| 1. |
- Högberg, Niclas, 1979-, et al.
(författare)
-
Intestinal intraluminal glycerol and plasma I-FABP levels in preterm infants with necrotizing enterocolitis
- 2016
-
Ingår i: Clinics in Surgery. ; 1:1085, s. 1-6
-
Tidskriftsartikel (refereegranskat)abstract
- Background/Purpose: Necrotizing enterocolitis (NEC) is highly associated with prematurity and is characterized by bowel necrosis and multi-organ failure. There is a strong need for improved diagnostic methods to reduce the significant morbidity and mortality associated with NEC. The aim of this single centre prospective study was to investigate the possibility to detect early signs of NEC, by using rectal intraluminal microdialysis and plasma intestinal fatty acid binding protein (I-FABP) in preterm infants admitted to a level III neonatal intensive care unit.Methods: The study was performed on extremely preterm infants with a gestational age of less than 28 weeks. During a 4-week period after birth, rectal intraluminal microdialysate levels of glucose, lactate, pyruvate and glycerol were measured, and plasma was collected for I-FABP analysis. Infants not developing NEC served as controls. Results: Microdialysis revealed signs of intestinal hypoxic or ischemic damage and cell membrane degradation, with a marked increase of both intraluminal glycerol and plasma I-FABP in infants developing NEC, as well as in infants suffering from other complications. The microdialysate levels of glucose, lactate and pyruvate were too low to be evaluated in this setting. All infants tolerated the microdialysis well without any complications.Conclusion: Elevated levels of intraluminal glycerol and plasma I-FABP suggests mucosal cell membrane degradation and hypoxic or ischemic damage in preterm infants developing NEC, as well as in preterm infants suffering from other complications such as volvulus, sepsis or respiratory distress. However, it was not possible to predict development of NEC before clinical diagnosis using these markers.
|
|
| 2. |
- Högberg, Niclas, 1979-, et al.
(författare)
-
Genes regulating tight junctions and cell adhesion are altered in early experimental necrotizing enterocolitis
- 2013
-
Ingår i: Journal of Pediatric Surgery. - : Elsevier BV. - 0022-3468 .- 1531-5037. ; 48:11, s. 2308-2312
-
Tidskriftsartikel (refereegranskat)abstract
- Background/purpose:Necrotizing enterocolitis (NEC) represents one of the gravest complications in preterm infants and carries significant morbidity and mortality. Increased intestinal permeability may play an important role in the pathogenesis of NEC. In this study we investigated the genes regulating structural proteins such as tight junctions (TJ) and cell adhesion in a neonatal rat model of early NEC, as well as the expression of TJ proteins by immunohistochemistry staining.Methods:The studies were performed on Sprague-Dawley rat pups. Experimental NEC was induced using hypoxia/reoxygenation treatment on day 1 after birth. Intestinal specimens from the ileum were obtained, mRNA was purified and the transcriptome was analyzed using microarray. Immunohistochemistry staining was performed for TJ proteins.Results:We found several TJ genes such as claudins 1, 8, 14, 15 and gap junction protein to be affected. Immunohistochemistry staining for TJ protein claudin-1 revealed decreased levels in experimental NEC compared to controls. Alterations in genes involved in the inflammatory response was confirmed, along with several genes regulating proteins used as biomarkers for NEC.Conclusion:This study indicates that tight junctions and cell adhesion may play a critical role in the pathogenesis of early experimental NEC. Better understanding of the pathogenesis of NEC may lead to novel strategies for the prevention and treatment of NEC.
|
|
| 3. |
- Högberg, Niclas, 1979-, et al.
(författare)
-
Intestinal ischemia measured by intraluminal microdialysis
- 2012
-
Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - : Informa UK Limited. - 0036-5513 .- 1502-7686. ; 72:1, s. 59-66
-
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.
|
|
| 4. |
- Högberg, Niclas, 1979-, et al.
(författare)
-
Intraluminal intestinal microdialysis detects markers of hypoxia and cell damage in experimental necrotizing enterocolitis
- 2012
-
Ingår i: Journal of Pediatric Surgery. - : Elsevier BV. - 0022-3468 .- 1531-5037. ; 47:9, s. 1646-1651
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND/PURPOSE:Necrotizing enterocolitis (NEC) represents one of the gravest complications in premature infants and carries significant morbidity and mortality. There is a great need for improved diagnostic methods to reduce the severity and incidence of NEC. The aim of the study was to investigate if intraluminal microdialysis can detect intestinal ischemia in newborn rats with induced experimental NEC.METHODS:The studies were performed on 1-day-old Sprague-Dawley rat pups. Experimental NEC was induced using hypoxia/reoxygenation treatment. Microdialysis catheters were rectally inserted and placed in the rectosigmoid part of the colon. Microdialysate levels of glucose, lactate, pyruvate, and glycerol were measured. Intestinal specimens were collected at the end of the experiments for microscopic evaluation.RESULTS:Intraluminal microdialysis revealed signs of intestinal hypoxia and cellular damage, with a marked increase of lactate and glycerol. Microscopic evaluation confirmed intestinal damage in the NEC group.CONCLUSION:Intraluminal microdialysis can detect intestinal hypoxic stress and mucosal cell membrane decay in a rat model of NEC. Intestinal intraluminal microdialysis is easily accessible through the rectum and may be a useful noninvasive complement to other methods in the assessment of NEC.
|
|
| 5. |
|
|
| 6. |
- Stenbäck, Anders, et al.
(författare)
-
Proprietary non-animal stabilized hyaluronic acid/dextranomer gel (NASHA/Dx) for endoscopic treatment of grade IV vesicoureteral reflux : Longterm observational study
- 2020
-
Ingår i: Journal of Pediatric Urology. - : ELSEVIER SCI LTD. - 1477-5131 .- 1873-4898. ; 16:3
-
Tidskriftsartikel (refereegranskat)abstract
- Background Since 1993, children aged >1 year with persistent grade III-V vesicoureteral reflux (VUR) and febrile urinary tract infections (UTIs) attending Uppsala University Hospital have undergone endoscopic injection with proprietary non-animal stabilized hyaluronic acid/dextranomer gel (NASHA/Dx; Deflux (R)). Objective Investigate long-term incidence of UTI, bladder dysfunction, ureteral reimplantation and overall clinical findings following endoscopic injection of NASHA/Dx. Study design Children with grade IV VUR diagnosed by voiding cystourethrogram (VCUG) and dilating VUR persisting for >1 year were included in this study. 15-25 years after endoscopic treatment, patients' hospital charts were studied. Information on bladder function and UTIs was obtained via questionnaire, 8-18 years after endoscopic treatment. Results 185 patients (69 boys, 116 girls) were included in the study; 237 grade IV VUR ureters were treated. All study patients were diagnosed with VUR after a febrile UTI (i.e. pyelonephritis). According to the last voiding cystourethrogram, 69% of ureters showed a positive response (VUR grade 0-I), 7% had VUR grade II and 23% had VUR grade >= III. 46 patients (25%) required ureteral reimplantation during follow-up. Among patients treated during the second 5-year period compared with the first (1998-2003 versus 1993-1998), there was a significant decrease in the rate of ureteral reimplantation (31% vs 16%; p = 0.0365). This difference may be attributable to developments over time in the injection technique. UTIs occurred in 30 patients (21% of the evaluable population): 28 females and 2 males. Febrile UTIs were reported in 14 patients (10%), all females. Forty-nine patients (34%) had bladder problems (e.g. underactivity, overactivity, incontinence). Five patients underwent ureteral reimplantation 'late', 6-10 years after the last endoscopic injection. In one male patient, calcification around the NASHA/Dx implantation site was observed during routine examination 2 years after endoscopic treatment; no intervention was required. No safety issues were observed in the remaining 97% of the study population. Conclusions This study represents the longest published followu-p of Grade IV VUR patients undergoing endoscopic treatment. Three-quarters of patients did not need ureteral reimplantation. Optimal injection technique and higher injection volume were associated with a reduced ureteral reimplantation rate. Treatment with NASHA/Dx was durable and well tolerated: long-term risks of UTI, bladder dysfunction and recurrent VUR were low. [GRAPHICS] .
|
|
| 7. |
- Stenbäck, Anders, et al.
(författare)
-
Retentio Testis
- 2015
-
Ingår i: Grottes barnkirurgi och barnurologi. - Lund : Studentlitteratur AB. - 9789144071510 ; , s. 241-246
-
Bokkapitel (övrigt vetenskapligt/konstnärligt)
|
|
| 8. |
- Stenbäck, Anders, 1971-
(författare)
-
Studies of Experimental Bacterial Translocation
- 2005
-
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.
|
|
| 9. |
- Stenbäck, Anders, et al.
(författare)
-
T-cell inhibition does not aggravate bacterial translocation from rat small bowel
- 2006
-
Ingår i: Transplant Immunology. - : Elsevier BV. - 0966-3274 .- 1878-5492. ; 16:3-4, s. 208-214
-
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.
|
|
| 10. |
|
|
