[Utilization of blood arising from therapeutic bleeding of genetic hemochromatosis].
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Biomedical subjects
Publications and source records attributed to M Bourel.
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The first part of this study deals with well known as well as new data on normal iron metabolism. The second part will concern Genetic Haemochromatosis, a recessively transmitted disease principally determined by a gene located on the sixth chromosome near the A locus of HLA system: phenotypic expression of the gene, clinical features, iron overload assessment, mechanism of iron toxicity, pathogenesis of iron overload. The third part considers iron overload secondary to anaemias, to chronic alcoholic liver diseases, to porphyria cutanea tarda, to chronic haemodialysis... and their relation to the Genetic Haemochromatosis. Beyond what is already well established still lies a large number of questions with answers, at this stage, uncertain or incomplete.
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.
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Medicine and archaeology are human sciences: their diagnostic claim consists of establishing the link between the singular case and the general model. Comparing and contrasting the two processes is not limited to a game of "similarities-differences". It makes possible a finer analysis of different methods of data collection, either with or without the help of instruments, and a comparison of different ways of handling and classifying symptoms observed and documentary evidence gathered. It shows that archaeology, in contrast to medicine (with physiology and health), has as a discipline, no real precisely defined reference. It is suggested that it is in the interest of medicine and archaeology to compare their own working methods...and their imperfections.
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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.
Cocultured adult rat hepatocytes and a human hepatoma cell line (HepG2) were maintained in an arginine-free medium with or without ornithine alpha-ketoglutarate. This drug increased greatly hepatocyte albumin secretion in both culture models. L-Ornithine was the component accounting for these effects since similar data were obtained by using this sole amino acid. Moreover, we observed that L-ornithine stimulation of albumin production was via polyamine synthesis. Since a correlated increase in albumin mRNA was observed, it may be postulated that ornithine alpha-ketoglutarate acts at a pretranslational level.
Two model systems are described for studying isolated hepatocytes in vitro: pure culture for short-term designs and co-culture with epithelial rat liver cells (for long duration procedures). Acute or chronic liver toxicities are discussed as well as indirect toxicities. Examples of species differences and genetic polymorphism are shown. Data on drugs used for the treatment of liver diseases are also presented.
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To understand the disturbances in protein synthesis observed during idiopathic hemochromatosis, various experimental models may be used. The aim of this research was to review the principal models employed and to demonstrate the value of hepatic tissue culture techniques in each. This method has already made it possible to explain several mechanisms involving the control of proteins in iron metabolism such as transferrin and ferritin. Tissue culture techniques of human hepatocytes should make it possible to elucidate the nature of the basic metabolic disorder in this disease responsible for the iron overload in the near future.
Haemorheological parameters were studied in 138 alcoholic subjects at different stages of the liver disease, compared to non alcoholic liver diseases and controls. Results showed 1) a decrease in whole blood filterability in the three groups of alcoholic patients associated with a decrease in erythrocyte ATP level, 2) an increase in blood and plasma viscosities, 3) morphological alterations visualized by scanning electron microscopy. These disturbances are correlated to the abnormalities of red cell membrane lipids composition: increase in cholesterol/phospholipids ratio, increase in saturated fatty acids and decrease in polyunsaturated fatty acids (arachidonic and linoleic acids). The responsibility of alcohol itself, in the genesis of these disturbances has been demonstrated by acute alcohol drinking experiments in healthy subjects.
We compared 609 haplotypes carrying the idiopathic hemochromatosis allele with 475 control haplotypes. Four haplotypes were more frequent in hemochromatosis: A3, B7 (actually A3, CW., B7, Bfs, DR2); A3, B14 (actually A3, CW., B14, BfF, DRW6); A11, B35; and A11, B5. The linkage disequilibrium for A3, B7 and A3, B14 (and probably also for A11, B5) was undeniably stronger in hemochromatosis than in controls. Two haplotypes--A3, B12 and A3, B15--were more frequent in hemochromatosis, without linkage disequilibrium. Four haplotypes in linkage disequilibrium in hemochromatosis--i.e., A2, B12; A1, B8; A9, B7; and A29, B12--were also found to have the same frequency and strength of linkage in controls. The dual observation (1) that haplotypes carrying A3 without either B7 or B14 were highly significantly more frequent in hemochromatosis than in controls and (2) that haplotypes carrying B7 or B14 but not A3 had the same frequency in hemochromatosis and controls led to the formal conclusion that only A3 is an independent marker for the hemochromatosis allele, B7 and B14 being involved only owing to the haplotypic mode of marking; the hemochromatosis allele can thus be mapped closer to locus A than to locus B. Our findings fit well with the hypothesis that the hemochromatosis mutation was a rare if not unique event that produced an ancestral HLA marking that was subsequently modified by recombinations and geographical scattering due to migrations.
A multi-centre random trial of 57 cases of alcoholic cirrhosis with refractory ascites was carried out; 29 patients received a LeVeen shunt and 28 were treated by conventional medical therapy. The effectiveness of the LeVeen shunt in reducing ascites was good in the first month, but was not different from conventional medical therapy by the end of one year. Complications were significantly more frequent in the surgical group. Of the 29 patients fitted with a LeVeen shunt, 25 developed one or more complications. Of the 28 patients in the medical control group, only 8 developed complications. The mortality rate of the two groups also differed significantly. Twelve patients in the surgical group (41%) died in the course of the first month against only 5 (18%) in the medical control group. By the end of one year, the mortality rate of the two groups was almost identical: 23 (79%) and 21 (75%) respectively. These observations confirm the poor prognosis for refractory ascites in cases of alcoholic cirrhosis and the inadvisability of attempting to treat it by implanting a LeVeen shunt.
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