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Biomedical subjects

G Marchesini

Publications and source records attributed to G Marchesini.

At least 127 records · Page 7Linked to original sources
PubMed1988

Caffeine intake, fasting plasma caffeine and caffeine clearance in patients with liver diseases.

The effects of a variable daily administration of caffeine on fasting levels of caffeine in plasma and in saliva were measured in 24 patients with liver disease and hepatocellular dysfunction of variable degree. For 2 consecutive days the patients received either 250 mg of caffeine (in 2 separate doses of 125 mg each at 8:00 a.m. and at 6:00 p.m.) or a single dose of 125 mg at 6:00 p.m. Caffeine clearance was also measured and the results were correlated with the galactose elimination capacity and with antipyrine clearance. At the beginning of the study, fasting caffeine concentrations were largely variable, without any relation to liver function. A strict negative correlation between fasting caffeine and caffeine clearance was only observed after 2 days of controlled caffeine administration (rs = -0.814). Under these conditions, fasting caffeine also correlated with antipyrine clearance (rs = -0.671, n = 20) and with galactose elimination (rs = -0.565). Our data prove that fasting caffeine concentrations after an evening dose may be used as an index of liver function only in subjects under a strictly controlled dietary caffeine intake. The large availability of caffeine in the diet makes the compound scarcely reliable for a correct measurement of liver function based on a single sample, and correct clearance determination is needed.

Body Weight↗
PubMed1987

Insulin resistance is the main determinant of impaired glucose tolerance in patients with liver cirrhosis.

To clarify the pathogenesis of impaired glucose tolerance in patients with cirrhosis, several factors possibly affecting carbohydrate metabolism were studied in 12 cirrhotic patients with different blood glucose responses to an oral glucose tolerance test. Glucose levels, 120 min after the load, were inversely and significantly related to insulin sensitivity, measured by means of the euglycemic "glucose clamp" technique (r = -0.746). Basal and glucose-induced insulin secretion (insulin and C-peptide levels) only slightly correlated with glucose tolerance, which was not related to functional liver cell mass (galactose elimination), portal-systemic shunting (degree of varices at endoscopy), or maximal glucose-independent insulin secretion (peak C-peptide levels after a glucagon test). Multiple regression analysis identified insulin sensitivity and liver cell mass as the independent variables able to explain most of the variance of 120-min blood glucose (about 84%), and both of them contributed considerably to the regression. While reduced insulin sensitivity is probably the main cause of impaired glucose tolerance, the reduced hepatocellular mass only appears to modulate the degree, and therefore the clinical relevance, of this defect.

Adult↗
PubMed1987

Insulin resistance in aged man: relationship between impaired glucose tolerance and decreased insulin activity on branched-chain amino acids.

The effects of glucose-induced hyperinsulinemia on plasma amino acid levels were measured in 50 subjects divided into five age groups. Following an oral glucose load the plasma levels of most amino acids decreased, the decline being more pronounced for the three branched-chain amino acids (valine, isoleucine, and leucine). A progressive insulin resistance was proved on the basis of an age-related impaired glucose tolerance and a normal or increased insulin response. The plasma disappearance of branched-chain amino acids significantly correlated with age (r = -.514). The effects of the prevailing plasma insulin on branched-chain amino acids, measured by the ratio of amino acid changes per total insulin response, progressively declined in older subjects (P = .0005), and strictly correlated with age (r = .652). Insulin resistance in the elderly similarly affects glucose and branched-chain amino acid metabolism, with possible relevant effects on whole-body protein turnover.

Aged↗
PubMed1987

Plasma clearances of branched-chain amino acids in control subjects and in patients with cirrhosis.

In an attempt to clarify the pathogenesis of the decreased branched-chain amino acid (BCAA) plasma concentrations in cirrhosis, the plasma clearances were measured in 7 patients with cirrhosis and in 7 age- and sex-matched control subjects. BCAA were given as prime-continuous infusions. The plasma clearances of valine, isoleucine, and leucine, calculated as infusion rate divided by steady state concentration, were low normal in cirrhotics despite hyperinsulinaemia, but different BCAA had different clearances (P less than 0.01). The endogenous basal appearance rates of BCAA, estimated by the basal concentrations multiplied by the plasma clearances, were lower in cirrhotics (P less than 0.025). The apparent theoretical volumes of distribution of BCAA, assessed by the ratio between the clearance and the concentration decay constant after infusion stop, were on average 67% of the total body weight, and were neither different among the three BCAA, nor between the two groups. The urea nitrogen synthesis rate did not increase significantly, suggesting that most of the infused BCAA nitrogen was taken up in peripheral tissues. The decreased concentration of BCAA in cirrhotics (394 +/- 81 mumol/l (mean +/- SD) in the present series vs 510 +/- 68 in controls; P less than 0.025) is not attributable to changes in plasma clearance. The most likely explanation is decreased afflux of BCAA into plasma.

Adult↗
PubMed1986

Evaluation of liver volume and liver function following hepatic resection in man.

In a longitudinal study liver volume and liver function were measured in a series of 12 patients undergoing partial liver resection for focal hepatic lesions. Ultrasonography revealed that liver volume, reduced by about 50% by the resection, progressively increased, and 6 months after surgery it returned to nearly normal values. A variable reduction in routine liver function tests was observed, possibly reflecting the influence of the different reserve synthetic capacity of the liver and, in the early postoperative phase, plasma half-life of liver products and blood loss or changes in plasma volume. The galactose elimination capacity was only marginally reduced in the early period (from a pre-surgery value of 2.49 +/- SE 0.21 mmol/min to 2.31 +/- 0.14 after 7 days; p = ns) and reached a nadir at 14 days (1.97 +/- 0.16; p less than 0.001). When expressed per unit of liver volume, the galactose elimination (22 +/- 2 mumol/min per unit before resection) progressively decreased during the regeneration phase from 36 +/- 4 at 14 days to 26 +/- 3 at 6 months (P vs 14-day: less than 0.01). At 6 months both galactose elimination and galactose elimination per unit of liver volume were no longer different from baseline values. Our data show that, following hepatic resection, both liver volume and liver function increase and progressively return to nearly normal values. In agreement with data obtained in animal studies, it appears that the metabolic activity of the remaining parenchyma is increased in the early postoperative phase, and it slows down in the course of regeneration.

Adult↗
PubMed1986

Sonographic evaluation of liver, spleen, and splanchnic vessels following partial liver resection.

The liver and spleen size and the splanchnic vessel caliber were evaluated by means of real-time ultrasonography in 12 consecutive patients who underwent a partial hepatic resection for benign or malignant lesions. All parameters were evaluated before surgery and 14 days, 28 days, two months, and six months after the partial hepatic resection. The liver size, which was halved after the resection, progressively increased during the follow-up. The splanchnic veins showed, at 14 and 28 days, a significant increase in caliber and a reduced compliance to breathing, which progressively returned to normal levels. The spleen size increased after partial hepatectomy and remained enlarged throughout the study. Ultrasonography was able to detect that partial hepatic resection is followed by a progressive regeneration of the residual parenchyma and by a transient increase in portal pressure, which returns to normal levels when the liver regenerates.

Adult↗
PubMed1985

Degeneration of the corticospinal tract following portosystemic shunt associated with spinal cord infarction.

The clinicopathological aspects of a case of myelopathy that followed the creation of a surgical porto-caval shunt for hepatic cirrhosis and oesophageal varices are presented. Degeneration of the lateral corticospinal tracts associated with diffuse bilateral ischaemic changes of the spinal gray matter and proliferation of Alzheimer type 2 glia in the brain and brain stem were the most prominent findings. The association of corticospinal tract degeneration and ischaemic lesions of spinal gray matter in absence of any anatomical cause of spinal cord infarction suggests that a modification of the spinal blood flow caused by creation of portosystemic shunts might be the basic pathogenetic mechanism of this complication of severe liver disease.

Brain↗
PubMed1985

Pancreatic beta-cell function in cirrhotic patients with and without overt diabetes. C-peptide response to glucagon and to meal.

To study the role of pancreatic beta-cell function in glucose intolerance and frank diabetes that sometimes develops in cirrhosis, the C-peptide response to a bolus IV injection of 1 mg of glucagon was measured in nine controls and in two groups of patients with cirrhosis. The first group comprised nine subjects with normal or high-normal fasting plasma glucose and no glycosuria; five of them had impaired glucose tolerance. The second group consisted of eight cirrhotics in whom frank diabetes had developed six to 48 months after the diagnosis of cirrhosis. They were characterized by fasting plasma glucose greater than 140 mg/dL and permanent glycosuria. No differences in the degree of liver impairment or portal-systemic shunting were observed between the two groups. Plasma glucose response to glucagon was similarly reduced in cirrhotic subjects. Basal C-peptide was high normal in patients with cirrhosis, and significantly increased in nondiabetic subjects. By contrast peak C-peptide levels and total C-peptide responses to glucagon were low normal in cirrhotics and significantly reduced in patients with cirrhosis and diabetes. In 14 patients the C-peptide response to a standard meal was also measured. It was significantly reduced in patients with cirrhosis and diabetes (six cases), as compared to cirrhotic subjects without diabetes. Peak C-peptide after IV glucagon significantly correlated with peak C-peptide after the meal (r = .927), or total C-peptide response to meal (r = .871). Impaired insulin secretion may add to insulin resistance in patients with liver cirrhosis, leading to the development of frank diabetes, characterized by fasting hyperglycemia and glycosuria.

Adult↗
PubMed1985

Portal pressure changes induced by medical treatment: US detection.

The portal venous system was studied by ultrasonography (US) in 18 patients with cirrhosis of the liver who had previous bleeding from large esophageal varices. Portal-tract pressure for ten of these patients also was measured by hepatic vein catheterization. After 21 days of treatment with atenolol, the calibers of their splanchnic veins decreased during expiration, while a response to breathing maneuvers was restored. The decrease in the caliber of the splenic and superior mesenteric veins seen by US appeared to correlate significantly with the decrease in portal pressure (P less than .05). Nonresponse to treatment also was detected by US. Real-time US may be routinely carried out as a noninvasive, easy-to-repeat technique for the study of portal system hypertension in patients with cirrhosis undergoing therapy with beta-adrenergic blocking agents.

Adult↗
PubMed1985

Splanchnic vein measurements in patients with liver cirrhosis: a case-control study.

The portal venous system was evaluated by real-time ultrasonography in 100 consecutive cirrhotic patients and 100 pair-matched controls to assess the sensitivity and specificity of ultrasound findings in detecting or excluding cirrhosis. The best discriminant findings were the expiration diameters of the superior mesenteric and the splenic vein and, chiefly, their sum corrected by body surface. In cirrhotics the calibers of the splanchnic veins significantly increase in relation to the extent of esophageal varices, but in individual patients this increase cannot predict the extent of varices, which are the main determinant of the bleeding risk.

Adult↗
PubMed1984

Insulin-dependent metabolism of branched-chain amino acids in obesity.

The effect of euglycemic hyperinsulinism on branched-chain amino acids (BCAA; valine, isoleucine and leucine) was evaluated in five obese subjects and five controls. A continuous intravenous insulin infusion raised plasma insulin to a steady-state level. An artificial endocrine pancrease that infused glucose was used to sustain euglycemia. Basal and steady-state insulin levels were significantly higher in the obese subjects than in the controls. The amount of glucose infused to maintain euglycemia and its ratio to steady-state insulin levels was significantly lower in the obese subjects, suggesting an impaired insulin action on glucose metabolism. Basal BCAA levels were similar in the two groups of subjects. During insulin infusion the decremental areas of BCAA below basal levels were significantly lower in the obese patients (63 +/- 5 nmol/mL X min v 143 +/- 8 nmol/mL X min, P less than 0.001), as was the ratio of the decremental areas of BCAA to the incremental areas of insulin (1.11 +/- 0.05 nmol/microU v 3.30 +/- 0.24 nmol/microU, P less than 0.001). Our data suggest that insulin resistance in obesity reduces hormonal effects on glucose as well as on BCAA metabolism.

Amino Acids, Branched-Chain↗
PubMed1984

The euglycemic clamp technique in patients with liver cirrhosis.

Tissue sensitivity to insulin and insulin metabolic clearance rate were assessed by means of the euglycemic clamp technique in 11 controls and 11 patients with liver cirrhosis. The method was carried out using an artificial endocrine pancreas. The amount of glucose infused to keep euglycemia, as well as the ratio of glucose infused to steady-state insulin level, were significantly lower in cirrhotics as compared to controls (p less than 0.001). The metabolic clearance rate of insulin did not show significant differences between the two groups. Our results confirm that a marked insulin resistance is present in cirrhotics, as previously shown by means of different techniques.

Adult↗
PubMed1983

Plasma amino acid response to protein ingestion in patients with liver cirrhosis.

The metabolic effects of a protein-rich meal were studied for 3 h in 10 controls and in 20 cirrhotic patients. After protein ingestion, blood glucose did not vary significantly. Insulin and glucagon levels rose in controls and, more markedly, in cirrhotics. Aromatic amino acids and tryptophan increased more in cirrhotics as a result of their decreased liver function. Similarly, branched-chain amino acids increased by 153 +/- 14 nmol/ml X min (mean +/- SE) in controls and by 259 +/- 27 nmol/ml X min in cirrhotics (p less than 0.02), in the presence of a markedly increased insulin response. Branched-chain amino acid metabolism mainly occurs in skeletal muscle under insulin control; in cirrhosis, it might be reduced as a consequence of insulin resistance. To support this hypothesis, the effects of the protein meal were compared with those of an oral glucose load in 15 cirrhotic patients. Branched-chain amino acid response to protein ingestion significantly correlated with blood glucose response to oral glucose (r = 0.714), and with insulin resistance during the glucose tolerance test, when assessed by the insulinogenic index (r = 0.628). Similarly, in 8 patients, increased branched-chain amino acid response also correlated with the index of tissue sensitivity to insulin obtained by means of the glucose clamp technique during continuous insulin infusion (r = -0.809). We conclude that liver cirrhosis is characterized by an abnormal branched-chain amino acid response to protein ingestion, which matches the well-known intolerance to oral glucose. Both alterations are possibly due to decreased peripheral insulin activity on substrates.

Amino Acids↗
PubMed1982

Muscle protein breakdown in uncontrolled diabetes as assessed by urinary 3-methylhistidine excretion.

In an attempt to evaluate muscle protein catabolism in patients with uncontrolled diabetes, urinary excretion of 3-methylhistidine was measured in eight diabetic subjects, during poor control and after achievement of satisfactory control. The results were compared with the excretion values of ten healthy subjects fed a similar amount of meat. In the diabetic patients in poor metabolic control, 3-methylhistidine excretion was significantly increased compared with the healthy subjects, and returned to normal when a satisfactory glycaemic control was achieved. No significant differences were observed between ketonuric and non-ketonuric uncontrolled patients. Improved glycaemic control reduced 3-methylhistidine excretion in both insulin-dependent and non-insulin-dependent diabetes. These results suggest increased protein catabolism causing muscle protein loss and negative nitrogen balance in diabetic patients with poorly controlled disease.

Adult↗