Is liver biopsy still needed in children with chronic viral hepatitis?

Liver biopsy is a standard method used for obtaining liver tissue for histopathological evaluation. Since reliable serological and virological tests are currently available, liver biopsy is no longer needed for the etiological diagnosis of chronic hepatitis B and C. However, liver histology remains the gold standard as a prognostic tool, providing information about the liver disease progression(grading of necroinflammatory activity and staging of fibrosis) and serving clinicians in the management and therapeutic decisions. In general, histopathological evaluation is indicated before starting the antiviral treatment. Main limitations of the liver biopsy include its invasive and painful procedure, sampling errors and the inter- and intra-observer variability. In addition, indications for the liver biopsy in pediatric patients with chronic viral hepatitis were questioned recently, and efforts have been made toward the development of non-invasive methods as an alternative to the liver biopsy. The most commonly used methods are novel imaging studies(elastography) and combinations of biomarkers. However, to date, none of these tests was validated in children with chronic viral hepatitis. In this review, we present the current status of the liver biopsy in the management of chronic viral hepatitis B and C in pediatric population, including specific indications, complications, contraindications, problems, limitations, and alternative non-invasive methods.     

Assessing the efficacy of allogeneic hematopoietic stem cells transplantation (allo‐HSCT) by analyzing survival end points in defined groups of acute myeloid leukemia patients: A retrospective,multicenter Polish Adult Leukemia Group study

The importance of allogeneic hematopoietic stem cell transplantation (allo‐HSCT) for survival outcomes in patients with acute myeloid leukemia (AML) currently remains unclear. The study aimed to compare measures of clinical treatment for patients with AML in CR1 (the first complete remission) with or without being subjected to allo‐HSCT. These consisted of leukemia‐free survival (LFS), overall survival (OS), cumulative incidence of relapse (CIR), and non‐relapse mortality disease (NRM). Subjects were 622 patients, median age of 44, forming part of the prospective, randomized, and multicenter clinical Polish Adult Leukemia Group trials during 1999–2008. The Mantel–Byar approach was used to assess allo‐HSCT on survival endpoints, accounting for a changing transplant status. Undergoing allo‐HSCT significantly improved the LFS and OS for the entire group of patients with AML in CR1, along with the DAC induction subgroup and for the group with unfavorable cytogenetics aged 41–60. The CIR demonstrated that allo‐HSCT reduced the risk of relapse for patients with AML in CR1 and those with an unfavorable cytogenetic risk. In addition, the NRM analysis showed that allo‐HSCT significantly reduced the risk of death unrelated to relapse for the entire group of AML patients in CR1 and aged 41–60. The allo‐HSCT treatment particularly benefitted survival for the AML in CR1 group having an unfavorable cytogenetic prognosis. Am. J. Hematol. 90:904–909, 2015. © 2015 Wiley Periodicals, Inc.     

MRI-guided focused ultrasound (MRgFUS) to treat facet joint osteoarthritis low back pain—case series of an innovative new technique

European Radiology - To evaluate the safety and efficacy of magnetic resonance-guided focused ultrasound (MRgFUS) to treat facet joint osteoarthritis pain. Patients with a positive response to...     

Interlaboratory comparison of a standardized toxicity test using the nematode Caenorhabditis elegans (ISO 10872)

A ring test was carried out within the standardization process of ISO 10872 to evaluate the precision of the toxicity test for the nematode Caenorhabditis elegans. Eight different laboratories tested aqueous solutions of the reference substance benzylcetyldimethylammonium chloride as well as native sediments and soils for toxic effects on the growth and reproduction of C. elegans. Validity criteria were met in all laboratories. Average median- and low-effect concentrations were determined to be 15.1 mg L(-1) (EC50) and 8.7 mg L(-1) (EC10) for growth and 7.5 mg L(-1) (EC50) and 3.8 mg L(-1) (EC10) for reproduction of C. elegans, with ECx values showing a high degree of reproducibility (CV(R) : <21% and <11% for EC10 and EC50, respectively) and repeatability (CV(r) : <20% and <7% for EC10 and EC50, respectively). The toxic effects of the sediments and soils revealed by the different laboratories were well related to each samples' degree of chemical contamination. Moreover, the effects showed an acceptable reproducibility (CV(R) : 5-33% and 0-28% for growth and reproduction, respectively) and repeatability (CV(r) : 3-13% and 0-12% for growth and reproduction, respectively). The present study confirms that the toxicity test with C. elegans according to ISO 10872 is a reliable and precise tool to assess the toxicity of aqueous media, freshwater sediments, and soils.     

Capsule endoscopy: a single-centre experience with the first 226 capsules.

BACKGROUND: Capsule endoscopy (CE) refers to a novel diagnostic method of imaging the gastrointestinal tract using a wireless capsule that transmits images to a data recorder while the device traverses the small intestine. OBJECTIVE: To review the authors' experience with CE to determine the indications, outcomes and management of positive findings. METHODS: Patients were prepared for CE with a single dose of magnesium citrate. Following an 8 h fast, a sensor array system was applied to the abdomen, the capsule was swallowed and the images were transmitted to a data recorder worn on the patient's side. Typically, the battery life of the capsule is 8 h, following which the data recorder is returned, downloaded to a computer workstation and reviewed. RESULTS: To date, 226 capsule studies have been performed in 209 patients. The indications included obscure bleeding (167 studies: 88 overt, 79 occult), anemia (14 studies), evaluation for inflammatory bowel disease (12 studies), screening for polyps (10 studies), pain (19 studies) and abnormal radiological imaging (4 studies). In the setting of obscure bleeding, a definitive source of bleeding was discovered in 85 studies. This included angiodysplasia (52 studies), mitotic lesions (10 studies) and ulcers (23 studies). A probable source of bleeding was found in another 10 capsule studies. In the setting of anemia without evidence of bleeding, the definitive findings included ulcers (three studies), angiodysplasia (two studies), mitotic lesions (one study) and celiac disease (one study). Of four patients with abnormal radiological imaging, CE demonstrated lesions in two. The results of 35 capsule studies led to laparotomy with curative surgical resection. In eight studies, the capsules became lodged within a stricture; none led to obstruction and three were managed endoscopically. CONCLUSION: The yield of CE in carefully selected patients with obscure bleeding approximates 51%. There appear to be few complications, and patient satisfaction appears high. Cost analysis and further studies of clinical outcomes are required to elucidate appropriate indications for this device.     

Influence of COX-2 Inhibition by Rofecoxib on Serum and Tumor Progastrin and Gastrin Levels and Expression of PPARγ and Apoptosis-Related Proteins in Gastric Cancer Patients

Cyclooxygenase-2 (COX-2) expression and certain growth hormones, such as gastrin, have been related to gastric carcinogenesis, but little is known about the factors that enhance this COX-2 expression and whether specific blockade of this enzyme has any influence on tumor growth and progression. Our objective was to determine the influence of a specific COX-2 inhibitor, rofecoxib (Vioxx), on serum and tumor levels of gastrin and its precursor, progastrin, as well as on tumor gene expression of COX-2, peroxisome proliferator-activated receptor gamma (PPAR), and apoptosis-related proteins (Bax and Bcl-2, caspase-3, and survivin). Twenty-four gastric cancer (GC) patients entered this study and were examined twice, once before and then following a 14-day treatment with Vioxx at a dose of 25 mg twice daily. For comparison, 48 age- and sex-matched healthy controls and 24 similarly matched Helicobacter pylori (Hp)-positive subjects were enrolled and treated with Vioxx as GC patients. Serum levels of anti-Hp and anti-CagA antibodies as well as IL-8 and TNF- were measured by enzyme-linked immunosorbent assay (ELISA), while serum and tumor contents of progastrin and amidated gastrin were determined by specific RIA. Tumor gene and protein expressions of COX-2, PPAR, Bax and Bcl-2, caspase-3, and survivin were determined by RT-PCR and western blot. The overall Hp and CagA seropositivity in 24 GC patients was significantly higher (82% and 47%) than in 48 controls (61% and 22%) but not in 24 Hp-infected subjects (100% and 38%). Serum IL-8 and TNF- values were significantly higher in GC patients than in controls without GC or Hp-infected controls. Median serum progastrin and gastrin levels were found to be significantly higher in GC than in controls without GC and in Hp-positive subjects. Treatment of GC patients with Vioxx resulted in a significant decrease in plasma and tumor contents of both progastrin and gastrin, and this was accompanied by the increment in tumor expression of COX-2, PPAR, Bax, and caspase-3 with a concomitant reduction in Bcl-2 and survivin expression. We conclude that: (1) GC patients show significantly higher Hp and CagA seropositivity than age- and sex-matched controls, but not Hp-positive subjects, indicating that infection with cytotoxic Hp is linked to GC. (2) Serum progastrin and gastrin levels are signficantly higher in GC patients than in matched controls, confirming that both gastrins may be implicated in gastric carcinogenesis. (3) GC patients exhibit significantly higher levels of IL-8 and TNF- than non-GC controls and Hp-positive subjects, probably reflecting more widespread gastritis in GC. (4) COX-2, PPAR, Bcl-2, and survivin were overexpressed in gastric tumor, but the inhibition of COX-2 activity by Vioxx resulted in a significant reduction in serum and tumor levels of progastrin and gastrin and serum IL-8 and TNF- levels, suggesting that gastrin and proinflammatory cytokines could mediate the up-regulation of COX-2 in gastric cancerogenesis. (5) Vioxx also enhanced expression of COX-2, PPAR, Bax, and caspase-3, while inhibiting the expression of Bcl-2 and survivin, suggesting that COX-2 blockade might be useful in chemoprevention against cancer possibly due to enhancement of the PPAR- and proapoptotic proteins-dependent apoptosis and the reduction in progastrin/gastrin-induced promotion of tumor growth.     

Test-retest stability analysis of resting brain activity revealed by blood oxygen level-dependent functional MRI

Purpose:

To assess test–retest stability of four functional magnetic resonance imaging (fMRI)‐derived resting brain activity metrics: the seed‐region‐based functional connectivity (SRFC), independent component analysis (ICA)‐derived network‐based FC (NTFC), regional homogeneity (ReHo), and the amplitude of low frequency fluctuation (ALFF).

Methods:

Simulations were used to assess the sensitivity of SRFC, ReHo, and ALFF to noise interference. Repeat resting blood oxygen level‐dependent (BOLD) fMRI were acquired from 32 healthy subjects. The intraclass correlation coefficient (ICC) was used to assess the stability of the four metrics.

Results:

Random noise yielded small random SRFC, small but consistent ReHo and ALFF. A neighborhood size greater than 20 voxels should be used for calculating ReHo in order to reduce the noise interference. Both the anterior cingulate cortex (ACC) and posterior cingulate cortex (PCC)‐based SRFC were reproducible in more spatially extended regions than ICA NTFC. The two regional spontaneous brain activity (SBA) measures, ReHo and ALFF, showed test–retest reproducibility in almost the whole gray matter.

Conclusion:

SRFC, ReHo, and ALFF are robust to random noise interference. The neighborhood size for calculating ReHo should be larger than 20 voxels. ICC > 0.5 and cluster size > 11 should be used to assess the ICC maps for ACC/PCC SRFC, ReHo, and ALFF. BOLD fMRI‐based SBA can be reliably measured using ACC/PCC SRFC, ReHo, and ALFF after 2 months. J. Magn. Reson. Imaging 2012;36:344–354. ©2012 Wiley Periodicals, Inc.     

Complete cerebral ischemia with short-term survival in rats induced by cardiac arrest. I. Extracellular accumulation of Alzheimer's β-amyloid protein precursor in the brain

The distribution of β-amyloid protein precursor (APP) was investigated immunocytochemically in rats subjected to global cerebral ischemia (GCI) induced by cardiac arrest. Rats underwent 10 min of GCIm with 3, 6, and 12 h and 2 and 7 days of survival. APP immunostaining was found extracellularly. Multiple extracellular APP immunoreactive deposits around and close to the vessels appeared as soon as 3 h after GCI. Extracellular accumulation of APP occurred frequently in the hippocampus, cerebral and cerebellar cortex, basal ganglia and thalamus and rarely in the brain stem. These deposits were labelled with antibodies against the N-terminal, β-amyloid peptide, and C-terminal domains of APP. Our data suggests that either proteolytically cleaved fragments of the full-length APP or the entire APP molecule accumulates extracellularly after GCI. This finding may not only implicate the participation of APP in postischemic tissue damage but also suggest the involvement of pathomechanisms operating in ischemia in Alzheimer's disease pathology.