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Yves Deugnier

Publications and source records attributed to Yves Deugnier.

27 records · Page 2Linked to original sources
PubMed2002

High vascular endothelial growth factor (VEGF) expression in chemically-induced hepatic microcancers in mice.

BACKGROUND/AIMS: In experimental carcinogenesis microcancers are defined as foci of altered hepatocytes showing vascular invasion. Vascular endothelial growth factor (VEGF) could be involved in such vascular extension. The aim of our study was to evaluate the in situ VEGF expression in chemically-induced microcancers. METHODS: Fourteen C3H male mice were submitted to a diethyl nitrosamine-induced carcinogenesis. Iron-dextran overload was performed in parallel in order to localize all iron-negative lesions. Animals were sacrificed at 24, 39 and 52 weeks of age. Liver sections were histologically (haematoxylin eosin safron (HES), Orcein and Perls' stains) and immunohistochemically (VEGF) studied. RESULTS: Microcancers represented 8% of 424 lesions that we found as compared to foci (35%), adenomas (51%), and overt cancers (6%). VEGF hepatocyte positivity was found in 74% of lesions, with a more frequent, intense, and homogenous expression in microcancers than in other lesions, especially at 24 and 39 weeks. CONCLUSIONS: In our model, we found a high VEGF expression in microcancer exhibiting progression in vessels. Early overexpression of VEGF, formerly named vascular permeating factor, could act as a permeability factor and favors the development of vascular breakdown in microcancers.

Alkylating Agents↗
PubMed2002

Iron overload disorders.

Because hepatic siderosis is a frequent finding, there is a risk of making it trite when elaborating the pathology report. Iron is increasingly considered an important cofactor of morbidity. Its finding in hepatic cells must be recognized, indicated, qualified, quantified, and interpreted. A systematic reasoning based on a strict semiological approach allows for guiding the clinician. Iron overload syndromes do not amount to genetic hemochromatosis only.

Ceruloplasmin↗
PubMed2002

Gender-specific phenotypic expression and screening strategies in C282Y-linked haemochromatosis: a study of 9396 French people.

Most features of C282Y-linked haemochromatosis support the implementation of population screening of the disorder in Caucasians. However, the penetrance of C282Y homozygosity is poorly documented and the strategy for population screening remains debated. Nine thousand three hundred and ninety-six subjects (3367 men, aged 25-40 years, and 6029 women, aged 35-50 years), attending three Health Appraisal Centres, were genotyped and assessed with respect to clinical and biochemical signs of haemochromatosis. Discriminant, logistic regression and graphic analysis were used to predict homozygosity. Results were validated in 135 homozygotes detected through other family and population studies. Fifty-four subjects (10 men and 44 women) were homozygous for C282Y. All men had abnormal iron status and most had mild clinical symptoms compatible with haemochromatosis. Identification of all homozygous men required a transferrin saturation (TS) threshold of 50% in the study group (90% specificity) and of 40% in the validation group. Homozygous women differed clinically from non-homozygotes for the presence of distal arthralgias only (18%vs 6%, P < 0.03). Thirteen (29%) were iron-deficient (serum ferritin < 13 micro g/l) and undetectable by biochemical tests. Although the population studied was not fully representative of the general population, our data strongly suggests that, in young men, large-scale screening for C282Y homozygosity is justified and can be achieved by using TS prescreening. However, in premenopausal women, large-scale screening remains to be justified with respect to the natural history of haemochromatosis and should be directly genotypic.

Adult↗
PubMed2002

Noninvasive prediction of cirrhosis in C282Y-linked hemochromatosis.

The aim of the present study was to examine the predictive accuracy of noninvasive clinical and biochemical variables associated with cirrhosis among patients with C282Y homozygous hemochromatosis. Sixteen clinical and laboratory variables were recorded at the time of diagnosis in 193 Canadian C282Y homozygous patients. All patients underwent percutaneous liver biopsy and 27 (14%) had biopsy specimen-proven cirrhosis. Prediction of cirrhosis was assessed first by univariate regression analysis. Variables significantly related to cirrhosis were then evaluated by stepwise linear multivariate regression. Receiver operating characteristic curve analysis of the most informative variables from multivariate analysis was then used to devise a clinically applicable index for the noninvasive prediction of cirrhosis. This index was then validated in 162 C282Y homozygous patients in France. Ferritin, blood platelets, and aspartate transaminase (AST) level were selected for the clinical index. The combination of ferritin levels of 1,000 microg/L or greater, platelet levels of 200 x 10(9)/L or less, and AST levels above the upper limit of normal led to a correct diagnosis of cirrhosis in 77% of Canadian patients. In the French patients, this led to a correct diagnosis of cirrhosis in 90%. In conclusion, in C282Y homozygous patients, a combination of easily measured laboratory variables (ferritin, platelets, AST) can be used to make the diagnosis of cirrhosis in approximately 81% of cases, reducing the need for liver biopsy.

Adult↗
PubMed2002

A nomogram to predict C282Y hemochromatosis.

Genetic testing of hemochromatosis has not been widely used as a diagnostic test because of unawareness of its existence and concerns about genetic discrimination. We developed a nomogram for the prediction of C282Y homozygotes for hemochromatosis from transferrin saturation and ferritin using Bayes theorem. The results of transferrin saturation and C282Y genotyping were available for 8,572 participants (5,042 men, and 3,530 women). The study group included patients in population-screening projects, referred cases, and family members. Likelihood ratios were calculated for transferrin saturation in predicting C282Y homozygotes. Pretest probabilities were estimated on the basis of serum ferritin concentration, and a predictive nomogram for men and women was created with the use of Bayes' theorem. In the highest-risk region of the nomogram in men, the probability of C282Y hemochromatosis was 89.7% (95% confidence interval = 85.1-94.3); in the lowest-risk zone it was 1.1% (0.4-1.9). The corresponding regions in women were 88.9% in the high zone (95% confidence interval = 77.0-100.0) and 6.5% in the lowest (95% confidence interval = 4.9-8.1). This approach allows the clinician to predict the probability of a patient's being a C282Y homozygote over a wide range of ferritin and transferrin saturation values instead of above a particular threshold.

Amino Acid Substitution↗
PubMed2002

Increased body iron stores in elite road cyclists.

BACKGROUND: One third of French elite road cyclists were found to have hyperferritinemia on antidoping control tests performed during the Tour de France in 1998. PURPOSE: This study was undertaken to determine whether hyperferritinemia corresponded to elevated body iron stores or not and, affirmatively, what were its mechanism, its clinical consequences, and its spontaneous course. METHODS: 83 elite road male cyclists presenting with hyperferritinemia, defined as serum ferritin level greater than 300 microg.L-1, were studied with respect to consumption of iron and other drugs, serum iron tests, HFE mutations, and hepatic iron concentration (HIC; N < 35 micromol.g-1 dry weight). RESULTS: All cyclists were asymptomatic and had normal physical and cardiac examination. Their median (range) serum ferritin, serum iron, and transferrin saturation levels were 504 microg.L-1 (306-1671), 20 micromol.L-1 (8.5-36.3), and 39% (20-76), respectively. HIC was increased in 24/27 up to 187 micromol.g-1. Allelic frequency of the H63D mutation was increased in cyclists when compared to controls (P = 0.04). However, iron tests did not differ according to HFE genotypes. Most cyclists (89%) had been supplemented with iron. The median iron supplementation was 25.5 g (range: 1.4-336) and correlated well (P = 0.002) with serum ferritin. Evolution of serum ferritin levels did not differ whether cyclists had been continuing iron supplementation or not. CONCLUSION: Hyperferritinemia in elite road cyclists accounted for increased body iron stores caused by and persisting after cessation of excessive iron supplementation. Even when mild, iron excess may expose to long-term complications and should be removed, at least at the time when professional cyclists retire. To prevent iatrogenic iron overload, supplementation with iron must be done according to serum ferritin follow-up and not either blindly or on the basis of serum iron determination only.

Adult↗
PubMed2002

[Non alcoholic steatohepatitis: a multifactorial, frequent, paucysymptomatic liver disease with a fibrotic outcome].

BACKGROUND: The aim of this study was to evaluate the morphological, clinical and biochemical characteristics of non alcoholic steatohepatitis to understand its pathogenesis. PATIENTS AND METHODS: From January 1993 to June 2000, 44 patients were selected on histological criteria. Alcohol intake, blood pressure, weight, glycaemia, lipid, immune, iron profiles hemochromatosis (HFE) gene mutations were analyzed. Patients were re-examined thereafter or in June 2000. RESULTS: Twenty one women and 10 men were included (mean age=54). Nineteen patients were asymptomatic (61.3%). Patients often presented with an increase in alanine aminotransferase. This was correlated with steatosis (P=0.008). Hypertension, excess weight, abnormal serum glucose levels and dyslipidaemia were respectively observed in 10 (32.2%), 24 (77.4%), 16 (51.6%) and 18 (58.1%) patients. Thirteen of these patients (41.9%) presented abnormal autoantibodies titers without autoimmune hepatitis; 18 (58.1%) presented an iron overload. A mutation of the HFE gene was detected in 14 of 25 patients (51.6%). Liver iron concentrations were not correlated to the extent of fibrosis extension or with mutations. CONCLUSION: Increased alanine aminotransferase levels usually revealed non alcoholic steatohepatitis. A high prevalence of autoantibodies, iron overload and mutation of the HFE gene were detected. Non alcoholic steatohepatitis should be diagnosed because it can be associated with cirrhosis.

Alanine Transaminase↗
PubMed2000

Clinical Consequences of New Insights in the Pathophysiology of Disorders of Iron and Heme Metabolism.

This review examines the clinical consequences for the practicing hematologist of remarkable new insights into the pathophysiology of disorders of iron and heme metabolism. The familiar proteins of iron transport and storage-transferrin, transferrin receptor, and ferritin-have recently been joined by a host of newly identified proteins that play critical roles in the molecular management of iron homeostasis. These include the iron-regulatory proteins (IRP-1 and -2), HFE (the product of the HFE gene that is mutated in most patients with hereditary hemochromatosis), the divalent metal transporter (DMT1), transferrin receptor 2, ceruloplasmin, hephaestin, the "Stimulator of Fe Transport" (SFT), frataxin, ferroportin 1 and others. The growing appreciation of the roles of these newly identified proteins has fundamental implications for the clinical understanding and laboratory evaluation of iron metabolism and its alterations with iron deficiency, iron overload, infection, and inflammation. In Section I, Dr. Brittenham summarizes current concepts of body and cellular iron supply and storage and reviews new means of evaluating the full range of body iron stores including genetic testing for mutations in the HFE gene, measurement of serum ferritin iron, transferrin receptor, reticulocyte hemoglobin content and measurement of tissue iron by computed tomography, magnetic resonance imaging and magnetic susceptometry using superconducting quantum interference device (SQUID) instrumentation. In Section II, Dr. Weiss discusses the improved understanding of the molecular mechanisms underlying alterations in iron metabolism due to chronic inflammatory disorders. The anemia of chronic disorders remains the most common form of anemia found in hospitalized patients. The network of interactions that link iron metabolism with cellular immune effector functions involving pro- and anti-inflammatory cytokines, acute phase proteins and oxidative stress is described, with an emphasis on the implications for clinical practice. In Section III, Dr. Brissot and colleagues discuss how the diagnosis and management of hereditary hemochromatosis has changed following the identification of the gene, HFE, that is mutated in most patients with hereditary hemochromatosis, and the subsequent development of a genotypic test. The current understanding of the molecular effects of HFE mutations, the usefulness of genotypic and phenotypic approaches to screening and diagnosis and recommendations for management are summarized.

Journal Article↗