Devendra I. Mehta

The Role of Extraesophageal Reflux in Otitis Media in Infants and Children

Objectives/Hypothesis: Gastroesophageal reflux disease (GERD) is common in children, and extraesophageal reflux disease (EORD) has been implicated in the pathophysiology of otitis media (OM). We sought to 1) determine the incidence of pepsin/pepsinogen presence in the middle ear cleft of a large sample of pediatric patients undergoing myringotomy with tube placement for OM; 2) compare this with a control population of pediatric patients undergoing middle ear surgery (cochlear implantation) with no documented history of OM; 3) analyze potential risk factors for OM in children with EORD demonstrated by the presence of pepsin in the middle ear cleft; and 4) determine if pepsin positivity at the time of myringotomy with tube placement predisposes to posttympanostomy tube otorrhea.

Epidermal Growth Factor Up-Regulates Sodium-Glucose Cotransport in Enterocyte Models in the Presence of Cholera Toxin

BACKGROUND Sodium-glucose cotransport by enterocytes is key to the successful implementation of oral rehydration in diarrhea. Confluent, differentiated Caco-2 cells have enterocyte-like characteristics. We have previously shown that short-term incubation of isolated rat jejunal enterocytes with epidermal growth factor (EGF) results in the up-regulation of sodium-glucose cotransport. The aim of this study was to examine the effect of EGF on Caco-2 cells in the presence of cholera toxin. METHODS Caco-2 cells grown on tissue culture dishes were used for glucose and sodium uptake studies and cells were grown on polycarbonate membranes for transport examinations. Effects of EGF on the kinetic parameters of sodium-glucose contransporter, thymidine transport, and on the activity of Na+/K(+)-ATPase were examined. The efficacy of basolateral vs apical EGF on sodium and glucose transport was compared after incubation of the monolayers with 10 nmol/L of cholera toxin. RESULTS EGF increased both glucose and sodium uptake and transport, and we observed a simultaneous increase in the activity of Na+/K(+)-adenosine triphosphatase (ATPase). Kinetic studies performed on brush-border membrane vesicles prepared from EGF-incubated confluent monolayers and on intact cells showed an increase in the maximum velocity but not the Michaelis constant, suggesting increased availability of transporters rather than conformational change. This effect was seen within minutes in both of the two putative transporters, high-affinity, low-capacity and low-affinity, high-capacity. There was no acute effect on thymidine uptake. Studies in the presence of cholera toxin demonstrated a significant up-regulation in sodium-glucose cotransport when EGF was applied from the basolateral side; the increase was smaller but significant with apical application. CONCLUSIONS Differentiated Caco-2 cells have two kinetically distinct sodium-glucose cotransporters. Short-term incubation of Caco-2 cells with EGF resulted in an up-regulation of sodium-glucose cotransport and subsequent increase in Na+/K(+)-ATPase activity. The effect of basolaterally applied EGF was more significant with or without incubation with cholera toxin. The early effect of EGF on glucose and sodium cotransport may have important therapeutic implications in diarrhea and dehydration states. The in vitro model described here uses a homogeneous cell population and provides a versatile system for uptake and transport studies.

ESPGHAN and NASPGHAN Report on the Assessment of Exocrine Pancreatic Function and Pancreatitis in Children.

The purpose of this clinical report is to discuss several recent advances in assessing exocrine pancreatic insufficiency (EPI) and pancreatitis in children, to review the array of pancreatic function tests, to provide an update on the inherited causes of EPI, with special emphasis on newly available genetic testing, and to review newer methods for evaluating pancreatitis.

Cytokine release, pancreatic injury, and risk of acute pancreatitis after spinal fusion surgery.

Acute pancreatitis after posterior spinal fusion in children is associated with high intraoperative blood loss. Inflammation, oxidative stress, and pancreatitis markers were assessed during this period. Five of the 17 patients studied developed acute pancreatitis 3–7 days after surgery. Intraoperative blood loss (4850±2315 vs 1322±617 ml) and peak tumor necrosis factor α levels (15.29±5.3 vs 8.27±4.6 pg/ml) in the immediate postoperative period were significantly higher in these five patients than in controls, respectively. No differences were noted in serum interleukin 8, interleukin 6, pancreatis-associated protein, or urine malondialdehyde levels. Urine trypsin-associated peptide, elevated initially in all patients, was significantly higher in the acute pancreatitis group at diagnosis. Length of stay was significantly longer in the acute pancreatitis group. Greater blood loss and peak tumor necrosis factor α are associated with subsequent risk of acute pancreatitis, suggesting a role of ischemia–reperfusion injury.

Short-Term Effect of Epidermal Growth Factor on Glucose Uptake in Endoscopic Biopsies

Epidermal growth factor (EGF) up-regulation of glucose absorption via increased Na+/glucose cotransporter (SGLT-1) activity has previously been described in rabbit jejunal brush-border membrane and in differentiated Caco-2 cells. The goal of the present study was to assess the in vitro effect of EGF (200 ng/ml) on glucose uptake in human mucosal specimens, and we describe a simple procedure that uses endoscopic biopsies for short-term gludose uptake measurements. Uptake values for the EGF-treated biopsies ranged from 2.7 to 29.0, with a mean uptake of 10.65, while uptake values for the untreated biopsies ranged from 0.9 to 17.5, with a mean uptake of 7.99 (P < 0.05, paired t test). This early effect of EGF on human enterocytes may have important therapeutic implications. A role in increasing the rate of internal rehydration is suggested.

Isolated pancreatic amylase deficiency: Probable error in maturation

A boy with failure to thrive and isolated pancreatic amylase deficiency is described. Immunoprecipitation confirmed only salivary isoamylase in duodenal fluid at ages 20 and 33 months. Because normal pancreatic amylase messenger RNA was detected by reverse-transcriptase polymerase chain reaction in the fluid, failure of the normal maturation of pancreatic amylase secretion may explain the deficiency.

Pediatric gastritis and peptic ulcer disease

Inflammation of the gastric and duodenal mucosa is the end result of an imbalance between mucosal defensive and aggressive factors. The degree of inflammation and imbalance between defensive and aggressive factors can then result in varying degrees of gastritis and/or mucosal ulceration. Gastritis and ulcers of the duodenum or stomach can be classified as primary or secondary. The majority of children with chronic gastritis and ulcers in the stomach or duodenum have secondary inflammation or mucosal ulceration. These secondary ulcers generally occur due to a systemic condition like head trauma or overwhelming sepsis, or as sequelae to drug ingestion (i.e. non-steroidal anti-inflammatory agents), but secondary gastroduodenal ulcers can also occur in specific disease conditions such as Zollinger-Ellison syndrome or Crohn’s disease.In almost all children with primary duodenal or gastric ulcers mucosal inflammation and, less frequently, ulceration is caused by a spiral shaped, gram-negative, microaerobic rodHelicobacter pylori. Recent epidemiological evidence has linked chronicH. pylori infection with the development of gastric carcinomas.