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Biomedical subjects

L S Eriksson

Publications and source records attributed to L S Eriksson.

At least 19 recordsLinked to original sources
PubMed1999

Rapid effect of lansoprazole on intragastric pH: a crossover comparison with omeprazole.

BACKGROUND: The time to onset of acid inhibition is considered an important factor when treating patients with reflux symptoms. This study was therefore designed to investigate the effect of 30 mg lansoprazole and 20 mg omeprazole on gastric pH after single-dose administration. METHODS: The study was of a randomized, open-label, single-dose and two-way crossover design with a washout period of at least 7 days in between. Fifteen healthy adult male and female subjects were included. The subjects were intubated with a pH catheter. Intragastric pH was measured every 4th sec for 10 min before and during 8 h after drug administration. Blood samples, for determination of plasma concentrations of lansoprazole and omeprazole, were obtained on 10 occasions during 6 h after drug administration. The area under the curve (AUC), the elimination halflife (t1/2), and the peak concentration (Cmax) of the two drugs were calculated. RESULTS: All subjects completed the study without major complications. The mean pH (0-8 h) after drug administration was 2.9 for lansoprazole and 2.0 for omeprazole (P = 0.0058). A pH of more than 4 was reached for the first time after 130 min with lansoprazole and after 250 min with omeprazole. AUC was 4919 +/- 2526 nmol/l x h for lansoprazole and 1352 +/- 1120 nmol/l x h for omeprazole. CONCLUSION: Single-dose administration of 30 mg lansoprazole is followed by a rapid absorption of the drug and hence a more efficient acid suppression than after single-dose administration of 20 mg omeprazole in healthy volunteers.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1997

Ursodeoxycholic acid treatment in patients with primary biliary cirrhosis. A Swedish multicentre, double-blind, randomized controlled study.

BACKGROUND: Ursodeoxycholic acid (UDCA) has been shown to improve serum levels of liver enzymes and bilirubin in primary biliary cirrhosis (PBC). However, it is still uncertain whether UDCA treatment also improves symptoms, liver histology, and survival without liver transplantation. METHODS: We randomized 116 patients with PBC to receive 0.5 g UDCA (n = 60) or placebo (n = 56) daily for 2 years. During the next 2 years, 80% of the UDCA-treated patients and 65% of the placebo-treated patients continued to take UDCA. RESULTS: UDCA improved serum enzyme values but not survival, symptoms, serum bilirubin levels, or liver histology. There was no significant difference in response between initially symptomatic and asymptomatic patients. CONCLUSIONS: UDCA in a dosage of 7.7 mg/kg body weight is of little benefit in PBC. This does not exclude the possibility that larger doses have beneficial effects.

Bile Acids and Salts↗
PubMed1996

Cyclophosphamide-induced acute liver failure requiring transplantation in a patient with genetically deficient debrisoquine metabolism: a causal relationship?

Severe liver damage can occur after treatment with cyclophosphamide. The possible linkage to genetically deficient drug metabolic capacity is unknown. A 58-year-old woman with rheumatoid arthritis was treated with oral cyclophosphamide 50 mg twice daily for 2 months. Due to poor response the dose was doubled and liver failure requiring transplantation developed within weeks. After surgery PCR amplification using DNA from leukocytes showed that she was homozygous for the mutated allele CYP2D6B, which is predictive of the poor metaboliser phenotype for debrisoquine, occurring in 7% of Caucasians. Our patient may have accumulated high levels of the hepatotoxic 4-hydroxylated cyclophosphamide metabolite. Pharmacogenetic methods can help in exploring mechanisms of unexpected severe adverse effects.

Antirheumatic Agents↗
PubMed1995

Primary sclerosing cholangitis and ulcerative colitis: evidence for increased neoplastic potential.

Primary sclerosing cholangitis (PSC) is a biliary destructive disease mostly affecting patients with ulcerative colitis (UC). PSC has been suggested to be an independent risk factor for the development of colorectal malignancy in UC. Patients with PSC also have an increased risk of developing cholangiocarcinoma. This study aimed at assessing the cumulative risk of colorectal neoplasia in PSC and UC, and also to determine risk factors for the development of cholangiocarcinoma. Fifty-eight PSC patients were included. Forty PSC patients having extensive UC were each matched to two control patients of the same age, with extensive colitis and a comparable duration of the colitis, but without PSC. All UC patients had been under colonoscopic surveillance with multiple biopsies. Among the 40 PSC patients with UC, 16 developed colonic dysplasia or carcinoma, versus 10 in the control group (P < .001). The absolute cumulative risk of developing colorectal dysplasia/carcinoma in the PSC/UC groups was 9%, 31%, and 50% after 10, 20, and 25 years of disease duration. In the group with UC only, the corresponding risk was 2%, 5%, and 10%, respectively (P < .001). Ten patients with PSC developed cholangiocarcinoma, all but one having UC. In the control group, no cholangiocarcinoma occurred. Patients with PSC and UC with colorectal neoplasia developed cholangiocarcinoma significantly more often compared with patients with UC and PSC without colonic dysplasia/carcinoma (P < .02). This study demonstrates not only that patients with PSC and UC have a significantly higher risk of developing colorectal neoplasia compared with patients having UC only, but also that patients with PSC and UC having colorectal neoplasia are more prone to develop cholangiocarcinoma.

Adolescent↗
PubMed1995

Influence of orthotopic liver transplantation on serum vitamin A levels in patients with chronic liver disease.

BACKGROUND: Low serum vitamin A levels are observed in many liver diseases, such as primary biliary cirrhosis (PBC) and alcoholic liver disease. The aim of this study was to investigate serum vitamin A in patients with advanced liver diseases before and after orthotopic liver transplantation (OLT). METHODS: Serum vitamin A (retinol) concentrations were investigated in 54 patients before (OLT) and in 21 patients 1, 2, 3, and 4 weeks and 2 and 3 months after OLT. Ten healthy subjects and 19 patients with inflammatory bowel disease (IBD) served as control groups. RESULTS: The mean serum retinol concentration before OLT was 0.64 +/- 0.1 mumol/l in patients with alcoholic and postnecrotic cirrhosis (n = 24), 1.06 +/- 0.48 mumol/l in patients with PBC (n = 14), 0.96 +/- 0.64 mumol/l in sclerosing cholangitis (n = 7), and 1.02 +/- 0.73 mumol/l in liver cancer (n = 9). These results were significantly lower than in healthy controls (2.34 +/- 0.54 mumol/l) and patients with IBD (2.7 +/- 0.74 mumol/l) (p < 0.001). CONCLUSIONS: After OLT, serum retinol levels increased significantly already after 1 week (1.4 +/- 0.1 mumol/l) (p < 0.001), normalized after 2 weeks (2.2 +/- 0.4 mumol/l), and remained normal during the observation.

Adult↗
PubMed1994

Splanchnic and peripheral glucose metabolism in cirrhosis.

The effects of glucose and insulin administration on splanchnic and leg exchange of glucose were investigated in seven patients with cirrhosis and six sex- and age-matched healthy controls using the catheter technique. After a basal period, glucose infusion (1 mg.kg-1.min-1) was given for 45 min, followed by a 2-h euglycemic insulin clamp (1 mU.kg-1.min-1). In the basal state insulin levels were significantly higher in patients than in controls (25 +/- 4 vs. 7 +/- 2 microU/ml). Net splanchnic glucose output tended to be lower in patients than in controls (0.50 +/- 0.16 vs 0.73 +/- 0.11 mmol/min nonsignificant), as did leg glucose uptake (0.06 +/- 0.01 vs 0.08 +/- 0.02 mmol/min, non-significant). Glucose infusion resulted in a significant rise in leg glucose uptake, while net splanchnic glucose output decreased in both groups. During the euglycemic insulin clamp, insulin concentrations rose to 110 +/- 10 and 80 +/- 8 microU/ml in patients and controls, respectively. C-peptide concentrations decreased in the healthy controls but were unchanged from the basal level in patients with cirrhosis. Glucose disposal during the last half hour of the clamp was 1.12 +/- 0.08 and 3.19 +/- 0.04 mmol/min in patients and controls, respectively (p < 0.001). Glucose was taken up by the splanchnic region in both groups but this uptake was significantly greater in patients than in controls (0.42 +/- 0.05 vs. 0.25 +/- 0.06 mmol/min, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Assessment for liver transplantation in patients with primary sclerosing cholangitis.

Recently three large studies have been presented in which the prognostic significance of clinical, laboratory and histological parameters measured early in the course of the disease was determined in primary sclerosing cholangitis patients. A different prognostic index was presented in each study. The aim of the present study was to evaluate these prognostic indices in a group of 37 patients with primary sclerosing cholangitis, assessed for liver transplantation. The results are compared to the outcome in the patients. At first referral, 12 patients were considered too healthy for transplantation and 17 were accepted for transplantation, six of whom died during the waiting time. Ten patients had cholangiocarcinoma or hepatocellular cancer. Albumin and bilirubin differed significantly between the patients accepted for transplantation and those considered too healthy. Only one prognostic index, presented by Dickson et al., could discriminate between "too healthy" and "in need of transplantation". However, the overlap between the groups was large, suggesting that this index may be of little or no help in the clinical situation with individual patients. Moreover, neither the prognostic index, nor any of the laboratory values could identify the patients with cancer. It is concluded that prognostic indicators have been found that may help to characterise primary sclerosing cholangitis patients. However, primary sclerosing cholangitis patients with an accompanying cholangiocarcinoma still cannot be identified.

Adult↗
PubMed1994

Ventilation-perfusion relationships and central haemodynamics in patients with cirrhosis. Effects of a somatostatin analogue.

The ventilation-perfusion relationships of the lung (VA/Q) and central haemodynamics were studied in seven patients with cirrhosis before and 30 min after a bolus injection of a somatostatin analogue, octreotide (Sandostatin, 50 micrograms i.v.), to elucidate the role of this substance in the hepatopulmonary syndrome. In the basal state all patients had normal spirometry but reduced diffusing capacity. Three patients had various degrees of hypoxaemia (6.9-8.3 kPa) and three had clubbing of the fingers. In the basal state VA/Q distributions, determined by inert gas elimination technique, showed an intrapulmonary shunt of 7.9 +/- 2.2% of cardiac output (range 1.5 to 17.1) and perfusion of lung regions with "low VA/Q" of 4.4 +/- 2.2% of cardiac output (range 0 to 15.4). After octreotide, the amount of shunting increased (10.9 +/- 4.4% of cardiac output; non-significant), while "low VAQ" was unchanged (3.7 +/- 1.3% of cardiac output). Arterial oxygen tension decreased from 10.2 +/- 1.1 to 9.7 +/- 1.1 kPa (non-significant). The mean pulmonary arterial pressure increased from 14.5 +/- 1.9 to 16.3 +/- 1.8 mmHg (p < 0.01). No alterations were seen in heart rate, stroke volume, cardiac output, central pressures or vascular resistances. The results of the present study do not support the hypothesis that octreotide improves hypoxaemia and ventilation-perfusion relationships in patients with hepatopulmonary syndrome.

Adult↗
PubMed1994

Insulin action on glucose transport in isolated skeletal muscle from patients with liver cirrhosis.

Insulin resistance, associated with liver cirrhosis, has been suggested to be localized in skeletal muscle. We used an in vitro incubation technique to determine insulin action on glucose transport in skeletal muscle obtained from seven patients with clinically stable alcoholic cirrhosis and seven healthy age- and sex-matched individuals. In addition, a euglycemic-hyperinsulinemic clamp procedure was performed to assess whole-body insulin-mediated glucose uptake. Insulin-mediated peripheral glucose utilization was 40% lower (p < 0.05) in the cirrhotic patients than in the healthy individuals. Intact skeletal muscle from the vastus lateralis portion of the quadriceps femoris muscle was obtained from each study participant. Thereafter, smaller skeletal muscle strips (approximately 18 mg) were dissected free and incubated in vitro to assess the rate of non-insulin- and insulin-stimulated 3-O-methylglucose transport. Insulin increased the rate of 3-O-methylglucose transport in a dose-dependent manner, with a maximal response observed in the presence of 200 microU/ml in skeletal muscle obtained from the cirrhotic patients and healthy individuals. The dose-response curve for insulin-stimulated 3-O-methylglucose transport did not differ between the groups. Furthermore, muscle glycogen content of needle biopsy specimens was comparable in the two groups. In conclusion, the present group of patients, with liver cirrhosis on an alcoholic basis, had a normal insulin-stimulated capacity for glucose transport at the cellular level irrespective of the degree of whole-body insulin resistance. The mechanism for the divergence between the in vivo and in vitro responses to insulin remains to be elucidated.

3-O-Methylglucose↗
PubMed1994

Cancer risk in primary biliary cirrhosis: a population-based study from Sweden.

A cohort of 559 patients in Sweden who satisfied predetermined criteria for the diagnosis of primary biliary cirrhosis was followed with respect to the incidence of cancer during the period of 1958 to 1988. The mean follow-up time from the time of primary biliary cirrhosis diagnosis was 9.0 +/- 5.4 yr. During the follow-up period, 148 patients died and the primary cause of death was liver insufficiency. An overall excess risk for cancer, standardized incidence ratio 1.6; 95% confidence interval, 1.1 to 2.2, was found in the cohort. In contrast to previous reports, we found no excess risk for breast cancer (standardized incidence ratio, 0.9; 95% confidence interval, 0.3 to 2.1). The number of hepatocellular cancers in the primary biliary cirrhosis cohort did not significantly differ from expected (standardized incidence ratio, 2.91; 95% confidence interval, 0.4 to 10.5).

Adult↗
PubMed1993

Influence of insulin on peripheral uptake of branched chain amino acids in the 60-hour fasted state.

The influence of insulin on branched chain amino acid (BCAA) metabolism was investigated in healthy subjects faster for 60-64 h, using the euglycemic insulin clamp technique and hepatic venous catheterization. As compared to the postabsorptive state, fasting resulted in a 50-80% decrease in glucose disposal during the clamps, indicating insulin resistance. However, the arterial concentrations of BCAA, which were increased by 200-220% after the fast, decreased to a similar extent during hyperinsulinemia, regardless of the fasting situation. The splanchnic exchange of BCAA was unaltered both in response to fasting itself and to fasting and hyperinsulinemia. The results suggest that insulin resistance during fasting does not influence BCAA metabolism. Furthermore, the changes in BCAA concentrations after a prolonged fast are due to altered peripheral metabolism of BCAA.

Journal Article↗
PubMed1993

Influence of insulin on glucose metabolism and lipolysis in adipose tissue in situ in patients with liver cirrhosis.

The influence of insulin on lipolysis and glucose metabolism in abdominal adipose tissue was studied in situ with the microdialysis technique during a euglycaemic insulin clamp (1 mU kg-1 min-1) in nine cirrhotic patients and 10 controls. The cirrhotic patients displayed a 50% decrease in glucose utilization rate during the clamp (P < 0.001). Dialysate glucose levels decreased similarly by 20-30%., in patients and controls, which in the presence of unchanged local blood flow in the adipose tissue in response to insulin, is at hand with a glucose uptake into the adipocytes of similar magnitude in both groups. Before and during the clamp, the arterial and dialysate levels of glycerol were higher in the patients than in the control subjects (ANOVA P = 0.001 and 0.048 in arterial blood and dialysate, respectively). In relative terms, however, insulin induced a 70% reduction of arterial and dialysate glycerol in both groups. The concentrations of lactate and pyruvate in the dialysate and blood increased in a similar way in both groups during hyperinsulinaemia. The results suggest an increased rate of lipolysis in cirrhotic patients. Insulin cannot lower it to normal, although it is still capable of achieving a relative reduction. No explanation was found in the adipose tissue to the insulin resistance to whole-body glucose utilization that was noted in the patients with cirrhosis.

Adipose Tissue↗
PubMed1993

Effect of vasoactive intestinal polypeptide (VIP) on pulmonary ventilation-perfusion relationships and central haemodynamics in healthy subjects.

Ventilation-perfusion relationships of the lung (VA/Q) and central haemodynamics were studied in nine healthy subjects before and during 30 min of vasoactive intestinal polypeptide (VIP) infusion (20 ng kg.min-1). During the infusion, arterial concentrations of VIP rose from 16.1 +/- 6.1 to 420 +/- 110 pmol l-1 and noradrenaline concentrations doubled (P < 0.01). VA/Q distributions, determined by inert gas elimination technique, were significantly shifted to lower values for VA/Q with slight increases in dispersions, but arterial oxygen tension remained unchanged. Heart rate, stroke volume and cardiac output rose 27, 44 and 80% respectively (P < 0.01). Systematic arterial pressure stabilized at a slightly lower level compared to basal (base line: 93 +/- 5 mmHg, VIP; 88 +/- 6 mmHg, P < 0.05). Right atrial and pulmonary capillary wedge pressures remained unchanged during VIP infusion, while pulmonary vascular resistance and systematic vascular resistance decreased significantly, by 25% (P < 0.03) and 53% (P < 0.01), respectively. It is concluded that VIP causes: (1) alterations in ventilation-perfusion distributions, but generates no shunt and does not cause hypoxaemia during 30 min infusion, (2) reduction of pulmonary and systemic vascular resistances and afterload reduction of the left ventricle, (3) reflex sympathoadrenal stimulation with increasing heart rate and myocardial contractility, and (4) a direct positive inotropic effect on the myocardium.

Adult↗
PubMed1993

A simplified method to determine galactose elimination capacity in patients with liver disease.

Galactose elimination capacity (GEC) is one of the most widely used liver function tests. It is relatively simple but still involves a number of capillary blood samples and is therefore fairly expensive. In the current study we present a simplified formula, based on GEC investigations in 103 cirrhotic patients, with which it is possible to estimate the GEC with one or two blood samples. Using this formula: GEC = [7.422--corrected B-galactose60 min]/4.575, we could accurately predict GEC in 24 additional patients.

Blood Specimen Collection↗
PubMed1992

Effect of insulin on human adipose tissue metabolism in situ. Interactions with beta-adrenoceptors.

The effects of insulin, and its interactions with catecholamines through beta-adrenoceptors, on human adipose tissue glucose utilization and lipolysis were investigated in vivo. Microdialysis of the extracellular compartment of abdominal subcutaneous adipose tissue was performed in healthy subjects of normal weight, before and during a 2-h hyperinsulinaemic (61 +/- 3 mU/l), euglycaemic clamp. The tissue was perfused with or without the beta-adrenergic agonist isoproterenol (10(-6) mol/l), and the tissue dialysate concentrations of glucose, glycerol (lipolysis index) lactate and pyruvate were determined. During the insulin infusion, glucose in adipose tissue decreased by 20% (p less than 0.001), despite arterial steady-state normoglycaemia. The concentrations of lactate and pyruvate increased gradually to a steady-state plateau of twice the basal level in adipose tissue and arterial blood. Insulin-induced suppression of glycerol (lipolysis index) was, if anything, more marked in adipose tissue than in plasma (65% vs 50% decrease from baseline levels, p less than 0.05). In situ perfusion of adipose tissue with isoproterenol, starting either at the beginning of the study period or at 45 min after initiation of the insulin infusion, resulted in marked and rapid elevations of all the investigated metabolites in the adipose tissue extracellular compartment (p less than 0.05-0.005). It is concluded that insulin action on glucose uptake and lipolysis in human adipose tissue in vivo is counteracted by beta-adrenoceptor stimulation. In contrast, insulin and beta-adrenoceptors have synergistic effects on non-oxidative glucose metabolism in human adipose tissue in situ.

Adipose Tissue↗