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Biomedical subjects

M Bourel

Publications and source records attributed to M Bourel.

At least 37 records · Page 2Linked to original sources

[Iron overload of the liver and protein synthesis. Progress made through experimental models].

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.

Animals↗

[Hemorheological disorders linked to alcoholism].

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.

Adenosine Triphosphate↗

A study of 609 HLA haplotypes marking for the hemochromatosis gene: (1) mapping of the gene near the HLA-A locus and characters required to define a heterozygous population and (2) hypothesis concerning the underlying cause of hemochromatosis-HLA association.

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.

Alleles↗

The treatment of refractory ascites by the LeVeen shunt. A multi-centre controlled trial (57 patients).

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.

Ascites↗

[Idiopathic hemochromatosis. Immunogenetics and diagnosis. Prevention by HLA genotypes].

Idiopathic hemochromatosis is an hereditary iron overload. The study of HLA types demonstrated clearly the linkage with HLA system. The preferential correlation established with A3 (72%) but other alleles were linked: B7, B14. HLA alleles were only the markers of hemochromatosis allele (H) and were not implicated in other iron overload. Family studied, defined two linked haplotypes: A3, Cw7, B7, Bw6, BfS, DR2, GLO1 et A3, Cw8, B14, Cw6, BfF, DRw6, GLO2. Demonstration of the recessive mode of inheritance was established by family studies. The affected siblings had the same HLA haplotype that the proband and homozygous or heterozygous expressed state was assessed in siblings. The HLA family types allowed to detect in 147 families 88 potential diseased patients among of them 73% had early blood-drawing.

Alleles↗

Diagnostic value of erythrocyte-free polyamines and histaminemia in malignant hepatic tumors and in liver cirrhosis.

The present study tries to evaluate the diagnosit value in malignant hepatic tumors of polyamines, of which the relationship with cellular kinetics is known, and histamine, of which catabolism follows a similar pathway. One hundred and fifty six patients were studied: 53 with malignant liver tumors (27 primary, 26 metastatic) and 103 with non-tumoral liver diseases of which 65 were cirrhotic and 38 non-cirrhotic. Erythrocyte polyamines (spermidine and spermine) and histamine levels were assayed. The results indicate the following. 1. Polyamine levels were significantly increased (a) in cirrhotic patients, not only when compared with controls (p less than 10(-8)), but also when compared with the non-cirrhotic patients (p less than 10(-7)); (b) in primary malignant hepatic tumors (p less than 10(-3)). 2. Histamine was significantly increased (a) in the non-tumoral liver diseases (p less than 10(-4)), but with no difference between cirrhotic and non-cirrhotic patients; (b) in the secondary malignant tumor patients, histamine levels were lower than in primary tumor patients (p less than 0.04). 3. There was no correlation, in all groups studied, between polyamine and histamine levels. These results suggest the following practical implications. 1. For non-tumor liver diseases, appreciably increased polyamine levels may represent a further argument favoring a cirrhotic condition. 2. In diagnosing hepatic scintigraphic defects, increased polyamine levels would suggest a primary malignant hepatic tumor; low histamine levels are more in favor of a secondary malignant hepatic process.

Adult↗

Iron overload of the liver in the baboon. An ultrastructural study.

Liver biopsies from 4 baboons taken during 15 months of iron-polymaltose injections, were compared with specimens from 2 controls. A morphometric method was used to assess ferritin concentration in various cells. Initially, ferritin and siderosomes were conspicuous in reticuloendothelial cells but rare in hepatocytes. Unusual findings included intranuclear ferritin and coalesced ferritin within bile canaliculi. With advancing overload, ferritin and hemosiderin increased not only in sinusoidal cells, but also in hepatocytes, with concomitant elevation of transaminases. The hepatocytes now showed evidence of damage and excessive collagen was present mainly around portal spaces. A year after cessation of iron injections, hepatocyte ultrastructure was near normal while sinusoidal cells were still heavily overloaded. The baboon appeared to be a useful model for the study of iron overload. Although in this study most of the damage was reversible, it is suspected that more prolonged overload, a different route of administration or other, more toxic iron compounds, may lead to cirrhosis similar to that of the iron-loading anemias.

Animals↗

[Value of ultrasound-guided cytopuncture in the diagnosis of tumors in cirrhosis. Study of 29 cases].

Ultrasonically guided fine needle aspiration biopsy is known to be of great value in the diagnosis of malignant liver disease, with an overall accuracy rate of 73-94 p. 100. However, investigators have essentially reported cases of liver metastases. In this report, we examined the diagnostic value of this method in the specific case of tumors associated with cirrhosis. Twenty-seven patients with cirrhosis (20 alcoholic, 4 post-hepatitis, 3 hemochromatosis) with ultrasonically suspected hepatic malignancy were studied. They all presented severe blood clotting disturbances and/or ascites. At the end of the study, all patients had proven malignancy (by post mortem biopsy in 14 cases and/or serum AFP greater than 500 microgram/l in 17 cases). There were 25 primary and 2 metastatic tumors. Twenty-nine fine needle aspiration biopsies were performed under ultrasonic guidance. material suitable for cytologic evaluation was obtained in 25 patients. In 14 cases, a diagnosis of malignant involvement of the liver was firmly established by cytological examination; it was suggested in 4 other cases. Tumor typing was possible in 12 primary and 2 metastatic tumors, in agreement with the proven diagnosis. The present study shows that fine needle aspiration biopsy under ultrasound guidance is a safe and accurate diagnostic procedure in malignant liver disease associated with cirrhosis.

Adult↗

[Culture of human hepatocytes. Findings and outlook].

Human hepatocytes can be obtained by portal vein perfusion in the presence of collagenase. A co-culture system is suitable for maintenance of high levels of specific functions. The field for the use of cultured hepatocytes is now being enlarged. Pharmacological, carcinological and virological studies on a cellular scale are within the bounds of possibility.

Animals↗

Genetic analysis of idiopathic hemochromatosis using both qualitative (disease status) and quantitative (serum iron) information.

An ongoing family study of idiopathic hemochromatosis in Brittany, France, allowed us to investigate the segregation of this trait and its linkage and association to the HLA-A locus in 147 pedigrees, comprising 1,408 individuals with over 900 characterized for relevant biological parameters and typed for HLA. The joint consideration of affection status and serum iron concentration reveals no dominance effect on the latter trait and documents the increased information afforded by the consideration of a biological correlate of liability to affection for disease exhibiting incomplete penetrance. Our overall results are in general agreement with published results on a Utah family study.

Female↗