Tom C Martinsen

St. Olavs Hospital, Nidaros, Sør-Trøndelag, Norway

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Publications (36)194.59 Total impact

  • Ase Riis · Tom C Martinsen · Helge L Waldum · Reidar Fossmark
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    ABSTRACT: Patients with Crohn's disease (CD) may need anti-inflammatory drugs for decades. Anti-TNF-α agents have good efficacy and adverse events similar to placebo in randomized controlled trials (RCTs), but there are still questions about long-term safety and efficacy. In this respect, reports from clinical practice may be useful. We currently report on the clinical experience with infliximab and adalimumab in a single-center cohort of patients with CD. Patients with CD treated with infliximab or adalimumab from 2000 to 2010 were reviewed. Patient and disease characteristics at start, reason for discontinuation, and adverse events were recorded retrospectively. Corticosteroid use, the need for hospitalization, and surgeries before and during anti-TNF-α therapy were recorded. Eighty-three patients had received anti-TNF-α treatment against CD, median treatment duration was 11.4 months (0.2-99.5), and follow-up time 59 months (8-135). Eighteen of 43 patients using corticosteroids at treatment start discontinued corticosteroids during TNF-α therapy. Need for hospitalizations (6.13 vs. 3.28 days/year, p < 0.001) and surgeries (0.56 vs. 0.16 operations/year, p < 0.001) were lower during anti-TNF-α therapy than before treatment. Twenty-six percent discontinued therapy due to adverse events and 26% due to lack or loss of response. Two of four deaths observed during follow-up were believed to be related to anti-TNF-α treatment. Anti-TNF-α therapy was beneficial in many patients with CD, but the majority of patients discontinued treatment during follow-up. Reports from clinical experience with anti-TNF-α treatment may be valuable for clinicians treating patients with CD.
    No preview · Article · Apr 2012 · Scandinavian Journal of Gastroenterology
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    ABSTRACT: We present a case of a gastric neuroendocrine carcinoma in a patient with a history of long-term proton pump inhibitor (PPI) use. A 49-year-old man using PPI for the last 15 years due to gastroesophageal reflux disease developed progressive dysphagia, dyspepsia and weight loss. Upper gastrointestinal endoscopy, endoscopic ultrasonography and abdominal CT diagnosed a malignant tumor localized to a hiatal hernia. Fasting serum chromogranin A and gastrin concentrations were elevated (32 nmol/l and 159 pmol/l, respectively). Helicobacter pylori PCR analysis of antral biopsies was negative. Biopsies from endoscopically normal oxyntic mucosa showed enterochromaffin-like (ECL) cell hyperplasia. Tumor biopsies revealed a poorly differentiated neuroendocrine carcinoma. Sevier-Munger staining, immunohistochemistry and electron microscopy indicated ECL cell as origin of the tumor cells. Concerns have previously been raised about the safety of long-term PPI use due to a possible increased risk of cancer. This case illustrates a patient with a poorly differentiated neuroendocrine carcinoma with ECL cell characteristics probably induced by hypergastrinemia secondary to long-term PPI use.
    No preview · Article · Nov 2011 · Scandinavian Journal of Gastroenterology
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    ABSTRACT: Gastric juice is a unique combination of hydrochloric acid and the proteolytic enzyme pepsin. Its main function is to inactivate ingested microorganisms. Prions cause fatal transmissible degenerative encephalopathies in animals and man. These diseases have attracted attention due to the proposed link between bovine spongiform encephalopathy in cattle and the occurrence of a new variant Creutzfeldt-Jakob disease in humans where the most probable route of transmission is via contaminated food. The role of gastric juice in the protection against these agents is not settled. The aim of this study was to examine if drug-induced gastric hypoacidity increases the susceptibility of prion infection transmitted by the oral route. Forty-six mice (tg338) were given brain homogenates contaminated with scrapie by gastric intubation. Twenty-two of these animals were concomitantly dosed with omeprazole increasing the median gastric pH from 1.2 to 5.3. After 381 days, the animals were sacrificed and all the brains were examined for detection of pathogenic prion proteins by enzyme-linked immunosorbent assay and western blot. Drug-induced decrease in gastric acidity more than doubled the rate (59% vs. 25%, p < 0.035) of brain infection compared to controls with normal gastric acidity at the time of inoculation. Our results demonstrate that the normal gastric juice constitutes a significant defense against prion disease in mice. Thus, gastric hypochlorhydria would be expected to enhance the susceptibility to prion infection by the oral route. This finding may have relevance to the pathogenesis of the new variant Creutzfeldt-Jakob disease and prion diseases in general.
    No preview · Article · Sep 2011 · Scandinavian Journal of Gastroenterology
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    ABSTRACT: Patients with chronic hypergastrinemia due to chronic atrophic gastritis or gastrinomas have an increased risk of developing gastric malignancy, and it has been questioned whether also patients with hypergastrinemia caused by long-term use of acid inhibiting drugs are at risk. Gastric carcinogenesis in humans is affected by numerous factors and progresses slowly over years. When using animal models with the possibility of intervention, a complex process can be dissected by studying the role of hypergastrinemia in carcinogenesis within a relatively short period of time. We have reviewed findings from relevant models where gastric changes in animal models of long-term hypergastrinemia have been investigated. In all species where long-term hypergastrinemia has been induced, there is an increased risk of gastric malignancy. There is evidence that hypergastrinemia is a common causative factor in carcinogenesis in the oxyntic mucosa, while other cofactors may vary in the different models.
    Full-text · Article · Jan 2011 · BioMed Research International
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    Helge L Waldum · Tom C Martinsen · Oyvind Hauso · Gunnar Qvigstad
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    ABSTRACT: Patients with chronic dyspepsia ought to be diagnosed as completely as possible before treatment is given. In addition to upper gastrointestinal endoscopy and determination of HP status, GERD should be excluded. When the outcome of the diagnostic procedures is negative, the diagnosis of NUD may be made. These patients should be given symptomatic treatment resulting in as little disturbance of normal physiology as possible. Owing to the problems related to PPI use, which until now have been underestimated, antacids or histamine-2 blockers should be the first choices. In the long term, this approach, which is correct from a clinical point of view, will also be less expensive.
    Preview · Article · Mar 2010 · Therapeutic Advances in Gastroenterology
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    Tom Martinsen · Ralph Herter · Jan Dybdahl · Helge Waldum

    Preview · Article · Mar 2010 · Tidsskrift for Den norske legeforening
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    ABSTRACT: Neuroendocrine differentiation is often found in gastric carcinomas, but the relevance of these cells in gastric carcinogenesis is debated. We applied immunolabeling at the electron microscopic level to study the ultrastructure of neuroendocrine cells in gastric carcinomas to ensure correct cellular classification of dedifferentiated cells. The immunogold labeling at electron microscopic level was compared with an established sensitive immunohistochemical method using light microscopy. Thirteen human gastric adenocarcinomas of the diffuse type were examined for neuroendocrine differentiation by chromogranin A (CgA) labeling at both the light and electron microscopic level. The ultrastructure of CgA-positive cells was compared with CgA-positive cells from controls. Nine of 13 tumors showed CgA-positive cells both at the light and electron microscopic level. The CgA-positive cells displayed altered ultrastructural features compared with controls. Some of the CgA-positive tumor cells had granules typical for enterochromaffin-like cells. Immunoelectron microscopy seems to provide both significant immunolabeling and sufficient ultrastructure to enhance classification of cells in neoplastic tissue.
    No preview · Article · Sep 2009 · Applied immunohistochemistry & molecular morphology: AIMM / official publication of the Society for Applied Immunohistochemistry

  • No preview · Article · Apr 2009 · Scandinavian Journal of Gastroenterology
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    ABSTRACT: Use of proton-pump inhibitors (PPIs) causes hypergastrinemia, and it is well known that gastrin has a trophic effect on the oxyntic mucosa. Some PPI users develop fundic gland polyps. The purpose of this study was to determine whether patients developing fundic gland polyps have a more pronounced gastric hypoacidity, hypergastrinemia or increased serum chromogranin A (CgA), which is an enterochromaffin-like (ECL) cell marker. Five PPI users who developed multiple fundic gland polyps during PPI use were included in the study. PPI users without fundic gland polyps (n = 6) as well as healthy individuals (n = 6) were used as controls. In PPI users, we measured 24-h gastric pH, serum gastrin and CgA during one day, with standardized meals, whereas only gastrin and CgA were measured in the healthy individuals. Helicobacter pylori status was determined. Gastric pH, serum gastrin and CgA did not differ significantly between PPI users with and those without fundic gland polyps. All patients with fundic gland polyps were H. pylori negative, whereas 4 out of 6 PPI users without fundic gland polyps were H. pylori positive. Fasting CgA levels were elevated in all PPI users, and CgA more than doubled during the day in all groups. Fundic gland polyps induced by PPIs are not related to the level of hypergastrinemia. Serum CgA is markedly affected by meals and should be measured in samples from fasting patients.
    No preview · Article · Feb 2008 · Scandinavian Journal of Gastroenterology
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    ABSTRACT: Neuroendocrine (NE) differentiation is reported in some cases of non-small cell lung cancer (NSCLC). The aim of this study was to evaluate the expression of NE markers in NSCLC using novel sensitive methods. 20 cases of NSCLC were examined using immunohistochemical (IHC) and immunoelectron microscopy (IEM) methods. In addition, circulating levels of the NE markers chromogranin A (CgA) and neuron-specific enolase (NSE) were measured. Using conventional IHC methods, two tumours (10%) showed immunoreactivity for synaptophysin (SYN), one (5%) for Cg and four (20%) for neural cell adhesion molecule (NCAM). Adding the tyramide signal amplification (TSA) technique, the number of immunoreactive tumours for both SYN and CgA increased to five (25%). No increased immunoreactivity was achieved for NCAM. Nine tumours (45%) were immunoreactive for SYN, CgA or NCAM. Using IEM, one of five representative samples that revealed IHC reactivity for CgA showed immunogold labelling of CgA in cytoplasmic vesicles. Elevated levels of circulating CgA or NSE did not correlate with positive IHC findings. In conclusion, using sensitive IHC methods NE differentiation was seen in a greater proportion of NSCLC than previously reported. Sensitive methods may improve our understanding of the tumour biology and represent an important diagnostic tool for future therapeutic modalities.
    No preview · Article · Mar 2007 · Apmis
  • M.Ø. Bendheim · R. Fossmark · H.L. Waldum · T.C. Martinsen
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    ABSTRACT: In a strain of inbred cotton rats, 25-50% of females develop spontaneous gastric hypochlorhydria and hypergastrinemia. Hypergastrinemic animals develop ECL cell derived gastric carcinomas located in the oxyntic mucosa, thus being an interesting animal model for studying the role of gastrin in gastric carcinogenesis. The response to gastric hypoacidity in cotton rats as regards the level of hypergastrinemia is far more pronounced than in the more commonly used laboratory rat. It is unknown whether the pronounced hypergastrinemic response in cotton rats is due to a greater population of G cells or a greater capacity of hormone synthesis in each G cell. The aim of the study was therefore to examine G cell population and ultrastructure in normogastrinemic and hypergastrinemic cotton rats by the use of immunhistochemical methods applied on both light- and electron-microscopy. Five hypergastrinemic vs. five normogastrinemic cotton rats were compared. Cotton rats with gastric hypochlorhydria have a 55-fold increase in serum gastrin levels and a 6-fold increase in G cell number, but this is not accompanied by significant changes in G cell ultrastructure. The lack of ultrastructural changes in these activated G cells indicates that previously reported changes in chronic stimulated G cells are just one of several ways G cells are activated.
    No preview · Article · Jan 2007 · Scandinavian Journal of Laboratory Animal Science
  • H.L. Waldum · T.C. Martinsen
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    ABSTRACT: Tobacco smoking has well-known negative health effects in the lungs (cancer and obstructive lung disease) as well as on the cardiovascular system. In the digestive tract tobacco smoking increases the risk of oral cancers, and does also slightly increase the risk of cancers at other locations, particularly the pancreas and the oesophagus. Use of smokeless tobacco has a slight carcinogenic effect in the mouth, but otherwise the data incriminating smokeless tobacco in the carcinogenesis at other locations of the digestive tract are scares and unconvincing.
    No preview · Article · Jul 2006
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    T C Martinsen · H L Waldum

    Preview · Article · Jul 2006 · Alimentary Pharmacology & Therapeutics
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    ABSTRACT: The lipid-lowering drug ciprofibrate stimulates gastrin-producing cells in the rat stomach without lowering gastric acidity. Although suggested to be a luminal action on antral peroxisome proliferator-activated receptor-alpha (PPAR-alpha), the mechanism is still not fully elucidated. Gastric bypass was surgically prepared in male Sprague-Dawley rats. Gastric-bypassed and sham-operated rats were either given ciprofibrate (50 mg.kg(-1).day(-1) in methocel) or vehicle alone for 7 wk. PPAR-alpha knockout (KO) and wild-type (WT) mice were either given ciprofibrate (500 mg.kg(-1).day(-1) in methocel) or vehicle alone for 2 wk. The concentration of gastrin in blood was analyzed. Antral G cell density and gastrin mRNA abundance were determined by using immunostaining and Northern blot analysis. Ciprofibrate did not raise plasma gastrin or G cell density in gastric-bypassed rats, although the gastrin mRNA level was slightly increased. In contrast, ciprofibrate induced hypergastrinemia, a 50% increase in G cell density, and a threefold increase in gastrin mRNA in sham-operated rats. In PPAR-alpha KO mice, ciprofibrate did not raise G cell density or the gastrin mRNA level. The serum gastrin level was reduced by ciprofibrate. In WT mice, ciprofibrate induced hypergastrinemia, a doubling of G cell density, and a threefold increase in gastrin mRNA. Comparing animals dosed with vehicle only, PPAR-alpha KO mice had higher serum gastrin concentration than WT mice. We conclude that the main effects of ciprofibrate on G cells are mediated from the antrum lumen, and the mechanism is dependent on PPAR-alpha. The results indicate that PPAR-alpha may have a role in the physiological regulation of gastrin release.
    No preview · Article · Jan 2006 · AJP Gastrointestinal and Liver Physiology
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    ABSTRACT: Poorly differentiated neuroendocrine cells can be difficult to recognise. Sensitive methods are needed to label cells that have lost their ultrastructural features and have reduced concentrations of neuroendocrine markers. In gastric neoplasms, enterochromaffin-like cells might dedifferentiate and lose their characteristic granules and secretory vesicles, making detection of such cells increasingly difficult. However, chromogranin A (CgA) immunogold labelling could provide sensitive and specific detection of gastric neuroendocrine cells. We present ultrastructural findings, CgA immunogold labelling as well as conventional immunohistochemical findings of two human enterochromaffin-like cell carcinoids. Electron-dense granules of poorly differentiated cells were less intensely labelled than granules in well-differentiated cells. Granules with atypical shape as well as punctuate granules previously found in neuroendocrine neoplasms were also CgA labelled. The CgA labelling efficacy after antigen retrieval in an alkaline solution was higher after heating in an autoclave at 135 degrees C compared to a microwave at 100 degrees C for both granules and secretory vesicles without significant deterioration of the ultrastructure. In conclusion, the use of CgA immunogold labelling could ensure a specific classification of cells with neuroendocrine granules and be a supplement to immunohistochemical examination of poorly differentiated tumours.
    No preview · Article · Aug 2005 · Apmis
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    ABSTRACT: The role of enterochromaffin-like (ECL) cells in gastric carcinogenesis is not fully understood. Spontaneous tumours developing in hypergastrinemic female cotton rats have an adenocarcinoma phenotype, but numerous cells in the dysplastic mucosa as well as in the carcinomas are positive for neuroendocrine markers. In the present study of female cotton rats with 2 and 8 months' hypergastrinemia, the oxyntic mucosa of the stomach was examined histologically and immunolabelled for histidine decarboxylase (HDC) and pancreastatin, and hyperplastic and neoplastic ECL cells were evaluated by electron microscopy. These animals developed hyperplasia of the oxyntic mucosa in general and of the ECL cells in particular after 2 months and dysplasia and carcinomas after 8 months. The immunoreactivity of the ECL cells in the oxyntic mucosa was increased at 2 months and declined at 8 months. These histological changes were associated with progressive loss of secretory vesicles and granules in ECL cells. We suggest that ECL cells in hypergastrinemic cotton rats dedifferentiate with time and that the gastric carcinomas may develop from ECL cells.
    No preview · Article · Jul 2005 · Apmis
  • Helge L Waldum · Tom Chr Martinsen · Eiliv Brenna

    No preview · Article · Apr 2005 · Gastroenterology
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    Tom C Martinsen · Kåre Bergh · Helge L Waldum
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    ABSTRACT: All vertebrates produce gastric acid. Its main function is inactivation of ingested microorganisms. The majority of microbiological pathogens ingested never reaches the intestine because of the gastric barrier. Although gastric hypochlorhydria is fairly common due to atrophic gastritis, gastric surgery or use of inhibitors of gastric acid secretion, the resulting susceptibility to infection has not been studied extensively. Drug-induced blockade of acid secretion leads to gastrointestinal bacterial overgrowth; the clinical significance of this is still controversial. Gastric acidity is known to protect against non-typhoid salmonellosis and cholera and it is suspected that it protects against several parasitic diseases as giardiasis and strongyloides. There is a lack of studies focusing on the impact of the gastric acidic barrier on viral infections. Concerning prion infections only a single study has been performed, demonstrating a possible role of gastric acidity in the protection against foodborne prion disease in mice. The combination of malnutrition and hypochlorhydria may contribute to the high prevalence of gastrointestinal infections in developing countries. Further studies are needed to evaluate the clinical consequences of impaired gastric acidity with respect to susceptibility to infections.
    Preview · Article · Mar 2005 · Basic & Clinical Pharmacology & Toxicology
  • R Fossmark · T C Martinsen · K E Bakkelund · S Kawase · S H Torp · H L Waldum
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    ABSTRACT: Among inbred female cotton rats (Sigmodon hispidus) 25%-50% of the animals develop spontaneous gastric carcinomas, whereas males have an incidence of less than 1%. The carcinomas are enterochromaffin-like (ECL)-cell derived. Animals with gastric carcinomas also have hypergastrinaemia and gastric hypoacidity, but the mechanism behind the hypoacidity is unknown. Carcinomas have been found in all female cotton rats with spontaneous hypergastrinaemia lasting more than 4 months, and a gastrin receptor antagonist prevents the development of carcinoma. The purpose of the present study was to investigate whether induced hypergastrinaemia in male cotton rats would also result in carcinomas. Hypergastrinaemia was induced by partial corpectomy of male cotton rats, aiming at removal of 80%-90% of the corpus. A control group was sham-operated. All partially corpectomized animals developed persistent hypergastrinaemia. Six months after the operation, 9 out of 13 partially corpectomized animals developed gastric cancer. In the dysplastic mucosa surrounding the tumours there was an increase in chromogranin A immunoreactive cells, where numerous cells also were stained using the Sevier-Munger technique. Tumour tissue also contained cells that were chromogranin A positive and stained by Sevier-Munger. ECL-cell carcinomas can be induced in male cotton rats by partial corpectomy. This supports a previous statement that spontaneous carcinomas in female cotton rats are caused by gastric hypoacidity and hypergastrinaemia. In hypergastrinaemic animals, ECL-cell carcinomas develop independently of gender within a relatively short period of time, and cotton rats therefore represent an interesting model for studying gastric carcinogenesis.
    No preview · Article · Oct 2004 · Scandinavian Journal of Gastroenterology
  • H L Waldum · R Fossmark · I Bakke · T C Martinsen · G Qvigstad

    No preview · Article · Jul 2004 · Scandinavian Journal of Gastroenterology

Publication Stats

462 Citations
194.59 Total Impact Points

Institutions

  • 2008-2012
    • St. Olavs Hospital
      • • Department of Gastroenterology
      • • Department of Medicine
      Nidaros, Sør-Trøndelag, Norway
  • 1996-2011
    • Norwegian University of Science and Technology
      • • Department of Cancer Research and Molecular Medicine
      • • Faculty of Medicine
      Nidaros, Sør-Trøndelag, Norway
  • 2004
    • Lund University
      Lund, Skåne, Sweden
  • 2001
    • University Hospital of North Norway
      Tromsø, Troms, Norway
    • NTNU Samfunnsforskning
      Nidaros, Sør-Trøndelag, Norway