Impact of antegrade enema initiation on healthcare utilization in pediatric patients: A population-based cohort study.

BACKGROUND: When constipation is refractory to first-line interventions, antegrade enema use may be considered. We aimed to assess the impact of this intervention on healthcare utilization. METHODS: We conducted a population-based, quasi-experimental study with pre-post comparison of the intervention group and a non-equivalent control group using linked clinical and health administrative data from Ontario, Canada. Subjects included children (0-18 years) who underwent antegrade enema initiation from 2007 to 2020 and matched controls (4:1) from the general population. To assess the change in healthcare utilization following antegrade enema initiation, we used negative binomial generalized estimating equations with covariates selected a priori. KEY RESULTS: One hundred thirty-eight subjects met eligibility criteria (appendicostomy = 55 (39.9%); cecostomy tube = 83 (60.1%)) and were matched to 550 controls. There was no significant difference in the change in the rate of hospitalizations (rate ratio (RR) 1.05, 95% confidence interval (CI) 0.35-1.75), outpatient visits (RR 1.05, 95% CI 0.91-1.18), or same-day surgical procedures (RR 1.51, 95% CI 0.60-2.43) across cases in 2 years following antegrade enema initiation compared with controls. Cases had an increased rate of emergency department (ED) visits, which was not observed in controls (RR 1.52, 95% CI 1.11-1.79), driven in part by device-related complications. CONCLUSIONS AND INFERENCES: Understanding healthcare utilization patterns following antegrade enema initiation allows for effective health system planning and aids medical decision-making. The observed increase in ED visits for device-related complications speaks to the need to improve preventive management to help mitigate emergency care after initiation of antegrade enemas.

Gastrointestinal Symptoms in Type 1 Diabetes: Relationship With Autoimmune and Microvascular Complications.

PURPOSE: To assess reported rates of gastrointestinal (GI) symptoms and their association with autoimmune diseases and microvascular complications in adults and children with type 1 diabetes. METHODS: The Gastrointestinal Symptom Scale was used to assess GI symptom type and severity in 2370 patients with type 1 diabetes aged 8 to 45 years evaluated as part of a clinical trial screening for celiac disease (CD). The presence and severity of GI symptoms and relationships with demographic, clinical, and other diabetes-related factors were evaluated. RESULTS: Overall, 1368 adults (57.7%) aged 19 to 45 years and 1002 (42.3%) pediatric patients aged 8 to 18 years were studied. At least 1 GI symptom was reported in 34.1% of adults as compared with 21.7% of children (P < 0.0001). Common symptoms in children included upper and lower abdominal pain while adults more frequently reported lower GI symptoms. Participants with GI symptoms had higher hemoglobin A1c (HbA1c) levels (68 ±â€…14mmol/mol; 8.35 ±â€…1.37%) than those without symptoms (66 ±â€…15mmol/mol; 8.22 ±â€…1.40%; P = 0.041). Patients with microvascular complications (nephropathy, retinopathy, and/or neuropathy) were 1.8 times more likely to report GI symptoms (95% CI: 1.26-2.60; P < 0.01) after adjusting for age and sex. No association was observed between GI symptoms and the presence of autoimmune conditions, including thyroid and biopsy-confirmed CD (odds ratio = 1.1; 95% CI: 0.86-1.42; P = 0.45). MAIN CONCLUSIONS: These results highlight that GI symptoms are an important clinical morbidity and are associated with increasing age, duration of type 1 diabetes, HbA1c, and microvascular complications but not with autoimmune comorbidities including CD.

Accuracy of Screening Tests for Celiac Disease in Asymptomatic Patients With Type 1 Diabetes.

INTRODUCTION: To evaluate the diagnostic performance of celiac serologic tests in asymptomatic patients with type 1 diabetes (T1D). METHODS: Patients with T1D asymptomatic for celiac disease were prospectively screened with immunoglobulin A anti-tissue transglutaminase. Test characteristics were calculated and optimal cutoffs for a positive screen determined. RESULTS: Two thousand three hundred fifty-three patients were screened and 101 proceeded to biopsy. The positive predictive value of immunoglobulin A anti-tissue transglutaminase at the assay referenced upper limit of normal (30CU) was 85.9%, and the sensitivity and specificity were 100% and 38%, respectively. DISCUSSION: Thresholds extrapolated from the general population for the diagnostic evaluation of celiac disease are not suitable for use in asymptomatic T1D patients. Population-specific screening cutoffs are required.

Impact of a Gluten-Free Diet on Quality of Life and Health Perception in Patients With Type 1 Diabetes and Asymptomatic Celiac Disease.

CONTEXT: Celiac disease (CD) is a common comorbidity seen in patients with type 1 diabetes (T1D) and is frequently asymptomatic. As chronic conditions requiring significant lifestyle changes, there are limited reports assessing changes in health-related quality of life (HRQoL) during transition to a gluten-free diet (GFD) in patients with T1D who are asymptomatic for CD. OBJECTIVE: This work aims to prospectively assess HRQoL and health perception in children and adults with T1D and asymptomatic CD after random assignment to GFD vs usual diet. METHODS: Patients with T1D aged 8 to 45 years without CD symptoms were serologically screened for CD, with positive results confirmed with intestinal biopsy. Participants were randomly assigned in an open-label fashion to a GFD or gluten-containing diet (GCD) for 12 months. Generic and diabetes-specific HRQoL and self-perceived wellness (SPW) were assessed longitudinally. RESULTS: A total of 2387 T1D patients were serologically screened. CD was biopsy-confirmed in 82 patients and 51 participants were randomly assigned to a GFD (N = 27) or GCD (N = 24). Excellent adherence to the assigned diets was observed. Overall, no changes in generic (P = .73) or diabetes-specific HRQoL (P = .30), or SPW (P = .41) were observed between groups over 12 months. Hemoglobin A1c (HbA1c) and gastrointestinal symptoms were consistent predictors of HRQoL and SPW. CONCLUSION: HRQoL and SPW were not significantly affected by the adoption of a GFD over 12 months, but worsened with symptom onset and increased HbA1c. Our findings indicate that transition to a GFD can be made successfully in this population without adversely affecting quality of life.

Screening and Treatment Outcomes in Adults and Children With Type 1 Diabetes and Asymptomatic Celiac Disease: The CD-DIET Study.

OBJECTIVE: To describe celiac disease (CD) screening rates and glycemic outcomes of a gluten-free diet (GFD) in patients with type 1 diabetes who are asymptomatic for CD. RESEARCH DESIGN AND METHODS: Asymptomatic patients (8-45 years) were screened for CD. Biopsy-confirmed CD participants were randomized to GFD or gluten-containing diet (GCD) to assess changes in HbA1c and continuous glucose monitoring over 12 months. RESULTS: Adults had higher CD-seropositivity rates than children (6.8% [95% CI 4.9-8.2%, N = 1,298] vs. 4.7% [95% CI 3.4-5.9%, N = 1,089], P = 0.035) with lower rates of prior CD screening (6.9% vs. 44.2%, P < 0.0001). Fifty-one participants were randomized to a GFD (N = 27) or GCD (N = 24). No HbA1c differences were seen between the groups (+0.14%, 1.5 mmol/mol; 95% CI -0.79 to 1.08; P = 0.76), although greater postprandial glucose increases (4-h +1.5 mmol/L; 95% CI 0.4-2.7; P = 0.014) emerged with a GFD. CONCLUSIONS: CD is frequently observed in asymptomatic patients with type 1 diabetes, and clinical vigilance is warranted with initiation of a GFD.

Outcomes of multi-gestational pregnancies affected by esophageal atresia - tracheoesophageal fistula.

BACKGROUND: Contemporary outcomes of infants with esophageal atresia with or without tracheoesophageal fistula (EA/TEF) from multi-gestational pregnancies compared to those of singleton pregnancies have not been reported. METHODS: A single-center retrospective review of EA/TEF patients born from 1999 to 2013 was performed. Patient demographics, gestational age (GA), birth weight, associated anomalies, requirement for gastrostomy tube and mortality were reviewed. RESULTS: Singleton EA/TEF patients outnumbered those from multi-gestational pregnancies nearly 10:1 (214 vs 22 patients). EA/TEF patients from multi-gestational pregnancies were more likely to be premature (77% vs. 32%), have lower birth weight (mean 1766 g vs. 2695 g), have associated duodenal atresia (18% vs. 6%) and require gastrostomy tube (41% vs. 33%) for feeding challenges compared to EA/TEF singletons. Mortality was also significantly greater for multi-gestational EA/TEF patients compared to singleton EA/TEF patients (18% vs. 6%). CONCLUSION: EA/TEF infants from multi-gestational pregnancies have greater clinical complexity and mortality than singleton EA/TEF patients. Parents of EA/TEF multi-gestational infants should be appropriately counseled and supported.

Requirement and Duration of Tube Feed Supplementation among Congenital Diaphragmatic Hernia Patients.

PURPOSE: Oral feeds pose a challenge for congenital diaphragmatic hernia (CDH) infants. Tube feed (TF) supplementation may be required to support the achievement of normal growth. The aim of this study was to determine the duration and factors associated with TF use in CDH infants at our institution. METHODS: A single centre retrospective chart review was performed for CDH-born infants who underwent repair between 2000 to 2013 (REB #1000053124). Patient demographics, perinatal management, and feeding status of infants with at least 1-year follow-up were reviewed. RESULTS: Of 160 CDH infants, 32 (20%) were discharged on partial or complete TF, and an additional 5 (3.1%) patients started TF post discharge. CDH infants with TF were more likely to have initial arterial blood pH < 7.25, patch repair, ECMO support, and prolonged ICU stay (p < 0.05). Time to TF discontinuation did not differ significantly between those partially or fully TF at discharge. Twelve patients (33.3%) remained TF at their last known follow-up. CONCLUSION: High risk CDH patients are likely to require TF to support their nutritional intake. Parents and caregivers need to be informed and properly supported. Long-term monitoring of CDH patient oral intake, growth, and development will be required. LEVEL OF EVIDENCE/TYPE OF STUDY: Level III Retrospective Study.

Online education for gluten-free diet teaching: Development and usability testing of an e-learning module for children with concurrent celiac disease and type 1 diabetes.

BACKGROUND AND OBJECTIVE: Celiac disease (CD), the most common genetically-based food intolerance, affects 3% to 16% of children with type 1 diabetes (T1D). Treatment involves lifelong adherence to a gluten-free diet (GFD). Individualized dietary education is resource-intensive. We, therefore, sought to develop and test the usability of an e-learning module aimed at educating patients and caregivers regarding implementation of the GFD in children with concurrent CD and T1D. METHODS: An interactive e-learning module was developed based on extensive review of CD, T1D, and educational literature. A mixed-methods usability testing approach was used to refine and evaluate the module, using qualitative semi-structured interviews, observations, and satisfaction and knowledge questionnaires in two iterative cycles. The module was refined based on themes identified from each usability cycle. RESULTS: Eighteen patients (8 in cycle 1, 10 in cycle 2) and 15 caregivers (7 in cycle 1, 8 in cycle 2) participated. Patient participants had CD and T1D for a mean (SD) of 6.1 ± 5.1 and 8.3 ± 5.5 years, respectively. Their mean age was 13.5 ± 4.5 years. Thematic analysis of usability interviews showed the module to be appealing and resulted in minor module revisions after each cycle to improve usability. Mean satisfaction scores post-module completion were high (4.67 ± 0.54), indicating participants were "very satisfied" with the education. Knowledge test scores increased significantly from pre- to post-module completion (P = 0.001). CONCLUSION: A multifaceted user-centered usability approach demonstrated that an innovative, interactive e-learning module is effective in knowledge retention and can provide comprehensive and accessible information in the implementation of the GFD teaching in children with CD and T1D.

In Screening for Celiac Disease, Deamidated Gliadin Rarely Predicts Disease When Tissue Transglutaminase Is Normal.

OBJECTIVE: While tissue transglutaminase (tTG) antibodies are the most established serological test for celiac disease, newer deamidated gliadin peptide (DGP) screening tests are increasingly being completed. No pediatric study has systematically assessed the incidence of celiac disease in patients with an isolated positive DGP result. We sought to determine the positive predictive value of DGP serology for biopsy-confirmed celiac disease in pediatric patients with elevated DGP and normal tTG, to help guide clinicians' decision making when screening for this common condition and avoid unnecessary invasive follow-up diagnostic testing. METHODS: A multicenter retrospective review of children, from birth to age 18, with isolated DGP immunoglobulin G (IgG) positive serology referred to 3 Canadian centers was completed. The positive predictive value of an isolated elevated DGP result was calculated. RESULTS: Forty patients with DGP positive, tTG negative serology underwent endoscopy with duodenal biopsy. Of these, only 1 patient had biopsy-confirmed celiac disease. This patient was IgA deficient. This yields a positive predictive value of 2.5% (95% confidence interval 0.1%-14.7%) for isolated DGP IgG positive serology. CONCLUSIONS: In isolation, DGP positive serology has a poor positive predictive value for celiac disease in children, especially in IgA sufficient individuals. Our findings suggest that DGP IgG testing should not be completed as part of the initial screening for celiac disease in the pediatric population as it does not effectively differentiate between individuals with and without the disease. Further research is needed to clarify to role of DGP IgG in children under the age of 2 and those with IgA deficiency.

Parental Health Beliefs, Socio-demographics, and Healthcare Recommendations Influence Micronutrient Supplementation in Youth with Celiac Disease.

To identify parental influences affecting micronutrient supplementation in children and adolescents (2-18 years of age) with Celiac Disease (CD), a multi-method (survey, focus groups) study was conducted. A 35-item questionnaire consisting of open- and closed-ended questions was launched nationally via Canadian Celiac Association internet sites. Five focus groups were conducted using a semi-structured interview guide. The survey and semi-structured interview guide content was vetted for face and content validity. Thematic analyses were conducted on the focus group content and open-ended survey questions, and χ(2) and Fischer's exact analysis were performed on closed-ended survey data. Survey respondents were predominantly mothers (97%) of female children (80 F, 49 M) between the ages of 9-12 (31%) with CD, residing in western provinces (55%) with a combined family income ≥$100 000/year (63%). Seventy-seven percent of parental respondent's children or adolescents consumed micronutrient supplements, for 1-5 years (52%), 7 days a week (65%), as both multi-vitamin and single vitamin preparations (40%). Parental influences on child micronutrient use included health beliefs and knowledge, parental supplement use, supplement characteristics, age of child (above or below 13 years), household routines, and provincial residential status (P < 0.05). Parents relied on health professional recommendation (69%; MD, RD) and the internet (21%) as sources of information regarding child micronutrient supplementation. Parental health beliefs and knowledge, socio-demographic factors, and practitioner recommendation influence micronutrient supplement use in children and adolescents with CD.

Design of a dietary intervention to assess the impact of a gluten-free diet in a population with type 1 Diabetes and Celiac Disease.

BACKGROUND: Celiac Disease occurs at a 5-10 fold greater prevalence in patients with type-1 diabetes (T1D), despite this increased risk, there is limited objective evidence regarding the impact of a Gluten-Free Diet (GFD) in the large proportion of asymptomatic (30-70%) patients with both autoimmune diseases. Given the requirements and intricacies inherent to each condition, we describe the rationale and design a dietary curriculum specifically addressing the educational requirements for children and adults with CD and diabetes as part of the CD-DIET Study. METHODS AND DESIGN: The CD-DIET Study (Celiac Disease and Diabetes - Dietary Intervention and Evaluation Trial) is a multicenter randomized controlled trial aimed at evaluating the safety and efficacy of a GFD in patients with asymptomatic celiac disease and T1D on key diabetes and patient-centered outcomes. DISCUSSION: Key dietary components of the trial include a description and evaluation of food consumption patterns including glycemic index and glycemic load, novel assessments of gluten quantification, and objective and subjective measures of GFD adherence. This dietary curriculum will establish rigorous guidelines to assess adherence and facilitate evaluation of a GFD on metabolic control, bone health and patient quality of life in patients with CD and diabetes. TRIAL REGISTRATION NUMBER: NCT01566110. Date of Registration: March, 2012.

Celiac Disease and Type 1 Diabetes in Adults: Is This a High-Risk Group for Screening?

The association between celiac disease (CD), an autoimmune condition involving intestinal inflammation related to gluten ingestion, and type 1 diabetes has long been recognized. CD prevalence rates 4 to 6 times greater in adults with type 1 diabetes than in the general population. Much of the existing literature focuses on important implications related to the impact of a gluten-free diet on short-term outcomes in metabolic control and quality of life. Canadian Diabetes Association guidelines recommend targeted CD screening in patients with type 1 diabetes who have classic symptoms, such as abdominal pain, bloating, diarrhea, unexplained weight loss or labile metabolic control; however, a significant proportion (40% to 60%) of patients may have mild or absent symptoms. Recent evidence suggests that adult patients with both conditions are at higher risk for diabetes microvascular comorbidities, increased mortality and impaired bone health if the CD is untreated. The purpose of this review is to describe the association between CD and type 1 diabetes and to summarize recent literature that evaluates risks in patients with both conditions.

Long-term burden of care and radiation exposure in survivors of esophageal atresia.

BACKGROUND: Patients with esophageal atresia with or without tracheoesophageal fistula (EA/TEF) historically have had a high risk of neonatal mortality but the majority of patients are now expected to live into adulthood. However, the long-term burden of care among recent EA/TEF survivors has not been documented. METHODS: A single-institution retrospective review of newborns with EA/TEF treated from 2001-2005 was conducted, including initial and total hospitalization length of stay, and number of clinic visits and procedures requiring general anesthesia in the first three years of life. Exposure to and number of radiological studies involving ionizing radiation (IR) were recorded. RESULTS: Seventy-one of 78 (91%) patients survived to discharge and 69 were included for analysis. Mean length of initial hospital stay was 51.3 (range 9-390) days. By age 3 years, patients required 4.5 (mean, range 1-23) procedures performed under general anesthesia, attended 13.5 (mean, range 3-40) outpatient visits and were exposed to 17.4 mSv (mean, range 3.0-59.9) of IR from 40 (mean, range 5-165) radiological studies. CONCLUSION: Patients with EA/TEF need complex and frequent hospital-based care from infancy to early childhood. Opportunities to critically review clinical services and imaging needs should be explored to improve the experience of patients and their families.

The Celiac Disease and Diabetes-Dietary Intervention and Evaluation Trial (CD-DIET) protocol: a randomised controlled study to evaluate treatment of asymptomatic coeliac disease in type 1 diabetes.

INTRODUCTION: Coeliac disease (CD) is an autoimmune condition characterised by gluten-induced intestinal inflammation, and observed at a 5-10 fold greater prevalence in type 1 diabetes. While universal screening for CD in patients with diabetes is frequently advocated, objective data is limited as to benefits on diabetes control, bone health or quality of life related to the adoption of a gluten-free diet (GFD) in the large proportion of patients with diabetes with asymptomatic CD. The Celiac Disease and Diabetes-Dietary Intervention and Evaluation Trial (CD-DIET) study is a multicenter, randomised controlled trial to evaluate the efficacy and safety of a GFD in patients with type 1 diabetes with asymptomatic CD. METHODS AND ANALYSIS: Children and adults (8-45 years) with type 1 diabetes will be screened for asymptomatic CD. Eligible patients with biopsy-proven CD will be randomly assigned in a 1:1 ratio to treatment with a GFD for 1 year, or continue with a gluten-containing diet. The primary outcome will evaluate the impact of the GFD on change in glycated haemoglobin. Secondary outcomes will evaluate changes in bone mineral density, blood glucose variability and health-related quality of life between GFD-treated and the regular diet group over a 1-year period. The study was initiated in 2012 and has subsequently expanded to multiple paediatric and adult centres in Ontario, Canada. ETHICS AND DISSEMINATION: The findings from this study will provide high-quality evidence as to the impact of GFD treatment on glycaemic control and complications in asymptomatic children and adults with CD and type 1 diabetes. TRIAL REGISTRATION NUMBER: NCT01566110.

Celiac Disease Alone and Associated With Type 1 Diabetes Mellitus.

OBJECTIVES: The aim of the study was to evaluate complication screening and follow-up patterns in a population with type 1 diabetes mellitus and celiac disease (T1D/CD) in relation to a matched cohort with celiac disease (CD) alone at our center. METHODS: We retrospectively reviewed the health charts of 41 children with T1D and biopsy-proven CD and compared anthropometrics and complication of screening within 2 years from CD diagnosis. Follow-up patterns were determined 3 years postdiagnosis. This population was then compared with a population with both symptomatic and asymptomatic CD matched for age and sex. RESULTS: In comparison with T1D/CD, patients with CD alone had a significantly lower height, weight and body mass index (BMI z score 0.01 vs 0.81, P = 0.001) and higher rates of screening for anemia (95% vs 71%, P = 0.003) and bone health (49% vs 29%, P = 0.05). Minimal rates of laboratory abnormalities were observed in either group, irrespective of symptoms at presentation, but CD alone more often presented with anemia than T1D/CD. Repeat serology testing was significantly more frequently performed in the T1D/CD group. Follow-up was equally variable with a median of 3 (range 0-4) visits with a gastroenterologist during the first 3 years postdiagnosis. CONCLUSIONS: These results suggest that patients with T1D/CD represent a distinct and possibly milder phenotype from CD alone. Complication screening was variable and negative for the majority of the patients. Guidelines for follow-up may need to be tailored to specific groups to standardize evaluation and complication screening, especially with regard to bone health.

Inflammatory bowel disease manifesting after surgical treatment for Hirschsprung disease.

Eight children developed chronic inflammatory bowel disease (IBD) 4 to 21 years after surgery for Hirschsprung disease. Three had trisomy 21 and 6 experienced chronic or recurrent enterocolitis. Four had a family history of IBD. Clinical presentation included chronic diarrhea, hematochezia, abscess, and fistula formation. Three required surgery for fistula, stricture, and small bowel obstruction and the other 5 were managed medically. Recognition of this condition may be important in the long-term follow-up of children with Hirschsprung disease, and patients who have carried a diagnosis of chronic enterocolitis may warrant further investigation looking for evidence of IBD.

A single center 26-year experience with treatment of esophageal achalasia: is there an optimal method?

PURPOSE: Treatment modalities for achalasia are evolving and remain controversial. Herein, we report the relative efficacy and outcomes after dilatation or myotomy in children with achalasia. METHODS: A retrospective analysis of all children treated for achalasia at a tertiary center from 1981 to 2007 was performed (n = 40). Demographics, presenting symptoms, perioperative parameters, and outcomes were analyzed using t tests and chi(2) statistics. RESULTS: Thirty patients were initially treated by esophageal dilatation (ED), whereas 10 were treated by laparoscopic or open Heller myotomy (HM). Both groups were similar with respect to age (10.6 vs 12.4 years; P = .19). There were 18 males and 12 females in the ED group, compared to 5 males and 5 females in the HM group (P = .72). Mean duration of symptoms before diagnosis, including dysphagia, vomiting, food sticking, chest pain, and weight loss, was 15.9 months for ED and 10.7 months for HM (P = .41). Mean time from diagnosis to initial intervention was 76 days in ED vs 86 days in HM (P = .78). Subsequent interventions by myotomy or both dilatation and myotomy were required in 9 (30%) of 30 patients in the ED group and 2 (20%) of 10 patients in the HM group (P = .70). A clear transition from open to laparoscopic approach occurred between 1995 and 2001. Mean operating times were comparable (186.3 vs 156.0 minutes; P = .48). Of 14 laparoscopic myotomies, 11 (79%) had fundoplication, and 2 (18%) of the 11 were converted to open procedure. Intraoperative mucosal perforation rates were similar between open and laparoscopic groups (17% vs 18%). At follow-up, 32% of ED patients vs 43% HM had complete symptom relief (mean follow-up duration, 75.2 months; SD, 196.5). CONCLUSION: Both dilatation and myotomy are effective immediate treatment of achalasia. A clear transition to and preference for laparoscopic approach has occurred in the treatment of achalasia in children.

Activated mucosal mast cells differentiate eosinophilic (allergic) esophagitis from gastroesophageal reflux disease.

OBJECTIVES: To evaluate the utility of activated mucosal mast cells (MC) in the differential diagnosis of eosinophilic esophagitis (EE) and gastroesophageal reflux disease (GERD). METHODS: Intraepithelial eosinophils and MC were quantified in esophageal biopsies from 25 children with EE, 22 children with GERD and 22 controls. MCs were identified by immunohistochemistry for MC tryptase, whereas MC activation status was evaluated by immunohistochemistry for immunoglobulin E (IgE) and by electron microscopy. RESULTS: Esophageal biopsies from patients with EE showed higher intraepithelial eosinophil counts (55 +/- 27.5 vs 6.9 +/- 9.7, P < 0.0001) and MC counts (26.3 +/- 12.7 vs 7.8 +/- 8.9, P < 0.0001) than those from patients with GERD. Almost all EE biopsies (24 of 25 patients; 96%) contained IgE-bearing cells compared with 9 of 22 (41%) GERD biopsies (P < 0.001). GERD biopsies with intraepithelial eosinophil counts >7/high-power field (suggesting an allergic component) contained IgE-bearing cells in 6 of 7 (86%) cases compared to 3 of 15 (20%) cases with eosinophil counts <7/h.p.f (P < 0.01). No intraepithelial eosinophils, MC or IgE-positive cells were present in controls. Electron microscopy confirmed the presence of intraepithelial MC and changes in cytoplasmic granules indicative of MC and eosinophil activation. CONCLUSIONS: Intraepithelial MC counts and IgE-bearing cells may help to differentiate EE and GERD and to define a subset of GERD patients in which an allergic component is present. The findings support a role for a MC-mediated hypersensitivity reaction in the pathogenesis of EE.

Lineage development in a patient without goblet, paneth, and enteroendocrine cells: a clue for intestinal epithelial differentiation.

We report a patient who presented with severe enterocolitis and apparent absence of Paneth, goblet, and enteroendocrine lineages from the small bowel and colon. The absorptive enterocyte seemed to be normal morphologically and functionally. Because normal enterocytes were present, we hypothesized that this patient had a developmental block in the differentiation of a common stem cell precursor for Paneth, goblet, and neuroendocrine lineages. By using antibodies to protein markers of each cell line, including some that are expressed early in the differentiation process, we aimed to study lineage development in this patient. From our data, we surmise that there may be a two-step process in lineage commitment. The stem cell may commit to an absorptive cell or a granule-containing cell. The daughter cell that is committed to the granule lineage then further commits to a goblet, enteroendocrine, or Paneth cell lineage.