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Biomedical subjects

G Marchesini

Publications and source records attributed to G Marchesini.

At least 109 records · Page 6Linked to original sources
PubMed1991

Elimination of infused branched-chain amino-acids from plasma of patients with non-obese type 2 diabetes mellitus.

Increased plasma levels of branched-chain amino-acids (BCAA) have been demonstrated in poorly controlled diabetes mellitus, and related to absolute or relative insulin deficiency. To study the pathogenesis of this alteration, the elimination of BCAA from plasma was measured in 8 patients with non-obese type 2 diabetes mellitus and in 8 age-matched control subjects during steady-state BCAA concentrations induced by a primed-continuous infusion. Fasting BCAA levels were increased by 40-50% in patients with diabetes. The plasma clearances of valine, isoleucine, and leucine, calculated as infusion rate divided by steady-state concentration, were reduced by 20% in diabetics, despite 50% hyperinsulinemia (P < 0.01). Basal BCAA levels and BCAA clearance were negatively correlated (r(2) = 0.46 - 0.56). The endogenous basal appearance rates of BCAA, estimated by the basal concentrations multiplied by the plasma clearances, were normal in diabetics, and there was no difference in the apparent volumes of distribution of BCAA. The increased basal concentration of BCAA in poorly controlled type 2 diabetics (693 [SD 114; n = 8] mumol/l vs 479 [88; n = 8] in controls (P < 0.005) is attributable to changes in plasma clearances, without any change in the efflux of BCAA into plasma. This may be due to insulin resistance.

Journal Article↗
PubMed1991

Thyroid gland size and function in patients with cirrhosis of the liver.

Thyroid dysfunction has long been reported in patients with liver disease, but limited information is available on thyroid gland size in cirrhosis. Most studies were carried out on small, selected series of patients, and no study has measured thyroid volume in relation to the etiology of liver disease. Thyroid volume was measured at ultrasound in 118 consecutive patients with cirrhosis of different etiology and 48 healthy subjects matched for age and sex. No subjects had evidence of overt thyroid disease. The mean volume was increased by 17% (from 16.0 [SD 5.2] ml in controls to 18.8 [7.6] in cirrhosis; P less than 0.025), and thyroid enlargement (antero-posterior diameter greater than 20 mm) was present in 38% of cases, in the presence of hormone values indicative of low-T3 syndrome. No significant differences in thyroid gland size were observed in relation to the extent of liver dysfunction or to the etiology of liver disease. The prevalence of thyroid nodules was similar in controls and in patients with cirrhosis. In only 8% of cases were laboratory values indicative of hypothyroidism, with low free triiodothyronine and raised thyroid-stimulating hormone levels; in these patients thyroid volume was decreased on average by 26%. This was mainly the case with patients with primary biliary and alcoholic cirrhosis. The largest mean thyroid volume was observed in patients with HBsAg + ve postnecrotic cirrhosis, whose thyroid volume was increased on average by 37%, and 53% of subjects had thyroid enlargement. This finding raises the question of a possible direct involvement of the thyroid in hepatitis B virus infection.

Female↗
PubMed1991

Effect of physical exercise on one-sample antipyrine clearance.

Moderate physical exercise for a few hours is not expected to reduce the hepatic elimination of drugs exhibiting capacity-limited metabolism (low-clearance drugs such as antipyrine). However, previous studies have shown that antipyrine half-life, measured by the multiple-sampling technique, is increased by exercise. A simplified one-sample procedure for antipyrine clearance determination is increasingly being used as a liver function test. The effects of exercise on this measurement have never been evaluated. We measured antipyrine clearance, using the one-sample, simplified procedure in a group of 50 young Italian army soldiers, while at rest and during a 6 hour march in the mountains (extra energy expenditure: 7.43 kjoule per min). Mean antipyrine clearance was on average 46.6 (SD 10.2) ml/min (range 30.5-65.4) while resting, and 46.2 (10.5) (range 25.5-64.8) while exercising (not different). No specific advice regarding physical exercise is needed whenever liver function is measured in outpatients by the one-sample, simplified antipyrine clearance test.

Adult↗
PubMed1991

Prognostic indicators in compensated cirrhosis.

In an attempt to identify variables predicting prognosis, 100 consecutive patients with compensated cirrhosis of the liver were followed for a mean of 4.9 (SD 0.7) yr. Fifty-one patients belonged to Child-Pugh class A, 49 to class B. At entry, five laboratory parameters were considered, together with sex, the grade of esophageal varices, and seven variables measured by ultrasonography (liver and spleen volume and the calibers of the splanchnic vessels). In a subgroup of 56 patients, the galactose elimination capacity also was determined. Forty-six patients were alive at the end of follow-up. Survival was analyzed according to Cox's model. Six parameters were able to predict survival (albumin, bilirubin, liver volume, prothrombin activity, cholesterol, varices). However, step-wise Cox regression analysis identified only four variables that independently correlated with survival: albumin, bilirubin, cholesterol, and liver volume. Galactose elimination failed to add any significance to routine liver function tests. This prospective study confirms the ability of routine liver function tests in predicting survival in compensated cirrhosis. The measurement of liver volume, easily obtained by ultrasonography, is also significant for prognosis, and may be introduced into clinical practice.

Actuarial Analysis↗
PubMed1991

Hepatic amino-nitrogen clearance to urea-nitrogen in control subjects and in patients with cirrhosis: a simplified method.

The functional hepatic nitrogen clearance during amino acid infusion is a measure of liver cell mass. The clinical feasibility of the test has so far been limited by methodological problems. A simplified procedure was used to measure the urea-nitrogen synthesis rate and functional hepatic nitrogen clearance in nine subjects with normal liver function and in nine patients with cirrhosis. The method was based on only four consecutive 2-hr urine collections and five blood samples. Total body water was calculated from a nomogram based on age and anthropometric data, whereas the gut urea hydrolysis was assigned one fixed fraction of synthesis (0.17 in control subjects and 0.26 in patients with cirrhosis). Finally, a solution of a single amino acid, alanine, was infused as substrate for urea synthesis. Urea-nitrogen synthesis rate increased linearly with increasing alpha-amino-nitrogen concentration, and the slope of the regression (functional hepatic nitrogen clearance) was reduced in cirrhosis from 37.5 +/- 7.0 L/hr to 18.4 +/- 6.7 L/hr; p less than 0.005. The hepatic nitrogen clearance was linearly related to the clinical status (Child-Pugh score), to routine liver function tests and to galactose elimination capacity (r = 0.869), a well-established, quantitative, liver function measure. The simplified method makes the measurement of hepatic nitrogen clearance suitable for routine clinical use. The test might prove useful to study the alterations of nitrogen metabolism in cirrhosis, with special reference to hepatic encephalopathy.

Adult↗
PubMed1990

Ultrasonographic follow-up of liver cirrhosis.

Ultrasonography and upper gastrointestinal endoscopy were prospectively used to study 100 consecutive patients with liver cirrhosis. After a period of 20 months to 55 months, 21 patients had died, 23 were lost at follow-up, and 56 patients were reevaluated. In the patients who died during follow-up, the entry liver volume, measured by means of the hepatic volumetric index, was lower as compared to the 56 cirrhotics who survived. During the study period, liver volume significantly decreased to values similar to those observed, at entry, in patients who died. Moreover, esophageal varices increased in size, and the splanchnic veins enlarged. Abdominal ultrasonography provides data regarding the natural history of liver cirrhosis, which might be used, in addition to tests of liver function and endoscopy, as prognostic factors in cirrhotic patients.

Adult↗
PubMed1990

Mathematical model to analyse urea synthesis following alanine infusion in control subjects and in patients with liver cirrhosis.

A three-compartment model was used to analyse the urea response to an alanine infusion in control subjects and patients with liver cirrhosis. Discriminant analysis showed a good separation between model coefficients of the two groups. A single parameter was derived, able to quantify the liver functional capacity. The method provides a useful diagnostic tool in patients with liver disease.

Alanine↗
PubMed1990

Glucose disposal, beta-cell secretion, and hepatic insulin extraction in cirrhosis: a minimal model assessment.

Factors controlling glucose metabolism after IV load were studied in nine patients with compensated cirrhosis and in six age-matched controls. The time courses of glucose, insulin, and C peptide were analyzed by means of the minimal model technique. In cirrhosis, insulin sensitivity was reduced by approximately 70% and glucose-dependent glucose uptake (glucose effectiveness) by 45%. Decreased glucose effectiveness explained 65% of the variance of glucose disappearance and correlated with the ratio of urinary creatinine to height, an independent measure of muscle mass (r = 0.839). beta-cell responsiveness to glucose, measured on C-peptide kinetics, was variable and increased on average by 170% and 107% (first-phase and second-phase, respectively). The total amount of insulin secreted by beta-cells in the course of the study was nearly doubled, whereas the basal insulin secretion rate was in the normal range. The time courses of hepatic extraction of insulin did not differ between groups, and basal extraction was on average 58% in controls and 56% in patients with cirrhosis. It was reduced to 30% in a single patient who had severe hepatocellular failure and large spontaneous portosystemic shunting. We conclude that the alterations in glucose metabolism of cirrhosis include a decreased insulin sensitivity, a reduced glucose effectiveness, and an increased pancreatic responsiveness to glucose, leading to hyperinsulinemia. The hepatic extraction of insulin is reduced only in the very advanced stages of the disease, possibly because of a large reserve capacity of the hepatic parenchyma.

Adult↗
PubMed1990

Long-term oral branched-chain amino acid treatment in chronic hepatic encephalopathy. A randomized double-blind casein-controlled trial. The Italian Multicenter Study Group.

In a double blind randomized study, branched-chain amino acids and placebo (casein) were compared as a treatment for chronic hepatic encephalopathy in cirrhosis. After a 15-day run-in period with controlled diet (45-65 g protein), the patients were administered, in addition to their diet, branched-chain amino acids (0.24 g/kg, 30 patients) or an equinitrogenous amount of casein (34 patients). One patient on branched-chain amino acids and two on casein were lost to the study. After 3 months, the index of portal-systemic encephalopathy significantly improved in patients on active treatment (from 40 [S.D. 14]% to 21 [17]), but was not in subjects receiving casein (from 37 [13]% to 36 [12]). Two or more parameters of the index improved in 24 patients treated with amino acids (80%; confidence limits, 61-92%), and only in 12 receiving casein (35%; confidence limits, 20-54%; p less than 0.001). Patients who did not improve were given an alternative treatment for 3 more months. Casein-treated patients given branched-chain amino acids rapidly improved. The changes in neuropsychologic function were associated with an improvement in semiquantitative nitrogen balance, which became consistently positive in amino acid-treated subjects; there was also a mild improvement in nutritional parameters and in liver function tests. The supplementation of oral branched-chain amino acids to the diet is superior to casein as a treatment for providing adequate nitrogen supply and improving the mental state of cirrhotic patients with chronic encephalopathy.

Adult↗
PubMed1990

Synthesis of urea after a protein-rich meal in normal man in relation to ageing.

An age-related decline in the functional capacity of the liver has been repeatedly demonstrated by means of dynamic tests. We measured the urea-N synthesis rate in response to a protein-rich meal in 24 healthy subjects divided into three age-groups (less than or equal to 55 years, 56-70 years; greater than or equal to 71 years). No differences were observed in the basal state. The peak urea synthesis and the mean urea synthesis in the 5 hours after the meal were blunted with increasing age, and a negative correlation was present between mean or peak urea synthesis and age (r = -0.572 and r = -0.541, respectively). No differences in basal and post-meal total alpha-amino-nitrogen or individual plasma amino acids were observed. Hormone responses were similar. Galactose elimination capacity was also reduced with increasing age, and correlated with mean and peak urea synthesis after a protein mean (r = 0.640 and r = 0.591, respectively). These data suggest that the capacity of the liver to produce urea in response to a protein-rich meal is reduced in the elderly in relation to a decreased functional liver cell mass.

Age Factors↗
PubMed1990

Analysis of the deterioration rates of liver function in cirrhosis, based on galactose elimination capacity.

The prognosis of cirrhotic patients may depend on their liver function, but very few data are available to predict life expectancy in individual subjects on the basis of their liver function tests. The yearly changes in liver function, based on galactose elimination capacity (GEC), were retrospectively analyzed in 76 cirrhotic patients. The first GEC measurement had always been performed at the time of diagnosis. From that time on, mean GEC changes (in mmol/min per year) were +0.13 [SD 0.60] in the 1st year (range: +1.42/-1.35), and -0.03 [0.30] in the 2nd year (P = ns). Only after 36 months could a significant deterioration in liver function be demonstrated, but GEC changes still ranged from +0.14 to -0.35. The trend in liver function was similar in patients with alcoholic and non-alcoholic cirrhosis, but in alcoholics a favourable effect of abstinence was proved. In individual subjects, 2 consecutive GEC measurements, at least 6 months apart, failed to predict the following GEC values. The coefficients of determination between expected and measured GEC or delta GEC were 0.13 and 0.36, respectively (n = 58). When forecasting was limited to 2 years (n = 38), still only 31% and 55% of GEC values and delta GEC variance was predictable on the basis of preceding GEC values. The study shows that no definite trends in liver function deterioration rates can be observed in cirrhosis. This limits the usefulness of liver function tests in predicting prognosis in cirrhotic patients.

Adult↗
PubMed1990

Mechanisms and consequences of the impaired trans-sulphuration pathway in liver disease: Part II. Clinical consequences and potential for pharmacological intervention in cirrhosis.

The liver is actively involved in the metabolism of the sulphur-containing essential amino acid, methionine. Methionine is transformed into S-adenosyl-L-methionine (SAMe) and then into sulphur-containing metabolites (cysteine, taurine and glutathione) via the trans-sulphuration pathway. Liver disease may affect the trans-sulphuration pathway and decrease the clearance of methionine, which leads to increased fasting methionine concentrations in blood and reduced formation of cysteine and glutathione. There is evidence that this defect, located at the level of SAMe-synthetase, may cause nutritional defects and contribute to negative nitrogen balance whenever non-essential sulphur-containing amino acids are not supplied in adequate amounts. In addition, cirrhotic patients may be at increased risk of hepatotoxicity after treatment with substances which are detoxified via glutathione. The SAMe-synthetase block may be overcome by administration of oral or intravenous SAMe, which improves the fasting amino acid profile and increases the hepatic glutathione concentration. Controlled studies on long term SAMe treatment in patients with cirrhosis are needed to confirm this possible beneficial effect.

Amino Acids↗
PubMed1989

A rapid method for the in vivo measurement of liver volume.

A method is described to calculate liver volume at US using real-time equipment. The method is based on the measurement of the 3 maximum diameters of the liver. Equations were derived by correlation vs CT volume measurement using the 3 diameters (multiple regression) or their product (simple regression) as independent variables in 20 subjects with and without liver disease. It is suggested that liver volume may be estimated as: y = -2364 + 89.2.(C-C) + 119.9.(A-P) + 59.6.(L-L) or y = 133.2 + 0.422.(C-C.A-P.L-L) where y is the volume (in ml), and C-C, A-P, and L-L are the 3 diameters (in cm). The two equations were validated in a second set of 22 subjects. US volume estimated according to Eq. 2 explained approximately 82% of the variance of the actual liver volume. The method is reproducible (interobserver variations less than 8%), rapid and easy-to-repeat. These features make it potentially useful in prospective longitudinal studies.

Adult↗
PubMed1989

Portal blood velocity and flow in aging man.

The portal blood velocity and flow were measured by means of pulsed echo-Doppler in 60 normal subjects of 4 different age groups (less than or equal to 40, 41-55, 56-70, greater than or equal to 71 years). All subjects had normal routine liver function tests and no history of liver disease. Portal blood velocity decreased from 15.7 +/- 3.2 cm/s in younger subjects to 12.4 +/- 1.7 in subjects over 71 years (ANOVA: p = 0.005). Similarly portal blood flow decreased (p = 0.025). Both portal blood velocity and flow were inversely correlated with age (r = -0.583 and -0.505, respectively). No changes in portal vein diameter were observed. The age-related decline in portal flow may account for the decrease in hepatic blood flow previously documented in the elderly.

Adult↗