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Biomedical subjects

S Møller

Publications and source records attributed to S Møller.

At least 73 records · Page 4Linked to original sources
PubMed1997

Effect of octreotide on systemic, central, and splanchnic haemodynamics in cirrhosis.

BACKGROUND/AIMS: Cirrhosis with portal hypertension is associated with changes in the splanchnic and systemic haemodynamics, and subsequent complications, such as bleeding from oesophageal varices, have led to the introduction of long-acting somatostatin analogues in the treatment of portal hypertension. However, reports on the splanchnic and systemic effects of octreotide are contradictory and therefore the aim of the present study was to assess the effects of continuous infusion of octreotide on central and systemic haemodynamics, portal pressures, and hepatic blood flow. METHODS: Thirteen patients with cirrhosis underwent liver vein catheterisation. Portal and arterial blood pressures were determined at baseline and 10, 30, and 50 min after a bolus injection of octreotide 100 micrograms, followed by continuous infusion of octreotide 100 micrograms/ h for 1 h. Hepatic blood flow, cardiac output, central and arterial blood volume, and central circulation time were determined at baseline and 50 min after the start of the octreotide infusion. RESULTS: The mean arterial blood pressure increased during the first 10 min (p < 0.0005), but returned to baseline after 50 min. The central and arterial blood volume (-16%, p < 0.005) and the central circulation time (-8%, p < 0.05) were significantly decreased after 50 min, whereas the cardiac output did not change significantly. The hepatic venous pressure gradient and the hepatic blood flow did not change significantly at any time after infusion of octreotide. CONCLUSIONS: Octreotide does not affect the portal pressure or hepatic blood flow, whereas it may further contract the central blood volume and thereby exert a potentially harmful effect on central hypovolaemia in patients with cirrhosis. However, these early effects do not exclude the possibility that administration of longacting somatostatin analogues over a longer period may have a beneficial effect.

Adult↗
PubMed1997

Continuous blood pressure monitoring in cirrhosis. Relations to splanchnic and systemic haemodynamics.

BACKGROUND/AIMS: Low arterial blood pressure is recognised as a distinctive factor in the hyperdynamic circulation in cirrhosis. 24-hour monitoring of the blood pressure and heart rate has recently revealed a reduced circadian variation with relation to liver function. However, associations with other clinical and haemodynamic characteristics have not been investigated and the aim of the present study was to identify splanchnic and systemic determinants of the 24-h blood pressure and heart rate in cirrhosis. METHODS: The variables were measured by an automatic ambulant device for monitoring blood pressure and related to the results of an invasive haemodynamic investigation, including measurements of intra-arterial blood pressure (9.00-11.00 h) in 37 patients with cirrhosis. RESULTS: The 24-h blood pressures were significantly lower and the heart rate was significantly higher in patients with cirrhosis than in matched controls (p < 0.05-0.001). To identify determinants of 24-h or intra-arterial blood pressures and heart rate, pertinent variables were included in a multivariate regression model. This model revealed that independent determinants of a low 24-h arterial blood pressure were a high post-sinusoidal resistance, a low plasma volume, a short central circulation time, and the presence of ascites. In contrast, a low intra-arterial blood pressure was determined by a low serum sodium, a low haemoglobin, and a high cardiac output. Diuretic treatment did not influence this model. CONCLUSIONS: Although the 24-h blood pressure and the intra-arterial blood pressure were determined by different variables, the overall results indicate that abnormalities in both splanchnic and central haemodynamics and sodium-water retention are important in the pathophysiology of arterial hypotension in patients with portal hypertension.

Adult↗
PubMed1997

Plasma YKL-40: a new potential marker of fibrosis in patients with alcoholic cirrhosis?

BACKGROUND: YKL-40 (human cartilage glycoprotein-39, or 38-kDa heparin-binding glycoprotein) is a mammalian member of a protein family that includes bacterial chitinases. YKL-40 mRNA is expressed by human liver and may play a role in tissue remodelling. The aims were to assess whether circulating YKL-40 is released or extracted in the hepatosplanchnic system and to localize YKL-40 in liver tissue. METHODS: Plasma YKL-40 was determined by radioimmunoassay in 25 patients with liver diseases (alcoholic cirrhosis (n = 20), chronic active hepatitis (n = 2), cirrhosis of unknown aetiology (n = 2), and fatty liver (n = 1) and in 18 subjects with normal liver function during a haemodynamic investigation with catheterization of liver vein and the femoral artery. Immunohistochemical studies of the localization of YKL-40 in cryostal liver biopsy specimens were obtained from eight other patients with alcoholic liver disease. RESULTS: Plasma YKL-40 was significantly increased in patients with alcoholic cirrhosis (median, 523 micrograms/l; P < 0.001) compared with controls (106 micrograms/l), and plasma YKL-40 in the hepatic vein was higher (P < 0.01) than that of the artery in both the patients and controls, showing release of YKL-40 from the hepatosplanchnic area. The release rate of YKL-40 from the hepatosplanchnic area was higher in patients with liver disease than in controls (11.0 versus 2.1 micrograms/min, P < 0.05). Furthermore, the highest plasma YKL-40 levels were found in patients with a moderate or severe degree of liver fibrosis, and immunohistochemical studies showed positive staining for YKL-40 antigen in areas of the liver biopsy with fibrosis. CONCLUSIONS: The increased plasma YKL-40 in patients with alcoholic cirrhosis may reflect the remodelling of liver fibrosis.

Adipokines↗
PubMed1997

Circulatory abnormalities in cirrhosis with focus on neurohumoral aspects.

Patients with cirrhosis exhibit characteristic hemodynamic changes with a hyperkinetic circulation and an abnormal distribution of the blood volume and neurohumoral regulation. Their plasma and noncentral blood volumes are increased, and the central and arterial blood volume and systemic vascular resistance are decreased. A peripheral arterial vasodilatation may be of pathogenic importance to the low systemic vascular resistance as it directly correlates to the degree of central hypovolemia. It may therefore be an important element in the development of the low arterial blood pressure and hyperkinetic circulation in cirrhosis. Various vasodilators such as atrial natriurectic peptide, calcitonin gene-related peptide, adrenomedullin, and nitric oxide are among potential candidates in the arterial vasodilatation in cirrhosis. Besides enhanced sympathetic nervous activity, activation of the renin-angiotensin-aldosterone system, and elevated circulating vasopressin, endothelin-1 may also be implicated in the 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 circulatory dysfunction influencing the course of the disease.

Blood Circulation↗
PubMed1996

[Determination of diurnal blood pressure variations in cirrhosis].

Cirrhotic patients have disturbed systemic haemodynamics with reduced arterial blood pressure, but this has not been investigated during daily activity and sleep. Systolic (SBP), diastolic (DBP), and man arterial blood pressure (MAP), and heart rate (HR) were measured by an automatic ambulatory device for monitoring blood pressure in 35 patients with cirrhosis and 35 healthy matched controls. During the day-time, SBP, DBP and MAP were significantly lower in the patients than in the controls (median 118 vs 127; 70 vs 78; 86 vs 94 mmHg, p < 0.0001 to p < 0.05). The night-time blood pressures were almost similar in the two groups (108 vs 110; 65 vs 67; 78 vs 82 mmHg, NS). Conversely, HR was significantly higher in the patients both in the day-time (86 vs 72 min-1, p < 0.0001) and night (80 vs 64 min-1, p < 0.0001). Consequently, the reduction in blood pressure and HR from day-time to night-time was significantly lower in the patients than in the controls (p < 0.0001 to p < 0.01). Multiple regression analysis revealed HR, serum albumin, serum sodium, and clotting factors 2, 7 and 10 as significant independent predictors of SBP in cirrhosis. In conclusion, cirrhotic patients have elevated HR, but surprisingly normal arterial blood pressure during the night-time, and the circadian variation in blood pressure and HR is diminished probably due to an almost unaltered cardiac output during the 24 hours. These results may reflect a major defect in the ability of optimal regulation of blood pressure in cirrhotic patients.

Adult↗
PubMed1996

Prognostic value of insulinlike growth factor I and its binding protein in patients with alcohol-induced liver disease. EMALD group.

Insulinlike growth factor I (IGF-I) is a single-polypeptide chain with important anabolic and endocrine activities. The liver is the major source of IGF-I and its binding protein, IGFBP-3. Circulating concentrations of IGF-I and IGFBP-3 are decreased in patients with chronic liver disease and correlate with the severity. The aim of this study was to assess the additional prognostic value of IGF-I and IGFBP-3 in patients entered in a large multicenter study (EMALD). Three hundred thirty-seven patients with alcohol-induced liver disease were studied in a randomized placebo-controlled trial of malotilate with a mean follow-up period of 569 days (range, 7-1,544). A multivariate Cox regression analysis of pertinent clinical and biochemical variables showed a significant independent prognostic value of years of alcohol intake, coagulation factors 2, 7, and 10, alkaline phosphatases, serum creatinine, and immunoglobulin (Ig) M. When IGF-I or IGFBP-3 were added into this model, a Cox regression analysis showed that either had a significant independent prognostic value. Because IGF-I and IGFBP-3 were closely correlated, they contained almost the same prognostic information. Inclusion of IGF-I gave these results: IGF-I (P < .03), alcohol intake (P < .02), coagulation factors 2, 7, and 10 (P < .01), creatinine (P < .001), and IgM (P < .01) contained independent prognostic information. Inclusion of IGFBP-3 gave these results: IGFBP-3 (P < .02), alcohol intake (P < .05), coagulation factors 2, 7, 10 (P < .01), creatinine (P < .001), and IgM (P < .02) were independent predictors of survival. In conclusion, IGF-I or IGFBP-3 provide important additional information on survival in patients with alcohol-induced liver disease.

Adult↗
PubMed1996

Effect of oxygen inhalation on systemic, central, and splanchnic haemodynamics in cirrhosis.

BACKGROUND/AIMS: Patients with cirrhosis exhibit a hyperdynamic circulation with increased cardiac output and low arterial blood pressure. The aim of the present study was to assess the effects of oxygen inhalation on systemic, central, and splanchnic haemodynamics and vasoactive systems in patients with cirrhosis (n = 19). RESULTS: Spirometry was normal, but the carbon monoxide diffusing capacity (transfer factor) was significantly decreased, 18.8 ml.min-1.mmHg-1 (-32% of that predicted, p < 0.0001), and correlated significantly with the cardiac output (r = 0.78, p < 0.0005), plasma volume (r = 0.72, p < 0.001) and the central and arterial blood volume (r = 0.67, p < 0.005). After inhalation of 100% oxygen over a period of 20 min, the cardiac output decreased from 7.4 to 6.6 l/min (p < 0.0005), and the systemic vascular resistance increased from 980 to 1124 dyn.s.cm-5 (p < 0.005). The change in systemic vascular resistance was significantly greater in patients with mild liver dysfunction than in those with severe liver dysfunction (p < 0.02). In contrast, no significant changes were seen in the arterial or portal venous pressures during inhalation of oxygen. Arterial concentrations of catecholamines, renin, endothelin-1, and calcitonin gene-related peptide were all increased in patients with cirrhosis, but only the catecholamine concentrations decreased significantly (noradrenaline -13%, p < 0.02 and adrenaline -16%, p < 0.01) in response to oxygen. CONCLUSION: During oxygen inhalation cardiac output decreases and systemic vascular resistance increases in association with a decrease in arterial concentrations of catecholamine, but oxygen supply in patients with cirrhosis does not normalise the hyperdynamic circulation or the low arterial blood pressure.

Administration, Inhalation↗
PubMed1996

Activity and three-dimensional distribution of toluene-degrading Pseudomonas putida in a multispecies biofilm assessed by quantitative in situ hybridization and scanning confocal laser microscopy.

As a representative member of the toluene-degrading population in a biofilter for waste gas treatment, Pseudomonas putida was investigated with a 16S rRNA targeting probe. The three-dimensional distribution of P. putida was visualized in the biofilm matrix by scanning confocal laser microscopy, demonstrating that P. putida was present throughout the biofilm. Acridine orange staining revealed a very heterogeneous structure of the fully hydrated biofilm, with cell-free channels extending from the surface into the biofilm. This indicated that toluene may penetrate to deeper layers of the biofilm, and consequently P. putida may be actively degrading toluene in all regions of the biofilm. Furthermore, measurements of growth rate-related parameters for P. putida showed reduced rRNA content and cell size (relative to that in a batch culture), indicating that the P. putida population was not degrading toluene at a maximal rate in the biofilm environment. Assuming that the rRNA content reflected the cellular activity, a lower toluene degradation rate for P. putida present in the biofilm could be estimated. This calculation indicated that P. putida was responsible for a significant part (65%) of the toluene degraded by the entire community.

Base Sequence↗
PubMed1996

Endothelins in chronic liver disease.

This review describes recent progress in the accumulation of knowledge about the endothelins (ETs), a family of vasoactive 21-amino acid polypeptides, in chronic liver disease. Particular prominence is given to the dynamics of ET-1 and ET-3 and their possible relation to the disturbed circulation and neurohumoral dysregulation found in cirrhosis. Recent studies have shown that the ET system is highly activated in most cirrhotic patients. Circulating ET-1 and ET-3 levels have a positive relation to the severity of the disease and fluid retention, with the highest values recorded in patients with functional renal failure. Studies on liver biopsies have revealed synthesis of ET-1 in hepatic endothelial and other cells, and recent investigations have identified the hepatosplanchnic system as a major source of ET-1 and ET-3 spillover into the circulation, with a direct relation to portal venous hypertension. In addition, marked associations with disturbance of systemic haemodynamics and with abnormal distribution of blood volume have been reported. Although the pathophysiological importance of the ET system in chronic liver disease is not completely understood, similarities to other vasopressive and antinatriuretic regulatory systems (i.e. the sympathetic nervous system, renin-angiotensin-aldosterone and vasopressin) are apparent, with respect to kinetics and haemodynamic dysregulation. Cirrhosis seems to be a pathophysiological condition with indications of the occurrence of ETs, not only as local modulators, but also as a system with potential importance for systemic regulation.

Animals↗
PubMed1996

Relation of calcitonin gene-related peptide to systemic vasodilatation and central hypovolaemia in cirrhosis.

BACKGROUND: The aetiology of the reduced systemic vascular resistance and abnormal 'filling' 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. METHODS: Thirty-one cirrhotic patients and six control subjects underwent an investigation with determination of systemic haemodynamics and circulating CGRP. RESULTS: Circulating CGRP was significantly increased in patients with cirrhosis (P < 0.02) and covaried directly with the severity of cirrhosis (P < 0.02). The increased CGRP covaried negatively with the reduced systemic vascular resistance (P < 0.02), the reduced central blood volume (P < 0.01), and reduced central circulation time (P < 0.002) and positively with the non-central blood volume (P < 0.05). CONCLUSIONS: 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.

Adult↗
PubMed1995

[Portal hypertensive gastropathy].

Portal hypertensive gastropathy (PHG) as defined by congestive changes in the gastric mucosa owing to increased portal pressure, was first described about ten years ago. Whereas definition and grading of severity are still under debate, there is general agreement that PHG is a new clinical entity. PHG is present in 50-80% of patients with liver cirrhosis. PHG is a major cause of upper gastrointestinal bleeding in patients with portal hypertension (25-90% depending on severity). Presence of portal hypertension is a prerequisite for the development of PHG, and reduction of portal pressure and splanchnic blood flow with beta-adrenergic blockers has shown promising results, but an established medical treatment of PHG does not exist. Trials with new vasoactive drugs are awaited.

Chronic Disease↗
PubMed1995

[Prediction of bleeding risks and death in cirrhosis based on hemodynamic and metabolic variables. A study of patients with esophageal varices without previous bleeding].

As identification of patients with liver cirrhosis who are at risk of bleeding or death is essential in terms of prophylaxis, we have determined the prognostic influence of various patient characteristics on risk of bleeding and death. Fifty-five cirrhotic patients with oesophageal varices without previous bleeding were included in the study and followed up after a medium observation period of 446 days (range:5-1211 days). A total of 55 clinical, biochemical, haemodynamic, and endoscopic variables were classified as either systemic haemodynamic, portal haemodynamic, or metabolic. Using univariate analysis the following variables showed a significant relation to an increased risk of bleeding or death: high plasma volume (p < 0.02), high azygos blood flow (p < 0.004), high hepatic venous pressure gradient (p < 0.02), marked prominence of varices (p < 0.05), poor nutritional status (p < 0.0001), low clotting factor 2, 7, 10 (p < 0.002), low incapacitation index (p < 0.004), low serum albumin (p < 0.005), high bilirubin (p = 0.05), high alkaline phosphatases (p < 0.02), low arterial oxygen saturation (p = 0.02), and encephalopathy (p < 0.007). In a Cox regression model poor nutritional status (p < 0.00005), serum bilirubin (p < 0.001), short central circulation time (p < 0.03), low serum albumin (p < 0.02), and low index of clotting factor 2, 7, 10 (p < 0.05) were independently associated with higher risk. In conclusion, the results support the prognostic value of metabolic variables as earlier described. The prognostic significance of central circulation time stresses the importance of the hyperdynamic systemic circulation in the increased risk.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

[The hepatorenal syndrome].

Renal dysfunction and abnormal sodium-water handling are frequent in liver disease. The term hepatorenal syndrome (HRS) denotes a functional type of renal failure characterized by a progressive decrease in the glomerular filtration rate (GFR), greatly increased sodium retention, a high urine/plasma ratio of solutes, azotaemia, and oliguria. The main pathogenic feature is reduced renal blood flow (RBF), especially in the cortex. The kidney is morphologically intact and has been shown to rapidly regain normal function after transplantation to a recipient with a healthy liver. Three factors should be considered in the pathogenesis of HRS: 1) decreased liver function; 2) deranged haemodynamics, including abnormal blood pressure, blood volume, and blood flow distribution; and 3) deranged neuro-humoral regulation. The prognosis in HRS is very poor, and therapy for HRS has proved disappointing. However future studies should be directed towards the reduced liver function and the haemodynamic abnormalities, especially the abnormal renal vasoconstriction. Implantation of a peritoneovenous shunt, paracentesis with plasma expansion, certain "blockers", and normalization of arterial blood pressure have reversed the HRS only in the more early stages. Liver transplantation is the ultimate treatment for the HRS.

Hemodynamics↗
PubMed1995

Noninvasive 24-hour ambulatory arterial blood pressure monitoring in cirrhosis.

Cirrhotic patients have disturbed systemic hemodynamics with reduced arterial blood pressure, but this has not been investigated during daily activity and sleep. Systolic (SBP), diastolic (DBP), and mean arterial blood pressure (MAP), and heart rate (HR) were measured by an automatic ambulant device for monitoring blood pressure in 35 patients with cirrhosis and 35 healthy matched controls. During the daytime, SBP, DBP, and MAP were significantly lower in the patients than in the controls (median 118 vs. 127; 70 vs. 78; 86 vs. 94 mm Hg, P < .0001 to P < .05). The nighttime blood pressures were almost similar in the two groups (108 vs. 110; 65 vs. 67; 78 vs. 82 mm Hg, NS). Conversely, HR was significantly higher in the patients both in the daytime (86 vs. 72/min, P < .0001) and at night (80 vs. 64/min, P < .0001). Consequently, the reduction in blood pressure and HR from daytime to nighttime was significantly lower in the patients than in the controls (P < .0001 to P < .01). Multiple regression analysis showed HR, serum albumin, serum sodium, and clotting factors 2, 7, and 10 as significant independent predictors of SBP in cirrhosis. In conclusion, cirrhotic patients have elevated HR, but surprisingly normal arterial blood pressure during the nighttime, and the circadian variation in blood pressure and HR is diminished, probably because of an almost unaltered cardiac output during the 24 hours. These results may reflect a major defect in the ability of optimal regulation of blood pressure in cirrhotic patients.

Adult↗
PubMed1995

Decreased right heart blood volume determined by magnetic resonance imaging: evidence of central underfilling in cirrhosis.

Whether the central blood volume is reduced or expanded in cirrhosis is still under debate. Accordingly, the current study was undertaken to assess the volume of the heart cavities. Ten cirrhotic patients and matched controls had their right and left ventricular end-diastolic volumes (RVDV and LVDV), and end-systolic volumes (RVSV and LVSV) determined by magnetic resonance imaging (MRI). RVDV (122 vs. control 166 mL, P < .02), RVSV (41 vs. 80 mL, P < .02) and right atrial volume (47 vs. 64 mL, P < .05) were significantly reduced in the patients. In contrast, LVDV (134 vs. 129 mL, NS), LVSV (54 vs. 40 mL, NS), and left atrial volume (70 vs. 57 mL, P = .08) were normal or slightly increased. The right ejection fraction (68% vs. 53%, P < .05) was significantly increased, but the left ejection fraction was slightly reduced (61% vs. 69%, NS). The central and arterial blood volume (CBV), assessed as the cardiac output (CO) multiplied by the central circulation time, was significantly decreased (1.47 vs. 1.81 L, P < .05). The noncentral blood volume (4.43 vs. 3.64 L, P < .02), plasma volume (4.05 vs. 3.27 L, P < .02), and CO (7.11 vs. control 5.22 L/min, P < .01) were significantly increased in the patients. CCT (13.1 vs. 20.0 sec, P < .005) and the right ventricular transit time (0.79 vs. 1.35 sec, P < .005) were significantly reduced, but the left ventricular transit time was normal (0.91 vs. 0.88 sec, NS). Systemic vascular resistance was reduced (991 vs. 1,490 dyn.sec/cm5, P < .01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Effect of volume expansion on systemic hemodynamics and central and arterial blood volume in cirrhosis.

BACKGROUND & AIMS: Systemic vasodilatation in cirrhosis may lead to hemodynamic alterations with reduced effective blood volume and decreased arterial blood pressure. This study investigates the response of acute volume expansion on hemodynamics and regional blood volumes in patients with cirrhosis and in controls. METHODS: Thirty-nine patients with cirrhosis (12 patients with Child-Turcotte class A, 14 with class B, and 13 with class C) and 6 controls were studied. During hepatic vein catheterization, cardiac output, systemic vascular resistance, central and arterial blood volume, noncentral blood volume, and arterial pressure were determined before and during a volume expansion induced by infusion of a hyperosmotic galactose solution. RESULTS: During volume expansion, the central and arterial blood volume increased significantly in patients with class A and controls, whereas no significant change was found in patients with either class B or class C. Conversely, the noncentral blood volume increased in patients with class B and C. In both patients and controls, the cardiac output increased and the systemic vascular resistance decreased, whereas the mean arterial blood pressure did not change significantly. CONCLUSIONS: Only in mild cirrhosis is the effective blood volume able to increase in response to volume expansion. Our results are consistent with the peripheral vasodilatation hypothesis and the circulatory hyporeactivity occurring in advanced cirrhosis.

Adult↗