bluuebunny/crossref_metadata_2025_split huggingface dataset:
Body composition by dual‐energy X‐ray absorptiometry in women with previous pre‐eclampsia or small‐for‐gestational‐age offspring
Authors: Berends AL , Zillikens MC , de Groot CJM , Rivadeneira F , Oostra BA , van Duijn CM , Steegers EAP 
Published: January 2009

Objective  To investigate differences in body composition and fat distribution between women with previous pre‐eclampsia or small‐for‐gestational‐age (SGA) offspring and those with uncomplicated pregnancies.Design  Cohort study.Setting  Population‐based study in a genetically isolated population in the southwest of the Netherlands.Population  Women after pregnancies complicated by pre‐eclampsia (n=45), SGA offspring (n=53) and uncomplicated pregnancies (n=106).Methods  Women were compared for body composition and fat distribution variables, assessed by dual‐energy X‐ray absorptiometry (DXA) and anthropometrics at a mean follow‐up time of 10.8 (SD ±5.9) years after pregnancy.Main outcome measures  Total lean and fat mass, android fat mass, gynoid fat mass, android‐to‐gynoid fat ratio, waist and hip circumference, waist‐to‐hip ratio.Results  Women with previous pre‐eclampsia compared with controls had higher mean total fat mass index (11.5 ± 0.6 versus 9.7 ± 0.4 kg/m2; P = 0.03), lean mass index (15.8 ± 0.3 versus 14.5 ± 0.2 kg/m2; P =0.001) and body mass index ([BMI]; 28.4 ± 0.8 versus 25.4 ± 0.5 kg/m2; P = 0.005). Their waist circumferences (90.7 ± 2.0 versus 78.5 ± 1.3 cm; P < 0.001) and waist‐to‐hip ratios (0.86 ± 0.01 versus 0.77 ± 0.01; P < 0.001) were also higher as well as android fat mass (2.8 ± 0.2 versus 2.1 ± 0.1 kg; P = 0.01) and android‐to‐gynoid fat ratios (0.45 ± 0.02 versus 0.39 ± 0.01; P = 0.02). Mean total fat, lean and BMI was not significantly different between women with previous SGA offspring and controls, yet waist‐to‐hip ratios (0.83 ± 0.01; P < 0.001) were higher. The observed differences in waist and hip circumference, waist‐to‐hip ratio and gynoid fat mass could not be attributed to differences in BMI.Conclusion  Women with previous pre‐eclampsia or SGA offspring pregnancies compared with those with uncomplicated pregnancies have a preferential fat accumulation in the abdominal over hip region, which may explain, at least partly, their increased cardiovascular risk.
Evaluation of postpartum blood loss after misoprostol‐induced labour
Authors: Elsedeek MShE , Awad EE , Elsebaey SM 
Published: January 2009

Objective To objectively evaluate postpartum blood loss after successful misoprostol induction and compare it with blood loss after oxytocin induction of labour.Design Prospective randomised study.Setting Labour ward in university maternity hospital.Population A total of 150 women up to third parity with completed 40 weeks of singleton normal pregnancy, average size cephalic fetus.Methods Cases were randomised between oxytocin induction and misoprostol induction. Blood was collected in suction set and measured in the delivery room starting after delivery of the fetus and was evaluated by pad weighing in the following 6 hours. Pre‐ and postdelivery haematocrit were measured and difference between the two values was assessed and analysed.Main outcome measures Success of induction, induction delivery interval, postpartum blood loss, and difference between pre‐ and postdelivery haematocrit.Results Induced labour was significantly faster with misoprostol induction (P< 0.001). Blood loss and haematocrit difference was significantly greater in the misoprostol group than in oxytocin group (P< 0.02 and 0.001, respectively). Blood loss in both groups was significantly correlated with higher initial Bishop score (P< 0.001 and 0.024, respectively) and short labour duration (P< 0.0002 and 0.0001, respectively).Conclusions Misoprostol induction is associated with increased blood loss especially when used in women with high Bishop score; therefore, it is better reserved for cases requiring cervical ripening.
Uterine and umbilical artery Doppler are comparable in predicting perinatal outcome of growth‐restricted fetuses
Authors: Ghosh GS , Gudmundsson S 
Published: January 2009

Objective  To compare umbilical and uterine artery Doppler in predicting outcome of pregnancies suspected of fetal growth restriction (FGR).Design  A prospective study included 353 singleton pregnancies complicated by an FGR fetus.Setting  University Hospital setting.Sample  Pregnancies suspected of FGR diagnosed by ultrasound fetal biometry during a 5‐year period.Main outcome measure  Perinatal outcome in relation to uterine and umbilical artery Doppler.Methods  The women underwent Doppler examination of the umbilical and uterine arteries. Results from the uterine, but not the umbilical artery, were blind to the woman and managing obstetrician. The Doppler results were related to perinatal outcomes including small for gestational age newborns, caesarean delivery, premature delivery (<37 weeks of gestation) and admission of the newborn to a neonatal intensive care unit.Results  Abnormal uterine artery Doppler velocimetry was seen in 120 (33.4%) pregnancies and abnormal umbilical artery Doppler in 102 (28.4%). There was a statistically significant correlation between abnormal Doppler of both the umbilical and uterine arteries and adverse outcome of pregnancy. The two vessels were comparable in predicting adverse outcome. Women with normal umbilical artery Doppler (251) were analysed separately. Abnormal uterine artery Doppler, seen in 61 (24.3%) of those women, showed a statistically significant correlation for adverse outcome of pregnancy.Conclusions  Doppler examinations of the uterine and/or the umbilical arteries seem to be comparable as predictors of outcome in pregnancies complicated by FGR. Including uterine artery Doppler in the surveillance of growth‐restricted fetuses might detect a group of pregnancies at high risk, even though the umbilical artery Doppler was normal.
Endothelium‐dependent contractions in SHR: a tale of prostanoid TP and IP receptors
Authors: Félétou Michel , Verbeuren Tony J , Vanhoutte Paul M 
Published: January 2009

In the aorta of spontaneously hypertensive rats (SHR), the endothelial dysfunction is due to the release of endothelium‐derived contracting factors (EDCFs) that counteract the vasodilator effect of nitric oxide, with no or minor alteration of its production. The endothelium‐dependent contractions elicited by acetylcholine (ACh) involve an increase in endothelial [Ca2+]i, the production of reactive oxygen species, the activation of endothelial cyclooxygenase‐1, the diffusion of EDCF and the subsequent stimulation of smooth muscle cell TP receptors. The EDCFs released by ACh have been identified as PGH2and paradoxically prostacyclin. Prostacyclin generally acts as an endothelium‐derived vasodilator, which, by stimulating IP receptors, produces hyperpolarization and relaxation of the smooth muscle and inhibits platelet aggregation. In the aorta of SHR and Wistar‐Kyoto rats, prostacyclin is the principal metabolite of arachidonic acid released by ACh. However, in SHR aorta, prostacyclin does not produce relaxations but activates the TP receptors on vascular smooth muscle cells and produces contraction. The IP receptor is not functional in the aortic smooth muscle cells of SHR as early as 12 weeks of age, but its activity is not reduced in platelets. Therefore, prostacyclin in the rule protects the vascular wall, but in the SHR aorta it can contribute to endothelial dysfunction. Whether or not prostacyclin plays a detrimental role as an EDCF in other animal models or in human remains to be demonstrated. Nevertheless, because EDCFs converge to activate TP receptors, selective antagonists of this receptor, by preventing endothelium‐dependent contractions, curtail the endothelial dysfunction in diseases such as hypertension and diabetes.Mandarin translation of abstract
Physical methods of nucleic acid transfer: general concepts and applications
Authors: Villemejane Julien , Mir Lluis M. 
Published: January 2009

Physical methods of gene (and/or drug) transfer need to combine two effects to deliver the therapeutic material into cells. The physical methods must induce reversible alterations in the plasma membrane to allow the direct passage of the molecules of interest into the cell cytosol. They must also bring the nucleic acids in contact with the permeabilized plasma membrane or facilitate access to the inside of the cell. These two effects can be achieved in one or more steps, depending upon the methods employed. In this review, we describe and compare several physical methods: biolistics, jet injection, hydrodynamic injection, ultrasound, magnetic field and electric pulse mediated gene transfer. We describe the physical mechanisms underlying these approaches and discuss the advantages and limitations of each approach as well as its potential application in research or in preclinical and clinical trials. We also provide conclusions, comparisons, and projections for future developments. While some of these methods are already in use in man, some are still under development or are used only within clinical trials for gene transfer. The possibilities offered by these methods are, however, not restricted to the transfer of genes and the complementary uses of these technologies are also discussed. As these methods of gene transfer may bypass some of the side effects linked to viral or biochemical approaches, they may find their place in specific clinical applications in the future.This article is part of a themed section on Vector Design and Drug Delivery. For a list of all articles in this section see the end of this paper, or visit: http://www3.interscience.wiley.com/journal/121548564/issueyear?year=2009
Optimizing the treatment of chronic hepatitis due to hepatitis C virus genotypes 2 and 3: a review
Authors: Tarantino Giuseppe , Craxì Antonio 
Published: January 2009

AbstractRecently several randomized trials involving exclusively HCV 2 and 3 patients have explored the possibility of reducing the duration of therapy with PEG IFNs and ribavirin to 12–16 weeks. Among these, the largest studies (ACCELERATE, NORTH‐C and NORDynamIC) have failed to demonstrate, by intention‐to‐treat analysis, that short treatment is non‐inferior to the standard duration of 24 weeks originated by phase 3 trials. Even though obtaining univocal conclusions from these studies are difficult to obtain due to some critical differences (trial design, genotypes 2/3 ratio, rate of cirrhosis at baseline, ribavirin dose, assays to detect HCV‐RNA etc), all have proved that a rapid virological response (HCV‐RNA negative at 4 weeks) is the strongest predictor of SVR. Therefore, excluding risk factors for virological relapse at baseline, and identifying in the early phase of treatment, features related to a sustained response, the decision to reduce the duration of treatment to less than 24 weeks in HCV‐2 and 3 patients can be response‐guided appropriately.Ongoing studies will assess whether extended 48 week regimens can benefit non‐RVR patients with HCV 2 or 3, especially those with more severe fibrosis.
The history of the “natural history” of hepatitis C (1968–2009)
Authors: Seeff Leonard B. 
Published: January 2009

AbstractIn the late 1960's, only types A and B hepatitis were believed to exist, distinguished by circumstances of exposure and incubation periods. In the early 1970's, studies of transfusion recipients were begun with the belief that hepatitis B would be responsible should transfusion‐associated hepatitis develop. After discovery of the viruses of hepatitis A and B, neither agent was found responsible, hence non‐A, non‐B (NANB) hepatitis. Initial follow‐up of these cases showed that ∼ 50% developed chronic hepatitis based on persistence of serum enzymes for at least 6 months. Approximately 15 years later, after the hepatitis C virus had been identified as the cause for NANB hepatitis, chronic hepatitis was found to develop more frequently as indicated by persistent viral infection in over 80% of infected adults but in only about 50% of infected children or young women. Follow‐up over 2 to 4 decades indicated that many infected persons developed progressive hepatic fibrosis, sometimes culminating in cirrhosis and/or liver cancer. Long‐term natural history studies have proved to be challenging because disease onset is often silent and progression extremely slow. Differing strategies have been used to determine the natural history, the descriptions and results of which are presented in this review.
Protease and polymerase inhibitors for the treatment of hepatitis C
Authors: Asselah Tarik , Benhamou Yves , Marcellin Patrick 
Published: January 2009

AbstractChronic hepatitis C is among the leading causes of chronicliver disease worldwide, with approximately 170 million people infected. The severity of disease varies from asymptomaticchronic infection to cirrhosis and hepatocellular carcinoma.Recently,advances have been made, with the combination of pegylated interferon (PEG‐IFN) and ribavirin leading to a sustained virological response (SVR) in approximately 55% of cases. In genotypes 2 or 3, SVR rates reach 80%; in genotype 1 SVR rates is 50%. Furthermore, SVR appears to be long lasting, associated probably with a reduction in the risk of cirrhosis and hepatocellular carcinoma. Despite this progress, treatment failure still occurs in about halfof the patients. Furthermore, therapy results in several side effects and high costs. These limitations have led to important development of novel compounds under the name of specifically targeted antiviral therapy for HCV (STAT‐C). Also, considering side effects and treatment cost, prediction of virologicalnon‐response is mandatory. The management of chronic hepatitis C must include better knowledge of viral cycle and mechanisms of non response. The development of new molecules such as HCV enzyme inhibitors is ongoing. The aim of this review is to summarize results obtained with STATC: protease and polymerase inhibitors.
New drugs for the treatment of hepatocellular carcinoma
Authors: Boucher Eveline , Forner Alejandro , Reig Maria , Bruix Jordi 
Published: January 2009

AbstractTreatment of hepatocellular carcinoma has dramatically changed in the last years. The better knowledge of the molecular mechanisms responsible of tumor initiation and progression has allowed the development of molecular targeted therapies that specifically block the disrupted pathways. Among all these new agents, Sorafenib is the only one that has shown efficacy in terms of survival in advanced stage in two randomized, double‐blind, controlled trials. The positive result of these two trials are the proof of the efficacy of molecular targeted therapies in hepatocellular carcinoma and opens the door to multipathway blockade and the use of these targeted therapies in the adjuvant setting. Other agents have shown promising results in phase 1‐2 trials but further studies are needed to demonstrate their efficacy. In the next years, efforts should be directed to identifying genomic and proteomic profiling that will help us to assess the prognosis and to define what treatment benefits whom, ultimately giving way to personalized medicine.
Hepatitis C genotype 4 therapy: increasing options and improving outcomes
Authors: Kamal Sanaa M. 
Published: January 2009

AbstractHepatitis C virus genotype 4 (HCV‐G4) is prevalent in the Middle East and Africa and has spread to several regions in Europe. HCV‐G4 represents a major health problem in Egypt, with a prevalence rate of 13%. Recently, HCV‐G4 has been spreading in Europe particularly among intravenous drug users (IDU) populations, who represent the main reservoir for HCV in Europe. This article reviews the current therapeutic strategies for HCV‐G4 infections in different populations. HCV‐G4 has been considered a difficult‐to‐treat genotype because of the poor sustained virological response (SVR) rates reported with a conventional interferon (IFN)‐based regimen. Pegylated IFN and ribavirin combination therapy was associated with significant improvements in SVR rates that currently exceed 60%, particularly with individualized therapy. Lower response rates have been reported in specific situations, namely chronic HCV‐G4 infection in IDUs and patients co‐infected with human immunodeficiency virus (HIV). Rapid and early virological responses have been useful tools for determination of the duration of therapy. In conclusion: therapy of HCV‐G4 has shown significant improvements, with higher sustained response rates and possibilities for a shorter duration. More research is required to optimize therapy in special populations such as IDUs and HIV‐co‐infected patients.
Retreatment of chronic hepatitis C: who and how?
Authors: Heathcote Jenny 
Published: January 2009

AbstractAll but about 10% of patients with chronic hepatitis C (CHC) (predominantly those infected with genotype 1) can respond to some degree to ‘combination’ therapy with interferon (IFN) and ribavirin. The slower the virological response to treatment, the less likely sustained viral clearance will take place. Many factors influence response to antiviral therapy; most cannot be reversed (e.g. sex, age, cirrhosis, genotype and viral load). A sustained viral clearance is considerably facilitated by compliance with full‐dose therapy for the prescribed time. The potential cause(s) for non‐response need(s) to be ascertained before attempting retreatment. The 10% of patients who are true ‘null’ responders may respond to the new specifically targeted antiviral therapies but whether the response can be sustained off‐therapy is unclear. Adjunctive therapies may facilitate response to retreatment if intolerance to treatment leading to diminished or absent doses was problematic in the past. Retreatment with a long‐acting IFN and an adequate ribavirin dose (15 mg/kg), but given for 72 weeks in prior relapsers following 48 weeks of treatment, will enhance sustained virological response (SVR) rates. No benefit is gained from changing one pegylated IFNα (PEG IFNα) to another unless the treatment duration is extended. Only α‐interferons are effective. For those individuals who still fail to achieve SVR, recruitment to trials of new treatments should be encouraged particularly for those with advanced liver disease. Lifestyle modification may be appropriate in attempt to reduce the chance of complications of liver disease, namely hepatocellular carcinoma, by smoking cessation, eliminating obesity and increasing coffee consumption.
Assessment of hepatitis C: non‐invasive fibrosis markers and/or liver biopsy
Authors: Bedossa Pierre 
Published: January 2009

AbstractChronic viral hepatitis is a prolonged inflammatory disease of the liver that may lead to the development of fibrosis, necro‐inflammation and other associated pathological features. Because fibrosis and its end‐point cirrhosis are the main causes of morbidity and mortality, fibrosis assessment is considered as the most relevant information for the evaluation of the severity of the disease and as a useful indicator for prognosis and treatment decision. Because fibrosis implies morphological damage, liver biopsy has come to be the natural gold standard for staging the disease. However, the high prevalence of chronic hepatitis C in addition to the cost and constraints generated by this procedure have triggered an intensive search for alternative methods for fibrosis evaluation. In this article, the strengths and weaknesses of liver biopsy and of non‐invasive markers will be reviewed and their respective roles in management of patients with chronic hepatitis C will be discussed.
Natural history of chronic hepatitis B virus infection and long‐term outcome under treatment
Authors: Liaw Yun‐Fan 
Published: January 2009

AbstractChronic hepatitis B virus (HBV) infection is a dynamic state of interactions among HBV, the hepatocytes and the immune system of the patient. Perinatally or early childhood‐acquired chronic HBV infection has a long ‘immune tolerant phase’, when patients are young, and HBeAg seropositive with a high viral load but with no significant liver disease. Persistent or episodic liver injuries during the ‘immune clearance phase’ may lead to decompensation, fibrosis progression or cirrhosis development in some patients, but may eventually lead to HBV‐DNA seroclearance with HBeAg seroconversion and entry into the ‘inactive phase’ with remission. Hepatitis may relapse, because of reactivation of HBV with precore or basal core promptor mutations, and develop ‘HBeAg‐negative chronic hepatitis’, in some patients. In contrast, HBsAg seroclearance may occur in those with sustained remission. During the course, HBV replication is the key driver of disease progression including development of cirrhosis and hepatocellular carcinoma (HCC). Among the currently available anti‐HBV drugs, the most extensive and longest experience has been gained with conventional interferon (IFN)‐α and lamivudine. A finite course of IFN therapy has long‐term benefit in achieving a cumulative response, increasing HBsAg seroclearance and reducing cirrhosis and/or HCC. Maintained virological response to lamivudine therapy has a similar long‐term benefit in reducing disease progression. Pegylated IFN and newer nucleos(t)ide analogues may have even better long‐term outcomes because of better therapeutic efficacy and/or a low risk of drug resistances. The treatment outcomes are still far from satisfactory. The development of safe and affordable anti‐HBV agents/strategies is needed to further improve outcomes.
HBeAg‐positive chronic hepatitis B: why do I treat my patients with pegylated interferon
Authors: Lau George K. K. 
Published: January 2009

AbstractWorldwide, chronic hepatitis B virus infection is a major cause of end‐stage liver disease and hepatocellular carcinoma. While the past two decades have brought major advances in the availability of treatments to help delay or prevent these outcomes, treatment of chronic hepatitis B remains a serious challenge. With the recent availability of potent new nucleot(s)ide such as entecavir, tenofovir and telbuvidine, I still use pegylated interferon (PEG‐IFN)‐α for the treatment of chronic HBeAg‐positive patients. This is based on its relatively higher effectiveness in restoring the host immune control on viral replication, resulting in sustained diseases remission in a proportion of patients, a finite course of therapy and the absence of viral resistance. The two major hindrances to its wide application are its lack of effectiveness in a large proportion of patients and its side‐effect profile. The former shortcoming can be circumvented to a certain extent with the use of response predictor models. Recently, based on long‐term follow‐up study, the better durability of sustained response further enhances the confidence in the use of PEG‐IFN‐α in chronic HBeAg‐positive patients.
Optimal therapy in genotype 1 patients
Authors: Farnik Harald , Mihm Ulrike , Zeuzem Stefan 
Published: January 2009

AbstractMost infections with hepatitis C virus (HCV) fail to resolve spontaneously and progress to chronic hepatitis C. Genotype 1 HCV accounts for most hepatitis C infections in North America, Western Europe, and Japan. Patients infected with HCV genotype 1 are the most resistant to treatment, which results in poor treatment outcomes. Although sustained virologic response (SVR) rates have significantly improved with introduction of combination therapy with pegylated interferon alfa and ribavirin, the rates are still lower than those in genotype 2 or 3 infections. This review discusses how treatment outcomes in patients with HCV genotype 1 infection can be optimized by using the drugs currently licensed for treatment of hepatitis C: pegylated interferon alfa‐2a/b and ribavirin. Dose modifications and variations of treatment duration are the two strategies that have been investigated best, so far. Treatment – naïve patients and non‐responders and relapsers to prior antiviral therapy are discussed separately.