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Biomedical subjects

S Møller

Publications and source records attributed to S Møller.

At least 19 recordsLinked to original sources
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

The acid-labile subunit of the ternary insulin-like growth factor complex in cirrhosis: relation to liver dysfunction.

BACKGROUND/AIMS: In the circulation, insulin-like growth factor-I (IGF-I) is bound in a trimeric complex of 150 kDa with IGF binding protein-3 (IGFBP-3) and the acid-labile subunit (ALS). Whereas circulating IGF-I and IGFBP-3 are reported to be low in patients with chronic liver failure, the level of ALS has not been described in relation to hepatic dysfunction. The aim of the present study was therefore to measure circulating and hepatic venous concentrations of ALS in relation to hepatic function and the IGF axis. METHODS: Twenty-five patients with cirrhosis (Child class A/B/C:5/10/10) and 30 controls with normal liver function were studied. During a haemodynamic investigation, blood samples were collected from the hepatic vein and femoral artery, and the plasma concentrations of ALS, IGF-I and IGFBP-3 were determined. RESULTS: Hepatic venous and arterial concentrations of ALS were significantly decreased in the cirrhotic patients compared with the controls (-69% and -68%, respectively, both p<0.001). IGF-I and IGFBP-3 were similarly decreased in the cirrhotic patients (-51%,p<0.001). A significant hepatic extraction of ALS was found in the controls (6%, p<0.01) and in the cirrhotic patients (8%, p=0.08). ALS correlated significantly with indicators of liver dysfunction, including the Child-Turcotte score (r=-0.69, p<0.0001), IGF-I (r=0.82, p<0.0001) and IGFBP-3 (r=0.74, p<0.0001). CONCLUSIONS: Circulating and hepatic venous ALS are decreased in patients with cirrhosis with significant relations to liver dysfunction and other components of the IGF complex. A small hepatic extraction was found in controls, which suggests extrahepatic production of ALS. Future studies should focus on organ-specific removal of ALS.

Adult↗
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↗
PubMed1999

Increased circulating leptin in alcoholic cirrhosis: relation to release and disposal.

Leptin is a cytokine peptide that decreases appetite and thereby food intake and increases energy expenditure. It is produced in fat cells, but recent animal experiments have shown expression of leptin in modified stellate hepatic cells. Because a change in circulating leptin in cirrhosis could be caused by an altered production rate, altered disposal rate, or both, the present study was undertaken to identify regions of leptin overflow into the blood stream and regions of leptin extraction. Patients with alcoholic cirrhosis (n = 16) and control patients without liver disease (n = 12) were studied during catheterization with elective blood sampling from different vascular beds. Blood samples for leptin determination (radioimmunoassay) were taken simultaneously from artery/hepatic vein, artery/renal vein, artery/iliac vein, and artery/cubital vein. Patients with cirrhosis had significantly increased circulating leptin (7.3 vs. control 2.6 ng/mL, P <.002) that correlated directly to ascitic-free body mass index (r = 0.71, P <.005). A significant renal extraction ratio of leptin was observed in control patients (0. 16) and in patients with cirrhosis (0.07), but the latter value was significantly lower than in the control patients (-44%, P <.05) and inversely correlated to serum creatinine (r = -0.60, P <.05). A significant, but equal, hepatosplanchnic extraction of leptin was observed in cirrhotic patients and control patients (0.08 vs. 0.07). In patients with cirrhosis a significant cubital venous-arterial difference in leptin was observed, but not in control patients. The iliac venous/arterial leptin ratio was significantly above 1.0 in both groups and of similar size (1.16 vs. 1.15), but a higher difference in concentration was found in the cirrhotic patients (+33%, P <.05). The spillover rates of leptin in cirrhotic patients may be even higher than estimated from the increased systemic veno-arterial gradients. In conclusion, the elevated circulating leptin in patients with cirrhosis is most likely caused by a combination of decreased renal extraction and increased release from subcutaneous abdominal, femoral, gluteal, retroperitoneal pelvic, and upper limb fat tissue areas. The hepatosplanchnic bed drained through hepatic veins could not be identified as a source of increased circulating leptin in cirrhosis, but a contribution by the portosystemic collateral flow cannot be excluded.

Adult↗
PubMed1999

Increased arterial compliance in decompensated cirrhosis.

BACKGROUND/AIMS: In patients with cirrhosis, the systemic circulation is hyperdynamic with low arterial blood pressure and reduced systemic vascular resistance. The present study was undertaken to estimate the compliance of the arterial tree in relation to severity of cirrhosis, circulating level of the vasodilator, calcitonin gene-related peptide (CGRP) and mean arterial blood pressure (MAP). METHODS: Arterial compliance (COMPart=deltaV/deltaP) was determined as the stroke volume relative to pulse pressure (i.e. systolic minus diastolic blood pressure) during a haemodynamic evaluation of portal hypertension in patients with biopsy-verified cirrhosis (Child-Turcotte classes A/B/C=10/15/6). RESULTS: COMPart was significantly higher in cirrhotic patients (n=31) than in controls (n=10) (1.44 vs 1.00 x 10(-3) l/mmHg, p<0.01). It increased significantly through the Child-Turcotte classes A, B, and C (1.02, 1.47, and 2.1 x 10(-3) l/mmHg, respectively, p=0.03). The stroke volume did not change significantly with the severity of the disease, but pulse pressure decreased through class A, B, and C (79, 65, and 50 mmHg, respectively, p<0.01). COMPart was slightly, but significantly correlated to the circulating level of CGRP (r=0.34, p<0.05), and a substantial but inverse correlation was present to MAP (r= -0.63, p<0.002). CONCLUSIONS: Elevated arterial compliance in cirrhosis is directly related to the severity of the disease and to the elevated level of circulating vasodilator peptide CGRP, and inversely related to the level of arterial blood pressure. The altered static and dynamic functions of the arterial wall in cirrhosis may have implications for the circulatory and homoeostatic derangement, and potentially for therapy with vasoactive drugs.

Adult↗
PubMed1999

Hepatic and renal extraction of circulating type I procollagen aminopropeptide in patients with normal liver function and in patients with alcoholic cirrhosis.

The circulating level and splanchnic and renal extraction of serum type I procollagen aminoterminal propeptide (PINP) was studied in 20 patients with normal liver function and in 15 patients with alcoholic liver cirrhosis. In patients with alcoholic cirrhosis, the concentration of PINP in the femoral artery blood was significantly higher than in the group of patients with normal liver function (median 145 microg/l, 95% CI 98-195 versus 57 microg/l, 95% CI 42-92, p<0.001). A significant decrease in the concentration of PINP between the femoral artery (median 57 microg/l, 95% CI 42-92) and the hepatic vein (median 45 microg/l, 95% CI 40-70, p<0.001) was found in patients with normal liver function. In this group we also observed a significantly higher concentration of PINP in femoral artery blood (median 60 microg/l, 95% CI 45-87) as compared with that in renal vein (median 50 microg/l, 95% CI 40-65, p<0.001). In contrast, serum-PINP did not differ between arterial and hepatic or venous venous blood in patients with alcoholic cirrhosis. Size-chromatography revealed no significant change in the ratio of the high and low molecular forms of PINP following extraction in liver and kidney. It is concluded that circulating PINP is extracted in the normal liver and kidney, and that the serum concentration of PINP is significantly higher in patients with alcoholic cirrhosis than in patients with normal liver function. Both the hepatic and the renal clearance of PINP are seriously impaired/reduced in patients with alcoholic cirrhosis.

Adult↗
PubMed1999

Elevated carboxy terminal cross linked telopeptide of type I collagen in alcoholic cirrhosis: relation to liver and kidney function and bone metabolism.

BACKGROUND: The carboxy terminal cross linked telopeptide of type I collagen (ICTP) has been put forward as a marker of bone resorption. Patients with alcoholic liver disease may have osteodystrophy. AIMS: To assess circulating and regional concentrations of ICTP in relation to liver dysfunction, bone metabolism, and fibrosis. METHODS: In 15 patients with alcoholic cirrhosis and 20 controls, hepatic venous, renal venous, and femoral arterial concentrations of ICTP, and bone mass and metabolism were measured. RESULTS: Circulating ICTP was higher in patients with cirrhosis than in controls. No overall significant hepatic disposal or production was found in the patient or control groups but slightly increased production was found in a subset of patients with advanced disease. Significant renal extraction was observed in the controls, whereas only a borderline significant extraction was observed in the patients. Measurements of bone mass and metabolism indicated only a mild degree of osteodystrophy in the patients with cirrhosis. ICTP correlated significantly in the cirrhotic patients with hepatic and renal dysfunction and fibrosis, but not with measurements of bone mass or metabolism. CONCLUSIONS: ICTP is highly elevated in patients with cirrhosis, with no detectable hepatic net production or disposal. No relation between ICTP and markers of bone metabolism was identified, but there was a relation to indicators of liver dysfunction and fibrosis. As the cirrhotic patients conceivably only had mild osteopenia, the elevated ICTP in cirrhosis may therefore primarily reflect liver failure and hepatic fibrosis.

Adult↗
PubMed1998

[Decompensation].

Fluid and sodium retention with peripheral oedema and ascites are often seen in decompensated patients with diseases of the liver, kidney and heart and in malignancies. Despite a careful clinical examination including relevant biochemical tests, decompensation is associated with diagnostic challenges. Two cases are presented where a haemodynamic investigation of the splanchnic and systemic circulation contributed to the establishment of a correct diagnosis, and the advantages of this diagnostic tool are discussed.

Ascites↗
PubMed1998

The organ extraction and splanchnic haemodynamic effects of octreotide in cirrhotic patients.

BACKGROUND: Intravenous octreotide is an established treatment of oesophageal variceal haemorrhage in the cirrhotic patient. AIM: To examine the organ extraction and splanchnic haemodynamic effects of octreotide in cirrhotic patients with portal hypertension. METHODS: Thirteen patients with cirrhosis had hepatic venous catheterization performed. Hepatic venous pressure gradient (HVPG), indocyanine green (ICG) clearance and hepatic blood flow (HBF) were determined in the basal state and during 60 min of octreotide infusion by bolus injection (0.75 microg/kg) followed by continuous infusion of 0.75 microg/kg x h. Blood samples were simultaneously drawn from the femoral artery and the hepatic and renal veins. RESULTS: The extraction fraction of octreotide in the liver was 0.05 (-0.01 - 0.14) (median (interquartile range)) and in the kidneys 0.16 (-0.06 - 0.35). The extraction fraction ratio (E(liver)/E(kidney)) was 0.69 (-0.20 - 1.06). Hepatic clearance was 47 mL/min (3-88) (n = 11). No correlations were found between liver biochemistry or galactose elimination capacity (GEC; a metabolic measure of liver function) and renal extraction fraction or liver clearance. Octreotide had no effect on HVPG or wedged hepatic venous pressure although free hepatic venous pressure increased during octreotide infusion: 6 mmHg (5-9) vs. 7 mmHg (6-10) (P = 0.02). No effect on HBF was observed while ICG clearance decreased significantly. CONCLUSIONS: Octreotide is extracted in cirrhotic patients by both the liver and the kidney, the latter being the most important organ of elimination. Octreotide decreases liver metabolic activity determined by the ICG clearance technique, but no significant effects of octreotide on HVPG or HBF could be demonstrated.

Adult↗
PubMed1998

Calcipotriol cream with or without concurrent topical corticosteroid in psoriasis: tolerability and efficacy.

The objectives of the study were to determine whether concurrent treatment with calcipotriol (50 microg/g) and either clobetasone 17-butyrate cream (0.5 mg/g) (moderate potency) or betamethasone 17-valerate cream (1 mg/g) (potent) or placebo (vehicle of calcipotriol) was more effective and/or caused less skin irritation than calcipotriol cream (50 microg/g) used twice daily. It was a multicentre, double-blind, parallel group study. Patients applied calcipotriol cream in the morning and either vehicle (n = 174), calcipotriol (n = 174), clobetasone (n = 175) or betamethasone creams (n = 176) in the evening for up to 8 weeks. Adverse events led to withdrawal in 20 patients (2.9%). The mean percentage change in PASI (psoriasis area and severity index) was -40.6 in the calcipotriol/vehicle group, -48.3 in the calcipotriol/calcipotriol group, -53.7 in the calcipotriol/clobetasone 17-butyrate group and -57.5 in the calcipotriol/betamethasone 17-valerate group. A statistically significant difference was seen between the four treatment groups (P = 0.006) with calcipotriol/vehicle being less effective than the other treatments. A statistically significant difference in favour of calcipotriol/betamethasone 17-valerate was seen between the calcipotriol/calcipotriol group and the calcipotriol/betamethasone 17-valerate group. The majority of adverse events were skin irritations, which were reported for 31.2% of patients treated with calcipotriol/vehicle, 34.3% of patients treated with calcipotriol twice daily and 23.8% vs. 17.1% of patients treated with calcipotriol/clobetasone 17-butyrate and calcipotriol/betamethasone 17-valerate, respectively. Skin irritation was seen statistically significantly less frequently in patients treated with calcipotriol/ clobetasone 17-butyrate or calcipotriol/betamethasone 17-valerate (P = 0.001), whereas no difference was seen between the other groups. In conclusion, calcipotriol applied twice daily was as effective as calcipotriol/clobetasone 17-butyrate, but slightly less effective than calcipotriol/betamethasone 17-valerate. The incidence of skin irritation was less for patients using concurrent corticosteroids, whereas treatment with calcipotriol/vehicle did not reduce the incidence of skin irritation when compared with calcipotriol twice daily.

Adult↗
PubMed1998

Neurohumoral fluid regulation in chronic liver disease.

Impaired homeostasis of the blood volume, with increased fluid and sodium retention, is a prevailing element in the deranged systemic and splanchnic haemodynamics in patients with liver disease. In this review, some basic elements of the circulatory changes that take place and of neurohumoral fluid regulation are outlined in order to provide an update of recent investigations on the neuroendocrine compensation of circulatory and volume dysfunction in chronic liver disease. The underlying pathophysiology is a systemic vasodilatation in which newly described potent vasoactive substances such as nitric oxide and vasodilating peptides seem to play an important role. The development of central hypovolaemia and activation of potent vasoconstricting systems such as the renin-angiotensin-aldosterone system and the sympathetic nervous system lead to a hyperdynamic circulation with increased heart rate and cardiac output. Moreover, patients exhibit an autonomic dys- and hyperfunction with vascular hyporeactivity to pressor stimuli. The circulatory dysfunction may be part of a multiorgan failure with disturbed haemodynamics of various vascular beds, including those of the splanchnic system, kidneys, brain and lungs. It is still an enigma why patients with chronic liver disease are at the same time overloaded and functional hypovolaemic with a hyperdynamic, hyporeactive circulation. Further research is needed to find the solution to this apparent haemodynamic conflict concerning the abnormal neurohumoral fluid regulation in chronic liver disease.

Adrenomedullin↗
PubMed1998

In situ gene expression in mixed-culture biofilms: evidence of metabolic interactions between community members.

Microbial communities growing in laboratory-based flow chambers were investigated in order to study compartmentalization of specific gene expression. Among the community members studied, the focus was in particular on Pseudomonas putida and a strain of an Acinetobacter sp., and the genes studied are involved in the biodegradation of toluene and related aromatic compounds. The upper-pathway promoter (Pu) and the meta-pathway promoter (Pm) from the TOL plasmid were fused independently to the gene coding for the green fluorescent protein (GFP), and expression from these promoters was studied in P. putida, which was a dominant community member. Biofilms were cultured in flow chambers, which in combination with scanning confocal laser microscopy allowed direct monitoring of promoter activity with single-cell spatial resolution. Expression from the Pu promoter was homogeneously induced by benzyl alcohol in both community and pure-culture biofilms, while the Pm promoter was induced in the mixed community but not in a pure-culture biofilm. By sequentially adding community members, induction of Pm was shown to be a consequence of direct metabolic interactions between an Acinetobacter species and P. putida. Furthermore, in fixed biofilm samples organism identity was determined and gene expression was visualized at the same time by combining GFP expression with in situ hybridization with fluorescence-labeled 16S rRNA targeting probes. This combination of techniques is a powerful approach for investigating structure-function relationships in microbial communities.

Acinetobacter↗
PubMed1998

Arterial hypoxaemia in cirrhosis: fact or fiction?

BACKGROUND: Although low arterial oxygen tension (Po2) has been claimed to occur in one to two thirds of patients with cirrhosis, hypoxaemia appears to be rare in clinical practice. AIMS: To assess the frequency of arterial hypoxaemia in cirrhosis in relation to clinical and haemodynamic characteristics. PATIENTS: One hundred and forty two patients with cirrhosis without significant hepatic encephalopathy (grades 0-I) (41 patients in Child class A, 57 in class B, and 44 in class C) and 21 patients with hepatic encephalopathy. RESULTS: Mean Po2 in kPa was 11.3 in Child class A, 10.8 in class B, 10.6 in class C, and 10.6 in patients with encephalopathy (p < 0.05). The fraction of patients with Po2 below the lower normal limit of 9.6 kPa was 10%, 28%, 25%, and 43%, respectively in class A, B, C, and in patients with encephalopathy (p < 0.05). Oxygen saturation (So2) in these groups was respectively: 96%, 96%, 96%, and 93% (NS). So2 was below the lower limit of 92% in 0%, 9%, 7%, and 24% (p < 0.05). In patients without hepatic encephalopathy, a multivariate regression analysis revealed that independent determinants of a low Po2 were a high arterial carbon dioxide tension, a low systemic vascular resistance, and a low indocyanine green clearance (p < 0.0001). CONCLUSION: The prevalence of arterial hypoxaemia in cirrhosis is about 22% in patients without encephalopathy, but it varies from 10-40% depending on the degree of hepatic dysfunction. Arterial hypoxaemia in patients with cirrhosis of differing severity seems lower than previously reported, and patients with severe arterial hypoxaemia are rare.

Adult↗
PubMed1998

The acid-labile subunit of human ternary insulin-like growth factor binding protein complex in serum: hepatosplanchnic release, diurnal variation, circulating concentrations in healthy subjects, and diagnostic use in patients with growth hormone deficiency.

Circulating insulin-like growth factor-I (IGF-I) is predominantly bound in the trimeric complex comprised of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS). Circulating concentrations of IGF-I, IGFBP-3 and ALS are believed to reflect the GH secretory status, but the clinical use of ALS determination is not known. We therefore, determined the: 1) hepatosplanchnic release of ALS by liver vein catheterization (n=30); 2) 24-h diurnal variation of ALS (n=8); 3) normal age-related ranges of circulating ALS (n=1158); 4) diagnostic value of ALS in 108 patients with childhood-onset GH deficiency (GHD). We found: 1) no significant arteriovenous gradient over the liver ofALS, IGF-I, and IGFBP-3; 2) the diurnal variation of ALS was 12% (mean coefficient of variation percent); 3) ALS levels increased throughout childhood with maximal levels in puberty, with a subsequent decrease with age in adults; and 4) ALS levels were below -2 SD in 57 of 79 GHD patients (sensitivity 72%) and above 2 SD in 22 of 29 patients with normal GH response (specificity 76%), which was similar, compared with the diagnostic utility of IGF-I and IGFBP-3. Finally, our findings indicate that hepatic ALS production is not measurable by this approach or, alternatively, that the liver is not the primary source of circulating ALS, IGF-I, or IGFBP-3 in humans. In conclusion, we have provided extensive normal data for a novel ALS assay and found that circulating ALS levels exhibit minor diurnal variation. We suggest that ALS determination may be used in future classification of adults suspected of GHD.

Adolescent↗