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Biomedical subjects

G Mazzella

Publications and source records attributed to G Mazzella.

At least 55 records · Page 3Linked to original sources

A controlled trial of human lymphoblastoid interferon in chronic hepatitis B in Italy.

Sixty-four heterosexual Italian carriers of HBsAg with chronic HBeAg and hepatitis B virus DNA-positive hepatitis were assigned randomly either to receive human lymphoblastoid interferon (injections of 5 million units per m2 three times per week for 6 months) or to serve as untreated controls. After 18 months of follow-up evaluation, 26 of the 33 treated patients (79%) had cleared hepatitis B virus DNA, 23 (70%) had lost HBeAg and 20 (61%) had seroconverted to anti-HBe. Fifteen of the 31 controls (48%) had cleared hepatitis B virus DNA (p = 0.01), 12 (39%) had lost HBeAg and nine (29%) had seroconverted to anti-HBe (p = 0.002). Eight treated patients but only one control had lost HBsAg and seroconverted to anti-HBs (24% vs. 3%, p = 0.01). Treated patients cleared hepatitis B virus markers after a mean interval of 4 months, compared with 8 months in the controls. All responders to interferon cleared intrahepatic HBcAg, and 50% showed histological improvement. The baseline hepatitis B virus DNA levels and the original histology were not predictive of a response to therapy; women appeared to respond better than men. Lymphoblastoid interferon provides an effective therapy in the heterosexual Italian patient with chronic hepatitis B.

Adolescent↗

Effect of ursodeoxycholic acid administration on biliary lipid secretion in primary biliary cirrhosis.

Ursodeoxycholic acid (UDCA) has been reported to improve liver function tests when administered to patients with cholestatic liver diseases, such as primary biliary cirrhosis (PBC). However, its effects on biliary lipid metabolism in patients with PBC are still unknown. In this study we report the effect that UDCA (600 mg/day, for four weeks) had on biliary cholesterol saturation index, biliary bile acid pattern and pool size, and biliary lipid output in seven female patients (ages 34-58 years) with PBC, stages I to III. A significant improvement of liver function tests was observed after four weeks of treatment. Saturation index was significantly decreased from 1.23 +/- 0.1 to 0.7 +/- 0.08 (P less than 0.02); this effect was due to the significant decrease of biliary cholesterol concentration from 6.7 +/- 0.36 to 3.6 +/- 0.37 percent molar (P less than 0.02). A significant decrease of cholesterol output (from 88 +/- 9 to 55 +/- 10 mumol/hr, P less than 0.02) was also observed. The amount of cholic acid, the predominant bile acid in bile, significantly decreased (from 47.3 +/- 3.5 to 35.4 +/- 2.6 percent molar, P less than 0.02), as did amounts of chenodeoxycholic and deoxycholic acids, while the amount of UDCA rose from 1.6 +/- 1.0 to 34.0 +/- 1.3 percent molar (P less than 0.02). Total bile acid pool size was not affected by UDCA, but the evaluation of individual bile acid pool sizes showed an increased proportion of UDCA relative to the endogenous bile acids.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Gallstone recurrence after successful oral bile acid treatment. A 12-year follow-up study and evaluation of long-term postdissolution treatment.

Recurrence is a major problem in the medical treatment of gallstones but its extent is still uncertain. The aim of this study was to determine the magnitude of this event and to assess the effectiveness of a postdissolution treatment in preventing it. We evaluated the long-term recurrence rate after 96 confirmed dissolutions observed in 86 subjects (71 women, 15 men) over a 12-yr follow-up period. A low-dose postdissolution treatment (ursodeoxycholic acid, 300 mg/day) was administered to 36 subjects, whereas in the remaining 60 cases no postdissolution treatment was given. By actuarial life-table analysis, the cumulative proportion of gallstone recurrence was 12.5% at the first year, rising to 61% at the 11th year. Postdissolution treatment was effective in reducing the frequency of gallstone recurrence (p = 0.0067), but this was mainly related to its effect on younger subjects (less than or equal to 50 yr old). In older subjects the recurrence rate was unaffected by treatment. The probability of gallstone recurrence was significantly higher in subjects with multiple stones before dissolution treatment than in those who had had solitary stones (p = 0.0091). No other factor predictive of gallstone recurrence could be identified.

Actuarial Analysis↗

Human lymphoblastoid interferon for the treatment of chronic hepatitis B. A randomized controlled trial.

The aim of this study was to demonstrate whether interferon alone could affect the course of chronic hepatitis B. A total of 66 patients have so far been randomly assigned to receive six months of interferon therapy or no therapy; three patients in the interferon group and two in the control group have withdrawn from the study. Loss of hepatitis B virus-DNA and hepatitis B e antigen was significantly higher in the patients receiving interferon than in the control group; a significant loss of hepatitis B surface antigen was observed only in patients who received interferon. The time to alanine aminotransferase normalization was significantly shorter in patients receiving interferon than in the control group. These data encourage the use of interferon in treatment of chronic hepatitis B.

Adult↗

Treatment of chronic hepatitis B with human lymphoblastoid interferon: results of a controlled trial.

The aim of this study was to evaluate the efficacy of human lymphoblastoid interferon (Wellferon) in the treatment of chronic hepatitis B virus (HBV) infection. To date 70 patients have entered the study, 33 randomized to receive interferon at doses of 5 MU/m2 i.m. daily for the first 4 weeks and three times weekly for 5 months thereafter and 31 acted as controls. Seventy-nine per cent of the treated group permanently cleared HBV DNA compared with 48% of the control group (p = 0.01): 69% of the treated patients and 38% of the controls who eliminated HBV DNA cleared HBeAg, HBeAb (p = 0.02). Twenty-four per cent of the treated patients and 3% (p = 0.01) of the control group had clearance of HBsAg and seroconversion to HBsAb. From these results it was concluded that interferon had a therapeutic effect on Italian heterosexual patients with chronic hepatitis B viral replication.

Clinical Trials as Topic↗

Bile acid malabsorption and bile acid diarrhea in intestinal resection.

Bile acid fecal excretion and dihydroxy bile acid concentration in the fecal water of patients with large (N = 6) and small (N = 8) ileal resection, colectomy (N = 5), and healthy controls (N = 10) have been studied in order to evaluate the degree of bile acid malabsorption and the occurrence of bile acid diarrhea in intestinal resections of different extent. Bile acid malabsorption was severe in large ileal resections, mild in small ones, and slight in colectomy. The fecal pH seems to be a limiting factor in the occurrence of a bile acid diarrhea, playing a critical role in determining the dihydroxy bile acid solubility in the fecal water. These results seem to suggest that the bile acids may induce water secretion in the colon not only in small but also in large ileal resections.

Adult↗

Diagnostic value of serum primary bile acids in detecting bile acid malabsorption.

Serum cholic and chenodeoxycholic acid conjugates were measured in fasting conditions and after meals in 14 patients with bile acid malabsorption due to ileal resection. Mean serum fasting levels of both primary bile acids did not differ from the controls. After meals, serum cholic acid peaks were lower in patients with ileal resection than in control subjects (p less than 0.001), while chenodeoxycholic acid peaks were reduced in colectomised patients (p less than 0.01). In the sera from patients with ileal resection, the glycine/glycine + taurine ratio for cholic and chenodeoxycholic acid increased (p less than 0.001) from morning to evening, and glycine/glycine + taurine ratio for chenodeoxycholic acid was significantly (p less than 0.01) different from the controls in the sera collected in the evening. The results are consistent with the concept of a better intestinal conservation of chenyl, mainly of the glycine conjugated from, than of cholylconjugates, in patients with ileal resection; this is probably because of passive absorption in the intestine. The postprandial peaks of serum cholic acid conjugates may therefore be regarded as a test of ileal dysfunction, while peaks of chenodeoxycholic acid conjugates suggest colonic impairment.

Adult↗

Serum primary bile acids in Gilbert's syndrome.

We studied some aspects of bile acid metabolism in 25 patients affected by Gilbert's syndrome, 5 patients with hemolytic anemia, and 25 control subjects in order to assess whether bile acids as well as bilirubin are affected in unconjugated hyperbilirubinemic conditions. We measured serum cholic and chenodeoxycholic acid conjugates fasting and postprandially, the plasma disappearance of intravenously injected cholyl[1-14C]glycine, 14CO2 in breath, and 14C in stools after oral administration of the same isotope. Mean serum fasting level of conjugated cholic acid was significantly reduced in hyperbilirubinemic patients (p less than 0.01) in comparison with the controls, while the postprandial elevation was similar. The cholyl[1-14C]glycine hepatic uptake was faster in the patients with Gilbert's syndrome, but no significant difference was found as far as 14CO2 in breath and 14C in stools were concerned. Additional in vitro studies showed that increasing bilirubin concentrations displace glycocholic acid and, to a lesser extent, glycochenodeoxycholic acid from their binding to albumin, the affinity constant of the latter bile acid being 30 times greater than that of the former one. This competition between bilirubin and bile acids explains the faster hepatic uptake of cholic acid conjugates and hence their lower serum levels in unconjugated hyperbilirubinemic conditions. In addition, low levels of cholic acid conjugates, together with normal serum chenodeoxycholic acid conjugate levels, discriminate Gilbert's syndrome from other causes of hyperbilirubinemia.

Adult↗

Effects of naloxone on ethanol and acetaldehyde-induced electroencephalographic changes in rabbits.

Rabbits treated with a single IV dose of ethanol, 0.6 g/kg, exhibited rapid EEG synchronization and behavioral changes that were reversed and, in part, prevented by the opiate antagonist, naloxone, 40 micrograms/kg. The continuous intracerebroventricular infusion of acetaldehyde, 10 or 120 micrograms/min. caused biphasic changes with EEG activation and severe bradycardia followed by overt synchrony during the post-infusion period. The results of the present study provide further evidence for the ability of naloxone to counteract some acute effects of ethanol. Moreover, they do not support a role of acetaldehyde itself as mediator of EEG changes associated with mild alcohol intoxication.

Acetaldehyde↗

Effect of chenodiol on the small intestine. Unimpaired structure and function during therapy for gallstone dissolution.

To test whether long-term oral dosage with chenodiol (chenodeoxycholic acid) used for dissolution of cholesterol gallstones would cause impairment of small-intestinal structuree or function, ten patients were studied before and after three months of oral chenodiol administration, 15 mg/kg of body weight per day. Small-intestinal structure was assessed by roentgenogram and intestinal biopsy, using both light and electron microscopy. Small-intestinal function was assessed by xylose, fat and vitamin B12, lactose, and bile-acid absorption. Bile acid metabolism was also characterized by the breath test for deconjugation using carbon dioxide labeled with radioactive carbon 14. No significant abnormalities were found. The results suggest that oral chenodiol administration does not impair intestinal structur or function in doses used for gallstone dissolution.

Administration, Oral↗

Serum bile acids in newborns and children.

A specific and sensitive radioimmunoassay for cholic, chenodeoxycholic, and lithocholic acid conjugates and for sulfolithocholylglycine was used to measure serum bile acids (BA) in infants and children. Elevated cholic and chenodeoxycholic acid values were observed in the first year of life in fasting infants. Newborn babies presented high levels of primary BA not correlated with those of the mothers. In premature newborn babies who had not yet been fed, meal induced a considerable reduction in the primary BA levels in serum. In normally fed babies, meal induced a significant increase in the primary BA levels in serum. These data suggest a progressive maturity throughout the first year of life of the serum BA determinants, i.e., gallbladder emptying, intestinal motility and absorption, and hepatic uptake.

Bile Acids and Salts↗

Results with six "kit" radioimmunoassays for primary bile acids in human serum intercompared.

We examined six radioimmunoassay procedures for measuring primary bile acids in human serum (two 3H-labeled and four 125I-labeled). A significant (p < 0.01) correlation was observed between measurements in the assay both for cholic acid and chenodeoxycholic acid, at low and high concentrations of serum bile acids. All kits were acceptable with respect to accuracy, precision, stability, and analytical recovery. All six procedures gave similar results for chenodeoxycholic and cholic acid in sera of 80 healthy subjects; the agreement was also close when the two primary bile acids were compared with their sum in serum. Normal values ranged from 0.4 to 2.5 mumol/L for conjugated chenodeoxycholic acid and from 0.3 to 1.5 mumol/L for conjugated cholic acid. The 125I assays do not require liquid-scintillation equipment but 125I induces a decrease in the affinity constant of antibody. The sensitivity of the assays was still adequate for measuring bile acids in the serum of healthy fasting persons and liver-disease patients.

Adult↗

[Kinetics of 14C-cholic acid in the baboon under normal conditions and in cholestasis. Description and validity of a multicompartmental model].

A multicompartmental model was applied to the study of the plasmatic and biliary kinetics of the 14C-Cholic acid intravenously injected into a baboon in normal and cholestatic condition. For the evaluation of transfer rates FORTAN IV procedures were used, utilizing Powell method. The degree of fitting was: in normal condition in serum 7% for free and 35% for conjugated Cholic acid, while in bile 5% and 4% respectively; in serum in cholestatic condition 7% for free and 12% for conjugates. The high degree of fitting and reliable estimation of transfer rates suggest that the multicompartmental model applied represents most likely the physio-pathological conditions studied.

Animals↗