Runar Almaas

• Størdal, Ketil; Almaas, Runar; Sanner, Helga; Sletner, Line & Stene, Lars Christian Mørch (2026). Incidence and co-occurrence of six autoimmune diseases in childhood: a population-based cohort study in Norway. The Lancet Child and Adolescent Health. ISSN 2352-4642. 10(6), s. 429–437. doi: 10.1016/S2352-4642(26)00008-8. Fulltekst i vitenarkiv
• Hukkinen, Maria; Fischler, Björn; Liliemark, Ulrika; Gatzinsky, Vladimir; Ekvall, Nils & Almaas, Runar [Vis alle 14 forfattere av denne artikkelen] (2025). Multicenter Study on Early Predictors of Biliary Atresia Outcomes. Journal of Pediatric Surgery. ISSN 0022-3468. 60(9). doi: 10.1016/j.jpedsurg.2025.162404. Fulltekst i vitenarkiv Vis sammendrag

  Objectives To compare liver biochemistry, aspartate aminotransferase-to-platelet ratio index (APRI) and patient characteristics for prediction of biliary atresia (BA) outcomes at time of portoenterostomy. Methods This was a retrospective observational study. Seven tertiary centers participated. Predictors of clearance of jaundice (COJ, bilirubin <20 μmol/L 6 months after portoenterostomy) and native liver survival (NLS, recorded at transplantation, death, or latest follow-up with NL) were analyzed with logistic regression and Cox regression. Cytomegalovirus (CMV) DNA detection in serum/urine or IgM antibodies were defined as CMV-associated BA. Results Out of 630 patients, 58 % achieved COJ. CMV-positive patients were older at portoenterostomy (74 vs 52 days, p < 0.001) whereas BA splenic malformation (BASM) patients were younger (median 47 vs 56 days, p = 0.001) and had equal COJ rates (56 %) compared to others. Absence of cirrhosis (p = 0.001) and CMV infection (p = 0.001), age <60 days at portoenterostomy (p < 0.001), and lower AST (p = 0.007–0.037) and APRI (p = 0.016) predicted COJ. While these variables also predicted NLS, in multivariable regression only COJ (hazard ratio, HR 15, p < 0.001), BASM (HR 1.9, p < 0.001), and portoenterostomy age >60 days (HR 1.3, p = 0.044) remained significant predictors of transplantation/death. Among COJ patients, only BASM predicted transplantation/death (HR 2.4, p = 0.002). Conclusions APRI is not superior to AST in the prediction of BA outcomes. However, in COJ patients, both are unrelated to NLS. Despite younger age at portoenterostomy and similar COJ rates compared to isolated BA, BASM strongly predicts shorter NLS. COJ is possible in CMV positive patients who, after achieving COJ, have similar NLS compared to other patients.

• Østensen, Inger Anniken Bjørnstad; Jensen, Unn; Skarbø, Anne-Britt; Line, Pål Dag & Almaas, Runar (2025). Lasting reduced motor function affecting quality of life after liver transplantation in children and adolescents. Journal of Pediatric Gastroenterology and Nutrition - JPGN. ISSN 0277-2116. 81(4), s. 943–951. doi: 10.1002/jpn3.70183. Fulltekst i vitenarkiv
• Jørgensen, Marianne Hørby; Almaas, Runar; Kharrazi, Gandom; Urbonas, Vaidotas; Kvistgaard, Helene & Wollen, Embjørg Julianne [Vis alle 9 forfattere av denne artikkelen] (2025). Various Regimens for Autoimmune Hepatitis in Northern European Children Show Equivalent Outcomes at 1 Year: A Retrospective Study. Journal of Pediatrics. ISSN 0022-3476. 284, s. 1–8. doi: 10.1016/j.jpeds.2025.114635. Fulltekst i vitenarkiv
• Roman, Giacomo; Lauritzen, Knut Husø; Harrison, Sean Philip; Bhattacharya, Anindita; Andresen, Marianne Seierstad & Mowinckel, Marie-Christine [Vis alle 16 forfattere av denne artikkelen] (2025). Ex vivo correction of severe coagulation Factor VII deficiency in patient-derived 3D liver organoids. Haematologica. ISSN 0390-6078. doi: 10.3324/haematol.2025.288046. Fulltekst i vitenarkiv Vis sammendrag

  Coagulation factor (F) VII deficiency is the most frequent among the rare, inherited bleeding disorders and is predominantly caused by missense mutations in the F7 gene. The disease phenotype ranges from asymptomatic cases to extremely severe hemorrhagic forms, requiring prophylactic injections with plasma-derived or recombinant FVII concentrates. In response, we have developed an autologous cell-based approach that corrects the disease-causing mutation in patient-derived induced pluripotent stem cells (iPSCs) and generates therapeutic, three-dimensional hepatic organoids (HOs). We report the CRISPRmediated correction of homozygous c.718G>C (p.G240R), a missense mutation associated with a severe, life-threatening bleeding phenotype. The HOs contain all liver cell types and exhibit key liver functions, including coagulation factor production. After correction, our data indicate that the patient-derived HOs secrete consistent amounts of functional FVII protein, resulting in improved thrombin generation times. These results represent a significant milestone toward the establishment of an autologous cell-based therapy for patients with FVII- and other coagulation factor deficiencies.

• Ziegler, Anders; Sæves, Ingjerd & Almaas, Runar (2024). Differences in bile acid profiles between cholestatic diseases – Development of a high throughput assay for dried bloodspots. Clinica Chimica Acta. ISSN 0009-8981. 562. doi: 10.1016/j.cca.2024.119864. Fulltekst i vitenarkiv
• Westerberg, Niklas Starck; Atneosen-Åsegg, Monica; Melheim, Maria; Dugarte, Maria Eugenia Chollet; Harrison, Sean Philip & Siller, Richard [Vis alle 8 forfattere av denne artikkelen] (2024). Effect of hypoxia on aquaporins and hepatobiliary transport systems in human hepatic cells. Pediatric Research. ISSN 0031-3998. doi: 10.1038/s41390-024-03368-0. Fulltekst i vitenarkiv
• Harrison, Sean Philip; Baumgarten, Saphira Felicitas; Dugarte, Maria Eugenia Chollet; Stavik, Benedicte; Bhattacharya, Anindita & Almaas, Runar [Vis alle 7 forfattere av denne artikkelen] (2024). Parenteral nutrition emulsion inhibits CYP3A4 in an iPSC derived liver organoids testing platform. Journal of Pediatric Gastroenterology and Nutrition - JPGN. ISSN 0277-2116. 78, s. 1047–1058. doi: 10.1002/jpn3.12195. Fulltekst i vitenarkiv Vis sammendrag

  Objectives Parenteral nutrition (PN) is used for patients of varying ages with intestinal failure to supplement calories. Premature newborns with low birth weight are at a high risk for developing PN associated liver disease (PNALD) including steatosis, cholestasis, and gallbladder sludge/stones. To optimize nutrition regimens, models are required to predict PNALD. Methods We have exploited induced pluripotent stem cell derived liver organoids to provide a testing platform for PNALD. Liver organoids mimic the developing liver and contain the different hepatic cell types. The organoids have an early postnatal maturity making them a suitable model for premature newborns. To mimic PN treatment we used medium supplemented with either clinoleic (80% olive oil/20% soybean oil) or intralipid (100% soybean oil) for 7 days. Results Homogenous HNF4a staining was found in all organoids and PN treatments caused accumulation of lipids in hepatocytes. Organoids exhibited a dose dependent decrease in CYP3A4 activity and expression of hepatocyte functional genes. The lipid emulsions did not affect overall organoid viability and glucose levels had no contributory effect to the observed results. Conclusions Liver organoids could be utilized as a potential screening platform for the development of new, less hepatotoxic PN solutions. Both lipid treatments caused hepatic lipid accumulation, a significant decrease in CYP3A4 activity and a decrease in the RNA levels of both CYP3A4 and CYP1A2 in a dose dependent manner. The presence of high glucose had no additive effect, while Clinoleic at high dose, caused significant upregulation of interleukin 6 and TLR4 expression.

• Rieneck, Klaus; Rasmussen, Karen Koefoed; Schoof, Erwin M.; Clausen, Frederik Banch; Holze, Henrietta & Bergholt, Thomas [Vis alle 17 forfattere av denne artikkelen] (2023). Hunting for the elusive target antigen in gestational alloimmune liver disease (GALD). PLOS ONE. 18(10), s. 1–25. doi: 10.1371/journal.pone.0286432. Fulltekst i vitenarkiv Vis sammendrag

  The prevailing concept is that gestational alloimmune liver disease (GALD) is caused by maternal antibodies targeting a currently unknown antigen on the liver of the fetus. This leads to deposition of complement on the fetal hepatocytes and death of the fetal hepatocytes and extensive liver injury. In many cases, the newborn dies. In subsequent pregnancies early treatment of the woman with intravenous immunoglobulin can be instituted, and the prognosis for the fetus will be excellent. Without treatment the prognosis can be severe. Crucial improvements of diagnosis require identification of the target antigen. For this identification, this work was based on two hypotheses: 1. The GALD antigen is exclusively expressed in the fetal liver during normal fetal life in all pregnancies; 2. The GALD antigen is an alloantigen expressed in the fetal liver with the woman being homozygous for the minor allele and the father being, most frequently, homozygous for the major allele. We used three different experimental approaches to identify the liver target antigen of maternal antibodies from women who had given birth to a baby with the clinical GALD diagnosis: 1. Immunoprecipitation of antigens from either a human liver cell line or human fetal livers by immunoprecipitation with maternal antibodies followed by mass spectrometry analysis of captured antigens; 2. Construction of a cDNA expression library from human fetal liver mRNA and screening about 1.3 million recombinants in Escherichia coli using antibodies from mothers of babies diagnosed with GALD; 3. Exome/genome sequencing of DNA from 26 presumably unrelated women who had previously given birth to a child with GALD with husband controls and supplementary HLA typing. In conclusion, using the three experimental approaches we did not identify the GALD target antigen and the exome/genome sequencing results did not support the hypothesis that the GALD antigen is an alloantigen, but the results do not yield basis for excluding that the antigen is exclusively expressed during fetal life., which is the hypothesis we favor.

• Almaas, Runar; Atneosen-Åsegg, Monica; Ytre-Arne, Mari Eknes; Melheim, Maria; Sorte, Hanne Sørmo & Cízková, Dana [Vis alle 16 forfattere av denne artikkelen] (2023). Aagenaes syndrome/lymphedema cholestasis syndrome 1 is caused by a founder variant in the 5’-untranslated region of UNC45A. Journal of Hepatology. ISSN 0168-8278. 79(4), s. 945–954. doi: 10.1016/j.jhep.2023.05.037. Fulltekst i vitenarkiv Vis sammendrag

  Background & Aims Lymphedema cholestasis syndrome 1 or Aagenaes syndrome is a condition characterized by neonatal cholestasis, lymphedema, and giant cell hepatitis. The genetic background of this autosomal recessive disease was unknown up to now. Methods A total of 26 patients with Aagenaes syndrome and 17 parents were investigated with whole-genome sequencing and/or Sanger sequencing. PCR and western blot analyses were used to assess levels of mRNA and protein, respectively. CRISPR/Cas9 was used to generate the variant in HEK293T cells. Light microscopy, transmission electron microscopy and immunohistochemistry for biliary transport proteins were performed in liver biopsies. Results One specific variant (c.-98G>T) in the 5’-untranslated region of Unc-45 myosin chaperone A (UNC45A) was identified in all tested patients with Aagenaes syndrome. Nineteen were homozygous for the c.-98G>T variant and seven were compound heterozygous for the variant in the 5’-untranslated region and an exonic loss-of-function variant in UNC45A. Patients with Aagenaes syndrome exhibited lower expression of UNC45A mRNA and protein than controls, and this was reproduced in a CRISPR/Cas9-created cell model. Liver biopsies from the neonatal period demonstrated cholestasis, paucity of bile ducts and pronounced formation of multinucleated giant cells. Immunohistochemistry revealed mislocalization of the hepatobiliary transport proteins BSEP (bile salt export pump) and MRP2 (multidrug resistance-associated protein 2). Conclusions c.-98G>T in the 5’-untranslated region of UNC45A is the causative genetic variant in Aagenaes syndrome. Impact and implications The genetic background of Aagenaes syndrome, a disease presenting with cholestasis and lymphedema in childhood, was unknown until now. A variant in the 5’-untranslated region of the Unc-45 myosin chaperone A (UNC45A) was identified in all tested patients with Aagenaes syndrome, providing evidence of the genetic background of the disease. Identification of the genetic background provides a tool for diagnosis of patients with Aagenaes syndrome before lymphedema is evident.

• Harrison, Sean Philip; Siller, Richard; Tanaka, Yoshiaki; Dugarte, Maria Eugenia Chollet; Morena-Barrio, María Eugenia de la & Xiang, Yangfei [Vis alle 36 forfattere av denne artikkelen] (2023). Scalable production of tissue-like vascularized liver organoids from human PSCs. Experimental and Molecular Medicine. ISSN 1226-3613. 55, s. 2005–2024. doi: 10.1038/s12276-023-01074-1. Fulltekst i vitenarkiv Vis sammendrag

  Abstract The lack of physiological parity between 2D cell culture and in vivo culture has led to the development of more organotypic models, such as organoids. Organoid models have been developed for a number of tissues, including the liver. Current organoid protocols are characterized by a reliance on extracellular matrices (ECMs), patterning in 2D culture, costly growth factors and a lack of cellular diversity, structure, and organization. Current hepatic organoid models are generally simplistic and composed of hepatocytes or cholangiocytes, rendering them less physiologically relevant compared to native tissue. We have developed an approach that does not require 2D patterning, is ECM independent, and employs small molecules to mimic embryonic liver development that produces large quantities of liver-like organoids. Using single-cell RNA sequencing and immunofluorescence, we demonstrate a liver-like cellular repertoire, a higher order cellular complexity, presenting with vascular luminal structures, and a population of resident macrophages: Kupffer cells. The organoids exhibit key liver functions, including drug metabolism, serum protein production, urea synthesis and coagulation factor production, with preserved post-translational modifications such as N-glycosylation and functionality. The organoids can be transplanted and maintained long term in mice producing human albumin. The organoids exhibit a complex cellular repertoire reflective of the organ and have de novo vascularization and liver-like function. These characteristics are a prerequisite for many applications from cellular therapy, tissue engineering, drug toxicity assessment, and disease modeling to basic developmental biology.

• Lin, Xiaolin; Wang, Wei; Yang, Mingyi; Damseh, Nadirah; Sousa, Mirta & Jacob, Fadi [Vis alle 29 forfattere av denne artikkelen] (2023). A loss-of-function mutation in human Oxidation Resistance 1 disrupts the spatial–temporal regulation of histone arginine methylation in neurodevelopment. Genome Biology. ISSN 1465-6906. 24(1). doi: 10.1186/s13059-023-03037-1. Fulltekst i vitenarkiv Vis sammendrag

  Background Oxidation Resistance 1 (OXR1) gene is a highly conserved gene of the TLDc domain-containing family. OXR1 is involved in fundamental biological and cellular processes, including DNA damage response, antioxidant pathways, cell cycle, neuronal protection, and arginine methylation. In 2019, five patients from three families carrying four biallelic loss-of-function variants in OXR1 were reported to be associated with cerebellar atrophy. However, the impact of OXR1 on cellular functions and molecular mechanisms in the human brain is largely unknown. Notably, no human disease models are available to explore the pathological impact of OXR1 deficiency. Results We report a novel loss-of-function mutation in the TLDc domain of the human OXR1 gene, resulting in early-onset epilepsy, developmental delay, cognitive disabilities, and cerebellar atrophy. Patient lymphoblasts show impaired cell survival, proliferation, and hypersensitivity to oxidative stress. These phenotypes are rescued by TLDc domain replacement. We generate patient-derived induced pluripotent stem cells (iPSCs) revealing impaired neural differentiation along with dysregulation of genes essential for neurodevelopment. We identify that OXR1 influences histone arginine methylation by activating protein arginine methyltransferases (PRMTs), suggesting OXR1-dependent mechanisms regulating gene expression during neurodevelopment. We model the function of OXR1 in early human brain development using patient-derived brain organoids revealing that OXR1 contributes to the spatial–temporal regulation of histone arginine methylation in specific brain regions. Conclusions This study provides new insights into pathological features and molecular underpinnings associated with OXR1 deficiency in patients.

• Østensen, Inger Anniken Bjørnstad; Skarbø, Anne-Britt; Sanengen, Truls; Line, Pål Dag & Almaas, Runar (2022). Impaired Neurocognitive Performance in Children After Liver Transplantation. Journal of Pediatrics. ISSN 0022-3476. doi: 10.1016/j.jpeds.2021.12.033. Fulltekst i vitenarkiv Vis sammendrag

  Objectives To assess longitudinal neurocognitive development after liver transplantation and evaluate factors associated with neurocognitive performance. Study design Data from neurocognitive testing of 65 children (aged <18 years) who underwent liver transplantation at Oslo University Hospital between 1995 and 2018 were collected from the testing program after transplantation. The parent-reported version of the Behavior Rating Inventory of Executive Function was used to assess executive function. Results A total of 104 neurocognitive tests were conducted on 65 patients. At the first test, conducted at a median of 4.1 years (IQR, 1.5-5.3 years) after transplantation and at a median age of 6.7 years (IQR, 5.4-10.5 years), the mean full-scale IQ (FSIQ) was 91.7 ± 14, and the mean verbal comprehension index was 92.0 ± 14.5. In the 30 patients tested more than once, there was no significant difference in FSIQ between the first test at a median age of 5.8 years (IQR, 5.2-8.5 years) and the last test at a median age of 10.8 years (IQR, 9.8-12.9 years) (87.4 ± 12.9 vs 88.5 ± 13.2; P = .58). Compared with the patients who underwent transplantation a age >1 year (n = 35), those who did so at age <1 year (n = 30) had a lower FSIQ (87.1 ± 12.6 vs 96.6 ± 13.8; P = .005) and lower verbal comprehension index (87.3 ± 13.8 vs 95.4 ± 13.0; P = .020). Age at transplantation (P = .005; adjusted for cholestasis: P = .038) and transfusion of >80 mL/kg (P = .004; adjusted for age at transplantation: P = .046) were associated with FSIQ. Conclusions Young age at transplantation and large blood transfusions during transplantation are risk factors for poor neurocognitive performance later in life. Children who undergo transplantation before 1 year of age have significantly lower neurocognitive performance compared with those who do so later in childhood. Cognitive performance did not improve over time after transplantation.

• Haflidadottir, Svanhildur; Østensen, Inger Anniken Bjørnstad; Matthews, Iren; Line, Pål Dag & Almaas, Runar (2022). Mycophenolate mofetil use is associated with reduced incidence of food allergy in liver transplanted children. Journal of Pediatric Gastroenterology and Nutrition - JPGN. ISSN 0277-2116. 75(2), s. 138–144. doi: 10.1097/MPG.0000000000003509. Fulltekst i vitenarkiv
• Almaas, Runar & Saugstad, Ola Didrik (2021). 50 Years Ago in THE JOURNAL OF PEDIATRICS: Pregnancy in Women with Galactosemia. Journal of Pediatrics. ISSN 0022-3476. 233, s. 118–118. doi: 10.1016/j.jpeds.2021.02.032. Fulltekst i vitenarkiv
• Thrane, Karl Julius; Müller, Lil-Sofie Ording; Suther, Lene Kathrine R; Thomassen, Kristian Stien; Holmstrøm, Henrik & Thaulow, Erik [Vis alle 9 forfattere av denne artikkelen] (2021). Spectrum of Fontan‑associated liver disease assessed by MRI and US in young adolescents. Abdominal Radiology. ISSN 2366-004X. 46, s. 3205–3216. doi: 10.1007/s00261-021-02994-0. Fulltekst i vitenarkiv Vis sammendrag

  Abstract Purpose Patients with Fontan circulation are at risk of developing hepatic fibrosis/cirrhosis. The mechanisms and disease development are unclear and early secondary liver cancer is a concern. This study will describe hepatic imaging findings in a national cohort of adolescents with Fontan circulation. Methods The patients prospectively underwent abdominal contrast enhanced magnetic resonance imaging (MRI) including diffusion-weighted imaging. Images were assessed for criteria of fibrosis / cirrhosis including characterization of hepatic nodules. These nodules were in addition, assessed by ultrasonography (US). Nodules ≥ 1 cm were investigated and monitored to evaluate malignant transformation. Clinical and hepatic serological data were recorded. Results Forty-six patients, median age of 16.5 years (15.4–17.9 years) were enrolled. All patients underwent US examination and MRI was performed in 35/46 patients. On MRI, 60% had hepatomegaly and 37% had signs of fibrosis/cirrhosis. Seven patients had together 13 nodules ≥ 1 cm in diameter. Only 4/13 (17%) where seen on US. Nodules had variable MRI signal characteristics including hepatobiliary contrast enhancement and two nodules revealed portal venous phase ‘wash-out’ on the first examination. No further imaging signs of malignancy were revealed during the follow-up period of median 24.4 (7–42) months. Conclusion The majority of adolescents with Fontan circulation had imaging findings of fibrosis/cirrhosis of varying severity. US had low detection rate of hepatic nodules compared to MRI. The imaging work-up before transition to adult cardiology care did not reveal findings suggestive of malignancy. However, the high prevalence of Fontan-associated liver disease calls for surveillance strategies even in childhood.

• Harrison, Sean; Siller, Richard; Tanaka, Yoshiaki; Xiang, Yangfei; Patterson, Benjamin & Kempf, Henning [Vis alle 29 forfattere av denne artikkelen] (2020). Scalable production of tissue-like vascularised liver organoids from human PSCs. BioRxiv. ISSN 0362-4331. doi: 10.1101/2020.12.02.406835. Fulltekst i vitenarkiv
• Atneosen-Åsegg, Monica; Melheim, Maria & Almaas, Runar (2020). MicroRNA in dried blood spots from patients with Aagenaes syndrome and evaluation of pre-analytical and analytical factors. Pediatric Research. ISSN 0031-3998. doi: 10.1038/s41390-020-01153-3. Fulltekst i vitenarkiv
• Lange, Charlotte de; Thrane, Karl Julius; Thomassen, Kristian Stien; Geier, Oliver; Nguyen, Bac & Tomterstad, Anders [Vis alle 12 forfattere av denne artikkelen] (2020). Hepatic magnetic resonance T1-mapping and extracellular volume fraction compared to shear-wave elastography in pediatric Fontan-associated liver disease. Pediatric Radiology. ISSN 0301-0449. 51, s. 66–76. doi: 10.1007/s00247-020-04805-y. Fulltekst i vitenarkiv Vis sammendrag

  Abstract Background Children with Fontan circulation are at risk of developing hepatic fibrosis/cirrhosis. Reliable noninvasive monitoring techniques are lacking or under development. Objective To investigate surrogate indicators of hepatic fibrosis in adolescents with Fontan circulation by evaluating hepatic magnetic resonance (MR) T1 mapping and extracellular volume fraction measurements compared to US shear-wave elastography. Materials and methods We analyzed hepatic native T1 times and extracellular volume fractions with modified Look-Locker inversion recovery. Liver stiffness was analyzed with shear-wave elastography. We compared results between 45 pediatric patients ages 16.7±0.6 years with Fontan circulation and 15 healthy controls ages 19.2±1.2 years. Measurements were correlated to clinical and hemodynamic data from cardiac catheterization. Results MR mapping was successful in 35/45 patients, revealing higher hepatic T1 times (774±44 ms) than in controls (632±52 ms; P &lt;0.001) and higher extracellular volume fractions (47.4±5.0%) than in controls (34.6±3.8%; P &lt;0.001). Liver stiffness was 1.91±0.13 m/s in patients vs. 1.20±0.10 m/s in controls ( P &lt;0.001). Native T1 times correlated with central venous pressures (r=0.5, P =0.007). Native T1 was not correlated with elastography in patients (r=0.2, P =0.1) or controls (r = −0.3, P =0.3). Extracellular volume fraction was correlated with elastography in patients (r=0.5, P =0.005) but not in controls (r=0.2, P =0.6). Conclusion Increased hepatic MR relaxometry and shear-wave elastography values in adolescents with Fontan circulation suggested the presence of hepatic fibrosis or congestion. Central venous pressure was related to T1 times. Changes were detected differently with MR relaxometry and elastography; thus, these techniques should not be used interchangeably in monitoring hepatic fibrosis.

• Bjørnland, Kristin; Hukkinen, Maria; Gatzinsky, Vladimir; Arnell, Henrik; Pakarinen, Mikko & Almaas, Runar [Vis alle 7 forfattere av denne artikkelen] (2020). Partial Biliary Diversion May Promote Long-Term Relief of Pruritus and Native Liver Survival in Children with Cholestatic Liver Diseases. European journal of pediatric surgery. ISSN 0939-7248. s. 1–6. doi: 10.1055/s-0040-1714657. Fulltekst i vitenarkiv Vis sammendrag

  Abstract Introduction Rare cholestatic liver diseases may cause debilitating pruritus in children. Partial biliary diversion (PBD) may relieve pruritus and postpone liver transplantation which is the only other alternative when conservative treatment fails. The aim was to report long-term outcome after PBD in a population of 26 million people during a 25-year period. Materials and Methods This is an international, multicenter retrospective study reviewing medical journals. Complications were graded according to the Clavien–Dindo classification system. Results Thirty-three patients, 14 males, underwent PBD at a median of 1.5 (0.3–13) years at four Nordic pediatric surgical centers. Progressive familial intrahepatic cholestasis was the most common underlying condition. Initially, all patients got external diversion, either cholecystojejunostomy (25 patients) or button placed in the gallbladder or a jejunal conduit. Early complications occurred in 14 (42%) patients, of which 3 were Clavien–Dindo grade 3. Long-term stoma-related complications were common (55%). Twenty secondary surgeries were performed due to stoma problems such as prolapse, stricture, and bleeding, or conversion to another form of PBD. Thirteen children have undergone liver transplantation, and two are listed for transplantation due to inefficient effect of PBD on pruritus. Serum levels of bile acids in the first week after PBD construction were significantly lower in patients with good relief of pruritus than in those with poor effect (13 [2–192] vs. 148 [5–383] μmol/L; p = 0.02). Conclusion PBD may ensure long-term satisfactory effect on intolerable pruritus and native liver survival in children with cholestatic liver disease. However, stoma-related problems and reoperations are common.

• Thorsteinsdottir, Hjørdis; Salvador, Cathrin Lytomt; Mjøen, Geir; Lie, Anine; Sugulle, Meryam & Tøndel, Camilla [Vis alle 9 forfattere av denne artikkelen] (2020). Growth Differentiation Factor 15 in Children with Chronic Kidney Disease and after Renal Transplantation. Disease Markers. ISSN 0278-0240. 2020:6162892, s. 1–8. doi: 10.1155/2020/6162892. Fulltekst i vitenarkiv Vis sammendrag

  Growth differentiation factor 15 (GDF-15) is strongly associated with cardiovascular disease (CVD). The aim of our study was to evaluate plasma and urinary levels of GDF-15 after pediatric renal transplantation (Rtx) and in children with chronic kidney disease (CKD) and its associations to cardiovascular risk factors. In this cross-sectional study, GDF-15 was measured in plasma and urine from 53 children with a renal transplant and 83 children with CKD and related to cardiovascular risk factors (hypertension, obesity, and cholesterol) and kidney function. Forty healthy children served as a control group. Plasma levels of GDF-15 (median and range) for a Tx (transplantation) cohort, CKD cohort, and healthy controls were, respectively, 865 ng/L (463-3039 ng/L), 508 ng/L (183-3279 ng/L), and 390 ng/L (306-657 ng/L). The CKD and Tx cohorts both had significantly higher GDF-15 levels than the control group (p < 0:001). Univariate associations between GDF-15 and hyperuricemia (p < 0:001), elevated triglycerides (p = 0:028), low HDL (p = 0:038), and obesity (p = 0:028) were found. However, mGFR (p < 0:001) and hemoglobin (p < 0:001) were the only significant predictors of GDF-15 in an adjusted analysis. Urinary GDF15/creatinine ratios were 448 ng/mmol (74–5013 ng/mmol) and 540 ng/mmol (5–14960 ng/mmol) in the Tx cohort and CKD cohort, respectively. In the CKD cohort, it was weakly correlated to mGFR (r = −0:343, p = 0:002). Plasma levels of GDF-15 are elevated in children with CKD and after Rtx. The levels were not associated with traditional cardiovascular risk factors but strongly associated with renal function.

• Haflidadottir, Svanhildur; Matthews, Iren & Almaas, Runar (2020). Cytokine profile in children with food allergy following liver transplantation. Pediatric Transplantation. ISSN 1397-3142. 24(2), s. 1–8. doi: 10.1111/petr.13657. Fulltekst i vitenarkiv Vis sammendrag

  Background LTX in children is associated with increased risk of food allergy, and the mechanisms underlying this are unknown. We wanted to study whether plasma cytokine profile differed in liver transplanted children, with and without food allergy, and whether it differed from untransplanted children with CLD. Methods Plasma cytokines, total and specific IgE in nine patients with food allergy were compared with 13 patients without food allergy following LTX, and also with seven untransplanted patients with CLD. Results No difference was found in the cytokine profile between liver transplanted patients with and without food allergy. Transplanted patients with food allergy having received a prescription of epinephrine had a significantly higher total IgE (2033 [234‐2831] vs 10 [5‐41] IU/L, P = .002) and MIP‐1b (52 [37‐96] vs 36 [32‐39], P = .035) compared with transplanted patients without food allergy. Two patients with severe food allergy responded favorably to conversion from tacrolimus‐based immunosuppression to MMF and corticosteroids with reduction in clinical symptoms, total IgE, specific IgE, IL‐1ra, IL‐4, RANTES, PDGF, MIP‐1a, and TNFα. The transplantation group had higher levels of IL‐1b, IL‐5, IL‐7, IL‐13, GCSF, IFNγ, and MIP‐1a compared with the CLD group. Conclusions No overall difference was found in plasma cytokine profile between patients with and without food allergy. Patients with severe food allergy had significant elevation of MIP‐1b. Discontinuation of tacrolimus reduced total and specific IgE and changed plasma cytokine profile. The plasma cytokine profile in liver transplanted children was different compared with children with CLD.

• Åsberg, Anders; Bjerre, Anna Kristina; Almaas, Runar; Luis-Lima, Sergio; Robertsen, Ida & Salvador, Cathrin Lytomt [Vis alle 10 forfattere av denne artikkelen] (2019). Measured GFR by Utilizing Population Pharmacokinetic Methods to Determine Iohexol Clearance. Kidney International Reports. 5(2), s. 189–198. doi: 10.1016/j.ekir.2019.11.012. Fulltekst i vitenarkiv Vis sammendrag

  Introduction There is an increasing demand for accurately measured glomerular filtration rate (GFR). Iohexol serum clearance has become a new gold standard, but it is challenging when GFR is low and 24-hour sampling is required for accurate results. The primary aim of this study was to develop an iohexol pharmacokinetic population model for accurate determination of individual GFR using limited sampling for up to 5 hours also when renal function is <40 ml/min. Methods A nonparametric iohexol population pharmacokinetic model was developed with rich data from 176 patients. In a validation cohort of 43 patients, a model-determined GFR (iohexol clearance) using different limited sampling strategies for up to 5 hours was compared with the strategy currently used in routine care, a log-linear 2-point method. In all, 1526 iohexol concentrations were used, from patients ranging in age from 1 to 82 years and GFR from 14 to 149 ml/min. Results The clinical 2-point method showed insufficient agreement compared with reference values; 15% of GFR values had an error of greater than ±10% even when sampling for 24 hours when estimating GFR <40 ml/min per 1.73 m2 (standard procedure). Restricted sampling the first 5 hours with the population model required 4 samples to determine GFR accurately. This strategy showed excellent agreement with the reference; <3% of GFR values had an error greater than ±10 %. Conclusion Using an iohexol population pharmacokinetic model allows for accurate determination of GFR within 5 hours when applying 4 optimally timed samples, even in patients with GFR <40 ml/min.

• Diab, Simone; Godang, Kristin; Müller, Lil-Sofie Ording; Almaas, Runar; Lange, Charlotte de & Brunvand, Leif [Vis alle 12 forfattere av denne artikkelen] (2019). Progressive loss of bone mass in children with Fontan circulation. Congenital Heart Disease. ISSN 1747-079X. s. 1–9. doi: 10.1111/chd.12848. Fulltekst i vitenarkiv
• Bjørnland, Kristin; Hinna, Maren Tveit; Aksnes, Gunnar; Stensrud, Kjetil Juul; Ertresvåg, Kjetil & Østensen, Inger Anniken Bjørnstad [Vis alle 12 forfattere av denne artikkelen] (2018). Outcome for biliary atresia patients treated at a low-volume centre. Scandinavian Journal of Gastroenterology. ISSN 0036-5521. 53(4), s. 471–474. doi: 10.1080/00365521.2018.1439097. Fulltekst i vitenarkiv Vis sammendrag

  Objectives: The importance of case load for treatment of extrahepatic biliary atresia (BA) is debated. The aim of this study was to register results of BA treatment in a small volume centre. Methods: Retrospective chart review study of patients with BA treated from 2000 to 2017. The institutional review board approved the study. Results: 45 babies were identified of which 42 (93%) are alive. 41 patients had a Kasai portoenterostomy (PE), two a hepaticojejunostomy and two a primary liver transplantation. The age at PE/hepaticojejunostomy was median 63 (4-145 days). Seven surgeons performed the operations, and the median duration of the diagnostic work-up was 8 (3-24) days. Clearance of jaundice was achieved in 23/43 (53%) babies, and 3- and 5-year native liver survival was 47% and 40% respectively. Clearance of jaundice post PE/hepaticojejunostomy was a strong predictor of native liver survival (adjusted OR: 0.027; 95%; P=0.009). Plasma level of conjugated bilirubin at time of referral was also a significant predictor of native liver survival (adjusted OR: 1.053; P=0.017). Conclusion: A small volume centre may achieve satisfactory results for BA patients. The study has, however, identified factors that may further improve results; earlier referral, optimizing diagnostic work-up, and establishing one dedicated surgical team.

• Almaas, Runar; Haflidadottir, Svanhildur; Kaldestad, Runa Helen & Matthews, Iren (2018). Asthma, Eczema, and Food Allergy in Children Following Liver Transplantation. Journal of Pediatrics. ISSN 0022-3476. s. 1–7. doi: 10.1016/j.jpeds.2018.08.050. Fulltekst i vitenarkiv
• Pakarinen, Mikko; Johansen, Lars Søndergaard; Svensson, Jan F.; Bjørnland, Kristin; Gatzinsky, Vladimir & Stenström, Pernilla [Vis alle 16 forfattere av denne artikkelen] (2018). Outcomes of biliary atresia in the Nordic countries – a multicenter study of 158 patients during 2005–2016. Journal of Pediatric Surgery. ISSN 0022-3468. 53(8), s. 1509–1515. doi: 10.1016/j.jpedsurg.2017.08.048. Fulltekst i vitenarkiv Vis sammendrag

  Background/purpose: Biliary atresia is the most common reason for newborn cholestasis and pediatric liver transplantation. Even after normalization of serum bilirubin after portoenterostomy, most patients require liver transplantation by adulthood due to expanding fibrosis. We addressed contemporary outcomes of biliary atresia in the Nordic countries. Methods: Data on center and patients characteristics, diagnostic practices, surgical treatment, adjuvant medical therapy after portoenterostomy, follow-up and outcomes were collected from all the Nordic centers involved with biliary atresia care during 2005–2016. Results: Of the 154 patients, 148 underwent portoenterostomy mostly by assigned surgical teams at median age of 64 (interquartile range 37–79) days, and 95 patients (64%) normalized their serum bilirubin concentration while living with native liver. Postoperative adjuvant medical therapy, including steroids, ursodeoxycholic acid and antibiotics was given to 137 (93%) patients. Clearance of jaundice associated with young age at surgery and favorable anatomic type of biliary atresia, whereas annual center caseload > 3 patients and diagnostic protocol without routine liver biopsy predicted early performance of portoenterostomy. The cumulative 5-year native liver and overall survival estimate was 53% (95% CI 45–62) and 88% (95% CI 83–94), respectively. Portoenterostomy age < 65 days and annual center caseload > 3 patients were predictive for long-term native liver survival, while normalization of serum bilirubin after portoenterostomy was the major predictor of both native liver and overall 5-year survival. Conclusions: The outcomes of biliary atresia in the Nordic countries compared well with previous European studies. Further improvement should be pursued by active measures to reduce patient age at portoenterostomy.

• Østensen, Inger Anniken Bjørnstad; Sanengen, Truls; Holter, Ellen; Line, Pål Dag & Almaas, Runar (2017). No effect of treatment with intravenous ganciclovir on Epstein-Barr virus viremia demonstrated after pediatric liver transplantation. Pediatric Transplantation. ISSN 1397-3142. 21(6). doi: 10.1111/petr.13010. Fulltekst i vitenarkiv
• Mathapati, Santosh Sadashiv; Siller, Richard; Impellizzeri, Agata Antonina Rita; Lycke, Eric Maximilian; Vegheim, Karianne & Almaas, Runar [Vis alle 7 forfattere av denne artikkelen] (2016). Small-molecule-directed hepatocyte-like cell differentiation of human pluripotent stem cells. Current protocols in stem cell biology. ISSN 1941-7322. 38, s. 1G.6.1–1G.6.18. doi: 10.1002/cpsc.13. Fulltekst i vitenarkiv
• Almaas, Runar; Jensen, Unn; Loennecken, Marianne; Tveter, Anne Therese; Sanengen, Truls & Scholz, Tim [Vis alle 7 forfattere av denne artikkelen] (2015). Impaired motor competence in children with transplanted liver. Journal of Pediatric Gastroenterology and Nutrition - JPGN. ISSN 0277-2116. 60(6), s. 723–728. doi: 10.1097/MPG.0000000000000757. Fulltekst i vitenarkiv
• Stølen, Linn Helene; Lilje, Rina; Jørgensen, Jens Veilemand; Bliksrud, Yngve Thomas & Almaas, Runar (2014). High Dietary Folic Acid and High Plasma Folate in Children and Adults with Phenylketonuria. JIMD Reports. ISSN 2192-8304. 13, s. 83–90. doi: 10.1007/8904_2013_260. Fulltekst i vitenarkiv
• Westheim, Birgitte Hamre; Aagenæs, Ingegerd; Østensen, Anniken Bjørnstad; Sanengen, Truls & Almaas, Runar (2013). Effect of Operator Experience and Frequency of Procedure Performance on Complication Rate After Ultrasound-Guided Percutaneous Liver Biopsies. Journal of Pediatric Gastroenterology and Nutrition - JPGN. ISSN 0277-2116. 57(5), s. 638–643. doi: 10.1097/MPG.0b013e3182a0c7a5. Fulltekst i vitenarkiv
• Haugaa, Håkon; Almaas, Runar; Thorgersen, Ebbe Billmann; Foss, Aksel; Line, Pål Dag & Sanengen, Truls [Vis alle 13 forfattere av denne artikkelen] (2013). Clinical experience with microdialysis catheters in pediatric liver transplants. Liver transplantation. ISSN 1527-6465. 19(3), s. 305–314. doi: 10.1002/lt.23578. Fulltekst i vitenarkiv
• Haugaa, Håkon; Thorgersen, Ebbe Billmann; Pharo, Anne Margrethe; Boberg, Kirsten Muri; Foss, Aksel & Line, Pål Dag [Vis alle 12 forfattere av denne artikkelen] (2012). Early bedside detection of ischemia and rejection in liver transplants by microdialysis. Liver transplantation. ISSN 1527-6465. 18(7), s. 839–849. doi: 10.1002/lt.23425. Fulltekst i vitenarkiv
• Haugaa, Håkon; Thorgersen, Ebbe Billmann; Pharo, Anne Margrethe; Boberg, Kirsten Muri; Foss, Aksel & Line, Pål Dag [Vis alle 13 forfattere av denne artikkelen] (2012). Inflammatory markers sampled by microdialysis catheters distinguish rejection from ischemia in liver grafts. Liver transplantation. ISSN 1527-6465. 18(12), s. 1421–1429. doi: 10.1002/lt.23503. Fulltekst i vitenarkiv
• Almaas, Runar; Hankø, Erik; Mollnes, Tom Eirik & Rootwelt, Terje (2012). Dexamethasone reduces bilirubin-induced toxicity and IL-8 and MCP-1 release in human NT2-N neurons. Brain Research. ISSN 0006-8993. 1458, s. 12–17. doi: 10.1016/j.brainres.2012.04.007. Fulltekst i vitenarkiv
• Westheim, Birgitte Hamre; Østensen, Anniken Bjørnstad; Aagenæs, Ingegerd; Sanengen, Truls & Almaas, Runar (2012). Evaluation of Risk Factors for Bleeding After Liver Biopsy in Children. Journal of Pediatric Gastroenterology and Nutrition - JPGN. ISSN 0277-2116. 55(1), s. 82–87. doi: 10.1097/MPG.0b013e318249c12a. Fulltekst i vitenarkiv
• Frøyland, Elisabeth; Pedersen, Elena Didenko; Kvissel, Anne Katrine; Almaas, R; Pharo, Anne Margrethe & Skålhegg, Bjørn Steen [Vis alle 8 forfattere av denne artikkelen] (2006). Effect of acidosis on IL-8 and MCP-1 during hypoxia and reoxygenation in human NT2-N neurons. Brain Research. ISSN 0006-8993. 1113, s. 64–73. Fulltekst i vitenarkiv
• Hankø, Erik; Hansen, Thor Willy; Almaas, Runar & Rootwelt, Terje (2006). Recovery after short-term bilirubin exposure in human NT2-N neurons. Brain Research. ISSN 0006-8993. 1103(1), s. 56–64. doi: 10.1016/j.brainres.2006.05.083. Fulltekst i vitenarkiv Vis sammendrag

  We used human NT2-N neurons to investigate delayed effects of short-term exposure to unconjugated bilirubin (UCB). Cell viability was evaluated with MTT reduction assays and nuclear morphology. A 6-h exposure to 1, 5, or 25 μM UCB and serum deprivation (SED) significantly diminished MTT reduction. 96 h after rescue of neurons with removal of UCB and re-incubation in the original serum-containing medium, delayed effects were evident as recovery (1 μM UCB), intermediate cell death (5 μM UCB), or near complete cell death (25 μM UCB). The impact of 6 h of SED alone appeared to be modest in rescued neurons. In this model, co-treatment with the specific caspase-3 inhibitor, zDEVD.FMK (100 μM), or the pancaspase inhibitor zVAD.FMK (100 μM) did not improve viability in rescued neurons exposed to 5 μM UCB, while treatment with the NMDA receptor antagonist MK-801 (1 μM) enhanced the number of undamaged nuclei (86 ± 14% versus 50 ± 12%, P = 0.001). MK-801 had, however, no impact on MTT reduction. In a different model with a 102-h continuous exposure to UCB and SED, we found a significant additional toxic impact of serum deprivation. Separate experiments suggested that this was a result of late caspase-mediated toxicity. We conclude that UCB-mediated effects may be reversible in this model. Blockade of excitotoxic mechanisms, but not caspase activity may prevent delayed cell death.

• Hankø, Erik; Hansen, Thor Willy; Almaas, Runar; Paulsen, Ragnhild Elisabeth & Rootwelt, Terje (2006). Synergistic Protection of a General Caspase Inhibitor and MK-801 in Bilirubin-Induced Cell Death in Human NT2-N Neurons. Pediatric Research. ISSN 0031-3998. 59(1), s. 72–77. doi: 10.1203/01.pdr.0000191135.6358. Fulltekst i vitenarkiv Vis sammendrag

  Unconjugated bilirubin (UCB) induces both apoptosis and necrosis in neurons. To investigate the role of caspases and excitotoxicity in UCB-induced cell death, we exposed NT2-N neurons to 5 µM UCB (a concentration known to induce apoptosis) or 2 µM staurosporine (positive apoptosis control) and investigated the effects of treatments with the specific caspase-3 inhibitor, zDEVD.FMK (20 and 100 µM), or the general caspase inhibitor, zVAD.FMK (20 and 100 µM), and/or the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 (10 µM) during a 24- or 48-h exposure. UCB increased caspase-3 activity 2.3-fold after 6 h. Despite this, treatment with zDEVD.FMK did not prevent cell death. zVAD.FMK (100 µM only) reduced apoptotic morphologies induced by UCB after 48 h, however, this effect was not reflected in MTT assays. MK-801 attenuated UCB-induced cell death after 24 h, but not significantly after 48 h. Similar effects were seen in the MTT assay. Combined treatment with MK-801 and zVAD.FMK synergistically reduced apoptotic morphologies after 24 and 48 h. MTT assays showed comparable effects after 24 h but did not show significant differences after 48 h. We conclude that NMDA receptor-mediated pathways and caspase-mediated pathways are involved in UCB-induced cell death in human NT2-N neurons. Concomitant inhibition of both pathways results in synergistic protection

• Ghanima, Waleed; Almaas, Vibeke Marie; Aballi, S; Dörje, C; Nielssen, BE & Holmen, LO [Vis alle 9 forfattere av denne artikkelen] (2005). Management of suspected pulmonary embolism (PE) by D-dimer and multi-slice computed tomography in outpatients: an outcome study. Journal of Thrombosis and Haemostasis. ISSN 1538-7933. 3(9), s. 1926–1932. Fulltekst i vitenarkiv Vis sammendrag

  Objectives: A prospective outcome study designed to evaluate a simple strategy for the management of outpatients with suspected pulmonary embolism (PE), based on clinical probability, D-dimer, and multi-slice computed tomography (MSCT). Methods: A cohort of 432 consecutive patients admitted to the emergency department with suspected PE was managed by sequential non-invasive testing. Patients in whom PE was ruled out were not given anticoagulants, but were followed-up for 3 months. Results: Normal D-dimer and low-intermediate clinical probability ruled out PE in 103 patients (24% [95% CI 20-28]). 17 patients had normal D-dimer, but high clinical probability and proceeded to MSCT. All patients proved negative for PE. A total of 329 (76%) patients underwent MSCT examination. PE was diagnosed in 93 patients (21.5% [95% CI 18-26]) and was ruled out by negative MSCT in 221 patients (51% [95% CI 46-56]). MSCT scans were determined as inconclusive in 15 (4.5%) patients. No patient developed objectively verified venous thromboembolism (VTE) during the 3-month follow-up period. However, the cause of death was adjudicated as possibly related to PE in two patients, resulting in an overall 3-month VTE risk of 0.6% (95% CI 0-2.2%). The diagnostic algorithm yielded a definite diagnosis in 96.5% of the patients. Conclusions: This simple and non-invasive strategy, combining clinical probability, D-dimer, and MSCT for the management of outpatients with suspected PE appears to be safe and effective.

• Ellingsrud, Elisabeth; Wibrand, F.; Almaas, Runar; Dalen, Ingvild; Lindstad, Julie K. & Rootwelt, Terje (2005). Acidosis during reoxygenation has an early detrimental effect on neuronal metabolic activity. Pediatric Research. ISSN 0031-3998. 57(4), s. 488–493. doi: 10.1203/01.PDR.0000155946.8223. Fulltekst i vitenarkiv Vis sammendrag

  We recently showed that acidosis is protective during hypoxia and detrimental during reoxygenation. We hypothesized that the detrimental effect of acidosis during reoxygenation was due to a negative effect on mitochondrial function. Human postmitotic NT2-N neurons were exposed to 3 h of hypoxia and glucose deprivation and then reoxygenated for 0, 1, 4, 9, or 21 h. The detrimental effect of acidotic reoxygenation on metabolic activity was evident already after 1 h of reoxygenation, when MTT [3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide] reduction (percentage of normoxic controls) was significantly higher in cells reoxygenated with neutral compared with acidotic medium both after acidotic hypoxia (83 ± 26% versus 67 ± 27%, p = 0.006) and after neutral hypoxia (51 ± 12% versus 41 ± 7%, p = 0.005). Hypoxanthine, a marker of cellular energy failure, increased more with acidotic compared with neutral reoxygenation both after acidotic hypoxia (after 21 h: 7.7 ± 2.7 versus 3.1 ± 1.9 µM, p < 0.001) and after neutral hypoxia (10.4 ± 2.6 versus 7.9 ± 2.8 µM, p = 0.001). During hypoxia and reoxygenation, there was an earlier reduction in the activity of complex IV compared with complexes II+III, and the ratio between these complexes fell during the first hour of reoxygenation. The reduction in complex IV activity was alleviated with acidotic hypoxia. Acidosis during reoxygenation, however, had no effect on the activity of either complex IV or complexes II+III. We conclude that acidosis during hypoxia increases neuronal survival and preserves complex IV activity. Acidosis during reoxygenation has an early detrimental effect on metabolic activity, but this is not mediated through an effect on the mitochondrial complexes IV or II+III.

• Hankø, Erik; Hansen, Thor Willy Ruud; Hansen, R; Almaas, Runar; Lindstad, Julie K. & Rootwelt, Terje (2005). Bilirubin induces apoptosis and necrosis in human NT2-N neurons. Pediatric Research. ISSN 0031-3998. 57. Fulltekst i vitenarkiv
• Almaas, Runar; Pytte, Morten; Lindstad, Julie K.; Wright, Marianne; Saugstad, Ola Didrik & Pleasure, David [Vis alle 7 forfattere av denne artikkelen] (2003). Acidosis has opposite effects on neuronal survival during hypoxia and reoxygenation. Journal of Neurochemistry. ISSN 0022-3042. 84(5), s. 1018–1027. Fulltekst i vitenarkiv Vis sammendrag

  J Neurochem. 2003 March Acidosis has opposite effects on neuronal survival during hypoxia and reoxygenation. Almaas R, Pytte M, Lindstad JK, Wright M, Saugstad OD, Pleasure D, Rootwelt T. Department of Pediatric Research, Rikshospitalet, N-0027 Oslo, Norway. runaralm@start.no To study the effect of extracellular acidosis on apoptosis and necrosis during ischemia and reoxygenation, we exposed human post-mitotic NT2-N neurones to oxygen and glucose deprivation (OGD) followed by reoxygenation. In some experiments, pH of the cell medium was lowered to 5.9 during either OGD or reoxygenation or both. Staurosporine, used as a positive control for apoptosis, caused Poly(ADP-ribose)-polymerase (PARP) cleavage and nuclear fragmentation, but no PARP cleavage and little fragmentation were seen after OGD. Low molecular weight DNA fragments were found after staurosporine treatment, but not after OGD. No protective effect of caspase inhibitors was seen after 3 h of OGD and 21 h of reoxygenation, but after 45 h of reoxygenation caspase inhibition induced a modest improvement in 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyltetrazolium bromide (MTT) cleavage. While acidosis during OGD accompanied by neutral medium during reoxygenation protected the neurones (MTT: 228 +/- 117% of neutral medium, p < 0.001), acidosis during reoxygenation only was detrimental (MTT: 38 +/- 25%, p < 0.01). We conclude that apoptotic mechanisms play a minor role after OGD in NT2-N neurones. The effect of acidosis on neuronal survival depends on the timing of acidosis, as acidosis was protective during OGD and detrimental during reoxygenation. PMID: 12603826 [PubMed - indexed for MEDLINE]

• Almaas, Runar; Saugstad, Ola Didrik; Pleasure, David & Rootwelt, Terje (2002). Neuronal formation of free radicals plays a minor role in hypoxic cell death in human NT2-N neurons. Pediatric Research. ISSN 0031-3998. 51(2), s. 136–143. Fulltekst i vitenarkiv
• Almaas, Runar; Robertson, Bengt; Linderholm, B.; Lundberg, E.; Saugstad, Ola Didrik & Moe, Aud (2000). Reversal of meconium inhibition of pulmnary surfactant by Ferrid Chloride, Copper Chloride, and Acetic Acid. American Journal of Respiratory and Critical Care Medicine. ISSN 1073-449X. 162, s. 1789–1794. Fulltekst i vitenarkiv
• Almaas, Runar; Saugstad, Ola Didrik; Pleasure, David & Rootwelt, Terje (2000). Effect of barbiturates on hydroxyl radicals, lipid peroxidation, and hypoxic cell death in human NT2-N neurons. Anesthesiology. ISSN 0003-3022. 92, s. 764–774. Fulltekst i vitenarkiv
• Rootwelt, Terje; Dunn, M.; Yudkoff, M.; Itoh, T.; Almaas, Runar & Pleasure, David (1998). Hypoxic cell death in human NT2-N neurons: Involvement of NMDA and Non-NMDA glutamate receptors. Journal of Neurochemistry. ISSN 0022-3042. 71, s. 1544–1553. Fulltekst i vitenarkiv
• Elsner, B.; Øyasæter, Stephanie; Almaas, Runar & Saugstad, Ola Didrik (1998). Diving seals, ischemia-reperfusion and oxygen radicals. Comparative Biochemistry and Physiology - Part C: Toxicology & Pharmacology. ISSN 1532-0456. 119(part A), s. 975–980. Fulltekst i vitenarkiv Vis sammendrag

  Keywords: seals; diving; oxygen radicals; hypoxanthine; superoxide dismutase

• Moen, Atle; Yu, Xing-Qing; Almaas, Runar; Curstedt, Tore & Saugstad, Ola Didrik (1998). Acute effects on systemic circulation after intratracheal instilation of Curosurf or Survanta in surfactant-depleted newborn piglets. Acta Paediatrica. ISSN 0803-5253. 87(3), s. 297–303. Fulltekst i vitenarkiv
• Rootwelt, Terje; Dunn, M.; Yudkoff, M.; Itoh, T.; Almaas, Runar & Pleasure, David (1998). Hypoxic cell death in human NT2-N neurons: Involvement of NMDA and non-NMDA glutamate receptors. Journal of Neurochemistry. ISSN 0022-3042. 71(4), s. 1544–1553. Fulltekst i vitenarkiv
• Almaas, Runar; Rootwelt, Terje; Øyasæter, Stephanie & Saugstad, Ola Didrik (1997). Ascorbic acid enhances hydroxyl radical formation in iron-fortified infant cereals and infant formulas. European Journal of Pediatrics. ISSN 0340-6199. 156, s. 488–492. Fulltekst i vitenarkiv
• Almaas, Runar; Sundar, Tom; Rootwelt, Terje & Saugstad, Ola Didrik (1997). Plasma hypoxanthine reacts more abruptly to changes in oxygenation than base deficit and uric acid in newborn piglets. Journal of Perinatal Medicine. ISSN 0300-5577. 25, s. 353–360. Fulltekst i vitenarkiv Vis sammendrag

  High postmortem concentrations of hypoxanthine (Hyp) have been found in vitreous humor of children dying of SIDS. We investigated the accumulation of Hyp in vitreous humor during hypoxia. Twenty-four piglets aged 9-15 days were exposed to continous hypoxemia (180 min 11% O2, n=6), long interval intermittent hypoxemia (60 min 11 O2, 20 min room air, n=7) or short interval intermittent hypoxemia (10 min 9% O2, 10 min room air with (n=6) or without (n=5) superimposed ligation of both carotid arteries). The increase in vitreous humor Hyp was four-fold higher (p<0.01) with ligation of the carotid arteries (14±2.4 to 38±8.9 mmol/l) than without ligation (15±2.8 to 21±5.9 mmol/l). During continous hypoxemia plasma Hyp (r=0.85), xanthine (r=0.89), uric (UA) (r=0.85), and base deficit (BD) (r=0.78) increased almost linearly (p<0.001). Ligation of the carotid arteries had a strong impact on Hyp accumulation in vitreous humor, suggesting that vitreous humor Hyp is not merely a filtration product of plasma Hyp, but reflects local hypoxia/ischemia in the eye.

• Rootwelt-Revheim, Terje; Almaas, Runar; Øyasæter, Stephanie; Moen, Atle & Saugstad, Ola Didrik (1995). Release of xanthine oxidase to the systemic circulation during resuscitation from severe hypoxemia in newborn pigs. Acta Paediatrica. ISSN 0803-5253. 84(5), s. 507–511. doi: 10.1111/j.1651-2227.1995.tb13683.x. Fulltekst i vitenarkiv
• Hukkanen, M.; Konttinen, Y. T.; Santavirta, S.; Nordsletten, Lars; Madsen, Jan Erik & Almaas, Runar [Vis alle 9 forfattere av denne artikkelen] (1995). Effect of sciatic nerve section on neural ingrowth into the rat tibial fracture callus. Clinical Orthopaedics and Related Research. ISSN 0009-921X. 311, s. 247–257. Fulltekst i vitenarkiv
• Stoltenberg, Lauritz; Sundar, Tom; Almaas, Runar; Storm, Hanne; Rognum, Torleiv Ole & Saugstad, Ola Didrik (1994). Changes in apnea and auto resuscitation in piglets after intravenous and intratechal interleukin-1-beta injection. Journal of Perinatal Medicine. ISSN 0300-5577. Fulltekst i vitenarkiv
• Nordsletten, Lars; Madsen, Jan Erik; Almaas, Runar; Rootwelt-Revheim, Terje; Halse, Johan & Konttinen, Yrjö T. [Vis alle 8 forfattere av denne artikkelen] (1994). The neuronal regulation of fracture healing. Effects of sciatic nerve resection in rat tibia. Acta Orthopaedica Scandinavica. ISSN 0001-6470. 65(3), s. 299–304. doi: 10.3109/17453679408995457. Fulltekst i vitenarkiv

Se alle arbeider i NVA

• Bruun, Dorthe Elise Rustand; Diab, Simone; Hjartåker, Anette; Almaas, Runar; Brunvand, Leif & Hansen, Kari Margrethe [Vis alle 7 forfattere av denne artikkelen] (2022). Vitamin D and calcium intake in children with Fontan circulation in relationship to vitamin D status and bone mineral density. Cardiology in the Young. ISSN 1047-9511. Fulltekst i vitenarkiv
• Landsverk, Hans Christian Erichsen; Almaas, Runar & Saugstad, Ola Didrik (2022). 50 Years Ago in THE JOURNAL OF PEDIATRICS: Hemiallogeneic Stem Cell Transplantation—from Last Resort to a Viable Treatment Option. Journal of Pediatrics. ISSN 0022-3476. 243, s. 213–213. doi: 10.1016/j.jpeds.2021.12.064. Fulltekst i vitenarkiv
• Almaas, Runar & Saugstad, Ola Didrik (2021). 50 Years Ago in THE JOURNAL OF PEDIATRICS: Diagnosis of Self-Mutilation and Hyperuricemia. Journal of Pediatrics. ISSN 0022-3476. 237, s. 86–86. doi: 10.1016/j.jpeds.2021.07.034. Fulltekst i vitenarkiv
• Almaas, Runar & Saugstad, Ola Didrik (2021). 50 years ago in THE JOURNAL OF PEDIATRICS: Hepatopulmonary syndrome: Transplantation Is the big difference. Journal of Pediatrics. ISSN 0022-3476. 229, s. 69–69. doi: 10.1016/j.jpeds.2020.08.074. Fulltekst i vitenarkiv
• Thorsteinsdottir, Hjørdis; Möller, Thomas; Bjerre, Anna Kristina & Almaas, Runar (2020). GDF-15 — A matter of the heart or the kidney? International Journal of Cardiology. ISSN 0167-5273. 313, s. 47–47. doi: 10.1016/j.ijcard.2020.03.017. Fulltekst i vitenarkiv
• Almaas, Runar (2019). Diagnosing autoimmune hepatitis in paediatric patients - we still haven't found what we are looking for. Acta Paediatrica. ISSN 0803-5253. 108(9), s. 1562–1563. doi: 10.1111/apa.14890. Fulltekst i vitenarkiv
• Stølen, Linn Helene; Almaas, Runar; Bliksrud, Yngve Thomas & Mathisen, Per (2010). HIGH PLASMA FOLATE LEVELS IN ADULTS WITH PKU ON PROTEIN SUBSTITUTE. The Journal of Inherited Metabolic Disease (JIMD). ISSN 0141-8955. 33, s. S170–S170. Fulltekst i vitenarkiv
• Lilje, Rina; Almaas, Runar; Bliksrud, Yngve Thomas; Motzfeldt, K & Jørgensen, J. V. (2010). HIGH PLASMA FOLATE LEVELS IN CHILDREN WITH PKU. The Journal of Inherited Metabolic Disease (JIMD). ISSN 0141-8955. 33, s. S169–S169. Fulltekst i vitenarkiv
• Hankø, Erik; Hansen, Thor Willy Ruud; Lindstad, Julie K.; Almaas, Runar & Rootwelt, Terje (2003). Bilirubin induserer apoptose og nekrose i humane NT2-N nevroner. Fulltekst i vitenarkiv
• Almaas, Runar; Pytte, Morten; Lindstad, Julie K.; Wright, Marianne; Pleasure, David & Rootwelt, Terje (2002). Acidosis has opposite effects on neuronal survival during hypoxia and reoxygenation. Fulltekst i vitenarkiv
• Almaas, Runar; Robertson, Bengt; Saugstad, Ola Didrik & Moen, Atle (1999). Inhibitory effect of meconium on surfactant is prevented by iron. Fulltekst i vitenarkiv
• Almaas, Runar; Robertson, Bengt; Saugstad, Ola Didrik & Moen, Atle (1999). Iron abolishes inhibitory effects of meconium. Fulltekst i vitenarkiv
• Almaas, Runar (2003). Hypoxia in Human NT2-N Neurons. The Role of Free Radicals and Glutamate. Universitetet i Oslo. ISSN 9788280720924. Fulltekst i vitenarkiv Vis sammendrag

  Kort sammendrag: Hvis barn får for lite oksygen før, under eller etter fødselen kan de utvikle hjerneskader. Det er stor forskningsaktivitet for å studere hvordan skadene utvikler seg, slik at man kan begrense skadene så mye som mulig. Dyremodeller og nerveceller fra gnagere brukes ofte for å studere utviklingen av hjerneskader. Menneskelige modeller har imidlertid vært vanskeligere tilgjengelig og man har hatt store vansker med å overføre lovende resultater i dyremodeller til mennesker bla pga artsforskjeller. Vi har laget en alternativ modell til dyrestudier der vi ndersøker skader etter mangel på oksygen på menneskelige NT2 celler. Opprinnelig kommer disse NT2 cellene fra en type kreftceller, men etter flere ukers dyrkning og behandling modnes cellene slik at de ligner nerveceller. Vi har undersøkt hvordan behandling med antioksidanter og ulike narkosemidler påvirker nervecelleskade etter oksygenmangel, og hva slags rolle lav pH/surt miljø har på skademekanismene. I motsetning til hva man har funnet i mange dyremodeller fant vi liten effekt av antioksidanter på de menneskelige cellene. Dette kan skyldes artsforskjeller. Et annet overraskende resultatet var at lav pH beskyttet nervecellene i den fasen hvor cellene hadde for lite oksygen, men var skadelig i gjenopplivingsfasen hvor cellene igjen fikk tilført oksygen. Tidligere har man stort sett studert effekten av lav pH i disse fasene under ett, men våre forsøk understreker at man bør undersøke disse fasene hver for seg. Denne modellen med menneskelige NT2 celler er et supplement til de etablerte metodene hvor man nytter celler fra gnagere. Vi kan her teste om behandling som virker lovende på nerveceller fra dyr virker tilsvarende på menneskelige celler

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