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Biomedical subjects

G Marchesini

Publications and source records attributed to G Marchesini.

At least 19 recordsLinked to original sources
PubMed2000

Nutritional treatment with branched-chain amino acids in advanced liver cirrhosis.

During the last 20 years there has been much interest in nutritional treatment for patients with advanced cirrhosis. Most studies have measured the potential benefit of nutritional supplements of dietary proteins, generic protein hydrolysates, or specific branched-chain amino acid (BCAA)-enriched formulas in regard to nutritional parameters and hepatic encephalopathy. The issue is not definitively settled; data are conflicting and meta-analyses have failed to produce unequivocal results. A consensus review, recently produced under the auspices of the European Society for Parenteral and Enteral Nutrition, concluded that: (1) patients with cirrhosis tend to be hypermetabolic, and a higher-than-normal supply of dietary proteins is needed to achieve nitrogen balance; (2) most patients tolerate a normal or even increased dietary protein intake, without risk of hepatic encephalopathy; (3) a modified eating pattern, based on several meals and a late evening snack, is useful; (4) in severely malnourished patients, amino acid supplements may be considered to provide the necessary amount of proteins to meet protein requirements; (5) in a few patients intolerant to the required protein intake, BCAA supplements may be considered to provide the necessary nitrogen intake without detrimental effects on the mental state, perhaps even improving it. Future studies are needed to quantify the advantage of nutritional support with amino acids or BCAA supplements on overall well-being, complications, and ultimately survival with a long-lasting disease where self-perceived health-related quality of life is a major outcome.

Amino Acids, Branched-Chain↗
PubMed1999

Association of nonalcoholic fatty liver disease with insulin resistance.

BACKGROUND AND PURPOSE: Nonalcoholic fatty liver disease is frequently associated with type 2 diabetes mellitus, obesity, and dyslipidemia, but some patients have normal glucose tolerance or normal weight. We tested the hypothesis that there is an association between nonalcoholic fatty liver disease and insulin resistance that is independent of diabetes and obesity. SUBJECTS AND METHODS: We measured anthropometric and metabolic variables in 46 patients with chronically elevated serum aminotransferase levels, "bright liver" on ultrasound scan, and normal glucose tolerance. Indexes of insulin resistance and secretion were determined using the homeostasis model assessment method. They were compared with 92 normal subjects who were matched for age and sex. RESULTS: Patients with nonalcoholic fatty liver disease were characterized by fasting and glucose-induced hyperinsulinemia, insulin resistance, postload hypoglycemia, and hypertriglyceridemia. Insulin resistance [odds ratio (OR) = 15 per percent increase, 95% confidence interval (CI): 3.0 to 70], fasting triglyceride level (OR = 3.1 per mmol/liter increase, 95% CI: 1.1 to 8.9), 180-minute blood glucose level (OR = 4.3 per mmol/ liter decrease, 95% CI: 1.6 to 12), and average insulin concentration in response to oral glucose (OR = 3.0 per 100 pmol/liter increase, 95% CI: 1.5 to 6.2) were independently associated with nonalcoholic fatty liver disease. The exclusion of overweight and obese subjects did not change the results. CONCLUSION: Nonalcoholic fatty liver disease is associated with insulin resistance and hyperinsulinemia even in lean subjects with normal glucose tolerance. Genetic factors that reduce insulin sensitivity and increase serum triglyceride levels may be responsible for its development.

Adolescent↗
PubMed1999

Prostaglandin E1 infusion and functional hepatic flow in control subjects and in patients with cirrhosis.

Metabolic effects of prostaglandin E1 have been previously demonstrated in cirrhosis, apparently independent of changes in large splanchnic vessel hemodynamics. The effects of prostaglandin E1 on functional liver blood flow were tested by measuring the extrarenal clearance of D-sorbitol in six controls and eight patients with cirrhosis during systemic superinfusion of saline or prostaglandin E1 (30 microg/hr), in random order. Doppler ultrasonography of systemic and splanchnic circulation was also performed before the test and at the end of the two study periods. Prostaglandin E1 infusion increased femoral blood flow by nearly 60% in controls and over 30% in cirrhosis, without any effect on mean arterial pressure and heart rate. Mesenteric artery and portal blood flow were unchanged, as were Doppler-measured resistance indices in the liver, spleen and kidney. Sorbitol-assessed functional hepatic flow was 30% lower in cirrhosis, and did not change systematically during prostaglandin E1 infusion. We conclude that prostaglandin E1, at doses able to elicit metabolic effects and changes in systemic hemodynamics, does not affect splanchnic blood flow and/or hepatic microcirculation in normal subjects and in portal-hypertensive patients with cirrhosis.

Aged↗
PubMed1999

Oxidative stress and anti-oxidant metabolites in patients with hyperthyroidism: effect of treatment.

OBJECTIVE: Oxygen free radicals (OFR) play a role in the pathogenesis of tissue damage in many pathological conditions via the peroxidation of membrane phospholipids. Experimental studies showed an elevated oxidative stress during hyperthyroidism, which is reduced by treatment. Therapy per se might decrease oxidative stress. DESIGN: Fasting plasma levels of thiobarbituric acid reacting substances (TBARS), vitamin E and coenzyme Q10 were measured in 22 hyperthyroid patients, before treatment for their thyroid disease, after 13.9 [SD 9.2] weeks, when they achieved an euthyroid state on thyrostatic drugs, and again after 47.7 [21.0] weeks, off therapy. No patient presented additional risk factors for increased lipoperoxidation and/or increased OFR levels. Smokers were asked to abstain from smoking overnight. METHODS: All analytes were measured by HPLC. RESULTS: In hyperthyroidism, plasma levels of TBARS were increased, whereas vitamin E and coenzyme Q10 were reduced. Average levels of TBARS and antioxidant agents returned to normal in euthyroid patients, without differences in relation to stop of thyrostatic therapy. CONCLUSIONS: Our data confirm the presence of oxidative stress and decreased anti-oxidant metabolites in hyperthyroid patients, which are corrected in euthyroidism, without any influence of thyrostatic drugs per se. Nutritional support with antioxidant agents, which are defective during hyperthyroidism, is warranted.

Adult↗
PubMed1999

Total and functional hepatic blood flow decrease in parallel with ageing.

OBJECTIVES: To study changes in hepatic blood flow with age. DESIGN: Functional hepatic flow (FHF) and total hepatic flow (THF) were determined by non-invasive methods in 40 normal subjects in four age groups (<45, 45-60, 61-75 and >75 years). All subjects had normal routine liver function tests and no history of liver disease. RESULTS: THF was measured by pulsed echo-Doppler, as the sum of portal and hepatic artery blood flow; FHF was measured by the hepatic clearance of D-sorbitol. THF significantly decreased with age, particularly in subjects over 75 (from 1445+/-220 ml/min to 1020+/-148; P<0.001), and a similar reduction was observed in FHF (from 1514+/-250 ml/min to 1015+/-163; P<0.001). THF and FHF were strictly correlated in the whole population (r = 0.871; P<0.001) and both correlated with age (r = -0.510 and r = -0.596; P<0.005). CONCLUSION: With ageing there is a reduction of hepatic blood flow without any additional intrahepatic shunting.

Adult↗
PubMed1999

Cardiovascular disease in cirrhosis--a point-prevalence study in relation to glucose tolerance.

OBJECTIVE: Impaired glucose tolerance or diabetes are frequently observed in cirrhosis. Overt diabetes was reported to affect long term survival of cirrhotic patients by increasing the risk of hepatocellular failure, without increasing the risk of diabetes-associated cardiovascular events. METHODS: We evaluated the prevalence of cardiovascular disease in 122 patients with cirrhosis, subdivided according to their glucose tolerance. The following parameters were considered: arterial pressure, peripheral vascular disease (ankle to brachial pressure ratio), ischemic heart disease, microalbuminuria, retinopathy. The prevalence of abnormal findings was compared with that observed in 60 randomly selected patients with noninsulin-dependent diabetes and in 40 controls. RESULTS: Noninsulin-dependent diabetic patients and patients with cirrhosis and diabetes were comparable for age, metabolic control, and smoking habits; the duration of diabetes was 5 yr longer for noninsulin-dependent diabetes. In cirrhosis, the prevalence of micro- and peripheral macroangiopathy, as well as coronary heart disease, was not different in relation to glucose tolerance, it was comparable to that of controls, and significantly lower than that observed in non-insulin-dependent diabetes. CONCLUSIONS: Cirrhotic patients, even in the presence of overt diabetes, are at low risk of cardiovascular disease. The low prevalence may be related to shorter duration of diabetic disease, also in relation to reduced life expectancy, as well as to liver disease-induced abnormalities protecting the cardiovascular system from atherosclerosis.

Adolescent↗
PubMed1999

Can oxypurines plasma levels classify the type of physical exercise?

BACKGROUND: A laboratory-based model able to describe muscle energy status during physical exercise and changes in myofibrillar composition in response to training would be desirable. Lactate and ammonia concentrations are not sufficient for a comprehensive knowledge of these systems. All muscle fibres, irrespective of the type, show ATP depletion and IMP accumulation following exhausting muscular exercise with quantitative differences due to the different concentrations of deaminase. We studied the plasma concentration of metabolites of oxypurine cascade to test their reliability to classify different exercises. METHODS: We studied 52 athletes, measuring plasma metabolites at the beginning and at the end of their specific field exercise (cycle pursuers, 8 cases; soccer players, 19; marathon runners, 25). K3EDTA-blood samples were assayed for plasma hypoxanthine, xanthine, and inosine, using an HPLC technique, as well as ammonia and lactate by means of enzymatic methods. RESULTS AND CONCLUSIONS: Basal oxypurines levels were not different in relation to any specific physical exercise. Post-exercise oxypurines, namely hypoxanthine, were more precise predictors of muscle energy exhaustion than strain intensity or duration. Plasma levels of hypoxanthine may be elevated also in the presence of normal xanthine and uric acid concentrations, due to an exhaustion of the enzymatic pathway, to a reduced activity of xanthine-oxidase or finally to a substrate-dependent inhibition of the process.

Ammonia↗
PubMed1998

Effects of systemic prostaglandin E1 on hepatic amino acid-nitrogen metabolism in patients with cirrhosis.

Prostaglandins of the E (PGE) series have long been considered "catabolic" hormones, but recent data suggest that they may be secreted in critically ill patients to counteract stress hormones, stimulating protein synthesis. Their use is under scrutiny to improve hepatic microcirculation and as cytoprotective agents. We tested the effects of PGE1 on hepatic and whole-body nitrogen metabolism in eight patients with cirrhosis. Urea-nitrogen synthesis rate, alpha-amino-nitrogen levels, and nitrogen exchange were measured in the basal, postabsorptive state and in response to continuous alanine infusion, in paired experiments, during superinfusion of PGE1 or saline. Splanchnic and systemic hemodynamics were assessed by echo-Doppler at the beginning and at the end of each experiment. PGE1 produced a rapid fall in plasma amino acids and in urea-nitrogen synthesis rate, as well as a positive nitrogen exchange. The slope of the regression of alpha-amino-nitrogen levels on urea-nitrogen synthesis rate, a measure of liver cell metabolic activity, was not affected, but the regression line was shifted rightward, suggesting a nitrogen-sparing effect of PGE1. Mesenteric artery and portal flow were unchanged, whereas femoral artery flow increased by 30%. Insulin and glucagon levels were not systematically different. We conclude that PGE1 reduces hepatic urea synthesis rate, independent of hormones and/or hepatic flow, possibly acting at the peripheral level on amino acid transport, thus reducing amino acid supply to the liver. The resulting net nitrogen sparing might be the basis for the beneficial effect of PGE1 in clinical hepatology.

Aged↗
PubMed1998

Quantification of gluconeogenesis in cirrhosis: response to glucagon.

BACKGROUND & AIMS: Accelerated starvation and early recruitment of alternate fuels in cirrhosis have been attributed to reduced availability of hepatic glycogen. The aim of this study was to measure gluconeogenesis (as a marker of protein oxidation) in relation to total glucose production and glucagon-stimulated glycogenolysis. METHODS: Glucose and urea production, gluconeogenesis, and glycogenolysis were calculated using stable isotope methods before and during glucagon infusion (3 ng. kg-1. min-1) in 5 cirrhotic patients and 5 matched controls before and after glycogen repletion. RESULTS: In the basal state, cirrhotic patients had a normal rate of glucose production, but the contribution of gluconeogenesis was increased (74.3% +/- 4.1% vs. 55. 6% +/- 12.1%; P < 0.005). Glycogen repletion normalized the rate of gluconeogenesis. The glycemic response to glucagon (3 ng. kg-1. min-1) was blunted in cirrhotic patients because of a lower rate of glycogenolysis (0.63 +/- 0.23 vs. 1.22 +/- 0.23 mg. kg-1. min-1; P < 0.01) and was not affected by glycogen repletion. Despite increased gluconeogenesis, the simultaneously measured rate of urea synthesis was lower in cirrhotic patients (3.11 +/- 1.02 vs. 5.0 +/- 1.0 mg/kg; P < 0.05). CONCLUSIONS: These data show that in cirrhosis, glucose production is sustained by an increased rate of gluconeogenesis. The hepatic resistance to glucagon action is not caused by reduced glycogen stores.

Adult↗
PubMed1998

Gender-dependent alterations in serum leptin in alcoholic cirrhosis.

BACKGROUND & AIMS: Leptin is a peptide that decreases food intake and increases energy expenditure. It is produced in fat cells, is stimulated by cytokines, and its levels in serum are higher in females. Because anorexia, hypermetabolism, and elevated cytokine levels are frequently observed in cirrhosis, we hypothesized that the serum leptin level would be elevated in cirrhosis. The aim of this study was to investigate the relationship of serum leptin to gender, body composition, and tumor necrosis factor (TNF). METHODS: Male (n = 18) and female (n = 10) abstinent alcoholic cirrhotic patients were studied and compared with control subjects (15 male and 8 female). Fat mass, fat-free body mass, and body cell mass were calculated by using H2[18O] and bromide dilution methodology. Serum leptin and TNF concentrations were measured by immunoassays. RESULTS: Fat mass was decreased only in male cirrhotics (P < 0.05), whereas body cell mass was decreased in both male and female cirrhotics (P < 0.01). Leptin levels were elevated in female (P < 0. 001) but not male cirrhotics compared with controls. When expressed per kilogram of fat mass, leptin was elevated in both male (P < 0. 01) and female (P < 0.01) cirrhotics. Women in both cirrhotic and control groups had higher leptin levels than men. TNF was elevated in both male and female cirrhotics and did not correlate with leptin levels. CONCLUSIONS: Cirrhotics have elevated serum leptin levels, which are related to both gender- and gender-dependent alterations in body composition.

Adult↗
PubMed1998

Zinc supplementation improves glucose disposal in patients with cirrhosis.

Zinc deficiency is common in cirrhosis, and was proved to affect nitrogen metabolism. In experimental animals, zinc status may also affect glucose disposal, and acute zinc supplementation improves glucose tolerance in healthy subjects. This study was aimed at measuring the effects of long-term oral zinc supplements on glucose tolerance in cirrhosis. The time courses of glucose, insulin, and C-peptide in response to an intravenous (i.v.) glucose load were analyzed by the minimal-model technique before and after long-term oral zinc supplements (200 mg three times per day for 60 days) in 10 subjects with advanced cirrhosis and impaired glucose tolerance or diabetes. The test was performed using a simplified procedure, based on 20 blood samples collected within 4 hours from the glucose load. Normal values were obtained in 25 age-matched healthy subjects. Zinc levels were low to normal or reduced before treatment, and were normalized by oral zinc. Glucose disappearance improved by greater than 30% in response to treatment. There were no changes in pancreatic insulin secretion and systemic delivery, or in the hepatic extraction of insulin. Insulin sensitivity (SI), which was reduced by 80% before treatment, did not change. Glucose effectiveness (SG) was nearly halved in cirrhosis before treatment (0.013 [SD 0.007] min(-1) v. 0.028 [SD 0.009] in controls; P < .001), and increased to 0.017 (SD 0.009) after zinc (P < .05 v. baseline). The return to normal of plasma zinc levels after long-term zinc treatment in advanced cirrhosis improves glucose tolerance via an increase of the effects of glucose per se on glucose metabolism. Poor zinc status may contribute to the impaired glucose tolerance and diabetes of cirrhosis.

Administration, Oral↗
PubMed1998

Effects of systemic prostaglandin E1 on splanchnic and peripheral haemodynamics in control subjects and in patients with cirrhosis.

Prostaglandins of the E series showed metabolic and clinical effects in patients with liver disease; changes in splanchnic haemodynamics might be involved. Blood flow in femoral and mesenteric artery and in the portal vein was measured by echo-Doppler in 10 controls and 14 cirrhotic patients, in response to the systemic infusion of a PGE1 analogue (30 micrograms/h for 2-6 h) or saline, performed in random order. Intraparenchymal resistive and pulsatility indices in the liver, spleen and kidney were also measured. In both groups PGE1 increased femoral artery flow by 40%, irrespective of infusion time. Heart rate increased slightly, whereas mean arterial pressure decreased. There were no changes in mesenteric artery and portal vein flow, as well as in resistance indices. Saline infusion increased femoral artery flow by 4%. PGE1 infusion does not produces significant effects on Doppler-assessed splanchnic hemodynamics in controls and in cirrhotic patients, in spite of significant effects on peripheral circulation.

Aged↗
PubMed1997

Glutathione kinetics in normal man and in patients with liver cirrhosis.

BACKGROUND/AIMS: The dynamics of glutathione in plasma has always been studied by bolus injections. Data are available suggesting that the low plasma levels of cirrhosis are due to decreased production in glutathione-producing tissues, mainly the liver. We aimed to measure the kinetics of glutathione during controlled steady-state conditions, and to determine the reasons for its reduced plasma levels in advanced cirrhosis. METHODS: The plasma clearance of glutathione was measured in six control subjects and in ten patients with cirrhosis during a 2-step infusion study, producing steady-state levels approximately 5 and 10 times basal values. The plasma disappearance curve after infusion stop was used to determine the apparent volume of distribution and half-life of glutathione, and the estimated basal appearance rate. RESULTS: The clearance of glutathione did not reject 1st-order kinetics, i.e., it was concentration-independent, and was nearly doubled in cirrhosis. The half-life of exogenous glutathione was not different, whereas the volume of distribution was larger in cirrhosis, in the same range as extracellular water. The endogenous basal appearance rate of glutathione was reduced by 50%, and correlated with liver function, measured by routine and dynamic tests. CONCLUSIONS: The data confirm that the primary defect responsible for reduced glutathione in liver disease is a reduced production, possibly related to hepatocyte dysfunction and a block along the pathway of methionine metabolism.

Adult↗
PubMed1997

Effect of lactulose on carbohydrate metabolism and diabetes mellitus.

BACKGROUND: Unabsorbable disaccharides, by reducing transit time and possibly glucose absorption, are expected to affect carbohydrate metabolism. AIM: To test the effects of a preparation containing fibre and lactulose in the form of biscuits on glucose and insulin levels in obesity. METHODS: In 10 obese patients glucose and insulin were measured in the fasting state and in response to a meal during two consecutive days on a strictly controlled diet; on one day a total of 11 biscuits (10 g dietary fibre, 2 g raw fibre +8.2 g lactulose) were randomly substituted for an equicaloric part of a diet. RESULTS: Glucose and insulin in response to breakfast and to lunch were blunted by dietary fibre and lactulose, without any trend towards post-meal hypoglycaemia. Average day-time glucose decreased by 0.53 +/- SD 0.28 mmol/L, and insulin by 74.6 +/- 45.2 pmol/L. Plasma amino acids were higher during supplementation, ruling out malabsorption as a cause of glucose flattening. CONCLUSION: Because of the rationale of the preparation, good compliance of patients, and significant results in short-term experiments, the association of fibre and lactulose deserves more careful evaluation in long-term clinical studies.

Blood Glucose↗
PubMed1997

Uncertainty in liver function assessment on the basis of single-point galactose concentration.

The uncertainty in liver function assessment based on single-sample galactose levels after galactose injection, in comparison to the standard procedure using the galactose elimination capacity (GEC), was assessed in 905 tests performed in a wide range of liver functions. The 45-min galactose levels significantly correlated with GEC, the correlation being better in subjects with a good liver function. In cirrhosis, the prediction using the 60-min galactose value was better than when the 45-min value was used. In the whole series, the 95% confidence interval of GEC predicted by 45-min galactose was as large as +/- 1.55mg x kg(-1) x min(-1) as absolute value, corresponding to a range from -41 to +47% of measured GEC. In cirrhosis, the 95% confidence interval was +/- 1.42 mg x kg(-1) x min(-1) and between -40 and +46% of measured GEC. The 60-min values were more predictive, but in Child class C patients the average error was 0.42 mg x kg(-1) x min(-1) (95% confidence interval -0.64 to +1.49, corresponding to -39 to +76% of measured GEC). The uncertainty was maintained within +/- 10% of measured values only in 50% of the tests. We conclude that the single-point galactose test introduces a considerable error, mainly in patients with more advanced liver disease, which may bias the decision-making process.

Analysis of Variance↗
PubMed1996

Efficacy of a surveillance program for early detection of hepatocellular carcinoma.

BACKGROUND: Contrasting data have so far been reported on the utility and efficacy of screening patients with cirrhosis for early detection of hepatocellular carcinoma (HCC). The goal of this study was to evaluate the efficacy of a regular ultrasonographic and laboratory follow-up for the early detection of small HCC, and to identify parameters correlated with a higher risk of developing HCC. METHODS: One hundred and sixty-four consecutive patients with liver cirrhosis living in Emilia Romagna, Italy, were enrolled in the period 1989-1991. All patients underwent clinical, biochemical, and ultrasonographic evaluations at entry and at 3- and 6-month intervals during follow-up. RESULTS: By April 1995, 34 patients had developed HCC. In 76% of the patients, ultrasonography identified HCC when it was still single and small (< 4 cm). At discriminant, logistic regression and univariate analyses, sex and the entry concentration of alkaline phosphatase, alpha-fetoprotein, gamma-glutamyl transpeptidase, and albumin were associated with a higher risk of developing HCC, whereas at multivariate analysis (Cox's model), only sex and the entry concentration of alkaline phosphatase, albumin, and alpha-fetoprotein were independently and significantly related to the appearance of HCC. CONCLUSIONS: A regular ultrasonographic follow-up, timed at 3- to 6-month intervals according to the risk of HCC development in patients with cirrhosis, allows the detection of liver carcinoma at an early stage in a high proportion of patients, possibly improving the prognosis of the disease.

Adult↗