Aprepitant triple therapy for the prevention of chemotherapy-induced nausea and vomiting following high-dose cisplatin in Chinese patients: a randomized, double-blind, placebo-controlled phase III trial.

PURPOSE: Aprepitant, an oral neurokinin-1 receptor antagonist, has demonstrated improved control of chemotherapy-induced nausea and vomiting (CINV) in previous studies. This is the first phase III study to evaluate the efficacy and tolerability of aprepitant in patients receiving highly emetogenic chemotherapy (HEC) in Asian countries. METHODS: This multicenter, double-blind, placebo-controlled trial assessed the prevention of CINV during the acute phase (AP), delayed phase (DP), and overall phase (OP). Patients receiving HEC were randomized to either an aprepitant group (day 1, aprepitant 125 mg; days 2-3, aprepitant 80 mg) or a standard therapy group (days 1-3, placebo). Both groups received intravenous granisetron and oral dexamethasone. The primary end point was complete response (CR; no emesis and no use of rescue therapy) during the OP. RESULTS: Of the 421 randomized patients, 411 (98%) were assessable for efficacy; 69.6% (142/204) and 57.0% (118/207) of patients reported CR during the OP in the aprepitant and standard therapy groups, respectively (P = 0.007). CR rates in the aprepitant group were higher during the DP (74.0% vs. 59.4%, P = 0.001) but were similar during the AP (79.4% vs. 79.3%, P = 0.942). Toxicity and adverse events were comparable in both groups. CONCLUSIONS: The addition of aprepitant to standard antiemetic treatment regimens for Chinese patients undergoing HEC provided superior CINV prevention and was well tolerated.

Evaluation of etoricoxib in patients undergoing total knee replacement surgery in a double-blind, randomized controlled trial.

BACKGROUND: Optimal postoperative pain management is important to ensure patient comfort and early mobilization. METHODS: In this double-blind, placebo- and active-controlled, randomized clinical trial, we evaluated postoperative pain following knee replacement in patients receiving placebo, etoricoxib (90 or 120 mg), or ibuprofen 1800 mg daily for 7 days. Patients ≥18 years of age who had pain at rest ≥5 (0-10 Numerical Rating Scale [NRS]) after unilateral total knee replacement were randomly assigned to placebo (N = 98), etoricoxib 90 mg (N = 224), etoricoxib 120 mg (N = 230), or ibuprofen 1800 mg (N = 224) postoperatively. Co-primary endpoints included Average Pain Intensity Difference at Rest over Days 1-3 (0- to 10-point NRS) and Average Total Daily Dose of Morphine over Days 1-3. Pain upon movement was evaluated using Average Pain Intensity Difference upon Knee Flexion (0- to 10-point NRS). The primary objective was to demonstrate analgesic superiority for the etoricoxib doses vs. placebo; the secondary objective was to demonstrate that the analgesic effect of the etoricoxib doses was non-inferior to ibuprofen. Adverse experiences (AEs) including opioid-related AEs were evaluated. RESULTS: The least squares (LS) mean (95% CI) differences from placebo for Pain Intensity Difference at Rest over Days 1-3 were -0.54 (-0.95, -0.14); -0.49 (-0.89, -0.08); and -0.45 (-0.85, -0.04) for etoricoxib 90 mg, etoricoxib 120 mg, and ibuprofen, respectively (p < 0.05 for etoricoxib vs. placebo). Differences in LS Geometric Mean Ratio morphine use over Days 1-3 from placebo were 0.66 (0.54, 0.82); 0.69 (0.56, 0.85); and 0.66 (0.53, 0.81) for etoricoxib 90 mg, etoricoxib 120 mg, and ibuprofen, respectively (p < 0.001 for etoricoxib vs. placebo). Differences in LS Mean Pain Intensity upon Knee Flexion were -0.37 (-0.85, 0.11); -0.46 (-0.94, 0.01); and -0.42 (-0.90, 0.06) for etoricoxib 90 mg, etoricoxib 120 mg, and ibuprofen, respectively. Opioid-related AEs occurred in 41.8%, 34.7%, 36.5%, and 36.3% of patients on placebo, etoricoxib 90 mg, etoricoxib 120 mg, and ibuprofen, respectively. CONCLUSIONS: Postoperative use of etoricoxib 90 and 120 mg in patients undergoing total knee replacement is both superior to placebo and non-inferior to ibuprofen in reducing pain at rest and also reduces opioid (morphine) consumption. CLINICAL TRIAL REGISTRATION: NCT00820027.

Unexplained gastrointestinal symptoms after abuse in a prospective study of children at risk for abuse and neglect.

PURPOSE: Unexplained gastrointestinal symptoms are more common in adults who recall abuse as a child; however, data available on children are limited. The aim of this study was to investigate the association of childhood maltreatment and early development of gastrointestinal symptoms and whether this relation was mediated by psychological distress. METHODS: Data were obtained from the Longitudinal Studies of Child Abuse and Neglect, a consortium of 5 prospective studies of child maltreatment. The 845 children who were observed from the age of 4 through 12 years were the subjects of this study. Every 2 years information on gastrointestinal symptoms was obtained from parents, and maltreatment allegations were obtained from Child Protective Services (CPS). At the age of 12 years children reported gastrointestinal symptoms, life-time maltreatment, and psychological distress. Data were analyzed by logistic regression. RESULTS: Lifetime CPS allegations of sexual abuse were associated with abdominal pain at age 12 years (odds ratio [OR] = 1.75; 95% confidence interval [CI] = 1.1-2.47). Sexual abuse preceded or coincided with abdominal pain in 91% of cases. Youth recall of ever having been psychologically, physically, or sexually abused was significantly associated with both abdominal pain and nausea/vomiting (range, OR = 1.5 [95% CI, 1.1-2.0] to 2.1 [95% CI, 1.5-2.9]). When adjusting for psychological distress, most effects became insignificant except for the relation between physical abuse and nausea/vomiting (OR = 1.5; 95% CI, 1.1-2.2). CONCLUSION: Youth who have been maltreated are at increased risk for unexplained gastrointestinal symptoms, and this relation is partially mediated by psychological distress. These findings are relevant to the clinical care for children who complain of unexplained gastrointestinal symptoms.

Recollection of childhood abdominal pain in adults with functional gastrointestinal disorders.

OBJECTIVE: It is hypothesized that adults who can recall abdominal pain as children are at risk of experiencing a functional gastrointestinal disorder (FGID), but this is not specific to any particular FGID. The aim of this study was to evaluate the association between recollecting abdominal pain as a child and experiencing a FGID. MATERIAL AND METHODS: A valid self-reported questionnaire of GI symptoms was mailed to a random population-based sample in Olmsted County, Minnesota. Logistic regression models adjusting for age, gender, body mass index (BMI), somatization, and other factors were used to estimate the odds ratios (ORs) for having a FGID in individuals recalling bouts of stomach or abdominal pain in childhood (before age 15). RESULTS: Overall, 2298 (55%) of a total of 4194 eligible adult subjects returned a completed questionnaire. Of the respondents, 213 (9%) recalled experiencing abdominal pain as children. Adults who recalled experiencing abdominal pain in childhood had greater odds for reporting symptoms of a FGID (OR 1.9; 95% CI 1.4-2.7). Recalling abdominal pain in childhood was significantly associated with irritable bowel syndrome (IBS) (OR 2.5; 95% CI 1.7-3.6) but not gastroesophageal reflux, dyspepsia, constipation, or diarrhea, adjusting for age, gender, BMI, somatic symptoms, marital status, and education. CONCLUSIONS: Recollection of childhood abdominal pain is specifically associated with IBS in adults. This suggests that a proportion of adults with IBS may have onset of symptoms of abdominal pain during childhood.

Parental worries and beliefs about abdominal pain.

BACKGROUND: Solicitous parental responses to stomachaches may perpetuate chronic abdominal pain in children. Discussing these issues in clinical practice is difficult because parents feel misunderstood and blamed for their child's pain. Focusing on parental worries and beliefs that motivate solicitous responses may be better accepted. OBJECTIVES: Our aim was to determine parental fears, worries, and beliefs about their child's chronic abdominal pain that influence parental responses to child's pain. MATERIALS AND METHODS: In 2 studies, a large online sample and a smaller community sample consisting of parents with children who have abdominal pain, we developed and evaluated a self-report questionnaire to assess parental Worries and Beliefs about Abdominal Pain (WAP). RESULTS: Principal component analysis identified 4 subscales: "pain is real," "desire for care," "worry about coping," and "exacerbating factors." The WAP is easily understood and possesses adequate initial reliability (Cronbach alpha=0.7-0.9). It shows good initial validity (ie, families who consulted a physician for their child's pain scored higher on the WAP than families who did not consult a physician and the WAP correlates with parental reactions to the child's pain). CONCLUSIONS: Discussing parents' fears and worries about their children's chronic abdominal pain may facilitate discussions of social learning of gastrointestinal illness behavior.

The role of psychological factors in pediatric functional abdominal pain disorders.

BACKGROUND: Pediatric functional abdominal pain disorders (FAPDs) are disorders of brain-gut dysregulation. Psychological factors are known to be related to etiology, maintenance, and exacerbation of pediatric FAPDs. With the evolving literature in the past two decades, a better understanding has emerged of precisely which psychological factors are associated with childhood FAPDs. PURPOSE: This narrative literature review summarizes the literature of both child and parent psychological factors in pediatric FAPD. Where anxiety and depression were major targets in the older literature, present-day focus is increasingly on pain-specific cognitions and coping strategies including disease threat and catastrophizing. In addition, parental reaction to a child's pain is increasingly recognized as an important moderator of a child's outcomes and has become an area for clinical intervention. Screening for these factors and integrative treatment approaches are recommended in childhood FAPD.

Ambulatory care for constipation in the United States, 1993-2004.

OBJECTIVES: Chronic constipation is one of the most common disorders seen in primary care. In order to examine longitudinal changes in the ambulatory care that occur in constipation evaluation and management, we examined national trends in physician office visits associated with constipation between 1993 and 2004. METHODS: Data were derived from the National Ambulatory Medical Care Survey (NAMCS) and the National Hospital Ambulatory Care Survey (NHAMCS) for 1993-2004. Patient visits were classified as encounters for constipation-related care. Analyses were performed by combining 4 yr of data (1993-1996, 1997-2000, and 2001-2004). RESULTS: Ambulatory visits for constipation increased from 4 million (95% CI 3.3-4.7 million) ambulatory visits for constipation annually during 1993-1996 period to 7.95 million (95% CI 6.6-9.4 million) visits during the 2001-2004 period. The proportion of medical visits for constipation increased for pediatricians, but decreased for adult primary care providers from 1993 to 2004. During the observed time period, the proportion of medical visits for constipation did not change for gastroenterologists. The primary treatment for constipation shifted from bulking agents (fiber) to osmotic laxatives. CONCLUSION: There has been a significant increase in physician office visits for constipation between 1993 and 2004, with the highest rate of increase in the pediatric population. Longitudinal trends indicate an increase in constipation-related visits for pediatricians. The primary treatment for constipation among medical providers shifted from using bulking agents to osmotic laxatives for unknown reasons.

Contributions of pain sensitivity and colonic motility to IBS symptom severity and predominant bowel habits.

OBJECTIVES: Irritable bowel syndrome (IBS) patients show pain hypersensitivity and hypercontractility in response to colonic or rectal distention. Aims were to determine whether predominant bowel habits and IBS symptom severity are related to pain sensitivity, colon motility, or smooth muscle tone. METHODS: One hundred twenty-nine patients classified as IBS with diarrhea (IBS-D, N = 44), IBS with constipation (IBS-C, N = 29), mixed IBS (IBS-M, N = 45), and unspecified IBS (IBS-U, N = 11) based on stool consistency, and 30 healthy controls (HC) were studied. A manometric catheter containing a 600-mL capacity plastic bag was positioned in the descending colon. Pain threshold was assessed using a barostat. Motility was assessed for 10 min with the bag minimally inflated (individual operating pressure [IOP]), 10 min at 20 mmHg above the IOP, and for 15-min recovery following bag inflation. Motility was also recorded for 30 min following an 810-kcal meal. RESULTS: Compared with HC, IBS patients had lower pain thresholds (medians 30 vs 40 mmHg, P < 0.01), but IBS subtypes were not different. IBS symptom severity was correlated with pain thresholds (rho =-0.36, P < 0.001). During distention, the motility index (MI) was significantly higher in IBS compared with HC (909 +/- 73 vs 563 +/- 78, P < 0.01). Average barostat bag volume at baseline was higher (muscle tone lower) in HC compared with IBS-D and IBS-M but not compared with IBS-C. The baseline MI and bag volume differed between IBS-D and IBS-C and correlated with symptoms of abdominal distention and dissatisfaction with bowel movements. Pain thresholds and MI during distention were uncorrelated. CONCLUSIONS: Pain sensitivity and colon motility are independent factors contributing to IBS symptoms. Treatment may need to address both, and to be specific to predominant bowel habit.

Incidence of presentation of common functional gastrointestinal disorders in children from birth to 5 years: a cohort study.

BACKGROUND & AIMS: Gastroesophageal reflux disease (GERD), abdominal pain of unknown origin, and constipation are thought to be causes for frequent medical visits during childhood. The aim of this study was to estimate the incidences, repeat presentation, clinical symptoms, and sociodemographic risk factors in children who medically presented for GERD, abdominal pain of unknown origin, and constipation from birth to 5 years. METHODS: This was a population-based, retrospective birth cohort study of all children born to mothers residing in Rochester, Minnesota who remained in the area until at least age 5 (n = 5718). The medical records of all individuals were searched for relevant diagnostic billing codes for GERD, abdominal pain of unknown origin, and constipation, without another underlying diagnosis, and manually reviewed. Parental sociodemographic factors collected from birth certificate records on patients and matched controls were compared. RESULTS: The incidence for childhood (age, <5 y) presentation of GERD, abdominal pain of unknown origin, and constipation was .9/1000 person-years, 4.5/1000 person-years, and 6.8/1000 person-years, respectively; there were no significant differences between boys and girls. Three or more medical visits by age 5 occurred in 11%, 19%, and 24% of children who were seen for abdominal pain of unknown origin, constipation, and GERD, respectively. Single parentage, maternal age (<18 y), and maternal education (

Medical presentation of constipation from childhood to early adulthood: a population-based cohort study.

BACKGROUND & AIMS: Constipation is a common disorder in children and adults, but the role of gender and early life risk factors remains undefined. The aims of the study were as follows: (1) to estimate the incidence of medical presentation for constipation in a population-based birth cohort, and (2) to examine factors associated with constipation presentation from childhood to adulthood. METHODS: A birth cohort of all children born between 1976 and 1982 to mothers who were residents of Rochester, Minnesota, and who remained in the community until age 5 was used for this study. Medical visits for constipation were identified by diagnoses codes and chart review. Subjects were followed up based on their diagnoses accumulated while younger than 21 years old, and 80% of subjects remained in the area until 18 years of age. RESULTS: Of 5299 birth cohort members without constipation presentation before age 5, the overall age- and sex-adjusted incidence was 3.9 per 1000 person-years. A higher incidence for constipation in females occurred beginning at 13 years to early adulthood (rate ratio, 2.6 for 13-16 y and 4.2 for 17 to <21 y). Children with a diagnosis for constipation at younger than 5 years of age had a significantly higher incidence for subsequent medical visits for constipation through adolescence and early adulthood compared with the incidence rate of children without an early medical presentation (rate ratio, 4.5 for 5-8 y, 2.5 for 9-12 y, and 3.9 for 17-20 y). CONCLUSIONS: Early medical presentation and female sex influence incident and repeat medical visits for constipation from childhood to early adulthood.

Pharmacotherapy for functional gastrointestinal disorders in children.

Functional gastrointestinal disorders are among the most common medical problems in pediatrics. However, only a few well-designed trials have evaluated the efficacy and safety of treatments in these conditions. Data obtained from studies conducted in adults are often utilized to tailor treatment to children with functional gastrointestinal disorders. This practice might lead to substantial medication under- or over-dosing, or use of drugs for an incorrect indication.

Audio-recorded guided imagery treatment reduces functional abdominal pain in children: a pilot study.

OBJECTIVE: This study was designed to develop and to test a home-based, guided imagery treatment protocol, using audio and video recordings, that is easy for health care professionals and patients to use, is inexpensive, and is applicable to a wide range of health care settings. METHODS: Thirty-four children, 6 to 15 years of age, with a physician diagnosis of functional abdominal pain were assigned randomly to receive 2 months of standard medical care with or without home-based, guided imagery treatment. Children who received only standard medical care initially received guided imagery treatment after 2 months. Children were monitored for 6 months after completion of guided imagery treatment. RESULTS: All treatment materials were reported to be self-explanatory, enjoyable, and easy to understand and to use. The compliance rate was 98.5%. In an intention-to-treat analysis, 63.1% of children in the guided imagery treatment group were treatment responders, compared with 26.7% in the standard medical care-only group (P = .03; number needed to treat: 3). Per-protocol analysis showed similar results (73.3% vs 28.6% responders). When the children in the standard medical care group also received guided imagery treatment, 61.5% became treatment responders. Treatment effects were maintained for 6 months (62.5% responders). CONCLUSION: Guided imagery treatment plus medical care was superior to standard medical care only for the treatment of abdominal pain, and treatment effects were sustained over a long period.

Early life risk factors that contribute to irritable bowel syndrome in adults: a systematic review.

BACKGROUND: Irritable bowel syndrome (IBS) is a common disorder that occurs in adults. The natural history of symptoms and risk factors that contribute to IBS may begin in childhood. The aim of this systematic review was to determine what early life factors contribute to the development of IBS in adolescents and adults. METHODS: A computer-assisted search of the PubMed database from 1966 to 2007 was performed. The selection criteria were: (a) studies conducted in adolescents or adults with IBS that (b) investigate premorbid factors occurring specifically during the childhood period and are (c) associated with the outcomes of symptoms, quality of life, health-care utilization, and interferences with work or disability. RESULTS: Twenty-five articles met inclusion criteria. The studies were categorized into articles examining the persistence of childhood gastrointestinal symptoms into adulthood, affluent childhood socioeconomic status and adult IBS, infantile and childhood trauma associated with the development of adult IBS, and social learning of illness behavior as predictors of adult IBS. CONCLUSION: Pediatricians should be aware of potentially modifiable childhood risk factors and should consider interventions such as early symptom management of recurrent functional abdominal pain with cognitive therapies and parent education about social learning of illness behavior. Early treatment may have a long-term impact. Research examining the effect of affluent childhood socioeconomic status and early childhood trauma in the evolution of functional gastrointestinal disorders may help identify causative factors of IBS.

Aerophagia and rumination: recognition and therapy.

Aerophagia and rumination syndrome are functional upper gastrointestinal disorders that are becoming increasingly recognized in otherwise-healthy children and adults. Aerophagia is primarily characterized by troublesome repetitive belching and abdominal symptoms that result from air sucking and swallowing. Rumination syndrome is primarily characterized by regurgitation occurring shortly after meal intake. Physiologic studies suggest that both disorders are a result of habitual behavior with associated esophageal and gastric physiologic deviations. However, the underlying etiology of these disorders remains unclear. Studies examining optimal treatments are lacking. However, therapeutic approaches utilizing biofeedback may be helpful in alleviating symptoms for patients with these conditions.

The epidemiology of childhood recurrent abdominal pain in Western countries: a systematic review.

OBJECTIVE: Recurrent abdominal pain (RAP) of childhood is a common problem encountered by clinicians. The aim of this study was to systematically review published literature about the prevalence, incidence, natural history, and co-morbid conditions of childhood RAP in western countries. METHODS: A computer-assisted search of MEDLINE, EMBASE, and Current Contents/Science Edition databases was performed. Study selection criteria included: (1) United States and European population and school-based samples of children; (2) diagnostic criteria of RAP; and (3) published in full manuscript form in English. Data were extracted, tabulated, and presented in descriptive form. RESULT: The prevalence of RAP ranged from 0.3 to 19% (median 8.4; IQR 2.3-14.7). Published studies in children demonstrate a higher prevalence of RAP in females, with the highest prevalence of symptoms between 4 and 6 yr and early adolescence. Identified studies demonstrated associations between RAP and the child's familial and socioeconomic environment. In addition, childhood RAP was reported to be associated with psychological co-morbidity in childhood and adulthood. Population/school-based studies have not, however, established the incidence of this disorder, what features predict long-standing symptoms, or whether RAP is a risk factor for adult functional bowel disorders. CONCLUSION: RAP is a common complaint of childhood with associated familial, psychological, and co-morbid conditions. Epidemiologic studies of RAP in children may offer information on the evolution of functional bowel disorders through the lifespan.

Esophageal motor activity in children with gastro-esophageal reflux disease and esophagitis.

OBJECTIVE: To evaluate esophageal body motor contractions occurring during esophageal reflux in pediatric patients with gastro-esophageal reflux disease (GERD). METHODS: Patients referred for the evaluation of GERD who were evaluated with combined 24-hour pH probe and esophageal manometry test (MP24) were included. Patients were separated into the following groups: Group C -- normal pH probe and normal EGD; Group 1 -- abnormal pH probe and normal EGD; and Group 2 -- abnormal pH probe and EGD with histologic esophagitis. Esophageal motor function during reflux episodes was analyzed. RESULTS: Twenty-five patients were included. All had a normal stationary esophageal manometry. Patients in Groups 1 and 2 had significantly more gastroesophageal reflux by pH probe than Group C (P < 0.01). During the MP24, patients in Group 1 and 2 had significantly fewer contractions per minute pre-, during, and post-GER (P < 0.05). There were significant differences in the number of isolated and prolonged contractions (>7 sec) during prolonged GERD episodes >5 minutes (P < 0.05). CONCLUSION: Children with GERD have a decreased number and abnormal esophageal body contractions with esophageal reflux. This suggests that children with GERD with and without esophagitis have impaired esophageal body acid clearance.

Gastric sensory and motor dysfunction in adolescents with functional dyspepsia.

OBJECTIVES: Validated, noninvasive studies were used to compare sensation and motor function of the upper gastrointestinal tract in adolescents with functional dyspepsia (FD) and in control subjects. STUDY DESIGN: Fifteen adolescents with FD and 15 healthy participants underwent standardized symptom assessment, a satiation nutrient drink test, and 13 C-Spirulina platensis breath test for gastric emptying of solids. Adolescents with FD also underwent measurements of fasting and postprandial gastric volume by means of single-photon emission computed tomography, and their results were compared with those from 15 healthy volunteers (age, 18 to 25 years). RESULTS: Compared with control subjects, adolescents with FD had significantly higher postprandial symptoms 30 minutes after reaching maximum satiation with the nutrient drink test and significant delay in the T 1/2 for gastric emptying of solids. Compared with healthy 18- to 25-year-old adults, adolescents had a diminished postprandial gastric volume response. By means of single-photon emission computed tomography, frequent baseline dyspeptic symptoms were associated with prolonged T 1/2 for gastric emptying and higher postprandial aggregate symptom score. A baseline increased severity of dyspepsia symptoms was associated with prolonged T 1/2 for gastric emptying. CONCLUSIONS: Adolescents with FD demonstrate increased postprandial symptoms after challenge, delayed gastric emptying, and a reduced gastric volume response to feeding.

Effects of desipramine and escitalopram on postprandial symptoms induced by the nutrient drink test in healthy volunteers: a randomized, double-blind, placebo-controlled study.

BACKGROUND: Antidepressants are widely used to treat functional gastrointestinal disorders but their effect on postprandial symptoms remains unstudied. We hypothesized that desipramine and escitalopram would enhance the maximum tolerated volume of nutrient ingested and decrease postprandial symptoms. METHODS: Healthy participants (n=45) all underwent an assessment of symptoms, anxiety and depression, and a standard nutrient drink test (Ensure). Participants were randomized to 11 days of desipramine (50 mg once daily), escitalopram (10 mg once daily) or identical placebo. RESULTS: The maximum tolerated gastric volumes were not significantly different on day 11 for desipramine (1,136+/-478 ml, mean+/-SD), escitalopram (1,198+/-422 ml) and placebo (1,231+/-318 ml). A univariate analysis indicated significant treatment group effects on total symptom scores (p=0.049), but after adjusting for age, gender, BMI and baseline scores, treatment effects were no longer significant (p=0.15). CONCLUSIONS: While this study does not rule out a beneficial effect of tricyclics or selective serotonin reuptake inhibitors in functional dyspepsia, neither desipramine nor escitalopram significantly altered the nutrient volume ingested or symptoms induced by the nutrient drink test in healthy volunteers.

Prolonged monitoring of esophageal motor function in healthy children.

OBJECTIVE: To describe diurnal variations of esophageal motor function in children using combined ambulatory 24-hour esophageal manometry and continuous intraluminal pH measurement (MP24). METHODS: Medical records of all patients referred for the performance of MP24 from 1995 to 2002 at a tertiary care center were reviewed. Patients were selected retrospectively for this study using the following inclusion criteria: (1) no dysphagia, (2) normal upper gastrointestinal barium radiograph, (3) normal esophagogastroduodenoscopy and biopsies, (4) normal stationary esophageal manometry, (5) normal esophageal pH probe, and (6) no gastrointestinal pathology appearing after long-term follow-up. Data from the MP24 of these children were retrospectively analyzed for differences between meal, upright, and supine periods using nonparametric univariate analysis. RESULTS: One hundred twenty-three children had MP24 during the study period. Eleven met the criteria for normality and were included. Their mean age was 12.4 +/- 1.5 years. The number of contractions/minute in the upper, middle, and lower esophageal body differed significantly during meals and in the upright and supine periods (P < 0.01). A significant increase in motor activity occurred during meals (P < 0.01). There was less motor activity observed in the supine position than in the upright position (P < 0.01). There were significant differences in effective (P < 0.05) and total propagated peristalsis among the meal, upright, and supine periods (P < 0.01), with the largest percentage of propagated contractions observed during meals. CONCLUSION: This study provides the first information on prolonged esophageal motor activity in pediatric patients without esophageal disease. MP24 in children demonstrates significant diurnal variations in esophageal motor function that is similar to the findings in studies of healthy adults.

Abnormalities in gastrointestinal motility are associated with diseases of oxidative phosphorylation in children.

OBJECTIVE: Disorders of the mitochondrial electron transport chain enzymes of oxidative phosphorylation (OXPHOS) have neurologic, musculoskeletal, ophthalmologic, cardiac, and GI manifestations. Many adult and pediatric patients with disorders of OXPHOS have abnormalities in intestinal motility. The purpose of this study was to describe pediatric patients who initially presented with signs of GI dysmotility and were later evaluated and found to have a disorder of OXPHOS. METHODS: Data were collected on six patients, including initial GI and neurologic symptoms, histology of skeletal muscle biopsies, mitochondrial DNA mutational analysis, OXPHOS enzyme assay, upper GI barium imaging, technetium-99M liquid gastric emptying scan, upper GI endoscopy, esophageal manometry, and antroduodenal manometry. RESULTS: All six children presented with symptoms of GI dysmotility within 2 wk of life. Patients later developed symptoms of neurologic disorders. All patients had abnormalities in OXPHOS enzyme analysis. Muscle histology showed nonspecific changes with no ragged red fibers. Sequencing of the mitochondrial DNA showed no recognized mutations. No patient had any evidence of intestinal obstruction or malrotation by upper GI barium imaging. Four patients had delayed gastric emptying. Three patients had endoscopic and histologic evidence of esophagitis. All six had demonstrable neuropathic abnormalities by antroduodenal manometry, including the following: nonpropagated antral bursts, absent migrating motor complexes, postprandial antral hypomotility, retrograde migrating motor complexes, and tonic contractions with the migrating motor complex. CONCLUSIONS: Abnormalities in GI motility may be an early presenting sign of disorders of OXPHOS in children.