bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diagnostic Criteria for Eosinophilic Esophagitis: A 5‐year Retrospective Review in a Pediatric Population
Authors: Lai Anita L , Girgis Safwat , Liang Yuanyuan , Carr Stuart , Huynh Hien Q 
Published: June 2009

ABSTRACTBackground:The diagnostic criterion based on the number of eosinophils (Eos) per high‐power field (HPF) does not appear to capture all patients with eosinophilic esophagitis (EE).Objectives:To determine whether EE has been underrecognized at our institution, clinical variables predicting EE, and whether the Luna eosinophil granule (LEG) stain detects eosinophils better than hematoxylin and eosin (HE).Materials and Methods:Esophageal biopsies of 202 children younger than 18 years old from 2000 to 2004 were reviewed and Eos/HPF was recorded. Clinical variables from charts were reviewed and a marginal logit model was used to determine significance. LEG stains for 60 randomly selected patients were prepared and compared to HE originals.Results:EE diagnoses have risen from none in 2000 to 23 in 2004. The clinically significant variables that predicted EE were improvement from EE treatment (160 times more likely to have EE; P < 0.0005), final endoscopic diagnosis of EE (31 times; P = 0.004), absence of vascular pattern on endoscopy (20 times; P = 0.008), and vertical furrows on endoscopy (29 times; P = 0.039). LEG stain appeared to be superior to HE in detecting low Eos/HPF (mean 24.82 and 38.53, respectively). Peak counts of eosinophils in the most involved HPF significantly correlated with highest average count of eosinophils per HPF in the most involved specimen (Pearson correlation 0.958).Conclusions:Misdiagnosed EE cases decreased but prevalence appeared to increase. LEG potentially can be a more sensitive stain. The key variables that predict EE were typical endoscopic findings and improvement from specific EE treatment.
Lymphocytic Leiomyositis and Myenteric Ganglionitis Are Intrinsic Features of Cystic Fibrosis: Studies in Distal Intestinal Obstruction Syndrome and Meconium Ileus
Authors: Smith Virpi V , Schäppi Michela G , Bisset W Michael , Kiparissi Fevronia , Jaffe Adam , Milla Peter J , Lindley Keith J 
Published: June 2009

ABSTRACTBackground:Cystic fibrosis (CF) is a multisystem disorder intrinsically associated with inflammation of mucosal surfaces. Because inflammation can result in enteric neuromuscular dysfunction we hypothesized that terminal ileitis in patients with CF may predispose to distal ileal obstruction syndrome (DIOS).Methods and Patients:Full‐thickness terminal ileal tissues from 6 children with CF and severe DIOS, 6 infants with complicated meconium ileus (MI), and 6 children with non‐CF intestinal atresia were studied.Results:Lymphocyte‐predominant mucosal and transmural ileal inflammation was present in 6 of 6 patients with DIOS. Lymphocytic ganglionitis was present in 4 of 6 although numbers of myenteric neurons were not decreased (5/5). Myocyte proteins were preserved (6/6). Mild submucosal fibrosis was common in DIOS (5/6) and transformation of submucosal fibroblasts to a myofibroblastic phenotype was noted in 4 of 6. Inflammatory changes were distinct from those described in fibrosing colonopathy. Antroduodenal manometry in an individual who had experienced MI/DIOS was consistent with a neuropathic pseudo‐obstructive process. Submucosal or transmural lymphocyte predominant inflammation was also present in 6 of 6 infants with complicated MI, which, when coupled with submucosal myofibroblast proliferation (5/6), appeared highly predictive of CF rather than non‐CF atresia. Histological findings at birth were similar, although milder, than those seen in DIOS, suggesting that these changes are a primary abnormality in CF.Conclusions:Submucosal or transmural inflammation of the ileum is common in newborns with CF and MI and older children with DIOS. Severe recurrent DIOS should be investigated with seromuscular and mucosal biopsy of the ileum to seek a transmural ileitis potentially amenable to anti‐inflammatory therapies.
Colonic Volvulus in Children With Intestinal Motility Disorders
Authors: Altaf Muhammad A , Werlin Steven L , Sato Thomas T , Rudolph Colin D , Sood Manu R 
Published: June 2009

ABSTRACTBackground:Chronic intestinal pseudo‐obstruction (CIP) is a condition characterized by symptoms of bowel obstruction in the absence of an anatomical cause. Patients with CIP and chronic intractable constipation (CIC) can also develop anatomical obstruction, and the presenting symptoms mimic those of underlying pseudo‐obstruction.Objectives:Our objectives were to evaluate the incidence, clinical presentation, and diagnostic investigations of colonic volvulus in children with intestinal motility disorders and to differentiate these episodes of colonic volvulus from the underlying motility disorder based on clinical presentation and imaging techniques.Materials and Methods:Patients records of children with colonic volvulus cared for at our institution over the previous 20 years were retrospectively reviewed. We identified 8 patients who were between 2 and 22 years of age at the time of diagnosis with colonic volvulus who also had CIP and CIC.Results:The mean age ± SD at presentation with colonic volvulus was 13.2 ± 5.05 years. All patients presented with worsening of abdominal distension and pain. The mean duration of symptoms of colonic volvulus before seeking medical help was 4.2 days (range 1–7 days). Water‐soluble contrast enema was the single most useful investigation for confirming the diagnosis. All patients required surgery. There was no mortality associated with colonic volvulus.Conclusions:Clinicians should be vigilant and include volvulus in the differential diagnosis of the acute onset of abdominal distension and pain in patients with CIP and CIC. Delay in diagnosis can result in bowel ischemia and perforation.
Effect of Maternal Diabetes on Postnatal Development of Brush Border Enzymes and Transport Functions in Rat Intestine
Authors: Sharma Ruchi , Kaur Jyotdeep , Mahmood Akhtar 
Published: June 2009

ABSTRACTAims/Hypothesis:The effect of alloxan‐induced maternal diabetes has been studied on the postnatal development of brush border enzymes in rat intestine.Materials and Methods:Diabetes was induced by injecting alloxan in rat mothers on day 3 of gestation.Results:There was no change in gestational period (22 days) in control and diabetic groups; however, the litter size was reduced (P < 0.001) in diabetic mothers compared with controls. Body weight of pups born to diabetic mothers was significantly low up to 45 days of postnatal age compared with controls. Analysis of brush border enzymes revealed elevated levels of lactase (76%), sucrase (46%), maltase (25%), trehalase (38%), alkaline phosphatase (57%), and leucine aminopeptidase (56%) up to 21 days of postnatal age in diabetic group compared with controls. However, in 30‐ to 45‐day‐old animals, the enzyme levels were either reduced in diabetic group or there was no change compared with controls. Western blot analysis corroborated the enzyme analysis data in purified brush borders. Also, 45 days after birth, the intestinal uptake of D‐glucose and glycine was significantly high (30%–61%) in pups from diabetic dams compared with controls.Conclusions:These findings indicate that alloxan‐induced maternal diabetes influences the postnatal development of intestine and the expression of various brush border enzymes and transport functions in rat intestine. This could affect the growth and development of the offspring during the postnatal period.
Chromosome Instability in Lymphocytes of Children With Coeliac Disease
Authors: Martin‐Arruti Maialen , Irastorza Inaki , de Prado Elena , Martin‐Sanchez Esperanza , Martin‐Guerrero Idoia , Ballesteros Javier , Vitoria Juan Carlos , Garcia‐Orad Africa 
Published: June 2009

ABSTRACTUndiagnosed individuals with celiac disease (CD) or those who do not comply with gluten‐free diet (GFD) are at a higher risk of developing malignancies. A possible origin of chromosomal alteration in autoimmune reaction could be mistakes in the rearrangement of V(D)J of the IgH gene. Our aim was to verify whether higher genomic instability was found in coeliac individuals and whether GFD reduced it. As marker of genomic instability we analysed the frequency of 2 translocations, t(14;18) and t(11;14), in peripheral blood by nested PCR, in 37 patients with CD at diagnosis, 27 patients with CD after 2 years on GFD, and 36 control individuals. No significant differences were found.
Diet‐dependent Mucosal Colonization and Interleukin‐1β Responses in Preterm Pigs Susceptible to Necrotizing Enterocolitis
Authors: Van Haver Els R , Sangild Per T , Oste Marijke , Siggers Jayda LA , Weyns Andre LM , Van Ginneken Christa J 
Published: June 2009

ABSTRACTObjectives:Intestinal colonization challenges the neonatal innate immune system, especially in newborns with an immature immune response lacking the supportive bioactive components from mother's milk. Accordingly, formula‐fed preterm pigs frequently show bacterial overgrowth, mucosal atrophy, and gut lesions reflecting necrotizing enterocolitis (NEC) within the first days after birth. We hypothesized that NEC development is related to a diet‐dependent bacterial adherence and a subsequent proinflammatory cytokine response in the gut mucosa immediately after introduction of enteral food.Materials and Methods:Premature piglets (92% gestation) received 2 to 3 days of total parenteral nutrition followed by 0, 8, or 17 hours of enteral formula or sow's colostrum feeding.Results:Following 8 hours, but not 17 hours, of colostrum feeding, a reduced number of intestinal samples with adherent bacteria (both Gram‐negative and Gram‐positive bacteria) was counted compared with 0 or 8 hours of formula feeding. Besides a more dense colonization, formula feeding leads to higher intestinal interleukin‐1β (IL‐1β) levels and more NEC‐like lesions from 8 hours onward. The load of adherent bacteria was especially high in NEC lesions. Toll‐like receptor 4 was detected in enteroendocrine, neuronal, and smooth muscle cells, potentially mediating the increase in IL‐1β levels by Gram‐negative bacteria.Conclusions:Formula feeding facilitates bacterial adherence and the development of a proinflammatory state of the intestine, which may be among the key factors that predispose formula‐fed preterm neonates to NEC.
Age‐ and Sex‐related Reference Ranges of Alanine Aminotransferase Levels in Children: European Paediatric HCV Network
Authors: England Kirsty , Thorne Claire , Pembrey Lucy , Tovo Pier‐Angelo , Newell Marie‐Louise 
Published: June 2009

ABSTRACTBackground:Serum alanine aminotransferase (ALT) levels are commonly used to indicate liver damage. Although elevated levels indicate possible liver injury, abnormalities, or disease, some patients with “normal” ALT levels have minimal to mild liver disease. Recently, ALT reference ranges for adults were queried and revised ranges proposed with lower upper limits of normality. The appropriateness of current paediatric ALT reference ranges is unclear.Material and Methods:Hepatitis C virus (HCV)–uninfected children from the European Paediatric HCV Network represent a large population of healthy children born to HCV‐infected mothers, with ALT observations collected prospectively from birth. Linear regression identified factors associated with ALT levels while accounting for within‐child repeated measurements. ALT centiles stratified by sex were calculated using maximum penalized likelihood methods and LMS software.Results:A total of 1293 HCV‐uninfected children had 5011 ALT measurements during follow‐up. ALT levels significantly decreased with increasing age, whilst ALT levels were significantly lower in girls than boys. Reference cutoffs representing the 95th centiles before 18 months of age were 60 U/L for boys and 55 U/L for girls, decreasing to 40 U/L for boys and 35 U/L for girls after 18 months of age.Conclusions:These reference ranges represent a unique investigation of ALT levels in a healthy child population. We show lower and more detailed age‐related cutoffs of normality than available. Additionally, we demonstrate a significant effect of sex on ALT reference ranges, which has not previously been described in children younger than 5 years of age.
Isolation, Identification, and Characterization of Small Bioactive Peptides From Lactobacillus GG Conditional Media That Exert Both Anti‐Gram‐negative and Gram‐positive Bactericidal Activity
Authors: Lu Ruiliang , Fasano Serena , Madayiputhiya Nandakumar , Morin Nicholas P , Nataro James , Fasano Alessio 
Published: June 2009

ABSTRACTObjectives:Diarrheal diseases remain a major human plague that still claim millions of lives every year. Probiotics, including Lactobacillus GG (LGG), are known to have a beneficial effect on diarrheal diseases, but their mechanism of action has not yet been completely established. Therefore, the main objective of this work was to identify and characterize moieties elaborated by LGG that exert antibacterial activity.Materials and Methods:Lactobacillus GG conditional media was subjected to liquid chromatography/mass spectrometry. The identified peptides were synthesized by Symphony peptide synthesizer and purified by HPLC using Dynamax reverse‐phase C18 column. Using A600 measurement and tested for their antibacterial activity.Results:We identified 7 small peptides from LGG cultured media, 2 of which are NPSRQERR and PDENK, retained the antibacterial activity detected with LGG conditional media. The antibacterial activity was exerted against both Gram‐negative (Escherichia coli EAEC 042 and Salmonella typhi) and, with less potency, Gram‐positive (Staphylococcus aureus) bacteria.Conclusions:Lactobacillus GG elaborates small peptides showing various degrees of antibacterial activity. NPSRQERR showed the most potent antibacterial effect that was detected both in Gram‐negative and Gram‐positive microorganisms. These synthetic peptides may represent novel tools for the treatment of bacterial infectious diseases.
Antibodies Against Deamidated Gliadin as New and Accurate Biomarkers of Childhood Coeliac Disease
Authors: Prause Christian , Ritter Maria , Probst Christian , Daehnrich Cornelia , Schlumberger Wolfgang , Komorowski Lars , Lieske Ruediger , Richter Thomas , Hauer Almuthe C , Stern Martin , Uhlig Holm H , Laass Martin W , Zimmer Klaus‐Peter , Mothes Thomas 
Published: June 2009

ABSTRACTObjectives:Assays of tissue transglutaminase antibodies (anti‐tTG) represent the cornerstone of serological coeliac disease (CD) diagnostics. Assays of antibodies against native gliadin (anti‐nGli) lost importance due to low validity. We investigated the performance of new assays for antibodies against deamidated gliadin (anti‐dGli) in childhood CD.Methods:We retrospectively compared children (142 with active CD and 160 without CD, diagnosis confirmed or excluded by intestinal biopsy) concerning (immunoglobulin [Ig] G and IgA) anti‐nGli, anti‐tTG, and 2 different anti‐dGli assays.Results:IgG‐anti‐dGli1, IgG‐anti‐dGli2, and IgA‐anti‐tTG performed similarly. Area under the receiver‐operating characteristic curve (AUC) was 98.6%, 98.9%, and 97.9%; accuracy was 94.7%, 95.7%, and 96.7%. Anti‐dGli1 and anti‐dGli2 (IgG and IgA) and IgA‐anti‐tTG performed significantly better than IgA‐anti‐nGli and IgG‐anti‐nGli. Both IgG‐anti‐dGli showed higher AUC and accuracy than IgA‐anti‐dGli and IgG‐anti‐tTG. Combined evaluation of IgA‐anti‐tTG with one of the IgG‐anti‐dGli tests reduced the rate of falsely classified patients. At enhanced cutoff (specificity >99%), sensitivity was above 67% for both IgG‐anti‐dGli and IgA‐anti‐tTG. If IgA‐anti‐tTG assay was combined with one of the IgG‐anti‐dGli tests, then the fraction of patients identified with more than 99% specificity as coeliacs increased significantly above 84.5%. Combined evaluation of the 2 IgG‐anti‐dGli tests did not improve the performance.Conclusions:The new IgA and IgG‐anti‐dGli tests outperform conventional anti‐nGli assays. The validity of IgG‐anti‐dGli cannot be distinguished from IgA‐anti‐tTG. It should be studied prospectively whether antibody assays could replace biopsy in diagnosis of CD in a substantial segment of children.
Enteral Glutamine and/or Arginine Supplementation Have Favorable Effects on Oxidative Stress Parameters in Neonatal Rat Intestine
Authors: Kul Mustafa , Vurucu Sabahattin , Demirkaya Erkan , Tunc Turan , Aydinoz Seçil , Meral Cihan , Kesik Vural , Alpay Faruk 
Published: June 2009

ABSTRACTObjective:To investigate and compare the effects of enteral glutamine and arginine supply on lipid peroxidation and antioxidant enzyme levels in the small intestine of healthy breast‐fed rats.Materials and Methods:The study comprised 40 newborn Sprague‐Dawley rats born to 5 mother rats. Newborn rats were randomly divided into 4 groups. Starting from day 1 until day 21, group I received only breast milk; group II received breast milk and 200 mg/kg/day oral glutamine; group III received breast milk and 200 mg/kg/day oral arginine; and group IV received breast milk, 200 mg/kg/day glutamine, and 200 mg/kg/day arginine. Malondialdehyde levels and glutathione peroxidase (GPx) and superoxide dismutase activities were measured.Results:The lowest malondialdehyde levels were found in group II (P = 0.0001). Superoxide dismutase activity was found to be significantly higher in group II than group I (P < 0.001). Of the 4 groups, GPx activity was highest in group IV. GPx activity in group II was significantly higher than in group I (P = 0.001) or group III (P = 0.001). GPx activity was higher in group IV than in group I (P = 0.001) or group III (P = 0.001).Conclusions:Enteral glutamine alone or in the presence of arginine has favorable effects on oxidative stress not only in experimental models of hypoxia‐reoxygenation, but also in healthy newborn rats. This suggests that in premature neonates with insufficient oxidative resistance, glutamine and arginine supplementation may help prevent necrotizing enterocolitis.
Prevalence of Subclinical Vitamin K Deficiency in Cholestatic Liver Disease
Authors: Strople Jennifer , Lovell Glenda , Heubi James 
Published: June 2009

ABSTRACTBackground and Objective:Prothrombin time (PT), a surrogate marker of vitamin K deficiency, may underestimate the prevalence of vitamin K deficiency in cholestatic liver disease. This study investigated the frequency of vitamin K deficiency in children and adults with cholestatic liver disease by determining plasma protein induced in vitamin K absence II (PIVKA‐II), and assessed the relation between plasma PIVKA‐II levels and markers of cholestasis, measured PT, international normalized ratio (INR), serum undercarboxylated osteocalcin (ucOC), serum vitamins A and E, and serum 25‐hydroxyvitamin D levels.Patients and Methods:Blood was collected from patients with cholestatic liver disease for liver biochemistries, PT, INR, bile acids, 25‐hydroxyvitamin D, vitamin A, vitamin E, ucOC, and PIVKA‐II.Results:Thirty‐one patients were enrolled (age range 0.5–54 years, median age 5.7 years, 17 females). Nine patients (29%) had increased INRs, whereas 21 (68%) had elevated plasma PIVKA‐II levels. All patients with increased INRs had increased plasma PIVKA‐II. Fifteen of 21 patients with increased plasma PIVKA‐II were receiving supplemental vitamin K therapy (range 7.8–700 μg/kg/day). Plasma PIVKA‐II levels were positively correlated with serum conjugated bilirubin, bile acids, aspartate aminotransferase, alanine aminotransferase, PT, INR, and serum ucOC (P ≤ 0.02) and negatively correlated with serum 25‐hydroxyvitamin D levels (P = 0.01). Twenty‐two patients (71%) had vitamin D deficiency, 9 patients (29%) had vitamin A deficiency, and 2 patients (6%) had vitamin E deficiency.Conclusions:Despite vitamin K supplementation, elevation of plasma PIVKA‐II suggesting ongoing vitamin K deficiency is common in cholestatic liver disease. Better strategies for vitamin K supplementation and dosing guidelines are needed.
Intestinal Stem Cells
Authors: Garrison Aaron P , Helmrath Michael A , Dekaney Christopher M 
Published: June 2009

ABSTRACTThe epithelial cell lining of the gastrointestinal tract is the most rapidly proliferating tissue in the body. The constant state of renewal of differentiated epithelial cells is sustained by a continual supply of progeny from multipotent progenitors that originate from stem cells located within the intestinal crypts. In addition to supporting normal epithelial homeostasis, intestinal stem cells (ISC) are thought to play an important role in the rapid expansion of the gut during development, tissue regeneration following injury or surgical loss, and malignancy. Because of the lack of specific ISC markers required to isolate and characterize these cells, our current knowledge of the biology of ISC results largely from indirect measures of their behavior published during the past 40 years. The recent description of several potential ISC markers and the use of transgenic mice, both as a tool to lineage trace and to isolate specific cells expressing these markers, have provided a tremendous advancement to our current understanding of these cells. This brief review provides a general historical overview of our understanding of ISC and the tools available to study their behavior in the context of normal and pathological conditions, as well as potential future clinical applications that may result from this exciting area of research.
Role of oxidation‐triggered activation of JNK and p38 MAPK in black tea polyphenols induced apoptotic death of A375 cells
Authors: Bhattacharya Udayan , Halder Babli , Mukhopadhyay Sibabrata , Giri Ashok K. 
Published: June 2009

Theaflavins (TF) and thearubigins (TR) are the major polyphenols of black tea. Our previous study revealed that TF‐ and TR‐induced apoptosis of human malignant melanoma cells (A375) is executed via a mitochondria‐mediated pathway. In our present study we observed the role of the three most important MAPK (ERK, JNK, and p38) in TF‐ and TR‐induced apoptosis. TF and TR treatment of A375 cells led to sustained activation of JNK and p38 MAPK but not ERK, suggesting that JNK and p38 are the effector molecules in this polyphenol‐induced cell death. This idea was further supported by subsequent studies in which JNK and p38 activation was inhibited by specific inhibitors. Significant inhibition was found in TF‐ and TR‐treated A375 cell death pretreated with JNK‐ or p38‐specific inhibitors only. Further, we have found that TF and TR treatment induces a time‐dependent increase in intracellular reactive oxygen species generation in A375 cells. Interestingly, treatment with the antioxidant N‐acetyl cystein inhibits TF‐ and TR‐induced JNK and p38 activation as well as induction of cell death in A375 cells. We also provide evidence demonstrating the critical role of apoptosis signal‐regulating kinase 1 in TF‐ and TR‐induced apoptosis in A375 cells. Taken together our results strongly suggest that TF and TR induce apoptotic death of A375 cells through apoptosis signal‐regulating kinase 1, MAPK kinase, and the JNK–p38 cascade, which is triggered by N‐acetyl cystein intracellular oxidative stress. (Cancer Sci 2009; 100: 1971–1978)