Ove Muckadell - Academia.edu (original) (raw)

Papers by Ove Muckadell

BMJ, Sep 13, 2003

Helicobacter pylori is an important risk factor for peptic ulcers. If infection with H pylori is ... more Helicobacter pylori is an important risk factor for peptic ulcers. If infection with H pylori is cured, ulcers associated with H pylori do not recur. An H pylori "test and treat" strategy for patients with peptic ulcers having long term antisecretory treatment has been suggested, in the hope that eradicating H pylori would curtail the rising use of antiulcer drugs. 1 2 We describe the long term effect of eradicating H pylori on the use of antiulcer medication in a population of patients with peptic ulcers.

PLOS ONE, Dec 12, 2019

Background and aim Predicting overt hepatic encephalopathy (OHE) is important because the conditi... more Background and aim Predicting overt hepatic encephalopathy (OHE) is important because the condition is frequent, often requires hospitalization and is potentially preventable. The risk of OHE is related to pre-existing discrete cognitive defects, and for clinical practice it is recommended to apply two different psychometric tests to detect such deficits. We used the continuous reaction time test (CRT) and the portosystemic encephalopathy (PSE) syndrome test and examined their single and combined value for OHE prediction in cirrhosis patients. Patients and methods We studied 130 clinically mentally unimpaired cirrhosis patients by the two tests and followed them for an average of 38.5 months. The CRT measures velocity and stability of motor reaction times to 150 repeated auditory signals. The PSE is a five subset paperand-pencil test battery evaluating cognitive and psychomotor processing, speed and vision-motor coordination. We collected data on episodes of OHE during follow-up. The clinical course was analysed in patient groups according to the outcome of each test and of both tests together. No anti-HE treatment was initiated except for cases with OHE. Results At baseline, the CRT test was abnormal in 74 patients and the PSE in 47. During follow-up 35 patients (27%) experienced 74 OHE events. 23 patients with abnormal CRT experienced OHE (prediction sensitivity 65%). The PSE predicted OHE in 14 patients (prediction PLOS ONE |

Clinical Genetics, 2021

First‐degree relatives (FDRs) of familial pancreatic cancer (FPC) patients have increased risk of... more First‐degree relatives (FDRs) of familial pancreatic cancer (FPC) patients have increased risk of developing pancreatic ductal adenocarcinoma (PDAC). Investigating and understanding the genetic basis for PDAC susceptibility in FPC predisposed families may contribute toward future risk‐assessment and management of high‐risk individuals. Using a Danish cohort of 27 FPC families, we performed whole‐genome sequencing of 61 FDRs of FPC patients focusing on rare genetic variants that may contribute to familial aggregation of PDAC. Statistical analysis was performed using the gnomAD database as external controls. Through analysis of heterozygous premature truncating variants (PTV), we identified cancer‐related genes and cancer‐driver genes harboring multiple germline mutations. Association analysis detected 20 significant genes with false discovery rate, q < 0.05 including: PALD1, LRP1B, COL4A2, CYLC2, ZFYVE9, BRD3, AHDC1, etc. Functional annotation showed that the significant genes wer...

BMC Nephrology, 2018

Background: Liver cirrhosis is characterized by avid sodium retention where the activation of the... more Background: Liver cirrhosis is characterized by avid sodium retention where the activation of the renin angiotensin aldosterone system (RAAS) is considered to be the hallmark of the sodium retaining mechanisms. The direct effect of angiotensin II (ANGII) on the AT-1 receptor in the proximal tubules is partly responsible for the sodium retention. The aim was to estimate the natriuretic and neurohumoral effects of an ANGII receptor antagonist (losartan) in the late phase of the disease in a rat model of liver cirrhosis. Methods: Bile duct ligated (BDL) and sham operated rats received 2 weeks of treatment with losartan 4 mg/kg/day or placebo, given by gastric gavage 5 weeks after surgery. Daily sodium and potassium intakes and renal excretions were measured. Results: The renal sodium excretion decreased in the BDL animals and this was not affected by losartan treatment. At baseline the plasma renin concentration (PRC) was similar in sham and BDL animals, but increased urinary excretion of ANGII and an increase P-Aldosterone was observed in the placebo treated BDL animals. The PRC was more than 150 times higher in the losartan treated BDL animals (p < 0.001) which indicated hemodynamic impairment. Conclusions: Losartan 4 mg/kg/day did not increase renal sodium excretion in this model of liver cirrhosis, although the urinary ANGII excretion was increased. The BDL animals tolerated Losartan poorly, and the treatment induced a 150 times higher PRC.

American Journal of Gastroenterology, 2019

PLOS ONE, 2017

Background Minimal hepatic encephalopathy (MHE) is clinically undetectable and the diagnosis requ... more Background Minimal hepatic encephalopathy (MHE) is clinically undetectable and the diagnosis requires psychometric tests. However, a lack of clarity exists as to whether the tests are in fact able to detect changes in cognition. Aim To examine if the continuous reaction time test (CRT) can detect changes in cognition with anti-HE intervention in patients with cirrhosis and without clinically manifest hepatic encephalopathy (HE). Methods Firstly, we conducted a reproducibility analysis and secondly measured change in CRT induced by anti-HE treatment in a randomized controlled pilot study: We stratified 44 patients with liver cirrhosis and without clinically manifest HE according to a normal (n = 22) or abnormal (n = 22) CRT. Each stratum was then block randomized to receive multimodal anti-HE intervention (lactulose+branched-chain amino acids+rifaximin) or triple placebos for 3 months in a double-blinded fashion. The CRT is a simple PC-based test and the test result, the CRT index (normal threshold > 1.9), describes the patient's stability of alertness during the 10-minute test. Our study outcome was the change in CRT index in each group at study exit. The portosystemic encephalopathy (PSE) test, a paper-and-pencil test battery (normal threshold above-5), was used as a comparator test according to international guidelines. Results The patients with an abnormal CRT index who were randomized to receive the active intervention normalized or improved their CRT index (mean change 0.92 ± 0.29, p = 0.01).

American Journal of Physiology-Gastrointestinal and Liver Physiology, 1997

The role of the cystic fibrosis transmembrane conductance regulator (CFTR) in duodenal alkaline s... more The role of the cystic fibrosis transmembrane conductance regulator (CFTR) in duodenal alkaline secretion has not been directly examined. The aims of this series of experiments were to determine if CFTR mediates basal and stimulated duodenal epithelial HCO3- secretion. Utilizing the cystic fibrosis murine model (cftr(m1UNC)), we compared normal [CFTR(+/+)] littermates (34-46 days old) with CFTR(-/-) animals (34-39 days old). Anesthesia was induced and maintained with intraperitoneal Hypnorm-midazolam. The proximal duodenum (4-7 mm) was cannulated and perfused with 154 mM NaCl. Either forskolin (10(-6)-10(-4) M) or carbachol (10(-6)-10(-3) M) was perfused intraluminally to activate adenosine 3',5'-cyclic monophosphate (cAMP)- and Ca2+-mediated HCO3- secretion, respectively. Effluent volumes were weighed and HCO3- quantitated by back titration. Basal HCO3- secretion was diminished significantly (P < 0.01) in CFTR(-/-)vs. normal CFTR(+/+) mice (2.8 +/- 0.5 vs. 5.3 +/- 0.4 mi...

Scandinavian journal of clinical and laboratory investigation, 2017

Sodium retention in cirrhosis is associated with changes in the renin-angiotensin-aldosterone sys... more Sodium retention in cirrhosis is associated with changes in the renin-angiotensin-aldosterone system (RAAS), the sympathetic nervous system (SNS), and the glomerular filtration rate (GFR). We hypothesized that in cirrhosis the acute reactions of RAAS and SNS to volume expansion are qualitatively intact, but occurring from elevated baseline levels. Acute cardiovascular, neurohumoral and renal responses to central blood volume changes were studied in cirrhotic patients and healthy controls. In patients, baseline plasma renin concentration (PRC) was elevated 5-fold compared to controls (p < .001); it increased during standing (+144%, p < .001) and remained elevated during subsequent sitting (+118%, p < .001). At baseline, plasma angiotensin II (pANGII) was not elevated significantly (14 ± 2 vs. 9 ± 2 pg/mL) in contrast to plasma aldosterone (pAldo, +160%, p < .001). During orthostatic RAAS activation, the rise in pAngII per unit increase in PRC was 0.04 pg AngII/mIU and 0.4...

Gastroenterology, 1988

The effect of secretin at nearly physiologic plasma cpncentrations on the gastric emptying rate o... more The effect of secretin at nearly physiologic plasma cpncentrations on the gastric emptying rate of solid food was studied in 12 healthy men. A ggmTc colloid-lab&led pancake was used as the test meal. The gastric emptying rate was measured during 1 h using a dual-headed ycamera, and was expressed as the half-time of the emptying curve. To prevent etidogenous secretin release, 400 mg of cimetidine was given before the meal. Subjects were studied under three conditions: (1) during infusion of saline; (2) during cdntinuous infusion of secretin, 6.6 pmol/ kg .'h; and (3) during three intermittent lo-min periods of secretin infusion, 7.6 pmol/kg. h during each period. Both continuous and intermittent infusion of secretin increased half-emptying time, by 133% and 55%, respectively. The plasma secretin concentration in condition 1 was 0.6 pM; plateau concentration in condition 2 was 9.8 pM; and integrated mean concentration in condition 3 was 4.8 pM. It is concluded that secretin at approximately physiologic plasma concentrations retards gastric emptying of solid food in humans.

Therapeutic Advances in Gastroenterology, 2016

Background: The use of proton-pump inhibitors (PPIs) has increased over the last decade. The obje... more Background: The use of proton-pump inhibitors (PPIs) has increased over the last decade. The objective of this study was to provide detailed utilization data on PPI use over time, with special emphasis on duration of PPI use and concomitant use of ulcerogenic drugs. Methods: Using the nationwide Danish Prescription Registry, we identified all Danish adults filling a PPI between 2002 and 2014. Using descriptive statistics, we reported (i) the distribution of use between single PPI entities, (ii) the development in incidence and prevalence of use over time, (iii) measures of duration and intensity of treatment, and (iv) the prevalence of use of ulcerogenic drugs among users of PPIs. Results: We identified 1,617,614 adults using PPIs during the study period. The prevalence of PPI use increased fourfold during the study period to 7.4% of all Danish adults in 2014. PPI use showed strong age dependency, reaching more than 20% among those aged at least 80 years. The proportion of users mai...

Journal of Hepatology, 2015

Scandinavian Journal of Gastroenterology, 1986

Elevated concentrations of circulating substance P in patients with liver insufficiency have been... more Elevated concentrations of circulating substance P in patients with liver insufficiency have been ascribed to decreased hepatic degradation. To establish a possible biodegradation of the peptide in liver-intestine and kidneys, the concentration of endogenous immunoreactive substance P was determined in various vascular beds during a right-sided catheterization in 13 subjects without liver insufficiency. All subjects had normal values of circulating substance P, and no significant difference was found between systemic plasma and hepatic venous or renal venous concentrations of substance P. The results indicate that degradation of circulating endogenous substance P in man is not confined to liver-intestine or kidney but may take place in many tissues.