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Biomedical subjects

Helge L Waldum

Publications and source records attributed to Helge L Waldum.

At least 19 recordsLinked to original sources
PubMed2007

Octreotide induces apoptosis in the oxyntic mucosa.

Previous studies show that octreotide LAR causes regression of gastric ECL-cell carcinoids, reducing both number and size of tumours. This study examines the molecular mechanisms behind the antiproliferative effect of octreotide on the oxyntic mucosa. Female rats received octreotide LAR for 21 days. Serum gastrin was measured and tissue samples for RNA extraction and histology collected from the oxyntic mucosa. Affymetrix analysis showed regulated genes related to apoptosis and proliferation, and a large group of regulated growth-related transcription factors. Verification by real time qRT-PCR showed a high degree of consistency to the microarray results. Supporting the molecular results, histomorphometry showed significant decreases in the number of gastric glands, cells per gland and length of glands, and a tendency towards increased apoptosis and decreased proliferation. Thus, octreotide exerts a negative effect on oxyntic mucosal growth, and induces extensive gene expression changes relevant to growth regulation.

Animals↗
PubMed2006

Chronic inhalation of carbon monoxide: effects on the respiratory and cardiovascular system at doses corresponding to tobacco smoking.

Carbon monoxide (CO) is a dangerous poison in high concentrations, but the long-term effects of low doses of CO, as in the gaseous component of tobacco smoke, are not well known. The aims of our study were to evaluate the long-term effects of inhaled CO on the respiratory and cardiovascular system at doses corresponding to tobacco smoking and its effect on tumourigenesis and pulmonary neuroendocrine (NE) cells. Female Wistar rats were exposed to either CO (200 ppm) for 20 h/day (n=51) or air (n=26) for 72 weeks. Carboxyhaemoglobin was 14.7+/-0.3% in CO exposed animals and 0.3+/-0.1% in controls. In the lungs, no signs of pathology similar to that associated with cigarette smoking were observed, and no differences in number of pulmonary NE cells were observed between the groups. Chronic CO inhalation induced a 20% weight increase of the right ventricle (p=0.001) and a 14% weight increase of the left ventricle and interventricular septum (p<0.001). Histological examination of the myocardium did not reveal any signs of scarring. In the aorta and femoral artery, no signs of atherosclerosis were observed in CO exposed rats. No exposure related carcinogenic effects were observed. Spontaneous tumours were identified in 29% of CO exposed animals and in 28% of the controls. Our results suggest that low dose CO exposure is probably not responsible for the respiratory pathology associated with tobacco smoking. The effects on the cardiovascular system seem to involve myocardial hypertrophy, but not atherogenesis.

Animals↗
PubMed2006

A new method for visualization of gut mucosal cells, describing the enterochromaffin cell in the rat gastrointestinal tract.

OBJECTIVE: Enterochromaffin (EC) cells in the gastrointestinal tract have an important function as regulators of secretion, motility and sensation. The EC cell has traditionally been described as bottle-shaped, with basally located stores of serotonin. Stimuli acting on the apical membrane trigger serotonin release, which in turn activates the subepithelial sensory nerve terminals. To better describe the appearance of EC cells, we developed a new method for visualization of mucosal cells. MATERIAL AND METHODS: The stomach, small intestine and large intestine were excised from Sprague-Dawley rats and then fixed in formalin. The organs were everted and filled with pronase solution. Single cells and aggregates of formalin-fixed mucosal cells were collected by scraping the mucosa off the muscularis mucosa. EC cells were visualized by staining for immunoreactivity against serotonin. RESULTS: EC cells with luminal extensions and very long (up to 80 microM) basally located axon-like extensions, sometimes connecting to neuron-like structures, were found. Other EC cells had no or only short and blunt basal extensions. Dividing serotonin-containing EC cells were also seen. CONCLUSIONS: These findings could make an important contribution towards furthering our understanding of EC cell function in gastrointestinal physiology. This new method can also readily be used to give better visualization of the morphology of other mucosal cells.

Animals↗
PubMed2006

Capsule endoscopy in clinical routine in patients with suspected disease of the small intestine: a 2-year prospective study.

OBJECTIVE: Capsule endoscopy is a promising method for examining the small intestine. The study was performed to evaluate the use of capsule endoscopy in clinical routine in patients with suspected disease of the small intestine. MATERIAL AND METHODS: Consecutive patients with clinically suspected disease of the small intestine referred for capsule endoscopy between 1 January 2003 and 31 December 2004 were included in the study. All patients had previously completed a conventional diagnostic work-up with upper and lower endoscopy as well as abdominal CT scan or small-bowel enteroclysis. RESULTS: A total of 167 patients were referred during the time period and 195 procedures were performed. Seventeen (8.7%) of the procedures were unsuccessful, with no visualization of the small bowel. In the remaining procedures the caecum was reached in 83%. The reason for referral was gastrointestinal bleeding (30%), iron-deficiency anaemia (25%), abdominal pain (15%), diarrhoea (13%) and Crohn's disease (12%). Pathology was found in 27% of the patients, with the highest diagnostic yield in patients referred for Crohn's disease (60%) and the lowest yield (4%) in patients referred for abdominal pain. There were no complications, with the exception of one patient referred for Crohn's disease who had transient abdominal pain during the procedure. CONCLUSIONS: Capsule endoscopy is a safe and well-tolerated procedure. In unselected patients with clinically suspected disease of the small intestine, the procedure gives additional information to conventional diagnostic procedures in 27% of patients. Incomplete examination of the small intestine was frequent in our group of patients.

Adolescent↗
PubMed2005

Ciprofibrate stimulates the gastrin-producing cell by acting luminally on antral PPAR-alpha.

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.

Animals↗
PubMed2005

[Mutual evaluation as a method of quality assurance in hospital units].

BACKGROUND: Mutual visit schemes have been used in quality assurance of general practice. We have examined the effect of mutual evaluation in the quality assurance of patient care in hospital units. MATERIAL AND METHODS: Four university hospital units for medical gastroenterology received and performed one visit each. The visits were performed by one doctor and two nurses and lasted two days. The visit resulted in written reports that were first discussed locally and subsequently jointly in connection with a seminar. The evaluation was based on reported experiences, proposed improvements and surveys of patient satisfaction before and after the mutual evaluation process. A method was developed for surveying patient satisfaction with outpatient endoscopy. RESULTS AND INTERPRETATION: The mutual evaluation created enthusiasm, increased understanding and generated many proposals for improvement. Some improvement was observed in patients' satisfaction with the information given. The study suggests that mutual evaluation is a suitable method for quality assurance of patient care in hospital units.

Endoscopy, Gastrointestinal↗
PubMed2005

Molecular characterization of rat gastric mucosal response to potent acid inhibition.

Potent acid inhibition with proton pump inhibitors (PPIs) is widely used in clinical medicine, especially for gastroesophageal reflux disease. PPIs cause profound changes in the intragastric environment with near-neutral pH and increase serum concentration of the gastric secretagogue hormone gastrin. Long-term hypergastrinemia increases mucosal thickness and enterochromaffin-like cell density in gastric corpus mucosa and results in development of gastric carcinoids in experimental animals. Our aim was to study responses to potent acid inhibition by characterizing genome-wide gene expression changes in gastric corpus mucosa in rats dosed with the PPI omeprazole. Nine rats received 400 micromol/kg omeprazole daily for 10 wk. Seven rats received vehicle only. Analysis of gastric corpus with microarrays representing 11,848 genes identified 134 genes with changed gene expression levels in omeprazole-dosed rats. Several of the identified genes were previously known to be affected by potent acid inhibition. Of the 62 genes with known functions that changed gene expression levels after PPI dosing, 27 are known to be involved in proliferation and apoptosis and immune, inflammatory, and stress responses. Our study indicates that microarray analysis can detect relevant gene expression changes in the complex gastric tissue, and that cellular processes involved in cell growth and defense responses are strongly affected by PPI dosing. Many genes are identified that were not previously known to be affected by inhibition of gastric acid secretion or that have unknown biological functions. Characterization of the roles of these genes may give new insight into molecular responses to treatment with PPIs.

Animals↗
PubMed2005

[Capsule endoscopy--a new method for the diagnosis of diseases of the small intestine].

BACKGROUND: Diseases of the small intestine are rare and often difficult to diagnose because of a lack of sensitive methods. A new technique called wireless capsule endoscopy has recently been developed; it allows visualisation of the entire small intestinal surface. MATERIAL AND METHODS: The patient swallows a capsule containing a small digital camera, a battery and a radio transmitter. The capsule takes 2 pictures per second during its passage through the intestines; pictures are transferred by radio signals that are detected by sensors on the abdominal skin, stored on a data recorder and later analysed on a PC. RESULTS: By the end of November 2003 we had performed 80 capsule endoscopies in 69 patients. All patients were referred because of suspected small bowel disease and had been through an extensive diagnostic workup before capsule endoscopy was performed. Most of them were referred because of obscure gastrointestinal bleeding or iron deficiency anaemia. Small bowel pathology was found in one third of the patients. INTERPRETATION: Capsule endoscopy seems to be a major improvement in the diagnosis of small intestinal diseases. It is a non-invasive and painless procedure.

Adult↗
PubMed2005

Antiulcer drugs and gastric cancer.

Inhibitors of gastric acid secretion are efficient drugs in the treatment of acid-related diseases. However, by reducing gastric acidity, hypergastrinemia develops. Gastrin regulates its target cell, the enterochromaffin (ECL) cell, both functionally and tropicaly. Long-term hypergastrinemia in whatever species studied, has been shown to induce tumors originating from the ECL cell. In man, at least 10 years of hypergastrinemia, accompanied by high or reduced gastric acidity is necessary to induce ECL cell carcinoids. There are reports indicating development of ECL cell carcinoids after long-term treatment with proton pump inhibitors. Moreover, the ECL cell may give rise to gastric carcinomas of diffuse type, which have increased during the last decades. Furthermore, most of the carcinomas developing in patients with long-lasting hypergastrinemia are of ECL cell origin. Therefore, long-lasting iatrogenic hypergastrinemia induced by potent inhibitors of acid secretion may be expected to increase the occurrence of gastric carcinomas in the future.

Anti-Ulcer Agents↗
PubMed2005

Octreotide treatment for paraneoplastic intestinal pseudo-obstruction complicating SCLC.

Small cell lung cancer (SCLC) is often associated with paraneoplastic neurological syndromes like intestinal pseudo-obstruction. This syndrome is characterized by dysmotility of the bowel without mechanical obstruction. The pathogenesis of the syndrome is thought to involve autoimmune mechanisms with production of antineuronal antibodies and enteric neuronal degeneration. We report a patient with severe constipation as a clinical presentation of a paraneoplastic intestinal pseudo-obstruction complicating SCLC, who was successfully treated with the somatostatin analogue octreotide. This may be explained by effects of hormone-like substances from the tumor directly inhibiting the gut motility, rather than by autoimmune mechanisms.

Antineoplastic Agents, Hormonal↗
PubMed2005

Dedifferentiation of enterochromaffin-like cells in gastric cancer of hypergastrinemic cotton rats.

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.

Animals↗
PubMed2005

Gastric juice: a barrier against infectious diseases.

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.

Animals↗