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Biomedical subjects

D Festi

Publications and source records attributed to D Festi.

At least 73 records · Page 4Linked to original sources

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↗

US-guided percutaneous alcohol injection of small hepatic and abdominal tumors.

Fourteen lesions (nine hepatocellular carcinomas, four hepatic metastases from gastric carcinoma, and one peritoneal metastasis from transitional cell carcinoma) in 12 patients were treated with percutaneous injection of 95% ethyl alcohol under guidance with ultrasound. Requirements for this procedure included inadequate response to conventional treatment or refusal of surgery, easy identification of the tumor with sonography, and a tumor diameter less than 4 cm. Three to nine administrations (75 in all) were performed for each lesion according to its size and to the results of the fine needle biopsy. All lesions had posttreatment sonographic structural changes of fibronecrotic degeneration. All lesions less than 3.2 cm in diameter (11 cases) that underwent the final fine needle biopsy were negative for malignant cells and had volume reductions up to 100%. No biochemical changes or untoward clinical sequelae were detected. Percutaneous intratumoral alcohol injection is inexpensive, easy to perform, and potentially valuable in the treatment of selected small neoplastic lesions of the liver and abdomen.

Adult↗

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↗

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↗

Effect of ursodeoxycholic acid administration on biliary lipid composition and bile acid kinetics in cholesterol gallstone patients.

The effect of ursodeoxycholic acid (UDCA) on bile lipid composition and bile acid kinetics was evaluated in seven cholesterol gallstone patients following one month of UDCA administration (12 mg/kg/day). UDCA administration induces a significant reduction in the cholesterol saturation index (SI). After UDCA treatment, UDCA becomes the predominant biliary bile acid while chenodeoxycholic, cholic, and deoxycholic acid are significantly reduced. UDCA pool significantly increases, and chenodeoxycholic, cholic, and total bile acid pools significantly decrease. The reduction in bile lithogenicity during UDCA administration suggests that UDCA may be useful for cholesterol gallstone treatment in man.

Adult↗

Enterohepatic circulation of bile acids after cholecystectomy.

Bile acid metabolism was investigated in 10 patients after cholecystectomy, 10 gallstone patients, and 10 control subjects. Diurnal variations of serum levels of cholic and chenodeoxycholic acid conjugates were not abolished by cholecystectomy. Cholic acid pool size was significantly reduced in cholecystectomised patients and the fractional turnover rate and the rate of intestinal degradation of bile acid showed a significant increase. In cholecystectomised patients fasting bile was supersaturated in cholesterol, though less than in gallstone patients, but, in both, feeding resulted in improvement of cholesterol solubility in bile. These data suggest that after cholecystectomy the small intestine alone acts as a pump in regulating the dynamics of the enterohepatic circulation of bile acids and that the improvement of cholesterol solubility in bile is due to a more rapid circulation of the bile acid pool in fasting cholecystectomised patients.

Bile Acids and Salts↗

[Medical treatment of cholesterol cholelithiasis using chemodeoxycholic acid in man].

The results of a tiral using chenodeoxycholic acid in 400 patients with cholesterol gallstones are reported. The "qualifying points" of such treatment are compared with the literature data in clinical and laboratory terms. 54% of 300 in clinical and laboratory terms. 54% of 300 patients who received less than 12 mg/kg/day achieved dissolution in a mean time of 11 months, while 64% of the remainder (12-15 mg/kg/day) did so in an average of 8 months. Microcalculi proved most sensitive to treatment (65% of positive results). Lithiasis over 5 years standing and over-weight (10% over the ideal figure) were factors that imposed more protracted treatment. Careful selection of candidates was proved important by the results of quarterly liver and intestine performance examinations. These were more extensive and more clearly aimed than those proposed by other workers. They showed that the acid is neither hepato nor enterotoxic. Indeed, no serious side-effects were noted.

Bile Acids and Salts↗

[Changes in bile and blood lipid levels following chenodeoxycholic acid therapy].

Original and known methods and ordinary routine tests were used to evaluate changes in bile salts, phospholipids and cholesterol and in serum lipids induced in 50 patients during treatment with chenodeoxycholic acid (2-12 mg/Kg/day) for about 15 months. No significant differences in serum lipids, though a clear fall in triglycerides was noted in those who received 7-12 mg/Kg/day as opposed to 2-7 mg/Kg/day. There was a marked fall in the molar percentage of biliary cholesterol, followed by a significant reduction in the saturation index of Metzger. Once again, greater reduction was noted in patients receiving the higher dose range. A correlation between the dose used and the percentage of cholesterol in the bile was thus evident. After treatment, chenodeoxycholic acid was the main bile acid and there was a significant fall in cholic and deoxycholic acid. The desired drug effect can be obtained with low doses (7-12 mg/Kg/day) and a biliary chenodeoxycholic value well below 90%.

Bile↗