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Biomedical subjects

M Podda

Publications and source records attributed to M Podda.

At least 19 recordsLinked to original sources
PubMed1992

Comparison of spontaneous ascites filtration and reinfusion with total paracentesis with intravenous albumin infusion in cirrhotic patients with tense ascites.

OBJECTIVE: To compare the effectiveness and safety of spontaneous ascites filtration and reinfusion and total paracentesis plus intravenous albumin infusion in cirrhotic patients with tense ascites. DESIGN: Randomised trial of the two treatments. SETTING: Teaching hospital and district general hospital in Milan. PATIENTS: 45 consecutive cirrhotic patients with recurrent tense ascites and urinary sodium excretion rate less than 20 mmol/day. 35 fulfilled admission criteria and completed the study. 17 received spontaneous ascites filtration and 18 paracentesis plus albumin infusion. MAIN OUTCOME MEASURES: Body weight; urinary volume; serum and urinary electrolyte, serum fibrinogen, and plasma aldosterone concentrations; and plasma renin activity before the procedure and 24 hours and eight days afterwards. RESULTS: Both procedures were effective in all patients. Weight decreased in both groups and showed no substantial increase after eight days. In patients receiving ascites filtration, values decreased significantly (p less than 0.01) after 24 hours for platelet count (mean relative change 0.92; 99% confidence interval 0.86 to 0.98) and serum fibrinogen concentration (0.92; 0.88 to 0.98) but returned to pretreatment values after eight days; no laboratory and clinical signs of disseminated intravascular coagulation were noted. Three patients in this group had fever, which receded spontaneously. One patient in each group had dilutional hyponatraemia. CONCLUSIONS: Spontaneous ascites filtration and reinfusion is an effective treatment for tense ascites. Reinfusion of the patient's concentrated proteins provides savings without compromising safety.

Adult↗
PubMed1992

Ursodeoxycholic acid therapy in cystic fibrosis-associated liver disease: a dose-response study.

Previous studies from our groups have demonstrated improvements in biochemical markers of liver function when cystic fibrosis patients with associated liver disease were administered oral ursodeoxycholic acid. The magnitude of the response was somewhat less than that found when comparable doses (10 to 15 mg/kg body wt/day) of ursodeoxycholic acid are given to other liver disease patients; this may be explained by the bile acid malabsorption that is characteristic of the disease. For this reason a dose-response study was carried out in nine cystic fibrosis patients with liver disease to establish whether improved efficacy could be obtained with higher doses. Ursodeoxycholic acid in doses of 5, 10 and 15 mg/kg body wt/day was given orally for consecutive 2-mo periods in a replicated Latin-square design. After this, all patients received 20 mg/kg body wt/day. Liver function, individual serum bile acids and biliary bile acid composition were determined at entry and at the end of each treatment period. Our data demonstrate that the magnitude of the biochemical improvement in serum liver enzymes was significantly greater with higher doses of ursodeoxycholic acid; at 20 mg/kg body wt/day it was similar to that reported for patients with other liver diseases administered lower doses. Biliary ursodeoxycholic acid enrichment increased with increasing doses, attaining 42% +/- 6% of the total biliary bile acids with the highest dose. Fasting serum ursodeoxycholic acid concentrations increased during ursodeoxycholic acid administration but were variable and correlated poorly with the dose of ursodeoxycholic acid administered, whereas no correlation was found between serum ursodeoxycholic acid concentration and the proportion of ursodeoxycholic acid in bile.(ABSTRACT TRUNCATED AT 250 WORDS)

Bile Acids and Salts↗
PubMed1992

Antibodies to hepatitis C virus in primary biliary cirrhosis.

We investigated the prevalence of anti-HCV in 160 consecutive patients with primary biliary cirrhosis. By ELISA, 19 (12%) were positive, as compared to a 68% prevalence in 135 patients with chronic non-A, non-B hepatitis. Serum IgG levels were significantly higher in the anti-HCV positive group. By RIBA, seropositivity was confirmed for 4 patients, whereas 7 were indeterminate. A slight, non-significant reduction of life expectancy was found in anti-HCV positive patients. Until reliable and independent confirmatory tests become available, definitive conclusions on the importance of anti-HCV positivity in primary biliary cirrhosis are improper.

Adult↗
PubMed1992

Liver-cell dysplasia and hepatocellular carcinoma.

Liver-cell dysplasia is a well known histological entity with preneoplastic significance in experimental hepatic carcinogenesis. However, while the association of liver-cell dysplasia with hepatitis B virus can be considered as established, it is still controversial whether this lesion represents a premalignant condition in cirrhotic patients. Efforts have been made to render its morphological assessment more reliable, but no firm conclusions can be drawn from the available clinical studies, which are mainly retrospective or based on autopsy series. Preliminary results from a prospective study argue that liver-cell dysplasia is associated with an increased risk to hepatocellular carcinoma. The emergence of liver-cell dysplasia as a preneoplastic lesion in cirrhotic patients will have some impact in the future on their management, including selection for closer monitoring in early detection of hepatocellular carcinoma and for liver transplantation.

Adult↗
PubMed1992

Delayed activation of D-glucose transport in type II diabetes mellitus.

Peripheral insulin resistance is suggested to play an important role in the pathogenesis of type II diabetes mellitus. In this study we investigated insulin receptor binding, D-glucose transport under equilibrium conditions for insulin and the activation kinetics of insulin stimulated D-glucose transport in isolated human adipocytes from type II diabetics and healthy controls. While the insulin receptor binding affinity was not significantly different between both groups, basal and insulin stimulated glucose transport rates were reduced in adipocytes from type II diabetics compared to normal controls. The activation of D-glucose transport was significantly delayed in the diabetics, the time to achieve maximal transport rates was 7.7 +/- 1.1 vs. 4.2 +/- 1.4 min, respectively (p < 0.05). Thus a reduced velocity of glucose transport activation by insulin appears to be a further factor contributing to peripheral insulin resistance in type II diabetics.

Biological Transport↗
PubMed1991

Comparison of effects of chenodeoxycholic and ursodeoxycholic acid and their combination on biliary lipids in obese patients with gallstones.

To study the effects of different bile acids on biliary lipids in obese patients with radiolucent gallstones, 12 subjects were given chenodeoxycholic acid (CDCA) at a dose of 15 mg/kg/day, ursodeoxycholic acid (UDCA) at a dose of 15 mg/kg/day, and an equimolar combination of the two (7.5 + 7.5 mg/kg/day) in accordance with a double-blind crossover design. Mean molar percentage of cholesterol and cholesterol saturation index corrected for urso-rich bile (CSI) decreased significantly with all three treatments, but the combination was more effective in decreasing the CSI than either of the two bile acids given alone (p less than 0.05). Bile became desaturated in 10 of 12 patients receiving the combination, in 4 of 12 receiving CDCA, and 3 of 12 receiving UDCA alone. Combination treatment was well tolerated since mild diarrhea and slight increase in transaminases were observed only in a few patients. We conclude that the combined administration of CDCA and UDCA in equimolar doses is the treatment of choice for dissolution of gallstones in obese patients.

Bile Acids and Salts↗
PubMed1991

Effects of ursodeoxycholic acid on serum liver enzymes and bile acid metabolism in chronic active hepatitis: a dose-response study.

The effect of ursodeoxycholic acid administration on liver function tests and on bile acid metabolism was investigated in 18 patients with chronic active hepatitis. Three different doses of ursodeoxycholic acid--250 mg, 500 mg and 750 mg--were administered daily to each patient for consecutive 2-mo periods. The order of doses was randomly assigned according to a replicated Latin-square design. A significant decrease in serum transaminases and gamma-glutamyl transpeptidase occurred with the lowest dose of ursodeoxycholic acid, which corresponded to 4 mg/kg body wt/day, and no further significant decrease with the higher doses was seen. Biliary bile acid composition was determined by high-performance liquid chromatography and gas chromatography-mass spectrometry. At entry the relative proportions of major bile acids were similar to those observed in normal individuals. During treatment the mean percentage of ursodeoxycholic acid in bile (22% with the 250 mg dose, 32% with the 500 mg dose and 34% with the 750 mg dose) was lower than values previously reported for patients with gallstones and normal liver function. The major bile acids were cholic, chenodeoxycholic and deoxycholic acids. A number of unusual bile acids were identified by gas chromatography-mass spectrometry, but these accounted for only 3% to 5% of the total and did not change during ursodeoxycholic acid therapy. No correlation between the improvement in liver function tests and the percentage of ursodeoxycholic acid in bile existed. These data suggest that even a slight enrichment of bile with ursodeoxycholic acid, as is attained with 250 mg/day, is effective in improving biochemical markers of liver function in patients with chronic active hepatitis.

Adult↗
PubMed1991

Changes in bile acid composition in patients with primary biliary cirrhosis induced by ursodeoxycholic acid administration.

We describe a detailed study of the effects of ursodeoxycholic acid administration on bile acid composition of the serum and bile of patients with primary biliary cirrhosis. Gas chromatography-mass spectrometry was used to analyze bile acids from 10 patients with primary biliary cirrhosis before and during ursodeoxycholic acid administration (500 mg/day, corresponding to approximately 8 mg/kg body wt), after group separation of the unconjugated and conjugated fractions by lipophilic anion exchange chromatography. These studies were directed at assessing whether the beneficial role of ursodeoxycholic acid in primary biliary cirrhosis was the consequence of a shift in the hydrophobic/hydrophilic balance of the bile acid pool and whether the hypercholeresis might result from the cholehepatic circulation of unconjugated ursodeoxycholic acid in bile. In basal conditions, the unconjugated bile acids accounted for only 5.5% and 2.5%, respectively, of the total bile acids of serum and bile; cholic acid was the major component of the conjugated fraction of serum and bile (56.0% +/- 4.0%, mean +/- S.E.M.), and ursodeoxycholic acid was present in only trace amounts. The conjugated fraction contained many unusual bile acids (representing 16.5% +/- 1.3% of total) including C25 bile acids, iso-chenodeoxycholic acid and several oxo-bile acids. After ursodeoxycholic acid administration biochemical indices of liver function all improved, but the proportions of the unconjugated bile acids in serum and bile did not significantly change.(ABSTRACT TRUNCATED AT 250 WORDS)

Bile↗
PubMed1991

Failure of ursodeoxycholic acid to prevent a cholestatic episode in a patient with benign recurrent intrahepatic cholestasis: a study of bile acid metabolism.

Ursodeoxycholic acid was administered to a patient with benign recurrent intrahepatic cholestasis to prevent cholestatic episodes. A detailed study of bile acid metabolism in this patient was carried out in the anicteric and icteric phases before and after ursodeoxycholic acid (750 mg/day) administration. Urinary, biliary and serum bile acids were measured by gas chromatography-mass spectrometry and by high-performance liquid chromatography techniques. During the anicteric phase the daily urinary excretion and serum concentrations of bile acids were within normal ranges, indicating normal hepatic uptake and secretion of bile acids during the cholestasis-free period. Only slight qualitative differences from normal individuals were observed; the relative proportions of deoxycholic acid in the bile and serum were higher, and 12-oxo-lithocholic acid was the predominant urinary bile acid. During the icteric phase a marked increase in the urinary excretion of primary bile acids and C-1, C-2, C-4 and C-6 hydroxylated metabolites was found. Serum bile acid concentrations increased before the rise in bilirubin, suggesting an acute disturbance in bile acid transport at the onset of the cholestatic attack. After ursodeoxycholic acid administration in the anicteric phase, bile became enriched with the exogenous bile acid, but little qualitative change was found in the other metabolites present in the urine, serum or bile during the anicteric or icteric phases. Prolonged administration of ursodeoxycholic acid failed to prevent recurrence of a cholestatic episode, suggesting that in benign recurrent intrahepatic cholestasis, oral ursodeoxycholic acid may be of little benefit in the treatment or prevention of cholestasis despite marked enrichment of the bile acid pool with this hydrophilic bile acid.

Adult↗
PubMed1990

Effects of ursodeoxycholic acid and taurine on serum liver enzymes and bile acids in chronic hepatitis.

Hydrophobic bile acids have been shown to be hepatotoxic, whereas treatment with ursodeoxycholic acid, a hydrophilic bile acid, has improved liver function indices in patients with chronic liver disease. Taurine administration has also been suggested to be useful for chronic hepatitis, taurine-conjugated bile acids being more hydrophilic than glycine-conjugated bile acids. To determine if taurine and ursodeoxycholic acid are beneficial and if their effects are additive, a double-blind, randomized trial was designed comparing the effects of ursodeoxycholic acid, taurine, and a combination of the two on indices of liver injury in 24 patients with chronic hepatitis. They were assigned at random to two of the four following treatments: ursodeoxycholic acid (600 mg/day), taurine (1.5 g/day), ursodeoxycholic acid plus taurine (600 mg + 1.5 g/day) or placebo, given in two successive cycles of 2 mo each, according to a balanced incomplete-block design. Ursodeoxycholic acid became the predominant biliary bile acid when administered alone or in combination with taurine, and taurine conjugate levels increased during taurine administration. Ursodeoxycholic acid reduced aspartate aminotransferase (35%), alanine aminotransferase (33%), and gamma-glutamyl transpeptidase (41%), whereas taurine alone did not. The addition of taurine to ursodeoxycholic acid produced only minor changes in the effects of ursodeoxycholic acid alone. Results were confirmed by the administration of ursodeoxycholic acid, in a successive open phase of the study, to the entire patient population, which was large enough for different subsets of patients to be compared. Serum bile acids were measured at entry and during the open phase: primary bile acids did not change, whereas ursodeoxycholic acid levels increased from trace amounts to very high levels, especially in patients with more severe histological disease. It is concluded that ursodeoxycholic acid, but not taurine, improves enzymatic indices of liver injury in chronic hepatitis.

Adult↗
PubMed1990

Effects of ursodeoxycholic acid therapy for liver disease associated with cystic fibrosis.

The hydrophilic bile acid ursodeoxycholic acid (UDCA) has recently been shown to improve indexes of liver function in adult patients with various liver diseases. The clinical and biochemical responses to UDCA administration (10 to 15 mg/kg body weight per day) were therefore investigated in nine patients with cystic fibrosis and evidence of liver disease. All patients were receiving pancreatic enzymes and taurine supplementation. Liver function tests were done and serum bile acid concentrations and biliary bile acid composition were determined before and during UDCA therapy; fat balance studies and fecal bile acid excretion were carried out before and 6 months after UDCA treatment. After 2 months of bile acid therapy, biliary bile acid composition was enriched in UDCA from approximately 5% before treatment to 25%, at the expense of cholic and chenodeoxycholic acids, thus making the pool more hydrophilic. This enrichment is lower than that reported for adults with chronic liver diseases. Serum concentrations of UDCA increased significantly but variably. UDCA became the predominant fecal bile acid excreted (12% to 67%), indicating a variable absorption of the administered bile acid. Liver function improved in all patients after 2 to 6 months of therapy, although the degree of improvement (aspartate aminotransferase, -34%; alanine aminotransferase, -41%; gamma-glutamyltranspeptidase, -41% alkaline phosphatase, -19%) was lower than that observed in adults with chronic liver diseases. Mean coefficient of fat absorption and growth rate were, on average, unaffected by UDCA therapy, although an improvement was noted for three patients with greater severity of steatorrhea. The study indicates that UDCA can be used safely in this patient population but that higher doses of UDCA may be of greater benefit in the treatment of the liver disease associated with cystic fibrosis.

Adolescent↗
PubMed1989

Effect of different doses of ursodeoxycholic acid in chronic liver disease.

Recent clinical studies have indicated that ursodeoxycholic acid (ursodiol), administered at dosages ranging between 10 and 15 mg/kg/day, improves liver function indices in both cholestatic and inflammatory chronic liver diseases. These dosages would be considered high for the use of ursodiol in gallstone dissolution therapy. To investigate the dose-response relationship to ursodiol administration, we planned a few studies in patients with primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC), and chronic hepatitis (CH). Patients with PBC were subdivided into two groups on the basis of their serum bilirubin values, with 2 mg/dl as the dividing line. Ursodiol was given at dosages of 250, 500, and 750 mg/day for consecutive periods of two months, the order of treatment being randomly assigned to each patient. The enrichment with ursodiol of biliary bile acids was similar in both PBC and CH and, within the PBC group, in both anicteric and icteric patients. Highly significant decreases in serum enzyme levels were observed in all groups with the 250 mg/day dose, corresponding to about 4-5 mg/kg/day. The two higher doses induced further improvements in serum enzyme levels, especially in patients with PBC, but no significant differences were found between the 500 and the 750 mg/day doses. The improvements were roughly proportional to the enrichment of conjugated biliary bile acids with ursodiol. Serum bilirubin levels, an important prognostic factor in PBC, were also significantly reduced by ursodiol administration in patients with initial serum levels higher than 2 mg/dl. The present study indicated that ursodiol is a potentially useful drug for chronic liver disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Bile↗
PubMed1989

Efficacy and safety of a combination of chenodeoxycholic acid and ursodeoxycholic acid for gallstone dissolution: a comparison with ursodeoxycholic acid alone.

Chenodeoxycholic acid (CDC) and ursodeoxycholic acid (UDC) have distinct physicochemical and metabolic properties which, being complementary, should favor more rapid removal of cholesterol from gallstones when both bile acids are administered together. To see if the combination is more effective and well tolerated, we have compared 5 mg/kg of CDC plus 5 mg/kg of UDC with a 10-mg/kg dose of UDC alone in 120 patients with radiolucent, sonographically confirmed gallstones and characteristics favoring complete dissolution. Ursodeoxycholic acid was chosen as the reference because it dissolves stones faster and is better tolerated than CDC. To minimize the influence of stone size, the major determinant of dissolution, patients were divided, on admission, into two groups according to the maximum stone diameter: 50 had stones less than or equal to 5 mm, 70 had stones greater than 5 mm but less than 15 mm. The effects of treatment on stone dissolution evaluated by cholecystography and ultrasonography at 6, 12, and 24 mo, were analyzed by the actuarial life-table method. In the group with smaller stones, significantly more patients had obtained complete dissolution after treatment with the combination (52%) than after treatment with UDC alone (24%) at 6 mo. After longer periods, results were still better with the combination, although the differences from UDC alone became smaller. In the patients with larger stones, rates of complete and partial dissolutions were higher after treatment with the combination (51% vs. 24% with UDC) at 6 mo and again the differences had become smaller after longer treatment. Although not statistically significant, stone calcification occurred more often with UDC (7 cases) than with the combination (1 case). We conclude that CDC plus UDC is preferable to UDC alone because it dissolves stones more quickly, with a lower incidence of stone calcification, and may result in reduced cost of treatment.

Bile↗
PubMed1975

[Bile secretion].

The canaliculus is the primary site for the formation of bile. Here, active secretion of bile acids creates an osmotic gradient between bile and blood, crossed passively by water and solutes. Numerous experimental data point to the existence of a canalicular bile fraction that is independent of the active transport of bile acids and related to active sodium secretion. The bile ducts are not mere conduits for the passage of bile, but can also change its volume and composition by means of both absorption and secretion. Nervous, vascular, hormonal and pharmacological factors serve to modify bile secretion. In most cases, however, their mechanism of action is virtually unknown.

Adenosine Triphosphate↗