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Biomedical subjects

J Fevery

Publications and source records attributed to J Fevery.

At least 91 records · Page 5Linked to original sources
PubMed1993

Renal clearance of bilirubin conjugates in newborns of different gestational age.

The renal excretion of bilirubin conjugates was analysed in 22 newborns. Bilirubin monoconjugate was the only metabolite detectable in urine samples and its renal excretion correlated with the creatinine excretion rate (r = 0.91). The renal clearance of bilirubin monoconjugates in newborns ranged between 380 and 2160 ml/1.73 m2 per 24 h (median: 790). According to the present findings the renal function should be monitored in newborns and infants with conjugated hyperbilirubinaemia.

Bilirubin↗
PubMed1993

Plasma collected from heparinized blood is not suitable for HCV-RNA detection by conventional RT-PCR assay.

Detection of hepatitis C virus-RNA (HCV-RNA) in serum or in plasma is considered a reliable marker for ongoing HCV infection. HCV-RNA was measured routinely in plasma collected from heparinized blood of patients with chronic hepatitis C and varying results were found. In this study, HCV-RNA was detected in peripheral blood mononuclear cells (PBMCs) and in serum of 16 out of 17 anti-HCV positive patients with chronic hepatitis C. In contrast, HCV-RNA was found in plasma collected from heparinized blood of only one of these seventeen patients. The addition of heparin to known HCV-RNA containing solutions before reverse-transcription and separately before PCR, demonstrated the inhibitory effect of heparin on the reverse transcription and amplification reaction. Furthermore, evidence is provided that plasma for PCR should be collected preferably into EDTA vacutainers. It is concluded, therefore, that plasma collected from heparinized blood is not suitable for HCV-RNA determination by RT-PCR. In addition, PBMCs might play an important role in the pathobiology of hepatitis C virus, since HCV-RNA was easily detected in PBMC of patients with chronic hepatitis C.

False Negative Reactions↗
PubMed1993

Percutaneous transhepatic cholecystostomy for acute complicated calculous cholecystitis in elderly patients.

OBJECTIVE: To assess the immediate and long-term outcomes of elderly patients with acute complicated cholecystitis treated by percutaneous cholecystostomy. To assess the results of bile cultures obtained in this group of patients. DESIGN: Case series. SETTING: Tertiary care center. PATIENTS: Thirty-two patients, with a mean (+/- S.D.) age of 78 +/- 8 years (range, 58-92 years), and who presented with acute cholecystitis complicated by empyema formation. Sixty-six percent had associated disorders, which rendered them at high risk for surgical intervention. INTERVENTION: Percutaneous transhepatic catheter drainage of the gallbladder, with a mean drainage time of 20 days (range 0-84 days). In addition, endoscopic sphincterotomy with removal of common bile duct stones was performed in six patients and percutaneous aspiration of an associated liver abscess in four cases. RESULTS: Percutaneous cholecystostomy was followed by rapid regression of clinical symptoms and of radiologic abnormalities in all patients. Sixteen cases (50%) underwent elective cholecystectomy 1-12 weeks after cholecystostomy. One of them died of aspiration pneumonia, whereas 15 had no post-operative problems and were discharged 9 days (mean) after surgery. Forty-four percent (14/32) were considered inoperable: they remained completely free of biliary symptoms and died of unrelated illness (22%) after a mean follow-up of 6 months (range, 1-22 months) or are still alive (22%) with a mean follow-up of 15 months (range, 5-36 months). Bile cultures were positive in 75% of the patients. Escherichia coli, other aerobic Gram-negative micro-organisms, and anaerobic bacterial species accounted for 35% (16/46), 28% (13/46), and 20% (9/46) of the isolated bacteria, respectively. All aerobic Gram-negative species tested in vitro were susceptible to gentamicin and to temocillin. CONCLUSIONS: Percutaneous transhepatic cholecystostomy is a safe and effective procedure in the treatment of elderly high-risk patients with acute cholecystitis complicated by empyema formation. It can be followed by elective cholecystectomy, if possible, or by expectant conservative management in patients who are inoperable because of systemic disease.

Aged↗
PubMed1993

Treatment of decompensated viral hepatitis B-induced cirrhosis with low doses of interferon alpha.

Seven patients with decompensated posthepatitis B cirrhosis were treated with low doses of interferon alpha. The initial plasma level of HBV-DNA ranged from 3.0 to 189.3 pg/ml, and that of ALT from 37 to 156 IU/l. Liver biopsies demonstrated ongoing piecemeal necrosis. In sera of all but one patient, HBV-DNA became undetectable by hybridisation techniques within 10 to 28 weeks. Plasma HBeAg became negative in four and HBe-antibodies positive in three patients. Serum transaminase levels showed a marked initial rise 3 to 13 weeks after onset of therapy; they dropped to normal values later in all except one patient. Therapy was initiated at 1 MU (million units) three times a week for 2 weeks and was increased to 2.5 MU for 16 weeks. Later, this dosage was raised to 5 MU three times a week in some patients. Complications included variceal haemorrhage, aggravation of ascites or of encephalopathy, development of pneumonia, recurrence of spontaneous bacterial peritonitis or of gastric ulcer bleeding. One year after stopping the therapy, three patients are well and without any feature of liver decompensation. Three patients died before they could undergo a liver transplantation. In one patient treatment was interrupted because of marked exacerbation of liver cell necrosis. It thus seems possible to suppress HBeAg and HBV-DNA in patients with decompensated cirrhosis. This is important to prepare them for possible liver transplantation. Interferon should be initiated at low doses and the patients be very carefully monitored. Prophylactic therapy for bacterial peritonitis and for variceal haemorrhage is warranted.

Alanine Transaminase↗
PubMed1992

Spontaneously diabetic biobreeding rats and impairment of bile acid-independent bile flow and increased biliary bilirubin, calcium and lipid secretion.

Chemically induced diabetes has been reported to induce profound changes in bile formation, but possible toxic effects of the streptozotocin or alloxan used cannot be excluded totally. This study was undertaken to evaluate biliary function in spontaneously diabetic female biobreeding rats with a diabetes duration of 2 wk and compare them with nondiabetic littermates. Diabetic animals evidenced glycosuria, hyperglycemia and hypoinsulinemia. Biliary concentration and secretion of bile acids, cholesterol and phospholipids were significantly increased, with no enhancement in the lithogenic index of bile. Bile flow and the biliary secretion of sodium, potassium, chloride and bicarbonate were significantly reduced despite the increased bile acid secretion. The cholestatic condition was confirmed by an increased serum concentration of bile acids and a higher activity in serum of the alkaline phosphatase liver isoenzyme. Biliary calcium concentration increased without any change in its serum concentration. A linear relationship was observed between biliary calcium and bile acid secretion. Serum concentration of unconjugated and of conjugated bilirubin was increased 1.6-fold and 8-fold, respectively, with a 1.5-fold enhanced biliary secretion of bilirubins despite the cholestasis; this points to an enhanced bilirubin production. An increased proportion of conjugated bilirubin was found in serum together with an enhanced bilirubin diconjugate/monoconjugate ratio in bile. A higher UDP-glucuronyltransferase activity and a delayed transit of bilirubin could account for these effects. Administration of insulin to diabetic animals tended to reverse the above reported changes. The spontaneously diabetic biobreeding rat thus represents a model of bile acid-independent cholestasis with enhanced biliary bile acid and calcium secretion and with presumably an enhanced bilirubin production.

Animals↗
PubMed1992

The origins and kinetics of bilirubin in dogs with hepatobiliary and haemolytic diseases.

In 35 dogs with spontaneous hepatobiliary liver disease the kinetics and the sources of bilirubin were quantified. The disorders were extrahepatic bile duct obstruction (n = 4), fulminant hepatitis (n = 2), (sub)acute hepatitis (n = 5), chronic active hepatitis (CAH) with cirrhosis (n = 6), hepatic lymphosarcoma (n = 5), centrizonal necrosis secondary to haemolytic anaemia (n = 6) and other (n = 2). The plasma disappearance of [3H]bilirubin was analyzed with a two-compartment model in all dogs. The ratio early labeled/late labeled bilirubin was determined by measuring the incorporation of [14C]glycine into erythrocyte haem and faecal stercobilin. By introducing this relation in the model analysis the bilirubin production rates from erythrocyte destruction (PE), ineffective erythropoiesis (PI) and hepatic haemoprotein (PL) could be quantified. Total bilirubin turnover was increased in both primary haemolytic disease and most cases of hepatobiliary disease. Erythrocyte survival was reduced in all cases but one. The bilirubin clearance was impaired to 30-50% of the normal value in most cases of hepatobiliary disease and also in primary haemolysis. In dogs with fulminant hepatitis, and cirrhosis with or without CAH, the clearance rates were reduced to values below 15% of normal. In these dogs both an impaired clearance and an increased production were important determinants of hyperbilirubinaemia. In other cases plasma bilirubin was primarily determined by increased production. These clearances and production rates were similar in haemolysis and in many cases of primary hepatobiliary disease. The hepatic haemoprotein turnover was quite variable in all subgroups, ranging from 1-74% of the total bilirubin turnover.(ABSTRACT TRUNCATED AT 250 WORDS)

Anemia, Hemolytic↗
PubMed1992

The origins and kinetics of bilirubin in healthy dogs, in comparison with man.

The origins and the kinetics of unconjugated bilirubin were assessed in 25 healthy dogs. Bilirubin kinetics were measured by the analysis of the plasma disappearance of [3H]bilirubin in a two-compartment model. The relative bilirubin productions from erythrocyte haem degradation and early labeled bilirubin were determined by measuring the incorporation of [14C]glycine in erythrocyte haem and in fecal stercobilin. The incorporation of this relation into the model permitted the quantitation of the bilirubin production from erythrocyte destruction, ineffective erythropoiesis and the catabolism of hepatic haemoproteins. The contribution of the three bilirubin sources to the plasma concentration was derived from the calculated fraction reflux into the plasma of bilirubin produced in the liver from hepatic haemoproteins. Other calculated model-dependent and -independent parameters were plasma bilirubin clearance, hepatic bilirubin extraction efficiency, pool sizes, and the fractional transfer rates which reflect the hepatic uptake process, reflux from liver to the plasma, and the conjugating enzyme activity. In plasma of healthy dogs only unconjugated bilirubin was detected. It averaged 0.68 mumol/l, which is far below levels in man. This is probably due to the 20-fold higher hepatic clearance rate in dogs (median 32.2; range 21.6-43.9 ml/kg per min). In addition, fasting hyperbilirubinaemia could not be documented in the dog. The total bilirubin turnover was 14.9 (12.6-17.1) mumol/kg (median and 95% range), with 67 (60-70)% derived from erythrocyte degradation, 5.3 (4.7-5.5)% from ineffective erythropoiesis and 27.7 (24.5-35.3)% from hepatic haemoproteins. The figures for the plasma bilirubin turnover were 12.3 (10.3-14.2) mumol/kg per day, 79 (75-84)%, 6.3 (6.0-6.6)% and 14.8 (9.2-18.9)%, respectively. The presented model permits the simultaneous quantitation of both the origins and the kinetics of bilirubin. The application of this approach in pathological conditions is expected to provide better insight in the pathophysiology of acquired hyperbilirubinaemia.

Animals↗
PubMed1992

Endoscopic biliary endoprosthesis in elderly patients with large bile duct stones: long-term follow-up.

OBJECTIVE: To assess the long-term evolution of elderly patients with large or impacted bile duct stones, treated by an endoscopic biliary endoprosthesis. DESIGN: Case series. SETTING: Tertiary care center. PATIENTS: Twenty-three patients with a mean (+/- SD) age of 86 +/- 5 years (range, 77-97 years). On admission, 96% were highly symptomatic. These patients represent 8.4% of a group of 273 elderly patients (greater than or equal to 70 years old) with choledocholithiasis treated by endoscopic sphincterotomy between November 1984 and May 1989. INTERVENTION: Endoscopic insertion of a biliary endoprosthesis. RESULTS: Eight-seven percent (20/23) remained completely free of biliary symptoms and died of unrelated illness (48%) after a mean follow-up of 23 months or are still alive (39%) with a mean follow-up of 52 months. In four cases, this asymptomatic evolution now extends for more than 5 years. CONCLUSION: Insertion of a biliary endoprosthesis offers an effective method for long-term treatment of non-extractable biliary stones in elderly patients.

Aged↗
PubMed1992

Vitamin A abuse: development of cirrhosis despite cessation of vitamin A. A six-year clinical and histopathologic follow-up.

We report the case of a 35-year-old man who contracted vitamin A-induced liver cirrhosis. Five years before, he had been investigated for vitamin A-induced non-cirrhotic portal hypertension. In this case, the clinical and histopathologic evolution from non-cirrhotic portal hypertension to cirrhosis was documented. In spite of the cessation of pharmaceutical vitamin A intake, the disease progressed. Therapy with colchicine and phenobarbital apparently did not influence evolution to cirrhosis. This suggests that vitamin A can trigger largely unknown mechanisms of liver fibrosis which seem to be self-perpetuating.

Adult↗
PubMed1992

Hepatitis C.

Until recently the diagnosis of non-A, non-B hepatitis was made by excluding other detectable viral infections of the liver. Progress in molecular biology made it possible to develop assays which can trace antibodies against the hepatitis C virus. This virus plays a major role in the pathogenesis of transfusion-related and sporadic non-A, non-B hepatitis and possibly of other liver diseases. Although the genome of a few isolates of the hepatitis C virus has already been decoded, the viral particles have not yet been visualized.

Genome, Viral↗
PubMed1991

Quantitation of urobilinogen in feces, urine, bile and serum by direct spectrophotometry of zinc complex.

Previous methods to quantitate urobilinogen lack precision due to either incomplete reduction of urobilin or to losses of pigment before the use of Ehrlich's aldehyde reaction or due to pigment precipitation, as occurs in Schlesinger's fluorescent assay. The present procedure modifies the latter assay to obviate described problems as it is based on direct spectrophotometry (or spectrofluorometry) of a zinc complex of urobilin in dimethylsulfoxide. The sample is extracted with dimethylsulfoxide to increase recovery of urobilinogen from samples of various origin (feces, urine, bile, serum etc.) and to prevent the precipitation of proteins. After oxidation of urobilinogen with iodine, the concentration of the resulting urobilin is directly determined from the absorption (or fluorescent) spectrum. High sensitivity and high specificity for the procedure result from the high value of absorption coefficient and by the characteristic absorption spectrum of zinc complex of urobilin, respectively. Within-day and day-to-day coefficients of variation of stool and bile samples range from 1.6 to 9.2%. The smallest concentration of urobilinogen measurable by spectrophotometry is approximately 0.5 mumol/l, by fluorometry it is 0.25 mumol/l. The recovery varies from 82.2 to 93.8% depending on re-extraction of the sample. The method is linear in the range of 1 to 35 mumol/l and of 0.5 to 17.5 mumol/l for spectrophotometric and fluorescent determinations, respectively. The results obtained with the present method correlated well with Ehrlich's determination (r2 = 0.912), but are approximately two-fold higher. Storage of the samples at -20 degrees C or extraction with dimethylsulfoxide prior to storage are good ways for sample preservation. Twenty stool samples from healthy adults were determined.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Light chain deposition disease of the liver associated with AL-type amyloidosis and severe cholestasis.

A 67-year-old man with a 3-month history of jaundice presented with hepatomegaly. Laboratory studies revealed abnormal liver tests with raised bilirubin. Renal function was normal. Endoscopic retrograde cholangiopancreatography revealed normal extrahepatic bile ducts. Liver biopsy showed severe bilirubinostasis and a typical bile infarct. Laminar and globular deposits of PAS-positive diastase-resistant non-congophilic material were observed in the sinusoidal walls. In addition, congophilic material was detected in the portal tracts. Immunohistochemistry revealed the presence of lambda-light chain deposits both in the sinusoids and in the portal tracts. Collagens type I and IV and fibronectin appeared markedly increased in the perisinusoidal space. On electron microscopy, the deposited material in the Disse spaces was mainly composed of fibrils indistinguishable from amyloid, admixed with small amounts of granular electron-dense material. The similarities of light chain deposition disease and AL amyloidosis are discussed.

Aged↗
PubMed1991

The influence of gestational age on bilirubin conjugation in newborns.

Unconjugated, mono- and diconjugated bilirubin levels were determined in serum soon after birth, and followed up for several days. Fourteen preterm neonates were studied with a gestational age below 33 weeks (n = 7) or between 34 and 37 weeks (n = 7), respectively, as well as 19 full-term newborns either untreated (n = 9) or treated by phototherapy (n = 10). Bilirubin and its derivatives were analysed by alkaline methanolysis and spectrometry after separation by thin-layer chromatography. In normal full-term neonates total and unconjugated bilirubin reached peak levels at days 2-4. Thereafter, a decline of 11% per day was detectable. Monoconjugates in serum amounted to 3.1 +/- 1.1% of total pigment and remained at that level. The relative amount of diconjugates increased from 0.55 +/- 0.25% (2-4th postnatal day) to 1.62 +/- 0.99% (9-13th day of life). The rapid decline of unconjugated bilirubin paralleled by an increase of diconjugates are an expression of the maturation process for bilirubin conjugation. The premature neonates with less than 33 weeks gestation exhibited an increase of unconjugated serum bilirubin up to the 4-5th postnatal day, the decline thereafter amounted 2% per day. The fraction of 2.3 +/- 1.1% monoconjugates was small and exhibited only a moderate increase in the follow up. In contrast diconjugates were undetectable or very low and remained at this level. These results suggest the presence of a more severe immaturity as well as a slower maturation process of bilirubin conjugation in preterm newborns.(ABSTRACT TRUNCATED AT 250 WORDS)

Bilirubin↗
PubMed1990

Urobilinogen-i is a major derivative of bilirubin in bile of homozygous Gunn rats.

Gunn rats lack bilirubin UDP-glycosyltransferases, but diazo-negative derivatives of bilirubin have been described in their bile. In order to investigate this alternative disposal of bilirubin, crude bile samples from Gunn and Wistar rats were directly analysed by h.p.l.c. Besides bilirubin (in Gunn rats) or its glycosides (in Wistar rats), two major compounds were detected. A yellow one corresponded to the previously documented vitamin B-2 and was equally prominent in Gunn rats or Wistar-rat bile. The other compound was colourless, but on standing in contact with air it was spontaneously oxidized to a pinkish-yellow pigment. It was far more prominent in Gunn-rat bile. Analysis of bile obtained after intravenous injection of [14C]bilirubin to Gunn rats demonstrated that this compound was highly labelled. Freezing and thawing of the bile resulted in the formation of a series of diazo-negative derivatives, demonstrating that the original compound was quite labile. Spectral (adsorption and fluorescent) and chromatographic (h.p.l.c., t.l.c. and paper chromatography) analysis of the oxidized form of the labelled compound allowed its identification as urobilin-i. The colourless compound secreted in bile was urobilinogen-i. Administration of neomycin and bacitracin to Gunn rats or gut resection suppressed the biliary excretion of urobilinogen and thus confirmed its intestinal origin. Urobilinogen seems thus to represent the major bilirubin derivative present in Gunn-rat bile. Its breakdown products might represent the so-far-unidentified diazo-negative polar bilirubin derivatives. Since only a small amount of bilirubin is present in Gunn-rat bile, the urobilinogen formed in the intestinal lumen seems to be derived from bilirubin reaching the gut via routes other than the biliary one.

Animals↗
PubMed1990

Effects of uridine diphosphate glucuronosyltransferase activity on the maximal secretion rate of bilirubin conjugates in the rat.

It is generally accepted that biliary secretion is rate-limiting for the plasma-to-bile transport of a saturating load of bilirubin. Previous studies from this laboratory have suggested a relationship between the hepatic bilirubin uridine diphosphate glucuronosyltransferase activity and the apparent maximal rate of bilirubin secretion (excretory transport maximum). The present study was undertaken to further investigate this relationship in rats with a wide range of transferase levels and to analyze the effects of transferase activity on the formation of bilirubin monoglucuronides and diglucuronides in vivo and in vitro. Animals with moderately decreased enzyme activity still showed a near-normal excretory transport maximum but decreased fractional amounts of conjugated bilirubins in plasma and liver and a decreased ratio of bilirubins diconjugates to monoconjugates in bile, liver, and plasma. A more pronounced decrease in the level of transferase activity yielded lower excretory transport maximum values as well. Enhanced transferase activities were obtained by pretreatment with a series of enzyme-inducing agents, usually at dosages not influencing bile flow. An enhanced transferase activity produced significant increases in bilirubin excretory transport maximum, decreased concentrations of both unconjugated and conjugated bilirubins in plasma, and an increased ratio of diconjugates to monoconjugates in bile and in liver. In all animals, the ratio of disconjugates to monoconjugates observed in bile was correlated with the ratio found after incubation of liver homogenates in vitro at low concentrations of bilirubin substrate. Overall, the relationship between bilirubin excretory transport maximum and uridine diphosphate glucuronosyltransferase activity can best be described by a hyperbolic curve. At "saturation" of the excretory transport maximum values, no increase of conjugates in liver or in plasma could be observed, suggesting that not the biliary secretion, per se, but rather the conjugation rate in vivo is rate-limiting. The latter seems lower than the in vitro assayed enzyme activity. The present investigations point to an equilibration of bilirubin pigments between plasma, liver, and bile. The in vivo conjugation rate can be estimated from the in vitro assay (but not at high enzyme activities) and determines the maximal biliary secretion rate, the ratio of diconjugates to monoconjugates in the three compartments studied, and the relative amount of conjugates in plasma. Our studies suggest that the conjugation rate in vivo rather than the biliary secretion step is the major determinant of the maximal bilirubin secretion rate.

Animals↗
PubMed1990

Increase in the relative amount of bilirubin diconjugates in rat bile and serum under infusion of phthaleins and indocyanine green.

The effect of organic anions on bilirubin metabolism and excretion was investigated in rats. Biliary excretion of bromosulfophthalein, bromcresol green and indocyanine green led to a significant decrease in excretion of bilirubin pigments and to an increase of their concentration in serum. This was concomitant with a marked increase in the ratio of bilirubin diconjugates to monoconjugates in bile and serum. These changes were unrelated to either bile flow, biliary lipid output, or hepatic activity of bilirubin UDP-glucuronyl transferase. Following bolus injection of [14C]bilirubin, peak excretory rate of radioactivity was markedly delayed in rats infused with bromosulfophthalein, as compared to controls. It is concluded that administration of the organic anions increased the ratio of bilirubin diconjugates to monoconjugates in bile and serum, by slowing down the intrahepatic transit of bilirubin pigments. This, in turn, allowed more efficient enzyme-catalyzed formation of bilirubin diconjugates from the intermediate bilirubin monoconjugates.

Animals↗