Michael J. Nowicki

The 13C-xylose breath test for the diagnosis of small bowel bacterial overgrowth in children

BACKGROUND We evaluated the clinical utility of the 13C-xylose breath test for the diagnosis of small bowel bacterial overgrowth in children. METHODS To determine the optimal dose of 13C-xylose, 29 healthy children, 3 to 12 years old, were randomly assigned to receive one of three doses of 13C-xylose (10, 25, or 50 mg). After an overnight fast, the oral dose of 13C-xylose was administered, and breath samples were collected every 30 minutes for 4 hours. Samples were analyzed for 13CO2 by gas chromatography with mass spectrometry. Using the 50 mg dose, we then performed nine breath tests with concurrent duodenal bacterial cultures in 6 children, 3 to 12 years old, with short-bowel syndrome (n = 2), immunodeficiency states (n = 1), and motility disorders (n = 3). RESULTS Excretion of 13CO2 in breath peaked at 2.5 hours in all three control groups. The 50-mg dose produced the highest median peak and the smallest range of 13CO2 excretion in breath within each time period. The time of peak 13CO2 excretion in breath varied among the diseased children; however, the six patients with small-bowel bacterial overgrowth (2 x 10(5)-3.5 x 10(5) gram negative rods) all had peak 13CO2 that exceeded the maximum breath 13CO2 level in breath of the control subjects at the corresponding time period (100% sensitivity). Of the three patients with negative cultures, two had negative breath test results and one had positive results (67% specificity). One subject had normalization of both duodenal culture and breath test results after antibiotic treatment of small-bowel bacterial overgrowth. CONCLUSIONS Our preliminary results suggest that with a dose of 50 mg 13C-xylose, breath test results reliably predict small-bowel bacterial overgrowth in susceptible children.

Overexpression of visfatin/PBEF/Nampt alters whole-body insulin sensitivity and lipid profile in rats

Background. Visfatin/PBEF/Nampt is an adipose-derived hormone proposed to exert insulin-mimicking effects and play a positive role in attenuating insulin resistance. However, the precise mechanisms underlying the beneficial effects of visfatin/PBEF/Nampt on insulin sensitivity remain unknown. Method. Euglycemic-hyperinsulinemic clamps were used in the same groups of rats to study the in vivo effect of visfatin/PBEF/Nampt on insulin sensitivity and glucose/lipid metabolism before and after the overexpression of visfatin/PBEF/Nampt protein, which was carried out by injection of pcDNA3.1-visfatin plasmid. Results. On day 4 after plasmid injection, plasma visfatin/PBEF/Nampt protein levels were significantly increased and displayed a hypocholesterolemic effect in both normal-chow (NC) and high-fat diet (HT) animals with pcDNA3.1-visfatin treatment. A second glucose clamp also demonstrated increased insulin sensitivity in pcDNA3.1-visfatin animals. Consistent with the clamp data, the extent of insulin receptor substrate (IRS)-1 tyrosine phosphorylation in response to insulin was significantly enhanced in the liver and adipose tissues. In addition, the mRNA expression of peroxisome proliferator-activated receptor-γ (PPARγ) and sterol regulatory element-binding proteins 2 (SREBP-2) in the liver and adipose tissues was also significantly upregulated in these animals. Conclusion. These results demonstrate that visfatin/PBEF/Nampt improves insulin sensitivity and exerts its hypocholesterolemic effects at least partially through upregulation of the tyrosine phosphorylation of IRS-1 protein and the mRNA levels of PPARγ and SREBP-2.

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.

Children will eat the strangest things: A 10-year retrospective analysis of foreign body and caustic ingestions from a single academic center

Background Foreign body (FB) ingestions are common in children presenting to the emergency department. Health care providers are quickly challenged to determine which children need urgent endoscopy for diagnostic or therapeutic reasons. We performed a retrospective study to determine if esophageal injury caused by FB ingestion correlated to presenting signs or symptoms, location of impaction, duration of impaction, or denomination of coin (as this was the most commonly ingested FB). Methods A retrospective chart review of children between birth and 17 years of age who presented for esophagogastroduodenoscopy for removal of upper gastrointestinal FB was performed. Demographic data collected from all children included age, sex, and race. For children with FB ingestion, the type of FB, location of the FB, underlying gastrointestinal pathology, duration of impaction, and endoscopic findings were recorded. Descriptive analysis of the data was performed using means, medians, SD, and percentages; &khgr;2 test was used to test the association between categorical variables. Results Over a 10-year period of review, a total of 3279 esophagogastroduodenoscopies were performed; 248 (7.8%) were done for FB removal. The mean age for children having endoscopy for FB removal was 3.9 (SD, 3.2) years (median, 3.1 years); there was a slight male predominance (male/female ratio = 1.6:1). The vast majority (81%) of retained FBs was coins. Most of the FBs were located in the upper esophagus (68%). Success rate for retrieval was greater for esophageal FBs (99%) than for more distally located FBs (70%; P < 0.001). Mucosal ulceration, seen in 59 children (30%), was related to a complaint of substernal pain but not vomiting, respiratory distress, or drooling. The finding of esophageal ulceration was not related to location of coin impaction or denomination of ingested coin but was related to duration of impaction and the unexpected finding of FB during chest radiograph. Underlying pathology was found more commonly in children with meat bolus impaction (100%) than in children with other FB ingestions (3.6%; P < 0.001). Conclusions Ingestion of FBs by children remains a significant problem faced by emergency department personnel. In our study, a complaint of substernal chest pain in children with an esophageal FB predicted esophageal ulceration. Also, esophageal FBs unexpectedly found on chest radiograph or known to be present greater than 72 hours were more likely to have esophageal ulceration. These clinical and historic clues can help direct appropriate prompt referral for endoscopic removal.

The buried bumper syndrome complicating percutaneous endoscopic gastrostomy in children.

Percutaneous endoscopic gastrostomy (PEG) tube placement is a well-established means of providing enteral nutrition to infants and children who cannot tolerate oral feeds. However, potential serious complications can occur with the use of PEG tubes. An increasingly reported complication is migration of the internal bolster into the abdominal wall, referred to as the buried bumper syndrome (BBS) (1–12). Most reported cases have been in adults. Between March 1999 and December 2000, we placed 30 PEG tubes by the pull technique (Microvasive Securi-T Initial Gastrostomy Kit, Boston Scientific Corp., Watertown, MA) under general anesthesia. Buried bumper syndrome occurred in 2 children (6.7%). We report our experience with this complication and review the literature.

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.

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.

The prevalence of hepatitis C virus (HCV) in infants and children after liver transplantation

Hepatitis C virus (HCV) is an important cause of liver injury following liver transplantation in adults. We hypothesized that the prevalence of HCV infection in children following liver transplantation would be lower than the prevalence in adults after liver transplantation because HCV-related liver disease leading to liver transplantation in children is low and children require less blood products than adults during transplantation. We therefore performed a cross-sectional study to determine the prevalence of HCV infection in children who had undergone liver transplantation. Serum samples were obtained from 62 of 65 (95.4%) consecutive patients surviving for more than six months after transplantation. Using a second-generation enzyme-linked, immunosorbent assay (ELISA-2) and a second-generation recombinant immunoblot assay (RIBA-II), antibodies to HCV were detected in 5.1% (3 of 59) of the subjects. Using a single-step, polymerase chain reaction (PCR), HCV RNA was detected in 6.2% (4 of 62). All HCV-positive children had undergone liver transplantation before the initiation of routine screening for HCV in blood donors; overall 30 patients were transplanted prior to routine screening of blood products for HCV. The prevalence of HCV in infants and children after liver transplantation in our study is substantially less than the rates reported in adults. This difference may be due, in part, to the lower volume of blood product exposure and to the fact that children, as opposed to adults, rarely have chronic HCV infection as a cause of end-stage liver disease.