[Behavioral activation programs: A tool for treating depression efficiently]. / L'activation comportementale : un outil simple et efficace dans le traitement de la dépression.

INTRODUCTION: Major depressive disorder (MDD) is a debilitating disorder, and its treatment often requires complex and costly psychological therapies. Behavioral activation (BA) is a simple, effective and affordable psychotherapy recommended in the treatment of MDD. OBJECTIVES: (i) Explain the theoretical basis of BA and its application in clinical practice. (ii) Review the randomized controlled trials examining BA as a treatment for MDD through a systematic search of the existing literature. METHODS: Medline and ClinicalTrials databases were searched with the following keywords: ("behavioral activation" OR "behavioural activation") AND ("therapy" OR "psychotherapy"). (i) Articles describing BA's theoretical foundations and principles of therapy were selected. (ii) Randomized controlled trials studying BA as a treatment for depression were selected according to the PRISMA criteria. RESULTS: (i) BA is a behavioral therapy that helps patients to increase their behaviors towards rewarding and/or pleasant activities, and to decrease avoidant behaviors maintaining negative affects by negative reinforcement. BA also tends to increase behaviors towards life-goals used as positive reinforcement contingencies. BA is a brief and cost effective therapy, which can be evaluated by specific psychometric scales. (ii) BA has a strong therapeutic effect in MDD as evaluated by several randomized controlled trials of good quality. CONCLUSION: BA is a simple, affordable and effective treatment for MDD. Data is insufficient to provide proof for the interest of using commitment to life-goals as reinforcement contingencies. Behavioral inhibition is encountered amongst several psychiatric disorders and more studies should be conducted to discuss its use for other diseases such as schizophrenia or anxiety disorders.

Functional near-infrared spectroscopy-based neurofeedback training targeting the dorsolateral prefrontal cortex induces changes in cortico-striatal functional connectivity.

Due to its central role in cognitive control, the dorso-lateral prefrontal cortex (dlPFC) has been the target of multiple brain modulation studies. In the context of the present pilot study, the dlPFC was the target of eight repeated neurofeedback (NF) sessions with functional near infrared spectroscopy (fNIRS) to assess the brain responses during NF and with functional and resting state magnetic resonance imaging (task-based fMRI and rsMRI) scanning. Fifteen healthy participants were recruited. Cognitive task fMRI and rsMRI were performed during the 1st and the 8th NF sessions. During NF, our data revealed an increased activity in the dlPFC as well as in brain regions involved in cognitive control and self-regulation learning (pFWE < 0.05). Changes in functional connectivity between the 1st and the 8th session revealed increased connectivity between the posterior cingulate cortex and the dlPFC, and between the posterior cingulate cortex and the dorsal striatum (pFWE < 0.05). Decreased left dlPFC-left insula connectivity was also observed. Behavioural results revealed a significant effect of hunger and motivation on the participant control feeling and a lower control feeling when participants did not identify an effective mental strategy, providing new insights on the effects of behavioural factors that may affect the NF learning.

A reappraisal of hepatic siderosis in patients with end-stage cirrhosis: practical implications for the diagnosis of hemochromatosis.

The aim of this study was to describe the histologic pattern of iron distribution in end-stage cirrhosis due to various causes and to test the reliability of the hepatic iron index (equal to hepatic iron concentration divided by age) in excluding or confirming associated hemochromatosis in such a condition. Large slices of the resected livers of 30 patients transplanted for alcoholic and/or viral end-stage cirrhosis were assessed histologically for iron distribution and biochemically for hepatic iron concentration in the least and the most iron-overloaded nodules of each case. HLA-A3 was used as the marker for the hemochromatosis gene in the population studied. Intranodular parenchymal siderosis was found in 23 cases (12 spotty, 11 diffuse) with diffuse intrabiliary iron deposits apparent in only two cases. Although in 14 patients the hepatic iron index was significantly high (> 1.9) so as to suggest hemochromatosis, these cases did not correspond to homozygous hemochromatosis with respect to the prevalence of HLA-A3 antigen. End-stage cirrhosis arising from different causes is frequently complicated by parenchymal siderosis that may mimic hemochromatosis, including a hepatic iron index greater than 1.9. The diagnosis of hemochromatosis in patients with end-stage cirrhosis, even those with a hepatic iron index greater than 1.9, should rely mainly on clinical and histologic data.

Histologic features of the liver in insulin resistance-associated iron overload. A study of 139 patients.

The aim of the present study was to describe histologic features of the liver in insulin resistance-associated hepatic iron overload (IR-HIO), defined as the association of metabolic disorders and hepatic iron overload. We included 139 patients in the study on the basis of one or more metabolic disorders and liver iron overload unrelated to usual causes. Liver biopsy specimens were reviewed, and histologic data were compared with those of a previously published, well-defined population with genetic hemochromatosis. Iron overload was characterized by a mixed pattern with iron deposits in hepatocytes and sinusoidal cells. Steatosis was present in 59.7% of patients with inflammation in 32.4% of cases. Periportal fibrosis was found in 67.4% of patients. These patients were older, had higher sinusoidal iron scores, and had a higher prevalence of steatosis and inflammation than patients without fibrosis. Iron overload in IR-HIO was histologically different from that in genetic hemochromatosis.

Inhibition of iron toxicity in rat hepatocyte cultures by pyoverdin Pa A, the peptidic fluorescent siderophore of Pseudomonas aeruginosa.

The effect of pyoverdin Pa A (an iron chelator isolated and purified from Pseudomonas aeruginosa ATCC 15692) was studied in rat hepatocyte cultures overloaded with iron. Iron overload was achieved by adding 80 mum-ferric nitrilotriacetate to the culture medium. One day after iron treatment, significant increases in aspartate aminotransferase and lactate dehydrogenase in the culture medium were measured; under similar conditions, albumin and transferrin secretions were decreased. Pyoverdin Pa A (100 mum in the medium) appeared to be as effective as desferrioxamine B (100 mum) in the protection of hepatocytes, cultured for 1 day in the presence of 80 mum-ferric nitrilotriacetate, against the toxic effects of iron overload. In rat hepatocytes cultured for 1 day in the presence of 1 mum Fe(55), pyoverdin Pa A or desferrioxamine B in the medium decreased iron uptake by the cells. When hepatocytes were cultured for 1 day in the presence of 1 mum-Fe(55) and then for a further day in the presence of 100 mum-Pa A or desferrioxamine but not iron, both chelators decreased the intracellular iron level and increased the concentration of the metal in the culture medium.

[Epidemiology of hepatitis C virus infection in 1,304 HCV positive patients: variations according to the origin of transmission and year of diagnosis]. / Epidémiologie de l'infection virale C chez 1,304 sujets VHC positif. Variations en fonction du mode de contamination et de l'année du diagnostic.

UNLABELLED: The evolution of epidemiological data on hepatitis C virus infection is poorly documented and thus the impact of screening is difficult to evaluate. AIM: To study epidemiological variations based on the origin of transmission and the year of diagnosis of hepatitis C virus infection. METHODS: The files of all 1304 patients seen in the hepatology unit of the Rennes University Hospital were analyzed (retrospectively before and prospectively after October 1995) in relation to epidemiological features. RESULTS: Despite widespread screening which is the source of 60% of the diagnoses, the total number of new cases of hepatitis C infection per year has not increased. Compared to patients diagnosed in the first years following the discovery of the virus, patients recently identified were younger (42 +/- 14 years) and frequently drug addicts (40%). Aminotransaminases were normal in 20% of cases. The frequency of cirrhosis has declined (17%). There has been a decrease in the proportion of patients who undergo liver biopsy (50%) and treatment with interferon (one third of patients). CONCLUSIONS: The impact of screening on the number of newly treated patients seems to be lower than previously predicted.

[Histochemical detection of hepatic iron. A comparative study of four stains]. / Détection histochimique du fer hépatique. Etude comparative de quatre colorations.

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.

[The diagnosis of hemochromatosis in the era of the gene]. / Le diagnostic de l'hémochromatose à l'heure du gène.

The discovery of the hemochromatosis gene has deeply changed and simplified the diagnosis of the disease. In a given individual, establishing the diagnosis relies, from now on, on a simple blood sample showing the couple: elevated transferrin saturation and homozygous C282Y mutation (= C282Y +/+). Liver biopsy should only be performed when iron overload is massive in order to detect cirrhosis (or bridging fibrosis), i.e. in a prognostic view. Practically, liver biopsy is confined to the following two situations: when the C282Y +/+ patient exhibits hepatomegaly and/or an increase in serum transaminases and/or a serum ferritin level above 1,000 micrograms/L; whenever, despite a strong bio-clinical suspicion of iron overload, genetic testing does not show the expected homozygosity for C282Y. At the family level, evaluating the risk for hemochromatosis is now "instantaneous" thanks to genetic testing. One must, however, keep in mind in interpreting the data of the family members that: clinical expression of the homozygous status is not constant; heterozygosity for C282Y does not per se lead to significant iron overload, but may constitute a co-factor exacerbating (or increasing the risk of) other hepatic or non hepatic diseases. Heterozygosity exposes also to the risk of homozygosity among the offspring; this knowledge of C282Y status must be balanced by the negative impact from the standpoint of possible societal genetic discrimination.

[Genetic hemochromatosis and the HFE gene]. / Hémochromatose génétique et gène HFE.

The discovery of the HFE gene has lead to considerable improvement in the understanding and the management of genetic hemochromatosis. More than 90% of well-defined patients are homozygous for the C282Y mutation, and genetic testing has become an important diagnostic tool. The significance of the other mutations in the HFE gene remain controversial: only C282Y/H63D compound heterozygotes could present with a phenotype compatible with hemochromatosis, but with a mild expression and a low penetrance. The link between iron overload and HFE mutation is explained by the interaction between HFE protein, beta-2-microglobulin and transferrin receptor, which is abolished by the C282Y mutation, but is not yet fully understood.

[Iron overload and public health]. / Surcharges en fer et santé publique.

Genetic hemochromatosis, due to its frequency (about 300,000 cases in France) and to its severity, must be considered as a public health burden. Its curability--insofar as its diagnosis has been made early--and the disposal of non invasive and reliable phenotypic (transferrin saturation) and genotypic (HFE C282Y mutation) tests make its diagnosis easy. Thus, diagnosis faced with early clinical and biological symptoms must be promulgated as screening in probant families. General screening is still hampered by ethical and socio-economic obstacles, but should be evaluated in large prospective studies. Otherwise, the recently described insulin resistance-associated liver iron overload syndrome might account for epidemiological associations that have been reported between increased body iron stores and cancerous, cardio-vascular and hepatic disorders. This might extend markedly the impact of iron overload in public health and lead to broaden screening and prevention to all iron overload conditions.

[Genetics and physiopathology of hemochromatosis]. / Génétique et physiopathologie de l'hémochromatose.

Thanks to the discovery of the HFE gene and of its mutations, it is now established that the most frequent form of hemochromatosis is related to homozygosity for the mutation C282Y, and that other types of hemochromatosis, unrelated to HFE mutations, do exist such as the juvenile hemochromatosis. From a pathophysiological standpoint, the C282Y mutation impairs HFE protein expression at the surface of the membrane and disturbs the cellular entry of iron (carried by circulating transferrin) into the cryptic duodenal cell. This, in turn, is likely to lead to an aberrant programmation of the degree of iron influx from the digestive lumen into the apical duodenal cells. The resulting hyperabsorption, which forms the basis of iron overload in hemochromatosis, is likely to implicate an overexpression of the transmembrane iron carrier DMT1. It is remarkable to observe that these major improvements in the knowledge of hemochomatosis have been accompanied by similar improvements in the understanding of normal iron metabolism.

[Diagnosis and treatment of genetic hemochromatosis]. / Diagnostic et traitement des hémochromatoses génétiques.

Genetic hemochromatosis is an autosomal recessive disease, characterized by an increased iron absorption, leading to progressive iron overload. The fully expressed phenotype comprises fatigue, skin pigmentation, liver disease with hepatomegaly, cirrhosis and hepatocellular carcinoma, and diabetes. Arthralgias are frequent, cardiopathy or impotence may occur. This presentation is now unfrequent with earlier diagnosis, and patients are often asymptomatic--with only biochemical expression--or pauci-symptomatic (mild fatigue, arthralgias or increased transaminases). Transferrin saturation is always increased. Serum ferritin is proportional to iron burden. Diagnosis is now easy, since most patients are homozygote for the C282Y mutation of the HFE gene. Liver biopsy can be useful to quantify iron overload and assess liver fibrosis. The disease can be lethal due to liver disease, carcinoma or heart disease, but life expectancy goes to normal if patients are treated before the occurrence of cirrhosis. Treatment relies on regular venesections. Familial screening is essential.