- MD PhD - professor in medicine /pathologyedit
<br><strong><em>Background:</em></strong> Molecular understanding of lung development is crucial for developing therapies and diagnostic tools. Animal models with altered thyroid hormone signaling provide... more
<br><strong><em>Background:</em></strong> Molecular understanding of lung development is crucial for developing therapies and diagnostic tools. Animal models with altered thyroid hormone signaling provide mechanistic insight into thyroid-dependent neonatal lung disease. Repression of Klf2 (Krüppel-like factor 2), a suggested T3 target gene, is associated with disrupted lung development in mice. Klf2 is proposed to be specifically involved in type I pneumocyte differentiation. <b><i>Objectives:</i></b> To explore mechanisms of thyroid-dependent lung disease, we studied developing chicken fetuses with experimentally induced hypothyroidism. <b><i>Methods:</i></b> Morphology and the expression of a panel of molecules linked to Klf2 were assessed using histology, immunohistochemistry, Western blot and qPCR. <b><i>Results:</i></b> Methimazole injections at E14 hampered lung maturation. The effects of methimazole were evident in several tissue compartments, and impacted on both pneumocyte and vascular differentiation, suggesting cellular and molecular pleiotropy. <b><i>Conclusions:</i></b> Concomitant expression changes in a panel of selected microRNAs regulated by Klf2 suggest importance in lung development. These microRNAs may thus represent potential clinical targets and diagnostic and prognostic tools in thyroid-dependent lung disease
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Background: Malaria is one of the most common causes of mortality worldwide. The World Health Organization (WHO) has recently recommended that treatment should be guided by a laboratory diagnosis. The aim of this study is to explore... more
Background: Malaria is one of the most common causes of mortality worldwide. The World Health Organization (WHO) has recently recommended that treatment should be guided by a laboratory diagnosis. The aim of this study is to explore patient and health care factors associated with intravenous antimalarial treatment of malaria test-negative patients at a district hospital in a malaria endemic area. Study design: A cross-sectional study of 91 patients admitted for intravenous antimalarial treatment was done at a district hospital in northern Cameroon in July and August 2010. Socio-cultural and clinical factors were studied in relation to quality blood smear results. Results: Thirty-two per cent of all intravenous antimalarials were administered to patients with a negative malaria test. Test negative patients older than 40 years of age received significantly more often intravenous antimalarials than the youngest patients (OR = 7.9, 95% CI = 1.9-32.4, p = 0.004). Few differential diagnoses were identified in the study population, and patients older than 30 years of age had malaria less often than the youngest patients (OR = 0.3, 95% CI = 0.08-0.9 and OR = 0.09, 95% CI = 0.02-0.4). Conclusion: This study supports previous reports of over-diagnosis and treatment of malaria in endemic areas. The results suggest that differential diagnoses are important, especially in adults with febrile illnesses to ensure the correct diagnosis and treatment. Further studies are needed to explore the findings and to develop strategies to improve the management of malaria and its differential diagnoses.
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We studied 50 patients (36 males and 14 females) with chronic hepatitis C who were admitted consecutively to our medical department during the period 1987-91. Eight patients (16%) had had a blood transfusion, 17 (34%) had used intravenous... more
We studied 50 patients (36 males and 14 females) with chronic hepatitis C who were admitted consecutively to our medical department during the period 1987-91. Eight patients (16%) had had a blood transfusion, 17 (34%) had used intravenous drugs and 25 (50%) were "sporadic cases" with no identifiable risk factor except that at least five had been tattooed. Most of the patients had moderate symptoms, including tiredness and asthenia. Few were jaundiced. A percutaneous liver biopsy was performed in 27 patients and showed chronic persistent hepatitis in 12 of them, chronic active hepatitis in six and cirrhosis in nine. Three patients with cirrhosis died; one from hepatoma, one from an endstage cirrhosis with bleeding and coma hepaticum, and one from septicaemia.
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Staphylococcus lugdunensis is a coagulase-negative Staphylococcus (CoNS), and part of the normal skin flora. The bacterium is an emerging pathogen that, unlike other CoNS, resembles coagulase-positive Staphylococcus aureus infections in... more
Staphylococcus lugdunensis is a coagulase-negative Staphylococcus (CoNS), and part of the normal skin flora. The bacterium is an emerging pathogen that, unlike other CoNS, resembles coagulase-positive Staphylococcus aureus infections in virulence, tissue destruction, and clinical course. We report a fatal case following minor surgery. The frequency of S. lugdunensis infections has probably been underestimated and under-reported in the past as few clinical laboratories routinely identify coagulase-negative Staphylococci.
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BACKGROUND The International Neuroblastoma Pathology Committee, which is comprised of six member pathologists, was convened with the objective of proposing a prognostically significant and biologically relevant classification based on... more
BACKGROUND The International Neuroblastoma Pathology Committee, which is comprised of six member pathologists, was convened with the objective of proposing a prognostically significant and biologically relevant classification based on morphologic features of ...
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Tumour necrosis factor (TNF) is involved in the pathogenesis of several diseases. In mice, human TNF signals only through p55, one of two murine TNF receptors. We here report a study of growth, viability and morphological alterations in... more
Tumour necrosis factor (TNF) is involved in the pathogenesis of several diseases. In mice, human TNF signals only through p55, one of two murine TNF receptors. We here report a study of growth, viability and morphological alterations in transgenic mice expressing a low constitutive and tissue-restricted level of human TNF in vivo. The transgene was expressed solely in T cells. The transgenic mice showed a marked failure to thrive and a rapid cellular depletion in spleen and thymus. Slight fibrosis was seen in most tissues investigated, in addition to immature adipose tissue and irregular lymphocytic areas. Serum levels of hTNF were only slightly increased in the transgenic mice, enough, however, to cause an inflammatory reaction. All the symptoms were abrogated by an inhibitory hTNF antibody, demonstrating the essential role of hTNF in this phenotype. Transgenic mice constitute a multidimensional system allowing observation of disease processes over time in all tissues. The effects of hTNF were seen first and foremost in the lymphoid organs of the transgenic mice, verifying their cells as major targets at low levels of hTNF expression in the T-cell compartments. Chronic, low levels of TNF expression cause profound disturbances in lymphoid tissue development resulting in cachexia and premature death.
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Antenatal corticosteroids and surfactant replacement therapy have dramatically reduced mortality caused by lung disease in premature babies. Knowledge about mechanisms regulating epithelial differentiation of the respiratory membrane is... more
Antenatal corticosteroids and surfactant replacement therapy have dramatically reduced mortality caused by lung disease in premature babies. Knowledge about mechanisms regulating epithelial differentiation of the respiratory membrane is limited, as are effects of pharmacological interventions. The chicken fetus is a valuable model for exploring pharmacological actions on developing organs. However, more precise information about the timing of developmental events in the chicken lung is needed for human correlation. Characterization of morphological development and protein expression in the respiratory membrane of the developing chicken lung to create a platform for pharmacological testing in a human context. Fetal chicken lungs, embryonic days (E) 7-20, were characterized by morphology and protein expression of epithelial differentiation markers. This was compared with publications on the same processes during human lung development. The respiratory membranes of developing chicken and human lungs show basic similarities. In chicken, surfactant protein B is expressed in cuboidal type II epithelial cells from E17. Aquaporin 5 is expressed in the epithelium from E7 and selectively in type I pneumocytes from E17. The type I pneumocyte and endothelial marker, caveolin 1, is expressed in the endothelium from E7 to E20. Despite phylogenetic distance, central aspects of cellular development in the chicken and human lung are similar. The fetal chicken model has important additional advantages to mammalian models, including fetal independence and short incubation, and is thus well suited for in vivo studies of lung maturation relevant to human development.
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BackgroundVisualization of the lesions in the lower genital tract is the mainstay for diagnosis of the four lesions found in female genital schistosomiasis (FGS), but colposcopes are generally not available in low‐resource... more
BackgroundVisualization of the lesions in the lower genital tract is the mainstay for diagnosis of the four lesions found in female genital schistosomiasis (FGS), but colposcopes are generally not available in low‐resource settings.ObjectiveWe sought to review handheld devices that could potentially be used for FGS diagnosis.Search strategyWe searched Medline and Embase 2015–2019 for handheld devices used in cervical cancer screening and FGS diagnosis.Selection criteriaWe excluded studies that did not compare the device to standard‐of‐care colposcopes or histopathology.Main results and conclusionIn 11 studies, four handheld colposcopes, two smartphones, and one compact digital camera were evaluated. Two handheld colposcopes were found to be potentially adequate for FGS diagnosis, namely Gynocular and Mobile ODT. The smartphones and digital camera did not have sufficient magnification to diagnose grainy sandy patches, one of the FGS lesion types. Customized software should be made to...
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To investigate risk factors for stillbirths by cause, using the Causes of Death and Associated Conditions (CODAC) classification system for perinatal deaths. Case-control study. Two university hospitals in Oslo, Norway, January 1990... more
To investigate risk factors for stillbirths by cause, using the Causes of Death and Associated Conditions (CODAC) classification system for perinatal deaths. Case-control study. Two university hospitals in Oslo, Norway, January 1990 through December 2003. Women with stillbirth after 22 gestational weeks (n = 377) and controls with live births (n = 1 215), and a subsample of 105 cases and 262 controls. Socio-demographic, clinical and thrombophilic risk factors for stillbirths were assessed by cause of death in univariate and multivariable logistic regression analyses. Stillbirths were classified according to CODAC based on information from medical records and validated placenta histology. Causes of stillbirths in percentages, prevalence, odds ratios and adjusted odds ratios for potential risk factors. Approximately half of the women (n = 190) had placental and 19.4% (n = 73) unknown cause of stillbirth. Placental-associated conditions were registered in 18% (n = 68) of cases with a non-placental or an unknown cause. Smoking and small-for-gestational age were more prevalent in all causal groups, compared with controls, whereas twin pregnancy, hypertension and diabetes were more prevalent only among women with placental and unknown causes of stillbirth. The F2rs179963 polymorphism and combined thrombophilia were significant risk factors for stillbirth with placental causes and antiphospholipid antibodies for stillbirth with non-placental causes. Two-thirds of all stillbirths (68%) were caused by or associated with placental pathology. Risk factors differed somewhat according to cause, apart from smoking and small-for-gestational age, which were significant risk factors across the causal groups.
Research Interests: Obstetrics, Medicine, Multivariate Analysis, Birth Weight, Norway, and 15 moreGestational diabetes, Pregnancy, Humans, Hypertension, Female, Classification, Adult, Odds ratio, Gestational Age, Case Control Study, Fetal death, Logistic Models, Case Control Studies, Cause of death, and Paediatrics and reproductive medicine
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Research Interests: Pathology, Evidence Based Practice, Atherosclerosis, Medicine, Biopsy, and 15 morePregnancy, Humans, Placenta, Preeclampsia, Female, Clinical Sciences, Adult, Cesarean Section, Suction, Pre Eclampsia, Acute Disease, foam cells, fibrinoid necrosis, Paediatrics and reproductive medicine, and Uterine Artery
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ABSTRACT
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We report on a woman with an Lp(a) lipoprotein level above the 99th centile of the population distribution of concentrations, who at the age of 43 had had deep vein thrombosis causing a pulmonary embolus and whose brother, who also had a... more
We report on a woman with an Lp(a) lipoprotein level above the 99th centile of the population distribution of concentrations, who at the age of 43 had had deep vein thrombosis causing a pulmonary embolus and whose brother, who also had a very high level, had suffered a cerebral infarction at the age of 43. She had given birth to three children, all with very low birth weight, one of whom died when 3 months old. The placentas had been small and ischemic. The concurrence of a very high Lp(a) lipoprotein level, familial thromboembolic disease and recurrent placental ischemia with delivery of children with low birth weight suggests the possibility that a very high Lp(a) lipoprotein concentration may predispose to placental insufficiency, presumably arising from pathological changes in maternal uterine vessels in the placental bed. If confirmed, a very high Lp(a) lipoprotein level may be a factor to consider in women who have repeated pregnancies with placental insufficiency and who give birth to children with low birth weight.
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Background Matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) are considered important both in atherosclerosis and remodeling after acute myocardial infarction (AMI). We aimed to study genetic expression and presence of MMP-2,... more
Background Matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) are considered important both in atherosclerosis and remodeling after acute myocardial infarction (AMI). We aimed to study genetic expression and presence of MMP-2, MMP-9, TIMP-1, TIMP-2 and the extracellular MMP-inducer (EMMPRIN) in coronary thrombi. Circulating levels and genetic expression in circulating leukocytes were also assessed, and relations to degree of myocardial injury measured by troponin T and time from symptom to PCI were explored. Expression of cell markers were also analyzed, indicating relations to cell types. Methods Intracoronary thrombi were aspirated from 33 patients with ST-elevation myocardial infarction (STEMI). Blood samples with Pax-gene tubes were drawn at end of PCI and the next day. RNA was isolated from thrombi and leukocytes, and genes were relatively quantified by RT-PCR. Each thrombus was preserved for histology and immunohistochemistry analyzes. Results Genes coding for the f...
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Background The NLRP3-inflammasome and the IL-6-pathways, i.e. the inflammasome signaling axis, seems to be central mechanisms in the inflammatory response related to myocardial reperfusion injury after revascularization. The beneficial... more
Background The NLRP3-inflammasome and the IL-6-pathways, i.e. the inflammasome signaling axis, seems to be central mechanisms in the inflammatory response related to myocardial reperfusion injury after revascularization. The beneficial results shown by treating MI-patients with canakunimab, an antibody blocking IL1-β, in the CANTOS trial*, and by treatment of NSTEMI patients with the IL6-receptor antagonist tocilizumab**, are looked upon as proof of concept for inflammasome inhibition. Purpose To study whether genes encoding inflammasome-related proteins are present in coronary thrombi and in circulating cells from STEMI patients, and whether these are related to the degree of myocardial injury as measured by troponin T, and time from symptoms to PCI. Methods Intracoronary thrombi were aspirated from 33 patients with STEMI treated with primary PCI. The thrombi were snap-frozen in RNA-later solution for gene expression analyses. Peripheral blood samples with Pax-gene tubes were drawn...
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A case of an accidentally discovered, nonsymptomatic cavernous angioma of the middle ear in a 29-year-old white male Caucasian is presented together with a review of the relevant literature. The lesion is documented with computer... more
A case of an accidentally discovered, nonsymptomatic cavernous angioma of the middle ear in a 29-year-old white male Caucasian is presented together with a review of the relevant literature. The lesion is documented with computer tomography, light microscopy, and immunohistochemistry.
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Background and objectives Severe anaemia is an important cause of mortality in developing countries. However, few studies have explored the use of and possibilities for blood transfusion services. The aims of this study are to explore... more
Background and objectives Severe anaemia is an important cause of mortality in developing countries. However, few studies have explored the use of and possibilities for blood transfusion services. The aims of this study are to explore the use of blood transfusion services at a hospital in sub‐Saharan Africa and to assess the quality of the transfusion services according to WHO guidelines.Materials and methods Patient age, gender, haemoglobin (Hb) level, diagnosis, hospital department and replacement donations were recorded for all blood transfusions administered at a district hospital in Malawi in January 2010. The laboratory equipment and procedures were scored according to WHO guidelines.Results The mean Hb of transfused patients was 4·8 g/dl. Fifty‐seven per cent (59/104) of the transfusions were given to children diagnosed with malaria, and 17% (18/104) were given to pregnant women. During the study period, blood was in stock and available for transfusion within 1 h of requis...
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type of inflammation-induced change in glycosylation for one of these proteins, al-acid glycoprotein (AGP). This regards the induction on A G P of NeuAca2~3Gal f l l~4(Fuca l~3) GlcNAc-R, the determinant for bloodgroup SLe x (sialyl-Lewis... more
type of inflammation-induced change in glycosylation for one of these proteins, al-acid glycoprotein (AGP). This regards the induction on A G P of NeuAca2~3Gal f l l~4(Fuca l~3) GlcNAc-R, the determinant for bloodgroup SLe x (sialyl-Lewis X). Variations in the degree of a l~3-fucosyla t ion (Lewis X) were detected by changes in the affinity of AGP towards Aleuria aurantia lectin (AAL) in crossed affinoimmunoelectrophoresis (CAIE) of patient sera. Five forms of AGP could be distinguished differing in reactivity towards A A L (A0" nonreactive with AAL, A1-A4: reactive with AAL). A strong transient increase in the serum levels of the forms A3 and A4 was detected after laparotomy, severe burning and primary sectio caesarea. A constitutive elevated level of these two forms was detected in sera of patients suffering from rheumatoid arthritis or mammary tumours relative to control sera. The acute-phase-induced increase in fucosylation of AGP, at least partly represented an increased expression of sialyl-Lewis-X determinants on AGP. This was revealed by the staining of AGP with the monoclonal antibody CSLEX-1 on Western blots, after isolation of the various AAL-reactive fractions of AGP from patient sera by immunoaffinity chromatography and fractionation by preparative CAIE with AAL. A direct correlation between the expression of sialylLewis-X groups on AGP, the reactivity with A A L and the degree of fucosylation was established. Because the interaction between leukocytes and inflamed endothelium is mediated via sialylated Lewis-X structures on leukocytes and the endothelial selectin ELAM-1, we postulate that the inflammation-induced increase in the AAL-reactive fractions of A G P represent a physiological feed-back response of the inflammatory reaction.
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Limbal stem cell deficiency can be treated with transplantation of cultured human limbal epithelial cells (LEC). It can be advantageous to produce LEC in centralized labs and thereafter ship them to eye clinics. The present study used... more
Limbal stem cell deficiency can be treated with transplantation of cultured human limbal epithelial cells (LEC). It can be advantageous to produce LEC in centralized labs and thereafter ship them to eye clinics. The present study used transport simulations of LEC to determine if vigorous shaking during transport altered the viability, morphology and phenotype during a 4 day-long storage of LEC with a previously described serum-free storage method. Inserts with LEC cultured on amniotic membranes were sutured to caps inside air-tight containers with generous amounts of 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES)-buffered minimal essential medium (MEM). The containers were distributed among the following testing conditions: 6 hours with full containers, 36 hours with full containers, 36 hours with container three quarters full of medium, and 36 hours with container full of medium containing a shear-protecting agent (Pluronic-F68). Compared to stored, but non-transported ...
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Staphylococcus lugdunensis is a coagulase-negative Staphylococcus (CoNS), and part of the normal skin flora. The bacterium is an emerging pathogen that, unlike other CoNS, resembles coagulase-positive Staphylococcus aureus infections in... more
Staphylococcus lugdunensis is a coagulase-negative Staphylococcus (CoNS), and part of the normal skin flora. The bacterium is an emerging pathogen that, unlike other CoNS, resembles coagulase-positive Staphylococcus aureus infections in virulence, tissue destruction, and clinical course. We report a fatal case following minor surgery. The frequency of S. lugdunensis infections has probably been underestimated and under-reported in the past as few clinical laboratories routinely identify coagulase-negative Staphylococci.
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Ultrasound-guided percutaneous needle biopsy proved to be a reliable and safe method to obtain material for histopathological and immunohistochemical diagnosis prior to treatment in childhood malignancies. A principal tumour... more
Ultrasound-guided percutaneous needle biopsy proved to be a reliable and safe method to obtain material for histopathological and immunohistochemical diagnosis prior to treatment in childhood malignancies. A principal tumour identification could be obtained by a combined morphological and phenotypic examination of 38 small-sized tumour biopsy specimens using a fairly limited panel of immunological reagents, including antibodies to leucocyte common antigen (CD 45), certain B- and T-cell markers, various intermediate filaments (cytokeratin, desmin and vimentin), and neuroblastoma cells (UJ 167.11, A2B5, and UJ 13A; the latter recognizes NCAM). Five undifferentiated neuroblastomas were all positive with the neuroblastoma antibodies but negative for the other markers, including vimentin. The negative reactivity for desmin and vimentin was the major immunohistochemical distinction between neuroblastomas and rhabdomyosarcomas. In addition, limited reactivity with the neuroblastoma antibodies was seen in blastematous parts of Wilms&#39; tumour, duct-like structures in a hepatoblastoma, and in tumour cells in a few undifferentiated myelo- and lympho-proliferative lesions. This study shows the importance of a combined evaluation of morphology and the pattern of immunoreactivity employing multiple markers.
Research Interests: Pathology, Biology, Immunohistochemistry, Medicine, Humans, and 15 moreChild, Rhabdomyosarcoma, Monoclonal Antibodies, Differential Diagnosis, Clinical Sciences, Neuroblastoma, Fluorescent Antibody Technique, Antibody, Hepatoblastoma, Cytokeratin, Vimentin, Keratins, Child preschool, Wilms tumor, and Lymphoproliferative disorders
In order to study the connection between occupation and sinonasal cancer we have reviewed the files and histological sections of 70 patients (24 females and 46 males) treated at the Department of Oto-rhino-laryngology, National Hospital... more
In order to study the connection between occupation and sinonasal cancer we have reviewed the files and histological sections of 70 patients (24 females and 46 males) treated at the Department of Oto-rhino-laryngology, National Hospital of Norway. Detailed information concerning previous occupations was obtained by telephone interviews according to a standardized questionnaire. This pilot study revealed a strong association between wood dust exposure and sinonasal cancer. Of 12 wood dust exposed men, 11 had been exposed exclusively to softwood. While squamous cell carcinoma was the predominant type of cancer in joiners, carpenters and loggers, non-Hodgkin lymphomas appeared to be associated with employment in saw- and planingmill firms. A nationwide case-control study is under preparation for further substantiation of the health hazards connected with exposure to softwood and other possible occupational factors related to sinonasal cancer.
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Tumour necrosis factor (TNF) is involved in the pathogenesis of several diseases. In mice, human TNF signals only through p55, one of two murine TNF receptors. We here report a study of growth, viability and morphological alterations in... more
Tumour necrosis factor (TNF) is involved in the pathogenesis of several diseases. In mice, human TNF signals only through p55, one of two murine TNF receptors. We here report a study of growth, viability and morphological alterations in transgenic mice expressing a low constitutive and tissue-restricted level of human TNF in vivo. The transgene was expressed solely in T cells. The transgenic mice showed a marked failure to thrive and a rapid cellular depletion in spleen and thymus. Slight fibrosis was seen in most tissues investigated, in addition to immature adipose tissue and irregular lymphocytic areas. Serum levels of hTNF were only slightly increased in the transgenic mice, enough, however, to cause an inflammatory reaction. All the symptoms were abrogated by an inhibitory hTNF antibody, demonstrating the essential role of hTNF in this phenotype. Transgenic mice constitute a multidimensional system allowing observation of disease processes over time in all tissues. The effects of hTNF were seen first and foremost in the lymphoid organs of the transgenic mice, verifying their cells as major targets at low levels of hTNF expression in the T-cell compartments. Chronic, low levels of TNF expression cause profound disturbances in lymphoid tissue development resulting in cachexia and premature death.
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The chemokine CXCL13 and its receptor CXCR5 are crucial for lymphocyte trafficking, also in non-lymphatic tissue. Since inflammatory mechanisms have been suggested to play a role in the development of heart failure (HF), we hypothesized... more
The chemokine CXCL13 and its receptor CXCR5 are crucial for lymphocyte trafficking, also in non-lymphatic tissue. Since inflammatory mechanisms have been suggested to play a role in the development of heart failure (HF), we hypothesized that CXCL13/CXCR5 could be involved in this process. We found increased plasma levels of CXCL13 in HF patients corresponding to NYHA class (n=110), accompanied by enhanced mRNA levels of CXCR5 in circulating T cells (14%, p α -MHC (p