Vertical transmission has become the most common mode of transmission of hepatitis C virus （HCV） in children.The rate of perinatal transmission from an HCVinfected mother to her child ranges from 2% ...to 5% and the prevalence of HCV in children in developed countries ranges between 0.1% and 0.4%.Spontaneous viral clearance seems to be dependent on the genotype and has been reported between 2.4%-25%.For chronically infected patients,treatment with recombinant polyethylene glycol （PEG）-interferon α-2b and daily ribavirin has now been approved as standard treatment for children 2-17 years of age.In five large prospective studies,a total of 318 children and adolescents aged 3-17 years were treated either with subcutaneous PEG-interferon α-2b at a dose of 1-1.5 μg/kg or 60 μg/m2 once a week in combination with oral ribavirin （15 mg/kg per day） or PEG-interferon α-2a with ribavirin.Subjects with genotype 1 and 4 received the medication for 48 wk and individuals with genotype 2 and 3 mainly for 24 wk.Overall sustained viral response （SVR） was achieved in 193/318 （60.7%） of treated patients.Stratified for genotype;120/234 （51%） with genotype 1,68/73 （93%） with genotype 2/3,and 6/11 （55%） with genotype 4 showed SVR.Relapse rate was between 7.7% and 17%.Overall,treatment was well tolerated;how-ever,notable side effects were present in approximately 20%.According to recent experiences in the treatment of chronic hepatitis C in children and adolescents,a combination of PEG-interferon α with ribavirin has been found to be well tolerated and highly efficacious,particularly in individuals with genotype 2/3.Thus,this treatment can be recommended as standard of care until more effective treatment options will become available for genotype 1 patients.
To compare objective and subjective image quality parameters of three image reconstruction algorithms of different generations at routine multidetector computed tomographic (CT) examinations of the ...abdomen.
This institutional review board-approved study included 22 consecutive patients (mean age, 56.1 years ± 15.8 standard deviation; mean weight, 79.1 kg ± 14.8) who underwent routine CT examinations of the abdomen. A low-contrast phantom was used for objective quality control. Raw data sets were reconstructed by using filtered back projection (FPB), adaptive statistical iterative reconstruction (ASIR), and a model-based iterative reconstruction (MBIR). Radiologists used a semiquantitative scale (-3 to +3) to rate subjective image quality and artifacts, comparing both FBP and MBIR images with ASIR images. The Wilcoxon test and the intraclass correlation coefficient were used to evaluate the data. Measurements of objective noise and CT numbers of soft tissue structures were compared with analysis of variance.
The phantom study revealed an improved detectability of low-contrast targets for MBIR compared with ASIR or FBP. Subjective ratings showed higher image quality for MBIR, with better resolution (median value, 2; range, 1 to 3), lower noise (2; range, 1 to 3), and finer contours (2; range, 1 to 2) compared with ASIR (all P < .001). FBP performed inferiorly (0, range, -2 to 0; -1 range, -3 to 0; 0 range, -1 to 0, respectively; all, P < .001). Mean interobserver correlation was 0.9 for image perception and 0.7 for artifacts. Objective noise for FBP was 14%-68% higher and for MBIR was 18%-47% lower than that for ASIR (P < .001).
The MBIR algorithm considerably improved objective and subjective image quality parameters of routine abdominal multidetector CT images compared with those of ASIR and FBP.
Objective To determine whether longitudinal measurements of fecal S100A12, a fecal marker of intestinal inflammation, can identify very low birth weight infants at risk for necrotizing enterocolitis ...(NEC). Study design This prospective study included 145 preterm infants with birth weight <1500 g. Meconium and stool samples (n = 843) were collected prospectively on alternate days for 4 weeks, and fecal S100A12 and calprotectin were measured by enzyme-linked immunosorbent assay. Results Eighteen patients (12.4%) developed NEC. Gestational age and birth weight were significantly lower in the patients with NEC compared with unaffected reference infants. Fecal S100A12 levels were significantly higher in patients with severe NEC at onset of disease and also, in contrast to fecal calprotectin, at 4-10 days before onset of NEC compared with unaffected reference infants (ideal cutoff value, 65 μg/kg; sensitivity, 0.76; specificity, 0.56). Conclusions Fecal S100A12 level may be a helpful marker for predicting disease severity and early risk assessment for subsequent development of NEC. However, the use of fecal S100A12 as a predictive biomarker for NEC in very low birth weight infants may be limited due to a high interindividual and intraindividual variability in S100A12 fecal excretion.
In contrast to bacteria, microbiome analyses often neglect archaea, but also eukaryotes. This is partly because they are difficult to culture due to their demanding growth requirements, or some even ...have to be classified as uncultured microorganisms. Consequently, little is known about the relevance of archaea in human health and diseases. Contemporary broad availability and spread of next generation sequencing techniques now enable a stronger focus on such microorganisms, whose cultivation is difficult. However, due to the enormous evolutionary distances between bacteria, archaea and eukaryotes, the implementation of sequencing strategies for smaller laboratory scales needs to be refined to achieve as a holistic view on the microbiome as possible. Here, we present a technical approach that enables simultaneous analyses of archaeal, bacterial and eukaryotic microbial communities to study their roles in development and courses of respiratory disorders. We thus applied combinatorial 16S-/18S-rDNA sequencing strategies for sequencing-library preparation. Considering the lower total microbiota density of airway surfaces, when compared with gut microbiota, we optimized the DNA purification workflow from nasopharyngeal swab specimens. As a result, we provide a protocol that allows the efficient combination of bacterial, archaeal, and eukaryotic libraries for nanopore-sequencing using Oxford Nanopore Technologies MinION devices and subsequent phylogenetic analyses. In a pilot study, this workflow allowed the identification of some environmental archaea, which were not correlated with airway microbial communities before. Moreover, we assessed the protocol's broader applicability using a set of human stool samples. We conclude that the proposed protocol provides a versatile and adaptable tool for combinatorial studies on bacterial, archaeal, and eukaryotic microbiomes on a small laboratory scale.
Drug‐related Hepatotoxicity and Acute Liver Failure Murray, Karen F; Hadzic, Nedim; Wirth, Stefan ...
Journal of pediatric gastroenterology and nutrition,
2008-October, Letnik:
47, Številka:
4
Journal Article
Recenzirano
Odprti dostop
ABSTRACT
Drug‐induced acute liver failure (ALF) accounts for approximately 20% of ALF in children and a higher percentage of ALF in adults. Although most patients experience milder drug hepatotoxic ...reactions such as hepatitis, cholestasis, or asymptomatic enzyme elevation, it is important to recognize the potential for progression to ALF. The most common cause of drug‐induced ALF in children is acetaminophen (15% of all ALF in children in the United Kingdom and the United States), whereas other drugs such as antituberculous and antiepileptic therapy account for 5%. The pathogenesis of liver injury includes direct hepatotoxicity and idiosyncratic reactions for most drugs, although for others the mechanism of injury is assumed on the basis of clinical presentation and hepatic histological findings. We review the adult and pediatric literature of drug‐induced hepatotoxicity and ALF, with special attention to commonly used or offending medications, mechanism of the toxicity, clinical presentation, diagnosis, treatment, and prognosis. Although most of the available information is based on experience in adult patients, we have included that which is applicable to children, or we have cited pediatric examples. Enhanced awareness of the potential hepatotoxicity of commonly prescribed medications may minimize the frequency of serious hepatotoxicity and ALF in pediatric patients.
Over the last decades, the use of over-the-counter analgesics in the general population has increased in Germany. Ibuprofen is one of the most commonly used nonsteroidal anti-inflammatory drug ...(NSAID) and is frequently prescribed to children as an analgesic and/or antipyretic. Besides having a well-established safety and efficacy profile when used in appropriate doses, cases of NSAID-induced acute kidney injury (AKI) have been described in the pediatric population, particularly in the context of dehydration and in combination with other drugs. The ingestion of more than 400 mg/kg is associated with severe or life-threatening toxicity. This report is about two previously healthy adolescents, who developed AKI after taking high daily dose of ibuprofen as a pain reliever without any appropriate medical supervision. With these case reports, in addition to the side effect profiles of this analgesic, we would also like to present a certain therapeutic recommendation that we applied in these patients, and furthermore appeal to pediatricians to strictly set the indications for ibuprofen intake.
Conventional mammography is a decisive tool in detecting breast cancer. Continuous efforts are undertaken in order to further improve the image quality as well as to reduce the applied doses. The ...purpose of our study was to compare diagnostic image quality of dose reduced computed mammography with a new needle-based detector system to full dose powder imaging plates.
We retrospectively compared 360 randomly chosen mammographies performed on a GE Senographe DMR running the Agfa DX-M needle-based imaging plate system (NIP) with their preliminary examinations which were acquired at standard dose with the same GE mammography device and an Agfa CR85-X powdered storage phosphor imaging plate system (PIP). NIP-based mammographies were about 29.8 % dose-reduced. The preliminary examinations had to be performed not earlier than 2 years before the recent investigations. Exclusion criteria were changes in ACR level and appearance of the scored targets and not optimally positioned and exposed mammographies. The images were blinded and read separately twice by 2 mammography experts according to a 3-point score on diagnostic image quality and the visualization of parenchyma, cysts, fibroadenomas, physiologic lymph nodes, solitary microcalcifications and macrocalcifications.
Dose reduced NIPs showed a significantly better visualization of parenchyma at ACR II/III and solitary microcalcifications at ACR I-III mammographies (p < 0.001) whereas the difference in scoring macrocalcifications, cysts, fibroadenomas and physiologic lymph nodes was not significant. The reading showed an excellent intra- (r = 0.97/0.94) and interobserver agreement (r = 0.92).
With computed mammography using the needle-based detector system a significant dose reduction is possible without loss of diagnostic image quality.
In hepatocyte nuclei, hepatitis B virus (HBV) genomes occur episomally as covalently closed circular DNA (cccDNA). The HBV X protein (HBx) is required to initiate and maintain HBV replication. The ...functional nuclear localization of cccDNA and HBx remains unexplored.
To identify virus-host genome interactions and the underlying nuclear landscape for the first time, we combined circular chromosome conformation capture (4C) with RNA-seq and ChIP-seq. Moreover, we studied HBx-binding to HBV episomes. In HBV-positive HepaRG hepatocytes, we observed preferential association of HBV episomes and HBx with actively transcribed nuclear domains on the host genome correlating in size with constrained topological units of chromatin. Interestingly, HBx alone occupied transcribed chromatin domains. Silencing of native HBx caused reduced episomal HBV stability.
As part of the HBV episome, HBx might stabilize HBV episomal nuclear localization. Our observations may contribute to the understanding of long-term episomal stability and the facilitation of viral persistence. The exact mechanism by which HBx contributes to HBV nuclear persistence warrants further investigations.
There is a lack of knowledge regarding the connection between the ocular and nasal epithelia. This narrative review focuses on conjunctival, corneal, ultrastructural corneal stroma, and nasal ...epithelia as well as an introduction into their interconnections. We describe in detail the morphology and physiology of the ocular surface, the nasolacrimal ducts, and the nasal cavity. This knowledge provides a basis for functional studies and the development of relevant cell culture models that can be used to investigate the pathogenesis of diseases related to these complex structures. Moreover, we also provide a state-of-the-art overview regarding the development of 3D culture models, which allow for addressing research questions in models resembling the in vivo situation. In particular, we give an overview of the current developments of corneal 3D and organoid models, as well as 3D cell culture models of epithelia with goblet cells (conjunctiva and nasal cavity). The benefits and shortcomings of these cell culture models are discussed. As examples for pathogens related to ocular and nasal epithelia, we discuss infections caused by adenovirus and measles virus. In addition to pathogens, also external triggers such as allergens can cause rhinoconjunctivitis. These diseases exemplify the interconnections between the ocular surface and nasal epithelia in a molecular and clinical context. With a final translational section on optical coherence tomography (OCT), we provide an overview about the applicability of this technique in basic research and clinical ophthalmology. The techniques presented herein will be instrumental in further elucidating the functional interrelations and crosstalk between ocular and nasal epithelia.
PDF
