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Biomedical subjects

R Orlando

Publications and source records attributed to R Orlando.

At least 163 records · Page 9Linked to original sources

Oral and intravenous pharmacokinetics of cimetidine in liver cirrhosis.

The bioavailability of p.o. and i.v. cimetidine was studied in 12 patients with compensated liver cirrhosis in a crossover study. Single doses of 200 and 400 mg cimetidine were used for both administration routes. Plasma concentration and urinary recovery were determined by the HPLC method. The pharmacokinetic data observed in these patients do not differ from those of normal subjects and patients. A positive correlation between AUC and cimetidine oral dose was found. Oral bioavailability of cimetidine was about 94% compared to that of the i.v. route. The p.o. dose of 400 mg produced AUC values similar to the i.v. dose of 400 mg. After 400 mg cimetidine p.o. the mean peak plasma level was higher and the time for which plasma levels remained above 0.5 mg/l was longer. There were no significant differences between plasma cimetidine levels after the intravenous administration of 200 and 400 mg. The urinary recovery of cimetidine was significantly higher after intravenous administration independently of the given dose. The pharmacokinetics of cimetidine does not appear to be altered in liver cirrhosis.

Administration, Oral↗

[Aspecificity of the immunodiffusion reaction for the diagnosis of non-A non-B viral hepatitis].

A precipitating antigen-antibody system was detected by immunodiffusion using acute and convalescent sera from patients with non-A, non-B (NANB) viral hepatitis in which the diagnosis was made by exclusion. The system showed identity with reference sera. Positivity for antigen was found in 5 out 13 patients with acute NANB hepatitis, but also in 3 out 8 patients with acute A hepatitis, in 6 out of 15 with acute B hepatitis and in 95 out of 221 voluntary blood donors. Antibody was detected in all the above mentioned categories of patients and also in normal subjects in percentages ranging from 9.1 to 25.0 percent. The lack of specificity observed is in contrast with results of other reported serological NANB related systems.

False Positive Reactions↗

Biliary excretion of simultaneously administered bilirubin and chenodeoxycholic acid in rats.

Crystalline bilirubin and chenodeoxycholic acid were administered intravenously and intraduodenally respectively in 19 anesthetized Sprague-Dawley rats in order to verify whether there exists an interference between their biliary excretion. When these two compounds were administered together, the biliary excretion of bilirubin and bile salts was significantly reduced the conjugation of bilirubin was not impaired while bile flow remained constant during the whole exerpimental period. These data seem to indicate a mutual interference between chenodeoxycholic and bilirubin metabolisms. It could be admitted that the excretory step is involved in determining the observed modifications.

Animals↗

Biliary excretion of simulateously administered bilirubin and chenodeoxycholic acid in rats with porta-caval shunt.

Portacaval shunting influences several metabolic processes of the liver. The aim of this work was to investigate whether bile salts and bilirubin reciprocally interfere with their biliary excretion in this experimental condition. 12 male Sprague-Dawley porta-caval shunted rats received simultaneously crystalline bilirubin (intravenously) and chenodeoxycholic acid (intraduodenally) 20-26 days after intervention. The biliary excretion of these two compounds was then studied. The results seem to indicate that there exists a mutual interference between bile salt and bilirubin excretion in the bile; moreover it is suggested that porta-caval shunting plays a secondary role in determining the observed interaction between bilirubin and bile salts metabolism in the liver.

Animals↗

Carcinoma of the stomach after gastric operation.

Seventeen cases of carcinoma of the stomach occurring late after previous gastric operation are presented. In all instances, patients had undergone gastroenterostomy, with or without gastric resection. Most patients had undergone the initial operation for peptic ulcer disease an average of 18 years before presenting with the tumor. Endoscopic biopsy of the gastroenterostomy and gastric cytologic evaluation offered a high degree of sensitivity and specificity in making the diagnosis. These tumors appeared to originate in the gastric mucosa near the stoma. Survival was poor with both curative and palliative therapy. Alkaline bile reflux, achlorhydria and bacterial colonization are discussed as possible causes. Patients who have undergone partial gastric resection are at increased risk for the development of carcinoma of the stomach remnant. We recommend that any patient in whom new upper gastrointestinal symptoms develop more than 10 hears after partial gastrectomy should undergo endoscopy with biopsy of the gastric mucosa adjacent to the anastomosis.

Adenocarcinoma↗

A modeling study of the effect of fasting on bilirubin kinetics in Gilbert's syndrome.

The mechanism of fasting hyperbilirubinemia (FH) is not fully understood. We investigated basal bilirubin kinetics in 20 Gilbert's patients and in 7 healthy volunteers. The study was repeated in seven of these Gilbert's patients after 48-h fasting. A two-compartment model proved to be adequate for interpreting crystalline bilirubin kinetics in these individuals. The parameters of bilirubin kinetics were estimated by employing a maximum likelihood parameter estimation technique. Consistency of the model and uniqueness of the estimated parameter values (from the covariance matrix) were shown. Our results confirmed previous observations regarding impaired bilirubin kinetics in Gilbert's patients as compared to controls. The main results obtained from kinetic studies in Gilbert's patients after fasting were i) no modification in the bilirubin clearance, and ii) a more than twice increase of bilirubin turnover. These data indicate that FH is related to an increased bilirubin production (mainly intrahepatic). Furthermore, evidence arises from this study that the bilirubin tolerance test is a useful diagnostic test for Gilbert's syndrome.

Adolescent↗

Influence of rifamycin SV on bile acid metabolism in rats.

Sodium cholate was infused with or without Rifamycin SV in rats in order to determine the site of interference of the drug on hepatic bile salt metabolism. Both compounds were administered at rates such as to saturate their respective maximal excretory capacities. When Rifamycin SV was given, bile acid uptake and excretion significantly decreased, with a significant reduction of the percent of conjugated bile salts in bile. Rifamycin SV neither modified bile flow nor affected the correlation between bile flow and bile salt excretion. These data suggest that the antibiotic interferes with the three main steps of hepatic bile acid metabolism. The cholestatic effect and the modification of biliary bile salt output produced by Ryfamycin SV in rats, could be of clinical relevance.

Animals↗

An evaluation of bilirubin kinetics with respect to the diagnosis of Gilbert's syndrome.

1. The kinetics of the plasma disappearance of bilirubin (2 mg/kg intravenously) were studied in 106 patients with Gilbert's syndrome and in 13 normal subjects. 2. All patients had significant decreases in hepatic bilirubin clearance and transfer rates from plasma to liver, resulting in increased values for plasma retention at 4 h. The calculated value for unconugated bilirubin production was normal in 40% of patients and increased in the remainder. 3. In 29 of the Gilbert's patients their bromosulphthalein kinetics were studied 1 week before the bilirubin test. These results were essentially normal and it was concluded that the hepatic clearance mechanisms for bilirubin and bromosulphthalein are different. 4. In 10 patients the bilirubin transport maximum (Tm) was found to be low whereas the relative storage capacity (S) was normal. Phenobarbitone treatment in four patients resulted in an increase in Tm, and S decreased in two patients and remained unchanged in the other two. 5. These results support the hypothesis that there are several variants of Gilbert's syndrome and that the bilirubin tolerance test is a useful diagnostic test.

Adult↗