Fecobionics assessment of the effect of position on defecatory efficacy in normal subjects.

BACKGROUND: Defecation is a complex process and up to 25% of the population suffer from symptoms of defecatory dysfunction. For functional testing, diagnostics, and therapy of anorectal disorders, it is important to know the optimal defecation position. is The aim of this study was to evaluate defecation pressure patterns in side lying, seated and squatting defecation positions in normal subjects using a simulated stool device called Fecobionics. METHODS: The Fecobionics expulsion parameters were assessed in an interventional study design conducted from May 29 to December 9 2019. Subjects were invited to participate in the study through advertisement at The Chinese University of Hong Kong. The Fecobionics device consisted of a core containing pressure sensors at the front (caudal end) and rear (cranial end) and a polyester-urethane bag spanning most of the core length which also contained sensors. The Fecobionics bag was distended to 50 ml in the rectum of normal subjects (no present and past symptoms of defecatory disorders, no prior abdominal surgery, medication or chronic diseases). Studies were done in side lying (left lateral recumbent position), seated (hip flexed 90°) and squatting position (hip flexed 25°). Pressure endpoints including the rear-front pressure diagram and defecation indices were compared between positions. RESULTS: Twelve subjects (6 females/6 males, mean age 26.3 ± 2.6 [19.0-48.0] years) were included and underwent the planned procedures. The resting anal pressure for side lying and seated positions were 33.1 ± 4.1 cmH2O and 37.1 ± 4.0 cmH2O (p > 0.3). The anal squeeze pressure for side lying and seated positions were 98.4 ± 6.9 cmH2O and 142.3 ± 16.4 cmH2O (p < 0.05). The expulsion duration for the side lying, seated and squatting positions were 108.9 ± 8.3 s, 15.0 ± 2.1 s and 16.1 ± 2.9 s, respectively (p < 0.01 between lying and the two other positions). The maximum evacuation pressure for seated and squatting were 130.1 ± 12.4 cmH2O and 134.0 ± 11.1 cmH2O (p > 0.5). Rear-front pressure diagrams and distensibility indices demonstrated distinct differences in pressure patterns between the side lying position group and the other positions. CONCLUSIONS: The delay in expelling the Fecobionics device in the lying position was associated with dyssynergic pressure patterns on the device. Quantitative differences were not found between the seated and squatting position. Trial Registration http://www.clinicaltrials.gov Identifier: NCT03317938.

Theoretical Tools to Analyze Anorectal Mechanophysiological Data Generated by the Fecobionics Device.

A mechanical approach is needed for understanding anorectal function and defecation. Fecal continence is achieved by several interacting mechanisms including anatomical factors, anorectal sensation, rectal compliance, stool consistency, anal muscle strength, motility, and psychological factors. The balance is easily disturbed, resulting in symptoms such as fecal incontinence and constipation. Novel technologies have been developed in recent years for studying anorectal function. Especially, the Fecobionics device, a simulated feces, has gained attention recently. This facilitates new analysis of anorectal mechanical function. In this study, a theoretical model is developed to analyze anorectal mechanophysiological data generated by the Fecobionics device. Theoretical approaches can enhance future interdisciplinary research for unraveling defecatory function, sensory-motor disorders, and symptoms. This is a step in the direction of personalized treatment for gastrointestinal disorders based on optimized subtyping of anorectal disorders.

No beneficial effect of Polidocanol treatment in Achilles tendinopathy: a randomised controlled trial.

PURPOSE: Polidocanol injections have been used to treat chronic Achilles tendinopathy in clinical settings, but the few studies published show inconsistent results. The aim of this study was to evaluate the mid-term effect of Polidocanol in patients with chronic Achilles tendinopathy. It was hypothesised that patients treated with Polidocanol would have significant improvements in the outcome measures investigated compared to patients treated with a placebo treatment at mid-term follow-up. METHODS: This randomised controlled trial included forty-eight patients aged 32-77 years with a history of Achilles tendinopathy for at least 3 months and with neovascularisation demonstrated by ultrasonography was included. A minimum of 3 months of eccentric exercise treatment was required before participating. The patients were allocated to a maximum of two injection of either Polidocanol or Lidocaine (placebo). The primary outcome measure was pain during walking reported on a visual analogue scale. Secondary outcome measures were Foot and Ankle Outcome Score (FAOS), patient satisfaction with treatment and, shortly after inclusion, the Victorian Institute of Sports Assessment-Achilles questionnaire (VISA-A) was also included. Follow-up examinations were performed after 3 and 6 months. RESULTS: Pain during walking decreased during the 6-month follow-up period, but no significant differences were seen between the two groups. The same tendency was seen for FAOS and VISA-A in which both groups showed an improvement at 3- and 6-month follow-up, but no mid-term differences between the groups were seen. An equal number of patients in the two groups were satisfied with the treatment at follow-up. CONCLUSIONS: The results indicate that Polidocanol is a safe treatment, but the mid-term effects are the same as a placebo treatment. This further questions the use of Polidocanol in the treatment of chronic Achilles tendinopathy. LEVEL OF EVIDENCE: I.

Distensibility of the anal canal in patients with systemic sclerosis: a study with the functional lumen imaging probe.

AIM: Systemic sclerosis (SSc) is a generalized connective tissue disease that affects smooth muscle cells. Patients with SSc often have faecal incontinence caused by fibrotic degeneration of the internal anal sphincter (IAS). The functional lumen imaging probe (FLIP) is a novel method that allows the segmental biomechanical properties of the anal canal to be dynamically evaluated. The aim of the present study was to compare the segmental biomechanical properties of the anal canal in incontinent SSc patients and healthy controls. We hypothesized that the FLIP would reveal weaknesses of the IAS in the SSc patients. METHOD: We performed FLIP distensions, endoanal ultrasonography and standard anal manometry on 14 incontinent SSc patients [11 women, median age 60 years (range 35-80)] and 15 healthy volunteers [12 women, median age 54 years (range 33-67)]. The anal canal was divided into three parts for the biomechanical analysis: upper (surrounded by the IAS and the puborectalis), middle (IAS and external anal sphincter) and lower (external sphincter only). RESULTS: The middle anal canal was the segment most resistant to distension in all of the subjects, but it was less resistant in the SSc patients than in the controls (P < 0.01). Correspondingly, the endoanal ultrasonography showed that the IAS of the SSc patients was thinner than normal (P < 0.05), and the anal resting and squeeze pressures were lower (P < 0.05). Only minor distensibility differences were found in the upper anal canal. No changes were found in the lower anal canal. CONCLUSION: Faecal incontinence in SSc patients is associated with poor IAS function, causing increased distensibility of the middle anal canal.

Fecobionics in proctology: review and perspectives.

Fecobionics is a novel integrated technology for assessment of anorectal function. It is a defecatory test with simultaneous measurements of pressures, orientation, and device angle (a proxy of the anorectal angle). Furthermore, the latest Fecobionics prototypes measure diameters (shape) using impedance planimetry during evacuation of the device. The simultaneous measurement of multiple variables in the integrated test allows new metrics to be developed including more advanced novel defecation indices, enabling mechanistic insight in the defecation process at an unprecedented level in patients with anorectal disorders including patients suffering from obstructed defecation, fecal incontinence, and low anterior resection syndrome. The device has the consistency and shape of a normal stool (type 3-4 on the Bristol Stool Form Scale). Fecobionics has been validated on the bench and in animal studies and used in clinical trials to study defecation phenotypes in normal human subjects and patients with obstructed defecation, fecal incontinence, and low anterior resection syndrome after rectal cancer surgery. Subtypes have been defined, especially of patients with obstructed defecation. Furthermore, Fecobionics has been used to monitor biofeedback therapy in patients with fecal incontinence to predict the outcome of the therapy (responder versus non-responder). Most Fecobionics studies showed a closer correlation to symptoms as compared to current technologies for anorectal assessment. The present article outlines previous and ongoing work, and perspectives for future studies in proctology, including in physiological assessment of function, diagnostics, monitoring of therapy, and as a tool for biofeedback therapy.

Neurogenic adaptation contributes to the afferent response to mechanical stimulation.

This study aimed to characterize the effect of mechanical stimuli on mesenteric afferent nerve signaling in the isolated rat jejunum in vitro. This was done to determine the effect of mechanical stresses and strains relative to nonmechanical parameters (neurogenic adaptation). Mechanical stimulations were applied to a segment of jejunum from 15 rats using ramp distension with water at three rates of distension, a relaxation test (volume maintained constant from initial pressure of 20 or 40 mmHg), and a creep test (pressure maintained constant). Circumferential stress and strain and the spike rate increase ratio were calculated for evaluation of afferent nerve activity during the mechanical stimulations. Ramp distension evoked two distinct phases of afferent nerve signaling as a function of circumferential stress or strain. Changing the volume distension rate did not change the stress-strain relationship, but faster distension rate increased the afferent firing rate (P < 0.05). In the stress relaxation test, the spike rate declined faster and to a greater extent than the stress. In the creep test, the spike rate declined, despite a small increase in the strain. Three classes of mechanosensitive single-afferent units (low, wide dynamic range, and high threshold units) showed different response profiles against stress and strain. Low-threshold units exhibited a near linear relationship against the strain (R(2) = 0.8095), whereas high-threshold units exhibited a linear profile against the stress (R(2) = 0.9642). The afferent response is sensitive to the distension speed and to the stress and strain level during distension. However, the afferent nerve response is not a simple function of either stress or strain. Nonmechanical time-dependent adaptive responses other than those related to viscoelasticity also play a role.

Patients with esophageal motility disorders show distinct patterns based on axial force measurements.

BACKGROUND: Using manometry, the classification of motility-related disorders in the esophagus is vague and overlapping. We present a new method, which combines manometry and axial force measurements in a single catheter. AIM: The aim was to examine the manometric and axial force recordings during swallows. METHODS: Recordings from 20 patients suffering from diffuse esophageal spasms (DES) (8), achalasia (5) and other diseases including gastro-oesophageal reflux (7) were compared to recordings made in ten healthy subjects. The probe was capable of measuring axial force 6.5-cm proximal to the lower esophageal sphincter (LES) and pressures 8-, 10- and 12-cm proximal to the LES. After insertion, five dry and five wet swallows were made. Swallows were repeated with 0, 2, 4 and 6 ml of water in a bag mounted distal to the axial force recording site. Each contraction was analysed for duration and amplitude, and was categorised according to its configuration. RESULTS: The number of failed contractions measured with axial force was lower for the achalasia (P < 0.001) and DES groups (P < 0.001) compared to the healthy volunteers. The number of multi-peaked contractions was unchanged for the achalasia and DES groups while it increased for the group of healthy volunteers. On several occasions a negative traction force was encountered though the manometric pattern appeared normal. CONCLUSIONS: Measurements of axial force generated by primary peristalsis provide additional information about esophageal neuromuscular function in different diseases that is not demonstrable with manometry alone.

Rome III subgroups of functional dyspepsia exhibit different characteristics of antral contractions measured by strain rate imaging - a pilot study.

PURPOSE: Rome III defines two distinct entities of functional dyspepsia (FD), namely epigastric pain syndrome (EPS) and postprandial distress syndrome (PDS). We aimed at studying these subgroups of FD by simultaneously assessing antral strain, gastric accommodation and emptying and visceral hypersensitivity. MATERIALS AND METHODS: Strain during antral contractions was assessed by ultrasound strain rate imaging in 15 controls and 19 FD patients (8 EPS patients and 11 PDS patients). Gastric accommodation and emptying were assessed using B-mode ultrasonography. Symptoms were assessed by visual analogue scale (VAS). RESULTS: During fasting, antral strain in EPS patients (mean±SEM) was 61.4 ±â€Š6.4 %, significantly higher than in controls (47.5 ±â€Š3.3 %; p = 0.042) and in PDS patients (28.6 ±â€Š1.7 %; p = 0.001). PDS patients had lower strain than controls (p < 0.001). Postprandially, EPS patients had higher strain than both controls and PDS patients (p < 0.01) but no difference was found between controls and PDS patients. Compared with controls, PDS patients had significantly larger fasting proximal area than controls (14.9 ±â€Š1.6 cm2 vs. 7.8 ±â€Š0.2 cm2; p < 0.001), whereas EPS patients did not differ (12.1 ±â€Š1.9 cm2; p = 0.057). Gastric emptying fraction (1 - proximal area at 40 min postprandially/area at 1 min postprandial × 100) at 40 min postprandially in EPS patients 46.4 ±â€Š6.6 % was lower than in controls (62.9 ±â€Š1.3 %; p = 0.032), but higher than PDS patients (27.4 ±â€Š5.3 %; p = 0.018). CONCLUSION: Anterior radial strain measured by ultrasound strain rate imaging may discriminate between subgroups of FD and healthy controls. This study supports the Rome III classification of FD into EPS and PDS groups.

Functional luminal imaging probe: a new technique for dynamic evaluation of mechanical properties of the anal canal.

BACKGROUND: The muscle structures surrounding the anal canal are of major importance in maintaining continence but their anatomy and function vary along its length. Standard manometry does not provide detailed information about mechanical properties of the anal canal. A new functional luminal imaging probe (FLIP) has been developed for this purpose. The aim of our study was to investigate whether FLIP allows detailed evaluation of dynamic biomechanical properties along the length of the anal canal. METHODS: The in vitro validity and reproducibility of the FLIP system were tested. Fifteen healthy volunteers (age 32-65 years, mean 51 years), of whom 12 were females, were investigated. The integrity and dimensions of the anal sphincter apparatus were evaluated with endoanal ultrasonography and standard anal manometry. During standardized distensions with the FLIP, 16 cross-sectional areas of the anal canal were measured at 5-mm intervals. Distensibility of the following three segments was evaluated: upper anal canal (surrounded by the internal anal sphincter and the puborectalis muscle), mid-anal canal (surrounded by the internal anal sphincter and the external anal sphincter) and lower anal canal (surrounded by the external anal sphincter). Color contour plots were generated from the FLIP-based dynamic recordings of serial cross-sections. RESULTS: In vitro tests confirmed the validity and reproducibility of the FLIP system. The luminal geometry during distension and the biomechanical properties of the anal canal differed at the three levels. Both at rest and during squeeze the mid-anal canal was significantly less distensible than the upper (p < 0.01) and the lower (p < 0.05) anal canal. CONCLUSIONS: FLIP is a promising method for evaluation of the nonhomogeneous biomechanical properties along the length of the anal canal.

New developments in defecatory studies based on biomechatronics.

Introduction: Defecation is a complex process that is difficult to study and analyze directly. In anorectal disease conditions, the defecation process may be disturbed, resulting in symptoms including fecal incontinence and constipation. Current state-of-the-art technology measures various aspects of anorectal function but detailed analysis is impossible because they are stand-alone tests rather than an integrated multi-dimensional test. Objectives: The need for physiologically-relevant and easy-to-use diagnostic tests for identifying underlying mechanisms is substantial. We aimed to advance the field with integrated technology for anorectal function assessment. Methods: We developed a simulated stool named Fecobionics that integrates several tests to assess defecation pressures, dimensions, shape, orientation and bending during evacuation. A novelty is that pressures are measured in axial direction, i.e. in the direction of the trajectory. Using this novel tool, we present new analytical methods to calculate physiologically relevant parameters during expulsion in normal human subjects. Results: Data are reported from 28 human subjects with progressively more advanced versions of Fecobionics. A new concept utilizes the rear-front pressure (preload-afterload) diagram for computation of novel defecation indices. Fecobionics obtained physiological data that cannot be obtained with current state-of-the-art technologies. Conclusion: Fecobionics measures well known parameters such as expulsion time and pressures as well as new metrics including defecation indices. The study suggests that Fecobionics is effective in evaluation of key defecatory parameters and well positioned as an integrated technology for assessment of anorectal function and dysfunction.

Irritable bowel syndrome and risk of colorectal cancer: a Danish nationwide cohort study.

BACKGROUND: Little is known about the risk of colorectal cancer among patients with irritable bowel syndrome (IBS). METHODS: We conducted a nationwide cohort study using data from the Danish National Registry of Patients and the Danish Cancer Registry from 1977 to 2008. We included patients with a first-time hospital contact for IBS and followed them for colorectal cancer. We estimated the expected number of cancers by applying national rates and we computed standardised incidence ratios (SIRs) by comparing the observed number of colorectal cancers with the expected number. We stratified the SIRs according to age, gender, and time of follow-up. RESULTS: Among 57,851 IBS patients, we identified 407 cases of colon cancer during a combined follow-up of 506,930 years (SIR, 1.14 (95% confidence interval (CI): 1.03-1.25) and 115 cases of rectal cancer, corresponding to a SIR of 0.67 (95% CI: 0.52-0.85). In the first 3 months after an IBS diagnosis, the SIR was 8.42 (95% CI: 6.48-10.75) for colon cancer and 4.81 (95% CI: 2.85-7.60) for rectal cancer. Thereafter, the SIRs declined and 4-10 years after an IBS diagnosis, the SIRs for both colon and rectal cancer remained below 0.95. CONCLUSION: We found a decreased risk of colorectal cancer in the period 1-10 years after an IBS diagnosis. However, in the first 3 months after an IBS diagnosis, the risk of colon cancer was more than eight-fold increased and the risk of rectal cancer was five-fold increased. These increased risks are likely to be explained by diagnostic confusion because of overlapping symptomatology.

Novel bionics developments in gastroenterology: fecobionics assessment of lower GI tract function.

Biomechatronics (bionics) is an applied science that is interdisciplinary between biology and engineering (mechanical, electrical and electronics engineering). Biomechatronics covers a wide area and is probably best known in development of prosthetic limbs, vision aids, robotics and neuroscience. Although the gastrointestinal tract is difficult to study, it is particularly suited for a bionics approach as demonstrated by recent developments. Ingestible capsules that travel the tract and record physiological variables have been used in the clinic. Other examples include sacral nerve stimulators that seek to restore normal anorectal function. Recently, we developed a simulated stool termed fecobionics. It has the shape of normal stool and records a variety of parameters including pressures, bending (anorectal angle) and shape changes during colonic transit and defecation, i.e. it integrates several current tests. Fecobionics has been used to study defecation patterns in large animals as well as in humans (normal subjects and patient groups including patients with symptoms of obstructed defecation and fecal incontinence). Recently, it was applied in a canine colon model where it revealed patterns consistent with shallow waves originating from slow waves generated by the interstitial cells of Cajal. Furthermore, novel analysis such as the rear-front pressure (preload-afterload) diagram and quantification of defecation indices have been developed that enable mechanistic insight. This paper reviews the fecobionics technology and outlines perspectives for future applications.

Translating Fecobionics Into a Technique That Addresses Clinical Needs for Objective Perineal Descent Measurements.

INTRODUCTION: Perineal descent is a phenomenon associated with anorectal dysfunction. It is diagnosed by defecography but subjected to manual measurements on the images/videos and interobserver bias. Fecobionics is a simulated feces for assessing important physiological parameters during defecation. Here, we translate Fecobionics into a new method for estimation of perineal descent based on electronic signals from the embedded inertial measurement units (IMUs). METHODS: A displacement measurement method by a combined zero-velocity update and gravity compensation algorithm from IMUs was developed. The method was verified in a robot model, which mimicked perineal descent motion. RESULTS: The method correlated well with the reference (R = 0.9789) and had a deviation from the peak displacement (range 0.25-2.5 cm) of -0.04 ± 0.498 cm. The method was further validated in 5 human experiments with comparison to the benchmark defecography technology (R = 0.79). DISCUSSION: The proposed technology is objective, i.e., electronic measurements rather than by fluoroscopy or MRI. The development may impact clinical practice by providing a resource-saving and objective technology for diagnosing perineal descent in the many patients suffering from anorectal disorders. The technology may also be used in colon experiments with Fecobionics and for other gastrointestinal devices containing IMUs such as ingestible capsules like the Smartpill.

The preterm piglet - a model in the study of oesophageal development in preterm neonates.

AIM: Preterm infants have difficulty in attaining independent oral feeding. This can ensue from inadequate sucking, swallowing and/or respiration. In impeding bolus transport, immature oesophageal motility may also be a cause. As studies on the development of oesophageal motility are invasive in preterm infants, the preterm piglet was investigated as a potential research model. METHODS: Oesophageal motility (EM) of term (n = 6) and preterm (n = 15) piglets were monitored by manometry for 10 min immediately following bottle feeding on days 1-2 and 3-4 of life. RESULTS: Piglets' oral feeding performance and EM were similar to those of their human counterparts. Term piglets readily completed their feeding, whereas their preterm counterparts did not. They also presented with greater peristaltic activity and propagating velocity. Peristaltic activity remained unchanged over time in preterm piglets, but an increase in synchronous and decrease in incomplete motor activity were noted. Preterm piglets that developed symptoms analogous to necrotizing enterocolitis (NEC) demonstrated uncharacteristic oesophageal activity. CONCLUSION: Immature EM may cause oral feeding difficulties. NEC-like symptoms may adversely affect EM. The piglet is a valid research model for studying human infant oral feeding and oesophageal development.

Stepwise radiofrequency ablation of Barrett's esophagus preserves esophageal inner diameter, compliance, and motility.

BACKGROUND AND AIM: Stepwise endoscopic circumferential and focal radiofrequency ablation is safe and effective for the eradication of Barrett's esophagus. In contrast to other techniques, radiofrequency ablation appears to avoid significant esophageal scarring or stenosis. Our aim was to evaluate whether radiofrequency ablation has an adverse effect on esophageal function in patients treated for Barrett's esophagus containing intramucosal cancer and/or high-grade dysplasia. METHODS: Twelve patients with Barrett's esophagus containing intramucosal cancer or high-grade dysplasia were included in the study. After endoscopic resection of visible abnormalities, stepwise circumferential and focal ablation were performed every 2 months up to a maximum of five sessions. Measurement of the inner diameter was performed at 1-cm intervals in the distal esophagus. Manometry was performed using a water-perfused sleeve catheter. Compliance was evaluated using the functional lumen imaging probe (FLIP), measuring eight cross-sectional areas within a saline-filled bag with two pressure side holes, one proximal to and one inside the bag. Esophageal sizing, manometry, and compliance were recorded in patients at baseline and at least 2 months after the final ablation session. In addition, FLIP and manometry measurements were performed in 10 healthy volunteers. RESULTS: All patients achieved complete eradication of dysplasia and Barrett's esophagus, without severe complications or ablation-related stenoses. The esophageal diameter was unchanged by the ablation. Lower esophageal sphincter pressure and length and esophageal contraction amplitude before and after ablation were not significantly different. Baseline compliance was significantly different between healthy volunteers and Barrett's esophagus patients. Compliance was not, however, significantly changed by ablation. CONCLUSIONS: Stepwise circumferential and focal ablation of Barrett's esophagus is an effective and safe treatment modality for early Barrett's neoplasia that appears to preserve the functional characteristics of the esophagus.

Effect of serotonin on small intestinal contractility in healthy volunteers.

The physiological significance of serotonin released into the intestinal lumen for the regulation of motility is unknown in humans. The aim of this study was to evaluate the effect of serotonin infused into the lumen of the gastric antrum, duodenum or the jejunum, on antro-duodeno-jejunal contractility in healthy human volunteers. Manometric recordings were obtained and the effects of either a standard meal, continuous intravenous infusion of serotonin (20 nmol/kg/min) or intraluminal bolus infusions of graded doses of serotonin (2.5, 25 or 250 nmol) were compared. In addition, platelet-depleted plasma levels of serotonin, blood pressure, heart rate and electrocardiogram were evaluated. All subjects showed similar results. Intravenous serotonin increased migrating motor complex phase III frequency 3-fold and migrating velocity 2-fold. Intraluminal infusion of serotonin did not change contractile activity. Platelet-depleted-plasma levels of serotonin increased 2-fold following both intravenous and high doses of intraluminal infusions of serotonin. All subjects reported minor short-lived adverse effects following intravenous serotonin stimulation, while only half of the subjects reported minor short-lived adverse effects following intraluminal serotonin stimulations. We conclude that exogenous serotonin in the lumen of the upper part of the small intestine does not seem to change antro-duodeno-jejunal contractility significantly in healthy adult volunteers.

Measurement of the axial force during primary peristalsis in the oesophagus using a novel electrical impedance technology.

The oesophagus serves to transport food and fluid from the pharynx to the stomach. Oesophageal function is usually evaluated by means of manometry which is a proxy of the force in the radial direction. However, force measurements in the axial direction will provide a better measure of oesophageal transport function. The aim of this study was to develop a probe based on electrical impedance measurements to quantify the axial force generated by oesophageal contractions, i.e. probe elongation was associated with the axial force. Calibration with weights up to 200 g was done. The dispersion, creep, temperature and bending dependence were studied at the bench. Subsequently, the probe was tested in vivo in a healthy human volunteer. The probe showed good reproducibility and the dispersion was <0.04. Some dependence on temperature, creep and bending was found. Interpolation of the calibration curves made it possible to compensate for temperature fluctuations. The maximum deviation was 6.1 +/- 3.7% at loads of 50 g. The influence of creep showed a maximum net creep of 6.1 g after 8 s. The swallowed bolus size correlated with the axial force measurements (P = 0.038) but not with manometric measurements. In conclusion, the new technique measures axial force in the oesophagus and may in the future provide valuable information about oesophageal function.

Blood Flow Regulates Zebrafish Caudal Vein Plexus Angiogenesis by ERK5-klf2a-nos2b Signaling.

BACKGROUND: Vascular network formation induced by angiogenesis plays an important role in many physiological and pathological processes. However, the role of blood flow and underlying mechanisms in vascular network formation, for example for the development of the caudal vein plexus (CVP), is poorly understood. OBJECTIVE: The aim of this study was to explore the role of ERK5-klf2a-nos2b signaling in the CVP angiogenesis. METHOD AND RESULTS: In this study on tnnt2a-MO injection and chemical blood flow modulator treatment in zebrafish embryos, we demonstrated that decreased blood flow disrupted CVP formation. The hemodynamic force was quantitatively analyzed. Furthermore, CVP angiogenesis in zebrafish embryos was inhibited by disruption of the blood flow downstream effectors ERK5, klf2a, and nos2b in response to treatment with the ERK5 specific inhibitor and to injection of klf2a-MO, nos2b-MO. Overexpression of klf2a mRNA or nos2b mRNA restored vascular defects in tnnt2a or klf2a morphants. The data suggest that flow-induced ERK5-klf2a-nos2b signaling is involved in CVP angiogenesis in zebrafish embryos. CONCLUSION: We have demonstrated that blood flow is essential for vascular network formation, specifically for CVP angiogenesis in zebrafish. A novel genetic and mechanical mechanism was discovered in which ERK5 facilitates the integration of blood flow with the downstream klf2a-nos2b signaling for CVP angiogenesis.

Review article: acidity and volume of the refluxate in the genesis of gastro-oesophageal reflux disease symptoms.

BACKGROUND: A number of mechanisms, other than acid reflux, may be responsible for the symptoms of gastro-oesophageal reflux disease. AIM: To assess the importance of non-acid reflux mechanisms. METHODS: This review is based on presentations and discussion at a workshop, where specialists in the field analysed data relating to these mechanisms. RESULTS: Weakly acidic reflux, pH (4-7), detected with impedance-pHmetry is associated with regurgitation and atypical gastro-oesophageal reflux disease symptoms. It is not clear whether pepsin and trypsin can elicit symptoms, but bile can elicit heartburn. The magnitude of reflux-induced oesophageal distension can be determined by high frequency ultrasonography and is not reduced by proton pump inhibition, suggesting that persisting symptoms 'on' a proton pump inhibitor may still be due to oesophageal distension by non-acidic reflux. Exaggerated longitudinal muscle contraction can induce non-acid-related heartburn. Preliminary studies showed a positive effect of baclofen, surgery or endoscopic procedures to reduce weakly acidic reflux. CONCLUSION: Mechanisms other than acid reflux are involved in some of the symptoms of gastro-oesophageal reflux disease. Controlled outcome studies are needed to clarify their roles and the indications for antireflux procedures in patients with persistent symptoms whilst 'on' a proton pump inhibitor.