Copper(I)-Catalyzed Nitrile-Addition/N-Arylation Ring-Closure Cascade: Synthesis of 5,11-Dihydro-6H-indolo[3,2-c]quinolin-6-ones as Potent Topoisomerase-I Inhibitors.

In this paper, we present a copper(I)-catalyzed nitrile-addition/N-arylation ring-closure cascade for the synthesis of 5,11-dihydro-6H-indolo[3,2-c]quinolin-6-ones from 2-(2-bromophenyl)-N-(2-cyanophenyl)acetamides. Using CuBr and t-BuONa in dimethylformamide (DMF) as the optimal reaction conditions, the cascade reaction gave the target products, in high yields, with a good substrate scope. Application of the cascade reaction was demonstrated on the concise total syntheses of alkaloid isocryptolepine. Further optimization of the products from the cascade reaction led to 3-chloro-5,12-bis[2-(dimethylamino)ethyl]-5,12-dihydro-6H-[1,3]dioxolo[4',5':5,6]indolo[3,2-c]quinolin-6-one (2k), which exhibited the characteristic DNA topoisomerase-I inhibitory mechanism of action with potent in vitro anticancer activity. Compound 2k actively inhibited ARC-111- and SN-38-resistant HCT-116 cells and showed in vivo activity in mice bearing human HCT-116 and SJCRH30 xenografts. The interaction of 2k with the Top-DNA cleavable complex was revealed by docking simulations to guide the future optimization of 5,11-dihydro-6H-indolo[3,2-c]quinolin-6-ones as topoisomerase-I inhibitors.

A symptom severity questionnaire for patients suffering from functional gastrointestinal disorder: FGI-Checklist.

BACKGROUND AND AIM: A well-validated, comprehensive checklist of functional gastrointestinal (FGI) disorder (FGID) symptom severity for tracking symptom profile changes over time is lacking. We aim to develop and validate a comprehensive symptom severity checklist for FGID. METHODS: A 20-item scale, including both upper and lower gastrointestinal symptoms, was generated to measure the symptom severity commonly found in FGID. Patients who experienced at least monthly symptoms of FGID with negative endoscopy findings were invited to complete the FGI-Checklist, Patient Health Questionaire-9 for assessing depressive symptoms, and Patient Health Questionnaire-15 for assessing somatic symptoms at baseline. A subset of patients who met Rome III diagnostic criteria of gastroesophageal reflux disease, functional dyspepsia, and irritable bowel syndrome received medication treatment for 8-12 weeks and completed the FGI-Checklist again at a follow-up visit. Exploratory factor analysis was performed for subscales formation and psychometric properties were measured. RESULTS: Six hundred and forty-one patients were recruited for current study and 108 (16.8%) of them completed the FGI-Checklist again at follow-up. Exploratory factor analysis identified a five-factor solution accounting for 66.8% of the total variance. The five factors are named esophageal syndrome, reflux syndrome, functional dyspepsia syndrome, nausea and vomiting syndrome, and abdominal and bowel syndrome. The FGI-Checklist total score correlated with Patient Health Questionaire-9 and Patient Health Questionnaire-15 (all P < 0.001), which demonstrated good construct validity. Good item-internal consistency was found (Cronbach's alphas: 0.69-0.87). Responsiveness for reflux syndrome subscale, functional dyspepsia syndrome subscale, and abdominal and bowel syndrome subscale after medication treatment was significant (paired-t-test: all P < 0.01). CONCLUSION: The instrument, Checklist, is valid and reliable.

Nature and specificity of altered cognitive functioning in IBS.

BACKGROUND: It is unknown whether cognitive dysfunction found in patients with irritable bowel syndrome (IBS) was attributable to the different subtypes, ongoing pathophysiological processes, trait characteristics, or psychiatric comorbidity. METHODS: Forty Rome-III patients with IBS (20 diarrhea-predominant [IBS-D] and 20 constipation-predominant [IBS-C]) and 40 age-, sex-, education-matched healthy controls were systematically recruited and compared on their cognitive function with continuous performance test (CPT), Wisconsin Card Sorting Test (WCST) and emotional Stroop test. Beck Anxiety Inventory (BAI), Beck Depression Inventory-II (BDI-II), Patient Health Questionnaire-15 (PHQ-15) and a structured bowel symptom questionnaire were performed to measure anxiety, depressive, somatization, and bowel symptoms, respectively. Psychiatric diagnoses were ascertained with SCID-I (Structured Clinical Interview for DSM-IV Axis I Disorders). KEY RESULTS: Patients with IBS showed significantly increased standard deviation of reaction time (SDRT) (P = .003) on CPT, increased failure to maintain set (FMS) (P=.002), and percentage of perseverative errors (P = .003) on WCST. SDRT did not correlate with illness chronicity or bowel symptoms. FMS correlated with bowel symptom severity. In logistic regression models controlled for BAI, BDI-II, and PHQ-15, SDRT (AOR = 1.08, P = .025), but not FMS (P = .25) or percentage of perseverative errors (P = .24), significantly differentiated IBS from controls. Cognitive function was not significantly different between IBS-C and IBS-D (P > .05), or between pure IBS (n = 22) and IBS with generalized anxiety disorder (GAD) (n = 17) (P > .05). CONCLUSIONS & INFERENCES: Patients with IBS showed attentional and executive function impairment irrespective of subtypes but otherwise heterogeneous in terms of its state-trait correlations and overlap with anxiety comorbidity.

Functional dyspepsia susceptibility is associated with TGFB1 gene polymorphisms (RS4803455, RS1800469) in H pylori-negative Chinese population.

BACKGROUND: We previously published that altered expression of gastric TRPV1, BDNF, and peripheral cytokines was present in patients with functional dyspepsia. We herein examine whether genetic predisposition in altered biomarkers influences dyspeptic, sleep, and mood symptoms in patients with FD without previous infection. METHODS: Consecutive adult FD patients (Rome III) with no recent history of gastroenteritis and asymptomatic age- and sex-matched healthy controls were recruited for upper endoscopy. Subjects with GERD and IBS as predominant symptoms, diabetes mellitus, current or previous H pylori infection, psychiatric illness, and recent use of NSAID or PPI were excluded. The genetic associations with dyspeptic symptoms, sleep quality, and mood symptoms were evaluated. Genetic polymorphisms in TRPV1, TGFB1, TNF, COMT, BDNF, IL6, IL8, IL10, and IL12 were analyzed. KEY RESULTS: Twenty-nine male FD patients and 104 female FD patients were age matched (±3 years) with 81 healthy subjects. All had postprandial distress syndrome (PDS) as predominant subtype (PDS: 130, EPS: 3). SNPs in TGFB1 showed significant associations in dyspeptic patients after age and sex adjustment [for RS4803455: in the codominant model (C/A, OR = 0.34 (0.18-0.65), P = .004); in the dominant model (genotype C/C vs C/A-A/A, OR = 0.42 (0.23-0.77), P = .004); and in the overdominant model (genotype C/C-A/A vs C/A, OR = 0.38 (0.21-0.70), P < .001)] [for RS1800469: in dominant model (genotype A/A vs A/G-G/G, OR = 0.52 (0.27-0.99), P = .043)]. A allele in RS4803455 was associated with higher HADS depression score (P = .05) and epigastric burning sensation(P = .01). CONCLUSIONS AND INFERENCES: Our data showed that dyspeptic patients predispose genetic difference in TGFB1 which may influence the severity of dyspepsia.

The temporal relationship of daily life stress, emotions, and bowel symptoms in irritable bowel syndrome-Diarrhea subtype: A smartphone-based experience sampling study.

BACKGROUND: The current study aimed to model the moment-to-moment relationship between daily life stress, emotions, and bowel symptoms among patients with irritable bowel syndrome-diarrhea subtype (IBS-D) in the flow of daily life using a smartphone-based experience sampling method (ESM). METHODS: Patients with IBS-D (N = 27) and healthy controls (HC; N = 30) completed ESM ratings of their real-time daily life stress, which was defined as subjective stress related to daily activities, both positive and negative emotions, as well as bowel symptoms eight times a day for 14 consecutive days, following a baseline interview measuring bowel and mood symptoms. Moment-to-moment association between ESM variables was tested within and between groups using multilevel regression modeling. KEY RESULTS: Patients with IBS-D reported more severe bowel symptoms and lower positive affect than HCs, but levels of daily life stress and negative affect were comparable between groups. Time-lagged analysis of ESM data revealed that, among patients with IBS-D, daily life stress predicted a decrease in abdominal pain and urgency to defecation at a subsequent time point, whereas severity of bowel symptoms and occurrence of diarrhea predicted a subsequent increase in negative affect and daily life stress. The above associations were not found among HCs. CONCLUSIONS AND INFERENCES: ESM unveiled the dynamic relationship between bowel symptoms, stress, and emotionality. Patients with IBS-D responded to bowel symptoms with more stress and distress momentarily. Counter-intuitively, daily life activity stress appeared to ameliorate bowel symptoms, although a more rigorous study design is required to testify this claim. Psychological understanding of IBS-D is discussed.

Low-dose imipramine for refractory functional dyspepsia: a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Guidelines recommend the use of neuromodulators in patients with functional dyspepsia not responding to proton pump inhibitors (PPIs) and prokinetics; however, there is a lack of data from randomised controlled trials supporting their use. We aimed to assess the safety and efficacy of imipramine, a tricyclic antidepressant (TCA), in treatment-refractory functional dyspepsia. METHODS: In this single-centre, double-blind, randomised controlled trial, we enrolled consecutive patients with Rome II functional dyspepsia aged 18-80 years. Eligible patients were Helicobacter pylori-negative, had a normal upper gastrointestinal endoscopy and abdominal ultrasound, and remained symptomatic after open-label treatment with 8 weeks of esomeprazole and 4 weeks of domperidone. Patients completed questionnaires assessing dyspepsia symptoms, mood, and insomnia, and were then randomly assigned (1:1) via a computer-generated list of random numbers to receive imipramine (at a dose of 25 mg once nightly for the first 2 weeks, and then 50 mg thereafter) or placebo for 12 weeks. The primary endpoint was overall satisfactory relief of global dyspepsia symptoms at 12 weeks, via patient-reported assessment in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT00164775, and is completed. FINDINGS: Between Sept 11, 2005, and Aug 20, 2010, 107 patients with treatment-refractory functional dyspepsia were randomly assigned to receive imipramine (n=55) or placebo (n=52). Relief of global dyspepsia symptoms at 12 weeks occurred in 35 (63·6%, 95% CI 50·4-75·1) of 55 patients on imipramine compared with 19 (36·5%, 95% CI 24·8-50·1) of 52 on placebo (p=0·0051). Ten (18%) patients on imipramine discontinued the study due to adverse events (three dry mouth, two constipation, two drowsiness, and one each insomnia, palpitations, and blurred vision), compared with four (8%) on placebo (one dry mouth and constipation, and one each palpitations, worsening of gastro-oesophageal reflux, and limb paraesthesia). There were no serious adverse events. INTERPRETATION: Low-dose imipramine should be considered as a possible therapy for patients with functional dyspepsia refractory to both PPIs and prokinetics, although patients should be cautioned about the adverse event profile. FUNDING: None.

Effect of lie labelling on children's evaluation of selfish, polite, and altruistic lies.

This study investigates how 5- and 6-year-olds' evaluations of selfish, polite, and altruistic lies change as a result of whether these false statements are explicitly labelled as lies. We are also interested in how interpretive theory of mind may correlate with such evaluations with and without a lie label. Our results showed that labelling lowered children's evaluations for the polite and altruistic lies, but not for the selfish lies. Interpretive theory of mind correlated positively with the evaluation difference between the polite and altruistic lies and that between the selfish and altruistic lies in the label, but not in the non-label condition. Correlation between the selfish and altruistic lies and that between the polite and altruistic lies were stronger with than without labelling, after controlling for age, and verbal and non-verbal intelligence. We conclude that lie labelling biases children towards more negative evaluations for non-selfish lies and makes them see lies of different motives as more similar. If a lie label is applied, whether lies of different motives are still evaluated differently depends on interpretive theory of mind, which reflects the child's ability to represent and allow different interpretations of an ambiguous reality.

Chinese herbal medicine (Ma Zi Ren Wan) for functional constipation: study protocol for a prospective, double-blinded, double-dummy, randomized controlled trial.

BACKGROUND: Functional constipation is a common clinical complaint. Although the effectiveness of Ma Zi Ren Wan for alleviating functional constipation symptoms has been proven in a previous randomized placebo-controlled study, further evidence is needed to make clinical recommendations about Chinese herbal medicine. In particular, a comparison with conventional western medicine for functional constipation patients is needed. METHODS/DESIGN: This is a prospective, double-blinded, double dummy, randomized, controlled trial. After a 2-week run-in period, eligible patients (Rome III) with excessive traditional Chinese medicine syndrome will randomly be assigned to the Chinese medicine arm (Ma Zi Ren Wan and western medicine placebo), western medicine arm (senna and Chinese medicine placebo) or placebo arm (Chinese medicine placebo and western medicine placebo). Patients will undergo an 8-week treatment and an 8-week follow-up. The primary outcome is the responder rate for complete spontaneous bowel movement (CSBM) during treatment. Patients with a mean increase of CSBM ≧1/week in comparison with their baselines are defined as responders. The secondary outcomes include responder rate during follow-up, changes of colonic transit as measured with radio-opaque markers, individual and global symptom assessments, and reported adverse effects. DISCUSSION: This study is the first study to compare a Chinese Herbal Medicine (Ma Zi Ren Wan) with a laxative that is commonly used in the clinical practice of western medicine, and with a placebo. This study will complete the investigation of Ma Zi Ren Wan for functional constipation, and should, therefore, suggest recommendations for clinical practice. Furthermore, the process of first conducting a systematic review, then implementing a dose determination study followed by a placebo-control trial, and finally, comparing traditional Chinese medicine with an active conventional medicine in a controlled trial can be a reference to other researches on Chinese medicine interventions in the future. TRIAL REGISTRATION: NCT01695850.

Effect of probiotic bacteria on the intestinal microbiota in irritable bowel syndrome.

BACKGROUND AND AIM: In irritable bowel syndrome (IBS), the gut microbiota may be altered. Probiotic bacteria appear to be therapeutically effective. We characterized the mucosa-associated microbiota, and determined the clinical and microbiological effects of orally administered probiotic bacteria, in patients with IBS. METHODS: Mucosal microbiota from rectal biopsies of IBS patients and controls were assessed on the V1 and V2 variable regions of the 16S ribosomal RNA gene amplified using 454 pyrosequencing. Clinical symptoms and changes in mucosal microbiota were assessed in IBS patients before and after 4 weeks of treatment with probiotic mix VSL#3. RESULTS: Ten IBS subjects (eight female; mean age 46 years) were included. At week 4 of probiotic therapy, six patients showed symptom improvement on global symptom assessment compared with baseline (P = 0.031). Before therapy, intestinal microbiota of IBS subjects differed significantly from that of healthy controls, with less diversity and evenness than controls (n = 9; P < 0.05), increased abundance of Bacteroidetes (P = 0.014) and Synegitestes (P = 0.017), and reduced abundance of Actinobacteria (P = 0.004). The classes Flavobacteria (P = 0.028) and Epsilonproteobacteria (P = 0.017) were less enriched in IBS. Abundance differences were largely consistent from the phylum to genus level. Probiotic treatment in IBS patients was associated with a significant reduction of the genus Bacteroides (all taxonomy levels; P < 0.05) to levels similar to that of controls. CONCLUSION: In this pilot study, global and deep molecular analysis demonstrates an altered mucosal microbiota composition in IBS. Probiotic leads to detectable changes in the microbiota. These effects of probiotic bacteria may contribute to their therapeutic benefit.

Decreased Basal and postprandial plasma serotonin levels in patients with functional dyspepsia.

BACKGROUND & AIMS: Patients with diarrhea-predominant irritable bowel syndrome (IBS) have been found to have increased postprandial levels of serotonin (5-HT). Functional dyspepsia (FD) and IBS have been proposed to have common methods of pathogenesis, but little is known about the role of 5-HT in FD. METHODS: We measured postprandial levels of 5-HT in 54 patients with FD (based on Rome III criteria) and 28 asymptomatic healthy individuals (controls). Patients with gastroesophageal reflux disease and IBS as their predominant symptom were excluded. After an overnight fast, the subjects drank a liquid meal (Ensure; 1.06 kcal/mL at 30 mL/min) and underwent a (13)C-octanoic acid breath test to measure gastric emptying times. Blood samples were collected at 0, 30, 60, 90, and 120 minutes after the liquid meal for the 5-HT assay. RESULTS: Thirty-five patients with FD (65%) had postprandial distress syndrome, and 6 (11%) had a combination of postprandial distress syndrome and epigastric pain syndrome. There were no differences in rates of gastric emptying between patients with FD (103.6 ± 19.4 minutes) and controls (83.1 ± 4.0 minutes; P = .30). However, patients with FD had lower caloric intake (823.40 ± 44.1 kcal) than controls (1021 ± 68.2 kcal; P = .026). Patients with FD also had lower basal (P = .03) and postprandial plasma levels of serotonin at 30 minutes (P = .04), 60 minutes (P = .01), 90 minutes (P = .02), and 120 minutes (P = .002) than controls, as well as area under the curve values over the 120-minute time period (P = .005). Repeated-measures analysis of variance correlated 5-HT level with FD (P < .001). CONCLUSIONS: In contrast to patients with diarrhea-predominant IBS, those with FD have decreased basal and postprandial plasma levels of 5-HT. These findings indicate that the pathogenic mechanism of FD differs from that of diarrhea-predominant IBS, and that strategies to alter 5-HT levels or activity might be developed to treat patients with FD.

Peroral endoscopic myotomy for treatment of achalasia: from bench to bedside (with video).

BACKGROUND: Peroral endoscopic myotomy (POEM) is a novel approach to performing esophageal myotomy through a long submucosal tunnel. OBJECTIVE: This study aimed to investigate the feasibility and safety of POEM for treatment of achalasia. DESIGN: Preclinical animal study and prospective clinical study. PATIENTS: Consecutive patients diagnosed with achalasia with high-resolution manometry. INTERVENTIONS: POEM was standardized for preclinical and clinical studies. After submucosal injection, a mucosal incision was made 15 cm above the gastroesophageal junction (GEJ). A long submucosal tunnel was created to extend below the GEJ. The endoscopic myotomy started 10 cm above and extended 2 cm below the GEJ. We first conducted a preclinical animal study to confirm the safety of POEM. POEM was then performed for the treatment of achalasia in humans. MAIN OUTCOME MEASUREMENTS: Relief from dysphagia assessed by the dysphagia score and Eckhardt score. High-resolution manometry and pH monitoring were performed to evaluate the posttreatment effects and esophageal acid exposure. RESULTS: Seven 30-kg porcine models underwent POEM in the survival study. All of the pigs survived except 1, which sustained pneumomediastinum. POEM was performed for the treatment of achalasia in 16 patients. The mean operating time was 117.0 ± 34.1 minutes. All patients tolerated food on day 2, with a contrast study confirming no leakage. The median follow-up was 176.5 days (range 98-230 days). The postoperative basal lower esophageal sphincter pressure was significantly reduced (mean reduction, 13.9 ± 14.5 mm Hg; P = .005) and 4-second integrated relaxation pressure of the GEJ (mean reduction, 10.1 ± 7.4 mm Hg; P = .001). Of these patients, 58.3% had a normalized 4-second integrated relaxation pressure, whereas 20% had excessive esophageal acid exposure after the procedure. There was a significant improvement in quality of life 6 months after POEM measured by the Short Form-36 questionnaire. LIMITATION: Small sample size. CONCLUSIONS: POEM is a feasible, safe, and effective treatment for achalasia.

Does acupuncture therapy alter activation of neural pathway for pain perception in irritable bowel syndrome?: a comparative study of true and sham acupuncture using functional magnetic resonance imaging.

BACKGROUND/AIMS: Patients with irritable bowel syndrome (IBS) are characterized by abnormal central processing with altered brain activation in response to visceral nociceptive signals. The effect of electroacupuncture (EA) on IBS patients is unclear. The study is set to study the effect of EA on brain activation during noxious rectal distension in IBS patients using a randomized sham-controlled model. METHODS: Thirty IBS-diarrhea patients were randomized to true electroacupuncture or sham acupuncture. Functional MRI was performed to evaluate cerebral activation at the following time points: (1) baseline when there was rectal distension only, (2) rectal distension during application of EA, (3) rectal distension after cessation of EA and (4) EA alone with no rectal distension. Group comparison was made under each condition using SPM5 program. RESULTS: Rectal distension induced significant activation of the anterior cingulated cortex, prefrontal cortex, thalamus, temporal regions and cerebellum at baseline. During and immediately after EA, increased cerebral activation from baseline was observed in the anterior cingulated cortex, bilateral prefrontal cortex, thalamus, temporal regions and right insula in both groups. However, true electroacupuncture led to significantly higher activation at right insula, as well as pulvinar and medial nucleus of the thalamus when compared to sham acupuncture. CONCLUSIONS: We postulate that acupuncture might have the potential effect of pain modulation in IBS by 2 actions: (1) modulation of serotonin pathway at insula and (2) modulation of mood and affection in higher cortical center via ascending pathway at the pulvinar and medial nucleus of the thalamus.

Validation of Self-administrated Questionnaire for Psychiatric Disorders in Patients with Functional Dyspepsia.

INTRODUCTION: Psychiatric comorbidity is common in patients with functional dyspepsia (FD) but a good screening tool for psychiatric disorders in gastrointestinal clinical practice is lacking. AIMS: 1) Evaluate the performance and optimal cut-off of 12-item General Health Questionnaire (GHQ-12) as a screening tool for psychiatric disorders in FD patients; 2) Compare health-related quality of life (HRQoL) in FD patients with and without psychiatric comorbidities. METHODS: Consecutive patients fulfilling Rome III criteria for FD without medical co-morbidities and gastroesophageal reflux disease were recruited in a gastroenterology clinic. The followings were conducted at 4 weeks after index oesophagogastroduodenoscopy: self-administrated questionnaires on socio-demographics, dyspeptic symptom severity (4-point Likert scale), GHQ-12, and 36-item short-form health survey (SF-36). Psychiatric disorders were diagnosed with Structured Clinical Interview for DSM-IV Axis I Disorders (SCID) by a trained psychiatrist, which served as reference standard. RESULTS: 55 patients underwent psychiatrist-conducted interview and questionnaire assessment. 27 (49.1%) had current psychiatric disorders as determined by SCID (anxiety disorders: 38.2%, depressive disorders: 16.4%). Receiver operating characteristic curve analysis of GHQ-12 revealed an area under curve of 0.825 (95%CI: 0.698-0.914). Cut-off of GHQ-12 at >/=3 gave a sensitivity of 63.0% (95%CI = 42.4-80.6%) and specificity of 92.9% (95%CI = 76.5%-98.9%). Subjects with co-existing psychiatric disorders scored significantly lower in multiple domains of SF-36 (mental component summary, general health, vitality and mental health). By multivariate linear regression analysis, current psychiatric morbidities (Beta = -0.396, p = 0.002) and family history of psychiatric illness (Beta = -0.299, p = 0.015) were independent risk factors for poorer mental component summary in SF-36, while dyspepsia severity was the only independent risk factor for poorer physical component summary (Beta = -0.332, p = 0.027). CONCLUSIONS: Concomitant psychiatric disorders adversely affect HRQoL in FD patients. The use of GHQ-12 as a reliable screening tool for psychiatric disorders allows early intervention and may improve clinical outcomes of these patients.

Effects of dielectric parameters of human body on radiation characteristics of ingestible wireless device at operating frequency of 430 MHz.

In order to assess the sensitivities of the radiation characteristics and the compliance of ingestible wireless device (IWD) in human body due to the uncertainty and intersubject variability of dielectric properties of human body tissues, the specific absorption rate (SAR) and radiation characteristics of the IWD in two realistic human body models with changed and unchanged dielectric values are quantitatively compared using the finite-difference time-domain method. Simulations are carried out in 13 scenarios where the IWD is placed in the center positions of abdomens in the two body models at the operating frequency of 430 MHz with three orientations. Results show that the variation of radiation intensity near the surface of abdomen is around 2.5 dB within 20% variation of dielectric values. The maximum SAR values increase with the increase in conductivities of human body tissues and decrease with the increase in relative permittivities of human body tissues. A variation of up to 20% in conductivities and relative permittivities, alone or simultaneously, always causes a variation of SAR to be less than 10%. As far as the compliance of safety is concerned, the maxima of 1-g-averaged and 10-g-averaged SARs can reach 3.16 and 0.89 W/kg at the input power of 25 mW.

High incidence of mortality and recurrent bleeding in patients with Helicobacter pylori-negative idiopathic bleeding ulcers.

BACKGROUND & AIMS: The long-term prognosis of peptic ulcers associated with neither Helicobacter pylori nor nonsteroidal anti-inflammatory drugs (NSAIDs) is unknown. METHODS: This 7-year prospective cohort study recruited patients with bleeding ulcers from January to December 2000. H pylori-negative idiopathic bleeding ulcers were defined as having tested negative for H pylori, having no exposure to aspirin or analgesics within 4 weeks before endoscopy, and having no other identifiable causative factors. After ulcers healed, patients were divided into 2 groups: patients with prior H pylori-negative idiopathic bleeding ulcers (H pylori-negative idiopathic ulcer cohort; n = 120) and those with H pylori-positive, NSAID-negative bleeding ulcers who received eradication therapy (H pylori ulcer cohort; n = 213). Both groups were followed for

Radiation characteristics of ingested wireless device at frequencies from 430 MHz to 3 GHz.

In order to assess the compliance of high frequency ingested wireless devices (IWD) within the safety guidelines worldwide, the biological effects and the radiation efficiency of the IWD in a realistic human body model were studied using the Finite-Difference Time-Domain (FDTD) method. Simulations were carried out for three orientations of the IWD at seven positions in the human body model. Specific Absorption Rate (SAR), temperature rise, near field and far field characteristics were analyzed at frequencies from 430 MHz to 3 GHz. Results showed that the radiation intensity outside the body decreased with frequency. Furthermore, the orientation and position of the IWD, which gave maximum radiation efficiency, was frequency dependent. In our experiment, when the IWD was located at the front-most and back-most positions of the small intestine, the electric intensity outside the human body was maximum and minimum, respectively. The position influences the radiation efficiency of the IWD more than its orientation.

Obesity is associated with increased transient lower esophageal sphincter relaxation.

BACKGROUND AND AIMS: Obesity has been associated with gastroesophageal reflux disease (GERD) and its complication, but the mechanism is unclear. We evaluated the association between obesity and function of lower esophageal sphincter (LOS) in subjects without GERD. METHODS: We prospectively recruited consecutive obese (BMI >30) patients referred for weight reduction procedure and age- and sex-matched overweight (BMI 25-30) and normal weight (BMI > or =20 and <25) subjects. Exclusion criteria included esophagitis, reflux symptoms, use of proton pump inhibitor, hiatus hernia >2 cm, and diabetes mellitus with microvascular complication. All participants underwent combined 2-hour postprandial esophageal manometry and pH monitoring after a standard test meal followed by 24-hour ambulatory pH monitoring. RESULTS: Eighty-four subjects (obese, 28; overweight, 28; normal weight, 28) were studied. All 3 groups had comparable mean LOS pressure, LOS length, and peristaltic function. During the postprandial period, both obese and overweight groups had substantial increase in 2-hour rate of transient lower esophageal sphincter relaxation (TLOSR) (normal weight: 2.1 +/- 1.2 vs overweight: 3.8 +/- 1.6 vs obese: 7.3 +/- 2.0, P < .001), proportion of TLOSR with acid reflux (normal weight: 17.6% +/- 22.0% vs overweight 51.8% +/- 22.5% vs obese: 63.5% +/- 21.7%, P < .001), and gastroesophageal pressure gradient (GOPG) (normal weight: 4.5 +/- 1.2 mm Hg vs overweight: 7.1 +/- 1.4 mm Hg vs obese: 10.0 +/- 1.5 mm Hg, P < .001). Using multiple regression model, BMI (r(2): 0.70, B: 0.28, 95% CI: 0.24-0.33, P < .001) and waist circumference (r(2): 0.65, unstandardized regression coefficient [B]: 0.10, 95% CI: 0.08-0.11, P < .001) were significantly correlated with TLOSR. CONCLUSIONS: Obesity is associated with increased TLOSR and acid reflux during the postprandial period in subjects without GERD. Abnormal postprandial LOS function may be an early event in the pathogenesis of obesity-related GERD.

Experimental Study of Radiation Efficiency from an Ingested Source inside a Human Body Model*.

The attenuation of human body trunk at frequency range of 100MHz to 6GHz from an internal source was estimated using a simplified experimental model. Antennas were placed in the model which was filled with distilled water, 0.9% NaCl saline solution, and porcine body tissue alternately to determine the attenuation of the system. Saline has greater attenuation than water due to its higher conductivity, while porcine body tissue has attenuation bounded by saline solution and water. Estimated attenuation at the four ISM bands, 434MHz, 915MHz, 2.45GHz and 5.8GHz were given and all of these bands satisfied the safety and sensitivity requirements of a biomedical telemetry system. 915MHz and 2.45GHz are good choices for the wireless link because of their relatively larger electrical size of RF components such as antenna. In addition, with the growth in wireless LAN and Bluetooth technology, miniaturized antennas, camera modules, and other RF devices have been developed which can be employed in biomedical ingested or implanted devices. This paper gives a reference of attenuation values of a human body trunk of average size. It should be noted that the attenuation values can be different for different body size and different body composition, and therefore the values in this paper serves as a reference only.

Physiological factors of the small intestine in design of active capsule endoscopy.

Wireless capsule endoscope is a device used to examine the diseases in the small intestine. At present, the capsule endoscope moves through the gastrointestinal tract by natural propulsion of peristalsis. In order to achieve real-time diagnosis and treatment-related procedure, the capsule endoscope is required to be self-actuated and controlled. Different from soild environment, the small intestine is an extremely flexible tube. The unique structure and tissue cause many challenges for the capsule actuation. In this paper, the features, motility, and frictional force of the small intestine are analyzed for determining the design strategy. In-vitro experiment results show the power of magnetic force needed for driving the capsule and the factors that affect the magnitude of the driving force as well. Based on the analysis of the small intestime, a scheme of magnetically-actuated active endoscopy is proposed in the end.

Poly(ethylene glycol) enhances the surface activity of a pulmonary surfactant.

The primary role of lung surfactant is to reduce surface tension at the air-liquid interface of alveoli during respiration. Axisymmetric drop shape analysis (ADSA) was used to study the effect of poly(ethylene glycol) (PEG) on the rate of surface film formation of a bovine lipid extract surfactant (BLES), a therapeutic lung surfactant preparation. PEG of molecular weights 3,350; 8,000; 10,000; 35,000; and 300,000 in combination with a BLES mixture of 0.5 mg/mL was studied. The adsorption rate of BLES alone at 0.5 mg/mL was much slower than that of a natural lung surfactant at the same concentration; more than 200 s are required to reach the equilibrium surface tension of 25 mJ/m(2). PEG, while not surface active itself, enhances the adsorption of BLES to an extent depending on its concentration and molecular weight. These findings suggest that depletion attraction induced by higher molecular weight PEG (in the range of 8,000 to 35,000) may be responsible for increasing the adsorption rate of BLES at low concentration. The results provide a basis for using PEG as an additive to BLES to reduce its required concentration in clinical treatment, thus reducing the cost for surfactant replacement therapy.