Phyllis R. Bishop

REGULATION OF EICOSANOID PRODUCTION AND MITOGENESIS IN RAT INTESTINAL EPITHELIAL CELLS BY TRANSFORMING GROWTH FACTOR-ALPHA AND PHORBOL ESTER

Growth factors and tumor promoters have been shown to play a role in intestinal epithelial growth regulation and transformation. In this study, transforming growth factor-alpha (TGF alpha) and the tumor promoter, tetradecanoyl phorbol acetate (TPA), are shown to stimulate the production of eicosanoids by rat intestinal epithelial (RIE-1) cells in culture. A 4.5-kb mRNA, which hybridizes to the mouse cyclooxygenase-2 cDNA probe, is elevated 18-fold within 30 min after TGF alpha or TPA treatment. Stimulation of RIE-1 cells with TGF alpha leads to the increase of a protein (M(r) approximately 69,000), which binds a monospecific antibody to the mouse cyclooxygenase-2 protein. Dexamethasone markedly inhibits the increase of the 4.5-kb mRNA. Pretreatment of TGF alpha or TPA-stimulated RIE-1 cells with dexamethasone or cyclooxygenase inhibitors prevents the increase in eicosanoid production by these cells. Treatment of quiescent RIE-1 cells with TGF alpha stimulates mitogenesis. This mitogenic activity is blocked by pretreating the cells with dexamethasone or cyclooxygenase inhibitors. A mitogen-inducible cyclooxygenase gene is thus shown to be regulated by TGF alpha and TPA in rat intestinal epithelial cells. We suggest that products of an intestinal growth factor-inducible cyclooxygenase may play a role in the regulation of mitogenesis.

Multicenter, Randomized, Double-blind Study Comparing 10, 20 and 40 mg Pantoprazole in Children (5-11 Years) With Symptomatic Gastroesophageal Reflux Disease

Objective: To evaluate symptom improvement in 53 children (aged 5-11 years) with endoscopically proven gastroesophageal reflux disease (GERD) treated with pantoprazole (10, 20 and 40 mg) using the GERD Assessment of Symptoms in Pediatrics Questionnaire. Methods: The GERD Assessment of Symptoms in Pediatrics Questionnaire was used to measure the frequency and severity over the previous 7 days of abdominal/belly pain, chest pain/heartburn, difficulty swallowing, nausea, vomiting/regurgitation, burping/belching, choking when eating and pain after eating. Individual symptom scores were based on the product of the frequency and usual severity of each symptom. The sum of the individual symptom score values made up the composite symptom score (CSS). The primary end point was the change in the mean CSS from baseline to week 8. Results: Mean frequency and severity of each symptom significantly decreased (from P < 0.006 to P < 0.001) over time. Similar significant decreases in CSS at week 8 versus baseline (P < 0.001) were seen in all groups. Significant decreases from baseline in CSS were noted from weeks 1 to 8 in the 20-mg (P < 0.003) and 40-mg (P < 0.001) groups. The 20- and 40-mg doses were significantly (P < 0.05) more effective than the 10-mg dose in improving GERD symptoms at week 1. Adverse events were similar among the treatment groups. Conclusions: Pantoprazole (20 and 40 mg) is effective in reducing endoscopically proven GERD symptoms in children. Both 20 and 40 mg pantoprazole significantly reduced symptoms as early as 1 week.

Hepatic iron overload in children with sickle cell anemia on chronic transfusion therapy.

Hepatic iron overload is a serious complication of chronic transfusion therapy in patients with sickle cell disease (SCD). No firm consensus has been reached with regard to correlation between hepatic iron content (HIC) and variables including age, number of transfusions, and serum iron makers. Also, the role of HIC in determining hepatic injury is not well established. There is scarcity of data on chronically transfused children with SCD and no other confounding liver pathology. We aimed to further explore relationships between these variables in a cohort of children with SCD on chronic transfusion therapy naive to chelation. Liver biopsies obtained before starting chelation therapy from 27 children with sickle cell anemia receiving chronic transfusion therapy were evaluated for histologic scoring and determination of HIC. Average serum ferritin and iron saturation values were determined for 6 months before biopsy. Duration and total volume of transfusion were obtained from the medical records. All children were negative for human immunodeficiency virus, hepatitis B virus, and hepatitis C virus infections. Mean age at biopsy was 10.95±3.34 years. Mean duration and total volume of transfusions were 50.0±26.6 months and 17.4±9.6 L, respectively. Pearson product-moment bivariate correlation coefficients indicated significant correlations between HIC and histologic iron score, serum ferritin, iron saturation, age, and transfusion volume. After adjusting for transfusion volume, a significant correlation was only seen between HIC and transfusion volume. Mean HIC was 21.8±10.4 mg/g dry weight, with fibrosis observed in 10 patients and lobular inflammation in 9. HIC was higher in biopsies with fibrosis (28.2±3.8 mg/g) than biopsies without fibrosis (17.6±18.3 mg/g; P=0.012). HIC did not differ between biopsies with lobular inflammation (25.5±4.0 mg/g) and biopsies without inflammation (19.9±2.5 mg/g; P=0.22). These findings show that transfusion volume provides more insight on hepatic iron overload than serum iron markers.

Solitary rectal ulcer: a rare cause of gastrointestinal bleeding in an adolescent with hemophilia A.

Solitary rectal ulcer syndrome (SRUS) is a rarely reported condition in children. The typical presentation is one of anorectal pain with passage of blood and mucus per rectum in the setting of defecation abnormalities. Diagnosis is made via endoscopy and biopsy. Solitary rectal ulcer syndrome alone is usually a benign condition; however, significant morbidity can occur if complicated by underlying disease states. We report an adolescent with hemophilia A and SRUS who presented with a rectal bleed that required blood transfusion.

Safety of blind percutaneous liver biopsy in obese children: a retrospective analysis.

Goal To determine the safety and adequacy of blind percutaneous liver biopsy (PLB) in obese children. Background PLB is an important diagnostic tool that, while invasive, enjoys a relatively low major complication rate. An ever increasing reason for pediatric liver biopsy is nonalcoholic fatty liver disease associated with obesity. There is a lack of data assessing the safety of liver biopsy in obese compared to nonobese children. Study A retrospective study of all children over 5 years of age having PLB was conducted. Data collected included age, gender, weight, height, BMI, reason for biopsy, number of passes, biopsy length, number of portal triads per biopsy, and complication rates. Results A total of 107 biopsies were reviewed. All biopsies were successful. Overall, major complications occurred in 1.3% and minor complications in 8.4%; there were no deaths. Comparison revealed no difference for number of passes (1.5±0.7 vs. 1.7±0.7), biopsy length (2.0±1.3 cm vs. 1.5±1.1 cm), number of portal tracts per biopsy (9.8±5.8 vs. 9.9±3.4), or complication rates (major: 0% vs. 1.3%; minor: 10.0% vs. 7.8%) between obese and nonobese children. Conclusion Blind PLB can be safely carried out in obese children with no increase in complication rate compared with nonobese children. Similarly, there is no difference in number of passes, biopsy size, portal triads per biopsy, or biopsy success for obese children.

GASTROESOPHAGEAL REFLUX IN CHILDREN

Gastroesophageal reflux (GER) is a common disorder in infants and children with a high rate of spontaneous resolution. Some children, however, will continue to have problems and progress from functional GER to pathogenic GER. In children with functional GER, diagnostic testing and pharmacologic treatment is unnecessary. In more involved cases, there are a number of tests available that help to quantify and qualify the extent of disease. Treatment begins with conservative measures and progresses to acid neutralization/supression and medications to enhance motility. Should medical management fail to control the consequences of reflux disease, surgical intervention is warranted.

Developmental expression of endothelial nitric oxide synthase (eNOS) in the rat liver.

Transition from fetal to postnatal life requires significant changes in cardiac, pulmonary, and hepatic blood flow. As such, there must be changes in vascular control in these vascular systems. Vascular resistance, a major contributor to blood flow, is mediated in the ductus arteriosus and pulmonary vasculature by endothelial nitric oxide synthase (eNOS). This study was conducted to determine the ontogeny of hepatic eNOS expression and activity. Additionally, the expression and activity of inducible nitric oxide synthase (iNOS) was measured to determine whether perinatal hypoxia resulted in detectable levels. NOS mRNA and proteins were determined by reverse transcription PCR assay and semiquantitative Western blot analysis, respectively. NOS activity was measured by the formation of [14C]-citrulline from [14C]-arginine. Localization of eNOS within the liver was determined by immunohistochemistry. eNOS mRNA was detectable at low levels at 18-d gestation and increased after birth, reaching a maximum level (4.5-fold increase) at 20 d of life. Parallel patterns for eNOS protein and activity were seen, with 6.9-fold and 16.1-fold increases, respectively. In the prenatal rat, eNOS was localized to areas of extramedullary hematopoiesis, with little signal in the sinusoids. Postnatally, there was a decrease in staining in the hematopoietic cells and a gradual increase in the staining of the endothelium of the sinusoids and central veins. iNOS mRNA and protein could not be detected at any age. eNOS expression and activity are developmentally regulated, increasing after birth coincident with an initial relative hypoxia and an increase in shear forces upon closure of the ductus venosus.

Upper gastrointestinal bleeding in children: an 11-year retrospective endoscopic investigation

BackgroundUpper gastrointestinal bleeding (UGIB) may present as hematemesis, coffee-ground emesis, or melena requiring esophagogastroduodenoscopy (EGD) for diagnosis and/or therapy. Worldwide, differences exist for the etiology of UGIB reflecting geographical differences in common disease states. In the past 25 years, there have been improvements in endoscopic optics. This study was undertaken to determine: 1) if identifying a bleeding source in UGIB have improved with better endoscopic optics, 2) geographic differences in causes of UGIB, 3) differences in severity of UGIB based on clinical factors, and 4) the likelihood of fi nding a bleeding source based on symptom duration and time to endoscopy.MethodsA retrospective chart review was made on children having EGD for evaluation of UGIB. Data collected included type, etiology, and degree of bleeding.ResultsOf 2569 diagnostic procedures, 167 (6.5%) were performed for UGIB. The most common presentation was hematemesis (73.4%). Melena was associated with lower hemoglobin levels and higher transfusion rates. A source of UGIB was found in 57.0%, no cause in 11.4% and a questionable cause in 29.7%. A source was found less commonly in children with a history of UGIB less than one month and in those undergoing endoscopy over 48 hours after a bleeding episode.ConclusionsImproved endoscopic optics has not changed diagnostic ability for UGIB. Etiologic differences for UGIB in children from varying geographic areas are related to indication for endoscopy, patient selection, and co-morbid conditions. Duration of bleeding and time to endoscopy after a bleeding episode may help predict when endoscopy should be performed to determine a bleeding source.

Diarrhea: Case definition and guidelines for collection, analysis, and presentation of immunization safety data ,

. Gidudua,∗, D.A. Sackb, M. Pinac, M.J. Hudsond, K.S. Kohla, P. Bishope, A. Chatterjee f, E. Chiappinig, . Compingbutraa, C. da Costah, R. Fernandopulle i, T.K. Fischer j, P. Habera, W. Masanak, artins R. de Menezes l, G. Kangm, N. Khuri-Bulosn, L.A. Killiono, C. Nairp, G. Poerschkeq, B. Rathr, . Salazar-Lindos, R. Setseb, P. Wenger t, V.C.N. Wongu, K. Zamanv, he Brighton Collaboration Diarrhea Working Group

Juvenile Polyps and Juvenile Polyp Syndromes in Children A Clinical and Endoscopic Survey

In children, most colonic polyps are juvenile polyps with negligible risk for malignant transformation. The exception is juvenile polyposis syndrome (JPS) where there is a risk for developing colon cancer. The authors studied differences in clinical features and colonoscopic findings in children with solitary juvenile polyps (SJP), multiple juvenile polyps (MJP), and JPS. Methods. Children were identified as SJP (1 polyp), MJP (2-4 polyps), or JPS (>5 polyps). Demographic data, laboratory values, family history, and colonoscopic findings were recorded. Results. Children having polypectomy had juvenile polyps (93%), adenomatous polyps (5%), and Peutz–Jegher syndrome (3%). Juvenile polyps were classified as SJP (67%), MJP (16%), and JPS (17%). Children with SJP were younger, were more likely to have polyps limited to the rectosigmoid colon, and had larger polyps than children with MJP and JPS. Anemia was more common in JPS than MJP and SJP. Conclusion. Clinical and endoscopic findings differ between SJP, MJP, and JPS.