to treat infectious diseases. Materials and methods: Plants were harvested and ethanolic extracts were prepared. For selected extracts, fractionation with hydrophilic and hydrophobic solvents was undertaken. A luminometry-based assay was used for determination of mycobacterial growth in broth cultures and inside primary human macrophages in the presence or absence of plant extracts and fractions of extracts. Cytotoxicity was also assessed for active fractions of plant extracts. Results: Of the tested extracts, three exhibited a significant inhibitory effect on an avirulent strain of Mycobacterium tubercluosis (H37Ra) at the initial screening doses (125 and 6.25 mu g/ml). These were bark and leaf extracts of Khaya senegalensis and the leaf extract of Rosmarinus officinalis L. Further fractions of these plant extracts were prepared with n-hexane, chloroform, ethyl acetate, n-butanol, ethanol and water, and the activity of these extracts was retained in hydrophobic fractions. Cytotoxicity assays revealed that the chloroform fraction of Khaya senegalensis bark was non-toxic to human monocyte-derived macrophages and other cell types at the concentrations used and hence, further analysis, including assessment of IC50 and intracellular activity was done with this fraction. Conclusion: These results encourage further investigations to identify the active compound(s) within the chloroform fraction of Khaya senegalensis bark. (C) 2014 Elsevier Ireland Ltd. All rights reserved.

  • 149.
    Abu-Zidan, Fikri M.
    Linköpings universitet, Institutionen för biomedicin och kirurgi, Kirurgi. Linköpings universitet, Hälsouniversitetet.
    Role of platelet-activating factor in sepsis and shock: an experimantal study1995Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Objectives: To study the role of platelet-activating factor (PAF) on cardiovascular and pulmonary dysfunction in sepsis and shock.

    Design: Experimental study. Setting: Trauma research unit, university department of surgery, Sweden.

    Material: 76 juvenile domestic pigs. Interventions: The effects of a specific PAF receptor antagonist (BB-882) on haemodynamics and on PAF-induced haemodynamic changes were studied (n = 16). BB-882 was given as pretreatment in non-hypotensive Escherichia coli endotoxaemia (n = 9), during resuscitation after severe haemorrhagic shock (n = 7), hefore post-ischaemic shock which was induced by clamping the aorta above the coliac axis for 45 minutes (n = 8), and as pretreatment in post-haemorrhage septic shock: (n = 6). BB~882 groups were compared with controi groups having the same number of animals which received vehicle instead.

    Major outcome measures: Heart rate, intravascular pressures, cardiac output, pulmonary and systemic vascular resistance, arteriai blood gas tensions, lung thorax compliance, serum lactic acid and blood sugar concentrations, and packed cell volume.

    Results: BB-882 effectively counleracted the PAF-induced response on the mean systemic and pulmonary arteriai pressures. lt reduced the rise in pulmonary and systemic vascular resistance and improved the cardiac output in non-hypotensive and post-haemorrhage septic shock when given as pretreatment. lt reduced the hypertension in non-hypotensive sepsis and the hypotension in post-haemorrhage septic shock. BB-8B2 did not infiuence the endotoxin-induced hypoxia or reduced lung thorax compliance in non-hypotensive sepsis and post-haemorrhage septic shock. It did not improve the mean arterial pressure or the cardiac output in haemorrhagic shock alone but it reduced the systemic vascular resistanc'e and was associated with tachycardia and acidosis. It did not affect the post-ischaemic shock after clamping the aorta.

    Conclusion: PAF is a major mediator of the cardiovascular, but not pulmonary dysfunction in sepsis whether associated with shock or not, while its role on the cardiovascular dysfunction in haemorrhagic and post-ischaemic shock is small.

  • 150. Abu-Zidan, FM
    et al.
    Siosteen, AK
    Wang, Jianpu
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi.
    Al-Ayoubi, Fawzi
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi.
    Lennquist, Sten
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Östergötlands Läns Landsting, Katastrofmedicinskt centrum.
    Establishment of a teaching animal model for sonographic diagnosis of trauma2004Inngår i: Journal of Trauma, ISSN 0022-5282, E-ISSN 1529-8809, Vol. 56, nr 1, s. 99-104Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Ultrasound is widely accepted as a valuable diagnostic tool for detecting intra-abdominal and intrathoracic bleeding in trauma patients. Nevertheless, many doctors are reluctant to use it because they do not have sufficient training. This study aimed to define intraabdominal and intrathoracic fluid volumes that can be detected by sonography and their relation to fluid width in pigs to establish a clinically relevant animal model for teaching and training. Methods: Different volumes of normal saline were infused into the abdomen (50-2,000 mL) and chest (25-250 mL) in five anesthetized pigs. The maximum width of fluid as detected by ultrasound was recorded. The right upper quadrant, left upper quadrant, pelvis, and right paracolic section of the abdomen and right pleural cavity were studied. An experienced radiologist performed the studies. The effects on respiratory and cardiovascular functions were evaluated. Results: The sonographic findings in the pig were similar to those in humans. Up to 50 mL of intra-abdominal fluid and up to 25 mL of intrathoracic fluid could be detected by ultrasound. There was a significant correlation between the volume infused and the fluid width detected. The respiratory and cardiovascular monitoring of the animals showed that the infused intrathoracic volumes mimicked a survivable hemothorax. Conclusion: The pig may serve as an excellent clinically relevant model with which to teach surgeons detection of different volumes of intra-abdominal and intrathoracic fluids. The value of this model as an educational tool has yet to be tested.

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