CpG methylation and reduced expression of O6-methylguanine DNA methyltransferase is associated with Helicobacter pylori infection.

BACKGROUND & AIMS: The gastric epithelium genome undergoes extensive epigenetic alterations during Helicobacter pylori-induced gastritis. Expression of the gene encoding the DNA repair protein O6-methylguanine DNA methyltransferase (MGMT) might be reduced via hypermethylation of its promoter in patients with H pylori gastritis. We characterized expression of MGMT and its epigenetic regulation via CpG methylation in gastric tissue from patients with H pylori gastritis and investigated the effects of H pylori infection eradication on MGMT expression. METHODS: Gastric biopsy samples were collected from patients with H pylori gastritis before and after eradication and from H pylori-negative control subjects. AGS cells were cocultured with H pylori to study the effects of H pylori infection on MGMT RNA, protein expression, and CpG methylation. RESULTS: CpG methylation of MGMT was more frequent in the gastric mucosa of patients with H pylori gastritis (69.7%) than in those without (28.6%, P = .022). MGMT methylation was significantly reduced after H pylori eradication (from 70% to 48% of cases, P = .039), and mean levels of CpG methylation decreased from 12.6% to 5.7% (P = .025), increasing MGMT expression. MGMT methylation was significantly associated with CagA-positive H pylori (P = .035). H pylori reduced MGMT protein and RNA levels and induced MGMT CpG methylation in gastric AGS cells. CONCLUSIONS: H pylori gastritis, particularly in patients infected with H pylori CagA-positive strains, is associated with hypermethylation of MGMT and reduced levels of MGMT in the gastric epithelium. MGMT promoter methylation is partially reversible after eradication of H pylori infection. These data indicate that DNA repair is disrupted during H pylori gastritis, increasing mutagenesis in H pylori-infected gastric mucosa.

Treatment of chronic radiation proctitis with cryoablation.

BACKGROUND: Chronic radiation proctitis (CRP) is a common problem in patients receiving pelvic radiation. Current therapies have the potential for deep tissue injury with ulcerations, perforation, and fistula formation. Cryospray ablation therapy offers superficial ablation of mucosa and is a potential method to endoscopically treat CRP safely and effectively. OBJECTIVE: To determine tolerability of and response to cryotherapy in patients with radiation proctitis. DESIGN: Prospective case-series pilot study. SETTING: Baylor College of Medicine, Michael E. DeBakey Medical Center, Houston, Texas. PATIENTS: Ten patients were prospectively recruited with chronic hemorrhagic radiation proctitis. INTERVENTIONS: Endoscopic cryoablation of CRP. MAIN OUTCOME MEASUREMENTS: Symptom severity of CRP was obtained by using the Radiation Proctitis Severity Assessment Scale (RPSAS). Endoscopic assessment was obtained using the rectal telangiectasia density grade. The primary endpoint of the study was endoscopic improvement of CRP based on the change in rectal telangiectasia density at 3-month follow-up. Secondary endpoints included symptomatic improvement based on RPSAS and adverse events at 3 months. RESULTS: Ten patients with hemorrhagic radiation proctitis were treated with endoscopic cryoablation. Endoscopic severity improved as measured by rectal telangiectasia density from 2.7 to 1.7 (P=.004). Overall subjective clinical scores improved as determined by the Radiation Proctitis Severity Assessment Scale from 27.7 to 13.6 (P=.003). Endoscopic improvement correlated with symptom improvement. LIMITATIONS: Nonpowered case series pilot study. CONCLUSIONS: Cryoablation improved clinical and endoscopic indices in CRP. Further controlled studies are needed to identify the safety and efficacy of cryoablation for CRP.

Unreliability of results of PCR detection of Helicobacter pylori in clinical or environmental samples.

The aim of this study was to compare published Helicobacter pylori primer pairs for their ability to reliably detect H. pylori in gastric biopsy specimens and salivary samples. Detection limits of the 26 PCR primer pairs previously described for detection of H. pylori DNA in clinical samples were determined. Sensitivity and specificity were determined using primers with detection limits of <100 CFU/ml using 50 H. pylori-positive and -negative (by concordance by culture and histology) coded gastric biopsy specimens. These results were then confirmed with gastric biopsy specimens and saliva from patients with confirmed H. pylori status. Five of the twenty-six previously reported primer pairs (HP64-f/HP64-r, HP1/HP2, EHC-U/EHC-L, VAG-F/VAG-R, and ICT37/ICT38) had detection limits of <100 CFU/ml in the presence of gastric tissue. None had 100% specificity or sensitivity; all produced false-positive results. The HP64-f/HP64-r for ureA and HP1/HP2 for 16S rRNA individually had sensitivities and specificities of >90% with gastric biopsy specimens. No combinations of primer pairs improved the results. Using these five primer pairs, 54% of the positive saliva samples were determined to be false positive; both the HP64-f/HP64-r and the HP1/HP2 sets produced false positives with saliva. We conclude that clinicians should not rely on results using current PCR primers alone to decide the H. pylori status of an individual patient or as a basis for treatment decisions. The results of studies based on PCR identification of H. pylori in environmental samples should be viewed with caution. Possibly, specific primers sets can be identified based on the presence of multiple putative virulence factor genes.

Polyomavirus shedding in the stool of healthy adults.

We recently reported the frequent detection of polyomaviruses (BK virus [BKV] or simian virus 40 [SV40]) in 46% of stool samples from hospitalized children. In order to determine if adults exhibit fecal shedding of polyomavirus, single stool specimens from healthy adults were evaluated by PCR. Overall, 20 (18.2%) of 110 specimens were positive for human polyomaviruses: 9 with BKV, 9 with JC virus (JCV), 1 with SV40, and 1 with both JCV and SV40. Among the 94 subjects without immune compromise, 17 (18.1%) were excreting polyomaviruses. This shedding frequency in adults was significantly lower than that observed in children (P < 0.001). These findings support the hypothesis that the gastrointestinal tract may be a site of polyomavirus persistence, and they suggest a fecal-oral route of viral transmission.

Mechanical colon cleansing for screening colonoscopy: A randomized controlled trial.

OBJECTIVE: Effective screening colonoscopy depends on the quality of colon preparation. This study aimed to compare pulsed irrigation evacuation (PIE), polyethylene glycol (PEG) and sodium phosphate colon preparations. METHODS: Outpatients at a VA hospital were randomized using sealed envelopes. Preparations consisted of polyethylene glycol 4L, Fleet sodium phosphate 90 mL with four to six glasses water twice daily and 296 mL of magnesium citrate in the evening with PIE prior to colonoscopy. Colon cleansing was assessed blindly using a five-point scale: 0 (very poor) to 4 (excellent). RESULTS: Altogether 391 patients participated in the study (129 in the PEG group, 127 in the sodium phosphate and 135 in the PIE group), with a mean age of 62 years, of whom 75% were men. PIE and sodium phosphate were superior to PEG: median cleansing scored 4 (excellent) versus 3 with PEG (P < 0.01). Inadequate preparations were more common with PEG than PIE (18% vs 5%) (P < 0.01). Side-effects included vomiting: 37% in the sodium phosphate group versus 5% in the PEG and 2% in the PIE groups (P < 0.01). The three preparations were judged intolerable in ≤ 5%. CONCLUSIONS: PIE and sodium phosphate are superior to PEG for colon preparations. PIE is the preferred preparation for those at high risk of unsatisfactory preparations or with unsatisfactory traditional preparations.

Enterococcus gastritis.

Helicobacter pylori infection is the most common cause of gastritis with its associated sequelae. Gastritis secondary to other bacteria is rare. This report describes Enterococcus-associated gastritis in a 59-year-old diabetic man. Nine months after receiving treatment for H. pylori-associated gastritis, he underwent endoscopy to confirm H. pylori eradication and to evaluate the status of previously seen ulcers. Mucosal biopsy specimens revealed severe active but focal gastritis adjacent to gram-positive coccobacilli in short to long chains with no H. pylori. Culture grew an Enterococcus similar to E. hirae and E. durans. No treatment was given, and endoscopy done 2 months later showed complete resolution of the gastritis and absence of H. pylori or enterococci. Our patient's gastritis represents a previously undescribed manifestation of Enterococcus infection. It is possible that the presence of NSAID gastric mucosal injury and diabetes predisposed this individual to the development of transient Enterococcus gastritis.

Preoperative evaluation of hepatic lesions for the staging of hepatocellular and metastatic liver carcinoma using endoscopic ultrasonography.

BACKGROUND: Noninvasive imaging techniques, such as dynamic computed tomography (CT), magnetic resonance imaging and transabdominal ultrasonography are limited in their ability to detect hepatic lesions less than one cm. Intraoperative ultrasonography (IOUS) is currently the most sensitive modality for the detection of small hepatic lesions. However, IOUS is invasive requiring laparoscopy or formal laparotomy. We sought to evaluate the feasibility of using endoscopic ultrasonograhpy (EUS) for the detection and diagnosis of hepatic masses in patients with hepatocellular cancer (HCCA) and metastatic lesions (ML). We hypothesized that EUS could detect small (<1.0 cm) hepatic lesions undetectable by CT scan and could be used for biopsy of deep-seated hepatic lesions. METHODS: Consecutive patients referred for EUS with suspected liver lesions were evaluated between July 2000 and October 2001. All patients underwent EUS using an Olympus (EM30) radial echoendoscope. If liver lesions were confirmed and fine needle aspiration (FNA) was deemed necessary, a linear array scope was used and an FNA performed with a 22-gauge needle. Two passes were made for each lesion. RESULTS: 14 patients underwent evaluation with dynamic CT scans and EUS. In all 14 patients, EUS successfully identified hepatic lesions ranging in size from 0.3 cm to 14 cm (right lobe: n = 3, left lobe: n = 1, bilobar: n = 8). Moreover, EUS identified new or additional lesions in 28% (4 of 14) of the patients, all less than 0.5 cm in size (HCCA: n = 2, ML: n = 2), influencing the clinical management. In 2 of 14 patients EUS identified liver lesions, previously described as suspicious by CT scan, to be hemangiomas. Nine patients underwent EUS-guided FNA of hepatic lesions (deep seated: n = 3, superficial: n = 6). All FNA passes yielded adequate specimens (malignant: n = 8, benign: n = 1). CONCLUSIONS: Our preliminary experience suggests that EUS is a feasible preoperative staging tool for liver masses suspected to be HCCA or metastatic lesions. EUS can detect small hepatic lesions previously undetected by dynamic CT scans. Furthermore, EUS-guided FNA can confirm additional HCCA liver lesions or liver metastases, in deep-seated locations, upstaging patients and changing clinical management.

Dual proton pump inhibitor plus amoxicillin as an empiric anti-H. pylori therapy: studies from the United States.

BACKGROUND: Studies with CYP2C19 slow metabolizers have shown that the combination of a proton pump inhibitor (PPI) plus amoxicillin (dual therapy) can reliably cure more than 90% of Helicobacter pylori infections. Theoretically, the use of a PPI dose that provides equivalent acid suppression with fast metabolizers and slow metabolizers would achieve high cure rates irrespective of the CYP2C19 genotype. AIM: To evaluate high-dose PPI plus amoxicillin dual therapy for H. pylori eradication. METHODS: H. pylori-infected individuals (positive by 2 tests) received esomeprazole 40 mg plus amoxicillin 750 mg every 8 h for 14 days. The protocol was planned based on the "efficient identification strategy" requiring more than 90% success, with stop criteria of 6 or more failures within 50 patients or a cure rate of less than 80%. RESULTS: Thirty-six patients (5 women, 31 men), average age 58 years, were enrolled before achieving stop criteria. All were first H. pylori treatments. The intention-to-treat cure was achieved in 26/36 [72.2%; 95% confidence interval (CI) = 56-84%] and in 26/35 per protocol (74.2%; 95% CI = 56-87%). There were no significant side effects. Compliance was 85% or greater in all (100% in 91.6%). CONCLUSIONS: If the hypothesis that consistently high intragastric pH is required to reliably achieve more than 90% H. pylori eradication, our regimen was not sufficient. Success may require more than every 8 h dosing, the concomitant administration of sodium bicarbonate, or the use of a long-acting PPI. However, the result was positive in that dual therapy with the doses tested here was at least as successful as empiric triple therapy.

Obesity and gastroesophageal reflux disease and gastroesophageal reflux symptoms in children.

BACKGROUND: The association between body mass index (BMI) and gastroesophageal reflux disease (GERD) has been extensively studied among adults but few studies have examined such association in children. AIMS: 1) to determine the relationship between BMI in children and GERD, and 2) to use the National Center for Health Statistics (NCHS) values for BMI as a valid source for comparison. METHODS: We identified two cohorts of children aged between two and 17 years who were seen at Texas Children's Hospital (TCH). The first cohort consisted of children diagnosed with GERD based on upper gastrointestinal endoscopic and histologic evaluation, which was recorded in the Pediatric Endoscopic Database System-Clinical Outcomes Research Initiative (PEDS-CORI) at TCH. A diagnosis of GERD was based on the presence of erosive esophagitis or esophageal ulcers. Endoscopic reports that were incomplete or did not include demographic features, indications for endoscopy, or endoscopic findings were excluded. The second cohort consisted of all children with symptoms due to gastroesophageal reflux (GER) who received outpatient gastrointestinal (GI) consultation at TCH for any 9th revision of the International Statistical Classification of Diseases (ICD-9) code suggestive of GER. There was no overlap between the two cohorts as each child was indexed only once. Children with any comorbid illnesses were excluded. MEASUREMENTS: The records for each child namely, age, gender, height, and weight were obtained on the same date as that of the diagnosis. Using the growth curves published by the NCHS, the gender/age specific weight-for-age Z-score (WAZ), and height-for-age Z-score (HAZ) were calculated. BMI was calculated as the weight in kilograms divided by height in meters squared. Children having values greater than the 95th percentile for their age/gender-specific BMI were defined as obese. RESULTS: In a one-year period (January 2006 to December 2006), a total of 627 children who attended the GI clinic at TCH were identified with GERD symptoms of whom 131 underwent endoscopic examination. The mean age was 9.7 years; 42% were females; 57% were Caucasians; 15% were African Americans, and 28% were Hispanics. Using National Health and Nutrition Examination Survey (NHANES) data obtained from the same period as the the current data as a baseline for comparison, the BMI of children diagnosed with GERD was higher than the BMI reported by NHANES data. The final analysis of test proportion showed an overall proportion of 0.207 for the current study versus NHANES data (0.174). The current study also showed that more boys than girls have BMI greater than 95th percentile (24.7% vs 16.5%, respectively, OR = 1.7, 95% CI = 1.2-2.6, p = 0.04). CONCLUSIONS: Children diagnosed with GERD or those who presented with symptoms of GERD are more likely to be obese. The findings of this study show a possible association between obesity and GERD in children. Further understanding about the co-morbidity between GERD and obesity in children may have important implications on GERD management and treatment in children.

Capsule endoscopy for screening for short-segment Barrett's esophagus.

BACKGROUND: The rise in the incidence of esophageal adenocarcinoma has led to the development of new methods to screen for the precursor lesion, Barrett's esophagus. AIM: To evaluate the potential role of esophageal capsule endoscopy in identifying the presence of short-segment Barrett's esophagus. METHODS: Patients with biopsy-proven short-segment Barrett's esophagus underwent esophageal capsule endoscopy. The images were reviewed by two expert observers with no knowledge of the purpose of the study. The data collected included transit time, quality of image, presence or absence of Z-line, Schatzki's ring, hiatal hernia, and Barrett's esophagus (long or short, definite or suspected). RESULTS: Twenty patients were studied; in 18, the capsule passed into the stomach. Barrett's esophagus was identified or suspected in eight cases (44%) by one observer and three (16%) by the second (P= 0.14). Although the Z-line was seen in the 18 cases that were qualified by both observers, there was an agreement in only six cases as to whether it was regular or irregular. Erosive gastroesophageal reflux disease (GERD) was scored as present in three and absent in six patients by both readers. Nonexisting feline esophagus, varices, and distal esophageal stricture were suspected in one patient each. CONCLUSIONS: Esophageal capsule endoscopy had a high interobserver variability and a low yield for short-segment Barrett's esophagus. Esophageal capsule endoscopy cannot be recommended for screening for short-segment Barrett's esophagus.

Multidimensional measure for gastroesophageal reflux disease (MM-GERD) symptoms in children: a population-based study.

BACKGROUND: Gastroesophageal reflux disease (GERD) symptoms are very common in children with major presenting symptoms of abdominal pain, heartburn and regurgitation. The presence of GERD symptoms often result in an impaired health-related quality of life for both the patients and their parents. Evaluation of children with GERD symptoms continues to challenge physicians due to the lack of a validated measure for GERD symptoms. AIMS: To develop and test a multidimensional measure for GERD symptoms in children and to evaluate the responses of the measure among children attending pediatric gastroenterology (GI) clinics. METHODS: We conducted a cross-sectional study that enrolled children with GERD symptoms from pediatric GI clinic. All children and parents received a standardized questionnaire concerning socio-economic parameters, GERD symptoms, duration, frequency, intensity and missed activities due to GERD symptoms. Each child and parent pair was interviewed by a physician to complete baseline information for the multidimensional measure that consisted of four scales: symptoms scale (10 items), pain intensity scale (3 items); disability scale (3 items) and satisfaction scale (2 items). RESULTS: One hundred and thirty-three children participated in the study; 59% girls, ages 4 to 18 years, mean age = 10 +/- 3, 50%, 10 years and younger. There was an excellent correlation between the four-scales measure among children 7 years and younger (R = 0.70, p = 0.0001) and children >7 years (R = 0.74, p = 0.0001). The inter-item consistency (Cronbach's co-efficient alpha) for the symptoms items, pain intensity items, disability items and satisfaction items were 0.71, 0.74, 0.78 and 0.60, respectively, demonstrating adequate reliability of the measure. CONCLUSION: Children with GERD symptoms have good responses to the multidimensional measure for GERD symptoms, showing that the measure performed well across populations. The measure is reliable and specific for assessing the symptoms of GERD in children and is an appropriate outcomes measure for clinical trials involving GERD symptoms in children.

Failures in a proton pump inhibitor therapeutic substitution program: lessons learned.

The pathogenesis of patient dissatisfaction following involuntary therapeutic substitutions involving proton pump inhibitors (PPIs) is poorly understood. The aim of this study was to describe the patient population experiencing therapeutic failure and investigate whether failure was related to individual differences in response to the different PPIs. Treatment failures in a lansoprazole-rabeprazole therapeutic substitution program were compared to switch successes. A subgroup was randomized in a double-blind, double-dummy, crossover study to four 2-week periods of lansoprazole-rabeprazole-lansoprazole-rabeprazole or vice versa. Measures included overall rating of gastrointestinal reflux disease (GERD) symptoms for the past week as well as the frequency and distress scales of the GERD Symptom Assessment Scale. One hundred fifteen nonresponders were compared with 54 successful responders. Nonresponders consisted primarily of patients with GERD (74%, vs. 44% of responders; P = 0.005) who had undergone upper gastrointestinal endoscopy (50%, vs. 31% of responders; P = 0.02). Twelve patients completed the randomized treatment study. The interrater kappa coefficient for responder status was estimated to be 0.80 for lansoprazole and 0.21 for rabeprazole. The majority of PPI nonresponders had a clinical diagnosis of GERD and were receiving >/=40 mg of rabeprazole daily. This pilot study provides new insights into the design of subsequent studies of nonresponders in PPI therapeutic substitution programs.

Recurrent abdominal pain in school children: effect of obesity and diet.

AIMS: To study the epidemiology and some of the risk factors of childhood recurrent abdominal pain (RAP) in school age children. METHODS: We used a questionnaire concerning socioeconomic parameters, intensity, frequency, duration, nature of RAP and anthropometric measures. We used several criteria to identify RAP and the Wong-Baker FACES scale for pain intensity and calculated the gender/age-specific body mass index (BMI) Z-score using NCHS standards. Obesity was defined as a BMI>or=95th percentile for age and gender. RESULTS: A total of 925 children mean age of 9.5 years completed and returned the questionnaires. The prevalence of RAP was 24%; 22% among boys versus 26% among girls (p=0.28) and reached its peak among children aged 7-9 (29%) years. Children with BMI>or=95% percentile reported more RAP compared to those not obese (33.3% vs. 22.5%) (OR=1.8, p=0.01). There was an inverse correlation between fruit consumption and RAP prevalence with 20% among children reporting more than three serving of fruit per week compared to 40% of those who did not consume any fruits (p<0.002). Logistic regression analysis confirmed BMI>or=95th percentile and low consumption of fruits are significant risk factors for RAP. CONCLUSIONS: There is a significant association between RAP and obesity and both conditions are prevalent among children in this population. Understanding more about the co-morbidity between RAP and obesity could have important implications on RAP management and treatment.

A prospective study for the association of Helicobacter pylori infection to a multidimensional measure for recurrent abdominal pain in children.

BACKGROUND: There is a controversial association between Helicobacter pylori infection and recurrent abdominal pain (RAP) in childhood and inconsistent information on specific symptomatology of the infection. AIMS: To examine the prevalence of H. pylori infection among children with RAP compared to asymptomatic children. METHODS: Two prospective studies were conducted. The first study enrolled 223 children diagnosed with RAP from two pediatric gastroenterology clinics in Houston, Texas. Children were qualified if they were identified by their physician as having RAP. A new multidimensional measure for RAP (MM-RAP) consisting of four scales (pain intensity scale, symptoms scale, disability scale, and satisfaction scale) was administered to each child/parent. The second study enrolled 330 asymptomatic children from the same community who did not have any upper gastrointestinal symptoms. Symptomatic and asymptomatic children underwent (13)C-urea breath testing. RESULTS: In the first study, the prevalence of H. pylori in children with RAP was 11% and fell with age from 20% at age < or = 5 years to 7% for children > 10 years (OR = 2.7, 95% CI = 0.7-11.2). There was no association between the mother's educational level and H. pylori prevalence; (12% among children whose mothers completed college versus 11% among those who had elementary school, p = .8). No relationship was found between H. pylori and mean scores of the RAP scales. In the second study, the prevalence of H. pylori in asymptomatic children was 17% and increased with age from 11% for children < or = 5 years to 40% for children > 10 years (OR = 5.4, 95% CI = 2.0-13.8). The mother's educational level was inversely correlated with H. pylori (OR = 3.0, 95% CI = 2.2-6.1, p < .01). CONCLUSIONS: The epidemiologic patterns of H. pylori infection differed significantly between symptomatic and asymptomatic children. Younger children suffering from RAP are more likely to be infected with H. pylori than older children with the same complaint, suggesting that early acquisition may manifest in symptoms that lead to clinic visits.

Development of a multidimensional measure for recurrent abdominal pain in children: population-based studies in three settings.

OBJECTIVE: Recurrent abdominal pain (RAP) is a common problem in children and adolescents. Evaluation and treatment of children with RAP continue to challenge physicians because of the lack of a psychometrically sound measure for RAP. A major obstacle to progress in research on RAP has been the lack of a biological marker for RAP and the lack of a reliable and valid clinical measure for RAP. The objectives of this study were (1) to develop and test a multidimensional measure for RAP (MM-RAP) in children to serve as a primary outcome measure for clinical trials, (2) to evaluate the reliability of the measure and compare its responses across different populations, and (3) to examine the reliabilities of the measure scales in relation to the demographic variables of the studied population. METHODS: We conducted 3 cross-sectional studies. Two studies were clinic-based studies that enrolled children with RAP from 1 pediatric gastroenterology clinic and 6 primary care clinics. The third study was a community-based study in which children from 1 elementary and 2 middle schools were screened for frequent episodes of abdominal pain. The 3 studies were conducted in Houston, Texas. Inclusion criteria for the clinic-based studies were (1) age of 4 to 18 years; (2) abdominal pain that had persisted for 3 or more months; (3) abdominal pain that was moderate to severe and interfered with some or all regular activities; (4) abdominal pain that may or may not be accompanied by upper-gastrointestinal symptoms; and (5) children were accompanied by a parent or guardian who was capable of giving informed consent, and children over the age of 10 years were capable of giving informed assent. The community-based study used standardized questionnaires that were offered to 1080 children/parents from the 3 participating schools; 700 completed and returned the questionnaires (65% response rate). The questionnaire was designed to elicit data concerning the history of abdominal pain or discomfort. A total of 160 children met Apley's criteria and were classified as having RAP. Inclusion criteria were identical to those criteria for the clinic-based studies. Participating children in the 3 studies received a standardized questionnaire that asked about socioeconomic variables, abdominal pain (intensity; frequency; duration; nature of abdominal pain, if present, and possible relationships with school activities; and other upper gastrointestinal symptoms). We used 4 scales for the MM-RAP: pain intensity scale (3 items), nonpain symptoms scale (12 items), disability scale (3 items), and satisfaction scale (2 items). Age 7 was used as a cutoff point for the analysis as the 7-year-olds have been shown to exhibit more sophisticated knowledge of illness than younger children. RESULTS: A total of 295 children who were aged 4 to 18 years participated in the study: 155 children from the pediatric gastroenterology clinics, 82 from the primary care clinics, and 58 from the schools. The interitem consistency (Cronbach's coefficient alpha) for the pain intensity items, nonpain symptoms items, disability items, and satisfaction items were 0.75, 0.81, 0.80, and 0.78, respectively, demonstrating good reliability of the measure. The internal consistencies of the 4 scales did not significantly differ between younger (< or =7 years) and older (>7 years) children. There was also no significant variation in the coefficient alpha of each of the 4 scales in relation to gender or the level of the parent's education. Reliability was identical for the pain-intensity items (0.74) among children who sought medical attention from primary care or pediatric gastroenterology clinics. The intercorrelations of factor scores among the 4 scales showed a strong relationship among the factors but not high enough that correlations would be expected to be measuring the same items. The results of the factor analysis identified 5 components instead of 4 components representing the 4 scales. The 12 items of the nonpain symptoms scale were classified into 2 components; 1 component included heartburn, burping, passing gas, bloating, problem with ingestion of milk, bad breath, and sour taste (nonpain symptoms I), and the other included nausea/vomiting, diarrhea, and constipation (nonpain symptoms II). The program ordered the 5 components on the basis of the percentage of the total variance explained by each component and consequently by the strength of each components in the following order: nonpain symptoms I, pain intensity, pain disability, satisfaction, and nonpain symptoms II. Of the 20 items that composed the MM-RAP, 17 met the inclusion criteria of having a correlation of > or =0.40 on the primary factor analyses. The 3 items that assessed pain intensity met the inclusion criteria as well as the 2 items that assessed satisfaction. Two of the 3 items that assessed disability met the inclusion criteria; however, the missed school item did not. The sleep problem and the loss of appetite items in the nonpain items also did not meet the inclusion criteria in both components of the nonpain symptoms scale. However, the loss of appetite item met the inclusion criteria in the disability scale with a correlation of 0.6. The 2 items that did not meet the inclusion criteria (missed school days and sour taste) will be eliminated in the revised measure for RAP. CONCLUSION: The MM-RAP demonstrated good reliability evidence in population samples. Children who have RAP and are seen at pediatric gastroenterology or primary care pediatric clinics have similar responses, showing that the measure performed well across several populations. Age did not affect the reliability of responses. The MM-RAP included 4 dimensions, each with several items that may identify disease-specific dimensions. In addition, dividing the nonpain symptoms scale into 2 components instead of 1 component could assist in creating a disease-specific measure. The present study focused exclusively on developing the multidimensional measure for RAP in children that could assist physicians in evaluating the efficacy of RAP treatment independent of psychological evaluations. In addition, the measure was designed for use in clinical trials that evaluate the efficacy of RAP treatment and to allow comparison between intervention studies. In conclusion, we were able to identify 4 dimensions of RAP in children (pain intensity, nonpain symptoms, pain disability, and satisfaction with health). We demonstrated that these dimensions can be measured in a reliable manner that is applicable to children who experience RAP in various settings.