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Biomedical subjects

H Vilstrup

Publications and source records attributed to H Vilstrup.

At least 73 records · Page 4Linked to original sources
PubMed1995

Somatostatin prevents the postoperative increases in plasma amino acid clearance and urea synthesis after elective cholecystectomy.

The importance of glucagon on postoperative changes in hepatic amino-nitrogen conversion were investigated in six patients undergoing elective cholecystectomy for uncomplicated gall stones. Patients were given infusions of somatostatin (bolus of 6 micrograms/kg followed by continuous infusion of 6 micrograms/kg/h) from induction of anaesthesia to the end of investigation, the first postoperative day (30 hours). Controls were 16 patients undergoing the same procedures omitting the somatostatin infusion. In all patients blood concentration and plasma clearance of total alpha-amino-nitrogen, and amino acid stimulated rate of urea synthesis were measured. Elective cholecystectomy decreased blood alpha-amino-nitrogen concentration from mean (SEM) 2.9 (0.2) to 2.4 (0.1) mmol/l (p < 0.05), increased the clearance of total alpha-amino-nitrogen from 5.2 (0.3) to 6.6 (0.3) ml/s (p < 0.05), and increased the rate of amino acid stimulated urea synthesis from 27 (1) to 37 (2) mumol/s (p < 0.05) pointing to increased hepatic removal of amino-nitrogen at expense of plasma amino-nitrogen. Infusion of somatostatin prevented increase of glucagon for 24 hours after surgery, and prevented the negative changes in postoperative nitrogen homeostasis resulting from the postoperative changes in hepatic nitrogen conversion, suggesting glucagon as mediator. The exact mechanism remains in doubt, however, because of the multiple effects of somatostatin.

Adult↗
PubMed1994

[Attitude of the population to organ transplantation].

The attitude of the Danish population towards organ transplantation was examined by means of an interview study, executed by the Gallup Institute. From a sample population of 1391 persons above 18 years of age, 798 persons (70%) were interviewed, in the period April 24th to May 3rd 1992. When asked what they thought the general attitude toward transplantation was amongst the population, 65% answered "positive" or "very positive". The attitudes to three situations, namely to organ donation after the death of a parent, spouse or child was examined subsequently. Amongst those who had an opinion, 75% (72-76%) were positive and 25% (24-27%) were negative. The younger the interviewed person, the more positive the attitude. According to the Danish law the relatives can decide for or against organ donation if the deceased has not expressed her view on organ donation. In view of the general positive attitude of the population it is proposed that we introduce a system where every adult person is asked concerning his/her attitude, e.g. in connection with the yearly income tax form or renewal of the health insurance certificate.

Adult↗
PubMed1994

Control of non-insulin-dependent diabetes mellitus partially normalizes the increase in hepatic efficacy for urea synthesis.

The relation of urea synthesis rate to blood alanine concentration was assessed in seven healthy controls and eight patients with non-insulin-dependent diabetes mellitus (NIDDM) before (hemoglobin A1c [HbA1c] = 9.9% +/- 1.9%, mean +/- SD) and after (HbA1c = 7.9% +/- 0.8%) improvement of metabolic control. Following an overnight fast, alanine was infused at a rate of 2 mmol/(h.kg body weight [BW]). The hourly rate of urea synthesis was determined as the urinary excretion of urea corrected for accumulation of urea in total body water (TBW) and intestinal hydrolysis. The functional hepatic nitrogen clearance (FHNC) was calculated as the slope of the linear relation of urea synthesis rate to blood alanine concentration. The glucagon level was increased by twofold at the first investigation, but was not increased at the second. The insulin level was moderately increased at both investigations. In controls FHNC was 21.8 +/- 4.4 L/h, in poorly controlled patients it was increased to 36.6 +/- 4.3 L/h (P < .01), and following improvement of metabolic control it was not different from control levels at 28.6 +/- 4.3 L/h. By correlation analyses, FHNC was found only to be related to the fasting glucose value, albeit weakly (R2 = .39). In conclusion, hepatic kinetics of urea synthesis in poorly controlled NIDDM patients are changed in favor of increased conversion of alanine N to urea N at any amino acid concentration. This perturbation is partially normalized by improved metabolic control.

Adult↗
PubMed1994

Effect of lanreotide, a somatostatin analogue, on urea synthesis in normal man.

The aim was to investigate the effect of lanreotide (Angiopeptin) on urea synthesis. Lanreotide is a somatostatin analogue used in therapy trials of certain cancers. Cancer patients are often protein catabolic, thus the effect of lanreotide on whole body protein metabolism is of importance. We investigated the effect of lanreotide by measuring urea nitrogen synthesis rate (UNSR) and blood alpha-amino nitrogen levels before, during and after a 30 min iv infusion of 25 g of an electrolyte-free amino acid solution. 6 healthy male subjects were studied following, i) placebo (saline), ii) lanreotide 5 mug/kg, and iii) lanreotide 80 mug/kg. Lanreotide decreased urea nitrogen synthesis rate (mmol/h) during amino acid infusion significantly compared to saline, independent of dose of lanreotide (max +/- SE of urea nitrogen synthesis rate measurements in each study: 117 +/- 8 mmol/h (saline), 85 +/- 10 mmol/h (high dose) and 85 +/- 12 mmol/h (low dose)). This occurred in spite of significantly higher plasma alpha-amino nitrogen following lanreotide (peak +/- SE of alpha-amino nitrogen level in each study: 3.7 +/- 0.1 mmol/l placebo versus 4.8 +/- 0.2 mmol/l low dose and 4.7 +/- 0.4 mmol/l high dose (p < 0.01). We conclude that a single dose of lanreotide decreases whole body urea nitrogen synthesis rate thereby conserving body protein. The results indicate that long term lanreotide therapy may not lead to further protein catabolism in cancer patients.

Journal Article↗
PubMed1994

Effect of fructose on the capacity of urea-N synthesis in rats.

We studied the effect of fructose on hepatic conversion of amino-N to urea-N as quantified by the Capacity of Urea-N Synthesis (CUNS) determined in rats during alanine loading. There were 2 control groups, one without and one with infusion of somatostatin, in order to control the effects of insulin and glucagon. Somatostatin reduced CUNS from 8.5 +/- 0.5 mumol/(min x 100 g BW) to 6.3 +/- 0.3 mumol/(min x 100 g BW) (mean +/- SEM) (p < 0.01) and reduced glucagon concentrations by 75% (p<0.05). Insulin and glucose concentrations did not change. Fructose, at blood concentrations of about 1 mmol/l further reduced CUNS to 3.6 +/- 0.3 mumol/(min x 100 g BW) (p < 0.01). Insulin increased slightly (p < 0.05), but neither glucose nor glucagon changed. At increasing fructose concentrations up to 2 mmol/l there was no further effect on CUNS. Fructose in concentrations as used for parenteral nutrition and independent of glucoregulatory hormones, decreased hepatic amino acid catabolism.

Journal Article↗
PubMed1994

Regulation of urea synthesis by glucose and glucagon in normal man.

The separate effects of glucose and glucagon on alanine stimulated hepatic amino-N to urea-N conversion, quantified by the Functional Hepatic Nitrogen Clearance (FHNC) (i.e. the linear slope of the relation between urea synthesis rate and blood alpha-amino-N concentration), were studied in 7 healthy subjects. FHNC was measured four times in each: during constant infusion of alanine alone; alanine superimposed on constant glucose infusion; alanine superimposed on glucose and low stepwise glucagon infusions; and alanine super-imposed on glucose and high constant glucagon infusions. Glucose halved the glucagon response to alanine. This reduction was abolished by the low stepwise glucagon infusion, aimed at re-establishing portal glucagon levels. The high glucagon infusion resulted in 3-fold elevated glucagon levels. During alanine infusion alone FHNC was (mean +/- SEM) 32.5 +/- 1.9 l/h. Glucose reduced FHNC by 43% to 18.4 +/- 0.9 l/h (p < 0.01). The low stepwise glucagon infusion only partially normalized FHNC as reduced by glucose (to 24.6 +/- 1.5 l/h, (p < 0.01 vs alanine alone)). The high glucagon infusion increased FHNC by 35% despite hyperglycaemia (to 44.1 +/- 1.5 l/h, (p < 0.01 vs alanine alone)). The results show that both glucose and glucagon are independent but opposite regulators of hepatic amino-N conversion. The physiological glucose effect is accomplished by a combination of both the effect of glucose itself and the inhibition by glucose of the glucagon response to alanine. Hyperglucagonaemia increases FHNC and overrules the inhibition by glucose. This may explain the defect nitrogen sparing by glucose and to some extent the catabolism in hyperglucagonaemic stress conditions, despite prevailing hyperglycaemia.

Journal Article↗
PubMed1994

Effects of insulin and glucose on urea synthesis in normal man, independent of pancreatic hormone secretion.

We investigated the inhibitory effect of insulin and glucose on hepatic amino- to urea-nitrogen conversion independent of endogenous insulin and glucagon secretion. Alanine-stimulated urea synthesis kinetics, as quantified by functional hepatic nitrogen clearance, i.e. the slope of the linear relation between blood alpha-amino nitrogen concentration and urea synthesis rate, were measured four times in each of six healthy volunteers, namely during spontaneous hormone responses, and during hormonal control by somatostatin and maintenance of basal hormone levels and euglycaemia, hyperinsulinaemia (85 +/- 8 mU/l), or hyperglycaemia (8.4 +/- 0.5 mmol/l). Hormonal control and euglycaemia reduced functional hepatic nitrogen clearance (mean +/- SD) by two-thirds (from 32.9 +/- 5.2 l/h to 12.2 +/- 3.4 l/h, p < 0.01). Hyperinsulinaemia did not change this (13.2 +/- 2.8 l/h), whereas hyperglycaemia further reduced functional hepatic nitrogen clearance by 40% to 7.4 +/- 1.3 l/h (p < 0.01). The reduction by hormonal control and euglycaemia is attributable to the abolition of the glucagon response to alanine infusion, as glucagon is known to up-regulate functional hepatic nitrogen clearance. Insulin did not regulate hepatic amino- to urea-nitrogen conversion, implying that the effect of insulin on urea production is due to its effect on blood amino acid supply to the liver. In contrast, glucose in itself reduced hepatic amino nitrogen conversion, independent of the hormonal responses to glucose. This means that the hepatic component of the amino-N-sparing effect of glucose depends on hyperglycaemia but not on hyperinsulinaemia.

Adult↗
PubMed1994

Cerebral blood flow autoregulation is absent in rats with thioacetamide-induced hepatic failure.

Cerebral blood flow normally remains constant within a wide range of mean arterial blood pressure values. In fulminant hepatic failure, however, it is not known whether autoregulation of cerebral blood flow is maintained. In the present study, cerebral blood flow autoregulation was investigated in rats 3 days after induction of fulminant hepatic failure. Wistar rats were given intraperitoneal thioacetamide or saline injections. The mean arterial blood pressure was varied by means of norepinephrine infusion or venesection, respectively. As mean arterial blood pressure declined, repeated cerebral blood flow measurements were performed by the intracarotid 113Xenon injection method. The relation between mean arterial blood pressure and cerebral blood flow was examined by statistical regression analysis, and the lower limit of autoregulation was determined in each rat. Cerebral blood flow baseline values were unaltered in liver failure compared to the control group (73 (36-92) vs. 79 (57-87) ml.100 g-1.min-1, median and range). Baseline mean arterial blood pressure was also similar in the two groups (90 (75-113) vs. 95 (70-112)). Mean arterial blood pressure varied between 40 (35-50) and 110 (90-135) mmHg in the control rats and between 50 (45-68) and 110 (95-126) mmHg in the rats with liver failure. A lower limit of autoregulation was identified in all control rats at a mean arterial blood pressure of 67 (55-78) mmHg. Below this limit, cerebral blood flow declined in parallel with mean arterial blood pressure. None of the rats with liver failure exhibited autoregulation, and cerebral blood flow changed in parallel with mean arterial blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

The in vivo effect of interleukin-1 beta on urea synthesis is mediated by glucocorticoids in rats.

Interleukin-1 beta has been proposed as one mediator of parts of the catabolic response following surgery. However, it is not known whether such an effect is due to interleukin-1 beta itself or the associated changes in glucocorticoids. The effect of interleukin-1 beta on urea synthesis was investigated in rats given a high (10 micrograms kg-1) and a low dose (0.1 microgram kg-1) of recombinant interleukin-1 beta (NOVO, Denmark) 3 h prior to determination of the rate of urea synthesis in vivo. Urea synthesis increased dose-dependently after the low dose from 4.0 +/- 0.3 (control) to 6.3 +/- 0.3 (P < 0.01), and after the high dose to 7.7 +/- 0.3 mumol (min.100 gBW)-1 (P < 0.01). The blood concentration of amino acids fell during interleukin-1 beta treatment, so the effect on urea synthesis was not due solely to increased proteolysis, but was exerted predominantly in the liver. Pharmacological glucocorticoid receptor blockade (hormone analogue RU486, Roussel-Uclaf, Paris, France) given 1 h prior to the interleukin treatment, completely abolished the interleukin-1 beta induced increases in urea synthesis. The study demonstrates that interleukin-1 beta stimulates urea synthesis in vivo, and that the major part of the effect depends on glucocorticoid action.

Amino Acids↗
PubMed1994

Somatostatin-stimulated insulin-like growth factor binding protein-1 release is abolished by hyperinsulinemia.

It was demonstrated recently that administration of lanreotide and octreotide, two somatostatin octapeptide analogs, increased circulating insulin-like growth factor binding protein 1 (IGFBP-1) levels. The present study demonstrates that native somatostatin 14 shares this ability and that the increase in abolished by concomitant hyperinsulinemia within the physiological range. Five fasting healthy volunteers underwent a hyperinsulinemic as well as a normo-insulinemic (i.e. basal insulinemic) euglycemic clamp lasting 8 h (serum insulin levels remained constant, about 570 vs. 16 pmol/L). Immediately before the clamps, a somatostatin infusion (500 micrograms/h) was started and continued throughout. During normo-insulinemia, IGFBP-1 levels increased slowly from 6.3 +/- 6.2 to 36.1 +/- 14.8 micrograms/L (P < 0.05) reaching maximum after 7 h constant somatostatin infusion, whereas hyperinsulinemia induced a significant decrease from basal levels (from 4.7 +/- 5.4 to 1.1 +/- 1.5 micrograms/L) after 8 h (mean +/- SD, n = 5). These results may indicate hitherto unnoticed interactions of somatostatin and insulin on IGFBP-1 release with possible impact on IGF-I action at the cellular level.

Adult↗
PubMed1994

Dose-dependent stimulation of insulin-like growth factor-binding protein-1 by lanreotide, a somatostatin analog.

It was recently reported that octreotide, besides its many, almost obligatory, inhibitory actions, stimulates the release of insulin-like growth factor-binding protein-1. The present study sought to exclude the possibility that the inescapable preceding somatostatin analog-induced reduction in serum insulin participated in the observed effect. We, therefore, administered sc two clinically relevant doses (5 and 80 micrograms/kg) of lanreotide, another somatostatin octapeptide analog, which induced identical 60% initial suppressions of serum insulin. In spite of this, clear dose-dependent increases in insulin-like growth factor-binding protein-1 were observed, starting between 1-2 h after administration of lanreotide, and levels were still elevated several-fold 5 h after administration of 80 micrograms/kg lanreotide. In addition, we found that infusion of amino acids had no discernible effect on binding protein-1 release. The changes found in immunoreactive binding protein-1 were confirmed employing Western ligand blotting. The data indicate that the lanreotide-induced increase in binding protein-1 levels in serum is not due to the changes in circulating insulin. The magnitude and duration of the increase raise the possibility that the stimulation may have clinically relevant implications in somatostatin analog treatment.

Adult↗
PubMed1994

Effects of growth hormone (GH) administration on functional hepatic nitrogen clearance: studies in normal subjects and GH-deficient patients.

A decline in serum urea levels and urinary urea excretion is usually seen after GH administration in humans, indicating overall protein anabolism. Whether this reflects the diminished supply of alpha-amino acids for urea synthesis or a substrate-independent hepatic mechanism is unknown. To pursue this we measured the urea nitrogen synthesis rate (UNSR) and blood alanine levels before, during, and after a 4-h constant iv infusion of alanine (2 mmol/kg BW.h). UNSR was estimated hourly as urinary excretion corrected for gut hydrolysis and accumulation in total body water. The slope of the linear relationship between UNSR and circulating alanine levels represents the hepatic components of conversion of amino nitrogen and is denoted the functional hepatic nitrogen clearance (FHNC). Eight male volunteers were randomly investigated on three occasions: 1) after 12-h iv saline infusion, 2) after 12-h iv GH infusion (1 IU/h), and 3) after 2-day sc GH treatment (8 IU/day), followed by 12-h iv infusion of GH (1 IU/h). The UNSR (millimoles per h) during alanine infusion was significantly lower when the subjects were receiving GH therapy [maximum +/- SE, 133.0 +/- 6.9 (saline) vs. 96.7 +/- 11.1 (12-h GH; P < 0.01) vs. 106.5 +/- 7.5 (2-day GH; P < 0.05)]. FHNC (liters per h) was similar in all three studies [30.3 +/- 1.2 (saline) vs. 26.6 +/- 3.4 (12-h GH) vs. 27.0 +/- 2.6 (2-day GH)]. Six GH-deficient adult patients were randomly studied twice: 1) on regular daily (at 2000 h) sc GH therapy (3 IU/m2.day), and 2) after discontinuation of GH for 2 days. The UNSR during alanine infusion was likewise significantly lower when the patients were receiving GH therapy [147.7 +/- 11.7 mmol/h (no GH) vs. 123.9 +/- 9.1 mmol/h; P < 0.01]. FHNC (liters per h) values were similar in the two studies [29.2 +/- 3.8 (GH) vs. 27.5 +/- 4.5 (no GH)]. Our data confirm the anabolic action of GH and show that short term GH deprivation is associated with catabolism in terms of increased UNSR. The finding of unaltered FHNC suggests a GH-induced extrahepatic regulation of amino nitrogen conversion, rather than a substrate-independent hepatic mechanism.

Adult↗
PubMed1994

A rapid method for determination of hepatic amino nitrogen to urea nitrogen conversion ('the Functional Hepatic Nitrogen Clearance').

The Functional Hepatic Nitrogen Clearance (FHNC) is a measure of the functional liver mass as to conversion of amino-N to urea-N. FHNC is the slope of the linear regression of multiple samples (10-20) of urea-N synthesis rates (UNSR) on blood alpha-amino-N concentrations (alpha-AN) during infusion of amino acids. UNSR is measured as urinary urea-N excretion rate corrected for accumulation in total body water (TBW) and loss in gut. A simplified method which estimates FHNC from only two samples of UNSR and alpha-AN was developed. Urine was collected in two hourly intervals: before infusion of alanine, and from 2 to 3 h after start of alanine infusion. Blood-urea-N and alpha-amino-N was measured at the beginning and at the end of each urine sampling interval. TBW was estimated from a nomogram, and gut loss of urea was assigned a fixed value (14%). The two-sample FHNC was calculated as delta UNSR (mmol h-1)/delta mean alpha-AN (mmol l-1). Linear regression analysis of the two-sample estimates of FHNC on the 'true' multiple-sample values of FHNC in an independent population of control and cirrhotic subjects showed the two-sample estimates to be closely related with values of the multiple-sample method, the regression equation being: two-sample FHNC = -0.24 + 0.99 x multiple-sample FHNC, r2 = 0.98. A close relationship was also obtained when cirrhotic patients were considered alone: two-sample FHNC = 0.01 + 0.94 x multiple-sample FHNC, r2 = 0.98.(ABSTRACT TRUNCATED AT 250 WORDS)

Amines↗
PubMed1994

Effects of glucose on hepatic conversion of aminonitrogen to urea in patients with cirrhosis: relationship to glucagon.

Glucose reduces the hepatic conversion of aminonitrogen to urea, quantified by the functional hepatic nitrogen clearance (i.e., the slope of the linear relation between urea synthesis rate and blood alpha-aminonitrogen concentration). This is due to a direct effect of glucose and to inhibition of glucagon. In this study, the effect of glucose on functional hepatic nitrogen clearance was examined during spontaneous hormone responses and during hormonal control by somatostatin. In 7 control subjects (study 1) and 9 patients with cirrhosis (study 2), functional hepatic nitrogen clearance was assessed twice in each subject: during infusion of alanine and during alanine administration superimposed on a continuous glucose infusion (blood glucose, on average = 8.4 mmol/L). In study 3, 6 patients with cirrhosis had functional hepatic nitrogen clearance determined on three occasions: during infusions of alanine and of alanine superimposed on infusion of somatostatin with either euglycemia or hyperglycemia (blood glucose = 8.4 mmol/L). In the control subjects (study 1), functional hepatic nitrogen clearance was 32.5 +/- 1.9 L/hr, and glucose reduced it to 18.4 +/- 0.9 L/hr (p < 0.01). In the cirrhotic patients, functional hepatic nitrogen clearance was only 9.8 +/- 1.3 L/hr (p < 0.01 vs. controls), and glucose did not change it. In the control subjects, glucose reduced the glucagon response to alanine from 204 +/- 36 ng/L to 106 +/- 8 ng/L (p < 0.05). In the cirrhotic patients the mean fasting glucagon level was increased twofold (180 +/- 21 ng/L). The response to alanine increased to 968 +/- 265 ng/L; it was not reduced by glucose. In study 3, somatostatin and hyperglycemia reduced functional hepatic nitrogen clearance from 13.2 +/- 1.5 L/hr to 6.4 +/- 0.7 L/hr (p < 0.01). Somatostatin and euglycemia reduced functional hepatic nitrogen clearance to 9.2 +/- 1.2 L/hr (p < 0.01 vs. alanine and hyperglycemia). The results show that the reduction by glucose of hepatic aminonitrogen conversion is lost in cirrhotic patients. The markedly increased glucagon response to alanine was not suppressed by glucose. Inhibition of the glucagon response by somatostatin reestablished the glucose effect, which was in part due to inhibition of glucagon in itself. Thus hepatic aminonitrogen conversion in cirrhosis depends on increased glucagon levels. The hormone-independent effect of glucose is preserved if the hyperglucagonemia is abolished, but the spontaneous high glucagon level overrules the glucose effect. The results indicate reduced hepatic contribution to the nitrogen-sparing effect of glucose in cirrhotic patients.

Adult↗
PubMed1993

[Plasmapheresis as life-saving treatment in acute hepatic failure].

Emergency liver transplantation is the treatment of choice in acute liver failure without signs of spontaneous regeneration. However, many patients rapidly contract irreversible neurological complications before transplantation can be performed. We used high-volume plasmapheresis to increase the time span to obtain a donor liver. Four patients with acute liver failure of unknown cause and a galactose elimination capacity indicative of a virtually extinct liver function were assigned maximum priority for liver transplantation. Plasmapheresis were performed daily until transplantation. Each time 8-10 liters of patient plasma were replaced with an equal volume of fresh donor plasma. There were no major complications. None of the patients developed irreversible neurological complications for 48-144 h at which time liver transplantation was performed. High volume plasmapheresis increases the time to obtain a donor liver for emergency liver transplantation and optimizes the condition for the surgical procedure.

Acute Disease↗
PubMed1993

Effect of glucagon immunoneutralization on the increase in urea synthesis after hysterectomy in rats.

To study the effect of glucagon immunoneutralization on postoperative changes of urea synthesis, hysterectomized rats were given one injection of a specific high titre antibody against pancreatic glucagon 24 h before operation raising the plasma glucagon binding capacity to values 10-20 times higher than the plasma glucagon concentration in control animals. Earlier studies have shown that the spontaneous rate of urea-N synthesis (UNSR) doubles 3 h after operation, and that the Vmax of the process, the capacity of urea-N synthesis (CUNS) is 50% higher than normal values 24 h after operation. Therefore, the effect of glucagon on UNSR and CUNS were investigated 3 and 24 h postoperatively, respectively. Control animals were given non immune rabbit serum. Glucagon immunoneutralization partly normalized the early increase in UNSR 3 h postoperatively (control: 4.7 +/- 0.3, hysterectomy+serum: 6.7 +/- 0.4, hysterectomy+Gluc-Ab: 5.5 +/- 0.4 mumol (min.100 g BW)-1), but had no effect on the increase of CUNS 24 h postoperatively (control: 7.9 +/- 0.3, hysterectomy+serum: 9.5 +/- 0.3, hysterectomy+Gluc-Ab: 9.8 +/- 0.5 mumol (min.100 g BW)-1). This shows that glucagon is important for the early postoperative increase in the efficacy of urea synthesis, whereas the late increase in capacity seems not to depend on hyperglucagonemia.

Animals↗