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Biomedical subjects

J Fevery

Publications and source records attributed to J Fevery.

At least 109 records · Page 6Linked to original sources

Reversal of hepatorenal syndrome in four patients by peroral misoprostol (prostaglandin E1 analogue) and albumin administration.

Four consecutive patients with alcoholic cirrhosis and hepatorenal syndrome were treated with misoprostol, a synthetic methylester prostaglandin E1 analogue at twice the dosage advocated for anti-ulcer therapy (i.e., 0.4 mg four times per day orally) and albumin infusions. The mean urinary output obtained over the 3 days preceding misoprostol administration was 250, 315, 550 and 195 ml per 24 h, respectively, in the four patients, despite adequate volume expansion by plasma albumin to reach normal or high central venous pressure. Diuresis increased to 1450, 2440, 925 and 1300 ml, respectively, on days 2-4 after onset of therapy. Serum creatinine levels were 71, 51, 33 and 35 mg/l before and dropped to 26, 21, 13 and 17 mg/l during treatment. All patients had hyponatraemia (117-128 mequiv/l) which normalized, although they were continued on a low sodium intake of less than 10 mequiv per 24 h. Urinary sodium excretion increased from 0.4-3 mmol per 24 h, to 15-40 in the first two cases and only slightly to 3-5 in the last two patients. Three patients died after 10, 30 and 40 days due to oesophageal bleeding, encephalopathy or pulmonary infection, whereas one patient underwent an orthotopic liver transplantation when her serum creatinine attained a level of 13 mg/l. In the first patient, hepatorenal syndrome recurred 10 days after stopping the misoprostol treatment. High doses of misoprostol in the presence of adequate volume expansion thus seem to produce marked diuresis and creatininuria as well as mild natriuresis.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Subfractionation of serum bilirubins by alkaline methanolysis and thin-layer chromatography. An aid in the differential diagnosis of icteric diseases.

The determination of direct and indirect-reacting bilirubin fractions by diazo procedures does not allow a definite diagnosis of icteric diseases. Therefore, the clinical relevance of serum bilirubin subfractionation by alkaline methanolysis and subsequent thin-layer chromatography (AM-TLC) was evaluated. Esterified bilirubins could be detected and quantitated in all serum samples investigated. The ratio of serum esterified to total bilirubin was 10-28% in 60 healthy adults (mean 17 +/- 5% S.D.), 1-11% in 77 patients with Gilbert's syndrome (mean 6 +/- 2%), and 2 and 3%, respectively, in two patients with Crigler-Najjar disease type II. The difference was highly significant (p less than 0.001) and the overlap was restricted to three of 139 individuals. The ratio of esterified to total bilirubin was similar to that obtained with HPLC when corrected for with a blank run. The absolute concentration of bilirubin esters in serum from Gilbert's syndrome patients was similar to that from healthy controls, but the unconjugated pigment was increased. In patients with chronic haemolysis (n = 9) and chronic persistent hepatitis (n = 12), the hyperbilirubinaemia consisted of a proportional increase of both unconjugated and esterified bilirubin. As such, the ratio of conjugated to total bilirubin was not significantly different from control values. Patients with acute hepatitis during the first (n = 18) and third ('remission') week of the disease (n = 15), liver cirrhosis (n = 34), and extrahepatic cholestasis (n = 20) predominantly showed an increase in bilirubin conjugates.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Efficacy of interferon alfa-2b with or without prednisone withdrawal in the treatment of chronic viral hepatitis B. A prospective double-blind Belgian-Dutch study.

A prospective, double-blind study was carried out to assess the efficacy of interferon alfa-2b, with or without pre-treatment prednisone withdrawal, in patients with chronic hepatitis B. A total of 57 Belgian and Dutch patients were included in the study. Patients were divided into four treatment groups: Group A, prednisone withdrawal followed by interferon 5 million units per day; Groups B and C, placebo followed by interferon 5 or 1 million units, respectively; and Group D, untreated controls followed for 1 year. All treated patients received interferon for 16 weeks. Two of the 14 control patients lost hepatitis B e antigen during the year of study, and only one of 15 patients in the interferon 1 million units group. Among the 28 patients receiving 5 million units of interferon (with or without prednisone withdrawal), ten (36%) cleared hepatitis B e antigen during the study or within 6 months of the end of therapy. This was associated with a marked improvement in serum transaminase levels. When comparing Groups A and B, it was found that prednisone withdrawal therapy enhanced the response to interferon in patients with pre-treatment serum alanine aminotransferase levels below 100 IU/l, bringing the seroconversion rate up to 50%, compared to 17% on interferon alone. This effect was not seen in patients with high pre-treatment transaminase levels. All treatment responders showed a marked improvement in Knodell index score, whereas in the 15 non-responders from groups A and B, overall inflammatory activity remained the same in six, improved in five and worsened in four.(ABSTRACT TRUNCATED AT 250 WORDS)

Belgium↗

Arsenic and non-cirrhotic portal hypertension. A report of eight cases.

It was discovered that eight patients with complications of non-cirrhotic portal hypertension had received an arsenical preparation for psoriasis as Fowler's solution some years age. Seven of them were admitted for bleeding oesophageal varices. Upon admission, splenomegaly and hypersplenism were present. Liver tests were normal and palmar skin keratosis and melanosis were noted. Liver biopsy of six patients showed features of incomplete septal cirrhosis. Malignant skin lesions were present in half of the patients. One patient died from lung carcinoma and another from an ovarium neoplasm. Chronic arsenic intake should be actively looked for in all patients with psoriasis and non-cirrhotic portal hypertension. They should be followed up for many years for development of malignant lesions in skin, lung and liver. Liver abnormalities present in the biopsies are often minor and may escape detection.

Adult↗

Fatty liver hepatitis and type 5 hyperlipoproteinemia in juvenile diabetes mellitus. Case report and review of the literature.

A 28-year-old man with poorly controlled juvenile-onset diabetes mellitus presented with jaundice and type 5 hyperlipoproteinemia. A liver biopsy showed fatty liver hepatitis (steatonecrosis). This case represents one end in a spectrum of lipid disorders and liver disease in diabetes mellitus. With increasing insulin deficiency, liver steatosis and the more common type 4 hyperlipoproteinemia pattern may progress to fatty liver hepatitis and type 5 hyperlipoproteinemia.

Adult↗

Unconjugated and conjugated bilirubin pigments during perinatal development. II. Studies on serum of healthy newborns and of neonates with erythroblastosis fetalis.

A recently developed reverse-phase high-performance liquid chromatography procedure was applied to the analysis of bilirubins present in serum of neonates. In normal newborns, unconjugated (UCB) and conjugated bilirubins (CB) rose in parallel from day 2 to day 4: the average conjugated fraction remained between 1.2 and 1.6% of total pigment, significantly below the 3.6% documented in adults. However, the absolute concentration of conjugates was 2- to 6-fold higher than the serum levels in adults. Bilirubin conjugates were detected in all samples, but only 20% of these were bilirubin diconjugates, in contrast to a mean of 54% in the adult population. The increased absolute concentrations of UCB and CB together with the decreased fractional amount of conjugates and with the decreased diconjugates seem to be the result of an increased bilirubin production combined with a relative defective biliary secretion. Serum bile acids were high but did not correlate with the levels of bilirubin conjugates. The pattern of serum bilirubins was not different in 4 newborns with hemolytic syndromes. Cholestasis occurred in another child with hemolysis; this was evident from the high concentration and the high fractional amount of conjugates and from the high serum bile acids level.

Bile Acids and Salts↗

Percutaneous transhepatic cholecystostomy for acute complicated cholecystitis in elderly patients.

We report our experience with percutaneous transhepatic cholecystostomy in 10 elderly patients with acute cholecystitis, complicated by empyema formation. Most of these patients has severe underlying disease, rendering them at high risk for surgical intervention. In all patients, the percutaneous procedure was followed by a rapid regression of clinical symptoms and of radiologic abnormalities. Six were considered inoperable. Three of these remain free of biliary symptoms, respectively 22, 10, and 7 months after percutaneous cholecystostomy. Three others died of nonbiliary disease 1-4 months after cholecystostomy. Three patients underwent successful elective cholecystostomy 1-5 wk after percutaneous cholecystostomy. In one patient, cholecystectomy had to be performed because of recurrence of hydrops, 1 wk after catheter removal. In our opinion, percutaneous transhepatic cholecystostomy is a safe and effective procedure in the treatment of elderly patients with acute complicated cholecystitis. It can be followed by elective cholecystectomy in good surgical candidates, or by an expectant conservative management in high surgical risk patients.

Acute Disease↗

Chromatographic analysis and structure determination of biliverdins and bilirubins.

Recent applications of thin-layer chromatographic (TLC) and high-performance liquid chromatographic (HPLC) procedures has revealed an unexpected wide variety of naturally occurring unconjugated and conjugated bilirubins. Biliverdins seems to occur only in unconjugated forms, mainly as the IX alpha isomer. Several synthetic biliverdins and bilirubins present interesting models for biochemical and metabolic studies. Owing to recent recognition of the astounding heterogeneity of natural bilirubins and to the various artifactual changes that bile pigments can undergo, considerable confusion has existed, and still exists, with regard to the nomenclature of the bile pigments and their derivatives. To set a background for further discussion, the present review starts with a brief discussion of nomenclature and of the various characteristic forms of lability of the bile pigments. TLC and HPLC procedures for preparation and analysis of unconjugated biliverdins and bilirubins and their methyl ester and sugar ester conjugates, as well as procedures for analysis of bilirubin-protein conjugates, are then discussed. Since, in view of the lability and pronounced heterogeneity of bile pigments, it is important to assess the composition and nature of chromatographically isolated pigments, the review is concluded by a brief evaluation of various structural tests.

Animals↗

Thyroid hormones and the hepatic handling of bilirubin. I. Effects of hypothyroidism and hyperthyroidism on the hepatic transport of bilirubin mono- and diconjugates in the Wistar rat.

The effects of thyroidectomy and of thyroid hormone administration on the hepatic transport of endogenous bilirubin were investigated in the Wistar R/APfd rat. Hypothyroidism resulted in an enhanced hepatic bilirubin UDP-glucuronosyltransferase activity and in a decreased p-nitrophenol transferase activity. It caused a cholestatic condition with a 50% decrease in bile flow and bile salt excretion, and an increased proportion of conjugated bilirubin in serum. The biliary output of unconjugated and monoconjugated bilirubins decreased in parallel by about 65%, whereas the excretion rate of the diconjugate dropped by only 47%, resulting in an increased di- to monoconjugate ratio in bile. Hyperthyroidism was characterized by a decreased bilirubin and an increased p-nitrophenol transferase activity, and by an augmented bilirubin output in bile. The output of unconjugated and monoconjugated bilirubins increased in parallel by about 50 or 100%, whereas the excretion of the diconjugate increased by only 20 to 50%, depending on the dose of thyroxine administered; this resulted in a decreased di- to monoconjugate ratio in bile. A linear positive relationship was found between bilirubin UDP-glucuronosyltransferase activity and the ratio of bilirubin di- to monoconjugates present in bile or formed by in vitro incubation of liver homogenates at low concentration of bilirubin (10 to 15 microM), indicating that bile pigment composition is mainly determined by the conjugation activity in the liver. The inverse relationship observed between hepatic beta-glucuronidase activity and the ratio of di- to monoconjugates in bile warrants further investigation to analyze whether this enzyme activity also plays a possible role in the changes in bile pigment composition in hypo- and hyperthyroid rats.

4-Nitrophenylphosphatase↗

Similarities in maximal biliary bilirubin output in the normal rat after administration of unconjugated bilirubin or bilirubin diglucuronide.

The rate-limiting step in the overall plasma-to-bile transport of a saturating load of bilirubin is still a matter of controversy. We reassessed the apparent maximal biliary bilirubin excretion following i.v. infusion of unconjugated bilirubin and--for the first time--of highly purified bilirubin diglucuronide in the rat. The bilirubin diglucuronide preparation could be kept in a stable form at -20 degrees C for at least 2 months after addition of 3 mM sodium ascorbate. The biliary bilirubin excretion rates in animals with and without bile depletion in order to induce different flow rates were comparable after infusion of unconjugated bilirubin and of bilirubin diglucuronide. No significant hydrolysis of bilirubin diglucuronide seemed to occur during the hepatic transport of the pigment. Injection of bilirubin diglucuronide into rats which were already being infused with saturating doses of unconjugated bilirubin did not result in increased biliary bilirubin excretion. In contrast, a reversible inhibition of bilirubin output and bile acid-dependent bile flow was observed. If unconjugated and diglucuronidated bilirubin follow the same intracellular routes, the present results would suggest that conjugation did not restrict maximal biliary excretion. However, if exogenously administered diglucuronide utilizes a separate pathway, as was recently proposed, the biliary secretion of this exogenous conjugate might be restricted, presumably due to a toxic effect of the high local concentration of diglucuronide. The pathways utilized by the unconjugated pigment, on the other hand, could be primarily determined by the conjugating capacity.

Animals↗

Lincomycin treatment of guinea pigs causes formation of pigmented phosphate containing gallbladder sludge and stones.

We studied the mechanism of gallbladder sludge formation in guinea pigs (n = 30) treated with lincomycin (80 mg/kg/day) for 7 consecutive days. At sacrifice (day 8) gallbladders of treated animals contained turbid bile, sludge and in one animal a single gallstone. The precipitates were amorphous on X-ray diffraction. Infra-red spectroscopy revealed calcium phosphate as the major component. Compared to saline-treated controls (n = 15) concentrations of total protein, total phosphate and total bilirubin in gallbladder bile were significantly increased (P less than 0.05). The increase in total phosphate was due to the inorganic component, since phospholipid phosphorus was unchanged. The relative amounts of unconjugated bilirubin and of bilirubin mono- and diconjugates in gallbladder bile were unaffected by treatment as was beta-glucuronidase activity. However, sludge was enriched in unconjugated bilirubin compared to gallbladder bile. This was most probably caused by alkaline hydrolysis of bilirubin monoconjugates. To some extent, disproportionation of bilirubin monoconjugates in bile or sludge, either in vivo or during sample preparation, might also have led to increased unconjugated pigment.

Animals↗

Taurocholate increases the biliary output of bilirubin pigments in the rat, due to haemolysis.

In order to investigate the effect of bile salts on the biliary transport of bilirubin, we infused rats with taurocholate at 1-3 mumol/min/kg body weight. When administered in saline, taurocholate induced haemolysis, and a dose-dependent increase in biliary excretion and serum concentration of all bilirubin pigments. The addition of human or rat serum albumin to the infusate, at an albumin:taurocholate molar ratio equal to or above 200, completely prevented haemolysis and the above-mentioned alterations in bilirubin transport, without any change in the bile acid output. In order to mimic a haemolytic condition, an erythrocyte haemolysate was further added to the taurocholate-albumin solution. This again resulted in an increased bilirubin output. We suggest that taurocholate treatment increases bilirubin output due to the increased load of the pigment on the liver, as a result of the bile acid-induced haemolysis.

Animals↗

Somatostatin inhibits the effect of secretin on bile flow and on hepatic bilirubin transport in the rat.

Increasing amounts of porcine secretion (0.05 to 2.00 clinical units/h/100 g body wt) given to rats during a continuous infusion of bilirubin, increased bile flow and the apparent maximal biliary excretion of bilirubin ('Tm'). This increment was caused by an enhanced biliary output of bilirubin monoconjugates. The effect was dose dependent but maximal at a secretin infusion of 0.80 CU. Somatostatin 0.2 and 0.8 microgram/h/100 g body wt caused a dose related inhibition of the hepatic effects of secretin both on bile flow and on biliary output of bilirubin conjugates. As secretin elicits the release of somatostatin, a feed-back system could be envisaged whereby the somatostatin released stops the effects of secretin.

Animals↗

Thyroid hormones and the hepatic handling of bilirubin. II. Effects of hypothyroidism and hyperthyroidism on the apparent maximal biliary secretion of bilirubin in the Wistar rat.

This study was undertaken in the Wistar R/A Pfd rat to investigate the effects of hypothyroidism and of hyperthyroidism on the maximal biliary excretion (Tm) of bilirubin and on the concentration and composition of bilirubin in liver and plasma at the end of a bilirubin load. Hypothyroidism caused a cholestatic condition with a 50% decrease in bile flow and in bilirubin Tm, and with an increased proportion of conjugated bilirubin in liver and plasma. This was associated with an increased ratio of bilirubin diconjugates to monoconjugates in bile, liver, and plasma, which can be ascribed to the increased hepatic conjugation activity towards bilirubin and/or to the prolonged retention of bile pigments in the hepatocytes with increased conversion of monoconjugates to diconjugates. Cholestasis induced by hypothyroidism was further characterized by a decreased biliary output of unconjugated bilirubin. The latter phenomenon might represent an indirect effect related to a decreased output of bilirubin monoconjugates with impaired hydrolysis to unconjugated bilirubin; it might also reflect the cholestatic condition with decreased excretion of the unesterified bile pigment as such. Hyperthyroidism resulted in a 1.3-1.4-fold increase in bile flow. The maximal bilirubin concentration in bile decreased 1.3-1.4-fold, so that the apparent maximal bilirubin excretion rate remained unchanged at 115 nmol.min-1.100 g-1, as observed in untreated rats. Hyperthyroidism lowered the bilirubin UDP-glucuronosyltransferase activity, produced a decreased ratio of bilirubin di- to monoconjugates in bile and plasma, and a decreased ratio of conjugated to total bile pigment concentration in liver and in plasma. Similar findings are present in the heterozygous Gunn rat strain and in patients with hepatic bilirubin UDP-glucuronosyltransferase deficiency. We therefore propose the hyperthyroid rat as an experimental animal model of Gilbert's syndrome.

Animals↗