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| 2. |
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| 3. |
- Badylak, S, et al.
(författare)
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Resorbable Bioscaffold for Esophageal Repair in a Dog Model
- 2000
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Ingår i: Journal of Pediatric Surgery. - : Elsevier BV. - 0022-3468 .- 1531-5037. ; 35:7, s. 1097-1103
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Porcine-derived, xenogeneic extracellular matrix (ECM) derived from either the small intestinal submucosa (SIS) or urinary bladder submucosa (UBS) was used as a tissue scaffold for esophageal repair in a dog model. Methods: Patch defects measuring approximately 5 cm in length and encompassing 40% to 50% of the circumference of the esophagus or complete circumferential segmental defects measuring 5 cm in length were created by surgical resection in healthy adult female dogs. The defects were repaired with ECM scaffolds derived from either SIS or UBS. The animals were kept alive for periods ranging from 4 days to 15 months. Results: The xenogeneic scaffolds used for repair of the patch defects were resorbed completely within 30 to 60 days and showed replacement by skeletal muscle, which was oriented appropriately and contiguous with adjacent normal esophageal skeletal muscle, organized collagenous connective tissue, and a complete and intact squamous epithelium. No signs of clinical esophageal dysfunction were seen in any of the animals with the patch defect repair. The xenogeneic scaffolds configured into tubes for repair of the segmental defects all showed stricture within 45 days of surgery. Conclusion: These ECMs show promise as a treatment option for esophageal repair, but stricture remains problematic for complete tube grafts.
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| 4. |
- Donoso, Felipe, et al.
(författare)
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Outcome and management in infants with esophageal atresia : a single centre observational study
- 2016
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Ingår i: Journal of Pediatric Surgery. - : Elsevier BV. - 0022-3468 .- 1531-5037. ; 51:9, s. 1421-1425
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Tidskriftsartikel (refereegranskat)abstract
- Background/Purpose: A successful outcome in the repair of esophageal atresia (EA) is associated with a high quality pediatric surgical centre, however there are several controversies regarding the optimal management. The aim of this study was to investigate the outcome and management EA in a single pediatric surgical centre.Methods: Medical records of infants with repaired EA from 1994 to 2013 were reviewed.Results: 129 infants were included. Median follow-up was 5.3 (range 0.1-21) years. Overall survival was 94.6%, incidences of anastomotic leakage 7.0%, recurrent fistula 4.6% and anastomotic stricture 53.5% (36.2% within first year). In long gap EA (n = 13), delayed primary anastomosis was performed in 9 (69.2%), gastric tube in 3 (23.1%) and gastric transposition in one (7.7%) infants. The incidences of anastomotic leakage and stricture in long gap EA were, 23.1% and 69.2%, respectively. Peroperative tracheobronchoscopy and postoperative esophagography were implemented as a routine during the study-period, but chest drains were routinely abandoned.Conclusion: The outcome in this study is fully comparable with recent international reports showing a low mortality but a significant morbidity, especially considering anastomotic strictures and LGEA. Multicenter EA registry with long-term follow up may help to establish best management of EA.
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| 5. |
- Duraj, F, et al.
(författare)
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Tarmtransplantation
- 1998
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Ingår i: Läkartidningen. ; 28, s. 3172-
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 6. |
- Duraj, Frans, et al.
(författare)
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Tarmtransplantation : Första svenska tunntarmstransplantationen till en vuxen patient med pseudoobstruktion
- 1998
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Ingår i: Läkartidningen. - 0023-7205 .- 1652-7518. ; 95:28-29, s. 3172-3176
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Tidskriftsartikel (refereegranskat)abstract
- Recent advances, first and foremost the development of new immunosuppressive agents, have markedly improved the outcome of intestinal transplantation, which is a treatment option for patients with serious intestinal diseases who have become dependent on total parenteral nutrition. The first small bowel transplantation in Sweden was performed at Huddinge Hospital in 1997, in the adult patient with intestinal pseudo-obstruction. The article reports the course of this patient and an update of international progress in intestinal transplantation.
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| 7. |
- Gustafson, Elisabet, et al.
(författare)
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Control of IBMIR Induced by Fresh and Cryopreserved Hepatocytes by Low Molecular Weight Dextran Sulfate Versus Heparin
- 2017
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Ingår i: Cell Transplantation. - : Sage Publications. - 0963-6897 .- 1555-3892. ; 26:1, s. 71-81
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Tidskriftsartikel (refereegranskat)abstract
- Rapid destruction of hepatocytes after hepatocyte transplantation has hampered the application of this procedure clinically. The instant blood-mediated inflammatory reaction (IBMIR) is a plausible underlying cause for this cell loss. The present study was designed to evaluate the capacity of low molecular weight dextran sulfate (LMW-DS) to control these initial reactions from the innate immune system. Fresh and cryopreserved hepatocytes were tested in an in vitro whole-blood model using ABO-compatible blood. The ability to elicit IBMIR and the capacity of LMW-DS (100 mu g/ml) to attenuate the degree of activation of the cascade systems were monitored. The effect was also compared to conventional anticoagulant therapy using unfractionated heparin (1 IU/ml). Both fresh and freeze thawed hepatocytes elicited IBMIR to the same extent. LMW-DS reduced the platelet loss and maintained the cell counts at the same degree as unfractionated heparin, but controlled the coagulation and complement systems significantly more efficiently than heparin. LMW-DS also attenuated the IBMIR elicited by freeze thawed cells. Therefore, LMW-DS inhibits the cascade systems and maintains the cell counts in blood triggered by both fresh and cryopreserved hepatocytes in direct contact with ABO-matched blood. LMW-DS at a previously used and clinically applicable concentration (100 mu g/ml) inhibits IBMIR in vitro and is therefore a potential IBMIR inhibitor in hepatocyte transplantation.
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| 8. |
- Gustafson, Elisabet K., et al.
(författare)
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The Instant Blood-Mediated Inflammatory Reaction Characterized in Hepatocyte Transplantation
- 2011
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Ingår i: Transplantation. - 0041-1337 .- 1534-6080. ; 91:6, s. 632-638
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Tidskriftsartikel (refereegranskat)abstract
- Background. Hepatocyte transplantation (HcTx) has proven to be a safe procedure, although the functional results have been unsatisfactory, probably due to insufficient engraftment or a loss of transplanted mass or function. In this study, we investigate whether hepatocytes in contact with blood induce an inflammatory reaction leading to, similar to what happens in clinical islet transplantation, an instant blood-mediated inflammatory reaction (IBMIR) resulting in an early loss of transplanted cells. Methods. By using an experimental model that mimics the portal vein blood flow, we could study different parameters reflecting the effects on the innate immunity elicited by hepatocytes in contact with ABO-matched human blood. Results. We report that all aspects of the IBMIR such as platelet and granulocyte consumption, coagulation, and complement activation were demonstrated. Addition of various specific inhibitors of coagulation allowed us to clearly delineate the various stages of the hepatocyte-triggered IBMIR and show that the reaction was triggered by tissue factor. Analysis of a case of clinical HcTx showed that hepatocyte-induced IBMIR also occurs in vivo. Both the inflammatory and the coagulation aspects were controlled by low-molecular-weight dextran sulfate. Conclusion. Isolated hepatocytes in contact with blood induce the IBMIR in vitro, and there are indications that these events are also relevant in vivo. According to these findings, HcTx would benefit from controlling a wider range of signals from the innate immune system.
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| 9. |
- Gustafson, Elisabet
(författare)
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Thromboinflammation : in a Model of Hepatocyte Transplantation
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Hepatocyte transplantation is an attractive method for the treatment of metabolic liver disease and acute liver failure. The clinical application of this method has been hampered by a large initial loss of transplanted cells.This thesis has identified and characterized an instant blood-mediated inflammatory reaction (IBMIR), which is a thromboinflammatory response from the innate immunity that may partly explain the observed loss of cells. In vitro perifusion experiments were performed and established that hepatocytes in contact with blood activate the complement and coagulation systems and induce clot formation in conjunction with the recruitment of neutrophils. Within an hour, the hepatocytes were surrounded by platelets and entrapped in a clot infiltrated by neutrophils. Furthermore, hepatocytes expressed tissue factor (TF), and the reactions were shown to be initiated through the TF pathway. Monitoring of hepatocyte transplantation in vivo revealed activation of the same parameters as were noted in vitro.For the first time, von Willebrand factor (vWF) was identified on the hepatocyte surface, being demonstrated by flow cytometry and confocal microscopy. mRNA for vWF was also confirmed in hepatocytes. Complex formation between platelets and hepatocytes was also identified. Addition of antibodies targeting the binding site for vWF on the platelets reduced the complex formation.Two different strategies, systemic and local intervention, were applied to diminish the thromboinflammation elicited from the hepatocytes in contact with ABO-matched blood. Systemic inhibition with LMW-DS, in a clinically applicable dose, was found to be superior in controlling the IBMIR in vitro when compared to heparin. Cryopreserved hepatocytes elicited the IBMIR to the same extent as did fresh hepatocytes, and the IBMIR was equally well controlled with LMW-DS in both cryopreserved and fresh cells.Hepatocytes were coated with two layers of immobilized heparin in an attempt to protect the cells from the IBMIR. In vitro perifusion experiments showed heparinized hepatocytes triggered a significantly lower degree of IBMIR.
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| 10. |
- Hammarqvist, Folke, et al.
(författare)
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Age-related changes of muscle and plasma amino acids in healthy children
- 2010
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Ingår i: Amino Acids. - : Springer Science and Business Media LLC. - 0939-4451 .- 1438-2199. ; 39:2, s. 359-366
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the study was to explore if changes in muscle and plasma amino acid concentrations developed during growth and differed from levels seen in adults. The gradient and concentrations of free amino acids in muscle and plasma were investigated in relation to age in metabolic healthy children. Plasma and specimens from the abdominal muscle were obtained during elective surgery. The children were grouped into three groups (group 1: < 1 year, n = 8; group 2: 1-4 years, n = 13 and group 3: 5-15 years, n = 15). A reference group of healthy adults (21-38 years, n = 22) was included in their comparisons and reflected specific differences between children and adults. In muscle the concentrations of 8 out of 19 amino acids analysed increased with age, namely taurine, aspartate, threonine, alanine, valine, isoleucine, leucine, histidine, as well as the total sums of branched chain amino acids (BCAA), basic amino acids (BAA) and total sum of amino acids (P < 0.05). In plasma the concentrations of threonine, glutamine, valine, cysteine, methionine, leucine, lysine, tryptophane, arginine, BCAA, BAA and the essential amino acids correlated with age (P < 0.05). These results indicate that there is an age dependency of the amino acid pattern in skeletal muscle and plasma during growth.
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| 11. |
- Herlenius, Gustaf, et al.
(författare)
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Tarmtransplantation : experimentell terapi som blivit realistiskt alternativ
- 2004
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Ingår i: Läkartidningen. - 0023-7205 .- 1652-7518. ; 101:38, s. 2874-2878
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Tidskriftsartikel (refereegranskat)abstract
- Outcome after intestinal transplantation has improved dramatically since the introduction of novel immunosuppressive agents and refined surgical techniques. Small bowel transplantation is now considered to be the best treatment modality for patients with life threatening complications of intestinal failure and parenteral nutrition. We hereby review the international experience as well as the first ten cases of intestinal transplantation performed in Sweden.
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| 12. |
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| 13. |
- Högberg, Niclas, 1979-, et al.
(författare)
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Intestinal ischemia measured by intraluminal microdialysis
- 2012
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Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - : Informa UK Limited. - 0036-5513 .- 1502-7686. ; 72:1, s. 59-66
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To evaluate the possibility of detecting intestinal ischemia by intraluminal microdialysis and comparing the ileum and colon. Methods. The studies were performed on male Sprague-Dawley rats. In the fi rst part of the study, microdialysis catheters were placed in the sigmoid part of the colon and in the subcutaneous adipose tissue. In the second part of the study, microdialysis catheters were placed in the lumen of the ileum and the colon. The infrarenal aorta was clamped proximal to the cranial mesenteric artery. Microdialysate levels of glucose, lactate, pyruvate and glycerol were measured. Intestinal specimens were removed at the end of the ischemic period for microscopic evaluation. Results. Intraluminal microdialysis could detect early signs of ischemic injury in the ileum, as well as in the colon, with a marked increase of lactate, lactate/pyruvate ratio and glycerol. The increased levels of intraluminal glycerol showed a positive correlation to prolonged ischemia and to higher degrees of intestinal damage. Conclusion. Intraluminal measurement of glycerol is a good marker for intestinal ischemia. Intraluminal microdialysis in the colon is easily accessible through the rectum, and ay prove to be a valuable clinical tool for diagnosing intestinal ischemia.
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| 14. |
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| 15. |
- Lilja, Helene, et al.
(författare)
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Fetal rat hepatocytes : Isolation, characterization and transplantation in the Nagase analbuminernic rats
- 1997
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Ingår i: Transplantation. - 0041-1337 .- 1534-6080. ; 64:9, s. 1240-1248
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Tidskriftsartikel (refereegranskat)abstract
- Background. In contrast to adult hepatocytes, fetal hepatocytes (FH) are thought to be highly proliferative, less immunogenic, and resistant to cryopreservation and ischemic injury. These qualities could enhance FH engraftment, proliferation, and gene transfer requiring active DNA synthesis, Methods. Rat FH were obtained using the nonperfusion collagenase/DNase digestion method, Free and cultured cells were studied using electron microscopy, fluorescence-activated cell sorting, and Northern analysis using alpha-fetoprotein and albumin as markers of hepatocyte lineage, DNA synthetic activity was measured in quiescent and mitogen-stimulated fetal and adult hepatocytes by [H-3]thymidine incorporation, Susceptibility of cultured FH to retrovirally mediated gene transfer was studied using an amphotropic retroviral vector carrying the Escherichia coli lac-Z gene, Nagase analbuminemic rats were used as recipients to study the effects of intraportal FH transplantation, Analysis of serum albumin was carried out by enzyme-linked immunosorbent assay. Results, In fetal liver, 87+/-2%? of the cells showed morphological and molecular features of hepatocytes. DNA synthetic activity in nonstimulated cultured FH was 10 times greater than the maximal hepatocyte growth factor-driven response in adult rat hepatocytes., A total of 5-15% FH stained positive for X-gal; results of transduction in adult hepatocyte cultures were negative. In Nagase analbuminemic rat recipients, FH produced significant amounts of albumin only when a hepatic regenerative stimulus was applied. Immunohistochemistry confirmed presence of albumin-positive hepatocytes, Conclusions, Fetal rat liver from the late gestation period is highly enriched with hepatocyte progenitors, They are highly proliferative and susceptible to retroviral transduction and can engraft and function in the adult rat liver if transplanted under a hepatic regenerative stimulus.
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| 16. |
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| 17. |
- Meurling, Staffan, et al.
(författare)
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Short bowel syndrome
- 2000
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Ingår i: Journal of the Japanese Society of Pediatric Surgeons. - 0288-609X. ; 36:1, s. 77-80
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Tidskriftsartikel (refereegranskat)abstract
- Children with SBS have a high morbidity and mortality rate despite improvements in both enteral and parenteral nutrition. Improved medical treatment must sometimes be combined with surgical procedures including intestinal lengthening and transplantation, thereby improving the status of these children.
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| 18. |
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| 19. |
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| 20. |
- Stenbäck, Anders, 1971-
(författare)
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Studies of Experimental Bacterial Translocation
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- One of the main obstacles to maintaining patients with short bowel syndrome on parenteral nutrition, or successfully transplanting these patients with a small bowel graft, is the many severe infections that occur. Evidence is accumulating that translocating bacteria from the patient’s bowel causes a significant part of these infections. In this thesis bacterial translocation is studied in a Thiry-Vella loop of defunctionalised small bowel in the rat. Bacterial translocation to the mesenteric lymph nodes (MLNs) occurs in almost 100% of the rats after three days. No systemic spread of bacteria is observed unless there is additional immunosupression with depletion of Kupffer cells in the liver. However, blocking the function of α/β T cells does not increase the translocation. Removal of MLNs does not either aggravate bacterial translocation in the Thiry-Vella loop model. Conversely, after small bowel transplantation translocating bacteria spread systemically if the MLNs are removed. The Thiry-Vella loop should also be a suitable model for the testing of potentially translocation-inhibiting substances. Reinforcement of the intestinal barrier with glutamine or phosphatidylcholine proved insufficient in decreasing bacterial translocation. Even selective bowel decontamination with tobramycin failed to abolish bacterial translocation. Thus, it seems that the driving force for translocation in this model is strong regardless of the relatively small trauma of intestinal defunctionalisation. Flow cytometric studies of the immune cells in the spleen MLNs showed a decrease in MHC class II positive T cells in the MLNs of the Thiry-Vella loop. Concurrently the number of macrophages increased with time as observed by immunohistochemistry. The fraction of MHC class II negative macrophages increased in the spleens of rats treated with glutamine. In conclusion, the Thiry-Vella loop model offers possibilities of immunological as well as mechanistic studies on bacterial translocation from small intestine.
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| 21. |
- Stenbäck, Anders, et al.
(författare)
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T-cell inhibition does not aggravate bacterial translocation from rat small bowel
- 2006
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Ingår i: Transplant Immunology. - : Elsevier BV. - 0966-3274 .- 1878-5492. ; 16:3-4, s. 208-214
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Tidskriftsartikel (refereegranskat)abstract
- Background: T-cell mediated immunity has been proposed to have an important function in the defence against translocating microbes from the gastrointestinal tract. After small bowel transplantation massive T-cell immunosuppression is necessary to avoid rejection. As a consequence, infections with intestinal bacteria are the main contributors to mortality in this setting. This could further imply that T cells are important in limiting bacterial translocation. In a model for bacterial translocation from small bowel in the rat we examined the outcome of T-cell inactivation. Methods: The studies were performed in a model of bacterial translocation from a Thiry-Vella loop of small bowel in the rat. The animals were treated with an anti-α/β T-cell receptor monoclonal antibody (R73). Inhibition of T-cell activation was also made using the immunosuppressive drug cyclosporin A. All animals were sacrificed on day 3 postoperatively and translocation to the mesenteric lymph nodes, liver, spleen, lung and blood was evaluated. Results: Treatment with R73 resulted in an almost complete labelling of T cells but did not result in any increased bacterial translocation compared to animals treated with saline. Neither did immunosuppression with cyclosporin A. Conclusions: In the model of bacterial translocation from a defunctionalised loop of small bowel the inhibition of T cells does not increase bacterial translocation to mesenteric lymph nodes or promote the systemic spread of the translocating bacteria. This indicates that T cells do not have any important protective function against translocating microbes from defunctionalised small bowel.
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| 24. |
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| 25. |
- Wallander, J, et al.
(författare)
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Tunntarmstransplantation
- 1995
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Ingår i: Läkartidningen. ; 92, s. 1099-
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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