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Biomedical subjects

F Bendtsen

Publications and source records attributed to F Bendtsen.

At least 19 recordsLinked to original sources
PubMed2001

[Treatment of esophageal varices].

Patients with oesophageal varices without previous bleeding have a risk of 25-30% for the development of a bleeding episode within two years. It is important to identify patients with a high risk of bleeding due to the high mortality of 30-40% within six weeks after a bleeding episode. Treatment with a non-selective betablocker possibly combined with isosorbidnitrate should be initiated if an upper endoscopy shows the presence of medium- or large-sized oesophageal varices. Sclerotherapy or ligation initiated within a short time after start of an acute bleeding episode reduces mortality and risk of bleeding. Pharmacological treatment may have effect on the acute episode, and most data advocate for Terlipressin to be the first choice. If bleeding continues transjugular intrahepatic portosystemic shunt (TIPS) should be considered. Fifty to seventy percent of patients will experience a rebleeding episode if otherwise untreated. Endoscopic ligation should be preferred possibly in combination with a non-selective betablocker. If another bleed occurs the patient should be considered for TIPS or transplantation.

Adrenergic beta-Antagonists↗
PubMed2001

Dynamics of albumin in plasma and ascitic fluid in patients with cirrhosis.

BACKGROUND/AIMS: To determine dynamics of albumin in plasma and ascitic fluid of patients with cirrhosis. METHODS: Forty-seven patients were classified in four groups: I--patients without fluid retention; II--patients with ascites not resistant to subsequent diuretic treatment; III--recompensated patients during diuretic treatment; and IV--patients with diuretic-resistant ascites. Transvascular and transperitoneal albumin transports were quantified by 131I-/125I-labelled human albumin. RESULTS: TER(P) (i.e. the fraction of intravascular albumin (IVM) passing from plasma into the interstitial space per hour) was increased in all groups. In group IV patients the transport rate of albumin from plasma into the ascitic fluid (TER(PA)) was significantly higher than the transport rate from the ascitic fluid back into the plasma: TER(AP) (0.45 vs. 0.26% IVM/h, P < 0.002). In group II patients TER(PA) was similar to TER(AP) (0.27 vs. 0.25% IVM/h, ns). A direct correlation was found between TER(PA) and TER(AP) in both groups of patients (r = 0.78, P < 0.001). CONCLUSION: In non-resistant ascites, there is a steady state between the transport of albumin into the peritoneal cavity and back into the plasma, but in resistant ascites the former transport is elevated. Thus, local factors may be important to treatment of ascites.

Adult↗
PubMed2001

The insulin-like growth factor binding protein 3 ternary complex is reduced in cirrhosis.

BACKGROUND/AIMS: In healthy adults, serum insulin-like growth factor I (IGF-I), IGF binding protein 3 (IGFBP-3) and acid labile subunit (ALS) form a 150-kDa ternary complex under the control of growth hormone (GH). Approximately 80-90% of circulating IGF-I is bound to the ternary complex. In cirrhosis the GH/IGF axis is severely disturbed and the individual components of the ternary complex are reduced. However, the degree of ternary complex formation in cirrhosis has not previously been described. METHODS: Serum IGF-I, IGFBP-3, ALS, the 150-kDa ternary complex and IGFBP-3 proteolysis were all measured in six compensated and six decompensated cirrhotic patients and compared to six healthy controls. RESULTS: Patients with compensated cirrhosis had decreased levels of IGF-I (55%), IGFBP-3 (64%) and ALS (53%), and in the decompensated patients these levels were decreased even further: IGF-I (32%), IGFBP-3 (37%) and ALS (27%) compared to healthy controls. The levels of the ternary complex followed this pattern, with low levels seen in the compensated patients (66%) and a further reduction in the decompensated patients (27%). Ternary complex levels correlated negatively with the Child-Pugh score. No increase in IGFBP-3 proteolysis was found in cirrhotic patients compared to healthy controls. CONCLUSION: Cirrhosis is associated with reduced levels of the 150-kDa ternary IGFBP-3 complex correlating with the degree of liver disease.

Adult↗
PubMed2001

Oesophageal pressure-cross-sectional area distributions and secondary peristalsis in relation to subclassification of systemic sclerosis.

The aim of the present study was to correlate the severity of oesophageal motor dysfunction with the severity of cutaneous disease in systemic sclerosis (SS). Patients were divided into three groups based on the degree of skin involvement: type I, acrosclerosis distal to the wrist; type II, scleroderma extending above the wrist in proximal direction; type III, diffuse cutaneous systemic sclerosis. Impedance planimetry employing distensions with pressures up to 5 kPa with the concomitant measurement of oesophageal cross-sectional area (CSA) was used in combination with standard oesophageal manometry. Measurements were made at 7 and 15 cm above the lower oesophageal sphincter (LOS). Thirty patients (16 type I, six type II and eight type III patients) and 23 normal controls were included. LOS pressure was lower in SS patients than in normal patients, with the lowest values in type III. The CSAs were higher in SS patients than in controls at both sites (P < 0.001). The CSAs at the distal site were highest in type III, as compared to type I and II (P < 0.03). The CSA at the highest induced pressure (5.0 kPa) was 613 +/- 45, 719 +/- 79, and 808 +/- 115 mm2 in types I, II and III, respectively. No differences in CSA were found at the proximal site between the three types of SS. The distensibility did not differ between SS and normal patients at the distal site. The distensibility was lowest in SS patients (P < 0.001) at the proximal distension site. The distensibility did not vary with the type of SS at either site. Significant differences in contraction frequency of the secondary peristalsis as function of wall tension were demonstrated between the SS patients and controls at the distal site (P < 0.05). No differences were found at the proximal site. The contraction frequency and amplitude at the distal and proximal sites did not differ among the three types. In conclusion for most parameters studied, SS patients differed from normal patients. Among SS types, the most pronounced changes were found in type III.

Adult↗
PubMed2001

Effects of a long-acting formulation of octreotide on renal function and renal sodium handling in cirrhotic patients with portal hypertension: a randomized, double-blind, controlled trial.

Octreotide seems to have a beneficial effect on variceal bleeding, and long-term administration for the prevention of rebleeding is currently being evaluated. Experimental studies have suggested a beneficial effect of chronic octreotide treatment on renal function, while clinical studies have shown variable effects. Twenty-five cirrhotic patients with portal hypertension were randomized in a double-blind design to placebo or a single subcutaneous dose of a long-acting formulation of octreotide (octreotide-LAR) (20 mg). Renal function tests were performed before dosing and repeated after 30 days. The patients were in sodium steady state at the time of study. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured by a constant infusion clearance technique. Renal sodium handling was determined by lithium and sodium clearance measurements. Therapeutic serum levels of octreotide along with a reduction of insulin-like growth factor I (IGF-I) (P <.01) and an increase of IGF binding protein 1 (P <.05) were demonstrated. No effect of octreotide was observed on GFR, ERPF, or filtration fraction (GFR/ERPF). Changes in clearance and extraction fraction of sodium and lithium during octreotide treatment were not significantly different from those of placebo. In addition, no changes in free water clearance, urinary flow rate, or 24-hour Na excretion were demonstrated. A significant increase of mean arterial pressure (+5 mm Hg; P <.01) was observed after treatment with octreotide-LAR. It is concluded that in spite of increased arterial pressure, octreotide-LAR has no significant effect on renal hemodynamics and tubular function in clinically stable cirrhotic patients with portal hypertension.

Blood Pressure↗
PubMed2001

Endoscopic Doppler ultrasound for measurement of azygos blood flow. Validation against thermodilution and assessment of pharmacological effects of terlipressin in portal hypertension.

BACKGROUND: Endoscopic ultrasound (EUS) is a new modality allowing real-time flow measurements by means of the Doppler technique. The aim of the study was to evaluate azygos blood flow measurements by endoscopic ultrasound. METHODS: Measurements of azygos blood flow by EUS and by the thermodilution technique were compared in 20 patients with portal hypertension. The ability of EUS flowmetry to detect changes in the azygos and portal venous flow after an intravenous dose of 2 mg of terlipressin was evaluated in 13 of the patients in a double-blind, randomized, placebo-controlled, cross-over design. RESULTS: The EUS Doppler and thermodilution measurements correlated significantly (R=0.81, P < 0.001). The azygos blood flow was found to be 14% higher by the EUS method than by thermodilution. The coefficient of variation of the EUS Doppler measurements of the azygos blood flow was 14.8%. After administration of terlipressin, the azygos blood flow, as measured by EUS Doppler, decreased significantly by 23% from 915 to 704 ml/min (P = 0.014) and the portal venous flow decreased by 28% from 1170 to 789 ml/min (P = 0.03). No effects of placebo were detected. CONCLUSIONS: These results show that EUS measurement of the azygos blood flow correlate strongly to the measurements by the thermodilution technique, and EUS is moreover well tolerated by the patients. The method is applicable for monitoring pharmacological effects on the superior porto-systemic collateral circulation and portal venous flow in patients with portal hypertension.

Adult↗
PubMed2001

Effect of beta-adrenergic blockade on elevated arterial compliance and low systemic vascular resistance in cirrhosis.

BACKGROUND: Patients with cirrhosis exhibit a characteristic hyperdynamic circulation with increased cardiac output and heart rate and reduced systemic vascular resistance. The compliance of the arterial tree has recently been reported to be increased in these patients, who are often treated with beta-blockers, but the effect of this treatment on arterial compliance has not been investigated. The aim of the present study was therefore to assess the effects of propranolol on the arterial compliance of patients with cirrhosis. METHODS: Twenty patients with cirrhosis underwent a haemodynamic investigation with determination of splanchnic and systemic haemodynamics. Arterial compliance was determined as the ratio of the stroke volume to the pulse pressure and compared to normal values. RESULTS: All the patients had significant portal hypertension, with a mean hepatic venous pressure gradient (HVPG) of 17.8 mmHg, and responded to beta-blocker treatment with a significant reduction in the HVPG (-16%; P < 0.001). Arterial compliance was elevated (1.27 versus controls 1.01 ml/mmHg; P < 0.001), but remained almost unchanged during beta-adrenergic blockade (1.27 versus 1.29 ml/mmHg, +2%, ns), whereas systemic vascular resistance increased substantially (1083 versus 1378 dyn x s x cm-5, +27%; P < 0.001). The mean arterial blood pressure (-6%; P < 0.05), heart rate (-20%; P < 0.001), cardiac output (-25%; P < 0.001) and hepatic blood flow (-22%; P < 0.001) fell significantly. CONCLUSIONS: Treatment with beta-blockers increases small vessel (arteriolar) vascular tone towards the normal level, but does not affect the elevated compliance of the larger arteries in patients with cirrhosis.

Adrenergic beta-Antagonists↗
PubMed2001

Arterial compliance in patients with cirrhosis: stroke volume-pulse pressure ratio as simplified index.

Arterial function may be altered in patients with cirrhosis. We determined compliance of the arterial tree (C(1)) in relation to systemic and splanchnic hemodynamic derangement and clinical variables. C(1) and the stroke volume-pulse pressure index (SV/PP) were significantly higher (+62% and +40%, respectively; P < 0.001) in cirrhotic patients (n = 49) than in control subjects (n = 19), and a close correlation between C(1) and SV/PP was found in both cirrhotic patients (r = 0.86, P < 0.001) and control subjects (r = 0.96, P < 0.001). Univariate analysis showed significant relations between C(1) and SV/PP on one side and age, sex, body weight, portal pressure, systemic hemodynamics, biochemical variables, and severity of disease on the other. In the multiple-regression analysis, sex, age, mean arterial blood pressure, systemic vascular resistance, and biochemical variables were significant independent predictors of SV/PP (P < 0.005-0.00001). In conclusion, arterial compliance is elevated in cirrhosis. A simplified SV/PP index seems to reflect abnormalities in the arterial compliance of these patients.

Algorithms↗
PubMed2001

Splanchnic and systemic hemodynamic derangement in decompensated cirrhosis.

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.

Coronary Circulation↗
PubMed2000

Increased circulating calcitonin in cirrhosis. Relation to severity of disease and calcitonin gene-related peptide.

Increased circulating levels of the neuropeptide calcitonin gene-related peptide (CGRP) have recently been described in cirrhosis. CGRP is formed by alternative transcription of the calcitonin/alpha-CGRP gene, which also gives rise to calcitonin (CT). This study was undertaken to determine circulating plasma concentrations of CT in patients with cirrhosis in relation to the severity of disease and the plasma level of CGRP. Moreover, the kinetics of CT was evaluated for different organ systems by determination of arteriovenous extraction. Thirty-nine patients with cirrhosis (Child-Turcotte classes A/B/C, n = 10/22/7) were studied under a hemodynamic investigation and compared with 13 control subjects without liver disease. CT and CGRP in arterial and organ venous plasma were determined by radioimmunoassays. In patients with cirrhosis, circulating CT was significantly increased versus control (12.1 v 6.9 pmol/L, P < .001) and a direct relation to the Child-Turcotte score was found (P < .005). The increased circulating CT was directly correlated with increased CGRP (r = .29, P < .05). No significant arteriovenous extraction of circulating CT was observed in the kidneys, hepatosplanchnic system, lower extremities, or peripheral circulation, but there was a substantial rate of pulmonary disposal and clearance (P < .005). It is concluded that in addition to thyroid production, increased circulating CT in cirrhosis is most likely due to overexpression of the calcitonin/alpha-CGRP gene, with relation to the severity of disease and possibly to an accompanying pulmonary dysfunction.

Adult↗
PubMed2000

Serum YKL-40 is increased in patients with hepatic fibrosis.

BACKGROUND/AIMS: YKL-40, a mammalian member of the chitinase family, is a lectin that binds heparin and chitin. The function of YKL-40 is unknown, but it may function in tissue remodelling. The aims of this study were to assess the level of circulating YKL-40 in patients with various kinds and degree of chronic liver disease and its possible relation to liver fibrosis. METHODS: Serum YKL-40 levels were determined by radioimmunoassay in 129 patients with suspected liver disease and related to histological findings and immunohistochemical staining of YKL-40 in a liver biopsy taken simultaneously with the blood sample. RESULTS: The median serum YKL-40 was highest in patients with alcoholic cirrhosis (532 microg/l), in particular in patients with additional alcoholic hepatitis (740 microg/l). Patients with alcoholic cirrhosis, post-hepatitic cirrhosis (425 microg/l) and non-cirrhotic fibrosis (330 microg/l) had significantly higher serum YKL-40 than normal subjects (102 microg/l), patients with fatty liver (195 microg/l) or patients with viral hepatitis without fibrosis (174 microg/l). Serum YKL-40 was significantly (p<0.001) related to the degree of liver fibrosis with the highest levels in patients with moderate (466 microg/l) to severe (676 microg/l) fibrosis. Serum YKL-40 was also increased (p=0.018) in patients with slight fibrosis (270 microg/l) compared to patients without fibrosis. Immunohistochemical analysis demonstrated positive staining for YKL-40 antigen in areas with fibrosis, particularly areas with active fibrogenesis. YKL-40 staining was never found in hepatocytes. CONCLUSIONS: Our study indicates that the increased serum YKL-40 in patients with liver disease of various degree and aetiology seems to reflect fibrosis and fibrogenesis.

Adipokines↗
PubMed2000

Central and systemic haemodynamic effects of terlipressin in portal hypertensive patients.

AIMS/BACKGROUND: Cirrhotic patients exhibit a hyperdynamic and hyporeactive circulation with central hypovolaemia which may influence the course of the disease. As terlipressin, a vasopressin analogue, may modify systemic haemodynamics in these patients, the aim of the present study was to assess the acute effects of terlipressin on central and systemic haemodynamics. METHODS: Sixteen patients with alcoholic cirrhosis and portal hypertension had their systemic, central, and splanchnic haemodynamics determined at baseline and after a blind randomised bolus infusion (2 mg) of terlipressin/placebo. RESULTS: After terlipressin, the arterial blood pressure and the systemic vascular resistance increased by 26% and 61%, respectively (both p<0.001), and the cardiac output, heart rate, and arterial compliance decreased by 18%, 11%, and 32%, respectively (all p<0.001). The central circulation time increased by 36% (p<0.001), whereas the central and arterial blood volume only increased by 4% (p= 0.07). As expected, both portal pressure and hepatic blood flow decreased (17% and 29%, both p<0.001). The decrease in portal pressure after terlipressin was significantly related to the increase in systemic vascular resistance (r=-0.52, p<0.05) and the central circulation time (r=-0.80, p<0.0001). CONCLUSIONS: Terlipressin significantly attenuates the hyperdynamic circulation in portal hypertensive patients without a further contraction of the central and arterial blood volume. The systemic haemodynamic response to terlipressin is moreover associated with the decrease in portal pressure. Terlipressin may therefore have potentially beneficial effects on the hyperdynamic circulation in cirrhosis in addition to its effects on portal pressure.

Adult↗
PubMed2000

A phylogenetic analysis elucidating a case of patient-to-patient transmission of hepatitis C virus during surgery.

A phylogenetic hepatitis C virus (HCV) assay based on the core-Envelope 1 (C-E1) region was developed and used to elucidate a case of a patient-to-patient transmission. The index patient showed clinical symptoms of hepatitis seven weeks after surgery for hallux valgus under general anaesthesia. She progressed to a chronic persistent infection as indicated by positive HCV PCR results two years after surgery. Before her operation, a patient with HCV antibodies and positive HCV PCR had undergone surgery in the same room. There were two possibilities whereby the index patient could have been infected with hepatitis C, either through her work as a nurse or by transmission during surgery. By sequencing the 5' non-coding region PCR product, we found that both patients were infected with genotype 1a. Phylogenetic analysis with the variable C-E1 region suggested that the two patients clustered together with a bootstrap 100% in a tree with 75 sequence references. We further performed a phylogenetic analysis in this region with the genotype 1a reference sequences and an additional 25 genotype 1a sequences consecutively collected from Danish patients with HCV. The two patients still clustered together, supported by a high bootstrap 1000 value of 999. Homology analyses combined with the epidemiological findings indicate that the patient operated on in the same room before the index case was the most likely source of transmission. The mode of transmission could not be conclusively established, but a reusable part of the anaesthetic respiratory circuit is a possibility and a well known risk.

Adult↗
PubMed2000

Elevated circulating leptin levels in arterial hypertension: relationship to arteriovenous overflow and extraction of leptin.

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<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<0.001]. Circulating leptin was directly related to arterial blood pressure (r=0.38-0.62, P</=0.05-0.005) and immunoreactive insulin (r=0.51, P<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<0.02), and this ratio was correlated directly with the BMI (r=0.38, P=0.05) and immunoreactive insulin (r=0.43, P<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.

Adult↗