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This chapter reviews data on the pathways by which luminal, mainly duodenal, chemoreceptors modulate gastro-pyloro-duodenal motor function to control emptying of nutrients into the small intestine. The vagus mediates proximal gastric relaxation caused by nutrient stimulation of duodenal/jejunal mucosal chemoreceptors. Modulation of the spatial patterning and inhibition of antral contractions during duodenal chemoreceptor activation are somewhat conflicting: both vagal control and ascending intramural nerves appear to play a role. Intraduodenal nutrients stimulate the localized pyloric contractions that prevent transpyloric flow via ascending duodenal intramural nerve pathways. Though not yet formally investigated, patterns of activation of the duodenal brake motor mechanism suggest that duodenal loop mucosal chemoreceptors signal to a brake mechanism at the most aborad region of the duodenum via descending intramural duodenal nerves.Intrinsic intramural pathways are important in the control of the first stages of digestion.

per-oral endoscopic myotomy (POEM) has become a mainstream treatment for achalasia and is a promising therapy in spastic disorders.this is a retrospective study of prospectively collected data (case series). We present the first results of the use of POEM in patients with atypical spastic esophageal motor disorders that do not satisfy current Chicago Classification criteria. Seven consecutive patients with troublesome and persistent symptoms (12-180 months) related to atypical spastic esophageal motor dysfunction were systematically assessed before and after POEM, the extent of which was tailored by manometric findings. In five of the patients, other endoscopic or surgical procedures had failed.high-resolution manometry (HRM) showed a spastic esophageal body contractile segment in varying positions and lengths along the esophageal body which did not meet Chicago Classification criteria. After POEM, dysphagia and/or chest pain had either resolved or was greatly reduced. HRM 3-6 months after myotomy showed that the regions of spastic contraction targeted by myotomy had been ablated. There were no major complications. The clinical responses were fully maintained up to the most recent assessments after POEM (range 7-44 months).in our seven patients, POEM was a highly effective treatment for patients with troublesome symptoms related to atypical spastic esophageal motility disorders.

Background High-resolution manometric studies below the stomach are rare due to technical limitations of traditional manometry catheters. Consequently, specific motor patterns and their impact on gastric and small bowel function are not well understood. High-resolution manometry was used to record fed-state motor patterns in the antro-jejunal segment and relate these to fasting motor function. Methods Antro-jejunal pressures were monitored in 15 healthy females using fiber-optic manometry (72 sensors at 1 cm intervals) before and after a high-nutrient drink. Key results Postprandial motility showed a previously unreported transition point 18.8 cm (range 13-28 cm) beyond the antro-pyloric junction. Distal to the transition, a zone of non-propagating, repetitive pressure events (11.5 ± 0.5 cpm) were dominant in the fed state. We have named this activity, the duodeno-jejunal complex (DJC). Continuous DJC activity predominated, but nine subjects also exhibited intermittent clusters of DJC activity, 7.4 ± 4.9/h, lasting 1.4 ± 0.55 minutes, and 3.8 ± 1.2 minutes apart. DJC activity was less prevalent during fasting (3.6 ± 3.3/h; P = .04). 78% of fed and fasting state propagating antro-duodenal pressure events terminated proximally or at the transition point and were closely associated with DJC clusters. Conclusions and inferences High-resolution duodeno-jejunal manometry revealed a previously unrecognized transition point and associated motor pattern extending into the jejunum, consistent with the duodenal brake previously identified fluoroscopically. Timing suggests DJC activity is driven by chyme stimulating duodenal mucosal chemosensors. These findings indicate that the duodenum and proximal jejunum consists of two major functional motor regions.

BACKGROUND & AIMS: We aimed to develop and validate a deep-learning computer-aided detection (CAD) system, suitable for use in real time in clinical practice, to improve endoscopic detection of early neoplasia in patients with Barrett's esophagus (BE). METHODS: We developed a hybrid ResNet-UNet model CAD system using 5 independent endoscopy data sets. We performed pretraining using 494,364 labeled endoscopic images collected from all intestinal segments. Then, we used 1704 unique esophageal high-resolution images of rigorously confirmed early-stage neoplasia in BE and nondysplastic BE, derived from 669 patients. System performance was assessed by using data sets 4 and 5. Data set 5 was also scored by 53 general endoscopists with a wide range of experience from 4 countries to benchmark CAD system performance. Coupled with histopathology findings, scoring of images that contained early-stage neoplasia in data sets 2-5 were delineated in detail for neoplasm position and extent by multiple experts whose evaluations served as the ground truth for segmentation. RESULTS: The CAD system classified images as containing neoplasms or nondysplastic BE with 89% accuracy, 90% sensitivity, and 88% specificity (data set 4, 80 patients and images). In data set 5 (80 patients and images) values for the CAD system vs those of the general endoscopists were 88% vs 73% accuracy, 93% vs 72% sensitivity, and 83% vs 74% specificity. The CAD system achieved higher accuracy than any of the individual 53 nonexpert endoscopists, with comparable delineation performance. CAD delineations of the area of neoplasm overlapped with those from the BE experts in all detected neoplasia in data sets 4 and 5. The CAD system identified the optimal site for biopsy of detected neoplasia in 97% and 92% of cases (data sets 4 and 5, respectively). CONCLUSIONS: We developed, validated, and benchmarked a deep-learning computer-aided system for primary detection of neoplasia in patients with BE. The system detected neoplasia with high accuracy and near-perfect delineation performance. The Netherlands National Trials Registry, Number: NTR7072. ispartof: GASTROENTEROLOGY vol:158 issue:4 pages:915-+ ispartof: location:United States status: published

Lectures are seldom so good that they cannot be improved; so it is often a good idea to ask ourselves when they are over, “What went well”? and “What could I do better next time”? To help us to evaluate our performance in a lecture we might choose to ask for student feedback, peer review or take time ourselves for personal reflection.

Structural electrolytes provide mechanical properties approaching structural resin combined with a high degree of ionic conductivity. Here, structural electrolytes based on bisphenol A diglycidyl ether and the ionic liquid 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl) imide (EMIM-TFSI) were synthesised through reaction induced phase separation (RIPS) using isophorone diamine (iPDA) as a curing agent. The microstructure and properties of the resulting materials were controlled through both the initial formulations and the curing temperature. Curing at room temperature generated a bi-continuous structure and improved both mechanical performance and ionic conductivity of the resulting structural electrolytes. The balance between properties can be systematically adjusted; for example, a promising Young’s modulus of 800 MPa was obtained simultaneously with an ionic conductivity of 0.28 mS cm−1, for a formulation containing 35 vol% EMIM-TFSI. The lengthscale of the structural features was reduced by an order of magnitude by introducing multifunctional block-copolymers (MF-bcP) based on glycidyl methacrylate (GMA) and quaternised (2-dimethylamino)ethyl methacrylate (DMAEMA). Small angle neutron scattering (SANS), obtained during curing, identified at least two structural phases of different length scale, for the formulations containing MF-bcP, in agreement with microstructures observed using scanning electron microscopy. Such structural electrolytes may be required when using structural electrodes that also have finer characteristic lengthscales. The addition of the MF-bcP to formulations containing 35 vol% EMIM-TFSI produced structural electrolytes with a Young’s modulus of 530 MPa and an ionic conductivity of 0.64 mS cm−1.

As the style of healthcare delivery and patient expectations of medical care changes, there is a move toward more patient care and investigation being supplied beyond hospital wards in outpatient and other ambulatory care venues. Arguments are now being made that more undergraduate teaching should be provided in these venues where clinical problems more appro­ priate for student learning can be seen. But where can such venues be found, how can student learning be supported in these situations and who can help in student teaching beyond the traditional hospital wards?

High-quality data regarding the efficacy of acid-suppressive treatment for unexplained chest pain are lacking. The aim of this study was to evaluate the efficacy of esomeprazole in primary-care treatment of patients with unexplained chest pain stratified for frequency of reflux/regurgitation symptoms.Patients with a ≥ 2-week history of unexplained chest pain (unrelated to gastroesophageal reflux) who had at least moderate pain on ≥ 2 of the last 7 days were stratified by heartburn/regurgitation frequency (≤ 1 day/week (stratum 1) vs. ≥ 2 days/week (stratum 2)) and randomized to 4 weeks of double-blind treatment with twice-daily esomeprazole 40 mg or placebo. Chest pain relief during the last 7 days of treatment (≤ 1 day with minimal symptoms assessed daily using a 7-point scale) was analyzed by stratum in keeping with the predetermined analysis plan.Overall, 599 patients (esomeprazole: 297, placebo: 302) were randomized. In stratum 1, more esomeprazole than placebo recipients achieved chest pain relief (38.7% vs. 25.5%; P=0.018); no between-treatment difference was observed in stratum 2 (27.2% vs. 24.2%; P=0.54). However, esomeprazole was superior to placebo in a post-hoc analysis of the whole study population (combined strata; 33.1% vs. 24.9%; P=0.035).A 4-week course of high-dose esomeprazole provided statistically significant relief of unexplained chest pain in primary-care patients who experienced infrequent or no heartburn/regurgitation, but there was no such significant reduction in patients with more frequent reflux symptoms.

Summary This paper presents 21 new radiocarbon dates for Iron Age burials excavated at Wetwang Slack, East Yorkshire, including three chariot burials. The dates are analysed using a Bayesian approach, along with previous dates from the cemetery and from other chariot burials in the region. The model suggests that regular burial at Wetwang spanned the third and earlier second centuries cal BC, a shorter period than once thought, whilst the chariot burials all belong to a short-lived horizon centred on 200 cal BC. The dating of brooch types present in the burials is also reassessed. Our results imply that brooches of La Tene D form appeared in Britain in the later second century cal BC, in line with Continental evidence, but reinforcing the void in the later Iron Age sequence revealed in a recent study of decorated metalwork. Both this apparent gap and the end of the classic East Yorkshire mortuary tradition may well be manifestations of the more general changes that swept across Europe at this period, ushering in the new forms of political organization and social practices that define the Late Iron Age.

Esophageal peristalsis and basal gastroesophageal junction (GEJ) pressure correlate poorly with dysphagia. To determine intraluminal pressures that reflect GEJ function and to determine manometric correlates for dysphagia before and after fundoplication. The relationships between maximal intrabolus pressure, residual GEJ relaxation pressure and peak peristaltic pressure for water swallows were determined in normal volunteers and patients with reflux disease before and after fundoplication. GEJ anatomy was assessed by radiological, endoscopic and surgical criteria, whilst dysphagia was measured with a validated composite dysphagia score. Dysphagia was significantly associated with lower peak peristaltic pressure in the distal esophagus and the presence of a hiatus hernia preoperatively, as well as higher residual pressure on GEJ relaxation postoperatively. Peak distal peristaltic pressure and residual GEJ relaxation pressure were predictors of intrabolus pressure after total fundoplication (p

Pharyngeal manometry and impedance provide information on swallow function. We developed a new analysis approach for assessment of aspiration risk.We studied 20 patients (30-95 years old) with suspected aspiration who were referred for videofluoroscopy, along with controls (ages 24-47 years). The pharyngeal phase of liquid bolus swallowing was recorded with manometry and impedance. Data from the first swallow of a bolus and subsequent clearing swallows were analyzed. We scored fluoroscopic evidence of aspiration and investigated a range of computationally derived functional variables. Of these, 4 stood out as having high diagnostic value: peak pressure (PeakP), pressure at nadir impedance (PNadImp), time from nadir impedance to peak pressure (TNadImp-PeakP), and the interval of impedance drop in the distal pharynx (flow interval).During 54 liquid, first swallows and 40 clearing swallows, aspiration was observed in 35 (13 patients). Compared to those of controls, patient swallows were characterized by a lower PeakP, higher PNadImp, longer flow interval, and shorter TNadImp-PeakP. A Swallow Risk Index (SRI), designed to identify dysfunctions associated with aspiration, was developed from iterative evaluations of variables. The average first swallow SRI correlated with the average aspiration score (r = 0.846, P.00001 for Spearman Rank Correlation). An average SRI of 15, when used as a cutoff, predicted aspiration during fluoroscopy for this cohort (κ = 1.0).Pressure-flow variables derived from automated analysis of combined manometric/impedance measurements provide valuable diagnostic information. When combined into an SRI, these measurements are a robust predictor of aspiration.

Background and Aim: Helicobacter pylori infection remains common in East Asia, though its prevalence is decreasing in Western countries. H. pylori-related atrophic gastritis (AG) may reduce the likelihood of gastroesophageal reflux disease (GERD). We investigated the prevalence of H. pylori infection and AG and their association with endoscopic findings and symptom-defined GERD in Shanghai. Methods: A representative random sample of 3600 Shanghai residents aged 18–80 years was invited to complete a general information questionnaire and a Chinese version of the Reflux Disease Questionnaire, to provide blood samples for H. pylori serology and pepsinogen (PG) I/II assay (to detect AG, defined as PGI

Interpretation of exploding knowledge about Barrett's esophagus is impaired by use of several conflicting definitions. Because any histological type of esophageal columnar metaplasia carries risk for esophageal adenocarcinoma, the diagnosis of Barrett's esophagus should no longer require demonstration of intestinal-type metaplasia. Endoscopic recognition and grading of Barrett's esophagus remains a significant source of ambiguity. Reflux disease is a key factor for development of Barrett's esophagus, but other factors must underlie its development, since it occurs in only a minority of reflux disease patients. Neither antireflux surgery nor proton pump inhibitor (PPI) therapy has major impacts on cancer risk. Within a year, a major trial should indicate whether low-dose aspirin usefully reduces cancer risk. The best referral centers have transformed the accuracy of screening and surveillance for early curable esophageal adenocarcinoma by use of enhanced and novel endoscopic imaging, visually-guided, rather than blind biopsies and by partnership with expert pathologists. General endoscopists now need to upgrade their skills and equipment so that they can rely mainly on visual targeting of biopsies on mucosal areas of concern in their surveillance practice. General pathologists need to greatly improve their interpretation of biopsies. Endoscopic therapy now achieves very high rates of cure of high-grade dysplasia and esophageal adenocarcinoma with minimal morbidity and risk. Such results will only be achieved by skilled interventional endoscopists. Esophagectomy should now be mainly restricted to patients whose cancer has extended into and beyond the submucosa. Weighing risks and benefits in the management of Barrett's esophagus is difficult, as is the process of adequately informing patients about their specific cancer risk.

Objective The aim of this study was to determine the accuracy of the diagnosis of gastro-oesophageal reflux disease (GORD) by the Reflux Disease Questionnaire (RDQ), family practitioners, gastroenterologists and a test of esomeprazole therapy. Methods This was a single-blind, single-arm study over 3–4 weeks from September 2005 to November 2006. Each symptom-based diagnostic assessment was made blinded to prior diagnoses. Patients were those presenting to their family practitioner with troublesome upper gastrointestinal symptoms (n=308). The RDQ was completed and a symptom-based diagnosis was made by the family practitioner. Placebo esomeprazole was started. Gastroenterologists made a symptom-based diagnosis and then performed endoscopy with 48 h oesophageal pH and symptom association monitoring to determine the presence/absence of GORD. Symptoms were recorded during treatment with 40 mg of esomeprazole for 2 weeks. The main outcome measure was RDQ scoring for the presence of GORD compared with symptom-based diagnosis by family physicians and gastroenterologists. Results GORD was present in 203/308 (66%) patients. Only 49% of the patients with GORD selected either heartburn or regurgitation as the most troublesome symptom. Sensitivity and specificity, respectively, of the symptom-based diagnosis of GORD, were 62% and 67% for the RDQ, 63% and 63% for family practitioners, and 67% and 70% for gastroenterologists. Symptom response to esomeprazole was neither sensitive nor specific for the diagnosis of GORD. Conclusions The RDQ, family practitioners and gastroenterologists have moderate and similar accuracy for diagnosis of GORD. Symptom response to a 2 week course of 40 mg of esomeprazole does not add diagnostic precision. Clinical trial number NCT00291746.

The last 50 years have seen a transformation in the understanding and treatment of reflux disease. The development and wide use of flexible endoscopy and progressively more sophisticated approaches to measurement of pathophysiological factors have been major drivers of advances. The recognition and progressive elucidation of the mechanical events that comprise the transient lower esophageal sphincter relaxation and how they lead to reflux provide a novel and firm foundation for tailoring therapies that act directly to reduce occurrence of reflux episodes, either surgically or pharmacologically. Novel GABAB agonist drugs have been shown to inhibit transient relaxations and are currently being evaluated in clinical trials on patients with reflux disease. Better understanding has extended to recognition of the extraordinarily high prevalence of reflux disease and of the ability of proton pump inhibitor drugs to deliver major benefits to a high proportion of patients with reflux disease. The life of the Gastroenterological Society of Australia has spanned the period of these major advances. A large number of the members of the Society and their associates have contributed substantially to these advances.

Gastroesophageal reflux disease (GERD) affects >10% of the Western population. Conventionally, GERD is treated by reducing gastric acid secretion, which is effective in most patients but inadequate in a significant minority. We describe a new therapeutic approach for GERD, based on inhibition of transient lower esophageal sphincter relaxation (TLESR) with a proposed peripherally acting GABA(B) receptor agonist, (R)-(3-amino-2-fluoropropyl)phosphinic acid (AZD3355). AZD3355 potently stimulated recombinant human GABA(B) receptors and inhibited TLESR in dogs, with a biphasic dose-response curve. In mice, AZD3355 produced considerably less central side effects than the prototypical GABA(B) receptor agonist baclofen but evoked hypothermia at very high doses (blocked by a GABA(B) receptor antagonist and absent in GABA(B)-/- mice). AZD3355 and baclofen differed markedly in their distribution in rat brain; AZD3355, but not baclofen, was concentrated in circumventricular organs as a result of active uptake (shown by avid intracellular sequestration) and related to binding of AZD3355 to native GABA transporters in rat cerebrocortical membranes. AZD3355 was also shown to be transported by all four recombinant human GABA transporters. AR-H061719 [(R/S)-(3-amino-2-fluoropropyl)phosphinic acid], (the racemate of AZD3355) inhibited the response of ferret mechanoreceptors to gastric distension, further supporting its peripheral site of action on TLESR. In summary, AZD3355 probably inhibits TLESR through stimulation of peripheral GABA(B) receptors and may offer a potential new approach to treatment of GERD.

In 5 experiments, we studied precautionary decisions in which participants decided whether or not to buy insurance with specified cost against an undesirable event with specified probability and cost. We compared the risks taken for precautionary decisions with those taken for equivalent monetary gambles. Fitting these data to Tversky and Kahneman's (1992) prospect theory, we found that the weighting function required to model precautionary decisions differed from that required for monetary gambles. This result indicates a failure of the descriptive invariance axiom of expected utility theory. For precautionary decisions, people overweighted small, medium-sized, and moderately large probabilities-they exaggerated risks. This effect is not anticipated by prospect theory or experience-based decision research (Hertwig, Barron, Weber, & Erev, 2004). We found evidence that exaggerated risk is caused by the accessibility of events in memory: The weighting function varies as a function of the accessibility of events. This suggests that people's experiences of events leak into decisions even when risk information is explicitly provided. Our findings highlight a need to investigate how variation in decision content produces variation in preferences for risk.

The Los Angeles Classification for diagnosis and grading of reflux oesophagitis, first discussed at the 1994 World Congress of Gastroenterology, was published in its definitive form in 1999. The product of a demanding validation process, it consistently predicts the outcome of acid suppressant therapy, correlates with oesophageal acid exposure, and is the most reproducible and practical of oesophagitis grading systems. The attributes of the classification, which enhance the specificity of communication on reflux oesophagitis, are widely recognized, as it is now by far the most widely used method for description of reflux oesophagitis. Exclusion of minimal oesophageal mucosal change is, however, regarded as a significant limitation by some users, especially in Japan. Some data suggest that minimal changes may now be recognized with modern endoscopes; if this claim can be adequately validated, formal addition of criteria for minimal change could significantly improve the sensitivity of endoscopy for reflux disease.

To characterize gastroesophageal reflux episodes and esophageal acid clearance in patients with reflux esophagitis, we obtained 12-hour overnight esophageal pH and manometry recordings in 20 patients with macroscopic reflux esophagitis and in 15 healthy volunteers. Compared to the control subjects, the patients had less pressure in the lower esophageal sphincter (LES) and higher rates of reflux, acid clearance time, and esophageal acid exposure. However, many patients had normal values for one or more of these variables. Transient LES relaxation accounted for 96% of reflux episodes in control subjects and 60% in patients. The remaining 40% of reflux episodes in patients occurred as stress or free reflux. In the control subjects, only one reflux episode occurred during estimated sleep. Of 22 reflux episodes during estimated sleep in patients, most were associated with low basal LES pressure. During esophageal acid clearance, the major esophageal motor event was swallow-induced peristalsis rather than secondary peristalsis. We conclude that esophagitis patients have lower LES pressures, more reflux episodes, impaired esophageal acid clearance, and more esophageal exposure to acid than control subjects. Individual patients, however, exhibit heterogeneous abnormalities with respect to these variables. Transient LES relaxation is the major mechanism of gastroesophageal reflux in both patients and healthy subjects.

OBJECTIVES: AZD0865 is a gastric acid-suppressing agent that has a rapid onset of action and long duration of effect. This double-blind, randomized, multicenter study investigated the efficacy and safety of AZD0865 in the treatment of patients with nonerosive reflux disease (NERD). METHODS: Patients with troublesome heartburn for at least 6 months and no evidence of erosions at endoscopy were randomized to receive AZD0865 (25, 50, or 75 mg/day) or esomeprazole 20 mg/day, for 4 wk. Throughout the treatment period, patients reported the presence and intensity of heartburn and other NERD symptoms twice daily using an electronic diary. Twenty-four-hour ambulatory intraesophageal/intragastric pH monitoring was performed in a subset of patients on day 14. RESULTS: A total of 1,469 patients were randomized. The median time to sustained absence of heartburn (for 7 consecutive days) was approximately 12 days for all treatment groups and did not differ significantly for any of the AZD0865 doses or compared with esomeprazole. There were no significant differences among treatment groups in the cumulative incidence of sustained absence of heartburn during 4 wk treatment (i.e., 65-70%). The percentage of time for which intragastric pH was greater than 4 was significantly greater for AZD0865 75 mg/day compared with esomeprazole 20 mg (75% vs 60%, P < 0.05). AZD0865 was generally well tolerated although reversible elevations of liver transaminases occurred in some patients receiving the agent. CONCLUSIONS: AZD0865 did not provide clinical benefit over esomeprazole 20 mg in the management of patients with NERD.

Objectives: In mild gastroesophageal reflux disease, which accounts for the great majority of cases, the major burden of reflux occurs during daytime hours, after food intake. The aim of these analyses was to evaluate intragastric pH control during the typical 14-hour daytime awake period by proton-pump inhibitors (PPIs) given at over-the-counter (OTC) dosages. Methods: In one double-blind and three open-label, randomized, crossover studies, intragastric pH was monitored for 24 hours on day 5 of treatment. The 24-hour data have been reported previously. Post hoc analyses reassessed these studies for the 14-hour daytime period, comparing esomeprazole 20 mg with currently available OTC PPIs omeprazole, pantoprazole (not available in the US) and lansoprazole. Results: Subjects maintained intragastric pH >4 for a significantly greater mean percentage of the 14-hour daytime period with esomeprazole 20 mg compared with any of the PPI comparators at OTC dosages. Geometric mean ratios (95% confidence intervals) for esomeprazole 20 mg versus the comparators were: 1.45 (1.14–1.85; p = 0.003) versus omeprazole 20 mg; 2.50 (2.01–3.11; p < 0.0001) versus pantoprazole 20 mg; and 1.69 (1.46–1.97; p < 0.0001) and 1.89 (1.05–3.37; p = 0.03) versus lansoprazole 15 mg. A greater proportion of subjects had better pH control with esomeprazole than with the other PPIs (range: 69–97%). Conclusions: Across the 14-hour daytime period, esomeprazole 20 mg once daily given 30 minutes before breakfast for 5 days provided acid control for a significantly greater average proportion of time versus the PPI comparators omeprazole, pantoprazole and lansoprazole at currently available OTC dosages.

Background & Aims Histologic criteria have been refined for the diagnosis of gastroesophageal reflux disease (GERD). We aimed to evaluate these criteria for the assessment of GERD and to measure interassessor agreement. Methods We performed a post hoc analysis of data from the Diamond study (NCT 00291746), conducted in Europe and Canada on adults with frequent upper gastrointestinal symptoms who had not taken a proton pump inhibitor in the previous 2 months. GERD was diagnosed based on the presence of 1 or more of the following: reflux esophagitis, pathologic esophageal acid exposure, and/or positive symptom–acid association probability. Nonerosive reflux disease was defined as the presence of pathologic esophageal acid exposure and/or a positive symptom–acid association probability, but no reflux esophagitis. Biopsies collected from 336 patients from 0.5 cm and 2.0 cm above the Z line were evaluable; they were analyzed independently at pathology centers in Germany and Italy (biopsies from 258 and 195 patients, respectively). The primary outcomes were the accuracy of histologic criteria for the diagnosis of GERD, defined by endoscopy and pH monitoring, and interassessor agreement on histologic criteria. Results At the assessment site for basal cell layer thickness, total epithelial thickness was the best-performing criterion for diagnosis of investigation-defined GERD; it also identified nonerosive reflux disease, reflux esophagitis, and pathologic esophageal acid exposure at 0.5 cm and 2.0 cm above the Z line. Basal cell layer thickness and presence of dilated intercellular spaces did not identify patients with GERD. Among the criteria tested, the best agreement between assessments carried out at the 2 pathology centers was for total epithelial thickness at 0.5 cm and 2.0 cm above the Z line. Conclusions Based on an analysis of 336 patients with frequent upper gastrointestinal symptoms, total epithelial thickness is a robust histologic marker for GERD.

Interventional cardiologists act as leaders every time they step into a catheterization laboratory (cath lab), but leadership training is rarely included in cardiology training programs. Cath lab physicians should cultivate and practice effective leadership skills. Specifically, (1) before each procedure assess whether the cath lab team is prepared; (2) delegate authority to trainees and team members when appropriate; (3) use every procedure to improve the performance of team members through teaching, coaching, and mentorship; (4) debrief the team after adverse events; (5) develop the traits, styles, and skills associated with successful leadership; and (6) provide team training for the cath lab team.

OBJECTIVE: To evaluate the effect of baclofen, a gamma-amino-butyric-acid B receptor agonist that inhibits transient lower esophageal sphincter relaxation (TLESR), on the rates of TLESR, gastroesophageal reflux (GER), and gastric emptying (GE) in children with GER disease. STUDY DESIGN: The efficacy of 0.5 mg/kg baclofen was evaluated in a randomized, double-blinded, placebo-controlled trial in 30 children. Patients were intubated with a manometric/pH assembly and given 250 mL of cow's milk. Esophageal motility and pH were then measured for 2 hours (control period). Baclofen or placebo was then administered, and 1 hour later 250 mL of milk was given again and measurements performed for another 2 hours (test period). The GE rate was measured by the (13)C octanoate breath test. RESULTS: Baclofen significantly reduced the incidence of TLESR (mean, 7.3 +/- 1.5 vs 3.6 +/- 1.2 TLESR/2 hours; P < .05) and acid GER (mean 4.2 +/- 0.7 vs 1.7 +/- 1.0 TLESR + GER/2 hours; P < .05) during the test period compared with the control period. Baclofen significantly accelerated the GE rate (median [interquartile range], GE(t1/2), 61 minutes [39, 81 minutes] vs 114 minutes [67, 170 minutes]; P < .05). Baclofen had no effect on the swallowing rate, pattern of esophageal peristalsis, or lower esophageal sphincter pressure. CONCLUSIONS: Baclofen reduces GER in children by inhibiting the triggering of TLESR. Baclofen also accelerates GE

The report from the HUNT Study provides the most convincing evidence yet that weight loss has beneficial effects on occurrence and severity of heartburn and regurgitation and their response to acid suppressant therapy. These data should re-invigorate clinicians to encourage weight loss in their reflux disease patients.

Vegetation plays a key role in the environmental cycling and fate of many organic chemicals. A compound's location on or within leaves will affect its persistence and significance; retention in surface compartments (i.e., the epicuticular wax and cuticle) renders the compound more susceptible to photodegradation and volatilization, while penetration into the epidermal cell walls or cytoplasm will enhance susceptibility to metabolism. Here, for the first time, methodologies which combine plant and PAH autofluorescence with two-photon excitation microscopy (TPEM) are used to visualize and quantify compound photodegradation on and within living plant leaves. Anthracene, fluoranthene, and phenanthrene were introduced to living leaves of Zea mays and monitored in real time, in control treatments, and when subject to UV-A radiation. Compound photodegradation was observed directly; different degradation rates occurred for different compounds (anthracene > fluoranthene > phenanthrene) and in different locations (...

To combine manometry and impedance to characterize the mechanisms of gastroesophageal reflux (GER) and to explore their relation to the rate of gastric emptying (GE) and body position.Ten healthy preterm infants (35 to 37 weeks' postmenstrual age) were studied with the use of a micromanometric/impedance assembly. Episodes of GER were identified by impedance, and the mechanism(s) of GER triggering and GER clearance were characterized. GE was determined with a C13Na-octanoate breath test.Gastroesophageal reflux episodes (n=89) were recorded, consisting of 74% liquid, 14% gas, and 12% mixed. Transient lower esophageal sphincter relaxation (TLESR) was the predominant mechanism of reflux, triggering 83% of GER. Of 92 TLESRs recorded, 27% were not associated with reflux. Infants studied in the right lateral position had significantly (P.01) more GER, a higher proportion of liquid GER (P.05), and faster GE (P.005) when compared with infants studied in the left lateral position.In healthy preterm infants, GER is predominantly liquid in nature. Right-side positioning is associated with increased triggering of TLESR and GER despite accelerating GE.

Background & Aims: The diagnosis and management of Barrett's esophagus (BE) are controversial. We conducted a critical review of the literature in BE to provide guidance on clinically relevant issues. Methods: A multidisciplinary group of 18 participants evaluated the strength and the grade of evidence for 42 statements pertaining to the diagnosis, screening, surveillance, and treatment of BE. Each member anonymously voted to accept or reject statements based on the strength of evidence and his own expert opinion. Results: There was strong consensus on most statements for acceptance or rejection. Members rejected statements that screening for BE has been shown to improve mortality from adenocarcinoma or to be cost-effective. Contrary to published clinical guidelines, they did not feel that screening should be recommended for adults over age 50, regardless of age or duration of heartburn. Members were divided on whether surveillance prolongs survival, although the majority agreed that it detects curable neoplasia and can be cost-effective in selected patients. The majority did not feel that acid-reduction therapy reduces the risk of esophageal adenocarcinoma but did agree that nonsteroidal antiinflammatory drugs are associated with a cancer risk reduction and are of promising (but unproven) value. Participants rejected the notion that mucosal ablation with acid suppression prevents adenocarcinoma in BE but agreed that this may be an appropriate strategy in a subgroup of patients with high-grade dysplasia. Conclusions: Based on this review of BE, the opinions of workshop members on issues pertaining to screening and surveillance are at variance with published clinical guidelines.

Plication of the gastroesophageal junction by endoscopic suturing has been reported to improve symptoms and reduce acid exposure in patients with gastroesophageal reflux disease (GERD). The mechanisms underlying these effects are not well defined. The aims of our study were to determine the impact of endoscopic suturing of the gastroesophageal junction on lower esophageal sphincter (LES) function in patients with GERD.In 15 patients (7 males) with GERD (heartburn, % time esophageal pH4 greater than 4%, +/- history of erosive esophagitis within 6 months), two plications were performed circumferentially 1 cm below the gastroesophageal junction. Endoscopy and combined postprandial esophageal manometry and pH monitoring were performed before and 6 months after treatment; 24-h ambulatory pH monitoring and symptom assessment were also performed before, and at 6 and 12 months after treatment.Six months after treatment, the rate of transient LES relaxations (tLESRs) was decreased by 37% (p0.05) and basal LES pressure had increased from 4.3 +/- 2.2 mmHg to 6.2 +/- 2.1 mmHg (p0.05). The rate of postprandial reflux events and acid exposure time were not altered. Endoscopic suturing significantly reduced 24-h esophageal acid exposure from 9.6% (9.0-12.1) to 7.4% (3.9-10.1) at 6 months, due predominantly to a reduction in upright acid exposure. The reduction in total 24-h acid exposure was sustained to 12 months. At repeat endoscopy, only one plication was evident in 6 patients (40%) at 6 months. Seven patients (47%) remained off medications at 6 and 12 months follow-up.In patients with GERD, endoscopic suturing of the gastroesophageal junction results in a reduction in the rate of tLESRs, and an increase in basal LES pressure. These changes in LES function result in only a modest reduction in gastroesophageal reflux.