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Biomedical subjects

Hendrik Vilstrup

Publications and source records attributed to Hendrik Vilstrup.

At least 19 recordsLinked to original sources
PubMed2006

[Surgical risk for patients with liver disease].

Liver disease increases surgical risk. Thus, in patients with cirrhosis, the mortality after abdominal or heart surgery is 50-75% in Child-Pugh C, 20-30% in B and near normal in Child-Pugh A. Stable autoimmune hepatobiliary disease and steatosis without inflammation do not increase surgical risk, but the mortality after major abdominal surgery is increased in patients with fulminant hepatic failure (>90%), alcoholic hepatitis (50%) and acute viral hepatitis (10-15%).

Elective Surgical Procedures↗
PubMed2006

Synthesis of acute phase proteins in rats with cirrhosis exposed to lipopolysaccharide.

BACKGROUND: In patients with cirrhosis, infection is frequent and a leading cause of death. This is secondary to various immunologic abnormalities in both the innate and the adaptive immune system. However, it remains unclear whether cirrhosis affects the inflammatory systemic component of the innate immunity, 'the acute phase response', mostly effectuated by the liver itself. We hypothesized that rats with cirrhosis raise a reduced acute phase response induced by lipopolysaccharide (LPS). RESULTS: We examined the acute phase response induced by intraperitoneal injection of a low dose of LPS, in sham operated control animals and in rats with liver cirrhosis induced by bile duct ligation (BDL). We measured the serum concentrations of the most important acute phase proteins and their liver tissue gene expressions, assessed by mRNA levels. The BDL-model itself increased the serum concentration of alpha1-acid glycoprotein (alpha1AGP) and haptoglobin. LPS was lethal to 25% of the cirrhotic animals and to none of the controls. Twenty-four hours after LPS, the serum concentration of alpha1AGP and haptoglobin, the mRNA level of these acute phase proteins and of alpha2-macroglobulin and thiostatin rose to the same level in the animals with cirrhosis and in controls. CONCLUSION: In rats with experimental cirrhosis LPS caused high mortality. In the survivors, the cirrhotic liver still synthesized acute phase proteins as the normal liver, indicating a normal hepatic contribution to this part of the acute phase response.

Journal Article↗
PubMed2006

[Hepatic pruritus].

Pruritus is a key symptom of hepatic disease. In severe cases, this symptom ruins the patient's quality of life. Most likely it is caused by a protein-bound bile acid (metabolite) that stimulates opioid receptors in the brain. Symptomatic treatments that can reduce pruritus in selected patients include opioid receptor antagonists, biliary diversion, cholestyramine, ursodeoxycholic acid, rifampicin and phenobarbitone. Plasmapheresis or albumin dialysis may be useful when other treatment fails.

Adult↗
PubMed2006

Brain metabolism of 13N-ammonia during acute hepatic encephalopathy in cirrhosis measured by positron emission tomography.

Animal studies and results from 13N-ammonia positron emission tomography (PET) in patients with cirrhosis and minimal hepatic encephalopathy suggest that a disturbed brain ammonia metabolism plays a pivotal role in the pathogenesis of hepatic encephalopathy (HE). We studied brain ammonia kinetics in 8 patients with cirrhosis with an acute episode of clinically overt HE (I-IV), 7 patients with cirrhosis without HE, and 5 healthy subjects, using contemporary dynamic 13N-ammonia PET. Time courses were obtained of 13N-concentrations in cerebral cortex, basal ganglia, and cerebellum (PET-scans) as well as arterial 13N-ammonia, 13N-urea, and 13N-glutamine concentrations (blood samples) after 13N-ammonia injection. Regional 13N-ammonia kinetics was calculated by non-linear fitting of a physiological model of brain ammonia metabolism to the data. Mean permeability-surface area product of 13N-ammonia transfer across blood-brain barrier in cortex, PS(BBB), was 0.21 mL blood/min/mL tissue in patients with HE, 0.31 in patients without HE, and 0.34 in healthy controls; similar differences were seen in basal ganglia and cerebellum. Metabolic trapping of blood 13N-ammonia in the brain showed neither regional, nor patient group differences. Mean net metabolic flux of ammonia from blood into intracellular glutamine in the cortex was 13.4 micromol/min/L tissue in patients with cirrhosis with HE, 7.4 in patients without HE, and 2.6 in healthy controls, significantly correlated to blood ammonia. In conclusion, increased cerebral trapping of ammonia in patients with cirrhosis with acute HE was primarily attributable to increased blood ammonia and to a minor extent to changed ammonia kinetics in the brain.

Acute Disease↗
PubMed2006

Changes in bioactive IGF-I and IGF-binding protein-1 during an oral glucose tolerance test in patients with liver cirrhosis.

OBJECTIVE: Liver cirrhosis is characterized by reduced circulating IGF-I and this has been linked to an adverse clinical outcome. Therefore, we investigated the dynamic changes in circulating total, free, and bioactive IGF-I, IGF-binding protein (IGFBP)-1, IGFBP-2, and IGFBP-1-bound IGF-I (binary complex) during an oral glucose tolerance test (OGTT) in patients with liver cirrhosis. METHODS: Seven Caucasian males with liver cirrhosis and seven healthy males matched for age (54.4+/-3.2 vs 54.6+/-4.4 years) and body mass index (25.3+/-1.2 vs 25.9+/-1.3 kg/m2) were studied. Blood samples were drawn at 0, 30, 60, 90, 120, 150, and 180 min for determination of serum total and free IGF-I, IGFBP-1, IGFBP-2, and binary complex, while bioactive IGF-I was measured at 0, 30, 60, 120, and 180 min. RESULTS: In comparison with healthy subjects, baseline levels of total (47%), free (36%), and bioactive IGF-I (51%) were lower, while IGFBP-1 (268%) was higher (P<0.05), IGFBP-2 (172%) tended to be higher (P>0.05), and the binary complex unchanged (approximately 100%) in cirrhotic patients. Serum total and free IGF-I, and IGFBP-2 remained unchanged in both study groups during the OGTT. Bioactive IGF-I decreased by 29% from baseline to 60 min in cirrhotic patients and remained low at the end of the OGTT (P<0.05). A similar tendency was observed in healthy controls (P=0.052). Concomitantly, IGFBP-1, binary complex, and IGFBP-1 saturation index decreased significantly in both groups. The disappearance of the binary complex was about twofold faster than that of IGFBP-1 (P < 0.05). CONCLUSION: Despite unchanged concentrations of total and free IGF-I, bioactive IGF-I declined significantly after an oral glucose load in patients with liver cirrhosis and the same tendency was observed in healthy subjects. We speculate that the reduction in bioactive IGF-I may be related to the higher levels of free IGFBP-1 and the faster disappearance of IGFBP-1-bound IGF-I.

Blood Glucose↗
PubMed2006

Discharge diagnoses of liver diseases in Nuuk Greenland compared to a Danish county hospital.

BACKGROUND: It is a frequently held notion that Inuits/Greenlanders are less prone to develop chronic liver disease than Europeans. High alcohol consumption and chronic viral infection are more frequent in Greenland than in Denmark. STUDY DESIGN: A cross-sectional study to examine the incidence and prevalence of liver discharge diagnosis with focus on cirrhosis among hospital-admitted patients in Greenland and Denmark. METHODS: Register-based ICD-10 discharge diagnoses from Queen Ingrid's Hospital, Greenland, (n = 1072) and Randers Central Hospital, Denmark, (n = 4599) were used to compare the incidence and prevalence of cirrhosis in hospitalised patients during 1998. RESULTS: Five patients (0.47%) in Greenland and 36 (0.78%) in Denmark had a liver discharge diagnosis (OR = 0.67, 95% CI: 0.26-1.72). Two patients (0.19%) in Greenland compared to 25 (0.54%) in Denmark had a cirrhosis associated discharge liver diagnosis (OR = 0.34, 95% CI: 0.08-1.45). The number of newly diagnosed discharged patients was smaller in Greenland, 2 (0.19%), vs. Denmark, 14 (0.30%), (OR = 0.61, 95% CI: 0.14-2.70). CONCLUSION: Discharge liver diagnoses were not more frequent in Greenland than in Denmark--if anything, the hospital prevalence and incidence of liver discharge diagnoses were lower. This may reflect fewer cirrhosis cases in Greenland, and/or a shorter survival time, or lack of follow up.

Adolescent↗
PubMed2005

Recombinant activated factor VII in an unselected series of cases with upper gastrointestinal bleeding.

INTRODUCTION: The mortality rate associated with UGI bleeding remains high at 7-14%. Pharmacologic and endoscopic interventions are the current standard treatment, but there are few alternative options should these fail. This study aimed to assess the efficacy and safety of recombinant activated factor VII (rFVIIa) in the rescue treatment of severe upper gastrointestinal (UGI) bleeding. METHOD: Eleven patients (age: 8-64 years) were treated with rFVIIa at 15.0-90 microg/kg to control UGI bleeds. All three pediatric/adolescent cases and four of the eight adults had UGI hemorrhage associated with liver disease; the origins of the bleeds for remaining adults were trauma (n=1), peptic duodenal ulcer (n=1), hemorrhagic gastritis with sepsis (n=1) and pancreatitis (n=1). RESULTS: Bleeding stopped in seven patients and was markedly reduced in two patients, while there was no change in two patients. Coagulation parameters displayed a tendency to improve, and transfusion requirements were reduced in most patients. In total, five patients died within 2 weeks of rFVIIa treatment. In each case, fatality was judged unrelated to rFVIIa treatment. No thromboembolic events occurred. CONCLUSIONS: These results suggest that, even if our data are optimistic, the use of rFVIIa in the treatment of severe UGI bleeding warrants further investigation in prospective, randomized trials.

Adolescent↗
PubMed2005

Contribution of defects in glucose uptake to carbohydrate intolerance in liver cirrhosis: assessment during physiological glucose and insulin concentrations.

It is well established that subjects with liver cirrhosis are insulin resistant, but the contribution of defects in insulin secretion and/or action to glucose intolerance remains unresolved. Healthy individuals and subjects with liver cirrhosis were studied on two occasions: 1) an oral glucose tolerance test was performed, and 2) insulin secretion was inhibited and glucose was infused in a pattern and amount mimicking the systemic delivery rate of glucose after a carbohydrate meal. Insulin was concurrently infused to mimic a healthy postprandial insulin profile. Postabsorptive glucose concentrations were equal (5.36 +/- 0.12 vs. 5.40 +/- 0.25 mmol/l, P = 0.89), despite higher insulin (P < 0.01), C-peptide (P < 0.01), and free fatty acid (P = 0.05) concentrations in cirrhotic than in control subjects. Endogenous glucose release (EGR; 11.50 +/- 0.50 vs. 11.73 +/- 1.00 mumol.kg(-1).min(-1), P = 0.84) and the contribution of gluconeogenesis to EGR (6.60 +/- 0.47 vs. 6.28 +/- 0.64 mumol.kg(-1).min(-1), P = 0.70) were unaltered by cirrhosis. A minimal model recently developed for the oral glucose tolerance test demonstrated an impaired insulin sensitivity index (P < 0.05), whereas the beta-cell response to glucose was unaltered (P = 0.72). During prandial glucose and insulin infusions, the integrated glycemic response was greater in cirrhotic than in control subjects (P < 0.05). EGR decreased promptly and comparably in both groups, but glucose disappearance was insufficient at the prevailing glucose concentration (P < 0.05). Moreover, identical rates of [3-(3)H]glucose infusion produced higher tracer concentrations in cirrhotic than in control subjects (P < 0.05), implying a defect in glucose uptake. In conclusion, carbohydrate intolerance in liver cirrhosis is determined by insulin resistance and the ability of glucose to stimulate insulin secretion. During prandial glucose and insulin concentrations, EGR suppression was unaltered, but glucose uptake was impaired, which demonstrates that intolerance can be ascribed to a defect in glucose uptake, rather than abnormalities in glucose production or beta-cell function. Although insulin secretion ameliorates glucose intolerance, impaired glucose uptake during physiological glucose and insulin concentrations produces marked and sustained hyperglycemia, despite concurrent abnormalities in glucose production or insulin secretion.

Carbohydrate Metabolism↗
PubMed2005

Magnesium supplementation and muscle function in patients with alcoholic liver disease: a randomized, placebo-controlled trial.

OBJECTIVE: The study was undertaken in order to evaluate the effect of magnesium (Mg) supplementation on muscle contents of Mg, muscle strength, muscle mass and sodium, potassium pumps (Na,K-pumps) in patients with alcoholic liver disease. Retrospectively, patients were also stratified according to spironolactone treatment. MATERIAL AND METHODS: The study comprised a placebo-controlled, randomized trial in which 59 consecutive patients with alcoholic liver disease were treated with Mg intravenously and orally (12.5 mmol daily) or placebo for 6 weeks. Muscle content of Mg, maximum isokinetic muscle strength, skeletal muscle mass and muscle content of Na,K-pumps were measured before and after Mg supplementation. RESULTS: Muscle Mg did not increase during the trial (paired t-test), but Mg supplementation and the duration of pre-study spironolactone treatment were independent predictors of muscle Mg (multiple regression). Muscle strength increased by 14% during the trial (p<0.001) and muscle mass increased by 11% (p=0.05), but with no difference between placebo and Mg treatment. Spironolactone treatment was associated with a 33% increase in the content of Na,K-pumps (p<0.001). CONCLUSIONS: Six weeks of Mg supplementation did not increase muscle Mg, although Mg supplementation and spironolactone treatment were independent predictors of muscle Mg. The intervention had no effect on muscle strength and mass, but both increased during the study, probably owing to the general care and attendance to the patients.

Administration, Oral↗
PubMed2005

Hepatic microcirculation assessed by positron emission tomography of first-pass ammonia metabolism in porcine liver.

AIMS/BACKGROUND: Intrahepatic branching of the hepatic artery (HA) to liver microcirculatory units, the acini, is more heterogeneous than that of the portal vein (PV). Furthermore, part of HA blood enters the sinusoid partially downstream between the in- and outlets. We examined the effects of these vascular variations on porcine hepatic first-pass ammonia metabolism, which is characterised by high uptake and separate periportal urea and perivenous glutamine formations. METHODS: (13)NH(3) was given via the PV, HA or caval vein, followed by 22 min dynamic liver positron emission tomography (PET) recordings in six pigs. Heterogeneity of liver (13)N-metabolism was quantified by the coefficient of variation of tissue (13)N-radioactivity measured 10 min after tracer infusion. Sinusoidal zonal clearances of (13)NH(3) into (13)N-urea and (13)N-glutamine were calculated by kinetic PET modelling. RESULTS: Liver metabolic heterogeneity was 0.65+/-0.20 (mean+/-SD, n=6) following (13)NH(3)-infusion into HA, 0.34+/-0.17 into PV and 0.10+/-0.02 into the caval vein. Clearance of (13)NH(3) to (13)N-urea was of similar magnitude following (13)NH(3) administration into HA and PV: 0.27+/-0.11 ml/min/g (mean+/-SD) and 0.29+/-0.09 ml/min/g, respectively. Clearances of (13)NH(3) to (13)N-glutamine when (13)NH(3) was given into HA and PV were also similar: 0.47+/-0.18 and 0.50+/-0.13 ml/min/g, respectively. CONCLUSIONS: The present measurements of the hepatic metabolism of (13)NH(3) showed metabolic heterogeneity compatible with variation of the HA supply of the acini. Second, results of PET modelling of the sinusoidal zonation metabolism of (13)NH(3) to (13)N-urea and to (13)N-glutamine did not indicate metabolically important partial downstream arterial entry into the sinusoids.

Ammonia↗
PubMed2005

Effect of lipopolysaccharide on in vivo and genetic regulation of rat urea synthesis.

BACKGROUND: The acute phase response causes a negative nitrogen balance. It is unknown whether this involves regulation of hepatic urea synthesis. METHODS: We examined the in vivo capacity of urea nitrogen synthesis (CUNS), mRNA levels of urea cycle enzyme genes and galactose elimination capacity (GEC) during moderate and severe acute phase response induced by low- and high-dose lipopolysaccharide (LPS) in rats. RESULTS: Low-dose LPS doubled CUNS (P<0.05), decreased the mRNA level of the rate-limiting urea cycle enzyme (arginino succinate synthetase (ASS) by 26% (P<0.05) and did not change GEC. High-dose LPS did not change CUNS, decreased the mRNA level of the flux-generating enzyme carbamoyl phosphate synthetase (CPS) by 11% (P<0.05) and the rate-limiting urea cycle enzyme (ASS) by 27% (P<0.05) and almost halved GEC (P<0.05). CONCLUSION: The moderate acute phase response up-regulated in vivo urea synthesis but had the opposite effect on gene level. The severe acute phase response decreased the functional liver mass that attenuated the increase in urea synthesis.

Animals↗
PubMed2004

Alcohol acutely down-regulates urea synthesis in normal men.

BACKGROUND: Human nitrogen balance studies suggest that alcohol up-regulates urea synthesis and promotes nitrogen catabolism, whereas animal studies conversely indicate that alcohol down-regulates urea synthesis, possibly via a redox effect. This study aimed to investigate the acute effects of alcohol exposure at a plasma concentration of about 10 mmol/liter on urea synthesis in healthy volunteers and to investigate whether methylene blue alleviates the effect of alcohol. METHODS: Eleven males were studied three times in a randomized sequence crossover design. They received either alanine infusion to control the rate of urea synthesis (control), alanine + alcohol, or alanine + alcohol + methylene blue. The substrate independent regulation of urea synthesis was studied by means of the functional hepatic nitrogen clearance, that is, the slope of the linear relation between blood amino nitrogen concentrations and rates of urea synthesis. RESULTS: Alcohol reduced functional hepatic nitrogen clearance to 37% and 51% during alcohol and alcohol + methylene blue infusion, respectively (p = 0.007). Accordingly, whole body nitrogen retention was higher during alcohol infusion. Glucagon, which up-regulates urea synthesis, increased during alcohol infusion. There was no change in insulin. Blood glucose was slightly lower at the end of the experiment when alcohol was infused. CONCLUSION: Low-dose infusion of alcohol acutely down-regulated urea synthesis in healthy volunteers, transiently favoring nitrogen preservation. The effect seemed not to depend on hormonal changes. It remains to be explored how the present results can be reconciled with the reported nitrogen wasting of chronic alcoholics.

Adult↗
PubMed2003

Impaired basal glucose effectiveness but unaltered fasting glucose release and gluconeogenesis during short-term hypercortisolemia in healthy subjects.

Excess cortisol has been demonstrated to impair hepatic and extrahepatic insulin action. To determine whether glucose effectiveness and, in terms of endogenous glucose release (EGR), gluconeogenesis, also are altered by hypercortisolemia, eight healthy subjects were studied after overnight infusion with hydrocortisone or saline. Glucose effectiveness was assessed by a combined somatostatin and insulin infusion protocol to maintain insulin concentration at basal level in the presence of prandial glucose infusions. Despite elevated insulin concentrations (P < 0.05), hypercortisolemia resulted in higher glucose (P < 0.05) and free fatty acid concentrations (P < 0.05). Furthermore, basal insulin concentrations were higher during hydrocortisone than during saline infusion (P < 0.01), indicating the presence of steroid-induced insulin resistance. Postabsorptive glucose production (P = 0.64) and the fractional contribution of gluconeogenesis to EGR (P = 0.33) did not differ on the two study days. During the prandial glucose infusion, the integrated glycemic response above baseline was higher in the presence of hydrocortisone than during saline infusion (P < 0.05), implying a decrease in net glucose effectiveness (4.42 +/- 0.52 vs. 6.65 +/- 0.83 ml.kg-1.min-1; P < 0.05). To determine whether this defect is attributable to an impaired ability of glucose to suppress glucose production, to stimulate its own uptake, or both, glucose turnover and "hot" (labeled) indexes of glucose effectiveness (GE) were calculated. Hepatic GE was lower during cortisol than during saline infusion (2.39 +/- 0.24 vs. 3.82 +/- 0.51 ml.kg-1.min-1; P < 0.05), indicating a defect in the ability of glucose to restrain its own production. In addition, in the presence of excess cortisol, glucose disappearance was inappropriate for the prevailing glucose concentration, implying a decrease in glucose clearance (P < 0.05). The decrease in glucose clearance was confirmed by the higher increment in [3-3H]glucose during hydrocortisone than during saline infusion (P < 0.05), despite the administration of identical tracer infusion rates. In conclusion, short-term hypercortisolemia in healthy individuals with normal beta-cell function decreases insulin action but does not alter rates of EGR and gluconeogenesis. In addition, cortisol impairs the ability of glucose to suppress its own production, which due to accumulation of glucose in the glucose space results in impaired peripheral glucose clearance. These results suggest that cortisol excess impairs glucose tolerance by decreasing both insulin action and glucose effectiveness.

Adult↗