Publications by authors named "Harald Aarset"

14 Publications

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A man in his twenties with fever and severe abdominal pain below the right costal margin.

Tidsskr Nor Laegeforen 2020 12 14;140(18). Epub 2020 Dec 14.

Background: Eosinophilic granulomatosis with polyangiitis (EGPA) is a multisystem disorder characterised by chronic rhinosinusitis, asthma, and pronounced peripheral blood eosinophilia. The most commonly involved organ is the lung. However, EGPA can affect any organ system, including the cardiovascular, gastrointestinal, renal, and central nervous systems.

Case Presentation: A previously healthy 24-year-old man was admitted to the hospital with fever and abdominal pain. He was treated with antibiotics due to suspicion of cholangitis, but his general condition did not improve. He was then given corticosteroids 1 mg/kg x 1 for suspected hypereosinophilic syndrome because of peripheral blood eosinophilia. The corticosteroids improved his condition. After a few days, however, he developed headache, paresis and impaired consciousness. CT cerebral venography revealed haemorrhaging secondary to cerebral venous sinus thrombosis. The patient developed brain herniation and died. Autopsy revealed that he suffered from EGPA.

Interpretation: Our patient had an unusual presentation with fever and abdominal pain. After the onset of fever and general symptoms, his vasculitis took an aggressive course. He did not have asthma, sinusitis, or allergies. According to the literature, about 96-100 % of EGPA cases are associated with asthma. Because EGPA is a rare disease, which can have a very serious course, increased knowledge and awareness of the condition is important to achieve early diagnosis and optimal treatment.
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http://dx.doi.org/10.4045/tidsskr.20.0150DOI Listing
December 2020

A Wolf in Sheep's Clothing.

J Anal Toxicol 2019 03;43(2):e7-e8

Department of Clinical Pharmacology, St. Olav University Hospital, Trondheim, Norway.

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http://dx.doi.org/10.1093/jat/bky080DOI Listing
March 2019

Runaway Train: A Leaky Radiosensitive SCID with Skin Lesions and Multiple Lymphomas.

Case Reports Immunol 2018 14;2018:2053716. Epub 2018 May 14.

Department of Hematology, Oslo University Hospital, Oslo, Norway.

The nuclease Artemis is essential for the development of T-cell and B-cell receptors and repair of DNA double-strand breaks, and a loss of expression or function will lead to a radiosensitive severe combined immunodeficiency with no functional T-cells or B-cells (T-B-SCID). Hypomorphic mutations in the gene can lead to a functional, but reduced, T-cell and B-cell repertoire with a more indolent clinical course called "leaky" SCID. Here, we present the case of a young man who had increasingly aggressive lymphoproliferative skin lesions from 2 years of age which developed into multiple EBV+ B-cell lymphomas, where a hypomorphic mutation in the gene was found in a diagnostic race against time using whole exome sequencing. The patient was given a haploidentical stem cell transplant while in remission for his lymphomas and although the initial course was successful, he succumbed to a serious pneumonia 5 months after the transplant. The case underscores the importance of next-generation sequencing in the diagnosis of patients with suspected severe immunodeficiency.
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http://dx.doi.org/10.1155/2018/2053716DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5977007PMC
May 2018

Two Hospitalizations and One Death After Exposure to Ortho-Fluorofentanyl.

J Anal Toxicol 2017 Oct;41(8):708-709

Department of Clinical Pharmacology, St. Olav University Hospital.

Two young males were hospitalized with miosis and respiratory dysfunction after exposure to a white powder obtained from a foreign source by mail. A few days later, one of the males was found dead at his home. A serum sample from one of the hospitalized patients and a blood sample from the deceased contained ortho-fluorofentanyl in concentrations of 2.5 and 2.4 ng/mL, respectively. It was concluded that death was caused by ortho-fluorofentanyl.
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http://dx.doi.org/10.1093/jat/bkx050DOI Listing
October 2017

Sudden Cardiac Death Following Use of the Synthetic Cannabinoid MDMB-CHMICA.

J Anal Toxicol 2016 Jan-Feb;40(1):86-7. Epub 2015 Sep 9.

Department of Clinical Pharmacology, St. Olav University Hospital, Trondheim, Norway Department of Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology, Trondheim, Norway

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http://dx.doi.org/10.1093/jat/bkv110DOI Listing
August 2016

The Norwegian PMS2 founder mutation c.989-1G > T shows high penetrance of microsatellite instable cancers with normal immunohistochemistry.

Hered Cancer Clin Pract 2014 21;12(1):12. Epub 2014 Apr 21.

Department of Pathology and Medical Genetics, St. Olavs University Hospital, Trondheim, Norway ; Department of Laboratory Medicine Children's and Women's Health, Norwegian University of Science and Technology, Trondheim, Norway.

Background: Using immunohistochemistry (IHC) to select cases for mismatch repair (MMR) genetic testing, we failed to identify a large kindred with the deleterious PMS2 mutation c.989-1G > T. The purpose of the study was to examine the sensitivity of IHC and microsatellite instability-analysis (MSI) to identify carriers of the mutation, and to estimate its penetrance and expressions.

Methods: All carriers and obligate carriers of the mutation were identified. All cancer diagnoses were confirmed. IHC and MSI-analysis were performed on available tumours. Penetrances of cancers included in the Amsterdam and the Bethesda Criteria, for MSI-high tumours and MSI-high and low tumours were calculated by the Kaplan-Meier algorithm.

Results: Probability for co-segregation of the mutation and cancers by chance was 0.000004. Fifty-six carriers or obligate carriers were identified. There was normal staining for PMS2 in 15/18 (83.3%) of tumours included in the AMS1/AMS2/Bethesda criteria. MSI-analysis showed that 15/21 (71.4%) of tumours were MSI-high and 4/21 (19.0%) were MSI-low. Penetrance at 70 years was 30.6% for AMS1 cancers (colorectal cancers), 42.8% for AMS2 cancers, 47.2% for Bethesda cancers, 55.6% for MSI-high and MSI-low cancers and 52.2% for MSI-high cancers.

Conclusions: The mutation met class 5 criteria for pathogenicity. IHC was insensitive in detecting tumours caused by the mutation. Penetrance of cancers that displayed MSI was 56% at 70 years. Besides colorectal cancers, the most frequent expressions were carcinoma of the endometrium and breast in females and stomach and prostate in males.
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http://dx.doi.org/10.1186/1897-4287-12-12DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4005455PMC
May 2014

Symptomatic primary (Al) amyloidosis of the stomach and duodenum.

Case Rep Gastrointest Med 2013 25;2013:525439. Epub 2013 Feb 25.

Department of Gastroenterology and Hepatology, St. Olavs Hospital, Prinsesse Kristinas Gate 1, 7006 Trondheim, Norway ; Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Prinsesse Kristinas Gate 1, 7489 Trondheim, Norway.

Primary (AL) amyloidosis of the gastrointestinal tract is relatively rare, and symptomatic amyloidosis of the stomach is even more seldom. We present the case of a patient who was referred to upper endoscopy because of weight loss, nausea, and vomiting. Large areas of intramucosal hemorrhages were seen, and biopsies resulted in profuse bleeding stopped with endoscopic clips. The biopsies showed amyloid depositions and further workup revealed that the patient also had cardiac and neuropathic involvements. The patient started treatment with dexamethasone, melphalan and bortezomib. After treatment was started the nausea and epigastric discomfort improved, and a reduction in the biochemical markers troponin T, NT-proBNP, and M-component was observed. Gastric amyloidosis is rarely seen at upper endoscopy in patients without a previously established diagnosis, but the unusual endoscopic findings and bleeding tendency after biopsy should be kept in mind by gastroenterologists.
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http://dx.doi.org/10.1155/2013/525439DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3596920PMC
March 2013

[A young woman with kidney failure].

Tidsskr Nor Laegeforen 2011 Oct;131(19):1897-9

Avdeling for nyresykdommer, St. Olavs hospital, Norway.

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http://dx.doi.org/10.4045/tidsskr.10.0597DOI Listing
October 2011

High dose chemotherapy with autologous stem cell support for patients with histologically transformed B-cell non-Hodgkin lymphomas. A Norwegian multi centre phase II study.

Br J Haematol 2011 Mar 17;152(5):600-10. Epub 2011 Jan 17.

Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Oslo, Norway.

We present a prospective phase II study of patients with relapse after chemotherapy showing transformation of follicular lymphoma to diffuse large B-cell lymphoma, performed before rituximab was included in standard treatment. Patients in complete (CR) or partial remission (PR) after salvage chemotherapy were eligible for high-dose chemotherapy with autologous stem cell support (HDT). Forty-seven patients from five Norwegian centres were included, of whom 30 (63%) received HDT. Eighteen (60%) achieved CR, seven (23%) PR and five (10%) had progressive disease following HDT. Median follow-up for the surviving patients was 75 months; median progression-free (PFS) and overall survival (OS) were 26 and 47 months, respectively. Median OS for all patients was 43 months, compared to only 10 months for patients not eligible for HDT. Patients receiving CD34(+) enriched/B-cell depleted grafts had inferior PFS and a trend for inferior OS compared to patients receiving non-purged grafts (Log Rank 0·025 and 0·151, respectively). In conclusion, two thirds of patients with transformation of follicular lymphoma were eligible for HDT. The majority of patients achieved CR and a considerable number had prolonged OS. The use of in vitro purged grafts did not result in a survival benefit compared to that of non-purged grafts.
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http://dx.doi.org/10.1111/j.1365-2141.2010.08519.xDOI Listing
March 2011

Current clinical criteria for Lynch syndrome are not sensitive enough to identify MSH6 mutation carriers.

J Med Genet 2010 Sep 28;47(9):579-85. Epub 2010 Jun 28.

Department of Pathology and Medical Genetics, St Olavs University Hospital, Trondheim, Norway.

Background: Reported prevalence, penetrance and expression of deleterious mutations in the mismatch repair (MMR) genes, MLH1, MSH2, MSH6 and PMS2, may reflect differences in the clinical criteria used to select families for DNA testing. The authors have previously reported that clinical criteria are not sensitive enough to identify MMR mutation carriers among incident colorectal cancer cases.

Objective: To describe the sensitivity of the criteria when applied to families with a demonstrated MMR mutation.

Methods: Families with an aggregation of colorectal cancers were examined for deleterious MMR mutations according to the Mallorca guidelines. All families with a detected MMR mutation as of November 2009 were reclassified according to the Amsterdam and Bethesda criteria.

Results: Sixty-nine different DNA variants were identified in a total of 129 families. The original Amsterdam clinical criteria were met by 38%, 12%, 78% and 25% of families with mutations in MSH2, MSH6, MLH1 and PMS2, respectively. Corresponding numbers for the revised Amsterdam criteria were 62%, 48%, 87% and 38%. Similarly, each of the four clinical Bethesda criteria had low sensitivity for identifying MSH6 or PMS2 mutations.

Conclusion: Amsterdam criteria and each of the Bethesda criteria were inadequate for identifying MSH6 mutation-carrying kindreds. MSH6 mutations may be more common than currently assumed, and the penetrance/expression of MSH6 mutations, as derived from families meeting current clinical criteria, may be misleading. To increase detection rate of MMR mutation carriers, all cancers in the Lynch syndrome tumour spectrum should be subjected to immunohistochemical analysis and/or analysis for microsatellite instability.
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http://dx.doi.org/10.1136/jmg.2010.077677DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2976029PMC
September 2010

Overexpression and involvement in migration by the metastasis-associated phosphatase PRL-3 in human myeloma cells.

Blood 2008 Jan 12;111(2):806-15. Epub 2007 Oct 12.

Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, and Department of Immunology and Transfusion Medicine, St Olavs University Hospital, Trondheim, Norway.

Multiple myeloma (MM) is characterized by accumulation and dissemination of malignant plasma cells (PCs) in the bone marrow (BM). Gene expression profiling of 2 MM cell lines (OH-2 and IH-1) indicated that expression of PRL-3, a metastasis-associated tyrosine phosphatase, was induced by several mitogenic cytokines. Cytokine-driven PRL-3 expression could be shown in several myeloma cell lines at both the mRNA and protein levels. There was significantly higher expression of the PRL-3 gene in PCs from patients with monoclonal gammopathy of undetermined significance (MGUS), smoldering myeloma (SMM), and myeloma than in PCs from healthy persons. Among 7 MM subgroups identified by unsupervised hierarchical cluster analysis, PRL-3 gene expression was significantly higher in the 3 groups denoted as "proliferation," "low bone disease," and "MMSET/FGFR3." PRL-3 protein was detected in 18 of 20 BM biopsies from patients with MM. Silencing of the PRL-3 gene by siRNA reduced cell migration in the MM cell line INA-6, but had no detectable effect on proliferation and cell-cycle phase distribution of the cells. In conclusion, PRL-3 is a gene product specifically expressed in malignant plasma cells and may have a role in migration of these cells.
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http://dx.doi.org/10.1182/blood-2007-07-101139DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2200854PMC
January 2008

Monoclonal B-cell hyperplasia and leukocyte imbalance precede development of B-cell malignancies in uracil-DNA glycosylase deficient mice.

DNA Repair (Amst) 2005 Dec 19;4(12):1432-41. Epub 2005 Sep 19.

Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim.

Ung-deficient mice have reduced class switch recombination, skewed somatic hypermutation, lymphatic hyperplasia and a 22-fold increased risk of developing B-cell lymphomas. We find that lymphomas are of follicular (FL) and diffuse large B-cell type (DLBCL). All FLs and 75% of the DLBCLs were monoclonal while 25% were biclonal. Monoclonality was also observed in hyperplasia, and could represent an early stage of lymphoma development. Lymphoid hyperplasia occurs very early in otherwise healthy Ung-deficient mice, observed as a significant increase of splenic B-cells. Furthermore, loss of Ung also causes a significant reduction of T-helper cells, and 50% of the young Ung(-/-) mice investigated have no detectable NK/NKT-cell population in their spleen. The immunological imbalance is confirmed in experiments with spleen cells where the production of the cytokines interferon gamma, interleukin 6 and interleukin 2 is clearly different in wild type and in Ung-deficient mice. This suggests that Ung-proteins, directly or indirectly, have important functions in the immune system, not only in the process of antibody maturation, but also for production and functions of immunologically important cell types. The immunological imbalances shown here in the Ung-deficient mice may be central in the development of lymphomas in a background of generalised lymphoid hyperplasia.
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http://dx.doi.org/10.1016/j.dnarep.2005.08.004DOI Listing
December 2005
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