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Biomedical subjects

R A Chamuleau

Publications and source records attributed to R A Chamuleau.

At least 19 recordsLinked to original sources
PubMed1992

Detection of hepatitis C viral RNA sequences in fresh and paraffin-embedded liver biopsy specimens of non-A, non-B hepatitis patients.

In this study methods of HCV-RNA detection in fresh frozen and formalin-fixed, paraffin-embedded liver biopsies are described. Of 22 untreated chronic non-A, non-B hepatitis patients and 6 control patients, a plasma sample and part of a liver biopsy were freshly frozen for hepatitis C virus (HCV) cDNA-PCR. From 16 of the same non-A, non-B hepatitis patients and from 5 of the same control patients formalin-fixed, paraffin-embedded liver tissue from the same biopsy was available also for HCV cDNA-PCR. In 13 of 22 non-A, non-B hepatitis patients HCV-RNA could be detected in plasma as well as in liver tissue. In the other 9 non-A, non-B hepatitis patients and in 6 control patients, no HCV-RNA was detectable in either plasma or liver tissue. The comparison between HCV cDNA-PCR results in fresh frozen versus formalin-fixed, paraffin-embedded liver biopsies showed that although detection of HCV-RNA in both correlated 100% the quantity of HCV-RNA was lower in the formalin-fixed, paraffin-embedded liver biopsies of 5 of 8 patients for whom end-point dilution titration of liver RNA was performed. We conclude that using the procedures described HCV-RNA can be reliably detected in both fresh-frozen and formalin-fixed, paraffin-embedded liver biopsies and that HCV cDNA-PCR in liver tissue may become an important assay, especially for monitoring anti-viral therapy.

Biopsy↗
PubMed1992

Liver biopsy versus ultrasound in methotrexate-treated psoriasis: a decision analysis.

Before starting methotrexate therapy for cases of recalcitrant psoriasis, a liver biopsy has been usual in order to exclude cirrhosis and moderate or severe fibrosis, which are contraindications for methotrexate treatment. As mortality and morbidity of liver biopsy are not negligible, and as this invasive procedure is unpleasant for the patient and urges clinical admission, we evaluated the possibility of ruling out severe liver pathology by means of ultrasonography, which we compared to liver biopsy. We made this comparison by means of a decision tree. The advantages of this analysis are the clear definition of the decision problem and its alternatives, and the possibility of calculating the risk of each alternative, thus being able to choose the best diagnostic method. In this study, the results of various research groups are discussed, in which liver biopsy and liver ultrasound were compared. In our decision tree we used some of these results and other assumptions, based on comparable studies. We varied the biopsy mortality and the sensitivity of ultrasound to show the change in the risk of each alternative. Our analysis shows that the differences of expected values between the liver biopsy branch and the ultrasonography branch are relatively small. Therefore, we advise each center, which has at its disposal a specialist in liver ultrasonography, to re-evaluate its guidelines with regard to the detection of severe liver pathology before starting methotrexate for the treatment of psoriasis.

Algorithms↗
PubMed1992

Amino acid release from cerebral cortex in experimental acute liver failure, studied by in vivo cerebral cortex microdialysis.

Both increased gamma-aminobutyric acid (GABA)-ergic and decreased glutamatergic neurotransmission have been suggested relative to the pathophysiology of hepatic encephalopathy. This proposed disturbance in neurotransmitter balance, however, is based mainly on brain tissue analysis. Because the approach of whole tissue analysis is of limited value with regard to in vivo neurotransmission, we have studied the extracellular concentrations in the cerebral cortex of several neuroactive amino acids by application of the in vivo microdialysis technique. During acute hepatic encephalopathy induced in rats by complete liver ischemia, increased extracellular concentrations of the neuroactive amino acids glutamate, taurine, and glycine were observed, whereas extracellular concentrations of aspartate and GABA were unaltered and glutamine decreased. It is therefore suggested that hepatic encephalopathy is associated with glycine potentiated glutamate neurotoxicity rather than with a shortage of the neurotransmitter glutamate. In addition, increased extracellular concentration of taurine might contribute to the disturbed neurotransmitter balance. The observation of decreasing glutamine concentrations, after an initial increase, points to a possible astrocytic dysfunction involved in the pathophysiology of hepatic encephalopathy.

Acute Disease↗
PubMed1992

Antiviral effect of prolonged intermittent lymphoblastoid alpha interferon treatment in chronic hepatitis B.

In a European multicentre study 40 patients with HBeAg positive chronic hepatitis B virus (HBV) infection were treated with 5 mega units of lymphoblastoid alpha-interferon daily according to the following regimen: a four week primer course, four weeks of rest and a second course lasting 16 to 30 weeks. After 52 weeks of follow up, a response (HBeAg seroconversion and HBV-DNA negativity) was observed in 22 patients (55%). HBsAg seroconversion occurred in five patients (12.5%). One patient exhibited a relapse for serum HBeAg and HBV-DNA after cessation of treatment. According to a response prediction model, the observed response rate was not related to the selection of patients likely to respond. The initial interferon course induced a reduction of the serum HBV-DNA and HBeAg levels of 87% and 18%, respectively, leading to a significantly lower level of viral replication activity at the start of the second longterm course compared with baseline. After 24 weeks of follow up (week 16 of the second course), 19 (48%) patients exhibited a response, 13 (32%) a partial response (HBeAg < 50% of initial level or HBV-DNA negative) and 8 (20%) no response. For eight of the 13 partial responders treatment was stopped at week 24 and viral replication rebounded to pretreatment values. In the last five partial responders prolongation of therapy up to week 38 led to a definite response and HBsAg seroconversion in three of the five patients. The results of this study suggest that a short primer course and prolongation of therapy may help to enhance the response rate of alpha-interferon therapy for chronic hepatitis type B.

Adolescent↗
PubMed1992

Reappearance of vanished bile ducts.

A 36-year-old Surinam woman with a severe form of toxic epidermal necrolysis of unknown origin is presented. Skin lesions healed gradually without scarring within 3 to 4 weeks, but eye lesions progressed to symblepharon and corneal opacification, resulting in almost complete blindness. In addition, toxic epidermal necrolysis was associated with severe intrahepatic cholestasis caused by vanished bile duct syndrome; viral hepatitis, primary biliary cirrhosis and primary sclerosing cholangitis were excluded. After about six months, intrahepatic chole-stasis improved spontaneously and a third liver biopsy taken after 51 weeks of illness revealed that the bile ducts had reappeared. At present, the patient is relatively well, with no jaundice, although parameters of cholestasis are still elevated: Alkaline phosphatase three times, and gamma GT thirty times the normal values. This sequence of events has to our knowledge never been reported in the literature.

Adult↗
PubMed1991

The relationship between plasma free fatty acids and experimentally induced hepatic encephalopathy in the rat.

Two experimental models of hepatic encephalopathy in the rat have been investigated in order to study the postulated relationship between plasma free fatty acids concentration (C6 - C22:0) and the degree of hepatic encephalopathy. As a model of chronic hepatic encephalopathy, porta caval shunted rats were studied for 15 weeks, whereas rats with acute liver ischemia were used as a model for acute hepatic encephalopathy. In porta caval shunted rats only a minor degree of hepatic encephalopathy developed, whereas plasma ammonia concentration increased significantly (82 +/- 8 to +/- 440 +/- 32 mumol/l). Acute liver ischemia induced severe grades of hepatic encephalopathy associated with high levels of plasma ammonia (+/- 1 200 mumol/l). Since no significant changes in plasma free fatty acids were observed during both chronic and acute hepatic encephalopathy no correlation between plasma free fatty acids and the stage of hepatic encephalopathy was found. Our data do not support an important role of free fatty acids in the pathogenesis of acute or chronic hepatic encephalopathy in the rat.

Acute Disease↗
PubMed1991

The use of in vivo proton NMR to study the effects of hyperammonemia in the rat cerebral cortex.

Using in vivo 1H NMR spectroscopy (1H MRS) and biochemical analysis, the effects of hyperammonemia on cerebral function were studied in three rat models: acute liver ischemia (LIS), administration of urease (UREASE) and administration of methionine sulfoximine (MSO). By means of localization in three dimensions signals were obtained exclusively from the cerebral cortex. Specially developed lineshape correction and fitting methods were used to quantitate the MRS signals. The following concentration changes were observed; a decrease in glutamate and (phospho)choline for all the models; an increase in glutamine in the LIS and UREASE model but a decrease in the MSO model; a marked increase in lactate in the LIS and UREASE group; a tendency to a decrease in N-acetylaspartate in all the models. These changes agree well with the changes in the post-mortem biochemically determined cerebral cortex glutamine and glutamate concentrations. Estimated absolute 1H MRS metabolite concentrations agree well with those obtained by other techniques; cerebral cortex glutamate, however, is underestimated by about 35% by NMR. The present data support the hypothesis that hyperammonemia is associated with a decreased availability of glutamate for neurotransmission.

Ammonia↗
PubMed1991

What the clinician can learn from MR glutamine/glutamate assays.

At present in vivo NMR spectroscopic studies of brain glutamate and glutamine concentrations relative to encephalopathy have mainly been performed in hepatic encephalopathy (HE). In vivo proton NMR studies were performed in rats with hyperammonemia and acute HE due to acute liver ischemia as well as in rats with hyperammonemia due to either repeated urease i.p. injection or i.p. administration of methionine sulfoximine, a well known inhibitor of glutamine synthetase. In man, in vivo proton NMR is described in patients with chronic liver disease: cirrhosis of different etiology and associated with different degrees of HE. In the experimental models proton NMR spectroscopy of the cerebral cortex revealed an increase in glutamine concentration, a decrease in glutamate concentration and a decrease in phosphocholine compounds. In humans no clear distinction between cerebral cortex glutamate and glutamine concentration could be made by in vivo 1H NMR spectroscopy. However, the combined glutamate/glutamine peak increased in a way compatible with an increased cerebral cortex glutamine concentration during chronic HE. In the cirrhotic patients too a decrease in cerebral cortex phosphocholine compounds was observed, the explanation of which is unclear. Both the experimental work and the clinical observations support the hypothesis that impairment of the glutamate/glutamine cycle between astrocytes and neurons plays a role in the pathogenesis of hepatic encephalopathy.

Animals↗
PubMed1991

Liver regeneration after partial hepatectomy in rats with defective bilirubin conjugation or biliary excretion.

The role of conjugated bilirubin in liver regeneration after partial hepatectomy (PH) was studied in Gunn rats, in transport-mutant (TR-) rats, and in rats with extrahepatic biliary obstruction. Ornithine decarboxylase (ODC) and thymidine kinase (TK) activities in liver homogenates and immunohistochemistry of in vivo bromodeoxyuridine (BrdU) incorporation in hepatic DNA were followed as regeneration parameters at 24 and 48 hr after PH. The results relative to TK activity and BrdU incorporation were consistent with significantly delayed hepatic DNA synthesis in Gunn rats in comparison to control Wistar and TR- rats. This delay in DNA synthesis was not reflected in the hepatic ODC activity. After one week of complete common bile duct obstruction (CBO), an increased TK activity and BrdU incorporation was seen. PH following CBO resulted in a further increase in ODC activity and BrdU incorporation. TK activity did not change, however. These data relative to the regulation of hepatic DNA synthesis after PH in Gunn rats and in rats with extrahepatic biliary obstruction suggest a possible stimulatory role for conjugated bilirubin in hepatic regeneration; however, the normal hepatic DNA synthesis in TR- rats studied before PH and the subnormal DNA synthesis seen 24 hr after PH in TR- rats and in rats with CBO indicate that conjugated bilirubin does not stimulate hepatic DNA synthesis.

Animals↗
PubMed1991

The effects of benzodiazepine-receptor antagonists and partial inverse agonists on acute hepatic encephalopathy in the rat.

Two benzodiazepine-receptor partial inverse agonists (Ro 15-4513, Ro 15-3505) and one benzodiazepine-receptor antagonist (flumazenil) were administered to rats with hepatic encephalopathy due to acute liver ischemia. Significant improvement (P less than 0.002) of both the clinical grade of hepatic encephalopathy and the electroencephalographic abnormalities was observed after administration of the benzodiazepine-receptor partial inverse agonists: comatose rats with no spontaneous righting reflex regained consciousness immediately after injection of the drug. Only slight improvement in clinical hepatic encephalopathy grade was seen after administration of 25 mg/kg of flumazenil. The present data strongly support a role of increased gamma-aminobutyric acid-ergic tone in the pathogenesis of acute hepatic encephalopathy and provide a rationale for trials of benzodiazepine-receptor partial inverse agonists to restore consciousness in hepatic encephalopathy in humans in the near future.

Animals↗
PubMed1991

Prevalence of anti-HCV antibodies confirmed by recombinant immunoblot in different population subsets in The Netherlands.

The prevalence of antibodies to hepatitis C virus (anti-HCV) was studied in various population subsets in the Netherlands with anti-HCV C100 enzyme linked immunosorbent assay (ELISA), and confirmed with recombinant immunoblot assay (RIBA). Anti-HCV C100 ELISA positivity and RIBA positivity were found in 39 (0.7%) and 5 (0.1%) of 5,434 blood donors from Amsterdam; 25 (5%) and 2 (0.4%) of 481 blood donors from Surinam (South America); 19 (9%) and 2 (1%) of 213 multitransfused patients; 28 (4%) and 15 (2%) of 633 hemodialysis patients; 179 (80%) and 150 (67%) of 225 hemophilia A and B patients; 8 (80%) and 4 (40%) of 10 intravenous drug abusers; 18 (15%) and 2 (2%) of 119 anti-HIV-positive homosexual men; 2 (2%) and none of 106 anti-HIV-negative homosexual men; 6 (32%) and 3 (16%) of 19 patients with acute hepatitis non-A, non-B (NANBH); 13 (65%) and 8 (40%) of 20 patients with chronic NANBH and/or cryptogenic cirrhosis; and 4 (40%) and 1 (10%) of 10 patients with idiopathic autoimmune chronic hepatitis. Among blood donors, a positive correlation between a history of jaundice after the age of 18 years and the presence of RIBA-confirmed anti-HCV antibodies was found. Among both blood donors and hemodialysis patients, a positive correlation of RIBA-confirmed anti-HCV positivity with elevated alanine aminotransferase levels, but not with the presence of anti-hepatitis B core antibodies was found.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1990

Methanethiol metabolism and its role in the pathogenesis of hepatic encephalopathy in rats and dogs.

The metabolism of methanethiol was studied in rats. Administration of a noncomatogenic dose of methanethiol through inspired air or injection into the upper colon resulted in an elevation of the concentrations of methanethiol mixed disulfides in serum (protein--S--S--CH3 and X--S--S--CH3, X yet unknown) and in urine (X--S--S--CH3). The concentrations of methanethiol mixed disulfides proved to be a relative measure of exposure to methanethiol. The levels of volatile sulfur compounds methanethiol, dimethylsulfide and dimethyldisulfide in the air expired by rats exposed to a noncomatogenic dose of methanethiol through the colon were also elevated. Rats with acute hepatic encephalopathy caused by liver ischemia also showed elevation of methanethiol mixed disulfide levels on challenge of methanethiol through the colon or inspired air, but to a significantly smaller extent than did the corresponding sham-operated rats. This suggests that the liver is at least partly responsible for formation of methanethiol mixed disulfides. No additional toxic effects were observed in the rats with ischemic livers on methanethiol exposition when compared with normal rats, suggesting that the liver does not play an essential role in methanethiol detoxification. Metabolism of methanethiol by blood to sulfate, for example, might be more important. In rats with acute hepatic encephalopathy caused by liver ischemia and in dogs suffering from hepatic encephalopathy resulting from chronic liver disease, large and significant increases in ammonia levels were measured. However, the mean levels of methanethiol mixed disulfides in rats and dogs with hepatic encephalopathy were not different from the mean normal levels in these animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗