Papers by Flemming Bendtsen
Gastroenterology, 2004
Abbreviations used in this paper: rFVIIa, recombinant activated coagulation factor VII; UGIB, upp... more Abbreviations used in this paper: rFVIIa, recombinant activated coagulation factor VII; UGIB, upper gastrointestinal bleeding.
European Journal of Gastroenterology Hepatology, Oct 1, 2010
Randomized controlled trials have shown beneficial effects of vasoactive drugs, endoscopic treatm... more Randomized controlled trials have shown beneficial effects of vasoactive drugs, endoscopic treatment and prophylactic antibiotics on the outcome of bleeding oesophageal varices (BOV). However, translating guidelines based on randomized controlled trials into clinical practice is difficult. Our aims were to compare adherence to evidence-based guidelines in BOV between a specialized unit and a community hospital, and to investigate whether differences in adherence affected the outcome. Two cohorts hospitalized during 2000-2007 with a first episode of BOV were retrospectively enrolled, one in a community hospital comprising 66 patients and one in a specialized unit comprising 111 patients. Data on treatment, rebleeding and mortality were collected from medical records according to the Baveno III/IV Criteria. Treatments in the specialized unit versus the community hospital were: vasoactive drugs 79 vs. 66% (P = 0.06), prophylactic antibiotics 55 vs. 27% (P < 0.01), endoscopic treatment 86 vs. 74% (P= 0.04) and Sengstaken-Blakemore tube was used in 5 vs. 21% (P < 0.01). Secondary prophylaxis with pharmacological, endoscopic or transjugular intrahepatic portosystemic shunt therapy was initiated in 91 vs. 74% (P < 0.01) (specialized vs. community). Six-week mortality was 17 vs. 24% (P = 0.25) with 5-day mortality of 6 vs. 3% (P = 0.34) and mortality day 6-42, 12 vs. 22% (P = 0.07) (specialized vs. community). Failure to control bleeding and failure to prevent rebleeding were not statistically different. Our study shows that patients with BOV are more likely to receive therapy according to guidelines when hospitalized in a specialized unit compared with a community hospital. This however did not affect mortality.
Ugeskrift For Laeger, Sep 1, 2004
International Journal of Pancreatology Official Journal of the International Association of Pancreatology, Jul 1, 1990
To investigate the course of postprandial lipid solubilization in nine patients with chronic, alc... more To investigate the course of postprandial lipid solubilization in nine patients with chronic, alcoholic pancreatitis, luminal contents were aspirated from the proximal part of the jejunum for 180 min after a meal containing 1.5% fat. Six of the patients had pancreatic insufficiency, whereas three patients were without insufficiency. pH was measured continuously at two sites: at the level of the papilla of Vater and the aspiration site. The fraction of bile acids in the micellar phase of the jejunal aspirates correlated positively to both pH in the aspirates (p less than 0.05) and the fraction of fat solubilized (p less than 0.02). pH was below 4.0 for a longer period of time in the patients with insufficiency, compared to the patients without. However, pH fluctuated rapidly, and there was no correlation between the continuously measured values at the aspiration site and values in the aspirates. Lipid solubilization was not correlated to the lipase activity in the aspirates. We conclude that acidic bile acid precipitation most likely plays a dominant role in the pathophysiology of pancreatic steatorrhea although the methods available are too crude to disclose the precise course of events.
Journal of Hepatology, Mar 31, 1990
Clinical Gastroenterology and Hepatology the Official Clinical Practice Journal of the American Gastroenterological Association, Apr 1, 2010
We investigated mortality of patients with chronic pancreatitis (CP), compared with the Danish po... more We investigated mortality of patients with chronic pancreatitis (CP), compared with the Danish population and sought to determine whether clinical presentations of CP can be used in prognosis. We also investigated clinical factors associated with mortality and causes of death among these patients.
Pharmacology Amp Toxicology, Feb 28, 1999
The effects on plasma angiotensin-converting enzyme activity and renin activity of the two long-a... more The effects on plasma angiotensin-converting enzyme activity and renin activity of the two long-acting angiotensin-converting enzyme inhibitors, lisinopril and enalapril, alone and in combination with propranolol were studied. In an open, randomised, cross-over design 12 healthy volunteers received orally enalapril 20 mg alone, enalapril 20 mg in combination with propranolol 80 mg, lisinopril 20 mg alone, and lisinopril 20 mg in combination with propranolol 80 mg. Plasma angiotensin-converting enzyme activity and plasma renin activity were measured for 24 h after each treatment period. Lisinopril and enalapril reduced plasma angiotensin converting enzyme activity substantially and equally at six hr (-70%, P<0.05) and 12 hr (-65%, P<0.05), irrespective of combination with propranolol. At 24 hr plasma angiotensin-converting enzyme activity remained significantly suppressed only after lisinopril (-60%, P<0.05). Plasma renin activity increased almost ten times after ingestion of both angiotensin-converting enzyme inhibitors, but the effect lasted significantly longer after lisinopril than after enalapril. Beta-Adrenergic blockade blunted the effect on the increase in plasma renin activity induced by both angiotensin-converting enzyme inhibitors. Our results show that the effect of lisinopril on plasma angiotensin-converting enzyme activity and plasma renin activity lasted longer than that of enalapril. beta-Adrenergic blockade suppressed the effect on elevated plasma renin activity, but did not influence the effect of angiotensin-converting enzyme inhibitors on plasma angiotensin-converting enzyme activity.
Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver, Jan 17, 2015
Activated hepatic stellate cells synthesize the matrix metalloprotease ADAMTS13, which may be inv... more Activated hepatic stellate cells synthesize the matrix metalloprotease ADAMTS13, which may be involved in the development of liver cirrhosis and portal hypertension. Plasma ADAMTS13 activity has been reported as both increased and decreased in cirrhosis, but ADAMTS13 protein has not previously been examined. To evaluate ADAMTS13 protein in the hepatic circulation and the relation to disease severity, portal pressure, and systemic hemodynamics in cirrhotic patients. Sixty-one cirrhotic patients (Child class: A=22; B=21; C=18) and nine healthy controls underwent a liver vein catheterization with measurement of splanchnic and systemic hemodynamics, and plasma ADAMTS13 protein concentration in a hepatic vein and the femoral artery. ADAMTS13 protein concentrations were increased in cirrhotic patients compared with controls (774ng/ml [IQR: 585-955] vs. 538ng/ml [IQR: 484-631], p<0.03). There were no significant correlations to MELD score, Child Pugh score, portal pressure, nor systemic...
Clinical physiology and functional imaging, Jan 14, 2016
In patients with fluid retention, the plasma clearance of (51) Cr-EDTA (Clexp obtained by multiex... more In patients with fluid retention, the plasma clearance of (51) Cr-EDTA (Clexp obtained by multiexponential fit) may overestimate the glomerular filtration rate (GFR). The present study was undertaken to compare a gamma-variate plasma clearance (Clgv) with the urinary plasma clearance of (51) Cr-EDTA (Clu ) in patients with cirrhosis with and without fluid retention. A total of 81 patients with cirrhosis (22 without fluid retention, 59 with ascites) received a quantitative intravenous injection of (51) Cr-EDTA followed by plasma and quantitative urinary samples for 5 h. Clgv was determined from the injected dose relative to the plasma concentration-time area, obtained by a gamma-variate iterative fit. Clexp and Clu were determined by standard technique. In patients without fluid retention, Clgv , Clexp and Clu were closely similar. The difference between Clgv and Clu (Clgv - Clu = ΔCl) was mean -0·6 ml min(-1) 1·73 m(-2) . In patients with ascites, ΔCl was significantly higher (11·...
Gastroenterology, 1992
Thirteen patients with alcoholic cirrhosis had splanchnic and systemic hemodynamics assessed befo... more Thirteen patients with alcoholic cirrhosis had splanchnic and systemic hemodynamics assessed before and after ingestion of a standard liquid meal of 700 kcal (consisting of isocaloric proteins, lipids, and carbohydrates). Half of the patients (n = 6) were randomized to a treatment group receiving intravenous infusion of propranolol in combination with the meal. No significant effects were observed on systemic hemodynamics after the meal alone. Heart rate (-14%; P less than 0.01) and cardiac index (-24%; P less than 0.01) decreased after meal in combination with propranolol. The mean hepatic venous pressure gradient increased significantly after ingestion of the meal alone with a maximal effect after 30 minutes (+13%; P less than 0.05) and returned to baseline values after 2 hours. Meal in combination with propranolol had no significant effect on the hepatic venous pressure gradient. Hepatic blood flow increased substantially after the meal alone with a maximal effect after 30 minutes (+28%; P less than 0.01), whereas no significant effect was observed after meal in combination with propranolol. Azygos blood flow increased significantly after the meal alone (+36%; P less than 0.05), whereas this effect was abolished in combination with propranolol. In conclusion, ingestion of a peroral mixed meal in cirrhotic patients has, contrary to what is observed in normal controls, no effects on systemic hemodynamics. Substantial changes in splanchnic hemodynamics were observed, and these effects were all abolished when the meal was administered in combination with propranolol.
The aetiology of the reduced systemic vascular resistance and abnormal &#39;filling&#39; ... more The aetiology of the reduced systemic vascular resistance and abnormal &#39;filling&#39; of the vascular bed in cirrhosis is still obscure. As increased concentrations of the potent vasodilator calcitonin gene-related peptide (CGRP) have recently been reported in cirrhosis, we related CGRP to central and peripheral haemodynamics in patients with cirrhosis. Thirty-one cirrhotic patients and six control subjects underwent an investigation with determination of systemic haemodynamics and circulating CGRP. Circulating CGRP was significantly increased in patients with cirrhosis (P &lt; 0.02) and covaried directly with the severity of cirrhosis (P &lt; 0.02). The increased CGRP covaried negatively with the reduced systemic vascular resistance (P &lt; 0.02), the reduced central blood volume (P &lt; 0.01), and reduced central circulation time (P &lt; 0.002) and positively with the non-central blood volume (P &lt; 0.05). These results suggest that increased CGRP may play a role in the systemic vasodilatation in cirrhosis and may contribute to the abnormal distribution of the blood volume, which may lead to abnormal sodium and water handling.
Ugeskrift For Laeger, Sep 1, 2004
Canadian Journal of Gastroenterology Journal Canadien De Gastroenterologie, Feb 1, 2001
Patients with cirrhosis and portal hypertension exhibit characteristic hemodynamic changes with h... more Patients with cirrhosis and portal hypertension exhibit characteristic hemodynamic changes with hyperkinetic systemic circulation, abnormal distribution of blood volume and neurohumoral dysregulation. Their plasma and noncentral blood volumes are increased. Splanchnic vasodilation is of pathogenic significance to the low systemic vascular resistance and abnormal volume distribution of blood, which are important elements in the development of the concomitant cardiac dysfunction, recently termed 'cirrhotic cardiomyopathy'. Systolic and diastolic functions are impaired with direct relation to the degree of liver dysfunction. Significant pathophysiological mechanisms are reduced beta-adrenergic receptor signal transduction, defective cardiac excitation-contraction coupling and conductance abnormalities. Vasodilators such as nitric oxide and calcitonin gene-related peptide are among the candidates in vasodilation and increased arterial compliance. Reflex-induced, enhanced sympathetic nervous system activity, activation of the renin-angiotensin aldosterone system, and elevated circulation vasopressin and endothelin-1 are implicated in hemodynamic counter-regulation in cirrhosis. Recent research has focused on the assertion that the hemodynamic and neurohumoral abnormalities in cirrhosis are part of a general cardiovascular dysfunction, influencing the course of the disease with the reduction of organ function, with sodium and water retention as the outcome. These aspects are relevant to therapy.
Danish Medical Bulletin, 2011
INTRODUCTION: The relevance of needle type and ultrasound guidance in connection with complicatio... more INTRODUCTION: The relevance of needle type and ultrasound guidance in connection with complications and technical problems in paracentesis in cirrhotic patients has only been sparsely described. The aim of this study was to evaluate paracentesis in cirrhotic patients with refractory ascites, focusing on technique, complications, amount of ascites drained and prognosis.MATERIAL AND METHODS: This was a retrospective study based on 51 cirrhotic patients with refractory ascites undergoing paracentesis. A total of 209 paracenteses were performed using a pigtail catheter and an intravenous catheter. Ultrasound-guided puncture or no ultrasound-guided punctured were compared with regard to amount of drained ascites, technical problems and complications both immediate and within a week of the procedure. The impact of coagulopathy was also investigated.RESULTS: 12% immediate and 5% late complications occurred, most of which were minor. No significant differences in the frequency of complications were found when comparing a pigtail to an intravenous catheter (8% versus 21%, OR = 2.81 95% CI (0.86; 9.13)), nor did the amount of drained ascites differ significantly. Ultrasound guidance did not significantly decrease the frequency of complications (7% versus 9%, OR 1.34 95% CI (0.37; 4.84)). Coagulopathy did not significantly affect the risk of complications.CONCLUSION: Paracentesis in patients with cirrhosis is associated with a low frequency of serious complications, regardless of the technique deployed. Although the material is of limited size, it appears that coagulopathy does not increase the risk of complications following this procedure.
Clin Sci, 2000
Leptin, a peptide hormone produced mainly in fat cells, appears to be important for the regulatio... more Leptin, a peptide hormone produced mainly in fat cells, appears to be important for the regulation of metabolism, insulin secretion/sensitivity and body weight. Recently, elevated plasma leptin levels have been reported in patients with arterial hypertension. Because a change in circulating leptin concentrations in such patients could be caused by altered rates of production or disposal, or both, the aim of the present study was to identify regions of leptin overflow into the bloodstream and of leptin extraction. Patients with arterial hypertension (n=12) and normotensive controls (n=20) were studied during catheterization with elective blood sampling from different vascular beds (artery, and renal, hepatic, iliac and cubital veins). Plasma leptin was determined by a radioimmunoassay. Patients with hypertension had significantly elevated levels of circulating leptin (12.8 ng/l, compared with 4.1 ng/l in the controls; P&lt;0.001), and this was also the case when adjusted for body mass index (BMI) [0.435 and 0.167 ng/l per unit BMI (kg/m(2)) respectively; P&lt;0.001]. Circulating leptin was directly related to arterial blood pressure (r=0.38-0.62, P&lt;/=0.05-0.005) and immunoreactive insulin (r=0.51, P&lt;0.62), but not to plasma renin activity. A significant renal extraction ratio for leptin was seen in the hypertensive patients, but this was not significantly lower than that in the controls (0.09 compared with 0. 16; P=0.1). The hypertensive patients had a significantly higher hepatic venous/arterial leptin ratio than the controls (1.02 compared with 0.93; P&lt;0.02), and this ratio was correlated directly with the BMI (r=0.38, P=0.05) and immunoreactive insulin (r=0.43, P&lt;0.05). In both hypertensive patients and controls there was a significant spillover of leptin into the iliac vein, but not into the cubital vein. In conclusion, the high concentration of circulating leptin in patients with arterial hypertension is probably caused by increased release of leptin from abdominal (especially mesenteric and omental) and gluteal adipose tissue stores, and renal extraction is slightly reduced. Leptin kinetics in arterial hypertension require further investigation.
Scandinavian Journal of Gastroenterology, Apr 1, 2005
The clinical-pathological spectrum of fatty liver ranges from simple steatosis to end-stage fibro... more The clinical-pathological spectrum of fatty liver ranges from simple steatosis to end-stage fibrotic liver disease. However, no histological characteristics have been identified that can predict progression from pure steatosis to fibrotic liver disease in non-alcoholic fatty liver disease. The objective of this study was to investigate whether histological characteristics in patients with fatty liver without inflammation could predict mortality or development of cirrhosis. A total of 417 patients had a liver biopsy performed, which showed fatty liver without inflammation. The population consisted of 170 non-alcoholic and 247 alcoholic fatty liver patients. The study cohort was linked through their unique personal identification number to The National Registry of Patients and the nationwide Registry of Causes of Death. Median follow-up time was 19.9 years in the non-alcoholic group and 12.8 years in the alcoholic group. Overall mortality in the non-alcoholic group was not related to morphological findings in the index liver biopsy. Mortality was significantly (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05) higher in alcoholic patients with severe steatosis. One non-alcoholic patient (0.6%) developed cirrhosis versus 54 alcoholic patients (22%) during the follow-up period. In patients with non-alcoholic fatty liver without inflammation, patients at risk for premature death cannot be identified by histological characteristics in the index liver biopsy. Patients with alcoholic fatty liver have a high risk for development of cirrhosis and increased mortality with the severity of steatosis in the index liver biopsy.
The American Journal of Gastroenterology, Sep 1, 2009
Hepatology, 2011
We read with great interest the report by in a recently published issue of Hepatology. They found... more We read with great interest the report by in a recently published issue of Hepatology. They found different rates of hepatitis C virus (HCV) genotype distribution with respect to an interleukin-28B variant in Spanish individuals. The authors noted that the rs12979860 wild CC genotype, an independent predictor favoring a sustained virological response to peginterferon/ribavirin, was overrepresented among patients with a non-1 HCV genotype (HCV-non-1) versus hepatitis C virus genotype 1 (HCV-1)-infected patients (66.7% versus 39.1%, P < 0.001). However, the results require confirmation in a larger cohort and especially in Asian populations, in which HCV-non-1 is much more prevalent. To clarify the issue, we analyzed a large cohort in southern Taiwan, in which HCV infections are endemic 2 ; more than 40% of the patients were infected with HCV-2. 3 In all, 1005 patients were tested for associations between HCV characteristics and host genetic variants of rs8099917, a novel single nucleotide polymorphism that has a tremendous impact on the response to interferon-based therapy. For patients of Asian ethnicity, the carriage of the rs8099917 TT genotype could enhance the treatment outcomes of HCV-1 infection 4 and improve the early viral kinetics of HCV-2 infection. 5 With respect to the viral genotypes, 552 of the patients (54.9%) were infected with HCV-1, and 453 patients (45.1%) were infected with HCV-non-1 (43.4% with HCV-2, 0.1% with HCV-3, and 1.6% with an unclassified genotype). When patients were stratified according to their rs8099917 genotypes (TT versus TG/GG), the TT genotype was overrepresented among HCV-non-1-infected patients versus HCV-1 patients (91.4% versus 85.0%, P ¼ 0.002; . Multivariate logistic regression analysis demonstrated that HCV-1 infection and baseline HCV RNA levels were independent factors negatively associated with the carriage of the rs8099917 TT genotype with odds ratios of 0.58 (95% confidence interval ¼ 0.382-0.873, P ¼ 0.009) and 0.81 (95% confidence interval ¼ 0.652-0.997, P ¼ 0.047), respectively. Our findings were in agreement with Montes-Cano and et al.'s discovery that HCV-1 patients carry a higher rate of unfavorable alleles that might compromise treatment responses. In addition, the frequency of the rs8099917 TT genotype in our study (88%) was substantially higher than that reported in Swiss Caucasians (58%), 6 and this was in line with the finding that Asian populations had the highest rs12979860 C allelic frequency. 7 The host genotype-specific selection of the viral genotype may contribute to the higher proportion of HCV-non-1 distribution in Asian areas. 3 The divergence of the host genetic predisposition among patients with different HCV genotypes and ancestries might in part explain the substantially higher sustained virological response rates in Asian patients receiving peginterferon/ribavirin. 8,9 The real cause is not clear; it is postulated that there exists a selection pressure between the HCV viral genotype and host immune responses during evolution that might determine HCV genotype-specific treatment responses. 10 Whether the driving force of selection applies to viral replication as well as the preference of the viral genotype distribution in terms of host genetic diversities warrants further molecular-based studies in the future.
Journal of Human Hypertension, Jun 1, 1989
In an open, crossover study, the pharmacokinetic and pharmacodynamic profiles of lisinopril and e... more In an open, crossover study, the pharmacokinetic and pharmacodynamic profiles of lisinopril and enalapril, administered alone and in combination with propranolol, were evaluated in 12 volunteers. The maximum serum concentration (Cmax) of lisinopril and time to reach maximum concentration (Tmax) were 64 +/- 16 ng/ml and 7.5 +/- 1.5 h, respectively. The area under the serum curve (AUC) was 916 +/- 239 h. ng/ml. The Cmax of enalaprilat (89 +/- 34 ng/ml) was greater than that of lisinopril whilst Tmax was shorter (4.3 +/- 1.7 h) and AUC smaller (718 +/- 17 h.ng/ml) (P less than 0.01). Renal clearance of drug 48 h post-dosing showed that enalaprilat (164 +/- 38 ml/min) was cleared from plasma significantly more rapidly than lisinopril (82 +/- 16 ml/min) (P less than 0.001). Mean supine blood pressure decreased significantly with all treatments, as did heart rate. No significant changes were observed in either the serum concentrations or the urinary outputs of these ACE inhibitors following combination with propranolol, apart from a greater variability of Cmax after addition of propranolol to enalapril compared with lisinopril in combination.
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Papers by Flemming Bendtsen