Tore Gunnar Abrahamsen

• Andersen, Jintana Bunpan; Strand, Janne Maren; Stray-Pedersen, Asbjørg; Abrahamsen, Tore Gunnar; Stray-Pedersen, Arne & Flægstad, Trond [Show all 9 contributors for this article] (2026). Unmasking immunodeficiency in sudden infant deaths: no evidence of hidden immune disorders. Frontiers in Immunology. 17. doi: 10.3389/fimmu.2026.1860011. Full text in Research Archive Show summary

  Introduction Sudden infant death syndrome (SIDS) remains a leading cause of post-neonatal mortality, yet its underlying mechanisms are largely unknown. Evidence suggests that immune dysfunction may play a role in a subset of cases. However, the role of inborn errors of immunity (IEI), particularly severe combined immunodeficiency (SCID), has not been systematically explored. We aimed to study their potential role in SIDS and infant deaths from infectious disease. Methods We obtained mortality data for 2012–2017 from The Norwegian Cause of Death Registry and identified eligible infants by reviewing ICD-10 codes for infection-related deaths or SIDS. The medical history and autopsy reports were reviewed and infants with predisposition to infection were excluded. Genetic testing was performed on biobanked newborn dried blood spot samples following the protocol for identifying SCID/IEI in live-born infants. Results The study population consisted of 79 infants, of which 66% ( n  = 52) died of SIDS and 34% ( n  = 27) due to infection. The majority of the infants in both groups had at least one genetic IEI-related variant, but no findings were clearly pathogenic. Variants of uncertain significance in autosomal dominant disease genes were identified in 18% ( n  = 14). Heterozygous pathogenic variants in autosomal recessive genes were identified in 23% ( n  = 18). Risk factor variants were identified in 42% ( n  = 33), including two mannose-binding lectin 2 polymorphisms with alleles more frequently observed in the infection group compared to the general population. Discussion No missed cases of SCID/IEI were identified among infants who died from infections or SIDS. Yet a significant proportion of the cohort may carry genetic predispositions due to the presence of immune-related genetic variants. Even in the absence of overt immunodeficiency, these findings may reflect a latent vulnerability interacting with physiological and environmental factors.

• Martinsen, Karen Marie Bronken; Øverland, Torstein; Stray-Pedersen, Asbjørg; Abrahamsen, Tore Gunnar; Fevang, Børre & Landsverk, Hans Christian Erichsen (2025). A Norwegian cohort with STAT1-related disease – further expanding the clinical phenotype. Frontiers in Immunology. 16. doi: 10.3389/fimmu.2025.1620291. Full text in Research Archive Show summary

  Purpose: Inborn errors of immunity (IEIs) caused by mutations in STAT1 are associated with a broad range of clinical manifestations, ranging from relatively mild to life-threatening. Our aim was to give a clinical and molecular description of a Norwegian cohort with STAT1-related disease. Methods: This is a descriptive epidemiological study. Results: We present 23 patients with heterozygous STAT1 mutations, from 12 unrelated Norwegian families. Eighteen individuals had STAT1 gain-of-function (GOF) variants. Chronic mucocutaneous candidiasis (CMC) was the most common manifestation, observed in 94% of patients. Herpesviruses caused morbidity in one-third of patients, with severe complications such as varicella meningitis, varicella retinitis and ulcerative CMV esophagitis seen in 17%. Autoimmune hypertriglyceridemia with GPIHBP1 autoantibodies was diagnosed in one patient, adding a new entity to STAT1 GOF. Fifty percent of patients suffered chronic ophthalmologic manifestations. Severe gastrointestinal manifestations were observed in 22% of patients. Five of the 23 patients had STAT1 loss-of-function (LOF) variants. Mendelian susceptibility to mycobacterial disease (MSMD) was detected in three patients. Malignancy and autoimmunity were observed in two patients, both were heterozygous for the p.Ala246Thr variant, which is likely associated with a more complex phenotype. Significant viral infections were also observed. Presently, our cohort represents the largest nationwide study on STAT1-related disease. Conclusion: We report novel clinical manifestations in STAT1 GOF, and suggest that heterozygous STAT1 LOF might be a more complex condition than originally presumed.

• Berg, Annika Klungland; Diseth, Trond H; Abrahamsen, Tore G; Halvorsen, Kathleen; Reinfjell, Trude & Erichsen, Hans Christian (2021). Primary antibody deficiency: The impact on the quality of life and mental health of affected children and their parents. Acta Paediatrica. ISSN 0803-5253. 110, p. 1645–1652. doi: 10.1111/apa.15752. Full text in Research Archive Show summary

  Aim To evaluate health-related quality of life, mental health and treatment-related stress responses in children with primary antibody deficiency and both their parents. Methods Children and their parents completed the standardised questionnaires Pediatric Quality of life Inventory, Strength and Difficulties Questionnaire and Impact of Event Scale. Parents also completed standardised questionnaires regarding their own mental health and quality of life. The results were compared to those of healthy children, kidney transplanted children and children in remission from acute lymphoblastic leukaemia. Results Children with primary antibody deficiency reported a poorer health-related quality of life compared to healthy children and children in remission from acute lymphoblastic leukaemia. They reported poorer mental health compared with healthy children. Mothers of children with primary antibody deficiency reported poorer mental health compared to mothers of healthy children but comparable to mothers of chronically ill children. Parents reported a similar quality of life as the general Norwegian population. Treatment with subcutaneous immunoglobulin infusions at home is generally well tolerated, but some report severe treatment-related stress. Conclusion Primary antibody deficiency has a significant impact on quality of life and mental health of affected children. Patients and parents with severe treatment-related stress should be identified and helped.

• Popperud, Trine H.; Gul, Kiran A.; Brunborg, Cathrine; Olaussen, Richard W; Abrahamsen, Tore G & Osnes, Liv T. N. [Show all 7 contributors for this article] (2021). Thymectomy in Juvenile Myasthenia Gravis Is Safe Regarding Long Term Immunological Effects. Frontiers in Neurology. 12, p. 1–6. doi: 10.3389/fneur.2021.596859. Full text in Research Archive Show summary

  Thymectomy is an established treatment in adult MG and also recommended for the treatment of post-pubertal onset juvenile MG. Whether the youngest children should be thymectomized is still debated. Signs of premature aging of the immune system have been shown in studies on early perioperative thymectomy in children with congenital heart defect. In this retrospective cohort study the objective was to investigate the long-term effects of treatment related thymectomy on T cell subsets and T cell receptor rearrangement excision circles (TRECs) in peripheral blood of juvenile myasthenia gravis (MG) patients, as well as clinical occurrence of autoimmune disorders, malignancies and infectious diseases. Forty-seven patients with onset of myasthenia gravis before the age of 19 years were included; 32 (68.1%) had been thymectomized and 15 (31.8%) had not. They were studied at varying times after thymectomy (7–26 years). We found a significant lower number of naïve helper T cells (CD4+CD45RA+) with an increased proportion of memory helper T cells (CD4+CD45RO+), and a significant lower number of naïve cytotoxic T cells (CD8+CD27+CD28+) in the thymectomized patients. In addition they showed a significant reduction in the number of TRECs and proportion of recent thymic emigrants (RTE) compared to non-thymectomized patients. In none of them an increased frequency of malignancies or infections was found. Our findings indicate a premature aging of the immune system after thymectomy in juvenile MG, but associated clinical consequences could not be verified.

• Strand, Janne Maren; Gul, Kiran Aftab; Erichsen, Hans Christian; Lundman, Emma; Berge, Mona C. & Trømborg, Anette Kjoshagen [Show all 28 contributors for this article] (2020). Second-Tier Next Generation Sequencing Integrated in Nationwide Newborn Screening Provides Rapid Molecular Diagnostics of Severe Combined Immunodeficiency. Frontiers in Immunology. 11. doi: 10.3389/fimmu.2020.01417. Full text in Research Archive Show summary

  Severe combined immunodeficiency (SCID) and other T cell lymphopenias can be detected during newborn screening (NBS) by measuring T cell receptor excision circles (TRECs) in dried blood spot (DBS) DNA. Second tier next generation sequencing (NGS) with an amplicon based targeted gene panel using the same DBS DNA was introduced as part of our prospective pilot research project in 2015. With written parental consent, 21 000 newborns were TREC-tested in the pilot. Three newborns were identified with SCID, and disease-causing variants in IL2RG, RAG2, and RMRP were confirmed by NGS on the initial DBS DNA. The molecular findings directed follow-up and therapy: the IL2RG-SCID underwent early hematopoietic stem cell transplantation (HSCT) without any complications; the leaky RAG2-SCID received prophylactic antibiotics, antifungals, and immunoglobulin infusions, and underwent HSCT at 1 year of age. The child with RMRP-SCID had complete Hirschsprung disease and died at 1 month of age. Since January 2018, all newborns in Norway have been offered NBS for SCID using 1st tier TRECs and 2nd tier gene panel NGS on DBS DNA. During the first 20 months of nationwide SCID screening an additional 88 000 newborns were TREC tested, and four new SCID cases were identified. Disease-causing variants in DCLRE1C, JAK3, NBN, and IL2RG were molecularly confirmed on day 8, 15, 8 and 6, respectively after birth, using the initial NBS blood spot. Targeted gene panel NGS integrated into the NBS algorithm rapidly delineated the specific molecular diagnoses and provided information useful for management, targeted therapy and follow-up i.e., X rays and CT scans were avoided in the radiosensitive SCID. Second tier targeted NGS on the same DBS DNA as the TREC test provided instant confirmation or exclusion of SCID, and made it possible to use a less stringent TREC cut-off value. This allowed for the detection of leaky SCIDs, and simultaneously reduced the number of control samples, recalls and false positives. Mothers were instructed to stop breastfeeding until maternal cytomegalovirus (CMV) status was determined. Our limited data suggest that shorter time-interval from birth to intervention, may prevent breast milk transmitted CMV infection in classical SCID.

• Gul, Kiran Aftab; Strand, Janne Maren; Pettersen, Rolf Dagfinn; Brun, Henrik & Abrahamsen, Tore G (2020). T-cell Receptor Excision Circles in Newborns with Heart Defects. Pediatric Cardiology. ISSN 0172-0643. 41(4), p. 809–815. doi: 10.1007/s00246-020-02317-y. Full text in Research Archive Show summary

  Abstract In the fetus, the cardiac neural crest gives rise to both the thymus and the conotruncus of the heart. In newborn screening for severe T-cell lymphopenia neonates with congenital heart defects may be detected. In this study, we investigated the occurrence of T-cell lymphopenia in neonates with or without 22q11.2 deletion syndrome (del) suffering from heart defects. This retrospective cohort study included 125 patients with heart defects. T-cell receptor excision circles (TRECs), a measure for T-cell lymphopenia, were quantified by RT-PCR using stored newborn screening blood spots. Three patient groups were compared: non-conotruncal defects ( n  = 57), conotruncal defects ( n  = 42), and 22q11.2 del with conotruncal defects ( n  = 26). Significantly lower TREC values were detected in patients with 22q11.2 del and conotruncal heart defects compared to those with non-syndromic conotruncal ( p  < 0.001) and non-conotruncal ( p  < 0.001) defects. In contrast, no significant difference was found between patients with non-syndromic conotruncal and non-conotruncal heart defects ( p  = 0.152). Low TREC levels were obtained in neonates treated with heart surgery/intervention within 2 weeks after birth and in those with a fatal outcome ( p  = 0.02) independent of patient group. A correlation was found between low TREC numbers and oxygen saturation, SpO 2 below 95% ( p  = 0.017). The SpO 2 was significantly lower in the non-syndromic conotruncal group compared to non-conotruncal ( p  < 0.001) and 22q11.2 del group ( p  = 0.015). No correlation was found between low neonatal TRECs and infections needing hospitalization later in life ( p  = 0.135). Patients with 22q11.2 del and conotruncal defects have significantly lower TREC levels compared to patients with heart defects without this syndrome.

• Hope, Sigrun; Nærland, Terje; Høyland, Anne Lise; Torske, Tonje; Malt, Eva & Abrahamsen, Tore G [Show all 16 contributors for this article] (2020). Higher vitamin B12 levels in neurodevelopmental disorders than in healthy controls and schizophrenia A comparison among participants between 2 and 53 years. The FASEB Journal. ISSN 0892-6638. 34(6), p. 8114–8124. doi: 10.1096/fj.201900855RRR. Full text in Research Archive Show summary

  Recent studies suggest that both high and low levels of vitamin B12 (vitB12) may have negative health impacts. We measured VitB12 in patients with the Neurodevelopmental disorders (ND) (n = 222), comprised of Autism Spectrum Disorders, specific Developmental disorders, and Intellectual Disability (aged 2‐53 years), schizophrenia (n = 401), and healthy controls (HC) (n = 483). Age‐and gender‐adjusted vitB12 z‐scores were calculated by comparisons with a reference population (n = 76 148). We found higher vitB12 in ND (median 420 pmol/L, mean z‐score: 0.30) than in HC (316 pmol/L, z‐score: 0.06, P < .01) and schizophrenia (306 pmol/L, z‐score: −0.02, P < .001), which was significant after adjusting for age, gender, vitB12 supplement, folate, hemoglobin, leukocytes, liver, and kidney function (P < .02). In ND, 20% (n = 44) had vitB12 above 650 pmol/L, and 1% (n = 3) had below 150 pmol/L (common reference limits). In 6.3% (n = 14) of ND, vitB12 was above 2SD of mean in the age‐and gender‐adjusted reference population, which was more frequent than in HC (n = 8, 1.6%), OR: 4.0, P = .001. Low vitB12 was equally frequent as in HC, and vitB12 z‐scores were equal across the age groups. To conclude, vitB12 was higher in ND than in HC and schizophrenia, suggesting a specific feature of ND, which warrants further studies to investigate the underlying mechanisms.

• Grinde, Dina Mikhailovna; Øverland, Torstein; Lima, Kari; Schjalm, Camilla; Mollnes, Tom Eirik & Abrahamsen, Tore G (2020). Complement Activation in 22q11.2 Deletion Syndrome. Journal of Clinical Immunology. ISSN 0271-9142. 40(3), p. 515–523. doi: 10.1007/s10875-020-00766-x. Full text in Research Archive Show summary

  The 22q11.2 deletion syndrome (22q11.2 del), also known as DiGeorge syndrome, is a genetic disorder with an estimated incidence of 1:3000 to 1:6000 births. These patients may suffer from affection of many organ systems with cardiac malformations, immunodeficiency, hypoparathyroidism, autoimmunity, palate anomalies, and psychiatric disorders being the most frequent. The importance of the complement system in 22q11.2 del has not been investigated. The objective of this study was to evaluate the complement system in relation to clinical and immunological parameters in patients. A national cohort of patients (n = 69) with a proven heterozygous deletion of chromosome 22q11.2 and a group of age and sex matched controls (n = 56) were studied. Functional capacity of the classical, lectin, and alternative pathways of the complement system as well as complement activation products C3bc and terminal complement complex (TCC) were accessed and correlated to clinical features. All patients in our study had normal complement activation in both classical and alternative pathways. The frequency of mannose-binding lectin deficiency was comparable to the normal population. The patients had significantly raised plasma levels of C3bc and a slight, but not significant, increase in TCC compared with controls. This increase was associated with the presence of psychiatric disorders in patients. The present study shows no complement deficiencies in 22q11.2 deletion syndrome. On the contrary, there are signs of increased complement activation in these patients. Complement activation is particularly associated with the presence of psychiatric disorders.

• Aresvik, Dina Mikhailovna; Øverland, Torstein; Lima, Kari; Pettersen, Rolf Dagfinn & Abrahamsen, Tore G (2019). Lymphocyte Apoptosis and FAS Expression in Patients with 22q11.2 Deletion Syndrome. Journal of Clinical Immunology. ISSN 0271-9142. 39(1), p. 65–74. doi: 10.1007/s10875-018-0579-7. Full text in Research Archive
• Knudsen, Per Kristian; Gammelsrud, Karianne Wiger; Alfsnes, Kristian; Steinbakk, Martin; Abrahamsen, Tore G & Müller, Fredrik [Show all 7 contributors for this article] (2018). Transfer of a bla CTX-M-1-carrying plasmid between different Escherichia coli strains within the human gut explored by whole genome sequencing analyses. Scientific Reports. 8(1). doi: 10.1038/s41598-017-18659-2. Full text in Research Archive Show summary

  Horizontal transfer of antibiotic resistance determinants contributes to dissemination of antibiotic resistance. Such transfer of resistance genes within the human gut has been documented in some in vivo studies. The present study investigated seven bla CTX-M-1-carrying Escherichia coli isolates from three consecutive faecal samples collected from one cystic fibrosis patient in a nine-months period, by analysing whole genome sequencing data. The analyses showed that the seven E. coli isolates represented three genetically diverse strains. All isolates contained bla CTX-M-1-carrying Incl1 plasmids that shared a common 101 kb backbone differing by only four SNPs. The plasmids harboured by the three different E. coli strains varied within limited regions suggestive of recombination events, according to the phylogenetic topology of the genomes of the isolates harbouring them. The findings strongly suggest that horizontal transfer of a bla CTX-M-1-carrying plasmid had occurred within the patient´s gut. The study illustrates the within-host diversity of faecally carried resistant E. coli isolates and highlights the value of collecting multiple bacterial colonies from longitudinally collected samples to assess faecal carriage of resistant enterobacteria. The clustering of the plasmids with the corresponding E. coli strains carrying them indicates that the plasmids appear to have adapted to their respective E. coli hosts.

• Knudsen, Per Kristian; Brandtzæg, Petter; Høiby, Ernst Arne; Bohlin, Jon; Samuelsen, Ørjan & Steinbakk, Martin [Show all 9 contributors for this article] (2017). Impact of extensive antibiotic treatment on faecal carriage of antibiotic-resistant enterobacteria in children in a low resistance prevalence setting. PLOS ONE. 12(11). doi: 10.1371/journal.pone.0187618. Full text in Research Archive Show summary

  We prospectively studied the consequences of extensive antibiotic treatment on faecal carriage of antibiotic-resistant enterobacteria in a cohort of children with cystic fibrosis (CF) and a cohort of children with cancer compared to healthy children with no or low antibiotic exposure. The study was conducted in Norway in a low resistance prevalence setting. Sixty longitudinally collected faecal samples from children with CF (n = 32), 88 samples from children with cancer (n = 45) and 127 samples from healthy children (n = 70) were examined. A direct MIC-gradient strip method was used to detect resistant Enterobacteriaceae by applying Etest strips directly onto agar-plates swabbed with faecal samples. Whole genome sequencing (WGS) data were analysed to identify resistance mechanisms in 28 multidrug-resistant Escherichia coli isolates. The prevalence of resistance to third-generation cephalosporins, gentamicin and ciprofloxacin was low in all the study groups. At inclusion the prevalence of ampicillin-resistant E. coli and trimethoprim-sulfamethoxazole-resistant E. coli in the CF group compared to healthy controls was 58.6% vs. 28.4% (p = 0.005) and 48.3% vs. 14.9% (p = 0.001), respectively, with a similar prevalence at the end of the study. The prevalence of resistant enterobacteria was not significantly different in the children with cancer compared to the healthy children, not even at the end of the study when the children with cancer had been treated with repeated courses of broad-spectrum antibiotics. Children with cancer were mainly treated with intravenous antibiotics, while the CF group mainly received peroral treatment. Our observations indicate that the mode of administration of antibiotics and the general level of antimicrobial resistance in the community may have an impact on emergence of resistance in intestinal enterobacteria during antibiotic treatment. The WGS analyses detected acquired resistance genes and/or chromosomal mutations that explained the observed phenotypic resistance in all 28 multidrug-resistant E. coli isolates examined.

• Filip, Charles; Impieri, Davide; Aagenæs, Ingegerd; Breugem, Corstiaan C.; Høgevold, Hans Erik & Særvold, Tone [Show all 10 contributors for this article] (2017). Adults with 22q11.2 deletion syndrome have a different velopharyngeal anatomy with predisposition to velopharyngeal insufficiency. Journal of Plastic, Reconstructive & Aesthetic Surgery. ISSN 1748-6815. 71(4), p. 524–536. doi: 10.1016/j.bjps.2017.09.006. Full text in Research Archive Show summary

  Aim: To find out if subjects with 22q11.2 deletion syndrome (DS) have a different velopharyngeal anatomy which could cause velopharyngeal insufficiency (VPI). Methods: A prospective study of 16 subjects >16 years of age with 22q11.2 DS, without overt cleft palate and without previous VPI surgery, and 48 healthy controls >18 years of age were included in the study. Speech was recorded and scored blindly by two independent senior speech therapists. All 64 individuals had MRI scans, which were analyzed blindly by a consultant radiologist. Results: Subjects with 22q11.2 DS had a mild degree of weak pressure consonants (mean score); borderline to mild degree of hypernasality and audible nasal emission (mean score). All controls had normal speech. When comparing subjects (22q11.2 DS) to controls, we found the subjects to have the following: A shorter distance between left and right points of origin of the levator veli palatini muscle (LVP) (p < 0.0001); a more obtuse angle of origin of the LVP (bilaterally) (p < 0.009); a thinner LVP bilaterally and in the midline (p < 0.0001); a shorter LVP bilaterally (p < 0.0001); a shorter velum (p = 0.007); a larger osseous pharyngeal depth:velar length ratio (p = 0.01); a more obtuse anterior cranial base angle (nasion to sella to basion) (p < 0.0001) and posterior cranial base angle (sella to basion to foramen magnum) (p < 0.0001); a wider velopharyngeal width (p = 0.002) and a larger pharyngeal airway volume (p = 0.0007). Conclusion: Compared with healthy controls, adults with 22q11.2 DS showed a different velopharyngeal anatomy, which will make these individuals more prone to VPI.

• Gul, Kiran Aftab; Stiansen-Sonerud, Tonje; Fjærli, Hans Olav; Nakstad, Britt; Abrahamsen, Tore G & Inchley, Christopher (2017). Thymus activity measured by T-cell receptor excision circles in patients with different severities of respiratory syncytial virus infection. BMC Infectious Diseases. 17(18), p. 1–8. doi: 10.1186/s12879-016-2148-0. Full text in Research Archive Show summary

  Background Respiratory syncytial virus (RSV) infection is an important cause of hospitalization in previously healthy infants. Immunological mechanisms predisposing infants to severe disease are poorly understood. Early biomarkers for disease severity may assist clinical decisions. We investigated T-cell receptor excision circles (TREC), episomal DNA made during thymic T-cell receptor rearrangement, and a marker for thymus activity, both during disease and in neonatal screening cards as a risk factor for RSV disease severity. Methods One hundred thirteen patients hospitalized with RSV infection <12 months of age, grouped by disease severity, were available for this investigation, in which we conducted both a prospective and a case-control study. The prospective study included 47 RSV positive infants (mild n = 13, moderate n = 10, severe n = 24). TREC counts were determined by PCR of DNA extracted from EDTA-blood collected on hospitalization, and corrected for lymphocytes using ANCOVA. The case-control study included 85 newborns who later in infancy became RSV positive (mild n = 32, moderate n = 24, severe n = 29) and 47 newborns who never developed RSV disease as healthy controls included from health centres in the same catchment area. TRECs were measured using DNA extracted from dry blood spots from stored neonatal screening cards, followed by PCR. Student’s T-test compared patients with controls, ANOVA compared disease severity groups. Results During RSV infection patients in the severe disease group had significantly lower (p = 0.017) TREC/200 μL blood compared to the other two disease groups, after correction for lymphocyte count. Newborn TREC levels, were significantly higher in RSV patients compared to controls (p < 0.0001). No significant differences in TREC copies at birth were found between disease severities. Conclusion During acute RSV infection a lower number of TREC is found in the severe disease group. TREC has potential as an immunological marker for severe RSV infection. Higher neonatal TREC counts indicate that infants later presenting with severe RSV do not have reduced thymic activity at birth and probably no congenital T-cell defect.

• Stensvold, Hans Jørgen; Lang, Astri Maria; Strømmen, Kenneth; Abrahamsen, Tore G; Øglænd, Bjørn Edvin & Pripp, Are Hugo [Show all 7 contributors for this article] (2017). Strictly controlled glucose infusion rates are associated with a reduced risk of hyperglycaemia in extremely low birth weight preterm infants. Acta Paediatrica. ISSN 0803-5253. 107(3), p. 442–449. doi: 10.1111/apa.14164. Full text in Research Archive
• Sorte, Hanne Sørmo; Osnes, Liv T. N.; Fevang, Børre; Aukrust, Pål; Erichsen, Hans Christian & Backe, Paul Hoff [Show all 20 contributors for this article] (2016). A potential founder variant in CARMIL2/RLTPR in three Norwegian families with warts, molluscum contagiosum, and T-cell dysfunction. Molecular Genetics & Genomic Medicine. ISSN 2324-9269. 4(6), p. 604–616. doi: 10.1002/mgg3.237. Full text in Research Archive
• Aresvik, Dina; Lima, Kari; Øverland, Torstein; Mollnes, Tom Eirik & Abrahamsen, Tore G (2016). Increased Levels of Interferon-Inducible Protein 10 (IP-10) in 22q11.2 Deletion Syndrome. Scandinavian Journal of Immunology. ISSN 0300-9475. 83(3), p. 188–194. doi: 10.1111/sji.12406. Full text in Research Archive
• Stray-Pedersen, Asbjørg; Sorte, Hanne Sørmo; Samarakoon, Pubudu Saneth; Gambin, Tomasz; Chinn, Ivan K. & Akdemir, Zeynep H.C. [Show all 51 contributors for this article] (2016). Primary immunodeficiency diseases: Genomic approaches delineate heterogeneous Mendelian disorders. Journal of Allergy and Clinical Immunology. ISSN 0091-6749. 139(1), p. 232–245. doi: 10.1016/j.jaci.2016.05.042. Full text in Research Archive Show summary

  Background Primary immunodeficiency diseases (PIDDs) are clinically and genetically heterogeneous disorders thus far associated with mutations in more than 300 genes. The clinical phenotypes derived from distinct genotypes can overlap. Genetic etiology can be a prognostic indicator of disease severity and can influence treatment decisions. Objective We sought to investigate the ability of whole-exome screening methods to detect disease-causing variants in patients with PIDDs. Methods Patients with PIDDs from 278 families from 22 countries were investigated by using whole-exome sequencing. Computational copy number variant (CNV) prediction pipelines and an exome-tiling chromosomal microarray were also applied to identify intragenic CNVs. Analytic approaches initially focused on 475 known or candidate PIDD genes but were nonexclusive and further tailored based on clinical data, family history, and immunophenotyping. Results A likely molecular diagnosis was achieved in 110 (40%) unrelated probands. Clinical diagnosis was revised in about half (60/110) and management was directly altered in nearly a quarter (26/110) of families based on molecular findings. Twelve PIDD-causing CNVs were detected, including 7 smaller than 30 Kb that would not have been detected with conventional diagnostic CNV arrays. Conclusion This high-throughput genomic approach enabled detection of disease-related variants in unexpected genes; permitted detection of low-grade constitutional, somatic, and revertant mosaicism; and provided evidence of a mutational burden in mixed PIDD immunophenotypes.

• Stensvold, Hans Jørgen; Strømmen, Kenneth; Lang, Astri Maria; Abrahamsen, Tore G; Steen, Eline Kjørsvik & Pripp, Are Hugo [Show all 7 contributors for this article] (2015). Early enhanced parenteral nutrition, hyperglycemia, and death among extremely low-birth-weight infants. JAMA pediatrics. ISSN 2168-6203. 169(11), p. 1003–1010. doi: 10.1001/jamapediatrics.2015.1667. Full text in Research Archive Show summary

  Importance Efforts to optimize early parenteral nutrition (PN) in extremely low-birth-weight (ELBW) infants to promote growth and development may increase hyperglycemia risk. Recent studies have identified an association between early hyperglycemia and adverse outcomes in ELBW infants. Objectives To examine the prevalence of early hyperglycemia and clinical outcomes among ELBW infants before (2002-2005) and after (2006-2011) the implementation of an early enhanced PN protocol and to assess the independent effects of early enhanced PN and early hyperglycemia on mortality. Design, Setting, and Participants Observational cohort study in a level III neonatal intensive care unit. Prospectively collected clinical data in the neonatal intensive care unit’s medical database, nutritional information, and blood glucose levels were merged for analysis. All ELBW infants born between January 1, 2002, and December 31, 2011, without lethal malformations and still alive at 12 hours of life were eligible for inclusion in the study. Main Outcomes and Measures Mortality was the main outcome measure. Severe hyperglycemia was defined as 2 consecutive blood glucose levels exceeding 216 mg/dL at least 3 hours apart. A multivariable logistic regression model was applied to determine the independent effects of early enhanced PN and hyperglycemia on mortality. Results In total, 343 infants were included in the study, 129 in a historical comparison group before the enhanced PN protocol and 214 in the early enhanced PN group. Baseline characteristics were similar between the study groups. After the introduction of early enhanced PN, the prevalence of severe hyperglycemia during the first week of life was higher in the early enhanced PN group (11.6% [15 of 129] vs 41.6% [89 of 214], P < .001), as was the mortality (10.9% [14 of 129] vs 24.3% [52 of 214], P = .003). When adjusting for background characteristics, treatment, and nutritional data, early severe hyperglycemia remained a strong independent risk factor for death (odds ratio, 4.68; 95% CI, 1.82-12.03), together with gestational age (odds ratio, 0.62; 95% CI, 0.49-0.79). Conclusions and Relevance The implementation of an enhanced PN protocol was correlated with an increased prevalence of severe hyperglycemia and higher mortality. In the multivariable analysis, an enhanced PN regimen per se was not predictive of mortality, whereas early severe hyperglycemia remained strongly predictive of death. To avoid detrimental effects on outcomes in ELBW infants, the optimal composition of early PN to avoid postnatal growth failure must be carefully balanced against hyperglycemia risk.

• Gul, Kiran Aftab; Øverland, Torstein; Osnes, Liv T. N.; Baumbusch, Lars Oliver; Pettersen, Folf Dagfinn & Lima, Kari [Show all 7 contributors for this article] (2015). Neonatal Levels of T-cell Receptor Excision Circles (TREC) in Patients with 22q11.2 Deletion Syndrome and Later Disease Features. Journal of Clinical Immunology. ISSN 0271-9142. 35(4), p. 408–415. doi: 10.1007/s10875-015-0153-5. Full text in Research Archive
• Raastad, Ragnhild; Tvete, Ingunn Fride; Abrahamsen, Tore G; Berild, Dag; Leegaard, Truls Michael & Walberg, Mette [Show all 7 contributors for this article] (2015). A worrying trend in weight-adjusted paediatric antibiotic use in a Norwegian tertiary care hospital. Acta Paediatrica. ISSN 0803-5253. 104(7), p. 687–692. doi: 10.1111/apa.12994. Full text in Research Archive Show summary

  Aim The World Health Organization recommends the defined daily dose (DDD) as the standard unit of measurement for antibiotic use, but this is not applicable in children. We aimed to assess paediatric antibiotic use in a Norwegian tertiary care hospital using a novel weight-adjusted method. Methods We obtained antibiotic purchase data from the hospital pharmacy and administrative data for all admissions from 2002 to 2009 to the paediatric wards at Oslo University Hospital, Rikshospitalet. Recommended daily doses per 100 kg days (RDDs/kg days) were calculated based on national guidelines for paediatric antibiotic use, length of stay and estimated weight for sex and age using national growth references. Results Total antibiotic use increased significantly from 51.8 to 65.5 RDDs/100 kg days. We found statistically significant annual increases in the consumption of carbapenems (18.0%), third-generation cephalosporins (6.0%) and imidazole derivatives (6.6%) and a considerable difference between total antibiotic use measured in RDDs/100 kg days and DDDs/100 bed days for neonates. Conclusion Weight-adjusted antibiotic use provided a more meaningful description of the quantities of antibiotics consumed than DDDs/100 bed days, particularly for neonates. Total antibiotic use, use of meropenem, third-generation cephalosporins and imidazole derivatives increased significantly despite low prevalence of antibiotic-resistant pathogens.

• Stray-Pedersen, Asbjørg; Backe, Paul Hoff; Sorte, Hanne Sørmo; Mørkrid, Lars; Chokshi, N.Y. & Erichsen, Hans Christian [Show all 39 contributors for this article] (2014). PGM3 mutations cause a congenital disorder of glycosylation with severe immunodeficiency and skeletal dysplasia. American Journal of Human Genetics. ISSN 0002-9297. 95(1), p. 96–107. doi: 10.1016/j.ajhg.2014.05.007. Full text in Research Archive
• Bigorgne, Amélie E.; Farin, Henner F.; Lemoine, Roxane; Mahlaoui, Nizar; Lambert, Nathalie & Gil, Marine [Show all 22 contributors for this article] (2014). TTC7A mutations disrupt intestinal epithelial apicobasal polarity. Journal of Clinical Investigation. ISSN 0021-9738. 124(1), p. 328–337. doi: 10.1172/JCI71471. Full text in Research Archive
• Filip, Charles; Matzen, Per Michael; Aukner, Ragnhild; Moe, Marianne; Høgevold, Hans Erik & Åbyholm, Frank [Show all 8 contributors for this article] (2013). Superiorly Based Pharyngeal Flap for Treatment of Velopharyngeal Insufficiency in Patients With 22q11.2 Deletion Syndrome. The Journal of craniofacial surgery (Print). ISSN 1049-2275. 24(2), p. 501–504. doi: 10.1097/SCS.0b013e31827c84f2. Full text in Research Archive
• Nordgarden, Hilde; Lima, Kari; Skogedal, Nina; Følling, Ivar; Storhaug, Kari & Abrahamsen, Tore G (2012). Dental developmental disturbances in 50 individuals with the 22q11.2 deletion syndrome; relation to medical conditions? Acta Odontologica Scandinavica. ISSN 0001-6357. 70(3), p. 194–201. doi: 10.3109/00016357.2011.629624. Full text in Research Archive
• Lima, Kari; Abrahamsen, Tore G; Wolff, Anette Susanne Bøe; Husebye, Eystein Sverre; Alimohammadi, Mohammad & Kämpe, Olle [Show all 7 contributors for this article] (2011). Hypoparathyroidism and autoimmunity in the 22q11.2 deletion syndrome. European Journal of Endocrinology (EJE). ISSN 0804-4643. 165(2), p. 345–352. doi: 10.1530/EJE-10-1206. Full text in Research Archive
• Warris, A.; Onken, Annette; Gaustad, Peter; Janssen, W; Lee, H van der & Verweij, P. E. [Show all 7 contributors for this article] (2010). Point-of-use filtration method for the prevention of fungal contamination of hospital water. Journal of Hospital Infection. ISSN 0195-6701. 76(1), p. 56–59. doi: 10.1016/j.jhin.2010.03.014. Full text in Research Archive
• Aresvik, Diana; Pettersen, Folf Dagfinn; Abrahamsen, Tore G & Wright, Marianne (2010). 5-Fluorouracil-induced Death of Jurkat T-Cells - A Role for Caspases and MCL-1. Anticancer Research. ISSN 0250-7005. 30(10), p. 3879–3887. Full text in Research Archive
• Lima, Kari; Følling, Ivar; Eiklid, Kristin Louise; Natvig, Solveig & Abrahamsen, Tore G (2010). Age-dependent clinical problems in a Norwegian national survey of patients with the 22q11.2 deletion syndrome. European Journal of Pediatrics. ISSN 0340-6199. 169(8), p. 983–989. doi: 10.1007/s00431-010-1161-3. Full text in Research Archive
• Lima, Kari; Abrahamsen, Tore G; Følling, Ivar; Natvig, Solveig; Ryder, LP & Olaussen, Richard W (2010). Low thymic output in the 22q11.2 deletion syndrome measured by CCR9+CD45RA+T cell counts and T cell receptor rearrangement excision circles. Clinical and Experimental Immunology. ISSN 0009-9104. 161(1), p. 98–107. doi: 10.1111/j.1365-2249.2010.04152.x. Full text in Research Archive
• Lappegård, Knut Tore; Lappegård, KT; Lappegård, Knut Tore; Christiansen, Dorte; Christensen, D & Pharo, Anne [Show all 22 contributors for this article] (2009). Human genetic deficiencies reveal the roles of complement in the inflammatory network: Lessons from nature. Proceedings of the National Academy of Sciences of the United States of America (PNAS). ISSN 0027-8424. 106(37), p. 15861–15866. doi: 10.1073/pnas.0903613106. Full text in Research Archive
• Riise, OR; Handeland, KS; Cvancarova, M; Wathne, KO; Nakstad, Britt & Abrahamsen, Tore G [Show all 8 contributors for this article] (2008). Incidence and characteristics of arthritis in Norwegian children: A population-based study. Pediatrics. ISSN 0031-4005. 121. doi: 10.1542/peds.2007-0291. Full text in Research Archive
• Glosli, H; Stray-Pedersen, A; Brun, AC; Holtmon, LW; Tønjum, Tone & Chapgier, A [Show all 8 contributors for this article] (2008). Infections due to various atypical mycobacteria in a Norwegian multiplex family with dominant interferon-gamma receptor deficiency. Clinical Infectious Diseases. ISSN 1058-4838. 46. doi: 10.1086/525855. Full text in Research Archive
• Abrahamsen, Tore G; Andresen, Stein Erik; Haug, Ola; Lelek, Michaela; Ringertz, Signe H & Berild, Dag [Show all 12 contributors for this article] (2008). A controlled intervention study to improve antibiotic use in a Russian paediatric hospital. International Journal of Antimicrobial Agents. ISSN 0924-8579. 31(5), p. 478–483. doi: 10.1016/j.ijantimicag.2008.01.009. Full text in Research Archive Show summary

  A controlled intervention study was performed in a paediatric hospital in Russia to improve antibiotic use and to see whether improvements persisted. During October–December 2002, clinical and microbiological data, antibiotic use, costs and outcome were recorded at two wards for gastrointestinal infections (GIIs) and two wards for respiratory tract infections (RTIs). Guidelines for diagnosis and treatment of infections were developed and implemented at one ward for GIIs and one ward for RTIs in 2003. The other two wards served as controls. The same data were recorded during the same 3-month periods in 2003 and 2004. At the intervention ward, the percentage of patients with GII who received antibiotics decreased from 94% in 2002 to 41% in 2003, but increased to 73% in 2004. In RTI patients these percentages were 90% in 2002, 53% in 2003 and 83% in 2004. The proportions of patients who received antibiotics in 2004 were still lower than in 2002: risk difference (RD) = 0.217 (P ≤ 0.001) in GIIs and RD = 0.073 (P = 0.013) in RTIs. From 2002 to 2004 there was a decrease in cephalosporin use (P = 0.021) and an increase in penicillin use (P = 0.032) in pneumonia. There was no difference in mortality, duration of fever or duration of hospital stay between the intervention and control wards. Antibiotic use could be halved without compromising the quality of patient care, but 1 year after the intervention the use of antibiotics approached pre-intervention levels. Strategies to sustain the effect of interventions are needed.

• Winn, R.M.; Warris, A; Gaustad, Peter & Abrahamsen, Tore G (2007). The effect of antifungal agents and human monocytes on in vitro galactomannan release by Aspergillus spp. in liquid culture medium. APMIS - Journal of Pathologiy, Microbiology and Immunology. ISSN 0903-4641. 115, p. 1364–1369. Full text in Research Archive
• Stray-Pedersen, Asbjørg; Børresen-Dale, Anne-Lise; Paus, E; Lindman, C.R; Burgers, T. & Abrahamsen, Tore G (2007). Alpha fetoprotein is increasing with age in ataxia–telangiectasia. European journal of paediatric neurology. ISSN 1090-3798. 11(6), p. 375–380. doi: 10.1016/j.ejpn.2007.04.001. Full text in Research Archive Show summary

  The elevated serum alpha fetoprotein (AFP) concentration in ataxia–telangiectasia (A–T) patients has been known for decades, but the individual variation of AFP levels over time has not been studied. We have followed 12 patients (five girls and seven boys) for 1–12 years (mean 5.5 years) measuring in each patient AFP 2–8 (mean 4) times. Serum AFP levels were increased in all patients, mean 168.7 (range 40–373) kU/L, and without significant differences between the patients. There was a significant age related difference in the serum AFP level. A positive linear relationship (r=0.61, p=0.04) could be found between AFP level and age. Albumin levels were within normal range and did not change with age. Four patients had slightly increased aspartate aminotransferase (AST) levels. None of the patients had serological evidence of infectious hepatitis, and none had increased levels of carcinoembryonic antigen. Repeated standardized observations of gait function revealed no major difference in neurological deterioration between our patients. All had classical A–T disease and mainly truncating mutations; 21 out of 24 possible mutations were either frameshift or nonsense. Four were homozygous for the Norwegian ATM founder mutation. No correlation between serum AFP levels and the different ATM genotypes could be found. We conclude that serum AFP is not only elevated, but also is continuously increasing with age in patients with classical A–T disease.

• Klingenberg, Claus; Rønnestad, A; Anderson, A S; Abrahamsen, TG; Zorman, J & Villaruz, A [Show all 10 contributors for this article] (2007). Persistent strains of coagulase-negative staphylococci in a neonatal intensive care unit: virulence factors and invasiveness. Clinical Microbiology and Infection (CMI). ISSN 1198-743X. 13, p. 1100–1111. doi: 10.1111/j.1469-0691.2007.01818.x. Full text in Research Archive
• Abrahamsen, Tore G & Nordal, Helge Jostein (2007). Infeksjoner i nervesystemet. In Gjerstad, Leif; Skjeldal, Ola & Helseth, Eirik (Ed.), Nevrologi og nevrokirurgi (4. utg). Forlaget Vett & Viten AS. ISSN 9788241206283. p. 463–478. Full text in Research Archive
• Lehne, Gustav; Haneberg, Bjørn; Gaustad, Peter; Johansen, Per Wiik; Preus, Hans Ragnar & Abrahamsen, Tore G (2006). Oral administration of a new soluble branched β-1,3-D-glucan is well tolerated and can lead to increased salivary concentrations of immunoglobulin A in healthy volunteers. Clinical and Experimental Immunology. ISSN 0009-9104. 143(1), p. 65–69. doi: 10.1111/j.1365-2249.2005.02962. Full text in Research Archive Show summary

  The soluble branched yeast β-1,3-D-glucan (SBG) belongs to a group of carbohydrate polymers known to exert potent immunomodulatory effects when administered to animals and humans. A new oral solution of SBG has been developed for local application to the oropharyngeal and oesophageal mucosa in order to strengthen the defence mechanisms against microbial and toxic influences. In the present study oral administration of SBG has been investigated primarily for assessment of safety and tolerability in an early phase human pharmacological study (phase I). Eighteen healthy volunteers were included among non-smoking individuals. The study was an open 1 : 1 : 1 dose-escalation safety study consisting of a screening visit, an administration period of 4 days and a follow-up period. Groups of six individuals received SBG 100 mg/day, 200 mg/day or 400 mg/day, respectively, for 4 consecutive days. The dose increase was allowed after a careful review of the safety data of the lower dose group. No drug-related adverse event, including abnormalities in vital signs, was observed. By inspection of the oral cavity only minor mucosal lesions not related to the study medication were seen in seven subjects. Repeated measurements of β-glucan in serum revealed no systemic absorption of the agent following the oral doses of SBG. In saliva, the immunoglobulin A concentration increased significantly for the highest SBG dose employed. SBG was thus safe and well tolerated by healthy volunteers, when given orally

• Ørstavik, Karen Helene; Kristiansen, Marianne; Knudsen, Gun Peggy Strømstad; Storhaug, K; Vege, Åshild & Eiklid, Kristin Louise [Show all 9 contributors for this article] (2006). Novel splicing mutation in the NEMO (IKK-gamma) gene with severe immunodeficiency and heterogeneity of X-chromosome inactivation. American Journal of Medical Genetics. ISSN 0148-7299. 140(1), p. 31–39. doi: 10.1002/ajmg.a.31026. Full text in Research Archive Show summary

  We report on a family with three stillborn males, three affected males who were small for gestational age and died within 8 months, and one male who died at age 5 years. This boy had cone-shaped teeth and oligoodontia. He had serious bacterial infections and inflammatory bowel disease. Mutations in the NF-B essential modulator (NEMO) gene have recently been shown to be the cause of a group of ectodermal dysplasia and immunodeficiency disorders (EDA-ID). Analysis of the NEMO gene revealed a nucleotide change in the consensus sequence of the splicing donor site of exon 6 IVS6 + 5G A(1027 + 5G A), which has not previously been described in EDA-ID. RT-PCR analysis of fibroblast RNA from an aborted affected male fetus demonstrated a skipping of exons 4, 5, and 6 which resulted in a truncated protein of about 35 kDa revealed by NEMO antibody. The skipping of exons 4, 5, and 6 did not affect the ORF of the C-terminal of NEMO encoded by exons 7, 8, 9, and 10, which contains a coiled-coil motif (CC2), a leucin-zipper (LZ), and a zinc finger motif (ZF) sub-domains of NEMO. IB degradation was strongly impaired in the fetal fibroblasts, suggesting an impaired NF-B signaling. One healthy carrier had a completely skewed X-inactivation pattern with the normal X active, whereas the two other carriers had a random X-inactivation pattern. This family may represent a new phenotype within the EDA-ID disorders. From the heterogeneity in X-inactivation phenotype, we conclude that this mutation is not deleterious enough to be lethal for peripheral blood cells

• Wisløff, Torbjørn Fosen; Abrahamsen, Tore G.; Bergsaker, Marianne A Riise; Løvoll, Øistein; Møller, Per & Pedersen, Maren Kristine [Show all 7 contributors for this article] (2006). Cost effectiveness of adding 7-valent pneumococcal conjugate (PCV-7) vaccine to the Norwegian childhood vaccination program. Vaccine. ISSN 0264-410X. 24(29-30), p. 5690–5699. doi: 10.1016/j.vaccine.2006.04.042. Full text in Research Archive
• Abrahamsen, Tore G & Stray-Pedersen, Asbjørg (2006). Medfødt immunsvikt. In Wesenberg, Finn (Eds.), Veileder i generell pediatri. Norsk barnelegeforening (NBF). ISSN 9788280700407. Full text in Research Archive Show summary

  ISBN: 9788280700404, h.

• Wisløff, Torbjørn Fosen; Abrahamsen, Tore G; Bergsaker, Marianne A Riise; Løvoll, Øistein & Kristiansen, Ivar Sønbø (2006). Vaksinering - er det verdt pengene? Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 126, p. 2670–3. Full text in Research Archive
• Stray-Pedersen, Asbjørg; Aaberge, IS; Fruh, Andreas & Abrahamsen, Tore G (2005). Pneumococcal conjugate vaccine followed by pneumococcal polysaccharide vaccine; immunogenicity in patients with ataxia-telangiectasia. Clinical and Experimental Immunology. ISSN 0009-9104. 140(3), p. 507–516. Full text in Research Archive Show summary

  The immunodeficiency in Ataxia-telangiectasia (A-T) is characterised by low T and B cell counts, low levels of IgE, IgA and/or IgG2, and especially low levels of pneumococcal antibodies. The 23-valent pneumococcal polysaccharide vaccine (PPV23) has previously been shown not to be effective in A-T, but these patients are capable of making protective antibodies to other vaccines such as diphtheria and tetanus toxin, promising effect of the seven-valent pneumococcal conjugated vaccine (PCV7). Nine A-T patients and 25 age and sex matched controls were vaccinated with both PCV7 and PPV23, and three A-T patients were vaccinated with PCV7 only. In the A-T patients, no significant increase in pneumococcal antibody levels were observed after the single PCV7, while the subsequent PPV23 vaccination resulted in a significant increase in antibody levels to the PPV23 mix, as well as to serotype 4, 14, 19F and to the geometric mean of serotype 4, 6B, 14, 18C, 19F, 23F which increased from median 0.2 (range 0.1-0.5) microg/mL to 0.6 (0.2-1.5) microg/mL (P= 0.014). Compared to the patients' baseline levels, the vaccinations induced a 1.5- to 7-fold increase in antibodies to the six different serotypes tested. The increases in pneumococcal antibody titres were lower than those observed in the controls (9- to 34-fold increase). The results are valuable in planning the care of A-T patients, using PCV7 to trigger and PPV23 to booster the immune response and possibly prevent severe pneumococcal disease.

• Klingenberg, Claus; Aarag, Elizabeth; Rønnestad, A; Sollid, johanna u ericson; Abrahamsen, TG & Kjeldsen, Gry [Show all 7 contributors for this article] (2005). Coagulase-negative Staphylococcal Sepsis among Neonates: Association between Antibiotic Resistance, Biofilm Formation and the Host Inflammatory Response. The Pediatric Infectious Disease Journal. ISSN 0891-3668. 24, p. 817–822. Full text in Research Archive
• Rønnestad, Arild Erlend; Abrahamsen, Tore G; Medbø, Sverre; Reigstad, Hallvard; Lossius, Kristin & Kaaresen, Per Ivar [Show all 9 contributors for this article] (2005). Septicemia in the First Week of Life in a Norwegian National Cohort of Extremely Premature Infants. Pediatrics. ISSN 0031-4005. 115(3), p. 262–268. Full text in Research Archive Show summary

  OBJECTIVES.: To investigate the incidence, causes, predictors, and outcomes of septicemia in the first week of life in a national cohort of extremely premature infants. METHODS.: A prospective study of survival of all infants with gestational age of <28 weeks or birth weight of <1000 g who were born in Norway in 1999�2000 was performed. Data on the maternal prenatal history, delivery, and neonatal course, including detailed information on episodes of microbiologically verified septicemia, were collected on predefined forms. Septicemia was reported in 2 groups, ie, episodes diagnosed on the day of delivery (ie, very early-onset septicemia [VEOS]) and episodes diagnosed from day 2 to day 7 of life (ie, early-onset septicemia [EOS]). Logistic regression models were used for the selection of variables for predictor analysis in each group. RESULTS.: Of 462 included infants, VEOS occurred for 15 (32.5 per 1000 population) and EOS for 15 (35.5 per 1000 population). The most prevalent bacteria were Escherichia coli in VEOS (n = 9) and staphylococci (coagulase-negative staphylococci and Staphylococcus aureus) (n = 15) in EOS. Case fatality rates were 40% and 13%, respectively. Independent predictive factors for VEOS were clinical chorioamnionitis (odds ratio [OR]: 10.5; 95% confidence interval [CI]: 3.3-33.4) and high maternal age (OR: 1.2; 95% CI: 1.0-1.3), whereas not receiving systemic antibiotic therapy within 2 days of age (OR: 13.6; 95% CI: 3.7-50.2) and receiving nasal continuous positive airway pressure (n-CPAP) support at 24 hours of age (OR: 9.8; 95% CI: 2.5-38.4) independently predicted septicemia after the first day of life. CONCLUSIONS.: Whereas vertically transmitted septicemia was dominated by Gram-negative bacteria, with predictors being exclusively of maternal origin, EOS was dominated by typically nosocomial flora, with n-CPAP treatment at 24 hours of age being a powerful predictor. Early n-CPAP treatment, as opposed to mechanical ventilation, as a powerful predictor of septicemia in the early neonatal period, even with adjustment for early systemic antibiotic treatment, is a new observation among extremely premature infants that warrants additional study. Key Words: early-onset septicemia � neonatal septicemia � population-based study � prospective study � very low birth weight � extreme prematurity � predictor analysis � logistic regression Abbreviations: GA, gestational age � BW, birth weight � n-CPAP, nasal continuous positive airway pressure � VEOS, very early-onset septicemia � EOS, early-onset septicemia � CRIB, Clinical Risk Index for Babies � FSC, forward stepwise conditional � OR, odds ratio � CI, confidence interval � VLBW, very low birth weight � CONS, coagulase-negative staphylococci � IQR, interquartile range

• Rønnestad, Arild Erlend; Abrahamsen, Tore G; Medbø, Sverre; Reigstad, Hallvard; Lossius, Kristin & Kaaresen, Per Ivar [Show all 10 contributors for this article] (2005). Late-Onset Septicemia in a Norwegian National Cohort of Extremely Premature Infants Receiving Very Early Full Human Milk Feeding. Pediatrics. ISSN 0031-4005. 115(3), p. 269–275. Full text in Research Archive Show summary

  OBJECTIVES.: To investigate the occurrence of and risk factors for late-onset septicemia (LOS) in a national cohort of extremely premature infants who received very early full human milk feeding. METHODS.: A prospective study of all infants born in Norway in 1999 and 2000 with gestational age of <28 weeks or birth weight of <1000 g was performed. Extensive clinical information, including data on feeding practices and episodes of septicemia, was collected on predefined forms. LOS was defined as growth of bacteria or fungi in blood cultures in conjunction with clinical symptoms consistent with systemic infection occurring after day 6 of life. Cox regression models, including models allowing for time-dependent covariates, were applied in the analysis of LOS. RESULTS.: Of 464 eligible infants, 462 (99.6%) were enrolled and 405 (87.7%) survived until day 7. LOS was diagnosed for 80 (19.7%). The predominant pathogens were coagulase-negative staphylococci, followed by Candida spp. Case fatality rates associated with septicemia were 10% in general and 43% for Candida spp septicemia. Necrotizing enterocolitis or bowel perforation was diagnosed for 19 infants (4%). Enteral feeding with human milk was initiated within the third day for 98% of patients, and 92% were receiving full enteral feeding (FEF) with human milk within the third week. Both high Clinical Risk Index for Babies scores and an umbilical venous catheter in situ at 7 days of age significantly predicted LOS. However, the overall most influential risk factor for LOS was the number of days without establishment of FEF with human milk, with an adjusted relative risk of 3.7 (2.0�6.9) for LOS if FEF was not established within the second week of life. CONCLUSIONS.: The incidence and case fatality rate of septicemia for this cohort of extremely preterm infants were lower than values in comparable studies. The main difference, compared with other studies, was the feeding practice, and the data suggest that very early FEF with human milk significantly reduces the risk of LOS among extremely premature infants

• Abrahamsen, Tore G & Stray-Pedersen, Asbjørg (2005). Medfødt immunsvikt. In Wesenberg, Finn (Eds.), VEILEDER I AKUTT PEDIATRI. Norsk Barnelegeforening. Full text in Research Archive
• Abrahamsen, Tore G (2005). Feber. Helsenytt for alle. ISSN 0333-2861. Full text in Research Archive Show summary

  Feber er en del av kroppens forsvarssystem. Professor dr.med. Tore G. Abrahamsen ved Rikshospitalet sier at feber i seg selv ikke er farlig. - Den er et tegn på sykdom, og skal gjøre en jobb for at du skal bli frisk igjen, sier han. Oftest får man feber ved at man er rammet av bakterie- eller virusinfeksjon. Fjerner man feberen med febernedsettende medikamenter, kan man faktisk forlenge sykdomsforløpet. Det er også slik at barn tåler feber bedre enn voksne. Abrahamsen anbefaler avkjøling av kroppen på en skånsom måte som den beste egenbehandlingen av feber. Fuktige klær eller senket innetemperatur er gode eksempler. Dessuten bør man drikke mye for å erstatte væsketapet.

• Rønnestad, Arild; Abrahamsen, Tore G.; Medbø, Sverre; Reigstad, Hallvard; Lossius, Kristin & Kaaresen, Per Ivar [Show all 9 contributors for this article] (2005). Late-Onset Septicemia in a Norwegian National Cohort of Extremely Premature Infants Receiving Very Early Full Human Milk Feeding. Pediatrics. ISSN 0031-4005. 115, p. e269–e276. doi: 10.1542/peds.2004-1833. Full text in Research Archive
• Rønnestad, Arild; Abrahamsen, Tore G.; Medbø, Sverre; Reigstad, Hallvard; Lossius, Kristin & Kaaresen, Per Ivar [Show all 9 contributors for this article] (2005). Septicemia in the First Week of Life in a Norwegian National Cohort of Extremely Premature Infants. Pediatrics. ISSN 0031-4005. 115, p. e262–e268. doi: 10.1542/peds.2004-1834. Full text in Research Archive
• Warris, Adilia; Netea, M.G.; Verweij, Paul E.; Gaustad, Peter; Kullberg, Bart Jan & Weemaes, Corry M.R. [Show all 7 contributors for this article] (2005). Cytokine responses and regulation of interferon-gamma release by human mononuclear cells to Aspergillus fumigatus and other filamentous fungi. Medical Mycology. ISSN 1369-3786. 43(7), p. 613–621. doi: 10.1080/13693780500088333. Full text in Research Archive Show summary

  There is substantial evidence that the production of proinflammatory cytokines is important in host resistance to invasive aspergillosis. Knowledge of the host response towards other filamentous fungi is scarce, as most studies have focused on Aspergillus fumigatus. In addition, interferon-gamma (IFNγ) plays a crucial role in the control of invasive aspergillosis, but little is known about the regulation of IFNγ after stimulation of mononuclear cells by A. fumigatus. Cytokine responses to four different Aspergillus spp., Scedosporium prolificans, and a Rhizopusoryzae strain were compared for their ability to induce the release of tumour necrosis factor-alpha (TNFα) and interleukin(IL)-6 by human monocytes. S. prolificans induced significantly more TNFα and IL-6 release compared to A. fumigatus, while the various Aspergillus spp. induce comparable levels of these cytokines. By using specific cytokine inhibitors we were able to show that endogenous IL-1, but not IL-18 and TNFα, was required for IFNγ and IL-10 release upon stimulation with A. fumigatus hyphae, whereas conidia induced IFNγ stimulation is independent of these cytokines.

• Etokebe, Godfrey Essien; Abrahamsen, Tore G; Bogen, Bjarne & Spurkland, Anne (2004). Tumour necrosis factor receptor superfamily member 6 gene mutation detection by denaturing high-performance liquid chromatography. Scandinavian Journal of Immunology. ISSN 0300-9475. 59, p. 496–503. Full text in Research Archive Show summary

  Denaturing high-performance liquid chromatography (DHPLC) was evaluated as a tool for diagnostic screening of polymorphisms in the tumour necrosis factor receptor superfamily member 6 (TNFRSF6) also known as CD95, Apo-1 or Fas gene. Exons 1-9 of the TNFRSF6 gene were amplified from genomic DNA of 38 individuals, of which three were known to carry mutations in the TNFRSF6 gene. The TNFRSF6 gene amplicons were analysed for heterozygosity by DHPLC. Samples that displayed heterozygous variation by DHPLC were further analysed by sequencing. Comparison of DHPLC analysis with sequencing results showed an overall 100% concordance for samples in which heterozygosity was detected by DHPLC. Importantly, DHPLC was in all cases able to demonstrate the presence or absence of mutations in exon 9 encoding the death domain of the TNFRSF6 gene, which have been implied as the most frequent genetic cause of autoimmune lymphoproliferative syndrome. Comparison of DHPLC analysis with sequencing results showed an overall 100% concordance for samples in which heterozygosity was detected by DHPLC. In conclusion, DHPLC is a suitable method for the detection of genetic variation in the TNFRSF6 gene.

• Myhre, Anne Grethe; Stray-Pedersen, Asbjørg; Eide, E; Veimo, D.; Knappskog, P.M. & Abrahamsen, Tore G [Show all 7 contributors for this article] (2004). Chronic mucocutaneous candidiasis and primary hypothyroidism in two families. European Journal of Pediatrics. ISSN 0340-6199. 163(10), p. 604–611. Full text in Research Archive Show summary

  We describe the clinical and immunological features of two families with chronic mucocutaneous candidiasis (CMC) and primary hypothyroidism. Family A includes three siblings with both candidiasis and hypothyroidism and four individuals with hypothyroidism only. Family B includes four members with candidiasis, of whom one (a male child) also had hypothyroidism. All individuals affected with CMC had suffered from oral candidiasis and onychomycosis since infancy. Facial seborrhoic dermatitis, general folliculitis and scaling blepharitis were main manifestations. Hypothyroidism became evident during childhood. No thyroid antibodies were present in the affected siblings in family A, while the male in family B with hypothyroidism had antibodies against thyroid peroxidase at diagnosis. Immunological evaluation revealed intra-individual variations in serum immunoglobulin levels, lymphocyte subsets and proliferative responses, but there were no consistent abnormalities. Vaccine responses were normal. AIRE gene region microsatellite markers did not segregate with disease nor were autoantibodies typical for autoimmune polyendocrine syndrome type 1 detected in the families. Conclusion: The link between hypothyroidism and chronic mucocutaneous candidiasis remains to be identified.

• Stray-Pedersen, Arne; Jonsson, T.; Heiberg, A; Lindman, CR; Widing, E & Aaberge, Ingeborg Aase S. [Show all 8 contributors for this article] (2004). The impact of an early truncating founder ATM mutaion on Immunoglobulins,spesifc antibodies and lymphocyte populations in ataxia-telangiectasia patients and their parents. Clinical and Experimental Immunology. ISSN 0009-9104. p. 179–186. Full text in Research Archive
• Wright, Marianne; Clausen, Hanne K. & Abrahamsen, Tore G (2004). Liver cells respond to Aspergillus fumigatus with an increase in C3 secretion and C3 gene expression as well as an expression increase in TLR2 and TLR4. Immunology Letters. ISSN 0165-2478. 95(1), p. 25–30. Full text in Research Archive Show summary

  Fungal infections by molds like Aspergillus fumigatus are an increasing health problem which can be fatal in immuno-compromised patients. In healthy individuals, these infections are easily eliminated by the innate and acquired immune system. Complement factor 3 (C3) has a key place within the complement cascade and C3 RNA expression can therefore be used to monitor an impending immune response. Employing a liver cell line (HepG2) as a model system, we have examined their responses to A. fumigatus or beta-glucan, a major component of the fungal wall. C3 RNA expression was increased after stimulation with both LPS and A. fumigatus as well as after incubation with beta-glucan, although with different kinetics. C3 protein release into the supernatant followed an inverse bell-shaped curve when cells were incubated with A. fumigatus or beta-glucan while during LPS stimulation, the release was more stable. HepG2 cells also express Toll-like receptors (TLRs) and both for TLR2 and TLR4, an expression increase was found. These data demonstrate that liver cells are able to react specifically to a fungal pathogen without the help of Kupffer cells.

• Stray-Pedersen, Asbjørg; Jónsson, T; Heiberg, Arvid; Lindman, C.R; Widing, Eva & Aaberge, Ingeborg S. [Show all 8 contributors for this article] (2004). The impact of an early truncating founder ATM mutation on immunoglobulins, specific antibodies and lymphocyte populations in atacia-telangiectasia patients and their parents. Clinical and Experimental Immunology. ISSN 0009-9104. 137(1), p. 179–186. doi: 10.1111/j.1365-2249.2004.0249. Full text in Research Archive Show summary

  Eleven Norwegian patients (aged 233 years, seven males and four females) with Ataxia-telangiectasia (A-T) and their parents were investigated. Five of the patients were homozygous for the same ATM mutation, 3245delATCinsTGAT, a Norwegian founder mutation. They had the lowest IgG2 levels; mean (95% confidence interval) 0·23 (0·050·41) g/l versus 0·91 (0·581·26) g/l in the other patients (P = 0·002). Among the 11 A-T patients, six had IgG2 deficiency, six had IgA deficiency (three in combination with IgG2 deficiency) and seven had low/undetectable IgE values. All patients had very low levels of antibodies to Streptococcus pneumoniae 0·9 (0·41·4) U/ml, while normal levels were found in their parents 11·1 (8·713·4) U/ml (P < 0·001). A positive linear relationship between pneumococcal antibodies and IgG2 (r = 0·85, P = 0·001) was found in the patients. Six of 11 had diphtheria antibodies and 7 of 11 tetanus antibodies after childhood vaccinations, while 4 of 7 Hemophilus influenzae type b (Hib) vaccinated patients had protective antibodies. Ten patients had low B cell (CD19+) counts, while six had low T cell (CD3+) counts. Of the T cell subpopulations, 11 had low CD4+ cell counts, six had reduced CD8+ cell counts, and four had an increased portion of double negative (CD3+/CD4-/CD8-) gamma delta T cells. Of the 22 parents (aged 2364 years) 12 were heterozygous for the ATM founder mutation. Abnormalities in immunoglobulin levels and/or lymphocyte subpopulations were also observed in these carriers, with no correlation to a special ATM genotype

• Abrahamsen, Tore G (2003). Infeksjoner i sentralnervesystemet hos barn, Nevrologi og nevrokirurgi (3.utg)fra barn til voksen;undersøkelse, diagnose, behandling. Forlaget Vett & Viten AS. p. 477–479. Full text in Research Archive Show summary

  Omtale fra Forlagsentralen Boken er både en lærebok for medisinstudenter og en fagbok for allmennpraktiserende leger. Den dekker alle områder av nevrologien, den åpner med kapitler om klinisk-nevrologiske undersøkelser, og tar så for seg sykdomstilstander i detalj. Har ordlister og stikkordregister. © FS Informasjonstjenester ISBN: 8241205562

• Farstad, H; Gaustad, Peter; Kristiansen, P. A.; Perminov, G & Abrahamsen, Tore G (2003). Cerebral venous thrombosis and Escherichia coli infection in neonates. Acta Paediatrica Scandinavica. ISSN 0001-656X. 92(2), p. 254–257. Full text in Research Archive Show summary

  AIM: To present a possible association between cerebral venous thrombosis (CVT) and infection with Escherichia coli. METHODS: Four neonates with deep CVT occurring during an E. coli infection are presented. RESULTS: In these patients the thrombotic disease was found by Doppler ultrasonography. The thrombosis involved at least the sagittal sinus and the transverse sinus according to subsequent MRI scans. The E. coli strains did not produce verotoxin or haemolysin. Disseminated intravascular coagulation was not demonstrated. Three patients presented with seizures. At discharge, all of the patients had signs of neurological damage, but two of them have improved significantly since then. None of the patients has had recurrent (venous) thrombosis. CONCLUSION: E. coli infections in neonates may predispose to CVT, a finding that has clinical implications.

• Wathne, Karl-Olaf; Fjaerli, H.O.; Flaegstad, T & Abrahamsen, Tore G (2003). Flere barn bør vaksineres mot pneumokokker! Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 9(123), p. 1198–2000. Full text in Research Archive
• Amundsen, H. F.; Stray-Pedersen, Asbjørg; Tjønnfjord, Geir Erland & Abrahamsen, Tore G (2003). Kronisk neutrolpeni - inndeling og behandling. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 6(123), p. 624–626. Full text in Research Archive
• Amundsen, H. F.; Stray-Pedersen, Asbjørg; Tjønnfjord, Geir Erland & Abrahamsen, Tore G (2003). Pasienter med alvorlig kronisk neutropeni. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 6(123), p. 621–623. Full text in Research Archive
• Warris, A.; Netea, M.G.; Wang, Jacob Edward; Kullberg, B.J.; Gaustad, Peter & Verweij, P. E. [Show all 7 contributors for this article] (2003). Cytokine release in healthy donors and patients with chronic granulomatous disease upon stimulation with Aspergillus fumigatus. Scandinavian Journal of Infectious Diseases. ISSN 0036-5548. 35, p. 482–487. Full text in Research Archive
• Warris, A.; Klaassen, C.H.W; Meis, J.F.G.M.; Ruiter, M.T de; Valk, H.A. de & Abrahamsen, Tore G (2003). Molecular epidemiology of Aspergillus fumigatus isolates recovered from water, air and patients shows two clusters of genetically distinct strains. Journal of Clinical Microbiology. ISSN 0095-1137. 41, p. 4101–4106. Full text in Research Archive

View all works in NVA

• Abrahamsen, Tore G (2019). Helping on call paediatricians to identify acute primary immunodeficiency diseases. Acta Paediatrica. ISSN 0803-5253. 108(12), p. 2127–2128. doi: 10.1111/apa.15000. Full text in Research Archive
• Stray-Pedersen, Asbjørg; Sorte, Hanne Sørmo; Rødningen, Olaug Kristin; Lyle, Robert; Gonzaga-Jauregui, C G & Hanson, C I [Show all 16 contributors for this article] (2012). THE UTILITY OF EXOME SEQUENCING IN PRIMARY IMMUNODEFICIENCY DISEASES AND IMMUNODYSREGULATIVE DISORDERS. Journal of Clinical Immunology. ISSN 0271-9142. 32(Supp. 1), p. 184–185. Full text in Research Archive
• Aresvik, Dina; Pettersen, Folf Dagfinn; Abrahamsen, Tore G & Wright, Marianne (2008). 5-Fluorouracil Induced Cell Death in leukemic T-cell line Jurkat E6. Full text in Research Archive Show summary

  Background: Cytostatics are widely used to treat paediatric cancer with the intension to eliminate cancer cells by apoptosis. 5-Fluorouracil (5-FU) is frequently used in the treatment of malignancies. Previous studies with 5-FU and different cell lines indicate that the pro-apoptotic protein Bax and the tumor suppressor protein p53 are central actors in this process. The acute leukemic T-cell line Jurkat E 6 has mutations in both genes and 5-FU therefore needs to activate alternative death pathways. Previously, we have shown that incubation with 5-FU apparently triggers apoptosis in Jurkat cells in a dose-dependent manner, with a maximal response within 72 hours; death response was attenuated in presence of general caspase inhibitor. Methods: Jurkat T cells were treated with 5-FU for different time periods. Caspase-3 activity and changes in the mitochondrial membrane potential were measured by flow cytometry. Expression PARP and Mcl-1, was examined by Western blot. Results: Flow cytometric analysis showed activation of caspase-3 in a time- and dose-dependent manner. Using Western blot we observed decreasing levels of anti-apoptotic and increasing levels of pro-apoptotic proteins. Treatment with 5-FU induced a breakdown of the mitochondrial membrane potential. Conclusion: We proved that Jurkat T cells, previously thought of being resistant, can indeed be induced to undergo cell death, using adequate doses of 5-FU and over time. The apoptotic pathway induced by 5-FU in this cell line may provide a rational basis for the design of chemotherapy. Those findings may indicate new insight in cancer therapy.

• Aresvik, Dina; Pettersen, Folf Dagfinn; Abrahamsen, Tore G & Wright, Marianne (2008). 5-Fluorouracil Induces Cell Death in Jurkat E6 T cells. Full text in Research Archive
• Andersen, C; Pettersen, Renate Regine; Aresvik, D; Wright, Marianne & Abrahamsen, Tore G (2008). Gliotoxin mediated apoptotic cell death in Jurkat cells. International Journal of Infectious Diseases. ISSN 1201-9712. 12, p. S47–S47. Full text in Research Archive
• Aresvik, Dina; Pettersen, Folf Dagfinn; Abrahamsen, Tore G & Wright, Marianne (2007). 5-Fluorouracil induces Death in Jurkat E6 cells. Full text in Research Archive Show summary

  Chemotherapeutic drugs are widely administrated to treat cancer and may eliminate responsive cells by inducing apoptosis. The thymidylate synthase inhibitor 5-Fluorouracil (5-FU) is frequently used in the treatment of malignancies. Previous studies with different cell lines indicate that the pro-apoptotic protein Bax and the tumor suppressor protein p53 are central actors in this process. The leukemic T-cell line Jurkat E 6 does express transcripts for p53 and Bax but lacks the functional proteins due to mutations. 5-FU may activate alternative death pathways in Jurkat cells. We therefore have initiated studies on the impact of 5-FU on Jurkat cells. Jurkat T cells were treated with increasing doses of 5-FU for different time periods. Staurosporine was included as a positive control. In some experiments, cells were pretreated with a general caspase inhibitor, Z-VAD-FMK. Cell death was analyzed by flow cytometry, after Annexin V-Fluos and propidium iodide staining. Hydroethidine staining was used to determine mitochondrial ROS generation.Gene expression of pro- and anti-apoptotic proteins was examined by real-time PCR. Flow cytometry analysis shows that incubation with 5-FU triggers apoptosis in Jurkat cells. The cells die in a dose-dependent manner and a maximal response was observed within 72 hours. Using a pan-caspase inhibitor Z-VAD-FMK we observed that the death response was attenuated. We also observed increased mitochondrial ROS generation after 48 hours of incubation with 5-FU. Results from real-time PCR suggest that expression of anti-apoptotic proteins is increased. 5-FU induces apoptosis in Jurkat cells in a time- and dose-dependent manner. 5-FU signaling is mediated through caspase dependent and independent pathways. ROS production suggest mitochondrial involvement.

• Lappegård, KT; Christiansen, D; Abrahamsen, Tore G; Salvesen, Bodil; Lambris, JD & Mollnes, TE (2007). Complement is essential for phenotypic shift of leukocytes to a pro-inflammatory and pro-thrombotic state in a whole blood model of sepsis: Evidence from genetically complement-deficient patients. Molecular Immunology. ISSN 0161-5890. 44, p. 3919–3919. Full text in Research Archive
• Lappegård, KT; Christiansen, D; Fadnes, D; Abrahamsen, Tore G; Salvesen, Bodil & Lambris, JD [Show all 7 contributors for this article] (2007). Complement is essential for phenotypic shift of leukocytes to a pro-inflammatory and pro-thrombotic state in a whole blood model of inflammation: Evidence from genetically complement-deficient patients. Full text in Research Archive
• Abrahamsen, Tore G (2007). Livet med Marthe. [Journal]. Kvinner og Klær (KK). Full text in Research Archive Show summary

  Marthe (8) har immunsvikt. Jeg har brukt mye tid på Marthe, sier professor Tore Abrahamsen på Rikshospitalet. Han lover foreldrene at det finnes et svar. Et sted. En gang. Målet er å kunne stille en så nøyaktig diagnose som mulig, aller helst helt ned til det syke genet.

• Aresvik, Dina; Atneosen-Åsegg, Monika; Pettersen, Folf Dagfinn; Abrahamsen, Tore G & Wright, Marianne (2006). The effect of 5-FU om Jurkat E6 cells with respect to bcl-2 family proteins. Full text in Research Archive Show summary

  Programmed cell death or apoptosis is a mechanism that is involved in all aspects of life; including tissue homeostasis, the clearance of damaged cells and the immune defense. The use of chemotherapeutic agents in cancer patients is intended to induce stress and DNA damage in the cancer cells, hopefully leading to cell death. Apoptosis can occur in two ways: either by the extrinsic pathway and direct signaling of membrane death receptors or by the intrinsic path through regulation of bcl-2 family proteins, causing a loss of mitochondria membrane potential, thereby leading to apoptosis. Both paths involve a cascade of activated caspases which lead to DNA fragmentation and apoptosis. DNA damage is often followed by a cell cycle arrest and DNA repair mechanisms, but a substantial dose of chemotherapeutic agents will lead eventually to apoptosis. In addition, cancer cells often become resistant to anticancer drugs. The purpose of this study is to delineate the signal transduction pathway for 5-Fluorouracil (5-FU) in Jurkat E6 cells, a T cell line. 5-FU attacks directly nucleic acids and affects the cell cycle. First we have examined whether Jurkat T cells can be used to establish a model system in which to analyze these effects. We have treated them with 5-FU with increasing doses and time. By using flow-cytometry we have established death curves. We have further analyzed the expression of all possible pro- and anti-apoptotic proteins and verified the most relevant ones by Western blot. So far we observed that bak is present as a multimer after stimulation with Staurosporine and 5-FU.

• Abrahamsen, Tore G (2006). Diagnostikk av sepsis hos nyfødte. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 126(14), p. 1758–1758. Full text in Research Archive Show summary

  Ved nyfødtsepsis kan diagnostikken være vanskelig, og behandling med bredspektret antibiotika blir ofte startet før en infeksjon er verifisert når det foreligger klinisk mistanke. Symptomene er uspesifikke - det kan like gjerne være hypotermi som feber eller pustestopp (apné) som rask pust (takypné) - «Det er noe galt med denne ungen». I ettertid kan det vise seg at det i stedet for infeksjon foreligger for eksempel hjerneblødning. Påvisning av bakteremi hos disse barna begrenses av mengde blod og antall kulturer som det er mulig og forsvarlig å ta. Konvensjonell infeksjonsdiagnostikk, som leukocytter med differensialtelling og CRP i blod, er mål på en akuttfasereaksjon og kan også være forhøyet ved andre tilstander enn infeksjon. Den infeksjonsutløste leukocyttreaksjonen er heller ikke nødvendigvis som forventet. En umoden beinmarg kan hos noen nyfødte vise en ineffektiv granulopoese som gir leukopeni i stedet for leukocytose, muligens fordi beinmargen er «uttømt». Det er derfor ikke vanskelig å forstå at sepsis hos nyfødte gir legene «hodebry».

• Løvoll, Ø.; Wisløff, TF; Abrahamsen, Tore G; Pedersen, M.; Bergsaker, M.A.R. & Møller, P [Show all 7 contributors for this article] (2006). Cost-Effectiveness of Adding 7-Valent Pneumococcal Conjugate (PCV-7) Vaccine to the Norwegian Childhood Vaccination - Impact of Herd Immunity. The International Conference on Emerging Infectious Diseases: Abstracts Book. p. 177–177. Full text in Research Archive
• Klingenberg, Claus; Rønnestad, Arild Erlend; Anderson, Annaliesa; Abrahamsen, Tore G; Flægstad, Trond & Sollid, J.E. (2006). Persistent strains of coagulase negative staphylococci in a neonatal intensive care unit are characterized by high levels of biofilm production and antibiotic resistance. European Society for Pediatric Infectious Diseases, Meeting Abstract Book. Full text in Research Archive Show summary

  Background and aims Coagulase-negative staphylococci (CoNS) are the major cause of nosocomial sepsis in the neonatal intensive care unit (NICU). We wanted to investigate whether persistent CoNS strains possess specific bacterial characteristics compared with sporadic strains. Methods During a 12-year period we obtained 180 CoNS blood culture isolates from 150 neonates at one single NICU. All isolates were typed with pulsed field gel electrophoresis (PFGE). We also performed multi locus sequence typing (MLST) on 90 S. epidermidis isolates. Phenotypic antibiotic susceptibility to a broad range of antibiotics was analyzed with Etest. Virulence genes encoding methicillin and aminoglycoside resistance were detected with PCR. In addition, we analyzed phenotypic biofilm production and genetic determinants for biofilm formation. Results There was a high degree of concurrence between PFGE- and MLST- typing. Four S. epidermidis clusters contained 66 (6 - 9 - 15 - 36) isolates, one S. haemolyticus cluster 14 isolates, and one S. hominis cluster 7 isolates. The other 93 isolates were divided among 62 PFGE-types. S. epidermidis cluster strains were isolated from children with lower birth weight compared with non-clusters strains (1420 g versus 2034 g, p = 0.001). Cluster strains were evenly distributed among isolates causing sepsis and isolates considered as contaminants. Antibiotic resistance rates (methicillin, gentamicin, erythromycin, clindamycin and fusidic acid) and biofilm production were significantly higher among cluster strains compared with non-cluster strains. Conclusions CoNS cluster isolates were characterized by high levels of biofilm production and antibiotic resistance, enabling them to survive and persist in the NICU environment. Persistent strains colonized and invaded the smallest infants who were exposed to more invasive procedures and had longer hospital stay.

• Abrahamsen, Tore G (2005). Alvorlig immunsvikt. Behandlingsresultater i historisk perspektiv. Full text in Research Archive
• Abrahamsen, Tore G (2005). Immunsvikt ved gastrointestinale symptomer. Full text in Research Archive
• Klingenberg, Claus; Aarag, E.; Rønnestad, Arild Erlend; Sollid, J.E.; Abrahamsen, Tore G & Flægstad, Trond (2005). Biofilm forming coagulase-negative Staphylococci are associated with decreased neonatal inflammatory response in late onset sepsis. Full text in Research Archive Show summary

  Background: Coagulase-negative staphylococci (CoNS) are the most prevalent pathogens causing late onset sepsis in neonates. They are often multi-resistant to antibiotics and the ability to form biofilm is considered their main virulence determinant. The relationship between antibiotic resistance, biofilm formation and clinical outcome of CoNS infections is largely unknown. Methods: During a 12-year period we identified 150 neonates having 164 suspected septic episodes with growth of CoNS in blood culture. We examined the relationship between antibiotic resistance, phenotypic biofilm production and genetic determinants for biofilm formation in different CoNS species, and their correlation with neonatal inflammatory response. Results: Eighty-five episodes were defined as true sepsis, and 79 episodes of CoNS growth in blood culture were considered contaminations. Significantly higher prevalences of both phenotypic and genotypic β-lactam and aminoglycoside resistance were seen in invasive isolates compared with contaminants. Sixty-one percent of S. epidermidis isolates produced biofilm compared with 26 % of CoNS non-epidermidis (P < 0.001). As expected there was a strong correlation between the presence of icaD and biofilm production. We observed no difference in phenotypic biofilm production or genetic determinants for biofilm formation between invasive isolates and contaminants. C-reactive protein (CRP) levels as a marker of inflammatory response were higher in CoNS sepsis caused by methicillin and aminoglycoside resistant versus susceptible isolates (P = 0.031). In contrast, there was a significant association between a lower CRP response and biofilm positive isolates (P = 0.018). Antibiotic resistance was significantly correlated with biofilm production in S. epidermidis, but not in other CoNS species. Conclusions: Evasion of the host immune system by biofilm formation seems to be a clinically relevant mechanism in CoNS causing neonatal sepsis. The close contact of bacteria within a biofilm may facilitate horizontal exchange of genetic information. This might explain the high level of multidrug-resistance in biofilm positive S. epidermidis. The impact of antibiotic resistance and virulence determinants on clinical outcome of neonatal CoNS sepsis warrants additional clinical studies.

• Abrahamsen, Tore G (2005). Primær immunsvikt. Full text in Research Archive
• Abrahamsen, Tore G (2005). Foreldre har feberfobi. [Journal]. Aftenposten. Full text in Research Archive Show summary

  Barn trenger noen runder med feber i året. Feberen har en jobb å gjøre. Reduser pillebruken, råder barnelege Tore G. Abrahamsen. Mange foreldre lider av feberhysteri. Litt varme kinn og blanke barneøyne - og de iler til esken med febersenkende medisin. Jo høyere feber, jo sykere er barnet, tenker det bekymrede opphav. Som selvfølgelig vil barnets beste...

• Nordøy, I.; Stray-Pedersen, Asbjørg; Glosli, Heidi; Holtmon, L.; Szpinda, I. & Tønjum, Tone [Show all 8 contributors for this article] (2004). A family with atypical mycobacterial infections. Full text in Research Archive
• Ørstavik, Karen Helene; Kristiansen, Marianne; Knudsen, Gun Peggy Strømstad; Storhaug, K; Vege, Åshild & Eiklid, Kristin [Show all 9 contributors for this article] (2004). Novel splicing mutation in the NEMO (IKK-gamma) gene with impaired IkBa degradation in a family with severe immunodeficiency and both skewed and random X inactivation in female carriers. Full text in Research Archive
• Abrahamsen, Tore G (2004). Feber hos barn - venn eller fiende? Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 124(12), p. 1619–1619. Full text in Research Archive Show summary

  Førskolebarn er hyppig utsatt for sykdom, og om lag halvparten av disse sykdomsepisodene fører til kontakt med lege. Når et barn får feber, er det for foreldrene et konkret tegn på at barnet er sykt. For den moderne familie betyr det at dagsrytmen forandres: Barnet kan ikke gå i barnehagen, og en av foreldrene må være hjemme i stedet for å gå på arbeid. Det er dessuten mye angst knyttet til feber, og mange foreldre og helsepersonell synes å tro at jo høyere feberen er, desto alvorligere er infeksjonen. Hvorfor ikke da gi det syke barnet et febernedsettende legemiddel?

• Stray-Pedersen, Asbjørg; Aaberge, IS & Abrahamsen, Tore G (2004). Ataxia-teleangiectasia and antibody responses to pneumococcal conjugate vaccine plus pneumococcal polysaccharide vaccine. Full text in Research Archive
• Bergsaker, M.A.R.; Aaberge, IS; Abrahamsen, Tore G; Flægstad, Trond; Høiby, E. A. & Løvoll, Ø. [Show all 8 contributors for this article] (2004). Anbefalinger for bruk av konjugert pneumokokkvaksine. Full text in Research Archive
• Sigstad, Hanne Marie Høybråten; Bjerkely, B.; Stray-Pedersen, Asbjørg; Sandersen, Heidi & Abrahamsen, Tore G (2004). Description of daily life for children and adolescents with primary immunodeficiencies (PID) in Norway. Full text in Research Archive
• Berild, Dag; Abrahamsen, Tore G; Andresen, S.; Bjørløw, E. & Ivanova, S. (2004). The effect of a controlled intervention to improve antibiotic use in a Russian Paediatric hospital. Full text in Research Archive
• Warris, A.; Netea, M.G.; Gaustad, Peter; Kullberg, B.J.; Verweij, P. E. & Abrahamsen, Tore G (2003). Aspergillus fumigatus induces Amphotericin A (AmB) tolerance and inhibits AmB induced cytokine release. Full text in Research Archive
• Wright, Marianne; Clausen, H; Mollnes, Tom Eirik & Abrahamsen, Tore G (2003). Aspergillus fumigatus elicits a complement response in a liver cell line (HepG2 cells). Full text in Research Archive
• Stray-Pedersen, Asbjørg; Garred, P; Heggelund, Lars; Holmskow, U; Vermeesch, J. & Abrahamsen, Tore G (2003). A boy with severe pulmonal infectious problems due to NKX2.1 haploinsufficiency and mannan-binding lectin deficiency. Full text in Research Archive
• Abrahamsen, Tore G (2002). Indikasjon for anleggelse av blodkultur hos barn. Full text in Research Archive
• Steen-Johnsen, Jon; Abrahamsen, Tore G & Ørstavik, Karen Helene (2002). Genetisk drama med løsning etter 30 år. Full text in Research Archive
• Myhre, A. G.; Stray-Pedersen, Asbjørg; Eide, Elisabeth; Spangen, S.; Veimo, D. & Knutssøn, C. [Show all 8 contributors for this article] (2002). Chronic mucocutaneous candidiasis and primary hypothyroidism in two Norwegian families. Full text in Research Archive
• Myhre, A. G.; Stray-Pedersen, Asbjørg; Eide, Elisabeth; Spangen, S.; Abrahamsen, Tore G & Husebye, Einar (2002). Primary hypothyroidism and chronic mucocutaneous candidiasis in three siblings. Full text in Research Archive
• Stray-Pedersen, Asbjørg & Abrahamsen, Tore G (2008). Ataxia-telangiectasia and other Primary Immunodeficiency Diseases. Universitetet i Oslo. Full text in Research Archive
• Abrahamsen, Tore G.; Frøland, Stig S.; Sandven, Per & Berge, Magnhild (2007). Terapianbefaling: Behandling av profylakse av invasive soppinfeksjoner. Statens legemiddelverk. Full text in Research Archive
• Abrahamsen, Tore G & Erichsen, Hans Christian (2007). Single Nucleotide Polymorphisms in Genes Encoding Vitamin C Transport Proteins and Inflammatory Cytokines: Risk of Colon Adenoma and Preterm Birth. Universitetet i Oslo. ISSN 9788280726834. Full text in Research Archive Show summary

  Forsker og lege på barneavdelingen på Sykehuset Buskerud HF, Hans Christian Erichsen, har påvist en sammenheng mellom C vitamin og for tidlig fødsel. Prosjektet som ble utført ved National Institutes of Health i USA, er viktig av flere årsaker. For tidlig fødsel, dvs. mer enn tre uker før termin, er en av hovedårsakene til sykehusinnleggelse av spedbarn. Videre er for tidlig fødte barn mer utsatt for mange sykdommer enn barn født til termin. Sykehusinnleggelse og sykdom hos nyfødte medfører en stor belastning for foreldre og barn og er i tillegg også svært ressurskrevende for samfunnet. Det er tidligere påvist en sammenheng mellom lavt inntak av frukt og grønnsaker og for tidlig fødsel. En har antatt at C vitamin spiller en viktig rolle uten at en har kunnet fastslå dette sikkert. I doktoravhandlingen ”Single Nucleotide Polymorphisms in Genes Encoding Vitamin C Transport Proteins and Inflammatory Cytokines: Risk of Colon Adenoma and Preterm Birth” har Erichsen og hans kollegaer kartlagt og analysert to gener som er viktige for C vitamin transport i kroppen. Ved å analysere DNA hos ca. 250 kvinner som fødte for tidlig, og hos ca. 500 kvinner som fødte til termin, kunne en påvise at kvinner med en vanlig variant (hos 30%) av det ene genet, har tre ganger høyere risiko enn andre for å føde for tidlig. Resultatene fra dette forskningsarbeidet knytter for tidlig fødsel direkte til et av genene for C vitamin transport og støtter tidligere forskning som viser at lavt inntak av C vitamin kan øke risikoen for å føde for tidlig. I doktorgradsarbeidet undersøkte en også betydningen av C vitamin transport genene i forhold til risiko for tykktarmskreft. Resultatene kan tyde på at en genvariant er forbundet med redusert risiko for kreftutvikling.

• Rønnestad, Arild Erlend & Abrahamsen, Tore G (2006). Neonatal septicaemia: Epidemiology, diagnostic and therapeutic aspects. Universitetet i Oslo. ISSN 9788280728333. Full text in Research Archive
• Etokebe, Godfrey Essien & Abrahamsen, Tore G (2004). Physical separation of alleles at polymorphic loci. Universitetet i Oslo. Full text in Research Archive

View all works in NVA