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Background: Endoscopic ultrasound (EUS) is a unique example of POCUS, which allows the gastroenterologist to discuss subepithelial pathology immediately after an endoscopy. The challenges that are encountered to create an acoustic interface by adding free water during the endoscopy may be curtailing the full utilization of EUS during endoscopic procedures. Eosinophilic esophagitis (EoE) is a progressive inflammatory condition whose morbidity is related to esophageal wall remodeling. However, in clinical practice, in clinical guidelines, and in many trials, EoE outcomes are based on esophageal eosinophilia and symptoms. Hence, a method to identify and quantitate the thickening of the esophageal wall, could contribute to the management of this disease., Results: A modification of the approach employed to perform EUS during bronchoscopy was developed. An EUS miniprobe was positioned inside of a water filled balloon sheath. This technique permitted rapid and reproducible images acquisition of the total esophageal wall and its sublayers (mucosa, and submucosa + submucosa, which permitted derivation of the muscle layer). The presented series describes the results from  22 consecutive EoE patients. A full set of measurements from both the mid and distal esophagus were achieved in all EoE patients in an average time of less than 10 minutes., Conclusions: This pilot study supports further investigations evaluating this economical, convenient, and safe technique to follow EoE patients. In addition, this approach could be potentially employed in all patients who are found to have subepithelial gastrointestinal pathology during routine endoscopic procedures., (© 2024. The Author(s).)

Competing Interests: The author reports no conflicts of interest.

Background and Objective: To highlight and interpret two significant differences between eosinophilic esophagitis (EoE), a type 2 helper cell (Th2) disease, and three other representative Th2 diseases. EoE, asthma, atopic dermatitis (AD), chronic rhinosinusitis (CRS) and other Th2 diseases employ epithelial alarmins to recognize triggers, share a prototypical inflammatory cascade, and respond to glucocorticoids. However, EoE also has several distinguishing characteristics which may be explained by a distinct pathophysiologic mechanism., Methods: The following report consist of four related narrative reviews which combine comprehensive PubMed and Google searches. Two reviews were performed to identify and contrast all eligible studies describing serologic markers in EoE compared to asthma, AD, and CRS. Two additional reviews then compare the responses to parenteral biological therapies in EoE and in the same representative Th2 diseases., Key Content and Findings: Comprehensive literature searches definitively differentiate the absence of serologic markers in EoE compared to their identification in the other representative Th2 diseases. Similarly, a summary of therapeutic trials demonstrates that while EoE is unable to clinically respond to a variety of parenteral biological therapies, asthma, AD and CRS are very effectively treated with this same approach. A novel pathophysiology for EoE is proposed, and the emerging literature that support its existence is summarized., Conclusions: The fundamental properties described in this narrative regarding serologic signaling and response to parenteral therapy in EoE could be explained if EoE employs a unique application of the Th2 pathway. One potential mechanism consistent with these observations is that EoE employs exclusively esophageal mucosal constituents to initiate and generate the prototypical Th2 cascade and the fibrostenotic changes that follow., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tgh.amegroups.com/article/view/10.21037/tgh-22-15/coif). The authors have no conflicts of interest to declare., (2023 Translational Gastroenterology and Hepatology. All rights reserved.)

Objectives: The eosinophilic esophagitis (EoE) endoscopic reference score (EREFS) was developed to analyze adults with EoE and has been successfully applied to a pediatric cohort. The present study compares EREFS in younger and older children with EoE., Methods: The 99 patients were divided among 3 cohorts: 44 active EoE (EoE-A); 16 EoE remission (EoE-R); and 39 controls (esophageal dysfunction but <15 eos/hpf). The cohorts were then subdivided into 2 groups: younger (≤10 years) and older (>10 years) that were compared based on the composite and the individual components of their EREFS., Results: EREFS identified EoE-A in all children with an area under the receiving operating characteristics curve (AUC) of 0.85, in older children with an AUC of 0.90 and in younger children with an AUC of 0.77. Mean EREFS for ≤10 years was 1.26 ± 1.19 and 2.71 ± 1.33 for >10 years (P < 0.01). The 3 most common findings in our entire EoE-A cohort and in both ages were furrows, edema, and exudates. EREFS in patients with EoE-A had similar specificities (0.88 vs 0.89) and positive predictive values (0.89 vs 0.91) in both ages., Conclusions: The present investigation confirms the utilization of EREFS in Pediatric EoE. Furthermore, EREFS can detect EoE and document response to treatment in both younger and older children. EREFS, however, predicted EoE in the older children with a higher sensitivity (0.89 vs 0.63) and a higher negative predictive value (0.87 vs 0.59) than was seen in the younger cohort.

Pyoderma gangrenosum (PG) is a rare, necrotizing dermatologic condition associated with neoplastic and immune dysregulatory states, including adult and pediatric inflammatory bowel disease (IBD). Over the last decade, the elucidation of inflammatory mediators in PG has led to a plethora of localized and systemic corticosteroid sparing therapies including antibiotics, antiinflammatory, and immunomodulatory agents. Herein, we describe the case of a 17-year-old female with ulcerative colitis in clinical remission, who presented with a long-standing, large, deep, and painful lower extremity PG lesion. Following failed attempts both at local and at systemic therapies, her PG was successfully treated with the tumor necrosis factor-alpha (TNF-α) monoclonal antibody adalimumab, and the lesion remains in remission after four years of subcutaneous anti-TNF therapy. This case serves as the basis for our presenting a review of the pathogenesis, diagnostic criteria, differential diagnosis, therapies and treatment outcomes for pediatric IBD-associated PG. Our experience adds to earlier reports suggesting anti-TNF-α biologic therapy is most likely to achieve long-term resolution of IBD-associated PG in children and adolescents with severe lesions or who failed other treatments., Competing Interests: Disclosure: The authors declare no funding or conflicts of interest., (Copyright © 2020 The Author(s). Published by Wolters Kluwer on behalf of European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Background and Objective: EUS has been shown in two small series to be capable of documenting increases in the total esophageal wall thickness (TWT) in children and adults with eosinophilic esophagitis (EoE). To apply EUS-derived TWT in clinical situations or in scientific investigations in pediatric EoE, measurements of esophageal TWT in children of differing ages and heights are required., Materials and Methods: Thirty patients (18M: 12F, 7 months to 20 years and 10 months) with a history of esophageal symptoms, but no endoscopic or histologic criteria of EoE were studied using a through the scope 20 MHZ Olympus Ultrasound miniprobe UM-3R (Olympus America, Center Valley Pa 18034) through a GIF Q180 or 160 (Olympus) standard pediatric upper endoscope. The mucosa, the mucosa plus submucosa, and the TWT were measured in the mid- and distal esophagus immediately before taking diagnostic biopsies., Results: Measurements from both sites showed a statistically significant increase in TWT as a function of age (P < 0.001) and height (P < 0.001), as did the individual layers. The width of the mucosa and the submucosa were equivalent and together, they contributed more than half of the entire TWT. There were no significant differences between the means of the mid- and distal esophageal measurements. A multiple regression equation that can predict TWT based on age, with 95% confidence limits, is presented., Conclusions: EUS has demonstrated that esophageal TWT in a cohort of control children correlates with height and with age and has provided insights into the organization of the esophageal wall. Esophageal TWT values obtained by EUS can now be interpreted to recognize esophageal wall thickening throughout childhood., Competing Interests: None

Background and Aims: Altered vascular flow is known to both play a role in the pathogenesis and influence the severity of inflammatory bowel disease (IBD). This phenomenon has been described in other systemic conditions and contributes to disease progression by facilitating inflammation and thrombosis. Microvascular dysfunction may represent an early sign of generalized vascular disease (VD). It manifests by failure to achieve a normal response of vasodilation and increased blood flow following a period of vaso-occlusion. Although thromboembolic complications are well described in IBD, their pathogenesis is not fully understood. This study sought to assess microvascular responsiveness in pediatric subjects with IBD, by recording postocclusion peripheral arterial pulsatile volume changes., Patients and Methods: A total of 32 pediatric subjects were studied, including 16 with IBD and 16 age-matched controls. All patients with IBD were in clinical remission, and none had known VD. Vascular reactivity was evaluated using the Itamar Medical EndoPAT2000, a noninvasive device utilizing plethysmography to measure microvascular flow. Results were reported as the reactive hyperemia index (RHI), indicating post- to preocclusion pulsatile volume changes., Results: Baseline characteristics, including body mass index, plasma lipid levels, hemoglobin, and serum albumin, were similar in both study groups. All patients with IBD were in clinical remission, assessed by standard disease activity scoring methods. Measurements of microvascular function indicated patients with IBD exhibited a mean RHI both within the range associated with VD risk in adults (≤1.67) and significantly lower than that in controls (IBD vs control = 1.66 vs 2.02, P = 0.036)., Conclusions: Microvascular plethysmography is a safe and noninvasive method for assessing microvascular function in children with IBD. Patients with IBD in clinical remission demonstrate an attenuated, postocclusion microvascular hyperemic response, compared with the normal response in controls. These findings suggest pediatric IBD subjects with a mean RHI within the VD "at risk" range should be monitored for thromboembolic phenomena. Further studies in a larger patient population and over longer periods should be conducted to validate our findings and to determine the importance of these measurements in guiding IBD management.

Objectives: Helicobacter pylori (Hp) are the most common agents causing gastric mucosal injury worldwide. Foveolar hyperplasia is a key component of the stomach's reaction to injury. This study examines histopathologic characteristics associated with Helicobacter pylori and with non- Helicobacter pylori-associated gastropathy in children and adolescents, and compares the prevalence of foveolar hyperplasia among these disease subgroups and normal control subjects., Methods: Eighty-one gastric antral and corpus biopsies from subjects 2-19 years of age were studied. Twenty-two subjects with Helicobacter pylori gastritis were compared to 23 with non-Helicobacter pylori gastropathy and to 36 controls (normal biopsies). Foveolar length, full mucosal thickness, and the foveolar length: full mucosal thickness ratio were derived by a morphometric technique previously developed to analyze adult gastric tissue., Results: Compared to controls, Helicobacter pylori gastritis demonstrated significant increases in antral foveolar length (P < .0001), full mucosal thickness (P < .0001), as well as corpus foveolar length (P < .05) and corpus full mucosal thickness (P < .05). Non-Helicobacter pylori-associated gastropathy also was characterized by increased antral foveolar length (P < .0001) and full mucosal thickness (P < .001) but corresponding corpus measurements did not differ from controls. Antral foveolar length in non-Helicobacter pylori gastropathy was increased, when compared to Helicobacter pylori gastritis (P < .05), while corpus values were not. The non-Helicobacter pylori gastropathy group demonstrated increased antral foveolar length: full mucosal thickness ratios, compared with Helicobacter pylori gastritis (P < .001) and with normal controls (P < .0001)., Discussion: An objective, quantitative approach to measuring foveolar hyperplasia in adults was successfully applied to pediatric biopsies and yielded a richer characterization of gastric pathology in children. Foveolar hyperplasia appears to be a generalized phenomenon in the presence of pediatric Helicobacter pylori gastritis but is limited to the antrum in non-Helicobacter pylori gastropathy., (© 2018 John Wiley & Sons Ltd.)

An 11-year-old Caucasian boy, with a microdeletion in the 1q21.1-q21.2 region, had multiple medical conditions including gastroparesis documented initially at the age of 5. The patient had a history of poor feeding since infancy and had been treated for gastro-oesophageal reflux disease (GERD), constipation and multiple food allergies. As a consequence of the GERD and his concurrent immunoglobulin (IgG) subclass deficiency, the patient had multiple otolaryngologic (ENT) infections and required two sinus surgeries. The patient had poor weight gain (below the third percentile for weight-for-age) and required a short course of parenteral nutrition and eventually a gastrostomy tube. He was started on metoclopramide as treatment for gastroparesis with an increase in his appetite, oral intake and weight gain. However, severe headaches and worsening in his behaviour caused the agent to be discontinued. He had little weight gain and after a course of parenteral nutrition he was converted to a transpyloric feeding tube. Because of ongoing behavioural problems that interfered with his school performance, a psychiatrist started him on aripiprazole. After aripiprazole was prescribed at age 11, his appetite and oral intake dramatically increased and a repeat gastric emptying study was normal. The increased oral intake and weight gain continued, allowing removal of the feeding tube. More than 2 years later, on aripiprazole, he continues to gain weight without any supplemental feedings., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: The Accreditation Council for Graduate Medical Education has described 6 core competencies with which trainees should demonstrate proficiency. Using the Objective Structured Clinical Examination (OSCE), we aimed to assess 4 of these competencies among Pediatric Gastrointestinal (GI) fellows (PGs)., Methods: Eight first-year PGs from 6 medical centers in the New York area participated in a 4-station OSCE with trained standardized patient (SP) actors. The cases included an emergency department (ED) consult, or "ED Consult" for lower gastrointestinal bleeding; "Breaking Bad News" focusing on CF nutritional complications; "Second Opinion" for abdominal pain; "Transition of Care" for inflammatory bowel disease. At each station, attending faculty observed the encounters behind a 1-way mirror. SPs and faculties provided immediate feedback to the examined fellows. Previously validated OSCE checklists were used to assess performance. On completion, fellows attended debriefing sessions and completed surveys about the educational value., Results: Median overall milestone competency scores were 6.9 (PC1), 4.8 (PC2), 5.9 (MK1), 5.7 (MK2), 6.4 (ICS1), 6.9 (Prof1), and 6.7 (Prof3). Overall, fellows score highest (7/9) on the inflammatory bowel disease "Transition of Care" case, found the "Breaking Bad News" Cystic Fibrosis OSCE to be the most challenging, and were most comfortable with the "ED Consult" OSCE, as a commonly encountered scenario. Overall, the fellows rated the educational value of the program highly., Conclusions: To our knowledge, although the OSCE has been validated in other medical fields, this is the first OSCE program developed for PGs fellows. These OSCEs have included Accreditation Council for Graduate Medical Education competencies, serving to assess fellows' skills in these areas while exposing them to challenging medical and psychosocial cases that they may not frequently encounter.

Aim: To determine if packed red blood cell transfusions contribute to the development of parenteral nutrition associated liver disease., Methods: A retrospective chart review of 49 premature infants on parenteral nutrition for > 30 d who received packed red blood cell (PRBC) transfusions was performed. Parenteral nutrition associated liver disease was primarily defined by direct bilirubin (db) > 2.0 mg/dL. A high transfusion cohort was defined as receiving > 75 mL packed red blood cells (the median value). Kaplan-Meier plots estimated the median volume of packed red blood cells received in order to develop parenteral nutrition associated liver disease., Results: Parenteral nutritional associated liver disease (PNALD) was noted in 21 (43%) infants based on db. Among the 27 high transfusion infants, PNALD was present in 17 (64%) based on elevated direct bilirubin which was significantly greater than the low transfusion recipients. About 50% of the infants, who were transfused 101-125 mL packed red blood cells, developed PNALD based on elevation of direct bilirubin. All infants who were transfused more than 200 mL of packed red blood cells developed PNALD. Similar results were seen when using elevation of aspartate transaminase or alanine transaminase to define PNALD., Conclusion: In this retrospective, pilot study there was a statistically significant correlation between the volume of PRBC transfusions received by premature infants and the development of PNALD., Competing Interests: Conflict-of-interest statement: None of the authors involved in this study have any conflicts of interest.

Aim: To determine whether hepatocyte lipogenesis, in an in vitro cell culture model, is modulated by adjusting culture media monosaccharide content and concentration., Methods: Hepatocytes (Huh7), demonstrating glucose and fructose uptake and lipid biosynthesis, were incubated in culture media containing either glucose alone (0.65-0.72 mmol/L) or isosmolar monosaccharide (0.72 mmol/L) comprising fructose:glucose (F:G) molar ratios ranging from 0.58-0.67. Following a 24-h incubation, cells were harvested and analyzed for total protein, triglyceride (TG) and cholesterol (C) content. Significant differences (P < 0.05) among groups were determined using analysis of variance followed by Dunnett's test for multiple comparisons., Results: After a 24 h incubation period, Huh7 cell mass and viability among all experimental groups were not different. Hepatocytes cultured with increasing concentrations of glucose alone did not demonstrate a significant change either in C or in TG content. However, when the culture media contained increasing F:G molar ratios, at a constant total monosaccharide concentration, synthesis both of C and of TG increased significantly [F:G ratio = 0.58, C/protein (μg/μg) = 0.13; F:G = 0.67, C/protein = 0.18, P < 0.01; F:G ratio = 0.58, TG/protein (μg/μg) = 0.06; F:G ratio = 0.67, TG/protein = 0.11, P < 0.01]., Conclusion: In an in vitro hepatocyte model, glucose or fructose plus glucose support total cell mass and lipogenic activity. Increasing the fructose:glucose molar ratio (but not glucose alone) enhances triglyceride and cholesterol synthesis. These investigations demonstrate fructose promotes hepatocellular lipogenesis, and they provide evidence supporting future, in vivo studies of fructose's role in the development of hepatic steatosis and non-alcoholic fatty liver disease.

Background: Recently, publications in adults and children have documented a potential role of Helicobacter pylori (H. pylori) in decreasing the likelihood of obesity. The present study compares the prevalence of H. pylori colonization between obese (body mass index [BMI] ≥ 95th percentile) and healthy weight (BMI ≥ 5th to <85th percentiles) children seen at an inner city medical center in the United States., Methods: This retrospective study reviewed clinical features, BMI, and gastric histology of consecutive children aged 1-18 years undergoing an esophagogastroduodenoscopy. BMI percentile was calculated for age and gender. Helicobacter pylori colonization was determined by histopathologic identification of the organism. Multiple logistic regression was employed to measure the association between BMI and H. pylori colonization, controlling for baseline age, gender, and presenting symptoms., Results: Among 340 patients (51.5% female, mean age of 10.5 ± 4.7 years), 98 (29%) were obese and 173 (51%) were healthy weight. The H. pylori colonization rate of the entire cohort was 18.5% (95% CI = 14.7-23.0%). Among obese children, 10% had H. pylori colonization compared to 21% of the healthy weight children (RR = 2.1, 95% CI = 1.1-4.0). Conversely, 39% of noncolonized children, but only 21% of the infected children, were obese (RR = 1.8, 95% CI = 1.1-3.3). Multivariate analysis revealed that being colonized with H. pylori is associated with a 50% reduction in the odds of being obese (adjusted OR = 0.5, 95% CI = 0.2-1.0)., Conclusions: Our findings in a North American cohort are in agreement with studies from Asia and Europe suggesting that H. pylori infection decreases the prevalence of obesity in children. Further work to characterize the extent and nature of this relationship is warranted., (© 2014 John Wiley & Sons Ltd.)

Hepatic involvement is often encountered in gastrointestinal (GI) diseases, in part because of the close anatomic and physiologic relations between the liver and GI tract. Drainage of the mesenteric blood supply to the portal vein permits absorbed and/or translocated nutrients, toxins, bacterial elements, cytokines, and immunocytes to gain hepatic access. Liver problems in digestive disorders may range from nonspecific hepatocellular enzyme elevations to significant pathologic processes that may progress to end-stage liver disease. Hepatobiliary manifestations of primary GI diseases in childhood and adolescence are not uncommon and include several well-described associations, such as sclerosing cholangitis with inflammatory bowel disease. Liver damage may also result from the effects of drugs used to treat GI diseases, for example, the hepatotoxicity of immunomodulatory therapies. This review highlights the important features of the hepatic and biliary abnormalities associated with 3 common pediatric GI conditions: inflammatory bowel disease, celiac disease, and cystic fibrosis.

While sigmoid volvulus is commonly seen in older patients, it is rarely encountered in children and younger adults. Consequently, heightened awareness of this entity is required to avoid a delay in diagnosis. Among the pediatric and adult cases of colonic volvulus previously reported in the English literature, 23 of the affected individuals have also been diagnosed with Hirschsprung disease (HD). This report describes a 12-year-old male with a history of chronic constipation who presented with vomiting and abdominal distension and was found to have sigmoid volvulus with previously unrecognized HD. The case presentation is followed by a review of the literature describing colonic volvulus secondary to HD in children., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Salmonella osteomyelitis occurs infrequently in children without sickle cell disease. Similarly, acute osteomyelitis of the epiphysis has been rarely reported. We present a case of primary epiphyseal osteomyelitis caused by Salmonella in the distal femur of an otherwise healthy 17-month-old child. Before isolating an organism, parenteral nafcillin provided ineffective clinical, radiographic, and laboratory responses. Repeated fluoroscopic-guided percutaneous surgical drainages allowed for identification of the Salmonella, but did not resolve the epiphyseal infection, as the infection focus was missed. In the effort to eradicate the infection yet minimize further trauma to the epiphysis, computed tomography-guided drainage was performed and the infection subsequently resolved. Owing to its greater localization accuracy and minimal invasiveness, the computed tomography-guided intervention allowed for precise drainage without compromising the contiguous growth plate. At latest follow-up, the patient was ambulating well, had a normal knee examination, and had no evidence of leg length discrepancy or growth disturbance.

Objectives: Although many children with otolaryngologic (ENT) symptoms are being treated for gastroesophageal reflux (GER), how to diagnose GER in children with primarily or exclusively ENT symptoms has yet to be determined. This study compares the incidences of pathologic GER in the upper verses the lower esophagus in a cohort of children with ENT symptoms that were screened for GER., Methods: The results of extended dual channel intraesophageal pH probe monitoring obtained from 14 infants and 14 children with ENT symptoms were retrospectively analyzed. The percent of total monitoring time that the pH was less than 4, reflux index (RI) was determined. The upper limits of normal distal and proximal esophageal RI were based on published data. To evaluate our results, upper esophageal reflux (UER) was also determined in 27 infants and children without ENT or pulmonary symptoms, who had normal lower esophageal reflux (LER) values., Results: Mean upper esophageal RIs in the infants and children with normal LER were similar to previously published values for control infants and adults. Four (29%) of the ENT infants, 11 (79%) of the older ENT children, and 54% of the entire cohort had increased esophageal acid exposure. However, nine (60%) of the 15 pediatric ENT patients with GER had pH abnormalities limited to the upper esophagus., Conclusions: Standard distal pH probe monitoring alone gives a false negative result in a substantial proportion of the infants and children with ENT symptoms being evaluated for GER. Beyond its value in clinical practice, UER testing should be employed in research studies that evaluate the impact of GER therapy on ENT symptoms.

The prevalence of hepatitis C virus (HCV) infection and the risk factors associated with its transmission are described in a contemporary cohort of 55 children and adolescents with end-stage renal disease (ESRD). Thirty-seven patients were on dialysis or had been transplanted (ESRD) and 18 had chronic renal failure (CRF) but had not yet received dialysis. Seven (19%) tested positive for HCV by enzyme-linked immunosorbent assay (ELISA), polymerase chain reaction (PCR), or both. None of the children with CRF were infected. HCV infection was associated with length of time on dialysis, but not with age, gender, race, or units of blood transfused. These data corroborate earlier reports and confirm that children with ESRD continue to have a high prevalence of HCV. It is also shown for the first time that elevated transaminases should not be employed to predict HCV infection in this cohort, as all affected children had normal serum levels. Because of unique characteristics in this cohort, both ELISA and PCR are required to maximize HCV diagnostic sensitivity. Although HCV remains an important consideration in pediatric ESRD, the present study shows that recent advances in clinical practice have eliminated one of the major ways in which it was previously being transmitted.

Background: Platelet-activating factor (PAF) is a heterogeneous phospholipid that has been implicated as participating in a number of perinatal disease processes including necrotizing enterocolitis (NEC)., Methods: Baseline blood levels of PAF and related lipids (PAF-LL) were measured for 164 infants at risk for NEC from 3 neonatal intensive care units. Serial levels were obtained from the 11 infants in whom NEC developed., Results: The mean peak PAF-LL in the infants without NEC was 2.03 +/- 1.96 ng/mL. Infants with stage II (n = 6) and III (n = 5) NEC had elevated peak PAF-LL values (mean peak value 13.6 +/- 6.9 ng/mL). No PAF-LL measurements obtained from infants during stage II or III NEC were <2.03 ng/mL. Three infants had PAF-LL elevations before the development of any clinical or radiographic evidence of NEC. PAF-LL level increased as the severity of NEC increased and decreased with its resolution. Setting a PAF-LL level of 10.2 ng/mL as a cutoff for NEC had a positive predictive value of 100%., Conclusions: PAF-LL determinations can complement clinical and radiographic studies to diagnose and follow the progression of NEC. PAF-LL may have a role in the evolution of NEC.

Background: Smooth muscle tumors are the second most common malignancy encountered in children with acquired immunodeficiency syndrome (AIDS). This study reviewed the incidence and endoscopic appearance of smooth muscle tumors in the gastrointestinal tract of children with AIDS undergoing endoscopy., Methods: Retrospective review of all endoscopic records (n = 70) of children with AIDS from August 1988 to December 1997 at a tertiary care inner city hospital., Results: Three children with advanced AIDS (4%) were found to have smooth muscle tumors, all of which had the typical appearance of submucosal nodules with central ulceration. Some were hemorrhagic. They measured less than 1 to 4 cm in diameter. Two children had multiple tumors. All lesions except for one were located in the colon. Colonic biopsies revealed a leiomyoma in one patient and a smooth muscle tumor of uncertain malignant potential in another. The forceps biopsy of the single gastric mass was not deep enough to make the diagnosis of a smooth muscle tumor. A nonmalignant smooth muscle tumor grew from less than 5 mm to more than 4 cm in 1 year and was removed surgically. All three children are alive without any evidence of local spread or distant metastases despite no specific therapy for the smooth muscle tumor., Conclusions: Smooth muscle tumors in the GI tract of children with AIDS are relatively common. Further study of the long-term outcome for children infected with the human immunodeficiency virus who have these lesions are needed to establish prognosis and management guidelines.

Intestinal leiomyosarcomas are exceedingly rare in immunologically intact children, except during infancy. While leiomyosarcomas account for less than 2% of all soft tissue tumors in childhood, they are the second most frequent malignancy in children with the acquired immunodeficiency syndrome (AIDS). In this cohort they are often located in unusual sites for primary soft tissue tumors. This report describes a young girl with advanced AIDS, referred for evaluation of abdominal pain, hematochezia, and wasting syndrome. Colonoscopy revealed two 1- to 2-cm submucosal nodules with central umbilication. Repeat colonoscopy 18 months later revealed no changes in these lesions. Biopsy revealed a submucosal spindle-cell lesion, with necrosis and cellular atypia. Initially it was characterized as a partially excised low-grade leiomyosarcoma. However, the final consensus diagnosis was smooth muscle tumor of uncertain malignant potential. Because of her advanced AIDS, there was no attempt at surgical resection or chemotherapy. Thirty-six months after initial referral, she remains alive without radiographic or clinical evidence of local extension or metastases. Additional data are required to determine the long-term outcome of these indolent submucosal tumors in the digestive tracts of children with AIDS.

Objective: This paper presents the cases of two infants exposed to perinatal zidovudine in whom hypoperistalsis and intestinal pseudoobstruction developed., Study Design: Clinical case reports were prepared of two infants born to women infected with human immunodeficiency virus who were treated with perinatal zidovudine at a single inner-city medical school., Results: None of the previously described causes for this rare condition contributed to the symptoms in these two infants. In addition, the symptoms resolved shortly after discontinuation of zidovudine administration., Conclusions: Although a strict cause-and-effect relationship between the medication and the impairment in intestinal peristalsis was not proved, awareness of this association should be helpful for physicians caring for infants exposed to perinatal zidovudine.

Purpose: To help determine the etiology and most appropriate treatment regimen for hypergastrinemia, dysuria-hematuria and metabolic alkalosis following augmentation gastrocystoplasty., Materials and Methods: Two patients who presented with refractory metabolic alkalosis (1 with dysuria-hematuria) underwent extensive laboratory evaluation, complete upper gastrointestinal evaluation and intravesical pH probe placement., Results: Both patients eventually required high dose oral potassium chloride supplementation. Bladder mucosal pH was not reflected by buffered urinary pH. Both patients demonstrated significant gastroesophageal reflux and diminished overall gastric acid output., Conclusions: Outpatient maintenance on potassium chloride supplementation may be warranted in select patients and appears to be preferable to histamine blockade or omeprazole. Postoperative screening esophagogastroscopy and an additional surgical maneuver might be indicated to prevent possible adverse sequelae of reflux esophagitis. Gastrocystoplasty may be an inappropriate operation in children with renal insufficiency who have not had metabolic acidosis.

The distribution of the enzyme synthesizing nitric oxide (NO) has been characterized in several mammalian enteric nervous systems. Two methods, immunohistochemical staining, employing anti-nitric oxide synthase antibodies, and histochemical localization of NADPH-diaphorase (NADPH-D), have given the same results. On the other hand, few studies have investigated nitric oxide synthase (NOS) in the gastrointestinal mucosa. Our study demonstrated the presence and distribution of the enzyme, NADPH-D, throughout all layers of the neonatal piglet intestinal tract. In the neonatal piglet, NADPH-D activity was found in nerve fibers parallel to the circular and to the longitudinal muscles and in the ganglion cells of Auerbach's plexus. However, the majority of NADPH-D activity was localized to the mucosa. Furthermore, the most intense activity in the mucosa was observed in villous epithelial cells. Other mucosal cells which were NADPH-D positive included the glandular epithelium and crypt cells. In addition, glandular epithelium in the deeper submucosa had very strong NADPH-D activity. Our results support the hypothesis that locally produced NO mediates physiological functions in the intestinal mucosa and submucosa.

Rat monoclonal antibody FA/11 has been used to identify macrosialin, a sialoglycoprotein confined to murine mononuclear phagocytes and related cells. Originally identified as a macrophage-associated glycoprotein predominantly localized in intracellular membranes (Smith, M.J., and G.L.E. Koch. 1987. J. Cell Sci. 87:113), the antigen is widely expressed on tissue macrophages, including those in lymphoid areas, and is expressed at low levels on isolated dendritic cells. Immuno-adsorption experiments reported here show that macrosialin is identical to the major 87-115-kD sialoglycoprotein previously identified by lectin blotting in exudate but not resident peritoneal macrophages (Rabinowitz, S., and S. Gordon. 1989. J. Cell Sci. 93:623). Resident peritoneal macrophages express low levels of macrosialin antigen in a glycoform that does not bind 125I wheat germ agglutinin or 125I peanut agglutinin; inflammatory stimuli upregulate expression of this antigen (up to 17-fold), in an alternative glycoform that is detected by these lectins. Pulse-chase experiments reveal a 44-kD core peptide that initially bears high-mannose chains (giving Mr 66 kD) and is subsequently processed to a mature protein of Mr 87-104 kD. Each glycoform contains N-linked glycan, as well as O-linked sugar structures that show alternative processing. Poly-N-acetyllactosamine structures are detected in the exudate cell glycoform only. This new marker for mononuclear phagocytes illustrates two strategies by which macrophages remodel their membranes in response to inflammatory stimuli. Its predominantly intracellular location and restricted cell distribution suggest a possible role in membrane fusion or antigen processing.

Portal hypertension, an expected consequence of cirrhosis, often has an insidious course in children. A noninvasive technique using abdominal sonography has been previously employed by several investigators as a means of diagnosing this condition. Their technique involves sonographically measuring the diameter of the lesser omentum, which increases as a result of engorged collaterals. In this communication, the method is successfully employed in two children, an infant in whom cirrhosis developed who eventually died from acquired immunodeficiency syndrome, and one whose portal hypertension was relieved after orthotopic liver transplantation. Although successful in these two instances, the theoretical basis on which this technique is based is critically evaluated. Anatomical relationships are reviewed that would caution sonographers who attempt to duplicate these studies. Modifications of the technique that will minimize potential false positive results are also discussed.

Pigeon liver fatty acid synthetase which contains two subunits of 240,000 daltons each has been treated with elastase. This treatment yields four protein fragments which can be separated on sodium dodecyl sulfate (SDS)-gel electrophoresis. After the subunit protein has been treated with elastase, all of the partial enzyme activities catalyzed by the complex are present, but enzyme activity for fatty acid synthesis is lost. The formation of protein fragments during proteolysis has been followed by densitometric scanning of the SDS gels. The results of these scans have suggested that (a) there are two peptide components present in the highest molecular weight band, (b) both are rapidly digested to yield the second and third largest peptides, and (c) a further cleavage of the third largest peptide gives rise to the smallest of the four major peptides. Crossed-rocket immunoelectrophoretic analysis of the four protein fragments has confirmed these conclusions and established also that the three smallest peptides are homogeneous. Each of the four peptides has been isolated by preparative SDS-gel electrophoresis, and antibody to one has been prepared. This antibody fraction immunotitrates overall fatty acid synthetase activity and immunoprecipitates the native enzyme. Immunoelectrophoresis of the four elastase-digested synthetase products against this antibody showed some cross-reactivity with a peptide that was neither the precursor nor the product of the immunogen. This cross-reacting antibody was removed by reaction with the nonrelated protein to yield antibody specific for one region of the fatty acid synthetase complex.

The homogeneity of pigeon liver fatty acid synthetase has been rigorously tested by physicochemical techniques and crossed-rocket immunoelectrophoresis. The enzyme has also been incubated for 1 h at 100 degrees C in 2% sodium dodecyl sulfate and 0.1 M dithiothreitol. The number of protein components on gel electrophoresis and of dansylated amino acids increased as a function of incubation time. Furthermore, the minor proteins observed after gel electrophoresis cross-reacted with antibody raised to the synthetase. Proteolysis was not chemically mediated by the detergent, the reducing agent or the buffer conditions chosen. Several commercially prepared proteins were not degraded by this procedure, and two proteins were recalcitrant to hydrolysis when included in the same incubation mixture as the synthetase. The inclusion of certain microbial proteinase inhibitors decreased the amount of degradation. This demonstrated that hydrolysis of the synthetase is mediated by a specific vertebrate enzyme which retains activity under denaturing conditions at 100 degrees C. Further degradation is also observed after individual treatment of four limited digestion products from the pigeon liver fatty acid synthetase, suggesting the possibility of an inherent proteolytic activity within the complex.