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Abstracts des revues suivantes : Hepatology, Bristish Medical of Journal, The Lancet et The New England Journal of medicine
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Les derniers abstracts de la revue Hepatology : |
Date de mise en ligne : Jeudi 21 février 2008
Yoichi Hiasa, Hiroyuki Kuzuhara, Yoshio Tokumoto, Ichiro Konishi, Nobuyuki Yamashita, Bunzo Matsuura, Kojiro Michitaka, Raymond T. Chung, Morikazu Onji
Hepatitis C virus replication is inhibited by 22[beta]-methoxyolean-12-ene-3[beta], 24(4[beta])-diol (ME3738) through enhancing interferon-[beta]
A derivative of soyasapogenol, 22[beta]-methoxyolean-12-ene-3[beta], 24(4[beta])-diol (ME3738), ameliorates liver injury induced by Concanavalin A in mice. We examined whether ME3738 has independent antiviral effects against hepatitis C virus (HCV) using an established HCV replication model that expresses the full-length genotype 1a HCV complementary DNA plasmid (pT7-flHCV-Rz) under the control of a replication-defective adenoviral vector expressing T7 polymerase. Hepatocellular carcinoma (HepG2) cells, human hepatoma (Huh7) cells, or monkey kidney (CV-1) cells were transfected with pT7-flHCV-Rz, and infected with adenoviral vector expressing T7 polymerase. ME3738 or interferon-[alpha] (IFN-[alpha]) was added thereafter and then protein and RNA were harvested from the cells at 9 days after infection. HCV-positive and HCV-negative strands were measured by real-time reverse-transcription polymerase chain reaction and HCV core protein expression was measured using an enzyme-linked immunosorbent assay. The messenger RNA levels of innate antiviral response-related genes were assessed using real-time reverse-transcription polymerase chain reaction. ME3738 dose-dependently reduced HCV-RNA and core protein in hepatocyte-derived cell lines. The antiviral effect was more pronounced in HepG2 than in Huh7 cells. ME3738 increased messenger RNA levels of interferon-[beta] (IFN-[beta]) and of IFN-stimulated genes (2[prime]-5[prime] oligoadenylate synthetase, myxovirus resistance protein A [MxA]). Interferon-[beta] knockdown by small interfering RNA abrogated the anti-HCV effect of ME3738. Moreover, the anti-HCV effects were synergistic when ME3738 was combined with IFN-[alpha]. Conclusion: ME3738 has antiviral effects against HCV. The enhancement of autocrine IFN-[beta] suggests that ME3738 exerts antiviral action along the type I IFN pathway. This anti-HCV action by ME3738 was synergistically enhanced when combined with IFN-[alpha]. ME3738 might be a useful anti-HCV drug either with or without IFN-[alpha]. (HEPATOLOGY 2008.)
Date de mise en ligne : Lundi 05 mai 2008
Felix Flohr, Jan Harder, Jochen Seufert, Hubert E. Blum, Hans C. Spangenberg
Hypothyroidism in patients with hepatocellular carcinoma treated by transarterial chemoembolization
No abstract.
Date de mise en ligne : Jeudi 21 février 2008
Masaru Harada, Shinichiro Hanada, Diana M. Toivola, Nafisa Ghori, M. Bishr Omary
Autophagy activation by rapamycin eliminates mouse Mallory-Denk bodies and blocks their proteasome inhibitor-mediated formation
The proteasomal and lysosomal/autophagy pathways in the liver and other tissues are involved in several biological processes including the degradation of misfolded proteins. Exposure of hepatocyte cell lines to proteasome inhibitors (PIs) results in the formation of inclusions that resemble Mallory-Denk bodies (MDBs). Keratins are essential for MDB formation and keratin 8 (K8)-overexpressing transgenic mice are predisposed to MDB formation. We tested the hypothesis that PIs induce MDBs in vivo and that autophagy participates in MDB turnover. The effect of the PI bortezomib (which is used to treat some malignancies) on MDB formation was tested in K8-overexpressing mice and in cultured cells. Inclusion formation was examined using immune and conventional electron microscopy (EM). Bortezomib induced MDB-like inclusions composed of keratins, ubiquitin, and p62 in cultured cells. Short-term exposure to bortezomib induced similar inclusions in K8-overexpressing but not in nontransgenic mice, without causing liver injury. In bortezomib-treated mice, autophagy was activated in hepatocytes as determined by EM and biochemical analysis. Further activation of autophagy by rapamycin (Rap) decreased the number of inclusions in bortezomib-treated K8 transgenic mice significantly. Rap also led to resorption of spontaneously formed MDBs in aging K8-overexpressing mice. Immune EM demonstrated K8-positive and ubiquitin-positive structures in autophagic vacuoles in the mouse liver. Conclusion: PIs alone are sufficient to induce MDBs in susceptible animals, while Rap-mediated activation of autophagy prevents MDB formation and causes MDB resorption. These findings suggest that some patients treated with PIs may become predisposed to MDB formation. Autophagy provides a potential cellular mechanism for the resorption of cytoplasmic inclusions. (HEPATOLOGY 2008.)
Date de mise en ligne : Vendredi 01 février 2008
Martin Lagging, Nina Langeland, Court Pedersen, Martti Färkkilä, Mads Rauning Buhl, Kristine Mørch, Amar P. Dhillon, Åsa Alsiö, Kristoffer Hellstrand, Johan Westin, Gunnar Norkrans, NORDynamIC Study Group
Randomized comparison of 12 or 24 weeks of peginterferon [alpha]-2a and ribavirin in chronic hepatitis C virus genotype 2/3 infection
Previous trials investigating the efficacy of treatment durations shorter than the standard of 24 weeks for chronic hepatitis C virus (HCV) genotype 2/3 infections have yielded discordant results. The aims of this investigator-initiated phase III study were to compare the efficacy of 12 or 24 weeks of treatment and to identify patients suitable for short-term therapy. Three hundred eighty-two genotype 2/3-infected patients [intention-to-treat (ITT) population] at 31 centers in Denmark, Finland, Norway, and Sweden were randomized to 12 or 24 weeks of peginterferon [alpha]-2a (180 [mu]g/week) plus ribavirin (800 mg/day). Twelve weeks of therapy was inferior to 24 weeks in the ITT population (sustained viral response [SVR] rates: 59% versus 78%, P < 0.0001) and in the subgroups of patients infected with genotype 2 (56% versus 82%, P = 0.006) or 3 (58% versus 78%, P = 0.0015). These differences were observed regardless of the fibrosis stage. Age and HCV-RNA levels on days 7 and 29 were independent predictors of SVR. Short-term treatment was useful in patients < 40 years old, especially if HCV-RNA was undetectable on day 29, and also in patients [ge] 40 years old, provided that HCV-RNA was below 1000 IU/mL on day 7 in addition to being undetectable on day 29. If neither of these two criteria were met for patients [ge] 40 years old, 24 weeks of therapy was superior (P < 0.0001). Conclusion: Peginterferon/ribavirin treatment for 12 weeks in HCV genotype 2/3 infection is overall inferior to 24 weeks of treatment but may be useful in some patients with a rapid initial clearance of virus. (HEPATOLOGY 2008.)
Date de mise en ligne : Jeudi 31 janvier 2008
Christoph Neumann-Haefelin, Jörg Timm, Hans Christian Spangenberg, Natalie Wischniowski, Natalja Nazarova, Nadine Kersting, Michael Roggendorf, Todd M. Allen, Hubert E. Blum, Robert Thimme
Virological and immunological determinants of intrahepatic virus-specific CD8+ T-cell failure in chronic hepatitis C virus infection
Virus-specific CD8+ T-cells play an important role in the outcome of acute hepatitis C virus (HCV) infection. In the chronic phase, however, HCV can persist despite the presence of virus-specific T-cell responses. Therefore, we set out to perform a full-breadth analysis of the intrahepatic virus-specific CD8+ T-cell response, its relation to the peripheral T-cell response, and the overall influence of viral escape and the genetic restriction on intrahepatic CD8+ T-cell failure. Intrahepatic and peripheral CD8+ T-cells from 20 chronically HCV infected patients (genotype 1) were comprehensively analyzed using overlapping peptides spanning the entire HCV polyprotein in concert with autologous viral sequences that were obtained for all targeted regions. HCV-specific CD8+ T-cell responses were detectable in most (90%) chronically HCV-infected patients, and two thirds of these responses targeted novel previously undescribed epitopes. Most of the responses were detectable only in the liver but not in the peripheral blood, indicating accumulation and enrichment at the site of disease. Of note, only approximately half of the responses were associated with viral sequence variations supported by functional analysis as viral escape mutations. Escape mutations were more often associated with HLA-B alleles. Conclusion: Our results show an unexpected high frequency of intrahepatic virus-specific CD8+ T-cells, a large part of which continue to target the present viral antigens. Thus, our results suggest that factors other than mutational escape contribute to the failure of intrahepatic virus-specific CD8+ T-cells. (HEPATOLOGY 2008.)
Date de mise en ligne : Lundi 21 janvier 2008
Reiichiro Kuwahara, Alexander V. Kofman, Charles S. Landis, E. Scott Swenson, Els Barendswaard, Neil D. Theise
The hepatic stem cell niche: Identification by label-retaining cell assay
Label retention assays remain the state-of-the-art approach to identify the location of intraorgan epithelial stem cell niches, in situ and in vivo. They are commonly used in organs with rapid cell turnover but have not been applied to the liver, where cell turnover is very slow. We used a sublethal dose of acetaminophen administered coincident with bromodeoxyuridine to load possible hepatic stem cells in mice with label and then administered a second, sublethal chase of acetaminophen to accomplish "washout" of label from transit amplifying cell populations. Conclusion: Four possible hepatic stem cell niches are identified by this approach: the canal of Hering (proximal biliary tree), intralobular bile ducts, periductal "null" mononuclear cells, and peribiliary hepatocytes. These results confirm several different and often contradictory lines of investigation regarding the intrahepatic location of stem/progenitor cells and suggest that the liver has a multi-tiered, flexible system of regeneration rather than a single stem/progenitor cell location. (HEPATOLOGY 2008.)
Date de mise en ligne : Lundi 05 mai 2008
Eirini I. Rigopoulou, George N. Dalekos
Autoimmune hepatitis: Of host and pathogen
No abstract.
Date de mise en ligne : Jeudi 21 février 2008
Winston Dunn, Ronghui Xu, Jeffrey B. Schwimmer
Modest wine drinking and decreased prevalence of suspected nonalcoholic fatty liver disease
People at risk for coronary heart disease are often at risk for nonalcoholic fatty liver disease (NAFLD). The association of modest wine consumption with NAFLD has not been studied and the recommendation of wine for patients at risk for both diseases is controversial. The aim is to test the hypothesis that modest wine consumption is associated with decreased prevalence of NAFLD. We included Third National Health and Nutrition Examination Survey participants who either reported no alcohol consumption or preferentially drinking wine with total alcohol consumption up to 10 g per day. Suspected NAFLD was based on unexplained serum alanine aminotransferase (ALT) elevation over the cut point of the reference laboratory (ALT > 43) and the cut point based on the 95th percentile of healthy subjects (ALT > 30 for men; ALT > 19 for women). Multivariate analysis was adjusted for age, gender, race, neighborhood, income, education, caffeine intake, and physical activity. A total of 7,211 nondrinkers and 945 modest wine drinkers comprised the study sample. Based on the reference laboratory cut point, suspected NAFLD was observed in 3.2% of nondrinkers and 0.4% of modest wine drinkers. The adjusted odds ratio was 0.15 (95% confidence interval, 0.05-0.49). Using the healthy subject cut point, suspected NAFLD was observed in 14.3% of nondrinkers and 8.6% of wine drinkers. The adjusted odds ratio was 0.51 (95% confidence interval, 0.33-0.79). Conclusion: Modest wine consumption is associated with reduced prevalence of suspected NAFLD. The current study supports the safety of one glass of wine per day for cardioprotection in patients at risk for both coronary heart disease and NAFLD. (HEPATOLOGY 2008.)
Date de mise en ligne : Lundi 05 mai 2008
Daniel A. Langer, Amitava Das, David Semela, Ningling Kang-Decker, Helen Hendrickson, Steven F. Bronk, Zvonimir S. Katusic, Gregory J. Gores, Vijay H. Shah
Nitric oxide promotes caspase-independent hepatic stellate cell apoptosis through the generation of reactive oxygen species
Hepatic stellate cells (HSCs) contribute to portal hypertension through multiple mechanisms that include collagen deposition, vasoconstriction, and regulation of sinusoidal structure. Under normal physiologic conditions, endothelial nitric oxide (NO) synthase-derived NO exerts paracrine effects on HSCs; however, in cirrhosis, NO generation is impaired in association with concomitant HSC activation and changes in sinusoidal structure, events that contribute significantly to the development of portal hypertension. These concepts, in combination with recent evidence that induction of HSC-selective apoptosis may represent a useful target for treatment of chronic liver disease, led us to examine if NO may further limit HSC function through apoptosis. Indeed, both NO donors and endothelial NO synthase overexpression promoted HSC apoptotic pathways. HSC death conferred by NO occurred through mitochondrial membrane depolarization and through a caspase-independent pathway. Furthermore, NO-induced apoptosis of HSC did not occur through the canonical pathways of soluble guanylate cyclase or protein nitration, but rather through the generation of superoxide and hydroxyl radical intermediates. Lastly, HSC isolated from rats after bile duct ligation were more susceptible to NO-induced apoptosis. These data indicate that NO promotes HSC apoptosis through a signaling mechanism that involves mitochondria, is mediated by reactive oxygen species, and occurs independent of caspase activation. Conclusion: We postulate that NO-dependent apoptosis of HSCs may maintain sinusoidal homeostasis, and may represent an additional beneficial effect of NO donors for therapy of portal hypertension. (HEPATOLOGY 2008.)
Date de mise en ligne : Lundi 05 mai 2008
Hilde Herrema, Terry G. J. Derks, Theo H. van Dijk, Vincent W. Bloks, Albert Gerding, Rick Havinga, Uwe J. F. Tietge, Michael Müller, G. Peter A. Smit, Folkert Kuipers, Dirk-Jan Reijngoud
Disturbed hepatic carbohydrate management during high metabolic demand in medium-chain acyl-CoA dehydrogenase (MCAD)-deficient mice
Medium-chain acyl-coenzyme A (CoA) dehydrogenase (MCAD) catalyzes crucial steps in mitochondrial fatty acid oxidation, a process that is of key relevance for maintenance of energy homeostasis, especially during high metabolic demand. To gain insight into the metabolic consequences of MCAD deficiency under these conditions, we compared hepatic carbohydrate metabolism in vivo in wild-type and MCAD-/- mice during fasting and during a lipopolysaccharide (LPS)-induced acute phase response (APR). MCAD-/- mice did not become more hypoglycemic on fasting or during the APR than wild-type mice did. Nevertheless, microarray analyses revealed increased hepatic peroxisome proliferator-activated receptor gamma coactivator-1[alpha] (Pgc-1[alpha]) and decreased peroxisome proliferator-activated receptor alpha (Ppar [alpha]) and pyruvate dehydrogenase kinase 4 (Pdk4) expression in MCAD-/- mice in both conditions, suggesting altered control of hepatic glucose metabolism. Quantitative flux measurements revealed that the de novo synthesis of glucose-6-phosphate (G6P) was not affected on fasting in MCAD-/- mice. During the APR, however, this flux was significantly decreased (-20%) in MCAD-/- mice compared with wild-type mice. Remarkably, newly formed G6P was preferentially directed toward glycogen in MCAD-/- mice under both conditions. Together with diminished de novo synthesis of G6P, this led to a decreased hepatic glucose output during the APR in MCAD-/- mice; de novo synthesis of G6P and hepatic glucose output were maintained in wild-type mice under both conditions. APR-associated hypoglycemia, which was observed in wild-type mice as well as MCAD-/- mice, was mainly due to enhanced peripheral glucose uptake. Conclusion: Our data demonstrate that MCAD deficiency in mice leads to specific changes in hepatic carbohydrate management on exposure to metabolic stress. This deficiency, however, does not lead to reduced de novo synthesis of G6P during fasting alone, which may be due to the existence of compensatory mechanisms or limited rate control of MCAD in murine mitochondrial fatty acid oxidation. (HEPATOLOGY 2008.)
Date de mise en ligne : Jeudi 07 février 2008
Craig Lammert, Stefan Einarsson, Chandan Saha, Anna Niklasson, Einar Bjornsson, Naga Chalasani
Relationship between daily dose of oral medications and idiosyncratic drug-induced liver injury: Search for signals
Idiosyncratic drug-induced liver injury (DILI) is traditionally thought not to be dose-related. However, it has been pointed out that most medicines that were withdrawn from marketing or received a black-box warning because of hepatotoxicity were prescribed at daily doses greater than 50 mg/day. To examine the relationship between daily dose of medications and idiosyncratic DILI, we conducted a study with two aims. First, using two pharmaceutical databases, we examined the relationship between daily dose of commonly prescribed medicines in the United States and reported frequency of their selected hepatic adverse events. Second, we examined serious DILI cases reported to the Swedish Adverse Drug Reactions Advisory Committee (1970-2004) for any signals supporting the relationship between daily dose and idiosyncratic DILI. Medications were categorized into [le]10 mg/day, 11-49 mg/day, and [ge]50 mg/day groups. Among US prescription medicines, a statistically significant relationship was observed between daily dose of oral medicines and reports of liver failure (P = 0.009), liver transplantation (P < 0.001), and death caused by DILI (P = 0.004) but not alanine aminotransferase (ALT) > 3 × upper limit of normal (P = 0.10) or jaundice (P = 0.16). Of 598 eligible Swedish DILI cases, 9% belonged to the [le]10 mg/day group, 14.2% to the 11-49 mg/day group, and 77% of cases were caused by medications given at dose [ge]50 mg/day. A statistically significant relationship was noted between daily dose and poor outcome (death or liver transplantation) of Swedish DILI cases (2%, 9.4%, and 13.2% in [le]10, 11-49, and [ge]50 mg/day groups, respectively, P = 0.03). Conclusion: These data suggest a relationship between daily doses of oral prescription medications and idiosyncratic DILI. More studies are needed to validate these observations and to explore their implications. (HEPATOLOGY 2008.)
Date de mise en ligne : Lundi 04 février 2008
Peter Ferenci, Harald Brunner, Hermann Laferl, Thomas-Matthias Scherzer, Andreas Maieron, Michael Strasser, Gabriele Fischer, Harald Hofer, Martin Bischof, Rudolf Stauber, Michael Gschwantler, Petra Steindl-Munda, Katharina Staufer, Karin Löschenberger, Austrian Hepatitis Study Group
A randomized, prospective trial of ribavirin 400 mg/day versus 800 mg/day in combination with peginterferon alfa-2a in hepatitis C virus genotypes 2 and 3
We compared the efficacy and tolerability of 24 weeks of treatment with ribavirin 800 mg/day (group A) or 400 mg/day (group B) plus peginterferon alfa-2a 180 [mu]g/week in treatment-naive patients infected with hepatitis C virus (HCV) genotype 2 or 3. A total of 97 of 141 patients randomized to group A (68.8%, 95% confidence interval [CI] 60.5%-76.3%) and 90 of 141 patients randomized to group B (63.8; 95% CI 55.3%-71.7%) achieved a sustained virological response, defined as undetectable serum HCV RNA at the end of untreated follow-up (week 48). Among patients infected with genotype 3, the rate of sustained virological response was 67.5% (95% CI 58.4%-75.6%) in group A and 63.9% (95% CI 54.7%-72.4%) in group B, and among patients infected with genotype 2, the rate of sustained virological response was 77.8% (95% CI 54.2%-93.6%) in group A and 55.6% (95% CI 38.4%-83.7%) in group B. Relapse rates in the 2 treatment groups were similar (17% in group A and 20% in group B). The incidence of adverse events, laboratory abnormalities, and dose reductions was similar in the 2 treatment groups. Conclusion: The results suggest that when administered for 24 weeks with peginterferon alfa-2a, ribavirin doses of 400 and 800 mg/day produce equivalent outcomes in patients infected with HCV genotype 3. (HEPATOLOGY 2008.)
Date de mise en ligne : Lundi 04 février 2008
Samuel MartÃn-VÃlchez, Paloma Sanz-Cameno, Yolanda RodrÃguez-Muñoz, Pedro L. Majano, Francisca Molina-Jiménez, Manuel López-Cabrera, Ricardo Moreno-Otero, Enrique Lara-Pezzi
The hepatitis B virus X protein induces paracrine activation of human hepatic stellate cells
Chronic hepatitis B virus (HBV) infection is a major cause of liver fibrosis, eventually leading to cirrhosis and hepatocellular carcinoma. Although the involvement of the X protein of HBV (HBx) in viral replication and tumor development has been extensively studied, little is known about its possible role in the development of fibrosis. In this work we show that expression of HBx in hepatocytes results in paracrine activation and proliferation of hepatic stellate cells (HSCs), the main producers of extracellular matrix proteins in the fibrotic liver. Both human primary HSCs and rat HSCs exposed to conditioned medium from HBx-expressing hepatocytes showed increased expression of collagen I, connective tissue growth factor, [alpha] smooth muscle actin, matrix metalloproteinase-2, and transforming growth factor-[beta] (TGF-[beta]), together with an enhanced proliferation rate. We found that HBx induced TGF-[beta] secretion in hepatocytes and that the activation of HSCs by conditioned medium from HBx-expressing hepatocytes was prevented by a neutralizing anti-TGF-[beta] antibody, indicating the involvement of this profibrotic factor in the process. Conclusion: Our results propose a direct role for HBx in the development of liver fibrosis by the paracrine activation of stellate cells and reinforce the indication of antiviral treatment in patients with advanced HBV-related chronic liver disease and persistent liver replication. (HEPATOLOGY 2008.)
Date de mise en ligne : Vendredi 01 février 2008
Hung-Yun Lin, I-Chen Yu, Ruey-Shen Wang, Yei-Tsung Chen, Ning-Chun Liu, Saleh Altuwaijri, Cheng-Lung Hsu, Wen-Lung Ma, Jenny Jokinen, Janet D. Sparks, Shuyuan Yeh, Chawnshang Chang
Increased hepatic steatosis and insulin resistance in mice lacking hepatic androgen receptor
Early studies demonstrated that whole-body androgen receptor (AR)-knockout mice with hypogonadism exhibit insulin resistance. However, details about the mechanisms underlying how androgen/AR signaling regulates insulin sensitivity in individual organs remain unclear. We therefore generated hepatic AR-knockout (H-AR-/y) mice and found that male H-AR-/y mice, but not female H-AR-/- mice, fed a high-fat diet developed hepatic steatosis and insulin resistance, and aging male H-AR-/y mice fed chow exhibited moderate hepatic steatosis. We hypothesized that increased hepatic steatosis in obese male H-AR-/y mice resulted from decreased fatty acid [beta]-oxidation, increased de novo lipid synthesis arising from decreased PPAR[alpha], increased sterol regulatory element binding protein 1c, and associated changes in target gene expression. Reduced insulin sensitivity in fat-fed H-AR-/y mice was associated with decreased phosphoinositide-3 kinase activity and increased phosphenolpyruvate carboxykinase expression and correlated with increased protein-tyrosine phosphatase 1B expression. Conclusion: Together, our results suggest that hepatic AR may play a vital role in preventing the development of insulin resistance and hepatic steatosis. AR agonists that specifically target hepatic AR might be developed to provide a better strategy for treatment of metabolic syndrome in men. (HEPATOLOGY 2008.)
Date de mise en ligne : Jeudi 31 janvier 2008
Thomas Vanwolleghem, Jens Bukh, Philip Meuleman, Isabelle Desombere, Jean-Christophe Meunier, Harvey Alter, Robert H. Purcell, Geert Leroux-Roels
Polyclonal immunoglobulins from a chronic hepatitis C virus patient protect human liver-chimeric mice from infection with a homologous hepatitis C virus strain
The role of the humoral immune response in the natural course of hepatitis C virus (HCV) infection is widely debated. Most chronically infected patients have immunoglobulin G (IgG) antibodies capable of neutralizing HCV pseudoparticles (HCVpp) in vitro. It is, however, not clear whether these IgG can prevent a de novo HCV infection in vivo and contribute to the control of viremia in infected individuals. We addressed this question with homologous in vivo protection studies in human liver-urokinase-type plasminogen activator (uPA)+/+ severe combined immune deficient (SCID) mice. Chimeric mice were loaded with chronic phase polyclonal IgG and challenged 3 days later with a 100% infectious dose of the acute phase H77C virus, both originating from patient H. Passive immunization induced sterilizing immunity in five of eight challenged animals. In the three nonprotected animals, the HCV infection was attenuated, as evidenced by altered viral kinetics in comparison with five control IgG-treated animals. Plasma samples obtained from the mice at viral challenge neutralized H77C-HCVpp at dilutions as high as 1/400. Infection was completely prevented when, before administration to naïve chimeric mice, the inoculum was pre-incubated in vitro at an IgG concentration normally observed in humans. Conclusion: Polyclonal IgG from a patient with a long-standing HCV infection not only displays neutralizing activity in vitro using the HCVpp system, but also conveys sterilizing immunity toward the ancestral HCV strain in vivo, using the human liver-chimeric mouse model. Both experimental systems will be useful tools to identify neutralizing antibodies for future clinical use. (HEPATOLOGY 2008.)
Date de mise en ligne : Jeudi 31 janvier 2008
Xudong Wu, Luyong Zhang, Emily Gurley, Elaine Studer, Jing Shang, Tao Wang, Cuifen Wang, Ming Yan, Zhenzhou Jiang, Phillip B. Hylemon, Arun J. Sanyal, William M. Pandak Jr, Huiping Zhou
Prevention of free fatty acid-induced hepatic lipotoxicity by 18[beta]-glycyrrhetinic acid through lysosomal and mitochondrial pathways
Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease and affects millions of people worldwide. Despite the increasing prevalence of NAFLD, the exact molecular/cellular mechanisms remain obscure and effective therapeutic strategies are still limited. It is well-accepted that free fatty acid (FFA)-induced lipotoxicity plays a pivotal role in the pathogenesis of NAFLD. Inhibition of FFA-associated hepatic toxicity represents a potential therapeutic strategy. Glycyrrhizin (GL), the major bioactive component of licorice root extract, has a variety of pharmacological properties including anti-inflammatory, antioxidant, and immune-modulating activities. GL has been used to treat hepatitis to reduce liver inflammation and hepatic injury; however, the mechanism underlying the antihepatic injury property of GL is still poorly understood. In this report, we provide evidence that 18 [beta]-glycyrrhetinic acid (GA), the biologically active metabolite of GL, prevented FFA-induced lipid accumulation and cell apoptosis in in vitro HepG2 (human liver cell line) NAFLD models. GA also prevented high fat diet (HFD)-induced hepatic lipotoxicity and liver injury in in vivo rat NAFLD models. GA was found to stabilize lysosomal membranes, inhibit cathepsin B expression and enzyme activity, inhibit mitochondrial cytochrome c release, and reduce FFA-induced oxidative stress. These characteristics may represent major cellular mechanisms, which account for its protective effects on FFA/HFD-induced hepatic lipotoxicity. Conclusion: GA significantly reduced FFA/HFD-induced hepatic lipotoxicity by stabilizing the integrity of lysosomes and mitochondria and inhibiting cathepsin B expression and enzyme activity. (HEPATOLOGY 2008.)
Date de mise en ligne : Lundi 21 janvier 2008
Guo-Xiang Yang, Zhe-Xiong Lian, Ya-Hui Chuang, Yuki Moritoki, Ruth Y. Lan, Kanji Wakabayashi, Aftab A. Ansari, Richard A. Flavell, William M. Ridgway, Ross L. Coppel, Koichi Tsuneyama, Ian R. Mackay, M. Eric Gershwin
Adoptive transfer of CD8+ T cells from transforming growth factor beta receptor type II (dominant negative form) induces autoimmune cholangitis in mice
We recently reported that mice with a T cell-restricted expression of a dominant negative form of transforming growth factor [beta] receptor type II (dnTGF[beta]RII) spontaneously develop autoimmune cholangitis that resembles human primary biliary cirrhosis (PBC), including antimitochondrial antibodies (AMAs) and extensive portal CD4+ and CD8+ lymphocytic infiltrates. On the basis of these data, we performed a series of experiments to determine whether the pathology was secondary to direct dnTGF[beta]RII disruption of the liver and/or alternatively the appearance of autoreactive T cells. First, using dnTGF[beta]RIIRag1-/- mice, we noted a normal hepatic and biliary structure. Hence, we performed a rigorous series of adoptive transfer studies, transferring Ly5.1+ unfractionated spleen cell CD4+ or CD8+ T cells from dnTGF[beta]RII mice into B6/Rag-/- (Ly 5.2) recipients. In unmanipulated dnTGF[beta]RII mice, there was a marked increase in CD4+ and CD8+ T cell biliary infiltrates with AMA. Indeed, B6/Rag-/- recipients of dnTGF[beta]RII unfractionated cells develop features of liver disease similar to PBC, suggesting that splenic loss of self-tolerance alone is sufficient to cause disease in this model and therefore that there is no specific abnormality in the biliary targets required for appearance of disease. More importantly, adoptive transfer of CD8+ but not CD4+ T cells into B6/Rag-/- mice led to liver histopathology remarkably similar to PBC, emphasizing a prominent role for CD8 T cell-mediated pathogenesis. In contrast, B6/Rag-/- recipients of CD4+ T cells from dnTGF[beta]RII mice predominantly developed inflammatory bowel disease associated with higher levels of serum interferon [gamma] and tumor necrosis factor [alpha]. Conclusion: These data suggest that in this model of PBC, autoreactive CD8+ cells destroy bile ducts. (HEPATOLOGY 2008.)
Date de mise en ligne : Jeudi 07 février 2008
Muhammad Y. Sheikh, Jinah Choi, Ishtiaq Qadri, Jacob E. Friedman, Arun J. Sanyal
Hepatitis C virus infection: Molecular pathways to metabolic syndrome
Chronic infection with hepatitis C virus (HCV) can induce insulin resistance (IR) in a genotype-dependent fashion, thus contributing to steatosis, progression of fibrosis and resistance to interferon therapy. The molecular mechanisms in genotype 1 patients that lead to metabolic syndrome are still ambiguous. Based on our current understanding, HCV proteins associate with mitochondria and endoplasmic reticulum and promote oxidative stress. The latter mediates signals involving the p38 mitogen-activated protein kinase and activates nuclear factor kappa B. This transcription factor plays a key role in the expression of cytokines, tumor necrosis factor alpha (TNF-[alpha]), interleukin 6, interleukin 8, tumor growth factor beta, and Fas ligand. TNF-[alpha] inhibits the function of insulin receptor substrates and decreases the expression of the glucose transporter and lipoprotein lipase in peripheral tissues, which is responsible for the promotion of insulin resistance. Furthermore, reduced adiponectin levels, loss of adiponectin receptors, and decreased anti-inflammatory peroxisome proliferator-activated receptor alpha in the liver of HCV patients may contribute to reduced fatty acid oxidation, inflammation, and eventually lipotoxicity. This chain of events may be initiated by HCV-associated IR and provides a direction for future research in the areas of therapeutic intervention. (HEPATOLOGY 2008.)
Date de mise en ligne : Vendredi 01 février 2008
Yannick Ladeiro, Gabrielle Couchy, Charles Balabaud, Paulette Bioulac-Sage, Laura Pelletier, Sandra Rebouissou, Jessica Zucman-Rossi
MicroRNA profiling in hepatocellular tumors is associated with clinical features and oncogene/tumor suppressor gene mutations
Molecular classifications defining new tumor subtypes have been recently refined with genetic and transcriptomic analyses of benign and malignant hepatocellular tumors. Here, we performed microRNA (miRNA) profiling in two series of fully annotated liver tumors to uncover associations between oncogene/tumor suppressor mutations and clinical and pathological features. Expression levels of 250 miRNAs in 46 benign and malignant hepatocellular tumors were compared to those of 4 normal liver samples with quantitative reverse-transcriptase polymerase chain reaction. miRNAs associated with genetic and clinical characteristics were validated in a second series of 43 liver tumor samples and 16 nontumor samples. miRNA profiling unsupervised analysis classified samples in unique clusters characterized by histological features (tumor/nontumor, P < 0.001; benign/malignant tumors, P < 0.01; inflammatory adenoma and focal nodular hyperplasia, P < 0.01), clinical characteristics [hepatitis B virus (HBV) infection, P < 0.001; alcohol consumption, P < 0.05], and oncogene/tumor suppressor gene mutations [[beta]-catenin, P < 0.01; hepatocyte nuclear factor 1[alpha] (HNF1[alpha]), P < 0.01]. Our study identified and validated miR-224 overexpression in all tumors and miR-200c, miR-200, miR-21, miR-224, miR-10b, and miR-222 specific deregulation in benign or malignant tumors. Moreover, miR-96 was overexpressed in HBV tumors, and miR-126* was down-regulated in alcohol-related hepatocellular carcinoma. Down-regulations of miR-107 and miR-375 were specifically associated with HNF1[alpha] and [beta]-catenin gene mutations, respectively. miR-375 expression was highly correlated to that of [beta]-catenin-targeted genes as miR-107 expression was correlated to that of HNF1[alpha] in a small interfering RNA cell line model. Thus, this strongly suggests that [beta]-catenin and HNF1[alpha] could regulate miR-375 and miR-107 expression levels, respectively. Conclusion: Hepatocellular tumors may have a distinct miRNA expression fingerprint according to malignancy, risk factors, and oncogene/tumor suppressor gene alterations. Dissecting these relationships provides a new hypothesis to understand the functional impact of miRNA deregulation in liver tumorigenesis and the promising use of miRNAs as diagnostic markers. (HEPATOLOGY 2008.)
Date de mise en ligne : Vendredi 01 février 2008
Maureen M. Jonas, Deirdre Kelly, Henry Pollack, Jacek Mizerski, Jeff Sorbel, David Frederick, Elsa Mondou, Franck Rousseau, Etienne Sokal
Safety, efficacy, and pharmacokinetics of adefovir dipivoxil in children and adolescents (age 2 to <18 years) with chronic hepatitis B
This study investigated the efficacy, safety, and pharmacokinetics of adefovir dipivoxil (ADV) in children and adolescents with chronic hepatitis B (CHB). A total of 173 treatment-naive and treatment-experienced children with hepatitis B e antigen (HBeAg)+ CHB were randomized to ADV or placebo. Randomization was stratified by age (2 to <7 years; >7 to <12 years; >12 to <18 years) and prior treatment. Significantly more ADV-treated subjects aged 12 to <18 years achieved the primary efficacy endpoint (serum hepatitis B virus [HBV] DNA <1,000 copies/mL and normal alanine aminotransferase) compared to placebo-treated subjects (23% versus 0%; P = 0.007). In the younger groups, differences between ADV and placebo at the end of blinded treatment were not statistically significant. More ADV-treated subjects had HBeAg seroconversion: 18 of 113 (15.9%) versus three of 57 (5.3%) (but P = 0.051), and more met the combined endpoint of HBeAg seroconversion, HBV DNA <1,000 copies/mL and normal alanine aminotransferase (12/113 versus 0/57; P = 0.009). No subject developed an ADV-associated mutation that has been linked to HBV DNA rebound (that is, mutations rtN236T or rtA181V). ADV plasma concentrations were comparable across groups and within the target range. ADV treatment was well tolerated; no new safety issues were identified. Treatment-related adverse events were reported for 12% of ADV-treated and 10% of placebo-treated subjects. After 48 weeks of ADV treatment, antiviral efficacy in subjects ages 12 to <18 years with HBeAg+ CHB was similar to that observed in a study in adult treatment-naive subjects with HBeAg+ CHB. ADV was not different from placebo in subjects aged 2 to 11 years despite adequate plasma ADV exposure in all three age groups. Conclusion: ADV showed significant antiviral efficacy in subjects aged 12 to 17 years with HBeAg+ CHB, but was not different from placebo in subjects aged 2 to 11 years. (HEPATOLOGY 2008.)
Date de mise en ligne : Jeudi 31 janvier 2008
Guilherme M. Campos, Kiran Bambha, Eric Vittinghoff, Charlotte Rabl, Andrew M. Posselt, Ruxandra Ciovica, Umesh Tiwari, Linda Ferrel, Mark Pabst, Nathan M. Bass, Raphael B. Merriman
A clinical scoring system for predicting nonalcoholic steatohepatitis in morbidly obese patients
Nonalcoholic steatohepatitis (NASH) is common in morbidly obese persons. Liver biopsy is diagnostic but technically challenging in such individuals. This study was undertaken to develop a clinically useful scoring system to predict the probability of NASH in morbidly obese persons, thus assisting in the decision to perform liver biopsy. Consecutive subjects undergoing bariatric surgery without evidence of other liver disease underwent intraoperative liver biopsy. The outcome was pathologic diagnosis of NASH. Predictors evaluated were demographic, clinical, and laboratory variables. A clinical scoring system was constructed by rounding the estimated regression coefficients for the independent predictors in a multivariate logistic model for the diagnosis of NASH. Of 200 subjects studied, 64 (32%) had NASH. Median body mass index was 48 kg/m2 (interquartile range, 43-55). Multivariate analysis identified six predictive factors for NASH: the diagnosis of hypertension (odds ratio [OR], 2.4; 95% confidence interval [CI], 1-5.6), type 2 diabetes (OR, 2.6; 95% CI, 1.1-6.3), sleep apnea (OR, 4.0; 95% CI, 1.3-12.2), AST > 27 IU/L (OR, 2.9; 95% CI, 1.2-7.0), alanine aminotransferase (ALT) > 27 IU/L (OR, 3.3; 95% CI, 1.4-8.0), and non-Black race (OR, 8.4; 95% CI, 1.9-37.1). A NASH Clinical Scoring System for Morbid Obesity was derived to predict the probability of NASH in four categories (low, intermediate, high, and very high). Conclusion: The proposed clinical scoring can predict NASH in morbidly obese persons with sufficient accuracy to be considered for clinical use, identifying a very high-risk group in whom liver biopsy would be very likely to detect NASH, as well as a low-risk group in whom biopsy can be safely delayed or avoided. (HEPATOLOGY 2008.)
Date de mise en ligne : Lundi 04 février 2008
Yann Malato, Leif E. Sander, Christian Liedtke, Malika Al-Masaoudi, Frank Tacke, Christian Trautwein, Naiara Beraza
Hepatocyte-specific inhibitor-of-kappaB-kinase deletion triggers the innate immune response and promotes earlier cell proliferation during liver regeneration
Nuclear factor [kappa]B (NF-[kappa]B) is one of the main transcription factors involved in liver regeneration after partial hepatectomy (PH). It is activated upon I[kappa]B phosphorylation by the I[kappa]B kinase (IKK) complex comprising inhibitor of kappaB kinase 1 (IKK1), inhibitor of kappaB kinase 2 (IKK2), and nuclear factor-B essential modifier (NEMO). We studied the impact of hepatocyte-specific IKK2 deletion during liver regeneration. A 70% PH was performed on IKK2f/f (wild-type) and IKK2[Delta]LPCmice (hepatocyte-specific IKK2 knockout mice). PH in IKK2[Delta]LPC compared with IKK2f/f mice resulted in weaker and delayed NF-[kappa]B activation in hepatocytes, while nonparenchymal liver cells showed earlier NF-[kappa]B activation and higher tumor necrosis factor expression. Additionally, these animals showed increased and earlier serum amyloid A and chemotactic cytokine L-1 levels followed by enhanced polymorphonuclear cell recruitment to the liver. These results correlated with earlier Jun kinase activity, c-myc expression, and matrix metalloproteinase-9 activity, suggesting earlier priming in IKK2[Delta]LPC mice after PH. These data preceded a more rapid cell cycle progression and earlier hepatocyte proliferation as evidenced through cyclin and 5-bromo-2-deoxyuridine analysis. Interestingly, despite faster G1/S progression, IKK2[Delta]LPC mice exhibited an enduring mitosis phase, because mitotic bodies were still observed at later stages after PH. Conclusion: We demonstrate that PH in IKK2[Delta]LPC mice triggers a more rapid and pronounced inflammatory response in nonparenchymal liver cells, which triggers earlier hepatocyte proliferation. (HEPATOLOGY 2008.)
Date de mise en ligne : Jeudi 07 février 2008
Beate Katharina Straub, Pamela Stoeffel, Hans Heid, Ralf Zimbelmann, Peter Schirmacher
Differential pattern of lipid droplet-associated proteins and de novo perilipin expression in hepatocyte steatogenesis
Fatty change (steatosis) is the most frequent liver pathology in western countries and is caused by a broad range of disorders such as alcohol abuse and metabolic syndrome. The surface layer of lipid droplets (LDs) contains members of a protein family that share homologous sequences and domains, the so-called PAT proteins, named after their constituents, perilipin, adipophilin, and TIP47. We characterized the LD-associated proteins in normal and diseased liver connected with LD accumulation. Adipophilin and TIP47 are expressed in LDs of vitamin A-storing hepatic stellate cells and additionally in LDs of steatotic hepatocytes. Perilipin, which was thought to be characteristic for LDs of adipocytes and steroidogenic cells, becomes de novo expressed in hepatocytes of human steatotic liver. Perilipin splice variant A was found in human steatotic hepatocytes by biochemical, molecular biological, and immunohistochemical methods. Its association with LDs is different from TIP47 and adipophilin, and depends on size and localization of the LDs, suggesting that the different PAT proteins play specific roles during maturation of LDs. (HEPATOLOGY 2008.)
Date de mise en ligne : Jeudi 17 janvier 2008
Matthew W. Lawless, Arun K. Mankan, Anthony W. Ryan, Suzanne Norris
Tauroursodeoxycholic acid: Relieving the pathogenesis of HFE C282Y hereditary hemochromatosis
No abstract.
Les derniers abstracts de la revue BMJ current issue : |
Date de mise en ligne : Jeudi 08 mai 2008
Godlee, F.
[EDITOR'S CHOICE] What our advisory board can, and can't, tell us
Date de mise en ligne : Jeudi 08 mai 2008
Perreira, K. M
Catégorie : Alcohol, Smoking, Culture, Breastfeeding and infant nutrition, Pregnancy
[EDITORIALS] Migration and health behaviour during pregnancy
Date de mise en ligne : Jeudi 08 mai 2008
Waller, J., Wardle, J.
Catégorie : Health Services Research, UK government, Drugs: immunological products and vaccines, Health education (including prevention and promotion), Adolescents, Sexually Transmitted Infections - other than HIV / AIDS, Cervical Screening
[EDITORIALS] HPV vaccination in the UK
Date de mise en ligne : Jeudi 08 mai 2008
Kidd, M. R
Catégorie : Confidentiality, World Wide Web, Other Medical Informatics
[EDITORIALS] Personal electronic health records: MySpace or HealthSpace?
Date de mise en ligne : Jeudi 08 mai 2008
Watt, A. M, Patkin, M., Sinnott, M. J, Black, R. J, Maddern, G. J
Catégorie : Work conditions (including pay and numbers), Other Surgery, Patient safety / Clinical risk / Medical error
[EDITORIALS] Scalpel injuries in the operating theatre
Date de mise en ligne : Jeudi 08 mai 2008
Bergstrom, S., Aronsson, A.
Catégorie : Regulation, Guidelines, Global health, Reproductive medicine, Drugs: obstetrics and gynaecology, Pregnancy
[EDITORIALS] Misoprostol in resource poor countries
Date de mise en ligne : Jeudi 08 mai 2008
Kurzer, M., Kark, A. E, Hussain, T.
[LETTERS] Outcomes other than recurrence should be analysed
Date de mise en ligne : Jeudi 08 mai 2008
Dixon, A.
[LETTERS] Let's get back to basics in managing melanoma
Date de mise en ligne : Jeudi 08 mai 2008
Lewars, M. D
[LETTERS] Article's recommendation of HRT is highly questionable
Date de mise en ligne : Jeudi 08 mai 2008
Lin, K. W
[LETTERS] Study's conclusion about screening is unwarranted
Date de mise en ligne : Jeudi 08 mai 2008
Singleton, P. D
[LETTERS] Beware of self selection and self fulfilling prophecy
Date de mise en ligne : Jeudi 08 mai 2008
Montgomery, B. D
[LETTERS] Free lunches are not the answer
Date de mise en ligne : Jeudi 08 mai 2008
Sie, A. H
[LETTERS] You must be joking
Date de mise en ligne : Jeudi 08 mai 2008
Oxley, C.
[LETTERS] Cool for cats
Date de mise en ligne : Jeudi 08 mai 2008
Tanne, J. H.
Catégorie : Regulation
[NEWS] US medical schools should say no to pharma support
Date de mise en ligne : Jeudi 08 mai 2008
Dyer, C.
Catégorie : Resource allocation (including rationing), Dementia
[NEWS] Appeal Court rules that NICE procedure was unfair
Date de mise en ligne : Jeudi 08 mai 2008
[NEWS] In brief
Date de mise en ligne : Jeudi 08 mai 2008
O'Dowd, A.
Catégorie : Socioeconomic Determinants of Health, Other Public Health
[NEWS] Cash incentives might help to change behaviour, MPs told
Date de mise en ligne : Jeudi 08 mai 2008
Christie, B.
Catégorie : Alcohol
[NEWS] Fifteen children a day attend Scottish emergency departments as result of drinking alcohol
Date de mise en ligne : Jeudi 08 mai 2008
Dyer, C.
Catégorie : UK government, Work conditions (including pay and numbers), Medicine and the law (incl forensic medicine), Getting and changing jobs (including job descriptions and contracts)
[NEWS] House of Lords rules against government's restriction on foreign doctors
Date de mise en ligne : Jeudi 08 mai 2008
Eaton, L.
Catégorie : Patient - other, Environmental Issues
[NEWS] Hospital finds space for art
Date de mise en ligne : Jeudi 08 mai 2008
Moszynski, P.
Catégorie : Global health
[NEWS] Campaigners draw attention to disfiguring childhood disease
Date de mise en ligne : Jeudi 08 mai 2008
Tanne, J. H.
Catégorie : Genetics
[NEWS] US Senate outlaws genetic discrimination
Date de mise en ligne : Jeudi 08 mai 2008
Mudur, G.
Catégorie : Reproductive medicine, Medicine and the law (incl forensic medicine), Ethics of reproduction
[NEWS] Proposals to strengthen ban on prenatal sex determination hide inaction, activists claim
Date de mise en ligne : Jeudi 08 mai 2008
Spurgeon, D.
Catégorie : Diabetes
[NEWS] Prevalence of pre-existing diabetes in pregnancy doubled in seven years in a Californian population
Date de mise en ligne : Jeudi 08 mai 2008
Stafford, N.
Catégorie : Professional conduct and regulation, Human Rights, Medicine and the law (incl forensic medicine)
[NEWS] German doctor stands trial for forcibly administering emetic to police suspect who died
Date de mise en ligne : Jeudi 08 mai 2008
Dyer, O.
[NEWS] Number of patients from Gaza getting travel permits for medical treatment falls by 90%, says charity
Date de mise en ligne : Jeudi 08 mai 2008
Moszynski, P.
Catégorie : Other Infectious Diseases, Global health, Travel medicine
[NEWS] UK doctors increasingly likely to encounter tropical diseases, symposium told
Date de mise en ligne : Jeudi 08 mai 2008
Siegel-Itzkovich, J.
Catégorie : Other imaging techniques, Global health
[NEWS] Imaging technology could be useful in poor countries
Date de mise en ligne : Jeudi 08 mai 2008
Richards, T.
Catégorie : Global health
[NEWS] Global health initiatives need to be better coordinated
Date de mise en ligne : Jeudi 08 mai 2008
Hitchen, L.
Catégorie : Other Epidemiology
[NEWS] Compulsory recording of patients' ethnic details will help to show disease trends
Date de mise en ligne : Jeudi 08 mai 2008
O'Dowd, A.
Catégorie : Socioeconomic Determinants of Health
[NEWS] Government to revise health inequality proposals
Date de mise en ligne : Jeudi 08 mai 2008
[SHORT CUTS] All you need to read in the other general journals
Date de mise en ligne : Jeudi 08 mai 2008
Wise, J.
Catégorie : Professional conduct and regulation, Other imaging techniques, Patient safety / Clinical risk / Medical error
[FEATURE] Everyone's a radiologist now
Date de mise en ligne : Jeudi 08 mai 2008
Martyn, C.
[OBSERVATIONS] The secret lives of doctors
Date de mise en ligne : Jeudi 08 mai 2008
Biegler, P.
Catégorie : Other Ethics, Drugs: psychiatry, Psychology, Mood disorders (including depression)
[ANALYSIS] Autonomy, stress, and treatment of depression
Date de mise en ligne : Jeudi 08 mai 2008
Molony, M.
[FILLERS] That was obstetrics that was
Date de mise en ligne : Jeudi 08 mai 2008
Guyatt, G. H, Oxman, A. D, Kunz, R., Falck-Ytter, Y., Vist, G. E, Liberati, A., Schunemann, H. J, for the GRADE Working Group
Catégorie : Other evidence based practice
[ANALYSIS] Going from evidence to recommendations
Date de mise en ligne : Jeudi 08 mai 2008
[FILLERS] Two kinds of surgery
Date de mise en ligne : Jeudi 08 mai 2008 Objective To compare health behaviours during pregnancy (smoking and alcohol consumption) and after birth (initiation and duration of breast feeding) between British/Irish white mothers and mothers from ethnic minority groups; and, in mothers from ethnic minority groups, to examine whether indicators of acculturation (generational status, language spoken at home, length of residency in the United Kingdom) were associated with these health behaviours. Design Prospective nationally representative cohort study. Setting England. Participants 6478 British/Irish white mothers and 2110 mothers from ethnic minority groups. Main outcome measures Any smoking during pregnancy; any alcohol consumption during pregnancy; initiation of breast feeding; breast feeding for at least four months. Results Compared with British/Irish white mothers, mothers from ethnic minority groups were less likely to smoke (15% v 37%) or consume alcohol (14% v 37%) during pregnancy but more likely to initiate breast feeding (86% v 69%) and breast feed for at least four months (40% v 27%). Among mothers from ethnic minority groups, first and second generation mothers were more likely to smoke during pregnancy (odds ratio 3.85, 95% confidence interval 2.50 to 5.93, and 4.70, 2.49 to 8.90, respectively), less likely to initiate breast feeding (0.92, 0.88 to 0.97, and 0.86, 0.75 to 0.99), and less likely to breast feed for at least four months (0.72, 0.62 to 0.83, and 0.52, 0.30 to 0.89) than immigrants, after adjustment for sociodemographic characteristics. There were no consistent differences in alcohol consumption. Among immigrants, for every additional five years spent in the UK the likelihood of mothers smoking during pregnancy increased by 31% (4% to 66%) and they were 5% (0% to 10%) less likely to breast feed for at least four months. Conclusions After immigration, maternal health behaviours worsen with length of residency in the UK. Health professionals should not underestimate women’s likelihood of engaging in risky health behaviours because of their ethnicity.
Hawkins, S. S., Lamb, K., Cole, T. J, Law, C., the Millennium Cohort Study Child Health Group
Catégorie : Alcohol, Smoking, Culture, Breastfeeding and infant nutrition, Pregnancy
[RESEARCH] Influence of moving to the UK on maternal health behaviours: prospective cohort study
Date de mise en ligne : Jeudi 08 mai 2008 Objective To assess the feasibility and acceptability of delivering a human papillomavirus (HPV) vaccine to adolescent girls. Design Prospective cohort study. Setting 36 secondary schools in two primary care trusts in Greater Manchester, United Kingdom. Participants 2817 schoolgirls in year 8 (12 and 13 year olds). Intervention Delivery of the bivalent vaccine at 0, 1, and 6 months over one school year. Main outcome measures Vaccine uptake for doses 1 and 2 of a three dose schedule. Results Vaccine uptake was 70.6% (1989/2817) for the first dose and 68.5% (1930/2817) for the second dose. Uptake was significantly lower in schools with a higher proportion of ethnic minority girls (P<0.001 for trend) or higher proportion of girls entitled to free school meals (P=0.029 for trend). The main reason for parents’ refusal of vaccination was insufficient information about the vaccine and its long term safety. Maintaining the vaccine schedule was challenging as 16.3% (dose 1) and 23.6% (dose 2) of girls missed their vaccination day and had to be offered alternative appointments. No serious adverse events were reported. Conclusion Delivery of the first two doses of HPV vaccine to adolescent schoolgirls is encouraging, but the success of the vaccination programme depends on high coverage for the third dose.
Brabin, L., Roberts, S. A, Stretch, R., Baxter, D., Chambers, G., Kitchener, H., McCann, R.
Catégorie : Health Services Research, UK government, Drugs: immunological products and vaccines, Health education (including prevention and promotion), Adolescents, Sexually Transmitted Infections - other than HIV / AIDS, Cervical Screening
[RESEARCH] Uptake of first two doses of human papillomavirus vaccine by adolescent schoolgirls in Manchester: prospective cohort study
Date de mise en ligne : Jeudi 08 mai 2008 Objectives To determine whether coronary angiography for suspected stable angina pectoris is underused in older patients, women, south Asian patients, and those from socioeconomically deprived areas, and, if it is, whether this is associated with higher coronary event rates. Design Multicentre cohort with five year follow-up. Setting Six ambulatory care clinics in England. Participants 1375 consecutive patients in whom coronary angiography was individually rated as appropriate with the Rand consensus method. Main outcome measures Receipt of angiography (420 procedures); coronary mortality and acute coronary syndrome events. Results In a multivariable analysis, angiography was less likely to be performed in patients aged over 64 compared with those aged under 50 (hazard ratio 0.60, 95% confidence interval 0.38 to 0.96), women compared with men (0.42, 0.35 to 0.50), south Asians compared with white people (0.48, 0.34 to 0.67), and patients in the most deprived fifth compared with the other four fifths (0.66, 0.40 to 1.08). Not undergoing angiography when it was deemed appropriate was associated with higher rates of coronary event. Conclusions At an early stage after presentation with suspected angina, coronary angiography is underused in older people, women, south Asians, and people from deprived areas. Not receiving appropriate angiography was associated with a higher risk of coronary events in all groups. Interventions based on clinical guidance that supports individualised management decisions might improve access and outcomes.
Sekhri, N., Timmis, A., Chen, R., Junghans, C., Walsh, N., Zaman, J., Eldridge, S., Hemingway, H., Feder, G.
Catégorie : Health Services Research, Sociology, Ischaemic heart disease, Other Cardiovascular Medicine, Radiological diagnosis, Other evidence based practice, Diagnostics tests
[RESEARCH] Inequity of access to investigation and effect on clinical outcomes: prognostic study of coronary angiography for suspected stable angina pectoris
Date de mise en ligne : Jeudi 08 mai 2008
Cummings, J R F., Keshav, S., Travis, S. P L
Catégorie : Small intestine, Inflammatory bowel disease, Drugs: gastrointestinal system, Drugs: immunological products and vaccines, Chronic diseases, Colorectal disease
[CLINICAL REVIEW] Medical management of Crohn's disease
Date de mise en ligne : Jeudi 08 mai 2008
Guthrie, J A., Sheridan, M. B
Catégorie : Pancreas and biliary tract, Radiological diagnosis
[PRACTICE] Investigation of abdominal pain to detect pancreatic cancer
Date de mise en ligne : Jeudi 08 mai 2008
[FILLERS] The golden tooth
Date de mise en ligne : Jeudi 08 mai 2008
Harrington, P.
Catégorie : Patients' views, Anxiety disorders (including OCD and PTSD)
[PRACTICE] Obsessive compulsive disorder with associated hypochondriasis
Date de mise en ligne : Jeudi 08 mai 2008
England, R.
[VIEWS & REVIEWS] The writing is on the wall for UNAIDS
Date de mise en ligne : Jeudi 08 mai 2008
Douglas, C.
[VIEWS & REVIEWS] Observations from on high
Date de mise en ligne : Jeudi 08 mai 2008
Spence, D.
[VIEWS & REVIEWS] The bland bombshell
Date de mise en ligne : Jeudi 08 mai 2008
Drife, J. O.
[VIEWS & REVIEWS] The Royal College of Lay People
Date de mise en ligne : Jeudi 08 mai 2008
Dalrymple, T.
[VIEWS & REVIEWS] Dangerous, ignorant, presuming fools
Date de mise en ligne : Jeudi 08 mai 2008
Hossain, M.
[VIEWS & REVIEWS] The Anatomy Lesson
Date de mise en ligne : Jeudi 08 mai 2008
Lichterman, B.
[OBITUARIES] Nikolai Pavlovich Napalkov
Date de mise en ligne : Jeudi 08 mai 2008
Brooks, N.
[OBITUARIES] Raphael Balcon
Date de mise en ligne : Jeudi 08 mai 2008
Hawkins, D.
[OBITUARIES] Cyril John Bintcliffe
Date de mise en ligne : Jeudi 08 mai 2008
Watts, D.
[OBITUARIES] Ralph Fallows
Date de mise en ligne : Jeudi 08 mai 2008
Booth, P. W.
[OBITUARIES] Anthony Gabriel
Date de mise en ligne : Jeudi 08 mai 2008
Matheson, D., Clark, C., Howden, C.
[OBITUARIES] Lillian Mary Matheson
Date de mise en ligne : Jeudi 08 mai 2008
Keene, J.
[OBITUARIES] John Campbell Miller
Date de mise en ligne : Jeudi 08 mai 2008
Surtees, J., Nash, P., Watson, B., Steer, B.
[OBITUARIES] Paul Hex Venn
Date de mise en ligne : Jeudi 08 mai 2008
[MINERVA]
Date de mise en ligne : Jeudi 08 mai 2008
Roberts, C. M L, Birnie, A. J, Hewitt, M., Forman, K., Murphy, R., Ravenscroft, J. C
[MINERVA]
Les derniers abstracts de la revue New England Journal of Medicine : |
Date de mise en ligne : Jeudi 24 avril 2008 Background There is an urgent need to determine whether oversulfated chondroitin sulfate (OSCS), a compound contaminating heparin supplies worldwide, is the cause of the severe anaphylactoid reactions that have occurred ...
Kishimoto, T. K., Viswanathan, K., Ganguly, T., Elankumaran, S., Smith, S., Pelzer, K., Lansing, J. C., Sriranganathan, N., Zhao, G., Galcheva-Gargova, Z., Al-Hakim, A., Bailey, G. S., Fraser, B., Roy, S., Rogers-Cotrone, T., Buhse, L., Whary, M., Fox, J., Nasr, M., Dal Pan, G. J., Shriver, Z., Langer, R. S., Venkataraman, G., Austen, K. F., Woodcock, J., Sasisekharan, R.
EARLY RELEASE: Contaminated Heparin Associated with Adverse Clinical Events and Activation of the Contact System
Date de mise en ligne : Dimanche 27 avril 2008
Miller, J. W.
EARLY RELEASE: Preliminary Results of Gene Therapy for Retinal Degeneration
(No abstract is available for this citation)
Date de mise en ligne : Dimanche 27 avril 2008 Early-onset, severe retinal dystrophy caused by mutations in the gene encoding retinal pigment epithelium-specific 65-kDa protein (RPE65) is associated with poor vision at birth and complete loss of vision in ...
Bainbridge, J. W.B., Smith, A. J., Barker, S. S., Robbie, S., Henderson, R., Balaggan, K., Viswanathan, A., Holder, G. E., Stockman, A., Tyler, N., Petersen-Jones, S., Bhattacharya, S. S., Thrasher, A. J., Fitzke, F. W., Carter, B. J., Rubin, G. S., Moore, A. T., Ali, R. R.
EARLY RELEASE: Brief Report: Effect of Gene Therapy on Visual Function in Leber's Congenital Amaurosis
Date de mise en ligne : Lundi 28 avril 2008 Leber's congenital amaurosis (LCA) is a group of inherited blinding diseases with onset during childhood. One form of the disease, LCA2, is caused by mutations in the retinal pigment epithelium-specific ...
Maguire, A. M., Simonelli, F., Pierce, E. A., Pugh, E. N., Mingozzi, F., Bennicelli, J., Banfi, S., Marshall, K. A., Testa, F., Surace, E. M., Rossi, S., Lyubarsky, A., Arruda, V. R., Konkle, B., Stone, E., Sun, J., Jacobs, J., Dell'Osso, L., Hertle, R., Ma, J.-x., Redmond, T. M., Zhu, X., Hauck, B., Zelenaia, O., Shindler, K. S., Maguire, M. G., Wright, J. F., Volpe, N. J., McDonnell, J. W., Auricchio, A., High, K. A., Bennett, J.
EARLY RELEASE: Brief Report: Safety and Efficacy of Gene Transfer for Leber's Congenital Amaurosis
Date de mise en ligne : Mardi 29 avril 2008
Hirschhorn, J. N., Gennari, L.
EARLY RELEASE: Bona Fide Genetic Associations with Bone Mineral Density
(No abstract is available for this citation)
Date de mise en ligne : Mardi 29 avril 2008 Background Bone mineral density influences the risk of osteoporosis later in life and is useful in the evaluation of the risk of fracture. We aimed to identify sequence variants associated ...
Styrkarsdottir, U., Halldorsson, B. V., Gretarsdottir, S., Gudbjartsson, D. F., Walters, G. B., Ingvarsson, T., Jonsdottir, T., Saemundsdottir, J., Center, J. R., Nguyen, T. V., Bagger, Y., Gulcher, J. R., Eisman, J. A., Christiansen, C., Sigurdsson, G., Kong, A., Thorsteinsdottir, U., Stefansson, K.
EARLY RELEASE: Multiple Genetic Loci for Bone Mineral Density and Fractures
Date de mise en ligne : Mercredi 07 mai 2008
Kushner, B. H., Cheung, N.-K. V.
EARLY RELEASE: Neuroblastoma -- Linking a Common Allele to a Rare Disease
(No abstract is available for this citation)
Date de mise en ligne : Mercredi 07 mai 2008 Background Neuroblastoma is a malignant condition of the developing sympathetic nervous system that most commonly affects young children and is often lethal. Its cause is not known. Methods We performed ...
Maris, J. M., Mosse, Y. P., Bradfield, J. P., Hou, C., Monni, S., Scott, R. H., Asgharzadeh, S., Attiyeh, E. F., Diskin, S. J., Laudenslager, M., Winter, C., Cole, K. A., Glessner, J. T., Kim, C., Frackelton, E. C., Casalunovo, T., Eckert, A. W., Capasso, M., Rappaport, E. F., McConville, C., London, W. B., Seeger, R. C., Rahman, N., Devoto, M., Grant, S. F.A., Li, H., Hakonarson, H.
EARLY RELEASE: Chromosome 6p22 Locus Associated with Clinically Aggressive Neuroblastoma
Date de mise en ligne : Mercredi 07 mai 2008 Long-term care has all the makings of a great campaign issue. It affects a large portion of the population, it is expensive (it currently accounts for about 10% of all ...
Stevenson, D. G.
PERSPECTIVE: Planning for the Future -- Long-Term Care and the 2008 Election
Date de mise en ligne : Mercredi 07 mai 2008 Patients ideally deserve to have a compassionate doctor, but might they be satisfied with one who is simply well-behaved? When I hear patients complain about doctors, their criticism often has ...
Kahn, M. W.
PERSPECTIVE: Etiquette-Based Medicine
Date de mise en ligne : Mercredi 07 mai 2008
The HAPO Study Cooperative Research Group
ORIGINAL ARTICLE: Hyperglycemia and Adverse Pregnancy Outcomes
In this large, multinational study, glucose levels that were increased during pregnancy but were below levels diagnostic of diabetes were significantly associated with increased risks of birth weight above the 90th percentile and C-peptide levels above the 90th percentile, as well as with other adverse pregnancy outcomes. These results indicate the need to reconsider current thresholds for diagnosing and treating hyperglycemia during pregnancy.
Date de mise en ligne : Mercredi 07 mai 2008
Rowan, J. A., Hague, W. M., Gao, W., Battin, M. R., Moore, M. P., the MiG Trial Investigators
ORIGINAL ARTICLE: Metformin versus Insulin for the Treatment of Gestational Diabetes
This open-label trial compared insulin with metformin (with supplemental insulin if required) for the treatment of gestational diabetes mellitus. The rates of neonatal complications were similar in the two groups, and more women in the metformin group than in the insulin group reported that they would choose their assigned treatment again. These results provide support for the use of metformin as initial treatment for gestational diabetes in women who require pharmacologic therapy.
Date de mise en ligne : Mercredi 07 mai 2008
Haissaguerre, M., Derval, N., Sacher, F., Jesel, L., Deisenhofer, I., de Roy, L., Pasquie, J.-L., Nogami, A., Babuty, D., Yli-Mayry, S., De Chillou, C., Scanu, P., Mabo, P., Matsuo, S., Probst, V., Le Scouarnec, S., Defaye, P., Schlaepfer, J., Rostock, T., Lacroix, D., Lamaison, D., Lavergne, T., Aizawa, Y., Englund, A., Anselme, F., O'Neill, M., Hocini, M., Lim, K. T., Knecht, S., Veenhuyzen, G. D., Bordachar, P., Chauvin, M., Jais, P., Coureau, G., Chene, G., Klein, G. J., Clementy, J.
ORIGINAL ARTICLE: Sudden Cardiac Arrest Associated with Early Repolarization
An electrocardiographic pattern of early repolarization (elevation of the QRS-ST junction) is generally believed to be benign. In this study, however, researchers found that among case subjects with idiopathic ventricular fibrillation, the prevalence of early repolarization was significantly increased, as compared with that among control subjects. These findings will lead to a reconsideration of the clinical significance of early repolarization.
Date de mise en ligne : Mercredi 07 mai 2008
Wilde, A. A.M., Bhuiyan, Z. A., Crotti, L., Facchini, M., De Ferrari, G. M., Paul, T., Ferrandi, C., Koolbergen, D. R., Odero, A., Schwartz, P. J.
ORIGINAL ARTICLE: Brief Report: Left Cardiac Sympathetic Denervation for Catecholaminergic Polymorphic Ventricular Tachycardia
A surgical procedure for cardiac sympathetic denervation successfully controlled recurrent polymorphic ventricular tachycardia in three patients with a heritable form of catecholaminergic polymorphic ventricular tachycardia.
Date de mise en ligne : Mercredi 07 mai 2008
Schuetz, C., Huck, K., Gudowius, S., Megahed, M., Feyen, O., Hubner, B., Schneider, D. T., Manfras, B., Pannicke, U., Willemze, R., Knuchel, R., Gobel, U., Schulz, A., Borkhardt, A., Friedrich, W., Schwarz, K., Niehues, T.
ORIGINAL ARTICLE: Brief Report: An Immunodeficiency Disease with RAG Mutations and Granulomas
This report describes three unrelated girls with an immunodeficiency disease associated with disseminated granulomas and compound heterozygous mutations in the RAG1 or RAG2 recombination activating genes. Unlike severe combined immunodeficiency disease with null mutations in RAG1 or RAG2, this immunodeficiency disorder did not present with severe infection in early childhood, probably because the RAG mutations allowed a low level of recombinase activity.
Date de mise en ligne : Mercredi 07 mai 2008
Kerbel, R. S.
REVIEW ARTICLE: Molecular Origins of Cancer: Tumor Angiogenesis
The dependency of the growth of tumors on blood vessels, once considered a doubtful proposition, has become a major avenue of research and drug development. This review discusses the results of recent investigations into tumor angiogenesis and surveys the mechanisms of action of antibodies and drugs that inhibit angiogenesis.
Date de mise en ligne : Mercredi 07 mai 2008 An 83-year-old woman with long-standing atrial fibrillation who had previously undergone atrioventricular nodal ablation and pacemaker placement presented with symptoms of progressive heart failure. Physical examination was notable for elevated ...
Stewart, G. C., Nohria, A.
IMAGES IN CLINICAL MEDICINE: Giant Left Atrium
Date de mise en ligne : Mercredi 07 mai 2008 Photodynamic therapy is a noninvasive therapy for nonhyperkeratotic actinic keratoses and basal-cell carcinoma. Photodynamic therapy involves the activation of a photosensitizing drug by visible light to produce activated oxygen species ...
Sanmartin, O., Guillen, C.
IMAGES IN CLINICAL MEDICINE: Fluorescence Diagnosis of Subclinical Actinic Keratoses
Date de mise en ligne : Mercredi 07 mai 2008
Huffman, J. C., Park, L. T., Welch, C. A., Nierenberg, A. A., Januzzi, J. L., Pomerantz, S. R.
CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL: Case 14-2008 -- A 78-Year-Old Man with Anergia and Anhedonia Associated with Cardiovascular Surgery
A 78-year-old man was admitted to the inpatient psychiatry service because of anergia and anhedonia of 33 months' duration. His symptoms began shortly after he was told he needed repair of an abdominal aortic aneurysm, persisted despite multiple trials of antidepressant medications, and worsened after repair of the aneurysm. An episode of major depression had occurred at the age of 58 years after coronary-artery bypass surgery and had responded to electroconvulsive therapy. A management decision was made.
Date de mise en ligne : Mercredi 07 mai 2008 Pregnancy is associated with relative carbohydrate intolerance and insulin resistance. Gestational diabetes mellitus (carbohydrate intolerance first diagnosed during pregnancy) has long been recognized as a risk factor for a number ...
Ecker, J. L., Greene, M. F.
EDITORIAL: Gestational Diabetes -- Setting Limits, Exploring Treatments
Date de mise en ligne : Mercredi 07 mai 2008 For more than 60 years, physicians have been fascinated by a peculiar electrocardiographic pattern called "early repolarization."1 When Google is queried, more than 1 million hits turn up on this ...
Wellens, H. J.
EDITORIAL: Early Repolarization Revisited
Date de mise en ligne : Mercredi 07 mai 2008
Semenza, G. L.
CLINICAL IMPLICATIONS OF BASIC RESEARCH: A New Weapon for Attacking Tumor Blood Vessels
The vascular endothelial growth factor is the target of the antiangiogenic drug bevacizumab. Another protein, placental growth factor, also represents a promising target for countering tumor angiogenesis.
Date de mise en ligne : Mercredi 07 mai 2008 To the Editor: On the basis of the Corticosteroid Therapy of Septic Shock (CORTICUS) study, Sprung et al. (Jan. 10 ...
Daley, M. R., Seam, N., Luboshitzky, R., Qupti, G., Bollaert, P.-E., Marik, P. E., Pastores, S. M., Kavanagh, B. P., Manoach, S., Sprung, C. L., Singer, M., Annane, D., the CORTICUS Study Group
CORRESPONDENCE: Corticosteroids for Septic Shock
Date de mise en ligne : Mercredi 07 mai 2008 To the Editor: Brunkhorst and colleagues (Jan. 10 issue)1 report that the Efficacy of Volume Substitution and Insulin Therapy in ...
Lacherade, J.-C., Outin, H., De Jonghe, B., Bracco, D., Schricker, T., Carvalho, G., Muller, L., Jaber, S., Lefrant, J. Y., Van den Berghe, G., Wilmer, A., Bouillon, R., Ellger, B., van den Heuvel, I., Poelaert, J., Brunkhorst, F. M., Reinhart, K., Engel, C.
CORRESPONDENCE: Insulin and Pentastarch for Severe Sepsis
Date de mise en ligne : Mercredi 07 mai 2008 To the Editor: Since the role of hepatotropic viruses in severe aplastic anemia is well established,1 we suggest that the ...
Lund, T., Tolar, J., Alexander, S. I., Reddel, R. R., Stormon, M. O.
CORRESPONDENCE: Chimerism and Tolerance in a Recipient of a Deceased-Donor Liver Transplant
Date de mise en ligne : Mercredi 07 mai 2008 To the Editor: With regard to the article by Wang et al. (Nov. 22 issue), it is increasingly recognized that ...
Pocock, S. J., Lubsen, J., Wang, R., Lagakos, S. W.
CORRESPONDENCE: More on Subgroup Analyses in Clinical Trials
Date de mise en ligne : Mercredi 07 mai 2008 To the Editor: The long-QT syndrome and catecholaminergic polymorphic ventricular tachycardia are the most common inherited cardiac channelopathies.1 Although the ...
Beckmann, B. M., Wilde, A. A.M., Kaab, S.
CORRESPONDENCE: Dual Inheritance of Sudden Death from Cardiovascular Causes
Date de mise en ligne : Mercredi 07 mai 2008 To the Editor: Early repolarization, consisting of an elevation of the QRS-ST junction (J point), QRS notching or slurring (J ...
Nam, G.-B., Kim, Y.-H., Antzelevitch, C.
CORRESPONDENCE: Augmentation of J Waves and Electrical Storms in Patients with Early Repolarization
Date de mise en ligne : Mercredi 07 mai 2008 Health care reform is back -- at least rhetorically. These two books suggest that both Democrats and Republicans are missing the boat, or perhaps rearranging deck chairs on a ship ...
Woolhandler, S., Himmelstein, D. U.
BOOK REVIEW: The Corrosion of Medicine: Can the Profession Reclaim Its Moral Legacy?; Worried Sick: A Prescription for Health in an Overtreated America
Date de mise en ligne : Mercredi 07 mai 2008 "Medicalization" occurs when conditions that were not previously construed as illnesses are defined and treated as medical problems. Accordingly, these problems are newly deemed to require treatment by physicians or ...
Fendrich, M.
BOOK REVIEW: The Medicalization of Society: On the Transformation of Human Conditions into Treatable Disorders
Les derniers abstracts de la revue The Lancet : |
Date de mise en ligne : Vendredi 09 mai 2008
The Lancet
Combating counterfeit drugs
Last week, the US Food and Drug Administration (FDA) told a Congressional hearing that it believes a contaminant found in batches of heparin, which have killed at least 81 patients, might have been deliberately added. The source of the contaminant?oversulfated chondroitin sulphate?has been traced back to a Chinese supplier of drug manufacturer Baxter International. Why the stocks might have been intentionally contaminated is unclear, but the fact that oversulfated chondroitin sulphate is structurally similar to heparin but about 100 times cheaper, raises the very real possibility that it could have been added by counterfeiters.
Date de mise en ligne : Vendredi 09 mai 2008
The Lancet
Cancer: a global response to a global problem
The International Cancer Genome Consortium (ICGC) is set to tackle the genetic make-up of human cancers by taking a global approach to hunt for major gene mutations. The ultimate aim is to improve the diagnosis, treatment, and prevention of cancer around the world. Indeed, cancer represents a health problem of alarming proportions. By 2050 it is estimated that more than 27 million cancer cases per year will be diagnosed, with 17·5 million deaths.
Date de mise en ligne : Vendredi 09 mai 2008
The Lancet
Funding philanthropy through innovation
Philanthropy, most would argue, is a good thing, and to be encouraged in all guises by all mechanisms. Yet donating money to charitable causes can be far from simple, particularly for businesses, given the complex tax and legal structures in many countries. Investing in not-for-profit organisations can be even more complicated?so much so, that many companies and individuals avoid doing so, despite wishing to invest in good causes.
Date de mise en ligne : Vendredi 09 mai 2008
Dominik Wolf, Anna Maria Wolf
Mesenchymal stem cells as cellular immunosuppressants
In today's Lancet, Katarina Le Blanc and colleagues provide intriguing results on the therapeutic potential of mesenchymal stem cells for treatment of acute steroid-refractory graft-versus-host disease (GVHD). GVHD is a serious complication after allogeneic stem-cell transplantation and has a high mortality. Most of the available second-line and third-line treatments for steroid-refractory acute GVHD induce severe immunodeficiency, which is commonly accompanied by lethal infectious complications.
Date de mise en ligne : Vendredi 09 mai 2008
Victor Aboyans, Philippe Lacroix
Carotid bruit: good for silent cardiovascular disease?
For centuries, physicians have been taught to use physical signs for the diagnosis of cardiovascular diseases. In today's Lancet, Christopher Pickett and colleagues lead us to reconsider cardiovascular physical signs. In a meta-analysis, the authors assessed carotid bruits as markers of cardiovascular prognosis, rather than for their ability to detect carotid lesions and subsequent risk of stroke. The researchers estimated that people with carotid bruits have twice the risk of myocardial infarction and cardiovascular death compared with people who do not.
Date de mise en ligne : Vendredi 09 mai 2008
Robin Mermelstein
Moving tobacco prevention outside the classroom
Too many adolescents still smoke. Worldwide, 9·5% of students aged 13?15 years smoke cigarettes, with the highest rates in European countries (19·1%). This rate of 19·1% suggests a susceptibility to start smoking in students who have never smoked cigarettes. Warren and colleagues suggested that the number of deaths attributed now to smoking-related diseases are probably underestimates, and are likely to exceed 10 million yearly worldwide by 2020. Cigarette smoking most commonly starts during adolescence, and dependence on nicotine might also develop during this period. Aggressive interventions are therefore needed for this group. School-based prevention programmes have been a mainstay of tobacco-control efforts, even though only about half of the studies of rigorous design show positive long-term effects for the intervention. Given that tobacco-prevention curricula are needed by many schools, the challenge becomes how to effectively enhance these programmes. The study by Rona Campbell and colleagues in today's Lancet, the ASSIST trial, provides promising evidence for a way to bolster the effectiveness of school-based programmes.
Date de mise en ligne : Vendredi 09 mai 2008
Matthias Egger, Andrew Boulle
Population effect of scaling up ART in resource-poor settings
The scale-up of antiretroviral therapy (ART) in resource-limited settings is based on a public-health approach to the provision of such treatment. Impressive progress has been made since 2004, and WHO's interim target of treating 3 million people has now been reached. The public-health goal of scaling up ART is not only to improve outcomes in those receiving treatment but also to reduce morbidity and mortality at the population level. In the absence of vital registration, and in settings where a large proportion of deaths occur outside the health system, population effects are difficult to assess. High-quality cohort studies of patients starting ART in resource-limited settings are increasingly available?eg, within the framework of the International epidemiological Databases to Evaluate AIDS (IeDEA). However, such cohort studies do not directly measure the population effectiveness of treatment.
Date de mise en ligne : Vendredi 09 mai 2008
John Eikelboom, Gordon Guyatt, Jack Hirsh
Guidelines for anticoagulant use in acute coronary syndromes
Guidelines published by authoritative societies have important influences on clinical practice. The authors of such guidelines, who are usually experts in the topic, comprehensively review research and generally make their recommendations with an explicit grading system.
Date de mise en ligne : Vendredi 09 mai 2008
Colleen O'Manique, Ronald Labonte
Rethinking (Product) RED
2 years ago, The Lancet announced the journal's partnership with (Product) RED, a business model launched by musician Bono and Bobby Shiver at the 2006 World Economic Forum. (RED) channels a portion of the profits from (RED)-branded goods to the Global Fund to Fight AIDS, Tuberculosis and Malaria. In addition to pledging US$30 000 to (Product) RED, The Lancet advertised the initiative, and editorialised that ?With (Product) RED they [business leaders] are?demonstrating leadership and commitment in areas of vital societal interest?.
Date de mise en ligne : Vendredi 09 mai 2008
Ara Darzi
Quality and the NHS Next Stage Review
Along with the white coat and stethoscope, the Hippocratic Oath?the injunction to do no harm?is one of the defining features of the medical profession in the public mind. It holds such significance and continues to resonate today precisely because it was the first time a clear distinction between curing and killing was drawn. Over two millennia since the oath was first taken, safety remains the first dimension of quality in advanced health systems. Today, health care is in transition from care to cure. The consequence has been the development of what Lewis Thomas has characterised as halfway technologies?those which have actually increased our capacity to do harm.
Date de mise en ligne : Vendredi 09 mai 2008
Samuel Loewenberg
US FDA feels the heat from Congressional hearings
A series of recent drug scandals and regulatory lapses in the USA are setting the stage for major reform of the US Food and Drug Administration. Experts say the agency needs more human and financial resources to ensure that the country's drug supply is safe. Samuel Loewenberg reports.
Date de mise en ligne : Vendredi 09 mai 2008
Sharmila Devi
Mauritius counts health successes
Mauritius has much to celebrate as it marks its 40th year of independence. Life expectancy has increased and infant mortality has fallen since the late 1960s. But drug addiction and chronic disease continue to challenge the island's health system. Sharmila Devi reports from Port Louis.
Date de mise en ligne : Vendredi 09 mai 2008
David Weatherall
Book: The scientific legacy of the hump-backed whale
At a time when the UK's scientific community is coming under increasing governmental pressure towards pursuing research that is perceived to be of more immediate commercial value, and when the buzz word for applicants for support for medical research is ?translational?, whatever that may mean, a book that discusses the interface between scientific research and commerce is bound to be of considerable interest. And if ?science? is interpolated between ?sex? and ?profits? in its title, there are all the ingredients for a best seller.
Date de mise en ligne : Vendredi 09 mai 2008
Katherine Nightingale
Book In Brief: A science canon
Why are children allowed, positively encouraged, to charge around science museums gasping at the wonders of the universe, but teenagers not? Why is failing high school chemistry used as currency at dinner parties, but admitting ignorance of the works of William Shakespeare cultural suicide? When and why, asks Natalie Angier, did adults fall out with science?
Date de mise en ligne : Vendredi 09 mai 2008
Dennis Palumbo
Book In Brief: On being resilient
A clear sign of Robert Wicks' understanding of the busy, often overwhelming life of the typical mental health professional appears early in this useful book, when he explains that he kept it as short as possible because clinicians have so little time.
Date de mise en ligne : Vendredi 09 mai 2008
Nellie Bristol
Profile: Donald R Hopkins: eradicating Guinea worm disease
Disease eradication has proven to be a rare and maddeningly elusive goal for global-health experts over the years. Despite Herculean attempts to abolish malaria, yellow fever, polio, and other scourges, only the smallpox campaign has been completely successful. But now efforts to eliminate Guinea worm disease (dracunculiasis) look likely to succeed. One man has been on the front lines of both successful efforts: Carter Center Vice President for Health Programs Donald R Hopkins.
Date de mise en ligne : Vendredi 09 mai 2008
Guy Kahane
Brain imaging and the inner life
?The intense intellectual and emotional life, and the heightening of sensations which came with the advance of civilization, made it clear to men that only a part of pain, pleasure, and profit of life lay in physical things. Thoughts, emotions, and sensations demanded legal recognition?, wrote Samuel Warren and Louis Brandeis in the landmark 1890 paper that first introduced the right to privacy to legal discourse. Warren and Brandeis saw themselves as articulating a moral idea that was already implicitly recognised but finally forced into the open by ?recent inventions and business methods??that is, by ?instantaneous? photography and tabloid gossip columns.
Date de mise en ligne : Vendredi 09 mai 2008
Clare Kapp
Obituary: Ivan Peter Toms
Physician, anti-apartheid and gay rights activist, and Executive Director of Cape Town City Health Department. Born in Johannesburg, South Africa, on July 11, 1952, he died of meningococcal meningitis in Cape Town on March 25, 2008, aged 55 years.
Date de mise en ligne : Vendredi 09 mai 2008
Regina Kunz, Marcel Wolbers, Tracy Glass, Johannes FE Mann
The COOPERATE trial: a letter of concern
In the context of a meta-analysis, we had reason to take an in-depth look at a study by Naoyuki Nakao and colleagues published in The Lancet in 2003. We detected implausibilities of serious concern.
Date de mise en ligne : Vendredi 09 mai 2008
Nandi Siegfried, David Pienaar
Health professionals don't feel secure in their own country
We support the recommendation of Edward Mills and colleagues (Feb 23, p 685) that countries recruiting health professionals from sub-Saharan Africa should make financial ?amends? to the region. However, we caution that such an action could become the means by which governments of rich countries appease their collective conscience, with little effect on the ongoing skills shortage in sub-Saharan African countries.
Date de mise en ligne : Vendredi 09 mai 2008
Satish Chand
Train and trap to trap and trash
In your Feb 23 Editorial (p 623), you propose, as the solution to the shortage of medical professionals in poor countries, to: ?[Demand] that rich countries stop actively recruiting from poorer nations?. You go on to argue that: ?Richer countries can no longer be allowed to exploit and plunder the future of resource-poor nations.?
Date de mise en ligne : Vendredi 09 mai 2008
Yang Tian, Lu Jun Hua, Wu Meng Chao
Chinese doctors' salaries
David McCoy and colleagues (Feb 23, p 675) give a detailed description of the ubiquitous low salaries of health workers in sub-Saharan Africa. A similar situation also exists in China.
Date de mise en ligne : Vendredi 09 mai 2008
Percy Mayta-Tristán, Andrés Dulanto-Pizzorni, J Jaime Miranda
Low wages and brain drain: an alert from Peru
David McCoy and colleagues, and the related Comment, show the diversity of factors related to low wages of sub-Saharan health professionals. In Peru, physicians' salaries have decreased to a quarter of 1976 salary levels, from S/.7974 to S/.1919 in 2004, adjusted for 2001 Peruvian nuevos soles. Physicians end up having two or more jobs to secure a decent income.
Date de mise en ligne : Vendredi 09 mai 2008
Kasonde Bowa
Zambia's health-worker crisis
In the World Report by Joseph Schatz (Feb 23, p 638) the numbers of doctors and nurses are inaccurate. The correct figures are 706 doctors and 8859 nurses. No mention is made of clinical officers (medical assistants) who number 1183.
Date de mise en ligne : Vendredi 09 mai 2008
Barbara Stilwell, Anne Wilson, Jim McCaffery
Non-physician clinicians in sub-Saharan Africa
Fitzhugh Mullan and Seble Frehywot (Dec 22, p 2158) have compiled some much needed information about the capacity of the existing health workforce in Africa to expand through increasing production of its non-physician clinicians (NPCs). We whole-heartedly support this proposal, and, at the same time, suggest that there are four further issues to be urgently addressed if NPCs are to realise their full potential.
Date de mise en ligne : Vendredi 09 mai 2008
The Lancet
Department of Error
Epstein JE. What will a partly protective malaria vaccine mean to mothers in Africa? Lancet 2007; 370: 1523?24?In this Comment (Nov 3), the fourth sentence of the third paragraph should have read: ?With the proportional analysis approach for the same data, the vaccine efficacy against acquiring an infection by 6 months of follow-up was 11%.?
Date de mise en ligne : Vendredi 09 mai 2008
The Lancet
Department of Error
Ceaser M. Euthanasia in legal limbo in Colombia. Lancet 2008; 371: 290?91?In this World Report (Jan 26), it was wrongly stated that active euthanasia is legal in Switzerland and Oregan, USA.
Date de mise en ligne : Vendredi 09 mai 2008
Katarina Le Blanc, Francesco Frassoni, Lynne Ball, Franco Locatelli, Helene Roelofs, Ian Lewis, Edoardo Lanino, Berit Sundberg, Maria Ester Bernardo, Mats Remberger, Giorgio Dini, R Maarten Egeler, Andrea Bacigalupo, Willem Fibbe, Olle Ringdén, on behalf of the Developmental Committee of the European Group for Blood and Marrow Transplantation
Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: a phase II study
Severe graft-versus-host disease (GVHD) is a life-threatening complication after allogeneic transplantation with haemopoietic stem cells. Mesenchymal stem cells modulate immune responses in vitro and in vivo. We aimed to assess whether mesenchymal stem cells could ameliorate GVHD after haemopoietic-stem-cell transplantation.
Date de mise en ligne : Vendredi 09 mai 2008
Christopher A Pickett, Jeffrey L Jackson, Brian A Hemann, J Edwin Atwood
Carotid bruits as a prognostic indicator of cardiovascular death and myocardial infarction: a meta-analysis
Although carotid bruits are deemed to be markers of generalised atherosclerosis, they are poor predictors of cerebrovascular events. We investigated whether a carotid bruit predicts myocardial infarction and cardiovascular death.
Date de mise en ligne : Vendredi 09 mai 2008
R Campbell, F Starkey, J Holliday, S Audrey, M Bloor, N Parry-Langdon, R Hughes, L Moore
An informal school-based peer-led intervention for smoking prevention in adolescence (ASSIST): a cluster randomised trial
Schools in many countries undertake programmes for smoking prevention, but systematic reviews have shown mixed evidence of their effectiveness. Most peer-led approaches have been classroom-based, and rigorous assessments are scarce. We assessed the effectiveness of a peer-led intervention that aimed to prevent smoking uptake in secondary schools.
Date de mise en ligne : Vendredi 09 mai 2008
Andreas Jahn, Sian Floyd, Amelia C Crampin, Frank Mwaungulu, Hazzie Mvula, Fipson Munthali, Nuala McGrath, Johnbosco Mwafilaso, Venance Mwinuka, Bernard Mangongo, Paul EM Fine, Basia Zaba, Judith R Glynn
Population-level effect of HIV on adult mortality and early evidence of reversal after introduction of antiretroviral therapy in Malawi
Malawi, which has about 80 000 deaths from AIDS every year, made free antiretroviral therapy available to more than 80 000 patients between 2004 and 2006. We aimed to investigate mortality in a population before and after the introduction of free antiretroviral therapy, and therefore to assess the effects of such programmes on survival at the population level.
Date de mise en ligne : Vendredi 09 mai 2008
Geoffrey A Donnan, Marc Fisher, Malcolm Macleod, Stephen M Davis
Stroke
Stroke is the second most common cause of death and major cause of disability worldwide. Because of the ageing population, the burden will increase greatly during the next 20 years, especially in developing countries. Advances have occurred in the prevention and treatment of stroke during the past decade. For patients with acute stroke, management in a stroke care unit, intravenous tissue plasminogen activator within 3 h or aspirin within 48 h of stroke onset, and decompressive surgery for supratentorial malignant hemispheric cerebral infarction are interventions of proven benefit; several other interventions are being assessed. Proven secondary prevention strategies are warfarin for patients with atrial fibrillation, endarterectomy for symptomatic carotid stenosis, antiplatelet agents, and cholesterol reduction. The most important intervention is the management of patients in stroke care units because these provide a framework within which further study might be undertaken. These advances have exposed a worldwide shortage of stroke health-care workers, especially in developing countries.
Date de mise en ligne : Vendredi 09 mai 2008
Guy Decaux, Alain Soupart, Gilbert Vassart
Non-peptide arginine-vasopressin antagonists: the vaptans
Arginine-vasopressin is a hormone that plays an important part in circulatory and water homoeostasis. The three arginine-vasopressin-receptor subtypes?V1a, V1b, and V2?all belong to the large rhodopsin-like G-protein-coupled receptor family. The vaptans are orally and intravenously active non-peptide vasopressin receptor antagonists that are in development. Relcovaptan is a selective V1a-receptor antagonist, which has shown initial positive results in the treatment of Raynaud's disease, dysmenorrhoea, and tocolysis. SSR-149415 is a selective V1b-receptor antagonist, which could have beneficial effects in the treatment of psychiatric disorders. V2-receptor antagonists?mozavaptan, lixivaptan, satavaptan, and tolvaptan?induce a highly hypotonic diuresis without substantially affecting the excretion of electrolytes (by contrast with the effects of diuretics). These drugs are all effective in the treatment of euvolaemic and hypervolaemic hyponatraemia. Conivaptan is a V1a/V2 non-selective vasopressin-receptor antagonist that has been approved by the US Food and Drug Administration as an intravenous infusion for the inhospital treatment of euvolaemic or hypervolaemic hyponatraemia.
Date de mise en ligne : Vendredi 09 mai 2008
Richard Feachem, Oliver Sabot
A new global malaria eradication strategy
On Oct 17, 2007, Bill and Melinda Gates called for complete eradication to be adopted as the new goal for the age-old fight against malaria, with the Director General of WHO, Margaret Chan, promptly echoing their conviction. Although debate over the wisdom of this target will continue, growing impatience with the low ambitions of current efforts, fuelled by reductions in morbidity and mortality in some countries and progress in the development of new drugs and the first-ever vaccine, will lead many decision makers to adopt eradication of malaria as the primary aim for their organisations.
Date de mise en ligne : Vendredi 09 mai 2008
Daniel Saura, Daniel Rodríguez, Francisco Marín, Gonzalo de la Morena, Inés Solís, Mariano Valdés
Unable to speak?because of a drip
In January, 2007, a 58-year-old woman started to cough and wheeze. She had a mild fever. She had no medical history of note, other than longstanding t


