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Biomedical subjects

S Møller

Publications and source records attributed to S Møller.

At least 91 records · Page 5Linked to original sources
PubMed1995

Endothelin-1 and endothelin-3 in cirrhosis: relations to systemic and splanchnic haemodynamics.

BACKGROUND/AIMS: Endothelins are isopeptides with potent vasoactive properties, but their implications in the hyperkinetic syndrome in cirrhosis are obscure. Therefore, the aim of the present study was to relate hepatic venous and circulating endothelin-1 and endothelin-3 to systemic and splanchnic haemodynamics. METHODS: Endothelin-1 and endothelin-3 were measured in samples from a hepatic vein and the femoral artery in 42 patients with cirrhosis, eight hypertensive controls and 10 normotensive controls. RESULTS: Hepatic venous endothelin-1 was significantly higher in the patients with cirrhosis, mean 21.2 +/- 0.9 pg/ml (SEM) than in the hypertensive controls, 12.4 +/- 2.4 pg/ml, and normotensive controls, 9.6 +/- 1.6 pg/ml (p < 0.00001). Similarly arterial endothelin-1 was significantly higher in the patients with cirrhosis than in the controls (p < 0.00001). Hepatic venous endothelin-1 was significantly correlated with the hepatic venous pressure gradient (r = 0.61, p < 0.00004), serum creatinine (r = 0.35, p < 0.03), diastolic blood pressure (r = -0.31, p < 0.05), central and arterial blood volume (-0.36, p < 0.05), central circulation time (r = -0.41, p < 0.02), and serum sodium (r = -0.56, p < 0.00002) in the patients with cirrhosis. The hepatosplanchnic release of endothelin-1, assessed as the arteriohepatic-venous difference adjusted for hepatic plasma flow, was higher in the group with cirrhosis, 1.5 +/- 0.4 ng/min, than in the normotensive controls, -0.1 +/- 0.2 ng/min (p < 0.01), and was furthermore correlated to the cardiac output in the group with cirrhosis (r = 0.35, p < 0.04). Hepatic venous endothelin-3 was higher in the patients with cirrhosis, 19.0 +/- 1.4 pg/ml (n = 23), as compared with hypertensive controls, 14.2 +/- 1.3 pg/ml, and normotensive controls, 10.0 +/- 1.4 pg/ml (p < 0.002). The same pattern was found in arterial endothelin-3. Hepatic venous endothelin-3 correlated significantly with central and arterial blood volume (r = 0.56, p < 0.02). The hepatosplanchnic release of endothelin-3 was higher in the patients with cirrhosis, 1.0 +/- 0.7 ng/min, than in the normotensive controls, -0.7 +/- 0.4 ng/min (p = 0.05). CONCLUSIONS: In the presence of cirrhosis, hepatic venous and circulating endothelin-1 and endothelin-3 are elevated with significant relations to systemic and splanchnic haemodynamics, and the hepatosplanchnic release of both peptides is increased. This suggests that the endothelin system is implicated in both systemic and portal haemodynamic abnormalities in cirrhosis, although this study does not allow conclusions on causal relationships.

Adult↗
PubMed1995

Concentrations, release, and disposal of insulin-like growth factor (IGF)-binding proteins (IGFBP), IGF-I, and growth hormone in different vascular beds in patients with cirrhosis.

The liver is thought to be the major source of circulating insulin-like growth factor (IGF-I) and IGF-binding protein-1 (IGFBP-1), whereas the primary production site of circulating IGFBP-3 remains unknown. As other tissues may contribute to the circulating pool of IGF-I and IGFBP, the aim of the present study was to assess the hepatic and renal arterio-venous difference and production rates of IGF-I, IGFBP-1, IGFBP-3, and GH in cirrhotic patients (n = 22) and matched control subjects (n = 27). IGFBP-1 and -3, IGF-I, and GH levels were measured by RIA in hepatic, renal, and peripheral veins and in the femoral artery. Levels of IGFBP-1 to -4 were additionally determined by Western ligand blotting. Hepatic venous IGFBP-1 was significantly increased in the cirrhotic patients (mean +/- SEM, 33.6 +/- 9.1 vs. 10.4 +/- 1.9 micrograms/L; P < 0.001), and arterio-renal-venous extraction was significant in both patients (6 +/- 2%; P < 0.01) and controls (11 +/- 1%; P < 0.001). Conversely, IGFBP-3 was decreased in the cirrhotic patients (1265 +/- 149 vs. 2712 +/- 137 micrograms/L; P < 0.001). IGFBP-3 correlated significantly with the wedged hepatic venous pressure (r = -0.49; P < 0.05), serum aspartate aminotransferase (r = -0.66; P < 0.01), serum bilirubin (r = -0.65; P < 0.01), serum albumin (r = 0.64; P < 0.01), and the Child score (r = -0.57; P < 0.01). IGF-I was significantly lower in the cirrhotics (57 +/- 10 vs. 143 +/- 11 micrograms/L; P < 0.001). No significant IGFBP-3 proteolysis was demonstrated in cirrhotics or controls. No significant differences were found in the values obtained simultaneously from hepatic, renal, and brachial veins or femoral artery, which suggests that no major net production or release of IGFBP-3 or IGF-I occurs in these tissues. No differences in IGFBP-2 or IGFBP-4 determined by Western ligan blot were found between patients and controls. The IGF-I concentrations correlated significantly with parameters of biochemical liver function. Basal GH concentrations were significantly higher in the cirrhotics (1.19 +/- 0.13 vs. 0.58 +/- 0.08 micrograms/L; P < 0.001). A significant hepatic disposal of GH was found in the patients (P < 0.05) and controls (P < 0.001).(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1995

Endothelin-1 and -3 plasma concentrations in patients with cirrhosis: role of splanchnic and renal passage and liver function.

Increased as well as decreased plasma concentrations of the endothelins, endogenous vasoactive peptides, have been reported in cirrhosis. This might be caused by alterations of hepatic or renal clearance or release. Therefore, the aim of the current study was to investigate the influence of splanchnic and renal passage and of liver function on plasma concentrations of endothelin-1 (ET-1) and endothelin-3 (ET-3) in patients with cirrhosis compared with controls. Eighteen patients with cirrhosis and 8 normotensive controls of similar age were investigated. Arterial and venous plasma samples were obtained simultaneously, and ET-1 and ET-3 concentrations were determined in extracted plasma by two separate radioimmunoassays. Arterial as well as hepatic and renal venous concentrations of ET-1 in cirrhosis (17.8 +/- 0.8 pg/mL, 19.1 +/- 0.9 pg/mL, and 16.8 +/- 0.8 pg/mL) were significantly (P < .001) higher than in controls (9.2 +/- 1.7 pg/mL, 9.0 +/- 2.0 pg/mL, and 8.4 +/- 1.9 pg/mL, respectively). The same held true for the corresponding ET-3 plasma concentrations in cirrhosis (19.3 +/- 1.6 pg/mL, 20.5 +/- 1.5 pg/mL, and 18.4 +/- 1.5 pg/mL, respectively) compared with controls (11.1 +/- 1.8 pg/mL, 11.3 +/- 1.5 pg/mL, and 10.1 +/- 1.7 pg/mL, respectively; P < .01). There was a significant (P < .05) renal net extraction of ET-1 and ET-3 in cirrhosis. In contrast, a significant (P < .05) net release of ET-1 and ET-3 (2.40 +/- 0.80 ng/min and 1.75 +/- 1.16 ng/min) during splanchnic passage was observed in cirrhosis, but not in controls (-0.24 +/- 0.51 ng/min, and -0.46 +/- 0.64 ng/min).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Optimized analysis of recurrent bleeding and death in patients with cirrhosis and esophageal varices. Copenhagen Esophageal Varices Sclerotherapy Project.

The course of cirrhosis after the first episode of variceal bleeding is characterized by recurrent episodes of bleeding and bleeding-free periods, with each new stage being associated with an initially high mortality rate. Analysis of the course of this disease is usually based on traditional survival models measuring observation time from admission to hospital. This approach cannot provide valid answers to the following clinically relevant questions: 1) what is the risk of death while bleeding? 2) what is the risk of continuing bleeding? 3) what is the risk of death after bleeding has stopped? 4) what is the risk of a new bleeding episode among those who remain alive and do not bleed? and 5) do the answers to the former four questions depend on the number of previous bleeding episodes or on the time since the first episode? These questions may be addressed using the multistage, competing risks model presented here. By measuring time from the start of each new bleeding or bleeding-free period, this model synchronizes the patients with respect to disease development and, hence, to level of the rate of new clinical events. This reduces the heterogeneity of risk levels in the patient group at any given time. In an analysis of 94 patients with cirrhosis admitted for their first episode of variceal bleeding, we estimated the mortality rates during bleeding and without current bleeding, the rate of cessation of bleeding and the rate of rebleeding. The influence of number of previous rebleedings and of the time since the first bleeding was examined using a Cox regression model for competing risks.(ABSTRACT TRUNCATED AT 250 WORDS)

Disease Progression↗
PubMed1994

Prognostic variables in patients with cirrhosis and oesophageal varices without prior bleeding.

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

Adult↗
PubMed1994

Short-term effect of recombinant human growth hormone in patients with alcoholic cirrhosis.

As growth hormone possesses anabolic properties that are active on protein metabolism, and thus of potential benefit to patients with chronic liver disease, we determined the metabolic effects of recombinant human growth hormone on insulin-like growth factor-I (IGF-I) its specific binding proteins, and liver function. Twenty consecutive patients with cirrhosis were randomized to recombinant human growth hormone (Norditropin, 4 I.U. twice daily) subcutaneously for 6 weeks (n = 10) or conventional medical treatment (n = 10). The serum concentrations of insulin-like growth factor-I in the recombinant human growth hormone group increased after 3 (p < 0.01) and 6 weeks (p < 0.02), whereas no significant changes were observed in the control group. The change in insulin-like growth factor-I during the treatment period was expressed as area under the curve (AUC). The AUCIGF-I was significantly larger in the recombinant human growth hormone group (median AUCIGF-I: 12.1, range: 0.0-54.7 weeks.nmol/l) than in the control group (median AUCIGF-I: 0.2, range: -10.6-9.9 weeks.nmol/l) (p < 0.007). Insulin-like growth factor binding protein-3 concentrations increased in the recombinant human growth hormone treated patients as well as in controls, whereas no change in insulin-like growth factor binding protein-1 concentrations was found. No significant changes were seen in the area under the curve for biochemical liver function tests. We conclude that administration of recombinant human growth hormone induces an increase in very low levels of insulin-like growth factor-I, even in patients with cirrhosis with advanced disease, but the clinical benefits remain to be demonstrated.

Adult↗
PubMed1994

Responses to nutrient starvation in Pseudomonas putida KT2442: analysis of general cross-protection, cell shape, and macromolecular content.

The physiology of Pseudomonas putida KT2442 with respect to growth and carbon starvation was studied. During the transition from growth to nongrowth, the cell shape changes from cylindrical to spheric, a change which is accompanied by reductions in cell size, DNA and ribosome content, and the rate of total protein synthesis. In addition, a pattern of general cross-protection develops, which enables the cells to survive environmental stresses such as high and low temperatures, elevated osmolarity, solvents, and oxidative agents. Cultures are almost fully viable during 1 month of carbon, nitrogen, and multiple-nutrient starvation and are considered to be in an active nondormant state. In contrast, strain KT2442 does not survive well under conditions of sulfate and phosphate starvation.

Adaptation, Physiological↗
PubMed1993

Urinary growth hormone (U-GH) excretion and serum insulin-like growth factor 1 (IGF-1) in patients with alcoholic cirrhosis.

Basal serum growth hormone (GH) levels are elevated and insulin-like growth factor 1 (IGF-1) concentrations in serum are suppressed in patients with chronic liver disease. The aim of this study was to measure the urinary GH (U-GH) excretion and IGF-1 concentrations in patients with cirrhosis and to correlate these both to clinical and biochemical characteristics and survival rate. Urinary GH excretion, IGF-1, and other biochemical parameters were measured in 36 patients with alcoholic cirrhosis, while in the control group of 34 healthy individuals only U-GH excretion was measured. U-GH excretion was significantly higher in patients than in the healthy controls (p < 0.00001), and increased with deteriorating liver function assessed by modified Child-Turcotte score (p < 0.01). The highest U-GH excretions were found in patients with hepatic encephalopathy (p < 0.003). IGF-1 levels were reduced in cirrhosis and correlated with liver function (p < 0.001). Serum IGF-1 concentrations below 3.1 nmol/l were associated with a poor prognosis (p < 0.004). The elevated U-GH in patients with alcoholic cirrhosis may reflect high serum levels of GH due to increased pituitary secretion or decreased hepatic degradation of GH. In addition, the IGF-1 levels reflect the degree of hepatic insufficiency and, thus, seem to provide new prognostic information.

Adult↗
PubMed1993

Elevated circulating plasma endothelin-1 concentrations in cirrhosis.

As endothelin-1 (ET-1), a potent vasoconstricting peptide, may play a role in the circulatory derangement and renal impairment in cirrhosis, the aim of the present study was to investigate plasma concentrations of ET-1 in different vascular beds in relation to clinical and biochemical parameters of liver function. Median brachial venous ET-1 concentrations were substantially higher in patients with cirrhosis (3.40 pg/ml, range: 1.25-7.84, n = 24) than in controls (1.53 pg/ml, range: 0.78-2.12, n = 11) (P < 0.00005). In patients with cirrhosis ET-1 was directly correlated to serum creatinine (r = 0.70, P < 0.0001) and aspartate aminotransferase (r = 0.44, P < 0.03) and negatively correlated to serum sodium (r = -0.58, P < 0.003). In patients who underwent liver vein catheterization (n = 8), no significant differences were found in ET-1 plasma concentration between the liver, renal, or femoral veins on the one hand and the femoral artery on the other (P > 0.1), indicating no major net elimination or release in the liver, kidney or lower limb. A significant negative correlation was found between systolic and diastolic blood pressures on the one hand and circulating ET-1 on the other (r = -0.71, P < 0.05). In conclusion, circulating ET-1 is elevated in cirrhosis and related to markers of systemic circulation and renal function, thus suggesting a role for ET-1 in the circulatory derangement and nephropathy in cirrhosis. Locations of major net elimination or release of ET-1 were not identified.

Adult↗
PubMed1992

Who benefits from endoscopic sclerotherapy of bleeding oesophageal varices? Proposal for differential indications. The Copenhagen Esophageal Varices Sclerotherapy Project.

The value of early sclerotherapy for variceal haemorrhage remains unsettled, possibly because the treatment may be beneficial to some patients and harmful to others. On the basis of a randomized clinical trial of sclerotherapy in 187 patients presenting with their first variceal haemorrhage, we examined the relationship between clinical, endoscopic and biochemical characteristics at admission and the treatment effect on mortality. As previously published, sclerotherapy had no overall effect on the very high mortality during the first 6 weeks (47%), but thereafter the mortality and risk of rebleeding were reduced. The analysis showed that in the 48% of the patients with disturbed consciousness and/or elevated plasma creatinine, sclerotherapy considerably increased short-term mortality, and this was not compensated for by increased long-term survival. Among patients without these characteristics, sclerotherapy reduced mortality in the 25% with ascites, but did not affect short-term mortality in the 27% without. Sclerotherapy significantly improved the long-term survival of these patients. The results suggest that sclerotherapy should not be used in patients with disturbed cerebral or renal function, whereas it may be beneficial in patients without these characteristics.

Adult↗
PubMed1992

Naloxone stimulation test in women with hypothalamic amenorrhea: a preliminary report.

We researched the possibility of the induction of ovulation by means of chronic opioid receptor blockade in 4 women with hypothalamic amenorrhea. Daily 4 mg naloxone were given as a bolus injection intravenously. By means of continuous determination of LH, FSH, 17-beta-estradiol (E2) and progesterone as well as of sonographic folliculometry follicular growth and subsequent ovulation should have been proved. Neither we found alterations of the basal values of LH, FSH, E2 and progesterone, nor we observed a follicular growth. These results lead us to the conclusion to put a naloxone stimulation test before further therapy. In this way opioid mediated hypothalamic ovarian insufficiencies can be registered and a therapy optimum can be reached early.

Adult↗
PubMed1992

Solvent and temperature effects on the excited singlet state absorption of diphenylbutadiene.

Nanosecond excited state absorption spectra of all-trans-1,4-diphenyl-1,3-butadiene (DPB) and a rigid s-cis DPB analog, 1,4-diphenyl-1,3-cyclopentadiene, were obtained in several hydrocarbon solvents at room temperature and low temperatures. Analysis of the excited state absorption spectra of these two molecules suggests the presence of excited state s-cis rotamers in DPB at room temperature.

Butadienes↗
PubMed1992

Insulin-like growth factor 1 and growth hormone in chronic liver disease.

Somatomedins or insulin-like growth factors (IGF) are peptides synthesized in the liver. IGFs have different anabolic and metabolic actions and are important in normal growth and development. The concentration of insulin-like growth factor 1 (IGF-1) is low in patients with chronic liver disease mainly due to the decreased liver function. Low levels of somatomedins are also seen in patients with growth hormone (GH) insufficiency, renal impairment, and malnutrition. GH stimulates the production of IGF-1, and both are part of a negative feedback system acting on hepatic, pituitary, and hypothalamic levels. The basal and stimulated GH concentration is pathologically elevated in patients with chronic liver disease and may be due to a disturbed regulation. Alterations in liver IGF receptors in patients with chronic liver disease still require investigation as they may be important for the liver function.

Chronic Disease↗
PubMed1991

Insulin-like growth factor 1 (IGF-1) in burn patients.

Variations in growth factor IGF-1 levels during wound healing were assessed in 23 patients with burns of varying extent and severity. The patients were followed during the postburn period and the IGF-1 levels were regularly measured by radioimmunoassay. All patients with large burns had reduced IGF-1 levels which correlated with the surface area of burn. The most plausible reason for the suppressed IGF-1 level in these patients may be diffusion from the burned skin as we have found a strong correlation between IGF-1 and serum albumin. The reduced IGF-1 levels may contribute to impaired wound healing in these patients.

Adult↗