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Recent studies have shown that chronic opioid use is associated with an increased risk of symptomatic esophageal motility disorders. Opioid-induced esophageal dysfunction (OIED) is most often identified in patients taking high doses of opioids. This condition is associated with poorer treatment outcomes than primary motility disorders and management of these cases is further complicated by the presence of chronic pain, opioid addiction, and physical and psychological comorbidity.We present the case of a 68-year-old Caucasian woman with OIED, induced by the chronic intake of low-dose Fentanyl and Tramadol prescribed to treat severe back pain. The clinical course highlights the sometimes difficult diagnosis and management of this recently recognized condition., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Background: Scintigraphy is used for overall assessment of gastric emptying. Adherence to an international consensus protocol is recommended to ensure quality; however, this has not been widely adopted because preparation of the "egg-beater" meal is inconvenient in clinical practice. In this report, we audit the tolerability and the results of gastric emptying scintigraphy with the 400 ml Tc-99 m-labeled liquid nutrient Nottingham Test Meal (NTM)., Methods: Results from 330 consecutive adult, non-diabetic patients with dyspeptic symptoms referred for gastric scintigraphy were analyzed. Gastric half-emptying time (T50) and validated measurements of early- and late-phase gastric emptying were acquired. Postprandial sensations of fullness, bloating, heartburn, nausea, and epigastric pain were recorded using 100 mm visual analog scales (VAS) before and 0, 30, and 90 min after NTM ingestion. Results were compared with those previously obtained in healthy subjects., Key Results: Almost all (98%) of the patients were able to consume the 400 ml NTM. Considering early- and late-phase gastric emptying, frequently observed patterns included normal early- with slow late-phase (25%) and fast early- with slow late-phase emptying (27%). Abnormal score of fullness and/ or dyspeptic symptoms were observed in 88% of dyspeptic patients. Abnormal fullness at T0 (after completed drink ingestion) was associated with slow late phase of gastric emptying, especially in women., Conclusions: Gastric scintigraphy with the NTM is simple to perform and well tolerated. Whether the identified abnormal gastric emptying patterns could predict different treatment outcome in patients with functional dyspepsia is the subject of ongoing prospective studies., (© 2022 The Authors. Neurogastroenterology & Motility published by John Wiley & Sons Ltd.)

Recurrent and persistent bouts of hiccups impact the quality of life by interfering with eating, social interaction and work. Popular home remedies, such as breath holding and drinking ice water, target activity in the vagal and phrenic nerves that are thought to trigger these repetitive, myoclonic contractions. However, the pathophysiology of hiccups and the mechanism by which any of these methods work are unclear. Indeed, so little is known that there is no agreement whether the 'Hic' sound is due to the abrupt closure of the epiglottis or the glottis, including the vocal cords.Investigations were performed in a 50-year-old, otherwise healthy male with recurrent hiccups, in whom contractions persisted for up to 4 hours. Hiccups were initiated by drinking carbonated soda. The aerodigestive tract was visualised by video fluoroscopy. Hiccups were terminated by drinking a non-viscous contrast agent through a forced inspiratory suction and swallow tool. This device requires significant suction pressure (-100 mm Hg) to draw fluid into the mouth and is effective in approximately 90% of cases. The images were analysed together with concurrent audio recordings to gain insight into 'what causes the 'hic' in hiccups' and how this commonplace but annoying problem can be treated., Competing Interests: Competing interests: AS reported non-financial support from the University of Texas Health Science Center at San Antonio; he is the patent inventor for the hiccup-relieving apparatus (the forced inspiratory suction and swallow tool (FISST)/ HiccAway), University of Texas licensed the device to Aim Dynamics and receives a royalty., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Measurement of breath hydrogen (H 2 ) and methane (CH 4 ) excretion after ingestion of test-carbohydrates is used for different diagnostic purposes. There is a lack of standardization among centers performing these tests and this, together with recent technical developments and evidence from clinical studies, highlight the need for a European guideline., Methods: This consensus-based clinical practice guideline defines the clinical indications, performance, and interpretation of H 2 -CH 4 -breath tests in adult and pediatric patients. A balance between scientific evidence and clinical experience was achieved by a Delphi consensus that involved 44 experts from 18 European countries. Eighty eight statements and recommendations were drafted based on a review of the literature. Consensus (≥80% agreement) was reached for 82. Quality of evidence was evaluated using validated criteria., Results: The guideline incorporates new insights into the role of symptom assessment to diagnose carbohydrate (e.g., lactose) intolerances and recommends that breath tests for carbohydrate malabsorption require additional validated concurrent symptom evaluation to establish carbohydrate intolerance. Regarding the use of breath tests for the evaluation of oro-cecal transit time and suspected small bowel bacterial overgrowth, this guideline highlights confounding factors associated with the interpretation of H 2 -CH 4 -breath tests in these indications and recommends approaches to mitigate these issues., Conclusion: This clinical practice guideline should facilitate pan-European harmonization of diagnostic approaches to symptoms and disorders, which are very common in specialist and primary care gastroenterology practice, both in adult and pediatric patients. In addition, it identifies areas of future research needs to clarify diagnostic and therapeutic approaches., (© 2021 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC. on behalf of United European Gastroenterology.)

Objective: Acid exposure time (AET) from ambulatory pH studies and reflux oesophagitis are independent measurements used by the Lyon classification to diagnose GORD. This study aimed to validate AET reference ranges and diagnostic thresholds by analysis of 96-hour wireless pH studies from healthy, asymptomatic controls (HCs) and patients with and without oesophagitis., Design: HC and consecutive patients referred for wireless pH studies (off acid suppressants for >7 days) underwent 96-hour pH studies at two tertiary referral centres. Erosive oesophagitis was categorised by the Los Angeles (LA) classification. Linear regression and receiver operating curve (ROC) analysis were performed to define optimal diagnostic cut-offs., Results: Prolonged, 96-hour pH studies were completed in 39 HCs (age 28 (18-53) years, 72% female) and 944 patients (age 46 (16-85) years, 65% female), of whom 136 (14.5%) had reflux oesophagitis. Median AET in HC was 1.3% (upper 95th percentile 4.6%) for any study day and 2.6% (upper 95th percentile 6.9%) for the worst day (24-hour period) during the study. ROC analysis for average AET differentiated HC from patients with moderate-to-severe oesophagitis (LA BCD; sensitivity 87%, specificity 95%, positive predictive value (PPV) 59%, negative predictive value 99% for a cut-off AET of 4.3%; area under the receiver operating curve 0.95). Specificity was higher, but PPV was substantially lower for severe oesophagitis (LA CD). 'Worst-day' analysis provided similar results; however, day-to-day variability was high., Conclusion: Diagnostic thresholds for average AET were identified that accurately discriminate between HCs and patients with erosive oesophagitis. The findings provide conditional support for diagnostic criteria for GORD proposed by the Lyon Consensus., Competing Interests: Competing interests: MRF has received research and/or educational funding from Medtronic, MMS/Laborie, Sandhill Scientific/Diversatek and Reckitt Benckiser. R-IR, ET, SZ, JMD, JJ, FW, TW: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

The need to classify targets and features in high-resolution imagery is of interest in applications such as detection of landmines in ground penetrating radar and tumors in medical ultrasound images. Convolutional neural networks (CNNs) trained using extensive datasets are being investigated recently. However, large CNNs and wavelet scattering networks (WSNs), which share similar properties, have extensive memory requirements and are not readily extendable to other datasets and architectures-and especially in the context of adaptive and online learning. In this paper, we quantitatively study several quantization schemes on WSNs designed for target classification using X-band synthetic aperture radar (SAR) data and investigate their robustness to low signal-to-noise ratio (SNR) levels. A detailed study was conducted on the tradeoffs involved between the various quantization schemes and the means of maximizing classification performance for each case. Thus, the WSN-based quantization studies performed in this investigation provide a good benchmark and important guidance for the design of quantized neural networks architectures for target classification.

Introduction: 13 C-breath tests are valuable, noninvasive diagnostic tests that can be widely applied for the assessment of gastroenterological symptoms and diseases. Currently, the potential of these tests is compromised by a lack of standardization regarding performance and interpretation among expert centers., Methods: This consensus-based clinical practice guideline defines the clinical indications, performance, and interpretation of 13 C-breath tests in adult and pediatric patients. A balance between scientific evidence and clinical experience was achieved by a Delphi consensus that involved 43 experts from 18 European countries. Consensus on individual statements and recommendations was established if ≥ 80% of reviewers agreed and <10% disagreed., Results: The guideline gives an overview over general methodology of 13 C-breath testing and provides recommendations for the use of 13 C-breath tests to diagnose Helicobacter pylori infection, measure gastric emptying time, and monitor pancreatic exocrine and liver function in adult and pediatric patients. Other potential applications of 13 C-breath testing are summarized briefly. The recommendations specifically detail when and how individual 13 C-breath tests should be performed including examples for well-established test protocols, patient preparation, and reporting of test results., Conclusion: This clinical practice guideline should improve pan-European harmonization of diagnostic approaches to symptoms and disorders, which are very common in specialist and primary care gastroenterology practice, both in adult and pediatric patients. In addition, this guideline identifies areas of future clinical research involving the use of 13 C-breath tests., (© 2021 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

The Chicago Classification v4.0 (CCv4.0) is the updated classification scheme for esophageal motility disorders using metrics from high-resolution manometry (HRM). A key feature of CCv.4.0 is the more rigorous and expansive protocol that incorporates single wet swallows acquired in different positions (supine, upright) and provocative testing, including multiple rapid swallows and rapid drink challenge. Additionally, solid bolus swallows, solid test meal, and/or pharmacologic provocation can be used to identify clinically relevant motility disorders and other conditions (eg, rumination) that occur during and after meals. The acquisition and analysis for performing these tests and the evidence supporting their inclusion in the Chicago Classification protocol is detailed in this technical review. Provocative tests are designed to increase the diagnostic sensitivity and specificity of HRM studies for disorders of esophageal motility. These changes attempt to minimize ambiguity in prior iterations of Chicago Classification, decrease the proportion of HRM studies that deliver inconclusive diagnoses and increase the number of patients with a clinically relevant diagnosis that can direct effective therapy. Another aim in establishing a standard manometry protocol for motility laboratories around the world is to facilitate procedural consistency, improve diagnostic reliability, and promote collaborative research., (© 2021 John Wiley & Sons Ltd.)

Chicago Classification v4.0 (CCv4.0) is the updated classification scheme for esophageal motility disorders using metrics from high-resolution manometry (HRM). Fifty-two diverse international experts separated into seven working subgroups utilized formal validated methodologies over two-years to develop CCv4.0. Key updates in CCv.4.0 consist of a more rigorous and expansive HRM protocol that incorporates supine and upright test positions as well as provocative testing, a refined definition of esophagogastric junction (EGJ) outflow obstruction (EGJOO), more stringent diagnostic criteria for ineffective esophageal motility and description of baseline EGJ metrics. Further, the CCv4.0 sought to define motility disorder diagnoses as conclusive and inconclusive based on associated symptoms, and findings on provocative testing as well as supportive testing with barium esophagram with tablet and/or functional lumen imaging probe. These changes attempt to minimize ambiguity in prior iterations of Chicago Classification and provide more standardized and rigorous criteria for patterns of disorders of peristalsis and obstruction at the EGJ., (© 2020 John Wiley & Sons Ltd.)

Since publication of Chicago Classification version 3.0 in 2015, the clinical and research applications of high-resolution manometry (HRM) have expanded. In order to update the Chicago Classification, an International HRM Working Group consisting of 52 diverse experts worked for two years and utilized formally validated methodologies. Compared with the prior iteration, there are four key modifications in Chicago Classification version 4.0 (CCv4.0). First, further manometric and non-manometric evaluation is required to arrive at a conclusive, actionable diagnosis of esophagogastric junction (EGJ) outflow obstruction (EGJOO). Second, EGJOO, distal esophageal spasm, and hypercontractile esophagus are three manometric patterns that must be accompanied by obstructive esophageal symptoms of dysphagia and/or non-cardiac chest pain to be considered clinically relevant. Third, the standardized manometric protocol should ideally include supine and upright positions as well as additional manometric maneuvers such as the multiple rapid swallows and rapid drink challenge. Solid test swallows, postprandial testing, and pharmacologic provocation can also be considered for particular conditions. Finally, the definition of ineffective esophageal motility is more stringent and now encompasses fragmented peristalsis. Hence, CCv4.0 no longer distinguishes between major versus minor motility disorders but simply separates disorders of EGJ outflow from disorders of peristalsis., (© 2020 John Wiley & Sons Ltd.)

Lactose is the main source of calories in milk, an essential nutriedigestion, patients with visceral hypersensitivity nt in infancy and a key part of the diet in populations that maintain the ability to digest this disaccharide in adulthood. Lactase deficiency (LD) is the failure to express the enzyme that hydrolyses lactose into galactose and glucose in the small intestine. The genetic mechanism of lactase persistence in adult Caucasians is mediated by a single C→T nucleotide polymorphism at the LCTbo -13'910 locus on chromosome-2. Lactose malabsorption (LM) refers to any cause of failure to digest and/or absorb lactose in the small intestine. This includes primary genetic and also secondary LD due to infection or other conditions that affect the mucosal integrity of the small bowel. Lactose intolerance (LI) is defined as the onset of abdominal symptoms such as abdominal pain, bloating and diarrhoea after lactose ingestion by an individual with LM. The likelihood of LI depends on the lactose dose, lactase expression and the intestinal microbiome. Independent of lactose digestion, patients with visceral hypersensitivity associated with anxiety or the Irritable Bowel Syndrome (IBS) are at increased risk of the condition. Diagnostic investigations available to diagnose LM and LI include genetic, endoscopic and physiological tests. The association between self-reported LI, objective findings and clinical outcome of dietary intervention is variable. Treatment of LI can include low-lactose diet, lactase supplementation and, potentially, colonic adaptation by prebiotics. The clinical outcome of these treatments is modest, because lactose is just one of a number of poorly absorbed carbohydrates which can cause symptoms by similar mechanisms., Competing Interests: Competing interests: MF has received research funding from Nestlé International for studies of lactose digestion and tolerance., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Esophageal manometry provides a detailed evaluation of esophageal contractility and, therefore, represents the reference method for diagnosis of esophageal motility disorders. Significance and clinical relevance have been further increased by implementation of high-resolution esophageal manometry (HRM), which reveals the functional anatomy of the esophagus in a visually-intuitive manner. The current 3 rd version of the international Chicago Classification (CC v3.0) gives standardized recommendations on performance and interpretation of HRM and serves as the basis for much of this expert consensus document. However, CC v3.0 gives only limited information with regards to the function of the lower and upper esophageal sphincters, the use of adjunctive tests including solid test meals and long-term ambulatory HRM measurements. In this expert consensus, we describe how to perform and interpret HRM on the basis of the CC v3.0 with additional recommendations based on the results of recent, high-quality clinical studies concerning the use of this technology to assess the causes of esophageal symptoms in a variety of clinical scenarios., Competing Interests: JK: Finanzielle Unterstützung für Forschungsvorhaben und Durchführung von Fortbildungsveranstaltungen sowie Honorare für Vorträge von Given Imaging/Medtronic und Standard Instruments.MF: Finanzielle Unterstützung für Forschungsvorhaben und Durchführung von Fortbildungsveranstaltungen sowie Honorare für Vorträge oder Teilnahme an Advisory Board-Sitzungen von Given Imaging / Medtronic, Medical Measurement Systems, Sandhill Scientific Instruments und Mui Scientific.Bei den anderen Autoren bestehen keine potenziellen Interessenkonflikte., (© Georg Thieme Verlag KG Stuttgart · New York.)

Increased acid reflux after meals is a key feature of gastro-esophageal reflux disease (GERD) and is the most important cause for patient symptoms, particularly heartburn and acid regurgitation. Chronic acid exposure also predisposes to associated pathologies including reflux esophagitis, esophageal stricture, Barrett's esophagus, and Barrett's carcinoma (esophageal adenocarcinoma). The severity of esophageal symptoms and mucosal damage is related to two key factors, (i) the acidity of the refluxate, which depends primarily on the gastric secretory output and its distribution within the stomach, and (ii) the frequency and duration of reflux events which depends on the efficacy of the reflux barrier at the gastro-esophageal junction and the esophageal clearance function. The concept of the acid pocket is an attempt to bring these two factors into a unified patho-mechanism.The acid pocket describes an area of unbuffered, highly acidic, gastric secretion in the proximal stomach adjacent to the esophago-gastric junction (GEJ) which forms in the postprandial period and is the source of acid refluxate into the esophagus. It is observed both in healthy individuals as well as in reflux patients. However, the presence of a hiatus hernia and/or a weak lower esophageal sphincter in patients allows the acid pocket to encroach on the gastro-esophageal junction. This results in very high acid exposure of the squamous epithelium of the distal esophagus, leading to mucosal damage and symptoms. Recently, the acid pocket has been proposed as a target for pharmacological and surgical therapies of GERD. Proton pump inhibitors and related medications reduce its acidity; whereas, alginate preparations, prokinetics, and fundoplication displace it away from the gastro-esophageal junction., Competing Interests: Mark Fox hat Gelder für Forschung und / oder Bildungsveranstaltungen erhalten von Nestle Research International, AstraZeneca, Reckitt Benckiser, Given Imaging/Covidien, Medical Measurement Systems und Sandhill Scientific Instruments.Matthias Sauter: keine, (© Georg Thieme Verlag KG Stuttgart · New York.)

Symptoms related to abnormal gastrointestinal motility and function are common. Oropharyngeal and oesophageal dysphagia, heartburn, bloating, abdominal pain and alterations in bowel habits are among the most frequent reasons for seeking medical attention from internists or general practitioners and are also common reasons for referral to gastroenterologists and colorectal surgeons. However, the nonspecific nature of gastrointestinal symptoms, the absence of a definitive diagnosis on routine investigations (such as endoscopy, radiology or blood tests) and the lack of specific treatments make disease management challenging. Advances in technology have driven progress in the understanding of many of these conditions. This Review serves as an introduction to a series of Consensus Statements on the clinical measurements of gastrointestinal motility, function and sensitivity. A structured, evidence-based approach to the initial assessment and empirical treatment of patients presenting with gastrointestinal symptoms is discussed, followed by an outline of the contribution of modern physiological measurement on the management of patients in whom the cause of symptoms has not been identified with other tests. Discussions include the indications for and utility of high-resolution manometry, ambulatory pH-impedance monitoring, gastric emptying studies, breath tests and investigations of anorectal structure and function in day-to-day practice and clinical management.

Chronic diarrhoea is a common problem, hence clear guidance on investigations is required. This is an updated guideline from 2003 for the investigations of chronic diarrhoea commissioned by the Clinical Services and Standards Committee of the British Society of Gastroenterology (BSG). This document has undergone significant revision in content through input by 13 members of the Guideline Development Group (GDG) representing various institutions. The GRADE system was used to appraise the quality of evidence and grading of recommendations., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Clinical history, questionnaire data and response to antisecretory therapy are insufficient to make a conclusive diagnosis of GERD in isolation, but are of value in determining need for further investigation. Conclusive evidence for reflux on oesophageal testing include advanced grade erosive oesophagitis (LA grades C and D), long-segment Barrett's mucosa or peptic strictures on endoscopy or distal oesophageal acid exposure time (AET) >6% on ambulatory pH or pH-impedance monitoring. A normal endoscopy does not exclude GERD, but provides supportive evidence refuting GERD in conjunction with distal AET <4% and <40 reflux episodes on pH-impedance monitoring off proton pump inhibitors. Reflux-symptom association on ambulatory reflux monitoring provides supportive evidence for reflux triggered symptoms, and may predict a better treatment outcome when present. When endoscopy and pH or pH-impedance monitoring are inconclusive, adjunctive evidence from biopsy findings (histopathology scores, dilated intercellular spaces), motor evaluation (hypotensive lower oesophageal sphincter, hiatus hernia and oesophageal body hypomotility on high-resolution manometry) and novel impedance metrics (baseline impedance, postreflux swallow-induced peristaltic wave index) can add confidence for a GERD diagnosis; however, diagnosis cannot be based on these findings alone. An assessment of anatomy, motor function, reflux burden and symptomatic phenotype will therefore help direct management. Future GERD management strategies should focus on defining individual patient phenotypes based on the level of refluxate exposure, mechanism of reflux, efficacy of clearance, underlying anatomy of the oesophagogastric junction and psychometrics defining symptomatic presentations., Competing Interests: Competing interests: CPG: consulting: Ironwood, Torax, Quintiles; teaching and speaking: Medtronic, Diversatek, Reckitt-Benckiser. ES: consulting: AbbVie, Allergan, MSD, Takeda, Sofar, Janssen; teaching and speaking: Medtronic, Reckitt-Benckiser, Malesci, Zambon. FZ: research support: Medtronic, Sandhill Scientific; consulting: Allergan, Reckitt-Benckiser; speaking and teaching: Ipsen Pharma, Biocodex, Coloplast, Takeda, Vifor Pharma, Mayoly Spindler. PJK: consulting: Ironwood. FM: teaching and speaking: Laborie, Medtronic; consulting: Allergan, Endostim. AJPMS: none. MV: Vanderbilt University and Diversatek co-own patent on mucosal impedance technology. DS: research support: Diversatek, Reckitt-Benckiser; OMOM, Jinshan Science & Technology (Group) Co. Ltd., Chongqing, China. MRF: research support: Given Imaging/Covidien, Reckitt Benckiser, Mui Scientific. Educational events: Given Imaging/Covidien, MMS, Sandhill Scientific Instruments. Speaking and teaching: Given Imaging/Covidien, Reckitt Benckiser, Shire, Almirall. MV: consulting: Torax. RT: teaching: Laborie. JT: consulting: Ironwood. AJB: research support: Danone, Bayer; speaking and/or consulting: MMS, Astellas, AstraZeneca, Bayer, Almirall and Allergan. JP: research support: Impleo; speaking and/or consulting: Medtronic, Diversatek, Torax, Ironwood, Takeda, AstraZeneca; stock options: Crospon. SR: research support: Sandhill Scientific, Crospon; teaching: Medtronic; speaker: Mayoly Spindler., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: Current investigations of stomach function are based on small test meals that do not reliably induce symptoms and analysis techniques that rarely detect clinically relevant dysfunction. This study introduces the large 'Nottingham Test Meal' (NTM) for assessment of gastric motor and sensory function by non-invasive imaging., Methods: NTM comprises 400 mL liquid nutrient (0.75 kcal/mL) and 12 solid agar-beads (0 kcal) with known breaking strength. Gastric fullness and dyspeptic sensations were documented by 100 mm visual analogue scale (VAS). Gastric emptying (GE) were measured in 24 healthy volunteers (HVs) by gastric scintigraphy (GS) and magnetic resonance imaging (MRI). The contribution of secretion to gastric volume was assessed. Parameters that describe GE were calculated from validated models. Inter-observer agreement and reproducibility were assessed., Key Results: NTM produced moderate fullness (VAS ≥30) but no more than mild dyspeptic symptoms (VAS <30) in 24 HVs. Stable binding of meal components to labels in gastric conditions was confirmed. Distinct early and late-phase GE were detected by both modalities. Liquid GE half-time was median 49 (95% CI: 36-62) min and 68 (57-71) min for GS and MRI, respectively. Differences between GS and MRI measurements were explained by the contribution of gastric secretion. Breaking strength for agar-beads was 0.8 N/m(2) such that median 25 (8-50) % intact agar-beads and 65 (47-74) % solid material remained at 120 min on MRI and GS, respectively. Good reproducibility for liquid GE parameters was present and GE was not altered by agar-beads., Conclusions & Inferences: The NTM provided an objective assessment of gastric motor and sensory function. The results were reproducible and liquid emptying was not affected by non-nutrient agar-beads. The method is potentially suitable for clinical practice., (© 2016 John Wiley & Sons Ltd.)

High-resolution esophageal manometry (HRM) is a recent development used in the evaluation of esophageal function. Our aim was to assess the inter-observer agreement for diagnosis of esophageal motility disorders using this technology. Practitioners registered on the HRM Working Group website were invited to review and classify (i) 147 individual water swallows and (ii) 40 diagnostic studies comprising 10 swallows using a drop-down menu that followed the Chicago Classification system. Data were presented using a standardized format with pressure contours without a summary of HRM metrics. The sequence of swallows was fixed for each user but randomized between users to avoid sequence bias. Participants were blinded to other entries. (i) Individual swallows were assessed by 18 practitioners (13 institutions). Consensus agreement (≤ 2/18 dissenters) was present for most cases of normal peristalsis and achalasia but not for cases of peristaltic dysmotility. (ii) Diagnostic studies were assessed by 36 practitioners (28 institutions). Overall inter-observer agreement was 'moderate' (kappa 0.51) being 'substantial' (kappa > 0.7) for achalasia type I/II and no lower than 'fair-moderate' (kappa >0.34) for any diagnosis. Overall agreement was somewhat higher among those that had performed >400 studies (n = 9; kappa 0.55) and 'substantial' among experts involved in development of the Chicago Classification system (n = 4; kappa 0.66). This prospective, randomized, and blinded study reports an acceptable level of inter-observer agreement for HRM diagnoses across the full spectrum of esophageal motility disorders for a large group of clinicians working in a range of medical institutions. Suboptimal agreement for diagnosis of peristaltic motility disorders highlights contribution of objective HRM metrics., (© 2014 International Society for Diseases of the Esophagus.)

Background & Aims: Management of patients with dysphagia, regurgitation, and related symptoms after antireflux surgery is challenging. This prospective, case-control study tested the hypothesis that compared with standard high-resolution manometry (HRM) with single water swallows (SWS), adding multiple water swallows (MWS) and a solid test meal increases diagnostic yield and clinical impact of physiological investigations., Methods: Fifty-seven symptomatic and 12 asymptomatic patients underwent HRM with SWS, MWS, and a solid test meal. Dysphagia and reflux were assessed by validated questionnaires. Diagnostic yield of standard and full HRM studies with 24-hour pH-impedance monitoring was compared. Pneumatic dilatation was performed for outlet obstruction on HRM studies. Clinical outcome was assessed by questionnaires and an analogue scale with "satisfactory" defined as at least 40% symptom improvement requiring no further treatment., Results: Postoperative esophagogastric junction pressure was similar in all groups. Abnormal esophagogastric junction morphology (double high pressure band) was more common in symptomatic than in control patients (13 of 57 vs 0 of 12, P = .004). Diagnostic yield of HRM was 11 (19%), 11 (19%), and 33 of 57 (58%), with SWS, MWS, and solids, respectively (P < .001); it was greatest for solids in patients with dysphagia (19 of 27, 70%). Outlet obstruction was present in 4 (7%), 11 (19%), and 15 of 57 patients (26%) with SWS, MWS, and solids, respectively (P < .009). No asymptomatic control had clinically relevant dysfunction on solid swallows. Dilatation was performed in 12 of 15 patients with outlet obstruction during the test meal. Symptom response was satisfactory, good, or excellent in 7 of 12 (58%) with no serious complications., Conclusions: The addition of MWS and a solid test meal increases the diagnostic yield of HRM studies in patients with symptoms after fundoplication and identifies additional patients with outlet obstruction who benefit from endoscopic dilatation., (Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Objectives: Enhanced characterization of esophageal peristaltic and sphincter function provided by esophageal pressure topography (EPT) offers a potential diagnostic advantage over conventional line tracings (CLT). However, high-resolution manometry (HRM) and EPT require increased equipment costs over conventional systems and evidence demonstrating a significant diagnostic advantage of EPT over CLT is limited. Our aim was to investigate whether the inter-rater agreement and/or accuracy of esophageal motility diagnosis differed between EPT and CLT., Methods: Forty previously completed patient HRM studies were selected for analysis using a customized software program developed to perform blinded independent interpretation in either EPT or CLT (six pressure sensors) format. Six experienced gastroenterologists with a clinical focus in esophageal disease (attendings) and six gastroenterology trainees with minimal manometry experience (fellows) from three academic centers interpreted each of the 40 studies using both EPT and CLT formats. Rater diagnoses were assessed for inter-rater agreement and diagnostic accuracy, both for exact diagnosis and for correct identification of a major esophageal motility disorder., Results: The total group agreement was moderate (κ=0.57; 95% CI: 0.56-0.59) for EPT and fair (κ=0.32; 0.30-0.33) for CLT. Inter-rater agreement between attendings was good (κ=0.68; 0.65-0.71) for EPT and moderate (κ=0.46; 0.43-0.50) for CLT. Inter-rater agreement between fellows was moderate (κ=0.48; 0.45-0.50) for EPT and poor to fair (κ=0.20; 0.17-0.24) for CLT. Among all raters, the odds of an incorrect exact esophageal motility diagnosis were 3.3 times higher with CLT assessment than with EPT (OR: 3.3; 95% CI: 2.4-4.5; P<0.0001), and the odds of incorrect identification of a major motility disorder were 3.4 times higher with CLT than with EPT (OR: 3.4; 2.4-5.0; P<0.0001)., Conclusions: Superior inter-rater agreement and diagnostic accuracy of esophageal motility diagnoses were demonstrated with analysis using EPT over CLT among our selected raters. On the basis of these findings, EPT may be the preferred assessment modality of esophageal motility.

MRI can assess multiple gastric functions without ionizing radiation. However, time consuming image acquisition and analysis of gastric volume data, plus confounding of gastric emptying measurements by gastric secretions mixed with the test meal have limited its use to research centres. This study presents an MRI acquisition protocol and analysis algorithm suitable for the clinical measurement of gastric volume and secretion volume. Reproducibility of gastric volume measurements was assessed using data from 10 healthy volunteers following a liquid test meal with rapid MRI acquisition within one breath-hold and semi-automated analysis. Dilution of the ingested meal with gastric secretion was estimated using a respiratory-triggered T1 mapping protocol. Accuracy of the secretion volume measurements was assessed using data from 24 healthy volunteers following a mixed (liquid/solid) test meal with MRI meal volumes compared to data acquired using gamma scintigraphy (GS) on the same subjects studied on a separate study day. The mean ± SD coefficient of variance between 3 observers for both total gastric contents (including meal, secretions and air) and just the gastric contents (meal and secretion only) was 3  ±  2% at large gastric volumes (>200 ml). Mean ± SD secretion volumes post meal ingestion were 64  ±  51 ml and 110  ±  40 ml at 15 and 75 min, respectively. Comparison with GS meal volumes, showed that MRI meal only volume (after correction for secretion volume) were similar to GS, with a linear regression gradient ± std err of 1.06  ±  0.10 and intercept -11  ±  24 ml. In conclusion, (i) rapid volume acquisition and respiratory triggered T₁ mapping removed the requirement to image during prolonged breath-holds (ii) semi-automatic analysis greatly reduced the time required to derive measurements and (iii) correction for secretion volumes provided accurate assessment of gastric meal volumes and emptying. Together these features provide the scientific basis of a protocol which would be suitable in clinical practice.

Objectives: This study aimed to resolve controversy regarding the effects of Helicobacter pylori eradication therapy and H. pylori infection in gastro-oesophageal reflux disease., Design: A randomized, double-blind, multicentre trial was performed in patients presenting with reflux symptoms. H. pylori-positive patients were randomized to receive either antibiotics or placebo for 7 days. H. pylori-negative patient controls received placebo. All received esomeprazole 20 mg b.d. for 7 days, followed by 40 mg o.d. to complete an 8-week course, and were followed up for 32 weeks by telephone., Results: In this study, 198/589 (34%) patients were H. pylori-positive and 113 H. pylori-negative patients served as controls. Baseline endoscopy revealed 63% Los Angeles grade 0A and 37% Los Angeles grade BCD oesophagitis with no difference between patient groups. Symptom improvement on esomeprazole was seen in 89%. H. pylori eradication was successful in 82%. H. pylori eradication had no effect on symptomatic relapse (hazard ratio 1.15, 95% CI 0.74-1.8; p = 0.5). Overall, H. pylori-positive patients had a lower probability of relapse compared to H. pylori-negative controls (hazard ratio 0.6, 95% CI 0.43-0.85; p = 0.004). Relapse hazard was modulated also by oesophagitis grade (BCD vs. 0A, hazard ratio 2.1, 95% CI 1.5-3.0)., Conclusion: Relapse of gastro-oesophageal reflux disease symptoms after a course of high dose acid suppression took longer for H. pylori-positive patients than H. pylori-negative controls; however eradication therapy had no effect on the risk of relapse; ClincialTrials.gov number, NCT00574925.

The pathophysiology of chronic cough and its association with dsymotility and laryngopharyngeal reflux remains unclear. This study applied high-resolution manometry (HRM) to obtain a detailed evaluation of pharyngeal and esophageal motility in chronic cough patients with and without a positive reflux-cough symptom association probability (SAP). Retrospective analysis of 66 consecutive patients referred for investigation of chronic cough was performed. Thirty-four (52%) were eligible for inclusion (age 55 [19-77], 62% female). HRM (ManoScan 360, Given/Sierra Scientific Instruments, Mountain View, CA) with 10 water swallows was performed followed by a 24-hour ambulatory pH monitoring. Of this group, 21 (62%) patients had negative reflux-cough SAP (group A) and 13 (38%) had positive SAP (group B). Results from 23 healthy controls were available for comparison (group C). Detailed analysis revealed considerable heterogeneity. A small number of patients had pathological upper esophageal sphincter (UES) function (n=9) or esophageal dysmotility (n=1). The overall baseline UES pressure was similar, but average UES residual pressure was higher in groups A and B than in control group C (-0.2 and -0.8mmHg vs. -5.4mmHg; P<0.018 and P<0.005). The percentage of primary peristaltic contractions was lower in group B than in groups A and C (56% vs. 79% and 87%; P=0.03 and P<0.002). Additionally, intrabolus pressure at the lower esophageal sphincter was higher in group B than in group C (15.5 vs. 8.9; P=0.024). HRM revealed changes to UES and esophageal motility in patients with chronic cough that are associated with impaired bolus clearance. These changes were most marked in group B patients with a positive reflux-cough symptom association., (© 2012 Copyright the Authors. Journal compilation © 2012, Wiley Periodicals, Inc. and the International Society for Diseases of the Esophagus.)

Background: Rumination is the voluntary, albeit subconscious return of gastric contents to the mouth. Currently, rumination syndrome and repetitive belching disorders are considered separate diagnoses, as defined by Rome III criteria and high-resolution oesophageal manometry (HRM)., Aim: To test the hypothesis that these conditions represent a common behavioural response to aversive digestive stimuli and that successful treatment can be directed at both the stimulus and the response., Methods: Case-note review of consecutive patients with a final diagnosis of behavioural digestive disorders between August 2009 and October 2011., Results: Thirty-five of 46 (76%) patients exhibited 'classical' rumination with abdomino-gastric strain (R-waves) driving gastric contents across the lower oesophageal sphincter; 5 (11%) had 'reflux-related' rumination with R-waves seen during gastro-oesophageal common cavity (reflux) events and 6 had (13%) supra-gastric belching. All received at least one biofeedback session at the time of diagnosis with a good response reported by 20/46 (43%) of the patients, which included 3 with supra-gastric belching. Additionally, rumination ceased in cases in which definitive treatment relieved the symptoms that triggered abnormal behaviour (e.g. fundoplication in 'reflux-rumination')., Conclusions: Rumination and many of its variations, excluding only some cases of supra-gastric belching, are associated with abdomino-gastric strain, a generic abnormal behavioural response to a variety of aversive digestive stimuli. All types of rumination can respond to biofeedback. High-resolution oesophageal manometry identifies subgroups with distinct mechanisms of disease that respond to specific management targeted at the symptoms that trigger the abnormal behaviour., (© 2012 Blackwell Publishing Ltd.)

Background: The function and structure of the gastro-esophageal junction (GEJ) determine its efficacy as a reflux barrier. This study presents a novel methodology for the quantitative assessment of GEJ and proximal gastric morphology from magnetic resonance (MR) imaging. Based on this data we propose a new conceptualization of the hypothesis that a flap valve mechanism contributes to reflux protection., Methods: 3D models of the GEJ and proximal stomach were reconstructed from MR images in 12 healthy volunteers during respiration and on eating a test meal to maximum satiation. A rotating plane analysis measured the gastro-esophageal insertion angle and span of contact. An ellipsoid fit provided quantitative assessment of gastric shape and orientation relative to a fixed anatomical reference point. Position of the esophageal insertion on the 'gastric ellipse' was noted. An ellipsoid-cylinder model was designed to analyze the relationships among parameters describing the GEJ morphology., Key Results: The insertion angle became more acute on expiration, but did not change with meal ingestion. In contrast the span of contact did not vary with respiration, but increased with gastric filling. Changes in gastric morphology with distension further augmented the span of gastro-esophageal contact in almost 70% of the studies., Conclusions & Inferences: Novel MR imaging and biophysical analysis of the GEJ and proximal stomach provide a quantitative description of structures contributing to the reflux barrier. Changes in these parameters during respiration and on eating support the hypothesis that structural components of a functional 'flap valve' like mechanism contribute to reflux protection., (© 2012 Blackwell Publishing Ltd.)

Purpose: The purpose of the study was to examine the impact of incorporating certified diabetes educator trainees into medical practices on patient diabetes outcomes., Methods: This was a mixed methods practice-based evaluation study undertaken in 2 primary care practices in high-poverty neighborhoods in Buffalo, New York. The evaluation entailed a physician-referred patient cohort with pre- and postanalysis of chart review data corresponding to the American Diabetes Association's diabetes indicators. Patient charts were reviewed at baseline and 12 months. A brief survey was administered to the providers and staff to ascertain the extent to which the certified diabetes educator trainees were perceived as useful as part of the medical practice team., Results: Among 74 patients enrolled in diabetes classes, A1C levels decreased from a mean of 8.8% to 8.3%. Among a subset of patients (35%) with poorly controlled diabetes at baseline (A1C ≥ 9), there was a 15% decrease in A1C levels. Overall improvement in A1C was observed among 219 patients seen by a diabetes educator, in either a diabetes education class or a one-on-one visit., Conclusions: Results suggest that having a certified diabetes educator trainee as part of the primary care practice team may advance diabetes care, as evidenced by improvements in glucose control. Responses from providers and staff suggest that the certified diabetes educator trainees were well integrated into the practices and were perceived as instrumental in educating patients to better manage their diabetes.

Clear cell change is seen in <1% of colonic tubular adenomas (TAs) and remains incompletely characterized. Associated adenocarcinomas can also demonstrate a clear cell phenotype. Eleven TAs with at least focal clear cell change with or without associated invasive adenocarcinoma, from 10 patients were studied. The lesions were stained with periodic acid-Schiff (PAS)/PAS-diastase and immunolabeled with antibodies to MUC2, MUC5AC, MUC6, CK7, CK20, and CDX2. Eight of 11 (77%) TAs with clear cell change had focal to extensive high-grade dysplasia. Two were associated with invasive clear cell adenocarcinoma. The adenomas and adenocarcinomas ranged from 0.5 to 3.5 cm. PAS/PAS-diastase stains showed minimal PAS(+) material in the clear cells. On immunohistochemical studies, the clear cells had decreased MUC2 labeling compared with the surrounding conventional adenoma in 9 of 11 (88%) cases, including the 2 clear cell adenocarcinomas. In 3 of the 11 lesions, the background TA showed at least focal MUC5 immunoreactivity, their associated clear cell area had decreased MUC5 labeling in all 3 cases. No immunoreactivity to MUC6 was observed in the background TAs and clear cells in all cases. Compared with background TA, both increased and decreased expression of CK7, CK20 (in quantity), and CDX2 (in intensity) were observed in the clear cells of TAs and adenocarcinomas. One of the clear cell adenocarcinomas was CK20, CK7, CDX2 and the other was CK20, CK7, CDX2-focal positive. Thus, although the clear cells have different MUC protein profiles than the background adenomatous epithelium, invasive clear cell adenocarcinomas retained the typical CK20(+)/CK7(-) profile of conventional adenocarcinomas. Our results indicate that clear cell adenocarcinomas can be primary to the colorectum with identifiable precursors. Awareness of them and their immunoprofile allows distinction from clear cell lesions from other sites.

WO3(4,4-bipyridyl)0.5 was doped with Na+ by ion implantation so as to alter the electronic structure. Single-crystal X-ray diffraction reveals layers of corner-shared WO5N octahedra linked by bipyridine. In the observed space group of Pbca, the fully-ordered bipyridyls form cages with Na+ disordered bimodally about the cage centre.

This study assessed the effects of meal volume (MV) and calorie load (CL) on gastric function. MRI and a minimally invasive fiber-optic recording system (FORS) provided simultaneous measurement of gastric volume and pressure changes during gastric filling and emptying of a liquid nutrient meal in physiological conditions. The gastric response to 12 iso-osmolar MV-CL combinations of a multinutrient drink (MV: 200, 400, 600, 800 ml; CL: 200, 300, 400 kcal) was tested in 16 healthy subjects according to a factorial design. Total gastric volume (TGV) and gastric content volume (GCV = MV + secretion) were measured by MRI during nasogastric meal infusion and gastric emptying over 60 min. Intragastric pressure was assessed at 1 Hz by FORS. The dynamic change in postprandial gastric volumes was described by a validated three-component linear exponential model. The stomach expanded with MV, but the ratio of GCV:MV at t(0) diminished with increasing MV (P < 0.01). Postprandial changes in TGV followed those of GCV. Intragastric pressure increased with MV, and this effect was augmented further by CL (P = 0.02); however, the absolute pressure rise was <4 mmHg. A further postprandial increase of gastric volumes was observed early on before any subsequent volume decrease. This "early" increase in GCV was greater for smaller than larger MV (P < 0.01), indicating faster initial gastric emptying of larger MV. In contrast, volume change during filling and in the early postprandial period were unaffected by CL. In the later postprandial period, gastric emptying rate continued to be more rapid with high MVs (P < 0.001); however, at any given volume, gastric emptying was slowed by higher CL (P < 0.001). GCV half-emptying time decreased with CL at 18 +/- 6 min for each additional 100-kcal load (P < 0.001). These findings indicate that gastric wall stress (passive strain and active tone) provides the driving force for gastric emptying, but distal resistance to gastric outflow regulates further passage of nutrients. The distinct early phase of gastric emptying with relatively rapid, uncontrolled passage of nutrients into the small bowel, modulated by meal volume but not nutrient composition, ensures that the delivery of nutrients in the later postprandial period is related to the overall calorie load of the meal.

Gastric emptying (GE) may be driven by tonic contraction of the stomach ('pressure pump') or antral contraction waves (ACW) ('peristaltic pump'). The mechanism underlying GE was studied by contrasting the effects of clonidine (alpha(2)-adrenergic agonist) and sumatriptan (5-HT(1) agonist) on gastric function. Magnetic resonance imaging provided non-invasive assessment of gastric volume responses, ACW and GE in nine healthy volunteers. Investigations were performed in the right decubitus position after ingestion of 500 mL of 10% glucose (200 kcal) under placebo [0.9% NaCl intravenous (IV) and subcutaneous (SC)], clonidine [0.01 mg min(-1) IV, max 0.1 mg (placebo SC)] or sumatriptan [6 mg SC (placebo IV)]. Total gastric volume (TGV) and gastric content volume (GCV) were assessed every 5 min for 90 min, interspersed with dynamic scan sequences to measure ACW activity. During gastric filling, TGV increased with GCV indicating that meal volume dictates initial relaxation. Gastric contents volume continued to increase over the early postprandial period due to gastric secretion surpassing initial gastric emptying. Clonidine diminished this early increase in GCV, reduced gastric relaxation, decreased ACW frequency compared with placebo. Gastric emptying (GE) rate increased. Sumatriptan had no effect on initial GCV, but prolonged gastric relaxation and disrupted ACW activity. Gastric emptying was delayed. There was a negative correlation between gastric relaxation and GE rate (r(2 )=49%, P < 0.001), whereas the association between ACW frequency and GE rate was inconsistent and weak (r2=15%, P = 0.05). These findings support the hypothesis that nutrient liquid emptying is primarily driven by the 'pressure pump' mechanism.

High-resolution manometry capable of pressure monitoring from the pharynx to the stomach together with pressure topography plotting represents an unquestionable evolution in oesophageal manometry. However, with this advanced technology come challenges and one of those is devising the optimal scheme to apply high-resolution oesophageal pressure topography (HROPT) to the clinical evaluation of patients. The first iteration of the Chicago classification was based on a systematic analysis of motility patterns in 75 control subjects and 400 consecutive patients. This review summarizes the analysis process as it has evolved. Individual swallows are analysed in a stepwise fashion for the morphology of the oesophagogastric junction (OGJ), the extent of OGJ relaxation, the propagation velocity of peristalsis, the vigour of the peristaltic contraction, and abnormalities of intrabolus pressure utilizing metrics that have now been customized to HROPT. These results are then synthesized into a comprehensive diagnosis that, although based on conventional manometry criteria, is also customized to HROPT measures. The resultant classification objectifies the identification of three unique subtypes of achalasia. Additionally, it provides enhanced detail in the description of distal oesophageal spasm, nutcracker oesophagus subtypes, and OGJ obstruction. It is our expectation that modification of this classification scheme will continue to occur and this should further clarify the utility of pressure topography plotting in assessing oesophageal motility disorders.

The assessment of gastric accommodation and emptying by different methodologies provides inconsistent results. We aimed to compare magnetic resonance imaging (MRI), barostat and 13C-acetate breath test (BT) for the assessment of gastric volume responses and emptying in healthy controls (HC) and patients with functional dyspepsia (FD). Eight HC and eight FD patients underwent: (i) continuous BT with simultaneous MRI in the upright position after ingestion of isocaloric, 300 kcal, 200 and 800 mL meals, both labelled with 100 mg of (13)C-acetate; and (ii) BT with gastric barostat after ingestion of the 200 mL meal. MRI measured total gastric volume and gastric content volume (GCV) at baseline, after filling and during emptying. Meal emptying half-times (T(1/2)) for MRI and BT were calculated (mean +/- SD). We found: (i) Initial GCV was lower in FD than in HC (762 +/- 22 vs 810 +/- 52 mL, P < 0.04) after the 800 mL meal but not the 200 mL meal. T(1/2)(MRI) was shorter for the 800 mL than the 200 mL meal (P < 0.001), but similar in HC and FD (200 mL: HC 117 +/- 30 min vs FD 138 +/- 42 min, ns; 800 mL: HC 71 +/- 16 min vs FD 78 +/- 27 min, ns). In contrast, T(1/2)(BT) was similar between meals and groups (200 mL: HC 111 +/- 11 min vs FD 116 +/- 19 min; 800 mL: HC 114 +/- 14 min vs FD: 113 +/- 17 min). (ii) Barostat measurements showed similar postprandial volume increases between groups. We conclude that direct measurements by MRI provide a sensitive, non-invasive assessment of gastric accommodation and emptying after a meal. In contrast to MRI, BT did not detect faster emptying of high-volume compared to low-volume liquid nutrient meals in HC or FD.

Background: When Pneumocystis DNA is recovered from respiratory specimens of patients without Pneumocystis pneumonia (PCP), patients are said to be colonised with Pneumocystis, although the significance of this state is unknown. Understanding risk factors for and outcomes of colonisation may provide insights into the life cycle and transmission dynamics of Pneumocystis jirovecii., Methods: We performed a cross sectional study of the prevalence and clinical predictors of Pneumocystis colonisation in 172 HIV infected, PCP negative inpatients undergoing diagnostic evaluation of 183 episodes of pneumonia at either the Medical Center of Louisiana at New Orleans between 2003 and 2005 or San Francisco General Hospital between 2000 and 2005. DNA was extracted from sputum and bronchoalveolar lavage specimens and amplified using a nested PCR assay at the mitochondrial large subunit (18S) ribosomal RNA locus. Colonisation was deemed present if Pneumocystis DNA was identified by both gel electrophoresis and direct DNA sequencing., Results: 68% (117/172) of all patients were colonised with Pneumocystis. No strong associations with colonisation were identified for any demographic factors. Among clinical factors, having a CD4+ T cell count

Manometry measures pressure within the oesophageal lumen and sphincters, and provides an assessment of the neuromuscular activity that dictates function in health and disease. It is performed to investigate the cause of functional dysphagia, unexplained "non-cardiac" chest pain, and in the pre-operative work-up of patients referred for anti-reflux surgery. Manometric techniques have improved in a step-wise fashion from a single pressure channel to the development of high-resolution manometry (HRM) with up to 36 pressure sensors. At the same time, advances in computer processing allow pressure data to be presented in real time as a compact, visually intuitive "spatiotemporal plot" of oesophageal pressure activity. HRM recordings reveal the complex functional anatomy of the oesophagus and its sphincters. Spatiotemporal plots provide objective measurements of the forces that move food and fluid from the pharynx to the stomach and determine the risk of reflux events. The introduction of commercially available HRM has been followed by rapid uptake of the technique. This review examines the current evidence that supports the move of HRM from the research setting into clinical practice. It is assessed whether a detailed description of pressure activity identifies clinically relevant oesophageal dysfunction that is missed by conventional investigation, increasing diagnostic yield and accuracy. The need for a new classification system for oesophageal motor activity based on HRM recordings is discussed. Looking ahead the potential of this technology to guide more effective medical and surgical treatment of oesophageal disease is considered because, ultimately, it is this that will define the success of HRM in clinical practice.

Polymerase chain reaction analysis, direct DNA sequencing, and histological staining were used to determine whether Pneumocystis jirovecii was present in lung tissue specimens obtained, at autopsy, from 58 infants without identifiable immunodeficiency. The results of genotyping of these specimens were compared with the results of genotyping of specimens obtained from 384 human immunodeficiency virus (HIV)-infected adults with Pneumocystis pneumonia. P. jirovecii DNA was detected at the mitochondrial large subunit rRNA and dihydropteroate synthase loci in 100% and 53%, respectively, of the specimens obtained from infants. All specimens obtained from adults tested positive for P. jirovecii at both loci. Genotype distributions at both loci were significantly different in the 2 populations (P < .0001). The observation of different strains circulating in immunocompetent infants and HIV-infected adults suggests independent transmission cycles that warrant further study.

Cadmium slowly accumulates in the liver and kidney and has a long biological half-life, estimated to be 2-3 decades in the kidney. If the kidney cadmium concentration reaches a critically high level, proximal tubular damage results, which can be followed by severe bone mineral loss. There are only a few measurements of cadmium bioavailability in foods; however, the data are indicative of lower utilization from foods than from inorganic salts. In animal tissues cadmium is bound primarily to a heat-resistant small protein with a high cysteine content (metallothionein), whereas little is known about the form in which cadmium occurs in the edible parts of plants. Low intakes of many nutrients exacerbate the effects of cadmium and supplemental intakes are protective. Newborn and young animals absorb much higher quantities of cadmium than adults. There is some evidence in animals that females may be more adversely affected than males. Itai-itai disease, a painful disease with kidney damage and bone demineralization, occurred in elderly Japanese women who had borne several children and who were exposed to cadmium via food and drinking water. Inasmuch as cadmium in the U.S. food supply affords an estimated safety factor of only 4- to 15-fold, it is important to establish factors that affect the bioavailability of cadmium from foods.

A semipurified diet based on soy protein was developed to induce mild zinc deficiency in five male volunteers. Each of seven daily menus provided (mean +/- SD) 2248 +/- 128 kcal, 56.6 +/- 5.7 protein, 261 +/- 30 g carbohydrate, 110 +/- 21 g fat, 8.5 +/- 1.4 g fiber, and 4.8 +/- 1.3 mg zinc. The analytical value for phytate:zinc molar ratio was 21 +/- 9. One subject, who received five of the menus for 28 wk, lost approximately 200 mg body zinc and 7% weight; zinc concentration declined 25% in plasma, 30% in lymphocytes, and 55% in neutrophils. This dietary model allowed simple formulation of new menus for subjects in diverse states of health. It caused no ill effects after prolonged consumption, and all deficiency symptoms were reversed by zinc supplementation of 30 mg/d for 20 wk. With simple manipulation, this dietary model may be used safely for gradual induction of zinc and/or other micronutrient deficiencies in humans.