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Biomedical subjects

L S Eriksson

Publications and source records attributed to L S Eriksson.

At least 55 records · Page 3Linked to original sources

Visual evoked potential--a tool in the diagnosis of hepatic encephalopathy?

Visual evoked potentials (VEP) have been suggested to be of value in the diagnosis of subclinical and mild hepatic encephalopathy. In the present study, a comparison between VEP and four psychometric tests (number connection test A and B, digit symbol and word memory test) was performed in 42 cirrhotic patients, 17 of whom had clinical signs of encephalopathy. The results were compared to sex- and age-matched healthy controls. The VEP latencies for P2 (the second positive wave) and N3 (the third negative wave) were 11% and 26% longer (P less than 0.01-0.001) in the patients than in the controls. Moreover, the latencies for N2 (the second negative wave) and P2 were longer in the encephalopathic as compared to the non-encephalopathic patients (P less than 0.05). There was a significant correlation between the latencies for N2 and number connection tests A and B and digit symbol test. However, of the patients with clinical encephalopathy, less than half had VEP latencies longer than the mean +/- 2 S.D. above those for the controls. In contrast, none of the encephalopathic patients had normal results on the psychometric tests. This study demonstrates that although statistically significant differences exist between groups of cirrhotic patients and controls, VEP is not a reliable tool for the diagnosis of encephalopathy in the individual patient.

Adult↗

Intravenous and subcutaneous administration of a long-acting somatostatin analogue: effects on glucose metabolism and splanchnic haemodynamics in healthy subjects.

The effect of SMS 201-995, a long-acting somatostatin analogue, on splanchnic blood flow and glucose metabolism, was investigated in five groups of healthy subjects. Groups A (n = 4), B (n = 5), C (n = 5) and D (n = 5) were studied before, during and after a 60-min intravenous infusion of SMS (1.7, 0.8, 0.2 and 0.1 micrograms min-1, respectively). Group E (n = 6) was investigated before and for 6 h after a subcutaneous injection of 25 micrograms of SMS. The splanchnic blood flow decreased by 20-25% in all groups in response to SMS and remained low during the entire observation periods. Arterial concentrations of glucose showed a 15-20% decline during SMS infusion in Groups A and B (P less than 0.05-0.01) and a less pronounced decrease in the other groups. Fifteen minutes after the end of infusion the glucose levels started to rise and in group A, the levels were significantly higher than basal (+25%, P less than 0.05-0.01) at 90-180 min after the end of infusion. The net splanchnic glucose production, determined in groups A and B, decreased by 65-75% in response to SMS infusion. Towards the end and immediately after the infusions, however, the net glucose output increased, but decreased again at 30-60 min after the end of infusion. Arterial, insulin and glucagon concentrations decreased significantly during infusion in all groups. This decline was more pronounced for insulin (50%) than for glucagon (20-25%) and insulin concentrations remained low for a longer period after the end of infusions.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Diet-induced thermogenesis in patients with liver cirrhosis.

Diet-induced thermogenesis after ingestion of a mixed meal was investigated in eight patients with documented liver cirrhosis and in eight age- and sex-matched healthy controls. Respiratory gas exchange was measured continuously for one hour in the basal state and for three hours after ingestion of a mixed liquid meal, consisting of 17% kJ protein, 28% kJ lipids and 55% kJ carbohydrates and dispensed to correspond to 60% of the individually computed energy expenditure. Arterial substrate and hormone concentrations were determined before and at timed intervals for three hours after the meal. Urine was collected for determination of nitrogen excretion. The patients' oxygen uptake, energy expenditure and respiratory quotient were similar to those of the controls in the basal state. After the meal, pulmonary oxygen uptake and energy expenditure rose markedly in both groups during the first hour and were subsequently stable. The average increase in oxygen uptake above basal during the whole study period was 21.2 +/- 1.8% and 22.3 +/- 1.2% (NS) in patients and controls, respectively. The corresponding increase in energy expenditure was 24.8 +/- 2.0% in the patients and 24.9 +/- 1.4% in the controls (NS). The respiratory quotient was elevated throughout the postprandial period in both groups but the quotient was significantly higher in the patients (P less than 0.05-0.001), suggesting a greater proportion of carbohydrate oxidation. The basal arterial concentrations of insulin and glucagon were significantly higher in the patients. After the meal the insulin level increased 10- to 20-fold in both groups. Glucose concentration rose significantly in both groups to a maximum of 8.82 +/- 1.00 and 8.03 +/- 0.95 mmol/l in patients and controls, respectively, at 60 min after the meal. This was accompanied by a fall in the levels of glycerol and ketone bodies in both groups, indicating decreased lipolysis. It is concluded that both the basal energy expenditure and the thermogenic response to a mixed meal are similar in patients with liver cirrhosis and in healthy controls. The patients' carbohydrate oxidation rose to a greater extent after the meal, probably as a consequence of excessive increases in insulin concentration, demonstrating that insulin resistance in these patients may be compensated for by postprandial hyperinsulinaemia.

Adult↗

Splanchnic metabolism of amino acids in healthy subjects: effect of 60 hours of fasting.

Brief starvation is accompanied by decreased circulating levels of most amino acids, which has been attributed to an increased splanchnic uptake of amino acids, primarily alanine, for gluconeogenesis. However, quantitative data on splanchnic exchange of amino acids and gluconeogenic precursors is lacking. Consequently, arterial concentrations and splanchnic exchange of whole blood amino acids, ketone bodies, glucose, and gluconeogenic precursors were measured in 16 prolonged fasted (60 to 64 hours) and 15 overnight fasted (12 to 14 hours) healthy, nonobese subjects. After the 60-hour fast net splanchnic glucose production decreased by 41% to 0.31 +/- 0.02 mumol/L (P less than .001), whereas the splanchnic uptake of gluconeogenic precursors increased and could account for the total glucose output. Net splanchnic uptake of taurine, threonine, serine, glycine, lysine, histidine, and arginine rose significantly in response to fasting (P less than .05 to .01) due to increased splanchnic fractional extraction. Although the splanchnic fractional extraction of alanine was augmented by 40% (P less than .001), net splanchnic uptake was not influenced by fasting. Total net splanchnic uptake of amino acids increased by 68%, from 231 +/- 44 mumol/min in the postabsorptive state to 388 +/- 63 mumol/min (mean +/- SEM) (P less than .05) in the 60-hour fasted state. However, only one half of this rise was accounted for by gluconeogenic amino acids.

Adult↗

Brain cortical amino acids measured by intracerebral dialysis in portacaval shunted rats.

The extracellular amino acid content was measured in the parietal cortex in portacaval and sham operated rats, using the brain dialysis technique. The amino acid content of the perfusate was determined for 10 min before and during stimulation with potassium chloride. Basal levels of aspartate, glutamine, glycine, methionie, valine, phenylalanine and leucine were 2-to 6-fold higher in the PC-shunted as compared to the sham operated rats. For glutamate, taurine, and GABA no differences were observed between the two groups. After KCl stimulation the release of glutamate and GABA increased significantly in both groups. For GABA this rise was approximately twice as high in the PC-shunted rats (+300%, P less than 0.01) as in the sham operated rats (+150%, P less than 0.01 as compared to basal). In the sham operated, but not in the PC-shunted rats, methionine and valine levels rose significantly (+200%, P less than 0.05) and glutamine release decreased (-50%, P less than 0.05). These findings suggest that the brain metabolism of amino acids is altered after a portacaval shunt. This could in turn alter the neurotransmission and partly explain the low spontaneous motor activity seen in these animals.

Amino Acids↗

Haemodynamic effects of a long-acting somatostatin analogue in patients with liver cirrhosis.

The influence of SMS 201-995 (octreotide, Sandostatin), a long-acting somatostatin analogue, on splanchnic haemodynamics was studied in 15 patients with liver cirrhosis and in 5 healthy individuals before, during, and after 60 min of intravenous SMS infusion (25 and 50 micrograms/h, respectively). No adverse effects of the SMS infusion were seen. In the basal state the estimated hepatic blood flow was 1.04 +/- 0.08 l/min (mean +/- SE) in the patients and 1.62 +/- 0.09 l/min (P less than 0.001) in the controls. At 15 min after the beginning of the infusion the blood flow had already decreased by 15-30% (P less than 0.05-0.01). The reduction was more marked in controls than in patients, and it persisted in both groups during and for 60 min after the infusion. Wedged hepatic venous pressure, measured in the patients, was 20 +/- 2 mmHg in the basal state and 18 +/- 1 mmHg during the infusion (P less than 0.05), and it remained at this level for 60 min after the infusion. Free hepatic venous pressure was unchanged throughout the study. Splanchnic oxygen uptake was similar in the two groups in the basal state and remained unaltered during and after SMS infusion. Both heart rate and arterial systolic and diastolic blood pressure remained unchanged during SMS administration. In summary, SMS infusion results in a fall in hepatic blood flow and a slight but significant decrease in wedged hepatic venous pressure, whereas no effect was noted on the systemic circulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Splanchnic and leg exchange of free fatty acids in patients with liver cirrhosis.

Splanchnic and leg exchange of free fatty acids (FFA), glycerol and ketone bodies, as well as FFA turnover, were determined in the post-absorptive state in 8 patients with liver cirrhosis and in 6 healthy control subjects. The catheter technique was used together with tracer ([14C]oleate) infusion. The arterial concentrations of FFA, glycerol and ketone bodies were 2-6-fold higher in the patients than in the controls. The FFA turnover was 230% greater in the patients, while the fractional turnover was similar in the two groups. In the splanchnic region as well as in the leg, both FFA uptake and release were increased 2-4-fold in the patients. The fractional uptake of FFA was reduced in both areas, indicating that the augmented uptake was due to the high circulating FFA levels alone. The splanchnic production of ketone bodies was four times higher in the patients than in the controls (295 +/- 30 vs 87 +/- 11 mumol/min). The fraction of FFA converted to ketone bodies was greater (42 +/- 6 vs 20 +/- 5%, P less than 0.05), indicating that the accelerated ketone body production was a combined effect of raised FFA uptake and altered intrahepatic metabolism of FFA. The splanchnic production of glucose was reduced by approximately 50% in the patients, while the uptake of glycerol was augmented. The leg uptake of 3-hydroxybutyrate was increased 300% and the release of glycerol was 200% greater in the patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗

The influence of a long-acting somatostatin analogue on splanchnic haemodynamics and metabolism in healthy subjects and patients with liver cirrhosis.

The influence of a long-acting somatostatin octapeptide analogue (SMS 201-995) on splanchnic circulation and metabolism has been studied in healthy subjects and in patients with liver cirrhosis. In healthy subjects doses of 5, 10, 50, or 100 micrograms SMS and in the cirrhotic patients 25 micrograms SMS were infused intravenously during 1 h. Measurements were obtained before, during, and for 1 h after SMS infusion. SMS infusion in healthy subjects resulted in a 25-35% reduction in hepatic blood flow. This effect was largely independent of the dose used. Splanchnic oxygen uptake was unchanged before and during SMS infusion. Insulin and glucagon levels fell markedly in response to SMS administration, and the blood concentration and splanchnic output of glucose decreased transiently. Patients with liver cirrhosis responded to SMS infusion similarly to the healthy subjects. Hepatic blood flow decreased by 25-35% and remained suppressed for at least 1 h after infusion. Wedge hepatic venous pressure was 18 +/- 2 mm Hg in the basal state and decreased progressively during and after SMS infusion (60 min after infusion, 15 +/- 2 mm Hg; P less than 0.01). The marked hyperinsulinaemia and hyperglucagonaemia seen in the basal state decreased significantly during SMS administration. As in the case of the controls, blood concentration and splanchnic output of glucose fell transiently during and after SMS infusion. It is concluded that SMS exerts a marked and prolonged suppressive effect on hepatic blood flow in both healthy subjects and patients with liver cirrhosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Peritoneo-venous shunting and endoscopic sclerotherapy in patients with portal hypertension.

Denver type peritoneo-venous (PV) shunting for intractable ascites was performed in 16 patients also treated with endoscopic injection sclerotherapy (ST) for variceal haemorrhage. Indications, timing and results of shunt insertion are detailed and discussed. Serial ST for eradication of varices could be completed in 10 patients a median of 7 months before PV shunting. The postoperative risk of bleeding was increased four times, i.e. the number of GI bleedings per month of follow-up, was 0.05 and 0.21 (p less than 0.05) respectively, before and after shunt operation. Two patients experienced their first variceal bleeding and 6 patients rebled during a median follow-up of 3 months after PV shunting. The Denver shunt succeeded in resolving ascites clinically in 13 patients within 7 days with a median decrease in weight of 10 kg, parallel to increased urinary output and reduced serum-creatinine. Three patients did not benefit from the shunt procedure due to terminal neoplastic disease (one patient), and severe hepatorenal failure, although the shunts were proven patent. Serious complications included clinically important consumptive coagulopathy, DIC-syndrome (two patients), myocardial infarction (one), pulmonary embolism (three), and sepsis following intervention of obstruction (one).

Adult↗

Infusion of ornithine-alpha-ketoglutarate in healthy subjects: effects on protein metabolism.

Infusion of ornithine-alpha-ketoglutarate (Ornicetil) has been suggested to improve nitrogen balance in trauma patients. Whether this anticatabolic effect is localised to the liver or to skeletal muscle is as yet unknown. Consequently, the splanchnic and leg exchange of amino acids, urea and ammonia were measured in seven healthy non-obese subjects in the basal state and during infusion of ornithine-alpha-ketoglutarate at a rate of 28 mg/min for 150 min. The results demonstrate a six-fold rise in arterial ornithine and an increased uptake by both splanchnic and leg tissues during infusion. The splanchnic uptake of threonine and lysine also increased, while no other alterations were seen in leg amino acid exchange. The arterial urea concentration decreased slightly (-6%, P<0.01) during the infusion in spite of an unchanged urea production from the liver. The ammonia concentration fell by 20% (P<0.05), while glycerol and ketone body concentrations did not change significantly. It is concluded that intravenous infusion of ornithine-alpha-ketoglutarate in healthy subjects does not significantly influence hepatic or skeletal muscle protein metabolism.

Journal Article↗

Ammonia metabolism during exercise in man.

Physical exercise is accompanied by increased plasma levels of ammonia but it is not known whether this rise primarily reflects accelerated formation in muscle or decreased removal by the liver. Consequently, leg and splanchnic exchange of ammonia was examined, using the catheter technique, in 11 healthy subjects at rest, during three consecutive 15 min periods of bicycle exercise at gradually increasing work loads (35%, 55% and 80% of maximum oxygen uptake) and for 60 min during post-exercise recovery. The basal arterial ammonia level was 22 +/- 2 mumol/l, the concentration rose curvilinearly in response to increasing work loads (peak value 84 +/- 12 mumol/l), and fell rapidly after exercise, reaching basal levels after 30-60 min. A linear regression was found for ammonia levels in relation to lactate concentrations at rest and during exercise (r = 0.85, P less than 0.001). A significant relationship was also observed between arterial ammonia and alanine levels (r = 0.75, P less than 0.001). Leg tissues showed a net uptake of ammonia in the basal state (2.4 +/- 0.5 mumol/min). During exercise this changed to a net production, which increased curvilinearly with rising work intensity (peak value 46 +/- 15 mumol/min) but reverted to a net ammonia uptake at 30-60 min after exercise. Splanchnic ammonia uptake (basal 12 +/- 2 mumol/min) did not change in response to exercise but increased transiently during the early post-exercise period. From the above observations we conclude that the hyperammonaemia of exercise comes primarily from muscle release, while the splanchnic removal of ammonia is essentially unaltered. Part of the ammonia formed in contracting muscle is most likely used in the synthesis of amino acids, mainly glutamine and probably alanine.

Adult↗

Influence of a 60-hour fast on insulin-mediated splanchnic and peripheral glucose metabolism in humans.

A brief period of starvation (2-3) depletes the hepatic glycogen stores but results in only a limited reduction of the muscle glycogen depots. In this situation insulin resistance contributes to the glucose intolerance, but it is not known which tissue or tissues are responsible for the decreased insulin sensitivity. The present study was therefore undertaken to examine the influence of a 60-h fast on insulin sensitivity in splanchnic and peripheral tissues in normal humans. Euglycemic (95 mg/dl) 1-mU insulin and hyperglycemic (215-225 mg/dl) glucose clamp studies were conducted for 2 h in overnight (12 h) and prolonged (60 h) fasted nonobese subjects. Splanchnic exchange of glucose and gluconeogenic precursors was measured using the hepatic vein catheter technique. During the euglycemic clamp, insulin infusion resulted in similar steady state insulin levels in 60-h and 12-h fasted subjects (73 +/- 7 vs. 74 +/- 5 microU/ml). Total glucose disposal was reduced by 45% after 60 h of fasting (4.0 +/- 0.3 vs. 7.6 +/- 1.1 mg/kg per min, P less than 0.05) and the splanchnic glucose balance reverted from a net release in the basal state (12 h fast, -1.7 +/- 0.2, and 60-h fast, -0.9 +/- 0.1 mg/kg per min, P less than 0.01) to a net uptake during the clamps that was similar after 60 h and 12 h of fasting (0.6 +/- 0.1 vs. 0.6 +/- 0.2 mg/kg per min). During the hyperglycemic clamp, insulin levels rose rapidly in all subjects. In the 12-h fasted group this rise was followed by a further gradual one, reaching significantly higher values than in 60-h fasted subjects during the second hour (67 +/- 15 vs. 25 +/- 2 microU/ml, P less than 0.05). Total glucose disposal was lower, though not significantly so, after the 60-h fast (2.6 +/- 0.4 vs. 5.4 +/- 1.3 mg/kg per min, 0.05 less than P less than 0.10), and as with the euglycemic clamp, the splanchnic glucose balance was altered from a basal net release to a net uptake during the clamp (1.3 +/- 0.2 vs. 1.1 +/- 0.2 mg/kg per min). After an overnight fast, splanchnic lactate uptake fell and the arterial lactate concentration rose in response to both hyperglycemia and hyperinsulinemia, whereas these variables were unchanged in the 60-h fasted subjects during both types of clamp studies.

Adult↗

Effects of captopril on hepatic venous pressure and blood flow in patients with liver cirrhosis.

To examine the possible contribution of the renin-angiotensin-aldosterone system to portal hypertension in patients with cirrhosis of the liver, seven such patients were studied with the hepatic venous catheterization technique, in the basal state, and after the intake of 12.5 to 25 mg of captopril. Hepatic venous wedge pressure was 22 +/- 2 mm Hg in the basal state and fell to 19 to 20 mm Hg at 45 to 90 minutes after the administration of captopril (P less than 0.05 to 0.01). Wedge to free hepatic venous pressure difference (basal 14 +/- 2 mm Hg) remained unchanged after captopril, and estimated hepatic blood flow was unaltered. Small but significant reductions in arterial blood pressures were seen after the administration of captopril. Aldosterone concentrations decreased whereas renin activity tended to increase after captopril. It is concluded that captopril inhibits the renin-angiotensin system in patients with cirrhosis of the liver, but fails significantly to decrease portal venous pressure. Captopril is thus unlikely to favorably influence the incidence of bleeding in these patients.

Angiotensin-Converting Enzyme Inhibitors↗

Influence of somatostatin on splanchnic haemodynamics in patients with liver cirrhosis.

The influence of intravenous somatostatin infusion (7.6 micrograms/min) on systemic and splanchnic haemodynamics was examined in 10 patients with liver cirrhosis and portal hypertension. The hepatic vein catheter technique was employed and indocyanine green dye was injected to evaluate hepatic blood flow. Mean wedged hepatic venous pressure fell from 24.9 +/- 2.8 in the basal state to 21.4 +/- 3.2 mmHg (P less than 0.2) at 60 min of infusion and the mean arterial pressure decreased from 87 +/- 5 to 80 +/- 6 mmHg (P less than 0.05). The rate of indocyanine green dye disappearance decreased from 8.7 +/- 1.9 to 6.6 +/- 1.7%/min (P less than 0.001) during the infusion, indicating decreased hepatic blood flow. Arterial-hepatic venous oxygen differences rose from 69 +/- 11 to 78 +/- 11 ml/l. Blood glucose levels fell from 4.84 +/- 0.31 to 3.79 +/- 0.33 mmol/l at 60 min of infusion (P less than 0.005). It is concluded that a continuous infusion of somatostatin in patients with liver cirrhosis and portal hypertension causes a decreased hepatic blood flow with augmented hepatic oxygen extraction and a modest reduction in mean wedged hepatic venous pressure. In view of the magnitude of the observed haemodynamic changes the findings do not suggest an important role for somatostatin in the treatment of patients with bleeding oesophageal varices.

Adult↗

Leucine uptake by splanchnic and leg tissues in man: relative independence of insulin levels.

The influence on leucine disposal of physiological alterations in plasma insulin concentrations was examined in three groups of healthy male subjects, six in each group. After an overnight fast the subjects received an intravenous infusion of either leucine (300 mumol/min for 150 min, series A), or leucine plus glucose (2.2 mmol/min, series B), or leucine, somatostatin (7 micrograms/min) and glucagon (1 ng/min, series C). Arterial concentrations of substrates and their net exchange across the splanchnic and leg tissues were determined with a catheter technique. Insulin concentrations rose from 12 +/- 2 to 20-22 mu-units/ml in series A, from 11 +/- 3 to 60-65 65 mu-units/ml in series B and decreased from 8 +/- 1 to approximately 5 mu-units/ml in series C. The basal leucine concentration for all subjects was 109 +/- 8 mumol/l and it rose progressively during the infusions. In series A, the level was 598 +/- 20 mumol/l after 150 min. The corresponding value was 542 +/- 38 mumol/l in series B and 651 +/- 25 mumol/l in series C. Significant differences were observed between series A and B (P less than 0.05) and series A and C (P less than 0.01) when data for 90-150 min of infusion were combined (analysis of variance). In all groups the leucine infusion resulted in an augmented net uptake of leucine across the leg (77-85 mumol/min) and across the splanchnic bed (61-72 mumol/min) but no significant intergroup differences were observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗