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Biomedical subjects

Y Deugnier

Publications and source records attributed to Y Deugnier.

At least 91 records · Page 5Linked to original sources

[Histochemical detection of hepatic iron. A comparative study of four stains].

Due to its specificity and easiness, Perls' stain is widely used in the histochemical assessment of liver iron content. However, it can underestimate slight iron overload, which can hamper screening for genetic hemochromatosis, especially in young people. The aim for the present study was to compare Perls' stain to three other specific iron stains (Tirmann-Schmeltzer (TRM); Hukill and Putt (HPT); Perls with Diaminobenzidine (DAB)), biochemical liver iron concentration (LIC) being used as the reference. 1) There is a significant difference between number of stained cells with TRM or DAB, compare with Perls' stain (p < 0.05). 2) Correlation (r) between histological assessment (T) and LIC was 0.39 for Perls' stain, 0.64 for TRM 0.53 for HPT and 0.64 for DAB. These data suggest that Perls' stain is not the most sensitive method for the assessment of slight iron overload. Tirmann-Schmeltzer's stain and Perls plus dAB should be preferred, especially in the screening of early liver siderosis.

Histocytochemistry↗

Acute infusions of bile salts increase biliary excretion of iron in iron-loaded rats.

The mechanisms of biliary excretion of iron are not well known. The aim of this study was to examine the effect of choleresis induced by several agents on biliary iron excretion in iron-loaded rats. Iron overload was obtained with a diet supplemented by 3% iron carbonyl during a 6-week period. Bile was collected with an external bile fistula. Biliary iron concentration was measured by atomic absorption spectrophotometry, and hepatic iron concentration was measured by a chemical method. Compared with controls, iron overload resulted in a 14-fold increase in hepatic iron concentration but only a 3.9-fold increase in biliary iron output. In iron-loaded rats, taurocholate infusion caused a 1.8-fold significant increase in biliary iron output. Dehydrocholate, given at the same dose, induced a significant but less pronounced (1.3-fold) increase in biliary iron output in spite of a higher bile flow. Taurochenodeoxycholate, tauroursodeoxycholate, and tauro-7-ketolithocholate induced an increase in biliary iron output similar to that observed with taurocholate. The canalicular bile salt-independent choleretic dihydroxydibutyl ether caused a significant but less pronounced increase in biliary iron output (1.4-fold). These results confirm that in iron-loaded rats biliary iron excretion is increased much less than hepatic iron concentration. They show that in iron loaded rats (a) bile salts can increase biliary iron secretion, and (b) this increase is related in part to choleresis and in part to bile salts themselves. This increase may be related to an interaction of iron with bile salt monomers and/or micelles.

Animals↗

Hepatitis B virus infection markers in genetic haemochromatosis. A study of 272 patients.

Serum hepatitis B virus (HBV) infection markers were studied in 272 patients with homozygous genetic haemochromatosis complicated (n = 33) or not (n = 239) with primary liver cancer (PLC). Controls consisted of 255 029 healthy blood donors from whom age- and sex-matched control groups were extracted for statistical evaluation using the Fisher exact test. In blood donors, HBsAg was positive in 0.075% of males and 0.04% of females. This population was not screened for anti-Hbs. Anti-Hbc alone (without HBsAg) was present in 3.7% of men and 1.8% of women. In patients with genetic haemochromatosis without liver cancer (183 males, 45.6 +/- 11.3 yrs and 56 women, 48 +/- 12.4 yrs), HBsAg was found in 1.1% of men and in none of the women. Anti-HBs was present in 7.3% of males and 1.8% of females. Anti-HBc alone was found in 13% of males (p less than 0.005 vs. controls) and 2.1% of females. From male patients with primary liver cancer complicating genetic haemochromatosis (32 males, 61.7 +/- 6.8 yrs and one female), 6.2% were HBsAg positive, 3.4% were anti-HBs positive and 16.6% anti-HBc positive (p = 0.05 vs. controls). No serum HBV marker was found in the woman. In conclusion, the prevalence of HBV infection markers--especially anti-HBc--is significantly increased in patients with genetic haemochromatosis complicated or not with primary liver cancer.

Adult↗

Short-term prednisolone followed by recombinant human alpha-interferon alone or combined with adenine-arabinoside in chronic hepatitis B. A prospective and randomized trial.

Twenty-nine patients with chronic hepatitis B, presenting both hepatitis B surface antigen and hepatitis B virus deoxyribonucleic acid in serum, were studied in a randomized trial treatment consisting of oral prednisolone for 28 days followed 14 days after steroid withdrawal, by either a 55 s.c. injection course of 5 M unit recombinant human alpha-interferon (group 1, 14 patients) or by adenine-arabinoside (for 21 days) combined from the fourteenth day on with the same 55 s.c. injection schedule of interferon (IFN) (group 2, 15 cases). The two groups were well matched with respect to demographic, biochemical, virological and histologic features. Significant side-effects leading to premature discontinuation of interferon were observed in only four cases in group 2 and were always reversible. Efficacy was judged on a mean follow-up period of 17 months. For the whole population, 17 patients (59%) exhibited a sustained serum hepatitis B virus deoxyribonucleic acid disappearance which corresponded to a marked improvement in liver function as demonstrated by a quasi-normalization of their serum transaminase values (ALT with n less than 22 UI/l: 23 +/- 24 vs. 139 +/- 115 before treatment; P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Increase in glycosylated and nonglycosylated serum ferritin in chronic alcoholism and their evolution during alcohol withdrawal.

Increase in serum ferritin, which occurs in 40 to 70% of chronic alcoholics, remains poorly understood. We tested the hypothesis which links hyperferritinemia in chronic alcoholism not only to ferritin release from damaged liver cells, but also to increased ferritin secretion. Fifty-eight chronic alcoholic patients hospitalized for alcohol withdrawal were subdivided into three groups according to liver damage. Their serum levels of ferritin and ferritin bound to concanavalin A (ferritin Con A, which represents glycosylated, i.e., secreted ferritin) were measured serially on days 1, 7, and 11 of withdrawal and compared with a control group. The results were: (1) Total serum ferritin increased in alcoholics. Both free and Con A ferritins increased in equal proportions, the ferritin Con A to total ferritin ratio remaining unchanged. The increase was dependent on liver disease, as both free and Con A ferritins increased significantly with the severity of liver illness. Serum ferritin levels were related to iron status: it correlated with hepatic iron concentration (obtained in 19 patients); however, high ferritin values were not related to the degree of iron overload, which remained low. Finally, there was no correlation between serum ferritin and the average of alcohol consumption. (2) Both free and Con A ferritin decreased by about 40% during alcohol withdrawal. In conclusion, we have demonstrated that (1) total serum ferritin is increased in chronic alcoholism and (2) that this ferritin increase is due in part to an increase in ferritin Con A, proof of the induction of ferritin secretion by alcohol in humans.

Adult↗

Malignant melanoma of the hepatic and common bile ducts. A case report and review of the literature.

We report a case of malignant melanotic melanoma involving the extrahepatic biliary tract in a 34-year-old white woman. The diagnosis was established using conventional light microscopic examination and immunohistochemical stains. The clinical absence of any primary cutaneous or visceral melanoma suggests that the tumor arose primarily from the biliary tract. To our knowledge, only two previous cases of malignant melanoma of the common bile duct have been reported in the literature.

Adult↗

[Indications and results of hepatic transplantation for cancer].

From April 1978 to 1st October 1990, 19 patients underwent liver transplantation for primary or secondary cancer of the liver. Eleven patients were transplanted for hepatocellular carcinoma secondary to cirrhosis, generally alcoholic (9 cases), hepatitis B (1 case) or secondary to haemochromatosis (1 cas). Three patients developed hepatocellular carcinoma in a normal liver, including one fibrolamellar cancer and three a proximal bile duct cancer. Lastly, two patients received a graft for secondary cancer from a colonic adenocarcinoma and a carcinoid tumour of the right colon. The operative mortality was nil for the transplantations for cancer in a normal liver, but there were 4 deaths out of the 11 cases of cancer secondary to cirrhosis. The actuarial survival of the overall series was 55% at 1 year and 31% at 2 years. The poorest survival was observed for cancers in a normal liver, with the exception of the fibrolamellar cancer in which recurrence was delayed. The longest survival was observed for cancers secondary to cirrhosis. At three years, the results of liver transplantation were equal to those of hepatic resections with a survival of 37%, despite the fact that the transplantation was generally performed for very large tumours.

Adult↗

Reversibility of hepatic fibrosis in experimentally induced cholestasis in rat.

The reversibility of hepatic fibrosis was investigated in an experimental model of extrahepatic cholestasis in the rat after common bile duct ligation for 2 weeks, followed by bilioduodenal anastomosis for 3 weeks. Bile duct ligation resulted in a transitory marked elevation in the serum concentration of 5'-nucleotidase, alkaline phosphatase, and bilirubin during the first 3 days. Then these levels decreased to threefold, twofold, and 100-fold the normal values, respectively, during the following 4 weeks. Histologic examination of the liver disclosed extensive bile duct proliferation and the formation of periportal fibrosis, with only slight inflammation and necrosis. The distribution of the major components of the hepatic extracellular matrix was analyzed 2 weeks after bile duct ligation, using the indirect immunoperoxidase method. Fibrous septa were found to be strongly stained for collagens I, pro-III, III and IV, fibronectin, and laminin. The most intense staining was found in enlarged periportal areas, collagen IV and laminin being particularly abundant around newly formed bile ducts. These changes paralleled high steady-state levels of alpha 1(I) and alpha 1(IV) collagen and B2 chain laminin mRNAs. Relief of the obstruction for 2 weeks resulted in a shift in the serum concentration of 5'-nucleotidase, alkaline phosphatase, and bilirubin toward normal values. A dramatic resorption of bile duct proliferations and periportal fibrosis were observed. Three weeks after bile duct repermeabilization, immunohistochemical study showed that the pattern of distribution of extracellular matrix components was almost normal, except for collagen IV, which remained abundant in the sinusoids when compared with the normal liver. In parallel, the steady-state B2-chain laminin mRNA level became lower than in cholestatic livers, whereas alpha 1(I) and alpha 1(IV) mRNAs were almost undetectable. These results show that hepatic fibrosis induced by experimental extrahepatic cholestasis in rat disappears in less than 3 weeks after relief of bile duct obstruction, suggesting that an active degradation of matrix protein occurs, except for collagen IV in the sinusoid.

Animals↗

Biochemical aspects of alpha-L-fucosidase in hepatocellular carcinoma.

Biochemical characteristics of alpha-L-fucosidase (alpha-L-fucoside hydrolase, EC 3.2.1.51) were studied in tumorous and nontumorous human hepatocellular carcinoma (n = 14). Five parameters were studied: (i) specific activity, (ii) thermostability, (iii) enzyme affinity for an artificial substrate (Km), (iv) isoenzyme patterns of the glycosidase before and after neuraminidase treatment and (v) pH influence on enzyme activity. The specific activity of alpha-L-fucosidase was significantly decreased in tumoral liver when compared to nontumoral liver. The curve of pH activity constantly showed a broad optimum centered near pH 5, whereas two optima were always observed in nontumoral areas. In contrast, there was no modification of the thermostability, the substrate affinity and the isoenzyme patterns of alpha-L-fucosidase in hepatocellular carcinoma.

Adenoma↗

Evaluation of computed tomography in the assessment of liver iron overload. A study of 46 cases of idiopathic hemochromatosis.

The aim of the present study was to evaluate the effectiveness of single-energy computed tomography in determining iron overload in idiopathic hemochromatosis, with special reference to slightly overloaded cases. Liver attenuation was determined in 100 patients (46 cases of idiopathic hemochromatosis, 32 cases of chronic liver disease, and 22 normal controls). The iron load was determined for the first two groups by biochemical determination of liver iron concentration (performed in all but 12 subjects in the chronic liver disease group) and hepatic histologic grading. The main results for liver attenuation (upper normal limit, 72 Hounsfield units) showed that despite a high specificity (0.96), this parameter was of low sensitivity (0.63). Although mean liver attenuation in idiopathic hemochromatosis (77 +/- 14) was significantly higher than in chronic liver diseases (53 +/- 17; p less than 10(-4) and normal controls (66 +/- 3; p less than 10(-3], and despite an overall good correlation between liver attenuation and liver iron concentration (r = 0.72; p less than 10(-3], liver attenuation was unable to detect moderate iron overload. Fourteen of 18 patients with a liver iron concentration of less than 150 mumol/g dry liver wt had liver attenuation values of less than 72. Moreover, 3 of 18 subjects with a liver iron concentration of greater than 150 had a liver attenuation of less than 72. Of these 17 false-negatives, only 7 could be attributed to associated steatosis. On the whole, single-energy computed tomography, when used on a routine basis for diagnosing iron overload, is of limited clinical value in idiopathic hemochromatosis due to its poor sensitivity. Hepatic histologic examination together with biochemical determination remains the most accurate means to assess liver iron.

Fatty Liver, Alcoholic↗