Breathing training on lower esophageal sphincter as a complementary treatment of gastroesophageal reflux disease (GERD): a systematic review.

OBJECTIVE: Gastroesophageal reflux disease (GERD) represents one of the most common gastrointestinal disorders, but is still a challenge to cure. Proton pump inhibitors (PPIs) are currently the GERD's standard treatment, although not successful in all patients; some concerns have been raised regarding their long term consumption. Recently, some studies showed the benefits of inspiratory muscle training in increasing the lower esophageal sphincter pressure in patients affected by GERD, thereby reducing their symptoms. MATERIALS AND METHODS: Relevant published studies were searched in Pubmed, Google Scholar, Ovid or Medical Subject Headings using the following keywords: "GERD" and physiotherapy", "GERD" and "exercise", "GERD" and "breathing", "GERD and "training". RESULTS: At the end of our selection process, four publications have been included for systematic review. All of them were prospective controlled studies, mainly based on the training of the diaphragm muscle. GERD symptoms, pH-manometry values and PPIs usage were assessed. CONCLUSIONS: Among the non-surgical, non-pharmacological treatment modalities, the breathing training on diaphragm could play an important role in selected patients to manage the symptoms of GERD.

Intra-bolus pressure and esophagogastric gradient, assessed with high-resolution manometry, are associated with acid exposure and proximal migration of refluxate.

Trans-sphincteric pressure gradient (TSPG) seems to play a relevant role in eliciting refluxes during transient lower esophageal sphincter relaxations (TLESRs). Intra-bolus pressure (IBP) is considered to be correlated to esophageal wall tone. We aimed to evaluate the relationship between IBP, TSPG during TLESRs and the dynamic properties of refluxate in gastroesophageal reflux disease. Sixteen non-erosive reflux disease (NERD), 10 erosive disease (ERD) patients and 12 healthy volunteers (HVs), underwent 24-hour impedance-pH monitoring and combined high-resolution manometry-impedance before and 60 minutes. After a meal, ERD patients presented a significantly lower mean IBP (4.7 ± 1.6 mmHg) respect to NERD patients (8.9 ± 2.8 mmHg) and HVs (9.2 ± 3.2 mmHg). NERD patients with physiological abnormal acid exposure time showed a mean IBP (10.4 ± 3.1 mmHg) significantly higher than that in NERD with pathological abnormal acid exposure time (5.1 ± 1.5 mmHg). The TSPG value was significantly higher during TLESRs accompanied by reflux than during TLESRs not associated with reflux, both in patients and in HVs. A significant direct correlation was found between IBP, TSPG and proximal spread of refluxes in patients and in HVs. Gastroesophageal reflux disease patients display different degrees of esophageal distension. An increased compliance of the distal esophagus may accommodate larger volumes of refluxate and likely facilitates the injuries development. Higher TSPG values appear to facilitate the occurrence of refluxes during TLESRs. In patients with NERD, higher TSPG and IBP values favor proximal spread of refluxate and hence may play a relevant role in symptom generation.

A critical review and meta-analysis of the perceptual pseudoneglect across psychiatric disorders: is there a continuum?

The phenomenon known as "perceptual pseudoneglect" refers to the leftward bias in visuospatial attention in non-clinical samples, possibly as a consequence of right hemisphere dominance for visuospatial attention. The degree of such a lateralized visuospatial attention bias is often assessed using the line bisection task. Interestingly, various psychiatric disorders may influence the expression of this phenomenon. The aim of this paper was to perform a critical appraisal of the literature on the expression of the perceptual pseudoneglect across all psychiatric disorders accompanied by meta-analytical evaluation of the data. Moreover, we will discuss whether this phenomenon may be considered as a trait marker across different psychiatric disorders.

Reflux pattern and role of impedance-pH variables in predicting PPI response in patients with suspected GERD-related chronic cough.

BACKGROUND: Gastro-oesophageal reflux disease (GERD) may contribute to the onset of chronic cough (CC); however, the multichannel intraluminal impedance-pH (MII-pH) monitoring is often within the normal range and the response to proton pump inhibitors (PPIs) unsatisfactory. The measure of impedance baseline (IB) increases the sensitivity of MII-pH in patients with typical symptoms. AIM: To evaluate the role of MII-pH variables, including IB, in predicting PPI response and to define the characteristics of the reflux pattern in CC patients. METHODS: Prospectively selected CC patients suspected GERD-related underwent MII-pH monitoring and, therefore, received a double dose of PPIs for at least 6 weeks. Patients filled symptom scores before MII-pH and after PPI therapy. MII-pH data were compared with those obtained in 60 non-erosive reflux disease patients with typical symptoms. RESULTS: A total of 156 CC patients entered the study: 68 (43.5%) responders and 88 (56.5%) nonresponders to PPIs. The number of reflux episodes was significantly higher in CC compared with that in typical symptoms patients. Nonresponder CC patients with a pathological acid exposure time (AET) and/or IB value were 43/88 (49%), while 15/88 (17%) presented only pathological AET (P < 0.001). CC patients with a pathological AET or IB, or with both a pathological AET and IB, showed a probability of PPI response twofold greater than patients with normal AET and IB. CONCLUSIONS: The presence of a pathological AET or pathological IB in CC patients is associated with a greater probability of PPI response. IB is a promising variable in patients with CC, as it increases the diagnostic yield of MII-pH and allows confirmation of the GERD diagnosis in these patients.

Dilated intercellular space diameter as marker of reflux-related mucosal injury in children with chronic cough and gastro-oesophageal reflux disease.

BACKGROUND: The diagnostic corroboration of the relationship between gastro-oesophageal reflux disease (GERD) and chronic cough remains challenging. AIMS: To compare oesophageal mucosal intercellular space diameter (ISD) in children with GERD, children with gastro-oesophageal reflux (GER)-related cough (GrC) and a control group, and to explore the relationship between baseline impedance levels and dilated ISD in children with GER-related cough. METHODS: Forty children with GERD, 15 children with GrC and 12 controls prospectively underwent oesophagogastroduodenoscopy (EGD) with oesophageal biopsies taken 2-3 cm above squamocolumnar junction. ISD were quantified using transmission electron microscopy. Impedance-pH monitoring with evaluation of baseline impedance in the most distal impedance channel was performed in both patient groups. RESULTS: A significant difference in mean ISD values was found between GrC patients (0.9 ± 0.2 µm) and controls (0.5 ± 0.2 µm, P < 0.001), whereas there was no difference between GrC and GERD group (1 ± 0.3 µm, NS). No difference was found in the mean ISD between GrC children with or without pathological oesophageal acid exposure time (1 ± 0.3 vs. 0.9 ± 0.2 µm), and there was no correlation between ISD and any reflux parameter. Finally, there was no correlation between ISD and distal baseline impedance values (r:-0.35; NS). CONCLUSIONS: In children with reflux-related cough, dilated intercellular space diameter appears to be an objective and useful marker of oesophageal mucosal injury regardless of acid exposure, and its evaluation should be considered for those patients where the diagnosis is uncertain. In children with reflux-related cough, baseline impedance levels have no role in identifying reflux-induced oesophageal mucosal ultrastructural changes.

Common variant at 16p11.2 conferring risk of psychosis.

Epidemiological and genetic data support the notion that schizophrenia and bipolar disorder share genetic risk factors. In our previous genome-wide association study, meta-analysis and follow-up (totaling as many as 18 206 cases and 42 536 controls), we identified four loci showing genome-wide significant association with schizophrenia. Here we consider a mixed schizophrenia and bipolar disorder (psychosis) phenotype (addition of 7469 bipolar disorder cases, 1535 schizophrenia cases, 333 other psychosis cases, 808 unaffected family members and 46 160 controls). Combined analysis reveals a novel variant at 16p11.2 showing genome-wide significant association (rs4583255[T]; odds ratio=1.08; P=6.6 × 10(-11)). The new variant is located within a 593-kb region that substantially increases risk of psychosis when duplicated. In line with the association of the duplication with reduced body mass index (BMI), rs4583255[T] is also associated with lower BMI (P=0.0039 in the public GIANT consortium data set; P=0.00047 in 22 651 additional Icelanders).

Acid reflux episodes sensitize the esophagus to perception of weakly acidic and mixed reflux in non-erosive reflux disease patients.

BACKGROUND: Non-erosive reflux disease (NERD) patients are more sensitive than erosive esophagitis patients to weakly acidic reflux and to the presence of gas in the refluxate. Intra-esophageal acid perfusion sensitizes esophageal receptors to mechanical and chemical stimuli. METHODS: To establish whether acid sensitization plays a role in the perception of weakly acidic and mixed reflux episodes, 29 NERD patients, responders and 14 non-responders to proton pump inhibitors (PPIs), underwent pH-impedance monitoring. Non-responders repeated the study while on PPIs. To assess the effect of acid exposure on symptom perception, the time period with pH below 4 was measured in 15- and 30-minute time-windows preceding the onset of each reflux episode. KEY RESULTS: Considering weakly acidic and mixed refluxes, both in responder and non-responder patients (off PPIs), the symptomatic refluxes were preceded by a significantly higher cumulative acid exposure than the asymptomatic refluxes. In all patients, following acid reflux, the percentage of symptomatic weakly acidic reflux episodes was significantly higher than that of asymptomatic refluxes. Non-responder patients, off-treatment, were characterized by a lower proportion of weakly acidic reflux and mixed reflux episodes. In the non-responder patients on PPI, only mixed and weakly symptomatic reflux episodes were preceded by a higher cumulative acid exposure. CONCLUSIONS & INFERENCES: In NERD patients, spontaneous acid reflux enhances subsequent reflux perception, regardless of acidity or liquid/mixed composition of episodes; in non-responder patients on PPIs, only the perception of mixed and weakly acidic reflux episodes seems to be mediated by a preceding acid exposure.

Relationship between baseline impedance levels and esophageal mucosal integrity in children with erosive and non-erosive reflux disease.

BACKGROUND: Baseline impedance measurement has been reported to be related to esophageal acid exposure and hypothesized to be a marker of microscopic changes of the esophageal mucosa. Aims of the study were to establish whether any relationship existed between the magnitude of intercellular space diameter (ISD) of esophageal mucosa and baseline impedance levels in children with gastro-esophageal reflux disease (GERD), and to compare baseline impedance levels between children with non erosive (NERD) and erosive (ERD) reflux disease. METHODS: Fifteen children (median age: 11.2 years) with NERD, and 11 with ERD (median age: 9.6 years) were prospectively studied. All patients underwent upper endoscopy. Biopsies were taken 2-3cm above the Z-line, and ISD was measured using transmission electron microscopy. All patients underwent impedance pH-monitoring, and baseline impedance levels were assessed in the most distal impedance channel. KEY RESULTS: Mean (±SD) ISD did not differ between NERD (1.0±0.3µm) and ERD (1.1 ± 0.3 µm, ns). Considering all patients together, no correlation was found between distal baseline impedance and ISD (r: -0.15; ns). Conversely, negative correlations were found between distal baseline impedance and acid exposure time (r: -0.76; P<0.001), long-lasting reflux episodes (r: -0.78; P<0.001), acid reflux episodes (r: -0.62; P<0.001), and acid clearance time (r: -0.79; P<0.001). Distal baseline impedance was significantly lower in ERD [1455 (947-2338) Ω] than in NERD children [3065 (2253-3771) Ω; P<0.01]. CONCLUSIONS & INFERENCES: In children with GERD baseline impedance levels are not useful in predicting reflux-induced ultrastructural changes in the esophageal mucosa, despite their ability to discriminate between NERD and ERD.

Platelet-activating factor and distinct chemokines are elevated in mucosal biopsies of erosive compared with non-erosive reflux disease patients and controls.

BACKGROUND: A distinction between symptomatic non-erosive reflux disease (NERD) and erosive esophagitis (EE) patients is supported by the presence of inflammatory response in the mucosa of EE patients, leading to a damage of mucosal integrity. To explore the underlying mechanism of this difference, we assessed inflammatory mediators in mucosal biopsies from EE and NERD patients and compared them with controls. METHODS: Nineteen NERD patients, 15 EE patients, and 16 healthy subjects underwent endoscopy after a 3-week washout from PPI or H(2) antagonists. Biopsies obtained from the distal esophagus were examined by quantitative real-time polymerase chain reaction (qPCR) and multiplex enzyme-linked immunosorbent assay for selected chemokines and lyso-PAF acetyltransferase (LysoPAF-AT), the enzyme responsible for production of platelet-activating factor (PAF). KEY RESULTS: Expression of LysoPAF-AT and multiple chemokines was significantly increased in mucosal biopsies derived from EE patients, when compared with NERD patients and healthy controls. Upregulated chemokines included interleukin 8, eotaxin-1, -2, and -3, macrophage inflammatory protein-1α (MIP-1α), and monocyte chemoattractant protein-1 (MCP-1). LysoPAF-AT and the chemokine profile in NERD patients were comparable with healthy controls. CONCLUSIONS & INFERENCES: Levels of selected cytokines and Lyso-PAF AT were significantly higher in the esophageal mucosa of EE patients compared with NERD and control patients. This difference may explain the distinct inflammatory response occurring in EE patients' mucosa. In contrast, as no significant differences existed between the levels of all mediators in NERD and control subjects, an inflammatory response does not appear to play a major role in the pathogenesis of the abnormalities found in NERD patients.

Measurement of acid exposure of proximal esophagus: a better tool for diagnosing non-erosive reflux disease.

BACKGROUND: The sensitivity of 24-h pH monitoring is poor in non-erosive reflux disease (NERD). In NERD patients, the proximal extent of acid reflux is one of the main determinants of reflux perception. The present study was aimed to compare the diagnostic accuracy of acid exposure time (AET), at 5 cm above the lower esophageal sphincter, with those at 10 cm and at 3 cm below the upper esophageal sphincter as well as the reproducibility of these parameters. METHODS: A total of 93 consecutive NERD patients, with typical symptoms responsive to proton pump inhibitor treatment, and 40 controls underwent esophageal manometry and multi-channel 24-h pH-test; 13 patients underwent the same study on two occasions. Symptom association probability (SAP) values were evaluated at each esophageal level. KEY RESULTS: The ROC curve indicates that the area under the curve was 0.79 at distal (SE=0.039), 0.87 (SE=0.032) at proximal (P=0.029 vs distal), and 0.85 (SE=0.033) at very proximal esophagus (P =0.148). AET showed a reproducibility of 61% (Kappa 0.22) at distal esophagus, 77% (Kappa 0.45) at proximal and 53% (Kappa 0.05) at very proximal esophagus. The percentage of patients with a positive SAP was not significantly different when assessed at the distal compared with the proximal esophagus. CONCLUSIONS & INFERENCES: In NERD patients, the diagnostic yield of the pH test is significantly improved by the assessment of AET at the proximal esophagus. As this variable seems to be less affected by the day to day variability, it could be considered a reliable and useful diagnostic tool in NERD patients.

Quetiapine fumarate for schizophrenia and bipolar disorder in young patients.

During the past decade, there has been a substantial increase in the prescribing of antipsychotics to young patients for a variety of pediatric psychiatric disorders. Quetiapine (Seroquel®) received its initial indication from the U.S. Food and Drug Administration for treatment of schizophrenia in 1997, and it received its second indication for the treatment of mania-associated bipolar disorder in 2004. Currently, in young patients, authorized quetiapine indications are schizophrenia in individuals aged 13 or older and manic episodes associated with bipolar I disorder in children 10 to 17 years old. Quetiapine has different pharmacological actions and acts as an antagonist for following receptors: D(2) receptor, serotonin 5-HT(2A) also known as α(1)-adrenoceptor, histamine 1 receptor and muscarinic acetylcholine receptor. Several studies have shown its favorable profile of effectiveness and tolerability in young bipolar and schizophrenic patients. However, the current data make it very clear that the risks and benefits of this drug need to be weighed individually for each patient.

Regional oesophageal sensitivity to acid and weakly acidic reflux in patients with non-erosive reflux disease.

The mechanisms underlying symptoms in non-erosive reflux disease (NERD) remain to be elucidated. Non-erosive reflux disease patients appear to be more sensitive to intraluminal stimula than erosive patients, the proximal oesophagus being the most sensitive. In order to assess regional oesophageal changes in reflux acidity and sensitivity to reflux, according either to the acidity or the composition of the refluxate, combined multiple pH and multiple pH-impedance (pH-MII) was performed in 16 NERD patients. According to multiple pH-metry, 29% and 12% of reflux events reached the middle and proximal oesophagus respectively, and 35% and 19% according to conventional pH-MII (P < 0.05). The per-individual analysis confirmed the difference between the two techniques. According to combined distal and proximal pH-MII, approximately 30% of distal acid reflux became weakly acidic at the proximal oesophagus. In all patients, the frequency of symptomatic refluxes, both acid and weakly acidic, was significantly higher at the proximal, compared with distal oesophagus (25 +/- 8%vs 11 +/- 2% for acid reflux and 27 +/- 8%vs 8 +/- 2% for weakly acidic reflux; P < 0.05). Compared with multiple pH-metry, pH-MII shows a higher sensitivity in the detection of proximal reflux. As approximately 30% of acid reflux becomes weakly acidic along the oesophageal body, to better characterize proximal reflux, in clinical practice, combined proximal pH-impedance monitoring should be used. In NERD patients, the proximal oesophagus seems to be more sensitive to both acid and weakly acidic reflux.

Intercellular space diameters of the oesophageal epithelium in NERD patients: head to head comparison between light and electron microscopy analysis.

BACKGROUND: Dilation of intercellular space diameters of oesophageal epithelium detected at transmission electron microscopy morphometry is a marker of tissue injury in non-erosive reflux disease patients. Semi-quantitative evaluation of intercellular space diameters using light microscopy seems to provide promising results. AIM/METHODS: To comparatively evaluate intercellular space diameters in the same patients, by means of morphometry and semi-quantitative analysis, both on light microscopy and transmission electron microscopy microphotographs, biopsies were taken in 29 non-erosive reflux disease patients at distal and proximal oesophagus. Twelve asymptomatic controls underwent the same protocol. RESULTS: Morphometric analysis on transmission electron microscopy microphotographs showed mean intercellular space diameter values of patients, at distal and proximal oesophagus, 3- and 2-fold, respectively, higher than those in controls (p<0.001). On light microscopy microphotographs, mean intercellular space diameter values of patients at distal oesophagus were higher than those in controls, an overlap between patients and controls being observed. The semi-quantitative score was positive in 79% of patients and in 25% of controls at distal esophagus. CONCLUSIONS: Intercellular space diameter morphometric analysis at light microscopy is widely available, allows intercellular space diameter to be quantitatively measured with good sensitivity and specificity and could represent a useful tool in non-erosive reflux disease diagnosis. Despite satisfactory sensitivity, the semi-quantitative score at light microscopy is hampered by much lower specificity than transmission electron microscopy- and light microscopy-morphometry.

Presence of gas in the refluxate enhances reflux perception in non-erosive patients with physiological acid exposure of the oesophagus.

OBJECTIVE: The mechanisms underlying symptoms in gastro-oesophageal reflux disease, particularly in non-erosive reflux disease (NERD), remain to be fully elucidated. Weakly acidic reflux and the presence of gas in the refluxate could be relevant in the pathogenesis of symptoms. METHODS: To assess the relationship between symptoms and weakly acidic, acid and mixed (liquid-gas) reflux, 24 h oesophageal pH-impedance monitoring was performed in 32 NERD and in 20 oesophagitis patients. In 12 NERD patients the study was repeated following 4 weeks treatment with a proton pump inhibitor (PPI). Impedance-pH data were compared with those of 10 asymptomatic controls. Heartburn and acid regurgitation were considered in the analysis of symptoms. RESULTS: 15 NERD patients showed a physiological acid exposure time (pH-negative). Weakly acidic reflux was significantly less frequent in patients (25% (2%), mean (SE)) than in controls (54% (4%), p<0.01). Gas was present in 45-55% of reflux events in patient groups and controls, and decreased following PPI treatment. In NERD pH-negative patients, weakly acidic reflux accounted for 32% (10%) (vs 22% (6%) in NERD pH-positive and 12% (8%) in oesophagitis patients) and mixed reflux for more than two-thirds of all symptom-related refluxes. Multivariate logistic analysis showed that in NERD pH-negative patients, the risk of reflux perception was significantly higher when gas was present in the refluxate (odds ratio, 3.2; 95% CI, 1.2 to 10; p<0.01). CONCLUSIONS: The large majority of symptoms, in all patients, are related to acid reflux. In NERD patients, the presence of gas in the refluxate significantly enhances the probability of reflux perception. These patients are also more sensitive to less acidic reflux than oesophagitis patients.

Effect of oesophagitis on proximal extent of gastro-oesophageal reflux.

Proximal oesophageal acid reflux is increased in gastro-oesophageal reflux disease (GORD) patients with oesophageal and extra-oesophageal symptoms, the latter particularly in presence of oesophagitis. This study was aimed to assess the proximal extent of reflux, both acid and weakly acidic, in GORD patients with and without oesophagitis and to characterize, using an animal model of GORD, the relationship between acute oesophagitis and proximal extent of reflux. Proximal extent of reflux was evaluated during 24-h pH-impedance monitoring in 17 oesophagitis, 27 non-erosive reflux disease (NERD) patients and 10 asymptomatic controls. In five adult cats, reflux events were simulated by intra-oesophageal retrograde injection of a radiopaque solution. Proximal extent of simulated reflux was fluoroscopically assessed before and after inducing acute oesophagitis. The percentage of proximal reflux was 11% in controls, 22% in NERD and 38% in oesophagitis patients (P < 0.05 vs NERD). Weakly acidic reflux showed higher proximal extent in oesophagitis than in NERD patients but it was less proximally propagated than acid reflux. In cats, proximal reflux was significantly increased during acute oesophagitis. Oesophagitis patients show higher proximal extent of reflux, acid and weakly acidic, when compared with NERD patients and controls. In the experimental model, acute oesophagitis favours proximal migration of simulated reflux.

Dilated intercellular spaces and acid reflux at the distal and proximal oesophagus in patients with non-erosive gastro-oesophageal reflux disease.

BACKGROUND: Acid exposure of proximal oesophagus and dilated intercellular space diameters of oesophageal epithelium are relevant in the perception of gastro-oesophageal reflux. AIM: To explain the relationship between gastro-oesophageal reflux disease symptoms, acid exposure and intercellular space diameter along the oesophageal epithelium and to assess time-related variability of intercellular space diameter. METHODS: Thirty-three non-erosive reflux disease (NERD), six erosive oesophagitis patients and 12 asymptomatic controls underwent oesophageal manometry and 24-h dual-channel oesophageal pH-monitoring following endoscopy. Biopsies were taken 5 cm above the LES and 10 cm below the UES, at comparable levels, as pH sensors. A total of 100 intercellular space diameters per patient/control were measured blindly at transmission electron microscopy. In 15 patients, the investigation was repeated after 1 year. RESULTS: In all NERD patients, acid exposure was higher at mid-proximal oesophagus (P < 0.01) and mean intercellular space diameters, at distal and mid-proximal oesophagus, was three- and twofold higher (1.5 and 0.82 micro m, respectively) compared with controls. Intra-patient intercellular space diameter values were stable over time, not overlapping with those of controls. CONCLUSIONS: Dilation of intercellular space diameter occurs along the distal and proximal oesophageal epithelium in NERD patients and could be responsible for the enhanced perception of proximal acid reflux. This finding appears to be time-reproducible and to represent a sensitive, histopathological marker of NERD.

Effect of hiatal hernia on proximal oesophageal acid clearance in gastro-oesophageal reflux disease patients.

BACKGROUND: Proximal acid reflux is common in gastro-oesophageal reflux disease and is a determinant of symptoms. Patients with hiatal hernia complain of more symptoms than those without and are less responsive to proton-pump inhibitors. AIM: To evaluate the role of hiatal hernia on spatiotemporal characteristics of acid reflux. METHODS: Thirty seven consecutive gastro-oesophageal reflux disease patients underwent endoscopy, videofluoroscopy, manometry and multichannel 24-h pH test. Data were compared with those of 15 asymptomatic controls. Multivariate linear regression was used for statistical analysis. RESULTS: At videofluoroscopy, hiatal hernia was found in 16 of 37 patients. The mean size of hiatal hernia was 3.4 cm. Patients showed significantly prolonged acid clearance time, both at proximal and distal oesophagus, compared with controls. Hiatal hernia patients showed a significantly delayed acid clearance, along the oesophageal body, compared with non-hiatal hernia patients. The prolonged acid exposure was maintained during upright and supine position. The presence of hiatal hernia significantly predicted acid clearance delay in the distal and proximal oesophagus [at 10 cm below upper oesophageal sphincter: Delta + 2.5 min (95% confidence interval: 0.4-4.5); P < 0.02]. CONCLUSIONS: The presence of hiatal hernia is a strong predictor of more prolonged proximal oesophageal acid exposure and clearance. Hiatal hernia is likely to play a role in the pathophysiology of gastro-oesophageal reflux disease symptoms, and should be taken into greater consideration in the treatment strategies of the disease.

Infliximab reverses growth hormone resistance associated with inflammatory bowel disease.

BACKGROUND: Increasing evidence shows that inflammation plays a major role in the aetiology of catabolism and wasting observed in inflammatory bowel disease via growth hormone resistance. AIM: To evaluate the effect of infliximab treatment on the growth hormone/insulin-like growth factor-1 axis. METHODS: Fourteen adults with active Crohn's disease or ulcerative colitis underwent three infliximab infusions at a dose of 5 mg/kg for induction of remission, plus two maintenance infusions 8 weeks apart. Blood samples were collected for the analysis of serum growth hormone, insulin-like growth factor-1, insulin-like growth factor-binding protein-3 and acid labile subunit. RESULTS: Serum insulin-like growth factor-1 and insulin-like growth factor-binding protein-3 concentrations, which were significantly lower in inflammatory bowel disease patients before treatment compared with controls (P < 0.01), significantly increased during the induction phase (+58% and +29%, respectively, after the second infusion, P < 0.01), and dropped to baseline levels during maintenance therapy. Both insulin-like growth factor-1 and insulin-like growth factor-binding protein-3 showed significant negative correlations with C-reactive protein (rho = -0.37, P = 0.002; rho = -0.35, P = 0.01, respectively). Growth hormone and acid labile subunit levels were not statistically different between controls and inflammatory bowel disease patients either at baseline or during treatment. CONCLUSIONS: Infliximab induction treatment reverses growth hormone resistance observed in active inflammatory bowel disease through the suppression of systemic inflammation. The restored growth hormone/insulin-like growth factor-1 axis is impaired again following the prolonged interval between maintenance infusions, possibly because of the subclinical reactivation of the inflammatory process.

Effect of endoscopic augmentation of the lower oesophageal sphincter (Gatekeeper reflux repair system) on intraoesophageal dynamic characteristics of acid reflux.

BACKGROUND AND AIMS: Improvements in symptoms following endoscopic procedures for gastro-oesophageal reflux disease (GORD) are seldom supported by normalisation of acid exposure time at the distal oesophagus. However, the distribution of gastric acid within the proximal oesophagus is a main determinant of symptom generation in GORD patients. In this study, our aim was to assess the effect of endoscopic insertion of hydrogel expandable prostheses into the oesophageal submucosa on spatiotemporal characteristics of gastro-oesophageal reflux. METHODS: Oesophageal manometry and multichannel ambulatory 24 hour pH monitoring were carried out in nine patients before and six months after the endoscopic procedure. Dynamic characteristics of gastro-oesophageal reflux in patients were also compared with those in 13 asymptomatic controls. RESULTS: Acid exposure time (AET) at the distal oesophagus decreased from 11.7% (95% confidence interval 6.1-21.8) at baseline to 7.7% (3.7-11.6) at follow up (NS). Of the nine patients, distal AET normalised in three. AET at the middle (7.6% (2.9-12.3)) and proximal (2.4% (0.1-4.8)) oesophagus decreased significantly in all patients (2.4% (0.3-4.5), p <0.01; 1.2% (0.2-2.2), p<0.05 respectively). Proximal extent of acid events significantly decreased in all patients at follow up (37.3% v 9.5%), reaching values observed in asymptomatic controls. Median GORD health related quality of life scores significantly improved from 35.5 at baseline to 9.4. CONCLUSIONS: Despite the lack of a significant improvement in traditional pH variables, endoscopic implant of hydrogel prostheses above the lower oesophageal sphincter significantly decreases proximal spread of acid reflux into oesophageal body. This effect would explain the improvement in symptoms in patients six months after therapy.