Craig A Friesen

• Children’s Mercy Kansas City

Objective In functional dyspepsia patients, duodenal mucosal eosinophilia has been associated with early satiety but is not present in all patients suggesting varied pathways to symptom generation. The objective of the current study was to explore metabolic differences comparing those with duodenal mucosal eosinophilia to those without eosinophilia...

Introduction Chronic inflammation of the gastrointestinal tissues underlies gastrointestinal inflammatory disorders, leading to tissue damage and a constellation of painful and debilitating symptoms. These disorders include inflammatory bowel diseases (Crohn’s disease and ulcerative colitis), and eosinophilic disorders (eosinophilic esophagitis and...

Mast cells have been implicated in abdominal pain-associated disorders of gut-brain interaction, such as functional dyspepsia. As such, ketotifen, a second-generation antihistamine and mast cell stabilizer, could represent a viable treatment option in these conditions. The primary aim of the current pilot study was to assess clinical response to ke...

The aims of the current study were to determine the frequencies of specific sleep disturbances in youth with abdominal pain-associated disorders of gut-brain interaction (AP-DGBIs) and to assess relationships with psychological dysfunction. This was a retrospective evaluation of 226 consecutive patients diagnosed with an AP-DGBI. All had undergone...

The purpose of the current study was to assess the frequency of overactive bladder syndrome (OBS) symptoms and their relationship to gastrointestinal symptoms in youth with abdominal pain-associated disorders of gut–brain interaction (AP-DGBI). This is a retrospective study of 226 youth diagnosed with an AP-DGBI. As part of standard care, all patie...

Rumination syndrome is characterized by repeated regurgitation with re-swallowing or spitting. It is associated with both medical and psychosocial complications. It is a disorder of gut-brain interaction resulting from complex and heterogenous interactions across biologic, psychologic, and social systems. Diaphragmatic breathing to compete with abd...

Objective The current study sought to explore how solicitous parenting predicts patient engagement in valued activities (i.e., activity engagement) and prioritization of controlling pain (i.e., pain willingness), two factors of pain acceptance. We also examined how solicitous parenting and abdominal pain severity interact to predict these two facto...

Background Pediatric Rome IV criteria are used to diagnose childhood functional gastrointestinal disorders (FGIDs). This study of pediatric gastroenterology physicians measured their agreement in (1) Making a pediatric Rome IV FGID diagnosis; and (2) Diagnostic testing for patients with FGIDs. Methods Pediatric gastroenterologists and pediatric ga...

Objectives: The primary objective was to describe patterns of care delivery locations in youth with abdominal pain-associated functional gastrointestinal disorders (AP-FGID) and assess for differences in patterns of care delivery by sex and race. A secondary objective was to describe cost variability within the emergency department (ED). Methods:...

The aim was to assess methods utilized in assessing mast cell involvement in functional abdominal pain disorders (FAPDs), specifically to describe variability in methods utilized to assess both mast cell density and activation and determine if a consensus exists. After a literature search identified 70 manuscripts assessing mast cell density, data...

Introduction: Rumination syndrome involves recurrent regurgitation of food and is believed to be underdiagnosed with patients experiencing long delays in diagnosis. It can be associated with significant social consequences, high rates of school absenteeism, and medical complications such as weight loss. The primary aims of the current review are to...

Recurrent abdominal pain is a common complaint in children and adolescents; however, it has been historically understudied and not well understood. Development of a discrete symptom-based diagnostic classification system to guide research and treatment has resulted in new research information being generated at an increasing rate. Although signific...

Background Rumination syndrome has been associated with increased duodenal eosinophils and intraepithelial lymphocytes in adults. The aims of the current study were to assess densities of antroduodenal eosinophils and mast cells and duodenal intraepithelial lymphocytes in youth with rumination syndrome and to compare cell densities in those with an...

While the biopsychosocial nature of inflammatory bowel disease (IBD) is now well accepted by clinicians, the need for integrated multidisciplinary care is not always clear to institutional administrators who serve as decision makers regarding resources provided to clinical programs. In this commentary, we draw on our own experience in building succ...

The aim of this study was to assess the relationship of heartburn in pediatric patients with functional dyspepsia (FD) and irritable bowel syndrome (IBS) with gastrointestinal symptoms, sleep disturbances, and psychologic distress. The overlap in symptoms of FD, IBS, and gastroesophageal reflux disease (GERD) predicts greater symptom severity and d...

Children undergoing colonoscopy and mucosal biopsies may show increased colonic mucosal eosinophils, which may or may not be associated with inflammatory bowel disease. There is not much clinical data on American children who have isolated increased colonic mucosal eosinophils. We sought to study the clinical correlates of children without inflamma...

Abdominal pain has been associated with disaccharidase deficiencies. While relationships with individual symptoms have been assessed, relationships between disaccharidase deficiencies and symptom complexes or inflammation have not been evaluated in this group. The primary aims of the current study were to assess relationships between disaccharidase...

Background/Purpose Most studies examining the components of the fear-avoidance model have examined processes at the group level. The current study used ecological momentary assessments to: (a) investigate the group and intraindividual relationships between pain fear, avoidance, and pain severity, (b) identify any heterogeneity between these relatio...

Background Chronic gastritis is a common histologic finding in children with functional dyspepsia (FD). While Th17 cells have been implicated in other forms of gastritis, they have not been evaluated in chronic gastritis. Aims The aim of the current study was to assess Th17 cells in children with FD with and without chronic gastritis. Methods Den...

Both mucosal inflammation and psychologic dysfunction have been implicated in irritable bowel syndrome (IBS). While some relationships between inflammation (mast cells and eosinophils) and depression have been reported in adults with IBS, relationships between inflammation and psychologic function have not been studied in children and adolescents....

Sucrase deficiency has been implicated in chronic abdominal pain. Testing for sucrase deficiency generally involves invasive procedures or lengthy clinical visits, but now noninvasive kits that allow home testing are available to test for sucrase deficiency. In order to assess feasibility and utility of at-home testing, we reviewed our experience i...

Background/Aims While stress has been implicated in functional dyspepsia (FD), the mechanisms by which stress results in symptoms are not well defined. The aim of the current study was to assess gastric myoelectric and autonomic changes in response to a physical stressor in youth with FD. Methods In a group of healthy controls and pediatric FD sub...

Introduction and Objectives Many of the symptoms of patients with lactose intolerance are due to fermentation of undigested lactose in the colonic lumen, which may also lead to inflammatory cell changes in the colonic mucosa. The objective of our project was to understand the histopathological changes involving infiltration of eosinophils and mast...

Introduction: While functional gallbladder disorder is a well-recognized and defined condition in adults, its pediatric analog, biliary dyskinesia, lacks uniformity in diagnosis. Yet, biliary dyskinesia is among the most common conditions resulting in cholecystectomy in youth and its frequency continues to rise. The primary aims of the current revi...

Background Meal‐related symptoms are common in paediatric functional dyspepsia (FD). There are only a small number of paediatric studies assessing mechanisms for meal‐related symptoms, and these have not utilized Rome IV criteria. The aim of the current study was to assess gastric myoelectric and autonomic nervous system (ANS) responses to both liq...

Background Congenital chloride diarrhea (CCD) in a newborn is a rare autosomal recessive disorder with life-threatening complications, requiring early diagnostics and treatment to prevent severe dehydration and infant mortality. SLC26A3 rs386833481 (c.392C>G; p.P131R) gene polymorphism is an important genetic determinant of CCD. Here, we report the...

Objective: Adolescents with chronic pain associated with functional gastrointestinal disorders (FGIDs) experience negative impacts on their health behaviors (i.e., sleep) and are at risk for a range of problems related to negative affect, which may serve to exacerbate one another in a reciprocal fashion. This study aimed to determine if the streng...

Objective: The current study aimed to determine if it was feasible and acceptable to use ecological momentary assessment (EMA) to assess individual associations between biopsychosocial contributors to chronic abdominal pain with two objective sensors and a mobile application. Specifically, we aimed to determine if it was possible to identify indiv...

Background: Pediatric functional gastrointestinal disorders (FGIDs) are common and well-accepted to be etiologically complex in terms of the contribution of biological, psychological, and social factors to symptom presentations. Nonetheless, despite its documented benefits, interdisciplinary treatment, designed to address all of these factors, for...

Objectives: Immunological studies in patients with lactase deficiency (LD) have suggested a role of colonic mucosal inflammatory cells in causation of some of the symptoms. We hypothesized that since eosinophils are associated with symptoms of abdominal pain and diarrhea; and patients with LD frequently manifest these symptoms, there may be an inc...

Objectives: The present study aimed to: (1) better understand physical activity levels in youth with chronic abdominal pain and (2) investigate the relationship between day-level physical activity related to next day pain intensity to identify any intraindividual heterogeneity. Methods: Seventy-one youth (M=13.34 y, SD=2.67 y) with chronic abdom...

Background In adults, there is a consensus for standards to diagnose gastroparesis utilizing a gastric emptying study as the key diagnostic modality but there is no consensus for a standard in pediatrics. Additionally, some cost savings might be achieved if symptoms could be utilized to predict patients with gastroparesis. The aims of the current s...

Background A few studies have reported increased numbers of mast cells (MC) in intestinal mucosa of patients with Crohn’s disease (CD). Also, several studies have established that eosinophils are increased in colonic mucosa of adults; however, the distribution of MC and eosinophils in gastroduodenal mucosa of children or adults with CD is not estab...

Acetaminophen (APAP) is a commonly used analgesic responsible for more than half of acute liver failure cases. Identification of previously unknown genetic risk factors would provide mechanistic insights and novel therapeutic targets for APAP-induced liver injury. This study used a genome-wide CRISPR-Cas9 screen to evaluate genes that are protectiv...

Although not required to establish the diagnosis, endoscopy with mucosal biopsy is commonly performed in the evaluation of children with dyspepsia. Traditionally, esophagogastroduodenoscopy (EGD) has been performed in children with abdominal pain to identify pathology or conversely, to “rule-out” organic disease in order to establish a diagnosis of...

Background Children with obesity are more likely to suffer gastroesophageal reflux disease, requiring acid‐suppression therapy with proton pump inhibitors (PPIs) and no guidelines regarding dosing. Objective To prospectively evaluate lean‐body‐weight‐based (LBW) dosing of the PPI pantoprazole for children with and without obesity. Methods Methods...

Headaches and abdominal pain are among the most common pediatric pain conditions. Mast cells have been implicated in the pathophysiology of migraines, as well as functional dyspepsia (FD) and irritable bowel syndrome (IBS). The primary aims of the current study were to assess headache prevalence in patients with FD and to assess the association bet...

Introduction and objective: Functional dyspepsia (FD) is a functional gastrointestinal disorder that affects a significant number of children presenting with chronic abdominal pain. A high proportion of these children undergo endoscopy to obtain mucosal biopsies which, by standard criteria, generally do not identify a clear explanation for symptom...

Familial adenomatous polyposis patients often present with non-malignant extra-intestinal manifestations which include dental anomalies that may be evident prior to the appearance of the colonic adenomas. The aims of this study were to describe the prevalence and type of dental anomalies and the relationships between gene mutations and dental anoma...

Acetaminophen overdose is the most common cause of acute liver injury (ALI) or acute liver failure in the US. Its pathogenetic mechanisms are incompletely understood. Additional studies are warranted to identify new genetic risk factors for more mechanistic insights and new therapeutic target discoveries. The objective of this study was to explore...

Background Gastroesophageal reflux disease (GERD) affects 15–25% of children and adolescents in the United States. The diagnosis of GERD in children is complex as reported symptoms or symptom profiles have been found to be unreliable. Frequently, the diagnosis must be confirmed by objective tests such as pH monitoring or histological evidence of es...

Background: There have been no empirical validations of the Rome III or Rome IV criteria in children. The aim of the current study was to examine whether symptoms naturally occur in a pattern consistent with Rome III and/or Rome IV pediatric criteria for functional dyspepsia (FD) and irritable bowel syndrome (IBS). Methods: We conducted a retros...

Background The purpose was to evaluate the overlap frequency of irritable bowel syndrome (IBS), gastroesophageal reflux disease (GERD), and overactive bladder syndrome (OBS), as well as other gastrointestinal and systemic symptoms, in functional dyspepsia (FD). Additionally, we sought to determine whether adult Rome III FD subtypes were uniquely re...

Background Limited dosing guidelines exist for overweight children (≈30% pediatric population). This prospective study examines the pharmacokinetics (PK) of pantoprazole (CYP2C19 substrate) in overweight vs. normal-weight children. Methods Using TaqMan techniques, 51 children (6–17 yrs) were genotyped for CYP2C19 loss-of-function (*2, *3, *4) and g...

Cow’s milk is the most common cause of food-protein-induced enterocolitis syndrome (FPIES). The aim of this study was to examine the clinical features and treatment outcomes of infants with severe FPIES to cow’s milk. We reviewed all infants ≤12 months of age who were hospitalized and diagnosed with severe FPIES to cow’s milk between 1 January 2011...

At the present time, it is nearly impossible to treat pediatric functional gastrointestinal disorders associated with pain in an evidence based fashion. This is due to the overall lack of controlled studies and, even more importantly, the complexity of the contributors to disease phenotype which are not controlled or accounted for in most therapeut...

Background Early manifestations of pediatric inflammatory bowel disease (IBD) can be relatively nonspecific. Initial mucosal biopsies may not be conclusive, delaying the diagnosis until subsequent biopsies demonstrate typical histologic features of IBD. We hypothesized that certain inflammatory cell types may be utilized as early histologic indicat...

Adult studies indicate a role for ghrelin in functional dyspepsia (FD) mediated through ghrelin's effect on gastric emptying (GE). This study examines the relationship between ghrelin, liquid GE, and pain in children with FD. Thirteen FD patients reporting symptoms consistent with post-prandial distress syndrome (PDS) and 17 healthy controls were e...

The purpose of this study was to evaluate associations between pediatric chronic abdominal pain and a variety of presumed triggers for abdominal pain in real-time. Associations were explored at the level of patient self-perception and empirically across the group. Thirteen patients (8 to 17 years) presenting for initial subspecialty evaluation of c...

Eosinophilic colitis is a well recognized clinical entity mainly associated with food allergies. Empiric treatment options include dietary allergen exclusion (extensively hydrolyzed protein formula and elimination diet), anti-allergy medications (antihistamines and leukotriene receptor antagonists) and corticosteroids. We evaluated the effectivenes...

Functional gastrointestinal disorders (FGID) are common clinical syndromes diagnosed in the absence of biochemical, structural, or metabolic abnormalities. They account for significant morbidity and health care expenditures and are identifiable across variable age, geography, and culture. Etiology of abdominal pain associated FGIDs, including funct...

This study examined the practices used by primary care pediatricians to assess and treat chronic abdominal pain (CAP), as an initial step in guiding clinical practice guideline (CPG) development. A survey was mailed to a random sample of office-based pediatrician members (primary care pediatricians [PCPs]) of the American Medical Association. PCPs...

An altered intestinal mucosal barrier has been demonstrated in subsets of patients with IBS and FAP and may be an additional biological factor contributing to symptom generation in children with FD. The objective of this study was to determine if intestinal permeability is increased in children/adolescents with functional dyspepsia (FD) and whether...

Background: Infliximab appears to be efficacious in the treatment of pediatric Crohn disease (CD). There are few large-scale pediatric studies on the complications of infliximab therapy. Methods: A retrospective review of all infliximab infusions administered to IBD patients at a tertiary children's hospital was undertaken. Data was obtained from a...

Expression of the pregnane X receptor (PXR) has been reported to be decreased in animal models of Inflammatory Bowel Disease (IBD). To investigate the differential expression of PXR in children with Crohn's disease, a type of IBD, RNA was extracted from archived intestinal biopsies from 18 children with Crohn's disease (CD) and 12 age-, sex-matched...

• Objective: To review functional gastrointestinal disorders (FGIDs) in children, with an emphasis on evidence-based diagnostic and treatment approaches. • Methods: Review of the literature. • Results: Chronic or recurrent abdominal pain is a common condition in children. No clinical practice guidelines currently exist for pediatric functional abdo...

BACKGROUND: Human pregnane X receptor (PXR) is a xenobiotic nuclear receptor responsible for transcriptional regulation of specific drug metabolizing enzymes (e.g., CYP3A4) and transporters (e.g., ABCB1). PXR dysregulation has also been implicated in the pathogenesis of IBD in a well-established model of chemically-induced IBD in mice, as well as s...

There is an increasing appreciation for the importance of inflammation as a pathophysiologic entity that contributes to functional gastrointestinal disorders including functional dyspepsia (FD). Importantly, inflammation may serve as a mediator between psychologic and physiologic functions. This manuscript reviews the literature implicating two inf...

To validate methods for determining mast cell density, extracellular major basic protein content, and presence of fibrosis in esophageal eosinophilia. Twenty specimens with > 20 eosinophils/high-power field (hpf) classified as high eosinophil density (HE) and 20 specimens with < 5 eosinophils/hpf classified as low esophageal density (LE) were ident...

Available for free download from: http://www.intechopen.com/books/dyspepsia-advances-in-understanding-and-management/inflammation-and-the-biopsychosocial-model-in-pediatric-dyspepsia

Recurrent abdominal pain is a common complaint in children and adolescents; however, it has been historically understudied and not well understood. Recently, an improved diagnostic classification system has resulted in new research information being generated at an increasing rate. Although significant gaps in our knowledge remain, we are gradually...

The objective of this study was to provide preliminary findings of efficacy and acceptability for “Gutstrong,” a minimal contact cognitive–behavioral treatment program being developed for adolescents with functional gastrointestinal disorders (FGIDs). Twenty adolescents (13 to 17 years) presenting for initial subspecialty evaluation of chronic abdo...

Background: Eosinophilic enterocolitis (EEC) is an emerging distinct inflammatory bowel disease of unknown etiology. There are no published data on the effect of infliximab (IFX) or adalimumab (ADA) for the treatment of refractory cases. Methods: A report of all pediatric cases with EEC treated with anti-tumor necrosis factor, identified after a...

Pediatric abdominal pain is a common childhood complaint. Available conceptualizations of the condition point toward an interdisciplinary approach to care as having the highest utility. The current study sets out to describe practice patterns among psychologists treating pediatric abdominal pain, the degree to which such practitioners engage in col...

Background Sleep disturbances are increasingly recognized as a common problem for children and adolescents with chronic pain conditions, but little is known about the prevalence, type, and impact of sleep problems in pediatric functional gastrointestinal disorders (FGIDs). The objectives of the current study were two-fold: 1) to describe the patter...

The objective of the current study was to assess the factor structure of the Illness Behavior Encouragement Scale (IBES) by Walker and Zeman (1992) among children with functional gastrointestinal disorders (FGIDs). Two hundred seventy nine children (63 % female), and 135 primary caregivers (90.8 % mothers), recruited from a large Midwestern childre...

This is a commentary of Cochrane review, published in this issue of EBCH, first published as: Kaminski A, Kamper A, Thaler K, Chapman A, Gartlehner G. Antidepressants for the treatment of abdominal pain-related functional gastrointestinal disorders in children and adolescents. Cochrane Database of Systematic Reviews 2011, Issue 7. Art. No.: CD00801...

This study aimed to compare efficacy of enema versus polyethylene glycol (PEG) 3350 for pediatric fecal impaction treatment. We conducted a prospective, randomized comparison of treatments of fecal impaction in children in a pediatric emergency department (ED). Treatment arms were a single milk and molasses enema in the ED or PEG 3350 for 3 days ou...

The current study was undertaken to determine the degree of activation of gallbladder mucosal mast cells, whether mast cell (MC) density or activation differ between patients with and without a positive clinical response to cholecystectomy, and whether either density or activation correlate with gallbladder emptying. Fifteen biliary dyskinesia (BD)...

The aim of the present study was to explore relations between antral or duodenal inflammatory cells and aspects of psychological functioning with clinical symptom presentation in children with functional dyspepsia (FD), as well as to determine whether histologic inflammation and/or psychopathology are differentially associated with FD subtypes as d...

To assess patient and family satisfaction with evaluation received through a multidisciplinary paediatric Abdominal Pain Clinic (APC) staffed by a paediatric gastroenterologist and a paediatric psychologist as compared to a traditional gastroenterology clinic (GI) staffed by a paediatric gastroenterologist only. Two hundred and ninety-eight familie...

To conduct a pilot study examining whether adding biofeedback-assisted relaxation training (BART) to medication treatment results in better clinical outcomes than medication treatment alone for children with functional dyspepsia (FD) associated with duodenal eosinophilia, a subgroup of children with recurrent abdominal pain. Twenty children were ra...

The aim of this study was to determine whether screening for food hypersensitivity could be a clinically useful biomarker for eosinophilic duodenitis in the pediatric population. Twenty-two patients with functional dyspepsia and 19 controls with no significant history of gastrointestinal or allergic disorders were enrolled. Participants underwent s...

The (13)C-acetate breath test represents a potential alternative to conventional scintigraphy to measure liquid gastric emptying (GE). The purpose of this study was to compare the (13)C-acetate breath test to gastric scintigraphy in children with functional dyspepsia. Simultaneous assessment of GE was performed in 28 children (9-17 years of age) us...

The aim of this study was to examine how children with abdominal pain presently are viewed, assessed, and treated by pediatric gastroenterologists across North America, as well as how perspectives have changed since initial release of the Rome criteria for functional gastrointestinal disorders approximately 15 years ago. One hundred seventy-four fu...

Alteration in autonomic function has been implicated as a possible pathophysiologic mechanism in functional dyspepsia (FD) in adults. This was a two-part study. For the first part of the study, nine children with FD and 28 controls underwent heart rate variability (HRV) analysis for 30 min baseline and for 60 min following a test meal. For the seco...

We have previously demonstrated the clinical efficacy of montelukast in a randomized double-blind controlled cross-over trial in patients with dyspepsia in association with duodenal eosinophilia. The mechanism of this clinical response is unknown but could involve a decrease in eosinophil density or activation. Twenty-four dyspeptic patients 8-17 y...

This study was designed to determine whether distinct subgroups of children with recurrent abdominal pain (RAP) could be identified based on patterns of psychological functioning. Two hundred and eighty-three children (ages 8-17 years), and a primary caretaker, completed the Behavior Assessment System for Children (BASC) during the initial evaluati...

The aims of the current study were to determine the activation states of antral eosinophils and mast cells and to evaluate the interactions of antral inflammatory cells with gastric emptying and electrogastrography (EGG) in 30 pediatric patients with functional dyspepsia. Eosinophil degranulation was moderate in 42% and extensive in 54% of patients...

The aim of this study was to investigate the correlation of gastric myoelectrical and autonomic activities in healthy children. Simultaneous recordings of electrogastrography (EGG) and electrocardiogram (ECG) were performed in healthy children before and after a solid meal and water loading respectively. The autonomic activity was assessed by spect...

To compare water load test consumption patterns between children with functional gastrointestinal disorders and healthy control children. Seventy-one children with recurrent abdominal pain completed the Behavioral Assessment Scale for Children-Self-Report Form and the Questionnaire on Pediatric Gastrointestinal Symptoms during their first visit to...

Objectives To compare water load test consumption patterns between children with functional gastrointestinal disorders and healthy control children. Methods Seventy‐one children with recurrent abdominal pain completed the Behavioral Assessment Scale for Children–Self‐ Report Form and the Questionnaire on Pediatric Gastrointestinal Symptoms during...

The current study examined whether electrogastrogram (EGG) recordings obtained from healthy children would be considered normal by standards established for adults and whether EGG patterns differ between children/adolescents and adults. Twenty-eight healthy children (54% females; ages 8-17 years; mean = 12.4 years) were evaluated and compared to 15...

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Inflammation has been implicated in functional gastrointestinal disorders, including functional dyspepsia and irritable bowel syndrome. This study was undertaken to evaluate gallbladder wall inflammatory cells in children with abdominal pain related to gallstones and biliary dyskinesia to determine the candidate cell types that may be contributing...