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Biomedical subjects

E Pisi

Publications and source records attributed to E Pisi.

At least 127 records · Page 7Linked to original sources

Muscle protein breakdown in liver cirrhosis and the role of altered carbohydrate metabolism.

The rates of muscle protein breakdown, as estimated by the urinary excretion of 3-methylhistidine, were assessed in 30 cirrhotics and 15 controls on a strictly controlled diet. 3-Methylhistidine excretion was increased in cirrhotics irrespective of the etiology of the disease, and correlated with basal glucagon levels and with the insulin/glucagon ratio. In nine cirrhotics and nine age- and sex-matched controls, similar correlations were found between 3-methylhistidine and the areas under 24-hr glucagon or insulin/glucagon curves. A larger amount of 3-methylhistidine was excreted during the nighttime than during the daytime, when glucagon secretion was suppressed and the insulin/glucagon ratio was increased. It is concluded that muscle protein catabolism is increased in cirrhotics, possibly as a result of hyperglucagonemia or the reduced insulin/glucagon ratio. These data agree with the clinical observation of a progressive reduction in lean body mass which becomes evident in an advanced stage of the disease.

Adult↗

Anticatabolic effect of branched-chain amino acid-enriched solutions in patients with liver cirrhosis.

An amino acid mixture rich in branched-chain amino acids and poor in aromatic amino acids was infused in six cirrhotics with altered plasma amino acid profile and normal mental state. The effect on muscle protein catabolism, as measured by urinary excretion of 3-methylhistidine, was assessed during two consecutive 3-day period in which patients received the amino acid mixture alone or in a hypertonic dextrose solution. During a 3-day basal period, cirrhotics showed increased rates of 3-methylhistidine excretion as compared to six matched healthy subjects. Both treatments reduced urinary 3-methylhistidine to normal. During treatment, branched-chain amino acids failed to normalize, plasma aromatic amino acid concentrations and ammonia declined, and alanine increased. Branched-chain amino acids are mainly oxidized in skeletal muscle with production of alanine. Reduced muscle protein catabolism following amino acid infusion is consistent with the physiological role of branched-chain amino acids in suppressing protein breakdown and stimulating protein synthesis. Long-term therapy with branched-chain amino acid-enriched mixtures may prove useful in advanced cirrhotics with severe muscle wasting.

Adult↗

Effect of euglycemic insulin infusion on plasma levels of branched-chain amino acids in cirrhosis.

To test the hypothesis that hyperinsulinism is responsible for reduced branched-chain amino acids in cirrhotics, plasma amino acids were sequentially determined in 8 controls and 8 matched cirrhotics during continuous i.v. insulin infusion. An artificial endocrine pancreas which infused glucose was used to sustain euglycemia. Basal plasma insulin levels were high and branched-chain amino acids were reduced in cirrhotics. Insulin infusion raised insulin levels to 3 to 4 times basal values. During the test, the decline in branched-chain amino acids was markedly higher in controls who had similar steady-state insulin levels. Not only did the level of branched-chain amino acids in controls reach the values seen in cirrhotics after 60 min, but the levels continued to fall at a significantly higher rate throughout the second hour. Glucose consumption and the ratio of glucose infused/steady-state insulin--a measure of tissue sensitivity to insulin--were markedly reduced in cirrhotics and positively correlated with the decline in branched-chain amino acids. In cirrhotics, insulin effects on carbohydrate and branched-chain amino acid metabolism were reduced. Low branched-chain amino acid levels in cirrhotics are not likely to depend only on hyperinsulinism.

Adult↗

Close association between basal cell layer antibodies and hepatitis B virus-associated chronic delta infection.

Antibodies reacting in immunofluorescence with the basal cell layer of rat forestomach (BCLA) have been detected in 36 of 121 (30%) hepatitis B virus (HBV)-mediated chronic liver disease (CLD), in 1 of 30 (3%) HBV-negative CLD, in 3 of 36 (8%) alcoholic liver disease (with no correlation with serum HBV markers), in 1 of 25 (4%) primary biliary cirrhosis, in none of 19 HBV-related HBsAg-negative CLD and 60 healthy blood donors. Of 352 hospitalized patients with miscellaneous diseases (including immunological conditions), the antibodies were found in four (1%). In the 36 BCLA positive cases from HBV-mediated CLD, evidence of chronic delta infection was found in 34. The overall prevalence of BCLA in 68 delta cases was 50% (58% in chronic active hepatitis, 46% in cirrhosis), and in 28 delta negative cases was 4% (p less than 0.00002). BCLA of delta cases were mainly of the IgG class (38 of 41 sera), and high titers (up to 40,960) were found in the majority (66% greater than or equal to 1:640). The high titer BCLA has to be considered a marker of chronic delta infection in HBV cases.

Adolescent↗

Basement membrane production by hepatocytes in chronic liver disease.

The immunohistologic distribution of fibronectin, laminin, type IV collagen and whole basement membrane was evaluated in liver biopsies from patients with chronic active liver disease. Fibronectin was consistently increased in the areas of piecemeal necrosis, portal tracts and fibrous septa. Laminin was not detected in normal liver parenchyma. In contrast, laminin positive linear basement membrane structures were prevalent in portal tracts, fibrous septa and the peripheral sinusoids of cirrhotic nodules. In areas of piecemeal necrosis, the hepatocytes, single or assembled in "rosettes", were frequently underlined by linear deposits of laminin and type IV collagen. This immunoreactivity was often polarized, being confined to the stromal side of liver cells, while the parenchymal side was negative for both proteins. Electron microscopy revealed a typical basement membrane in corresponding areas. Hepatocytes normally do not produce a basement membrane, but do so following chronic injury. We suggest that the polarized basement membrane accumulation by hepatocytes is a hallmark of hepatocyte regeneration following damage.

Basement Membrane↗

Portal venous flow in response to acute beta-blocker and vasodilatatory treatment in patients with liver cirrhosis.

The drugs currently under investigation in the prevention of recurrent gastrointestinal bleeding in cirrhosis are likely to decrease the portal pressure by means of a primary reduction of portal blood flow. The hemodynamic effects of beta-blocking agents and vasodilatory drugs were noninvasively measured in eight patients with cirrhosis by means of pulsed echo-doppler equipment. Portal caliber, blood velocity and flow were recorded hourly after a single dose of propranolol (40 mg p.o.) or atenolol (100 mg p.o.), and every 5 min after treatment with isosorbide dinitrate (5 mg sublingually). The drugs were administered at random with an interval of 2 days or more. The portal caliber decreased after atenolol, but did not change after propranolol and isosorbide. The blood velocity decreased by 29 +/- 2% 3 hr after propranolol, by 26 +/- 2% 3 hr after atenolol and by 31 +/- 3% 15 min after isosorbide. The portal blood flow decreased by 0.29 +/- 0.03 liters per min after propranolol, by 0.34 +/- 0.06 after atenolol and by 0.26 +/- 0.03 after isosorbide, without any difference among the various treatments. beta-blockers and vasodilatory drugs have comparable effects on portal blood flow. beta 1-selective and nonselective beta-blockers are similarly effective in keeping with the hypothesis that changes in portal blood flow are mainly due to the block of beta 1-receptors.

Adrenergic beta-Antagonists↗

Galactose elimination capacity and liver volume in aging man.

The galactose elimination capacity, a measure of the functional liver cell mass, and liver volume were measured in 50 normal subjects of five different age groups (less than 50, 51 to 60, 61 to 70, 71 to 80 and greater than 81 years). The volume of the liver was evaluated by ultrasonography. All subjects had normal routine liver function tests and no history of liver disease. Galactose elimination progressively decreased from 3.05 +/- 0.58 (S.D.) mmoles per min in younger subjects to 1.83 +/- 0.24 mmoles per min in subjects over 81 (p less than 0.00003), without any change in the apparent volume of distribution of the sugar. Similarly, the estimated volume of the liver decreased from 110 +/- 14 units to 75 +/- 13 units with increasing age (p less than 0.0002). Both galactose elimination capacity and the estimated liver volume inversely correlated with age (r = -0.728 and r = -0.579, respectively) whereas a positive correlation was observed between galactose elimination and the estimated liver volume (r = 0.520). Part correlation analysis confirmed that age, when entered in a multiple regression already containing body weight and estimated liver volume as independent variables, had a significant effect on liver function, whereas no significant independent effect of liver volume was present. Both age and body weight had a significant independent effect on the estimated liver volume. The maximum functional capacity of the liver, measured by galactose elimination, is reduced in the elderly. Although several factors may play a role, our data suggest that aging is associated with a slight decline in the intrinsic metabolic activity of the hepatic parenchyma.

Adult↗

Echo-Doppler measurement of splanchnic blood flow in control and cirrhotic subjects.

Blood flow in the splanchnic veins was studied in cirrhotics and matched controls by means of a system that combines a mechanical sector scanner with a pulsed Doppler. The measurements were validated in an in vitro model. Echo-doppler studies could be carried out reproducibly in only approximately two-thirds of cases because of poor echo transmission or incomplete cooperation. Portal blood velocity was significantly reduced in cirrhotics (10.5 +/- 0.6 cm/s versus 16.0 +/- 0.5 in controls; p less than 0.001), but portal blood flow was normal because of enlarged portal caliber. A complete hemodynamic evaluation of the splenic and superior mesenteric veins was possible in only a few subjects. In selected patients the technique may prove relevant in the study of hemodynamic effects of drugs and surgery on portal blood flow.

Adult↗

Rapid clearance of HBe antigen and development of anti-HBe antibody in acute viral hepatitis.

The behaviour of the HBe/anti-HBe system in AVH was evaluated, using Magnius technique, by testing serum samples from 47 patients; 29 of them were followed during the clinical evolution of the disease until complete remission was achieved. HBe was more frequent in samples taken from patients in the first 7 days after the onset of jaundice (18/33 = 54%) than in samples collected later (3/14 = 21%). During the clinical evolution of the disease we could always demonstrate the disappearance of HBe not later than 12 days after the onset of jaundice. In one patient studied from the incubation period HBe disappeared before any clinical or laboratory evidence of disease. In 8/29 cases (27%) anti-HBe developed starting from the 15th day of illness, but 4 of these had had no detectable HBe during the acute phase. No significant difference could be demonstrated between HBe +ve and -ve cases in the maximum values of SGPT and bilirubin and the duration of the disease. The changing pattern of the HBe/anti-HBe system could account for the different incidences of these markers reported by many authors in AVH. Our findings support the hypothesis that HBe develops in every HBsAg +ve AVH case. Therefore, it is not the presence of HBe in the early stage, but the persistence of this marker that might be important in predicting progression to chronicity.

Acute Disease↗

Antiperinuclear factor in an Italian series of patients with rheumatoid arthritis.

Serum samples from 90 cases of rheumatoid arthritis (RA), 218 control patients and 100 healthy controls were tested by indirect immunofluorescence for the presence of the antiperinuclear factor (APF), an autoantibody to the keratohyaline granules of human buccal mucosal cells. The sensitivity and specificity of the APF test for RA were 82 and 90%, respectively, slightly higher than those obtained when the same serum samples were tested for rheumatoid factor (RF) using a latex agglutination method. The diagnostic gain of APF in the RF-negative RA cases was greater than that of RF in the APF-negative cases (54% vs. 37%). In spite of a few technical disadvantages, the APF test should be therefore performed in the serological routine examination of rheumatic diseases. As APF was also found in 11% of degenerative joint disease (DJD) cases and the estimated prevalence ratio RA/DJD is, in Italy, 1/11, the predictive value of a negative APF test proved to be much higher than that of a positive test (98% vs. 40%) for the diagnosis of RA. APF was significantly associated with other autoantibodies (RF and antinuclear antibody).

Antibodies, Antinuclear↗

A simple method for purification of human monocytes and evaluation of IgG Fc-receptor-mediated phagocytosis.

A simple and reproducible, although not completely original method for purification of human monocytes and evaluation of IgG Fc-receptor-mediated phagocytosis has been set up and is described here. The purity of monocyte preparations obtained by the use of this method is quite elevated (over 95%), but the yield, although satisfactory for this purpose, is rather poor. As to the test of phagocytosis, a time-response curve using opsonized sheep erythrocytes showed that 10-min incubation gives the best and most reproducible results. A peroxidase reaction is suggested in order to obtain a better evaluation of erythrocytes within monocytes. The test has been proved suitable for evaluation of Fc-receptor function of monocytes in primary biliary cirrhosis, an immunological liver disease, and might be also useful in immune complexes-mediated conditions.

Adult↗

IgA antibodies to dietary antigens in liver cirrhosis.

Antibodies to dietary antigens (ovalbumin, beta-lactoglobulin, casein) have been detected by a micro-ELISA test in 47-50% of serum samples from patients with alcoholic liver cirrhosis, in 27-36% with non-alcoholic cirrhosis (HBV-related, autoimmune and primary biliary) and in 50-70% of cirrhotic patients with portacaval shunt. Dietary antibodies were mainly confined to the IgA class (90%). In patients with chronic active hepatitis dietary antibodies showed a low positivity (11%), similar to that of subjects with alcohol abuse without liver injury and of healthy subjects. Dietary antibodies were significantly associated with portal hypertension (evaluated on the presence of esophageal varices and/or ascites) both in alcoholic and non-alcoholic cirrhosis. The absence of dietary antibodies in the duodenal juice of cirrhotic patients positive for serum antibodies confirms that the intestinal mucosa is normal or slightly altered in liver cirrhosis. Unlike cirrhotics, untreated celiac patients showed a high prevalence of dietary antibodies also in the duodenal juice (55%).

Adult↗

Relationships between smooth muscle and cytoskeleton antibodies in human serum samples.

In order to characterize the relationship between smooth muscle antibodies (SMA) and antibodies directed to the cytoskeleton components (microfilaments, intermediate filaments and microtubules), 338 serum samples from patients with various diseases and from healthy control subjects were tested for SMA and anti-cytoskeleton antibodies using a conventional immunofluorescence method employing traditional substrates and vinblastine-treated fibroblasts. The correspondence between SMA and these antibodies turned out to be incomplete and more evident for anti-microfilaments and anti-microtubules than for anti-intermediate filaments antibodies. Our data confirm that SMA are a quite heterogeneous family of antibodies, whose specificities are not entirely related to the cytoskeleton components. Studies with purified antigens will probably characterize these specificities.

Antibodies↗