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- Arvidsson, Alf, et al.
(författare)
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För Sverige i tiden?
- 2009
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Ingår i: Kulturella perspektiv - Svensk etnologisk tidskrift. - Umeå. - 1102-7908. ; 18:2, s. 2-8
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Tidskriftsartikel (refereegranskat)
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- Cabric, Sanja, et al.
(författare)
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Islet Surface Heparinization Prevents the Instant-Blood Mediated Inflammatory Reaction in Islet Transplantation
- 2007
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 56:8, s. 2008-2015
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE—In clinical islet transplantation, the instant blood-mediated inflammatory reaction (IBMIR) is a major factor contributing to the poor initial engraftment of the islets. This reaction is triggered by tissue factor and monocyte chemoattractant protein (MCP)-1, expressed by the transplanted pancreatic islets when the islets come in contact with blood in the portal vein. All currently identified systemic inhibitors of the IBMIR are associated with a significantly increased risk of bleeding or other side effects. To avoid systemic treatment, the aim of the present study was to render the islet graft blood biocompatible by applying a continuous heparin coating to the islet surface.RESEARCH DESIGN AND METHODS—A biotin/avidin technique was used to conjugate preformed heparin complexes to the surface of pancreatic islets. This endothelial-like coating was achieved by conjugating barely 40 IU heparin per full-size clinical islet transplant.RESULTS—Both in an in vitro loop model and in an allogeneic porcine model of clinical islet transplantation, this heparin coating provided protection against the IBMIR. Culturing heparinized islets for 24 h did not affect insulin release after glucose challenge, and heparin-coated islets cured diabetic mice in a manner similar to untreated islets.CONCLUSIONS—This novel pretreatment procedure prevents intraportal thrombosis and efficiently inhibits the IBMIR without increasing the bleeding risk and, unlike other pretreatment procedures (e.g., gene therapy), without inducing acute or chronic toxicity in the islets.
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- Eich, Torsten, et al.
(författare)
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Positron emission tomography : A real-time tool to quantify early islet engraftment in a preclinical large animal model
- 2007
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Ingår i: Transplantation. - : Ovid Technologies (Wolters Kluwer Health). - 0041-1337 .- 1534-6080. ; 84:7, s. 893-898
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Tidskriftsartikel (refereegranskat)abstract
- Background. Clinical islet transplantation is currently being explored as a therapeutic option for persons with type I diabetes and hypoglycemic unawareness. Techniques to monitor graft survival are urgently needed to optimize the procedure. Therefore, the objective of the present study was to develop a technique for imaging survival of transplanted islets in the peritransplant and early posttransplant phase.Methods. Isolated porcine islets were labeled in vitro with 2-deoxy-2[18F]fluoro-D-glucose ([18F]FDG) and infused intraportally into anesthetized pigs (n=10). Dynamic examination was performed on a positron emission tomography/computed tomography hybrid system.Results. More than 95% of the radioactivity was confined to the islets at the time of transplantation. The peak percentage of infused radioactivity within the liver, quantified at the end of the islet infusion, was only 54±5.1%. The distribution of the radioactivity in the liver was found to be heterogeneous. A whole-body examination showed no accumulation in the lungs or brain; extrahepatic radioactivity was, except urinary excretion, evenly distributed in the pig body.Conclusions. Our results imply that almost 50% of the islets were damaged to the extent that the FDG contained was release within minutes after intraportal transplantation. The distribution of radioactivity without accumulation in the brain indicates that the activity is released from lysed islet cells in the form of [18F]FDG-6P rather than native [18F]FDG. The presented technique shows promise to become a powerful and quantitative tool, readily available in the clinic, to evaluate initial islet engraftment and survival.
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- Ericzon, Bo-Göran, et al.
(författare)
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Liver Transplantation for Transthyretin Amyloidosis
- 2009
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Ingår i: Recent Advances in Transthyretin Evolution, Structure and Biological Functions. - New York : Springer Berlin/Heidelberg. - 9783642006456 - 9783642006463 ; , s. 239-260
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Liver transplantation has until now proved to be the only treatment available that halts the progression of hereditary transthyretin (TTR) associated amyloidosis. The rationale behind the procedure is to replace the liver producing variant TTR with one that produces wild type TTR only, and thereby cease the production of amyloidogenic TTR (ATTR). Even though the transplantation does not improve the patient's symptoms, the progression of the disease comes to a halt for a majority of patients. However, unforeseen complications after the transplantation have emerged, in particular a continuous amyloid formation in the heart observed in non-ATTR Val30Met mutations. Thus, combined liver and heart transplantation has been performed in selected cases. Since the ATTR liver functions normally apart from a synthesis of the variant TTR, utilisation of ATTR-amyloid patients' livers for transplantation of liver disease patients has been performed. In a few patients, development of amyloid disease has been reported, but the procedure remains an important source of organs, especially for patients with hepatocellular cancer.
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- Eriksson, Olof, et al.
(författare)
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Positron emission tomography in clinical islet transplantation
- 2009
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Ingår i: American Journal of Transplantation. - : Elsevier BV. - 1600-6135 .- 1600-6143. ; 9:12, s. 2816-2824
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Tidskriftsartikel (refereegranskat)abstract
- The fate of islets in clinical transplantation is unclear. To elude on this positron emission tomography combined with computed tomography (PET/CT) was performed for 60 min during islet transplantation in five patients receiving six transplants. A fraction of the islets (23%) were labeled with 18F-fluorodeoxyglucose ([(18)F]FDG) and carefully mixed with unlabeled islets just prior to intraportal transplantation. The peak radioactivity concentration in the liver was found at 19 min after start of islet infusion and corresponded to only 75% of what was expected, indicating that islets are lost during the transplantation procedure. No accumulation of radioactivity was found in the lungs. A nonphysiological peak of C-peptide was found in plasma during and immediately after transplantation in all subjects. Distribution in the liver was heterogeneous with wide variations in location and concentration. Islets found in areas with concentrations of >400 IEQ/cc liver tissue varied between 1% and 32% of the graft in different subjects. No side effects attributed to the PET/CT procedure were found. Clinical outcome in all patients was comparable to that previously observed indicating that the [(18)F]FDG labeling procedure did not harm the islets. The technique has potential to be used to assess approaches to enhance islet survival and engraftment in clinical transplantation.
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- Johansson, Helena, et al.
(författare)
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Tissue factor produced by the endocrine cells of the islets of Langerhans is associated with a negative outcome of clinical islet transplantation
- 2005
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 54:6, s. 1755-62
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Tidskriftsartikel (refereegranskat)abstract
- There are strong indications that only a small fraction of grafts successfully engraft in clinical islet transplantation. One explanation may be the instant blood-mediated inflammatory reaction (IBMIR) elicited by tissue factor, which is produced by the endocrine cells. In the present study, we show that islets intended for islet transplantation produce tissue factor in both the transmembrane and the alternatively spliced form and that the membrane-bound form is released as microparticles often associated with both insulin and glucagon granules. A low-molecular mass factor VIIa (FVIIa) inhibitor that indirectly blocks both forms of tissue factor was shown in vitro to be a promising drug to eliminate the IBMIR. Thrombin-antithrombin complex (TAT) and FVIIa-antithrombin complex (FVIIa-AT) were measured in nine patients who together received 20 infusions of isolated human islets. Both the TAT and FVIIa-AT complexes increased rapidly within 15-60 min after infusion. When the initial TAT and FVIIa-AT levels were plotted against the increase in C-peptide concentration after 7 days, patients with an initially strong IBMIR showed no significant increase in insulin synthesis after 7 days. In conclusion, tissue factor present in both the islets and the culture medium and elicits IBMIR, which affects the function of the transplanted islets.
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- Korsgren, Olle, et al.
(författare)
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Optimising islet engraftment is critical for successful clinical islet transplantation
- 2008
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 51:2, s. 227-32
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Tidskriftsartikel (refereegranskat)abstract
- Clinical islet transplantation is currently being explored as a treatment for persons with type 1 diabetes and hypoglycaemia unawareness. Although 'proof-of-principle' has been established in recent clinical studies, the procedure suffers from low efficacy. At the time of transplantation, the isolated islets are allowed to embolise the liver after injection in the portal vein, a procedure that is unique in the area of transplantation. A novel view on the engraftment of intraportally transplanted islets is presented that could explain the low efficacy of the procedure.
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- Lannering, Birgitta, 1948, et al.
(författare)
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Classification, incidence and survival analyses of children with CNS tumours diagnosed in Sweden 1984-2005.
- 2009
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Ingår i: Acta paediatrica (Oslo, Norway : 1992). - : Wiley. - 1651-2227 .- 0803-5253. ; 98:10, s. 1620-7
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Tidskriftsartikel (refereegranskat)abstract
- AIM: Primary tumours in the central nervous system (CNS) are the second most common malignancy in childhood after leukaemia. Sweden has a high incidence and a high-survival rate in international comparative studies. This has raised the question about the type of tumours included in the Swedish Cancer registry. We therefore compared international data to the Swedish Childhood Cancer registry. METHODS: Central nervous system tumours registered in the Swedish Childhood Cancer Registry were reclassified according to ICCC-3. Incidence and survival analyses were performed in the study population. RESULTS: There were 1479 children (<15 years) in Sweden diagnosed with CNS tumours 1984-2005. The distribution of diagnoses was similar to that reported in other studies. The annual incidence was 4.2/100,000 children. The survival rates have not improved significantly between the two time periods before/after 1995 (70% vs. 74%; p = 0.10). CONCLUSIONS: The mean annual incidence of children with CNS tumours was 4.2/100,000 and has not increased during the study period. Survival rate for brain tumours at 10 years follow-up was 72%.
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