Therapeutic bacteriophages as a rescue treatment for drug-resistant infections - an in vivo studies overview.

Bacteriophages, highly prevalent in all environments, have found their use in medicine as an alternative or complement to antibiotics. The therapeutic use of bacteriophages was particularly popular in the 1920s and 1930s, until the discovery and introduction of antibiotics. Due to the dynamic growth of antibiotic resistance among bacterial strains, numerous international institutions (such as the FDA) have declared the search for novel treatment modalities to be of the highest priority. To date, bacteriophage therapy has not been registered for general use in Western countries. The regulation of biological medicinal products (within medicinal product regulation) does not contain a specific documentation frame for bacteriophages (only for vaccines, blood derived products, etc.) which, as active substances, need to meet specific requirements. Recently, the FDA allowed bacteriophage therapy to be used in the United States, via the Emergency Investigational New Drug scheme; clinical trials to compare the safety and efficacy of bacteriophage therapy are also permitted. To date, several therapeutic products of this type have made it to phase I or II; some clinical programmes have also been completed. This article cites numerous animal model studies and registered clinical trials, showing the safety and effectiveness of bacteriophage therapy, including infections caused by bacterial strains resistant to antibiotic treatment.

Amniotic band syndrome in dichorionic diamniotic twin pregnancy.

BACKGROUND: Amniotic band syndrome (ABS) is a rare disorder which leads to a number of deformities of the fetus body. The treatment depends on the severity of the defect and the extent of the deformity. CASE REPORT: A 36-year-old primigravida with a dichorionic diamniotic (DCDA) twin pregnancy was diagnosed during the first-trimester ultrasonography with fetal lower part edema of one twin caused by amniotic bands. A selective termination of the affected fetus was performed. The remainder part of the pregnancy was normal. A healthy newborn was delivered at term. After delivering the placenta, the presence of fetus papyraceus was detected. The amniotic bands were unidentifiable in the pathologist's examination. A reliable ultrasonographic diagnosis enables the detecting ABS in early pregnancy. CONCLUSION: In the case of ABS in DCDA twin pregnancy, conducting a selective termination of the affected fetus creates the opportunity for the proper development of the healthy fetus as well as reaching its full maturity. HIPPOKRATIA 2017, 21(1): 46-48.

Characterization of morphology and resistance to Blumeria graminis of winter triticale monosomic addition lines with chromosome 2D of Aegilops tauschii.

KEY MESSAGE: Allocation of the chromosome 2D of Ae. tauschii in triticale background resulted in changes of its organization, what is related to varied expression of genes determining agronomically important traits. Monosomic alien addition lines (MAALs) are crucial for transfer of genes from wild relatives into cultivated varieties. This kind of genetic stocks is used for physical mapping of specific chromosomes and analyzing alien genes expression. The main aim of our study is to improve hexaploid triticale by transferring D-genome chromatin from Aegilops tauschii × Secale cereale (2n = 4x = 28, DDRR). In this paper, we demonstrate the molecular cytogenetics analysis and SSR markers screening combined with phenotype analysis and evaluation of powdery mildew infection of triticale monosomic addition lines carrying chromosome 2D of Ae. tauschii. We confirmed the inheritance of chromosome 2D from the BC2F4 to the BC2F6 generation of triticale hybrids. Moreover, we unveiled a high variable region on the short arm of chromosome 2D, where chromosome rearrangements were mapped. These events had direct influence on plant height of hybrids what might be connected with changes at Rht8 loci. We obtained 20 semi-dwarf plants of BC2F6 generation carrying 2D chromosome with the powdery mildew resistance, without changes in spike morphology, which can be used in the triticale breeding programs.

Transmission of the Aegilops ovata chromosomes carrying gametocidal factors in hexaploid triticale (×Triticosecale Wittm.) hybrids.

The main aim of this work was to induce the chromosome rearrangements between Aegilops ovata (UUMM) and hexaploid triticale (AABBRR) by expression of the gametocidal factor located on the chromosome 4M. The Aegilops ovata × Secale cereale (UUMMRR) amphiploids and triticale 'Moreno' were used to produce hybrids by reciprocal crosses. Chromosome dynamics was observed in subsequent generations of hybrids during mitotic metaphase of root meristems and first metaphase of meiosis of pollen mother cells. Chromosomes were identified by genomic in situ hybridisation (GISH) and fluorescence in situ hybridisation (FISH) using pTa71, pTa791, pSc119.2 and pAs1 DNA probes. It has been shown that the origin of the genetic background had an influence on Aegilops chromosome transmission. Moreover, it has been reported that the preferential transmission of chromosome 4M appeared during both androgenesis and gynogenesis. It is also hypothesised that the expression of the triticale Gc gene suppressor had an influence on the semi-fertility of hybrids but did not inhibit the chromosome rearrangements. This paper also describes the double haploid production, which enabled to obtain plants with two identical copies of triticale chromosomes with translocations of Aegilops chromatin segments.

Allocation of the S-genome chromosomes of Aegilops variabilis Eig. carrying powdery mildew resistance in triticale (× Triticosecale Wittmack).

It has been hypothesized that the powdery mildew adult plant resistance (APR) controlled by the Pm13 gene in Aegilops longissima Schweinf. & Muschl. (S(l)S(l)) has been evolutionary transferred to Aegilops variabilis Eig. (UUSS). The molecular marker analysis and the visual evaluation of powdery mildew symptoms in Ae. variabilis and the Ae. variabilis × Secale cereale amphiploid forms (2n = 6x = 42, UUSSRR) showed the presence of product that corresponded to Pm13 marker and the lower infection level compared to susceptible model, respectively. This study also describes the transfer of Ae. variabilis Eig. (2n = 4x = 28, U(v)U(v)S(v)S(v)) chromosomes, carrying powdery mildew resistance, into triticale (× Triticosecale Wittm., 2n = 6x = 42, AABBRR) using Ae. variabilis × S. cereale amphiploid forms. The individual chromosomes of Ae. variabilis, triticale 'Lamberto' and hybrids were characterized by genomic and fluorescence in situ hybridization (GISH/FISH). The chromosome configurations of obtained hybrid forms were studied at first metaphase of meiosis of pollen mother cells (PMCs) using GISH. The statistical analysis showed that the way of S-genome chromosome pairing and transmission to subsequent hybrid generations was diploid-like and had no influence on chromosome pairing of triticale chromosomes. The cytogenetic study of hybrid forms were supported by the marker-assisted selection using Pm13 marker and visual evaluation of natural infection by Blumeria graminis, that allowed to select the addition or substitution lines of hybrids carrying chromosome 3S(v) which were tolerant to the powdery mildew infection.

Inter-observer agreement for diagnostic classification of esophageal motility disorders defined in high-resolution manometry.

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.

Introgression of A- and B-genome of tetraploid triticale chromatin into tetraploid rye.

An improvement of rye is one of the mainstream goals of current breeding. Our study is concerned with the introduction of the tetraploid triticale (ABRR) into the 4x rye (RRRR) using classical methods of distant crossing. One hundred fifty BC1F9 hybrid plants [(4x rye × 4x triticales) × 4x rye] obtained from a backcrossing program were studied. The major aim of this work was to verify the presence of an introgressed A- and B- genome chromatin of triticale in a collection of the 4x rye-tiritcale hybrids and to determine their chromosome compositions. In the present study, karyotypes of the previously reported BC1F2s and BC1F3s were compared with that of the BC1F9 generation as obtained after several subsequent open pollinations. The genomic in situ hybridisation (GISH) allowed us to identify 133 introgression forms in which chromosome numbers ranged between 26 and 32. Using four DNA probes (5S rDNA, 25S rDNA, pSc119.2 and pAs1), the fluorescence in situ hybridisation (FISH) was carried out to facilitate an exact chromosome identification in the hybrid plants. The combination of the multi-colour GISH with the repetitive DNA FISH singled out five types of translocated chromosomes: 2A.2R, 4A.4R, 5A.5R, 5B.5R and 7A.7R among the examined BC1F9s. The reported translocation lines could serve as valuable sources of wheat chromatin suitable for further improvements of rye.

Cytogenetic analysis of Aegilops chromosomes, potentially usable in triticale (X Triticosecale Witt.) breeding.

Chromosome identification using fluorescence in situ hybridization (FISH) is widely used in cytogenetic research. It is a diagnostic tool helpful in chromosome identification. It can also be used to characterize alien introgressions, when exercised in a combination with genomic in situ hybridization (GISH). This work aims to find chromosome identification of Aegilops species and Aegilops × Secale amphiploids, which can be used in cereal breeding as a source of favourable agronomic traits. Four diploid and two tetraploid Aegilops species and three Aegilops × Secale hybrids were analysed using FISH with pSc119.2, pAs1, 5S rDNA and 25S rDNA clones to differentiate the U-, M-, S(sh)- and D-subgenome chromosomes of Aegilops genus. Additionally, GISH for chromosome categorization was carried out. Differences in the hybridization patterns allowed to identify all U-, M-, S(sh)- and D-subgenome chromosomes. Some differences in localization of the rDNA, pSc119.2 and pAs1 sequences between analogue subgenomes in diploid and tetraploid species and Aegilops × Secale hybrids were detected. The hybridization pattern of the M and S genome was more variable than that of the U and D genome. An importance of the cytogenetic markers in plant breeding and their possible role in chromosome structure, function and evolution is discussed.

Aegilops-Secale amphiploids: chromosome categorisation, pollen viability and identification of fungal disease resistance genes.

The aim of this study was to assess the potential breeding value of goatgrass-rye amphiploids, which we are using as a "bridge" in a transfer of Aegilops chromatin (containing, e.g. leaf rust resistance genes) into triticale. We analysed the chromosomal constitution (by genomic in situ hybridisation, GISH), fertility (by pollen viability tests) and the presence of leaf rust and eyespot resistance genes (by molecular and endopeptidase assays) in a collection of 6× and 4× amphiploids originating from crosses between five Aegilops species and Secale cereale. In the five hexaploid amphiploids Aegilops kotschyi × Secale cereale (genome UUSSRR), Ae. variabilis × S. cereale (UUSSRR), Ae. biuncialis × S. cereale (UUMMRR; two lines) and Ae. ovata × S. cereale (UUMMRR), 28 Aegilops chromosomes were recognised, while in the Ae. tauschii × S. cereale amphiploid (4×; DDRR), only 14 such chromosomes were identified. In the materials, the number of rye chromosomes varied from 14 to 16. In one line of Ae. ovata × S. cereale, the U-R translocation was found. Pollen viability varied from 24.4 to 75.4%. The leaf rust resistance genes Lr22, Lr39 and Lr41 were identified in Ae. tauschii and the 4× amphiploid Ae. tauschii × S. cereale. For the first time, the leaf rust resistance gene Lr37 was found in Ae. kotschyi, Ae. ovata, Ae. biuncialis and amphiploids derived from those parental species. No eyespot resistance gene Pch1 was found in the amphiploids.

Physiology of the LES.

The purpose of this review is to consider the neuromuscular mechanism of LES contractility both by itself and in relation to the esophagogastric junction (EGJ) complex in order to appreciate the intricacies of EGJ valvular function.

The adult eosinophilic oesophagitis quality of life questionnaire: a new measure of health-related quality of life.

BACKGROUND: Eosinophilic oesophagitis (EoO) is a chronic disease characterised by significant symptoms and challenging treatment regimens. Health-related quality of life (HRQOL) is a useful way to direct patient care. EoO symptoms and treatment may impact patient HRQOL. Currently, there is no reliable and valid measure of adult EoO patient HRQOL. AIM: To validate the Adult Eosinophilic Oesophagitis Quality of Life (EoO-QOL-A) questionnaire as a measure of HRQOL in this population. METHODS: The EoO patients aged 18-70 recruited via an out-patient GI clinic and two EoO advocacy groups completed the preliminary EoO-QOL-A, demographic and clinical information, and measures of general HRQOL, psychological distress and EoO symptom severity. A subset of patients completed test-retest assessments. Scale reliability, internal consistency, factor structure, concurrent and convergent validity were evaluated. RESULTS: A total of 201 patients have participated. The study sample was primarily Caucasian, college-educated, and evenly split by gender. The average duration of disease was 7 years with duration of symptoms of 26 months prior to diagnosis. Patients reported were using both pharmacological and dietary treatments. Factor analysis yielded a 37-item, 5-factor structure: Eating/Diet Impact, Social Impact, Emotional Impact, Disease Anxiety and Choking Anxiety. The EoO-QOL-A demonstrated excellent internal consistency, split-half and test-retest reliability. Concurrent and convergent validity were supported by moderate correlations with established HRQOL measures, psychological distress and oesophageal symptoms. CONCLUSIONS: The EoO-QOL-A is a valid and reliable disease-specific HRQOL measure for adult EoO patients. Developing the Adult Eosinophilic Oesophagitis Quality of Life is an important step in guiding treatment practices, improving disease education and standardising research protocols.

Inter-observer reproducibility and analysis of gastric volume measurements and gastric emptying assessed with magnetic resonance imaging.

BACKGROUND: Magnetic resonance (MR) imaging provides direct, non-invasive measurements of gastric function and emptying. The inter-observer variability (IOV) of MR volume measurements and the most appropriate analysis of MR data have not been established. To assess IOV of total gastric volume (TGV) and gastric content volume (GCV) measurements from MR images and the ability of standard power exponential (PowExp), and a novel linear exponential (LinExp) model to describe MR data. METHODS: Ten healthy volunteers received three different volumes of a liquid nutrient test meal (200-800 mL) on 3 days in a randomized order. Magnetic resonance scans were acquired using a 1.5T system every 1-5 min for 60 min. Total gastric volume and GCV were measured independently by three observers. Volume data were fitted by PowExp and LinExp models to assess postprandial volume change and gastric emptying half time (T(50) ). KEY RESULTS: An initial rise in GCV and TGV was often observed after meal ingestion, thereafter GCV and TGV decreased in an approximately linear fashion. Inter-observer variability decreased with greater volumes from 12% at 200 mL to 6% at 600 and 800 mL. Inter-observer variability for T(50) was <5%. PowExp and LinExp models provided comparable estimates of T(50) ; however, only LinExp described dynamic volume change in the early postprandial period. CONCLUSIONS & INFERENCES: Gastric MR provides quantitative measurements of postprandial volume change with low IOV, unless the stomach is nearly empty. The novel LinExp model describes the dynamic volume changes in the early postprandial period more accurately than the PowExp model used in existing gastric emptying studies.

Esophageal symptoms questionnaire for the assessment of dysphagia, globus, and reflux symptoms: initial development and validation.

Esophageal symptoms often co-occur. A validated self-report measure encompassing multiple esophageal symptoms is necessary to determine their frequency and severity both independently and in association with each other. Such a questionnaire could streamline the diagnostic process and guide patient management. We aimed to develop an integrative measure that provides a clinical 'snapshot' of common esophageal symptoms. Internal reliability and content validity of a 38-item self-report Esophageal Symptoms Questionnaire (ESQ), measuring the frequency and severity of typical esophageal symptoms using Likert-rating scales were assessed in 211 patients presenting to gastroenterology and ENT outpatient tertiary care clinics. Reproducibility, concurrent and predictive validity were evaluated using the reduced-item ESQ. The 38-item ESQ had high internal reliability. Principal component analyses and item reduction methods identified three components, to which 30 of 38 items contributed significantly, providing 59% of total variance. The test-retest correlations were moderate-to-strong for 24 of 30 new items (r(s) ≥ 0.44, P < 0.05). The resultant subscales measuring dysphagia (ESQ-D), globus (ESQ-G), and reflux (ESQ-R) compared well against concurrent physician's 'working' diagnosis (odds ratio 1.04-1.09). The receiver operating characteristics were adequate-to-good for ESQ-D (area under the curve [AUC]= 0.87) and ESQ-G (AUC = 0.74), but poor for ESQ-R (AUC = 0.61) although it matched the content of the validated Reflux Disease Questionnaire. The brief 30-item ESQ shows good internal reliability and content validity as a summary of the extent of dysphagia, globus and reflux symptoms. As a tool measuring more than one esophageal symptom, ESQ could guide patient management by indicating which of the coexisting symptoms needs to be addressed first.

3D-high resolution manometry of the esophagogastric junction.

BACKGROUND: The esophagogastric junction (EGJ) is a complex structure that challenges accurate manometric recording. This study aimed to define EGJ pressure morphology relative to the squamocolumnar junction (SCJ) during respiration with 3D-high resolution manometry (3D-HRM). METHODS: A 7.5-cm long 3D-HRM array with 96 independent solid-state pressure sensors (axial spacing 0.75 cm, radial spacing 45°) was used to record EGJ pressure in 15 normal subjects. Concurrent videofluoroscopy was used to localize the SCJ marked with an endoclip. Ex vivo experiments were done on the effect of bending the probe to match that seen fluoroscopically. KEY RESULTS: 3D-high resolution manometry EGJ pressure recordings were dominated by an asymmetric pressure peak superimposed on the lower esophageal sphincter (LES) attributable to the crural diaphragm (CD). Median peak CD pressure at expiration and inspiration (51 and 119 mmHg, respectively) was much greater in 3D-HRM than evident in HRM with circumferential pressure averaging. Esophagogastric junction length, defined as the zone of circumferential pressure exceeding that of adjacent esophagus or stomach was also substantially shorter (2.4 cm) than evident in conventional HRM. No consistent circumferential EGJ pressure was evident distal to the SCJ in 3D-HRM recordings and ex vivo experiments suggested that the intra-gastric pressure peak seen contralateral to the CD related to bending the assembly rather than the sphincter per se. CONCLUSIONS & INFERENCES: 3D-high resolution manometry demonstrated a profoundly asymmetric and vigorous CD component to EGJ pressure superimposed on the LES. Esophagogastric junction length was shorter than evident with conventional HRM and the distal margin of the EGJ sphincteric zone closely correlated with the SCJ.

An alginate-antacid formulation (Gaviscon Double Action Liquid) can eliminate or displace the postprandial 'acid pocket' in symptomatic GERD patients.

BACKGROUND: Recently, an 'acid pocket' has been described in the proximal stomach, particularly evident postprandially in GERD patients, when heartburn is common. By creating a low density gel 'raft' that floats on top of gastric contents, alginate-antacid formulations may neutralise the 'acid pocket'. AIM: To assess the ability of a commercial high-concentration alginate-antacid formulation to neutralize and/or displace the acid pocket in GERD patients. METHODS: The 'acid pocket' was studied in ten symptomatic GERD patients. Measurements were made using concurrent stepwise pH pull-throughs, high resolution manometry and fluoroscopy in a semi-recumbent posture. Each subject was studied in three conditions: fasted, 20 min after consuming a high-fat meal and 20 min later after a 20 mL oral dose of an alginate-antacid formulation (Gaviscon Double Action Liquid, Reckitt Benckiser Healthcare, Hull, UK). The relative position of pH transition points (pH >4) to the EGJ high-pressure zone was analysed. RESULTS: Most patients (8/10) exhibited an acidified segment extending from the proximal stomach into the EGJ when fasted that persisted postprandially. Gaviscon neutralised the acidified segment in six of the eight subjects shifting the pH transition point significantly away from the EGJ. The length and pressure of the EGJ high-pressure zone were minimally affected. CONCLUSIONS: Gaviscon can eliminate or displace the 'acid pocket' in GERD patients. Considering that EGJ length was unchanged throughout, this effect was likely attributable to the alginate 'raft' displacing gastric contents away from the EGJ. These findings suggest the alginate-antacid formulation to be an appropriately targeted postprandial GERD therapy.

Manometric features of eosinophilic esophagitis in esophageal pressure topography.

BACKGROUND: Although most of the patients with eosinophilic esophagitis (EoE) have mucosal and structural changes that could potentially explain their symptoms, it is unclear whether EoE is associated with abnormal esophageal motor function. The aims of this study were to evaluate the esophageal pressure topography (EPT) findings in EoE and to compare them with controls and patients with gastro-esophageal disease (GERD). METHODS: Esophageal pressure topography studies in 48 EoE patients, 48 GERD patients, and 50 controls were compared. The esophageal contractile pattern was described for ten 5-mL swallows for each subject and each swallow was secondarily characterized based on the bolus pressurization pattern: absent, pan-esophageal pressurization, or compartmentalized distal pressurization. KEY RESULTS: Thirty-seven percent of EoE patients were classified as having abnormal esophageal motility. The most frequent diagnoses were of weak peristalsis and frequent failed peristalsis. Although motility disorders were more frequent in EoE patients than in controls, the prevalence and type were similar to those observed in GERD patients (P=0.61, chi-square test). Pan-esophageal pressurization was present in 17% of EoE and 2% of GERD patients while compartmentalized pressurization was present in 19% of EoE and 10% of GERD patients. These patterns were not seen in control subjects. CONCLUSIONS & INFERENCES: The prevalence of abnormal esophageal motility in EoE was approximately 37% and was similar in frequency and type to motor patterns observed in GERD. Eosinophilic esophagitis patients were more likely to have abnormal bolus pressurization patterns during swallowing and we hypothesize that this may be a manifestation of reduced esophageal compliance.

Do patients with globus sensation respond to hypnotically assisted relaxation therapy? A case series report.

Globus sensation is a bothersome and difficult symptom to treat. The aims of this study were to evaluate the acceptability and utility of hypnotically-assisted relaxation (HAR) in decreasing the perception of globus sensation and the effect of HAR on interdeglutitive upper esophageal sphincter (UES) pressure. Sixteen subjects with persistent globus sensation unresponsive to therapy for reflux disease and with normal esophageal/laryngeal imaging studies were invited to participate in a 7-session clinical protocol. Before and after HAR, subjects completed standard questionnaires including the esophageal symptoms questionnaire. High-resolution manometric assessment of respiratory augmentation and average resting UES pressure were assessed before and after HAR. Ten of the 16 subjects agreed to participate in the protocol. All participants were women with median age 51.5 (range 30-72 years). The participants found HAR acceptable and completed the entire 7-session trial. Globus symptom severity varied widely pre-treatment (median=52.5, range 16-72), and 9 of 10 subjects reported a reduction in globus symptomatology following treatment (median=14.0, range 3-19; P=.007). Only 1 subject exhibited abnormal respiratory augmentation of UES pressure (>27 mm Hg) prior to treatment and was normal following treatment (9.9 mm Hg). Resting UES pressure was normal in all subjects (<118 mm Hg). Group respiratory augmentation and average resting UES pressure were unaffected by HAR (P=.48, .89). This case series suggests that HAR can provide a substantial improvement in globus sensation irrespective of cause. UES function was unaffected. We suggest that HAR therapy is an acceptable and useful intervention for patients with globus sensation.

The contractile deceleration point: an important physiologic landmark on oesophageal pressure topography.

BACKGROUND: This study aimed to correlate oesophageal bolus transit with features of oesophageal pressure topography (OPT) plots and establish OPT metrics for accurately measuring peristaltic velocity. METHODS: About 18 subjects underwent concurrent OPT and fluoroscopy studies. The deglutitive Contractile Front Velocity (CFV) in OPT plots was subdivided into an initial fast phase (CFV(fast)) and subsequent slow phase (CFV(slow)) separated by a user-defined deceleration point (CDP). Fluoroscopy studies were analyzed for the transition from the initial rapidly propagated luminal closure associated with peristalsis to slow bolus clearance characteristic of phrenic ampullary emptying and to identify the pressure sensors at the closure front and at the hiatus. Oesophageal pressure topography measures were correlated with fluoroscopic milestones of bolus transit. Oesophageal pressure topography studies from another 68 volunteers were utilized to develop normative ranges for CFV(fast) and CFV(slow). KEY RESULTS: A distinct change in velocity could be determined in all 36 barium swallows with the fast and slow contractile segments having a median velocity of 4.2 cm s(-1) and 1.0 cm s(-1), respectively. The CDP noted on OPT correlated closely with formation of the phrenic ampulla making CFV(fast) (mean 5.1 cm s(-1)) correspond closely to peristaltic propagation and CFV(slow) (mean 1.7 cm s(-1)) to ampullary emptying. CONCLUSIONS & INFERENCES: The deceleration point in the CFV on OPT plots accurately demarcated the early region in which the CFV reflects peristaltic velocity (CFV(fast)) from the later region where it reflects the progression of ampullary emptying (CFV(slow)). These distinctions should help objectify definitions of disordered peristalsis, especially spasm, and improve understanding of impaired bolus transit across the oesophagogastric junction.

Effects of postgastric 13C-acetate processing on measurement of gastric emptying: a systematic investigation in health.

Uniform postgastric processing of the gastric emptying (GE) marker 13C-acetate (Ac) is an unverified assumption behind its widespread application to measure GE. This study assessed the postgastric processing of Ac administered by intraduodenal (i.d.) infusion simulating different physiological conditions. 13CO2 in breath was assessed in three groups of six volunteers after i.d. administration of A: Different caloric densities (0.75/1.5/3 kcal min(-1) in a 200 mL meal at constant 1 mg Ac min(-1) simulating a physiological range of nutrient delivery rates; B: different tracer delivery rates (0.5/1.0/2.5 mg Ac min(-1) simulating delayed, normal and increased GE; C1: a 500 mL meal resulting in same marker and caloric delivery compared to protocol A; C2: 50 mL water bolus injections of 12.5/25/50/100 mg Ac and C3 bolus injections of 50 mg Ac in 50/100/200 mL water in randomized order. A: 13CO2 excretion was independent of caloric load (P = 0.59). B: The dynamic of 13CO2 excretion was modulated by tracer elimination which was in turn dependent on the speed of tracer delivery, i.e. with faster deliveries resulting in lower 13CO2 recovery during infusion (P < 0.001). C: Increasing Ac doses resulted in decreased 13CO2 recovery (P < 0.001) over the first hour. 13CO2 recovery kinetics was independent of the volume delivered. This study shows 13C-acetate absorption and metabolism is independent of the volume and caloric delivery of test meals. The 'lag' in estimates of GE derived from 13CO2 breath tests is due to a postgastric, dose-dependent delay to 13CO2 elimination. This can be corrected for in analytical derivations of GE parameters based on 13C-acetate breath test measurements.

Transient lower oesophageal sphincter relaxation in achalasia: everything but LOS relaxation.

In conducting clinical high-resolution oesophageal pressure topography (HROPT) studies we observed that after subjects sat upright between series of supine and upright test swallows, they frequently had a transient lower oesophageal sphincter relaxation (TLOSR). When achalasia patients were studied in the same protocol, they exhibited a similar HROPT event leading to the hypothesis that achalasics had incomplete TLOSRs. We reviewed clinical HROPT studies of 94 consecutive non-achalasics and 25 achalasics. Studies were analyzed for a TLOSR-like event during the study and, when observed, that TLOSR-like event was characterized for the degree and duration of distal oesophageal shortening, the degree of LOS relaxation, associated crural diaphragm (CD) inhibition, oesophageal pressurization and upper oesophageal sphincter (UOS) relaxation. About 64/94 (68%) non-achalasics and 15/24 (63%) of achalasics had a pressure topography event after the posture change characterized by a prolonged period of distal oesophageal shortening and/or LOS relaxation. Events among the non-achalasics and achalasics were similar in terms of magnitude and duration of shortening and all were associated with CD inhibition. Similar proportions had associated non-deglutitive UOS relaxations. The only consistent differences were the absence of associated LOS relaxation and the absence of HROPT evidence of reflux among the achalasics leading us to conclude that their events were incomplete TLOSRs. Achalasic patients exhibit a selective defect in the TLOSR response suggesting preservation of all sensory, central and efferent aspects of the requisite neural substrate with the notable exception of LOS relaxation, a function of inhibitory (nitrergic) myenteric plexus neurons.