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Background: Patients with gastroesophageal reflux disease (GERD) have impaired esophageal mucosal integrity. Measurement of the mucosal integrity is complex and time-consuming. Electrical tissue impedance spectroscopy (ETIS) is a device that measures impedance of tissue in vivo during endoscopy. In this study, we aimed to validate ETIS as a measure of esophageal mucosal integrity., Methods: Electrical tissue impedance spectroscopy measurements were performed during upper endoscopy in 12 GERD patients and 11 healthy controls after cessation of proton pump inhibition. During endoscopy biopsies of the distal esophagus were obtained for transmission electron microscopy to determine dilation of intercellular spaces (DIS) and for Ussing chamber experiments to determine transepithelial permeability and transepithelial electrical resistance., Key Results: Extracellular impedance measured in vivo by ETIS was significantly lower in GERD patients compared to controls [mean (SD) 5621 (3299) Ω.m and 8834 (2542) Ω.m, respectively, P < 0.05]. We found a strong inverse relation between extracellular impedance determined by ETIS and DIS (r = -0.76, P < 0.05), and between extracellular resistance in vivo and transepithelial permeability of esophageal biopsies (r = -0.65, P < 0.01)., Conclusions & Inferences: Electrical tissue impedance spectroscopy is a new tool that can be used to evaluate esophageal mucosal integrity changes during endoscopy., (© 2013 John Wiley & Sons Ltd.)

Background: Oesophageal intraluminal impedance is currently used for assessment of reflux in gastro-oesophageal reflux disease (GORD). Oesophageal mucosa integrity may have a key role in heartburn perception in non-erosive reflux disease (NERD). Severe erosive oesophagitis is associated with low impedance baseline. We hypothesised that impedance baseline measurements could be used to evaluate changes in oesophageal mucosa integrity in man., Methods: We measured oesophageal impedance baseline before, during and after acid perfusion in rabbits and healthy subjects. Transepithelial resistance (TER) was determined and dilated intercellular spaces (DIS) were assessed in isolated rabbit oesophageal mucosa. Impedance baseline was measured retrospectively at different levels of the oesophagus in impedance-pH recordings from asymptomatic volunteers and patients with GORD., Results: In healthy subjects and rabbits, impedance baseline dropped dramatically during perfusion of control solution (pH 7.2) but after perfusion, impedance recovered. In rabbits, after perfusion with saline pH 1.5 and 1.0 impedance values remained a 39.1 ± 7.0% and 63.9 ± 6.5% (p < 0.05) lower respectively. There was a positive correlation between in vivo basal impedance and in vitro TER values (r = 0.72, p = 0.0021). Tissue showed no erosions but both acidic solutions induced DIS. In healthy subjects, after perfusion with saline pH 2.0 and 1.0 the impedance baseline remained lower a 21.9 ± 6.5% and 52.7 ± 5.0%, (p < 0.0001) respectively. Patients with GORD have a lower impedance baseline than healthy volunteers at the distal oesophagus., Conclusions: Impedance baseline measurements might be used to evaluate the status of the oesophageal mucosa and to study the role of the impaired mucosal integrity in acid-induced heartburn in healthy volunteers and in patients with GORD.

Objectives: Refractory heartburn despite acid suppression may be explained by ongoing gastroesophageal reflux disease (GERD) or functional heartburn (FH), i.e., symptoms without evidence of GERD. Impedance-pH monitoring (impedance-pH) detects acid and nonacid reflux and is useful for evaluating acid-suppressed, refractory patients. Intercellular space diameter (ISD) of esophageal epithelium measured by transmission electron microscopy (TEM) is a marker of epithelial damage present in both erosive and nonerosive reflux disease. ISD has not been used to study refractory heartburn or FH. Our aim was to compare ISD in healthy controls and refractory heartburn patients with GERD and FH., Methods: In refractory heartburn patients (heartburn more than twice/week for at least 2 months despite proton pump inhibitor (PPI) b.i.d.), erosive esophagitis and/or abnormal impedance-pH (increased acid exposure or positive symptom index) defined GERD; normal esophagogastroduodenoscopy (EGD)/impedance-pH defined FH. Asymptomatic, healthy controls had normal EGD and pH-metry. Mean ISD in each subject, determined by blinded TEM of esophageal biopsies, was the average of 100 measurements (10 measurements in each of 10 micrographs)., Results: In all, 11 healthy controls, 11 FH, and 15 GERD patients were studied. Mean ISD was significantly higher in GERD compared with controls (0.87 vs. 0.32 μm, P=0.003) and FH (0.87 vs. 0.42 μm, P=0.012). Mean ISD was similar in FH and controls (0.42 vs. 0.32 μm, P=0.1). The proportion of patients with abnormal ISD was significantly higher for GERD compared with FH (60 vs. 9%, P=0.014)., Conclusions: ISD is increased in refractory heartburn patients with GERD but not those with FH. Our findings suggest that measurement of ISD by TEM might be a useful tool to distinguish GERD from FH in patients with refractory heartburn.

Background/aims: At present, the dilation of esophageal intercellular spaces (ICS) is considered an early morphologic marker of acid damage in patients with GERD. Nevertheless, previous electron microscopic (EM) studies had focused only on the suprabasal layer of squamous epithelium or did not nearly specify which layer of squamous epithelium was studied. Therefore, we aimed to assess the volumetric amount of the ICS in all layers of SE in patients with GERD., Methods: In this study, 48 patients were prospectively included (NERD = 18, ERD = 17; Barrett's esophagus = 5, controls = 8). All patients with ERD and NERD had typical reflux symptoms, as assessed by a valid GERD questionnaire. ICS volume was assessed by electron microscopy in the superficial, prickle cell, and basal layers of esophageal squamous epithelium using the method of Weibel., Results: ERD was associated with increased ICS volume in the basal layer (LA-A, p = 0.038; LA-B, p = 0.005) and prickle cell layer (LA-A, p = 0.006; LA-B, p = 0.007) as compared to controls. Comparisons between NERD and ERD patients revealed more dilated ICS in the basal layer (LA-B, p = 0.007), prickle cell layer (LA-A, p = 0.008; LA-B, p = 0.001) and superficial layer (LA-B, p = 0.018) in patients with ERD., Conclusions: Not only the diameter but also the volume of the ICS is increased in patients with GERD. Furthermore, the dilation of ICS is present in all three layers of the SE, being more pronounced in the basal layer. These findings support the concept that the impairment of the esophagus begins in the deeper parts of the esophageal epithelium.

The study aims to determine whether light microscopy can be used to accurately measure the diameters of intercellular spaces between squamous epithelial cells in the lower esophagus, and whether changes in this outcome measure can be used as a diagnostic marker for gastroesophageal reflux disease (GERD). The study has two parts. Part 1 involves 42 asymptomatic controls and 119 patients with typical symptoms of GERD, including 58 with erosive esophagitis (EE), and 61 patients with nonerosive gastroesophageal reflux disease (NERD). All biopsies were taken from the lower esophagus. All samples were observed using an immersion objective, after which diameters were measured by computer-assisted morphometry. Part 2 involves 61 individuals who were randomly selected from part 1, including 19 controls, 13 with NERD and 29 with EE. Diameter measurements using both light microscopy and transmission electron microscopy (TEM) were performed for samples of 61 individuals. Samples from a total of 61 individuals (31 male, 30 female, mean age 44.3 ± 16.0 years) were observed using both light microscopy and TEM. Both methods showed significant differences between control and disease groups; the outcomes from the two methods had a certain correlation (r = 0.605, P = 0.000). Morphometric analysis of all 161 individuals (83 males, 78 females, mean age 41.4 ± 15.7) showed mean diameters from light microscopy to be 0.58 ± 0.16 µm for controls, 1.07 ± 0.30 µm for NERD, and 1.29 ± 0.20 µm for EE; differences between control and disease groups were significant (P<0.05). The optimal cut-off value from receiver operator characteristic analysis was 0.85 µm. Diagnoses were validated using the combination of symptoms of GERD, endoscopy, and 24 h ambulatory pH monitoring as the gold standard. At the optimal cutoff, sensitivity was 93.3% and specificity was 100%. The diameters of the intercellular spaces in squamous epithelium of lower esophagus from controls and in patients with GERD can be quantitatively measured using light microscopy. Dilated diameters can serve as a sensitive, specific, and objective indicator for diagnosis of GERD., (© 2010 Copyright the Authors. Journal compilation © 2010, Wiley Periodicals, Inc. and the International Society for Diseases of the Esophagus.)

Background and Aims: Bronchial asthma (BA) is considered an extra-esophageal syndrome of gastroesophageal reflux disease (GERD) with poor pathophysiological background. We analyzed the correlation between GERD and BA, examining esophageal epithelium with transmission electron microscopy (TEM), along with clinical findings., Methods: BA patients of controlled and partly-controlled levels were enrolled in the study. A pulmonary and gastrointestinal (GI) questionnaire was given. Patients with no symptoms joined the control group. Esophageal mucosal tissue was taken by esophagogastroduodenoscopy from both groups and processed for TEM. Intercellular space (IS) was measured with an image analyzing program, 100 times for each patient., Results: The control (n=20) and BA (n=20) groups revealed no significant differences in baseline characteristics. All BA patients were using corticosteroid inhalers, with seven patients having a recent history of acute exacerbation. Patients with at least one GI symptom made up 70% (14/20) of the BA group, and heartburn and/or regurgitation were detected in 40% of patients. Endoscopic findings of GERD were mucosal breaks (n=3). The IS of the control group was 0.389±0.297 um, while the BA group was 0.806±0.556 um (P=0.001). The presence of GERD symptoms (P=0.306) and a history of recent asthma attacks (P=0.710) did not show significant differences., Conclusions: The BA group showed a significant difference in the dilatation of IS compared to the control group, suggesting a higher prevalence of GERD in BA patients and a close pathophysiological correlation., (© 2010 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.)

Objectives/hypothesis: Laryngopharyngeal reflux (LPR) originates from regurgitation of gastric contents, a mechanism seemingly identical to gastroesophageal reflux disease (GERD). Some researchers postulate a connection between LPR and GERD, whereas some assert LPR is a disease apart from GERD. We examined symptoms of GERD from LPR patients, and performed gastrointestinal endoscopy and transmission electron microscopy (TEM) to evaluate GERD findings from these patients., Study Design: Prospective study at an academic tertiary care center., Methods: Control subjects had no symptoms or signs of LPR/GERD. LPR was diagnosed with a Reflux Symptom Index >13 and Reflux Finding Score >7, and were questioned for GERD-related symptoms and examined with esophagogastroduodenoscopy, then allocated into either an LPR without GERD or LPR with GERD group. Esophageal tissues were obtained from the squamocolumnar junction and managed for TEM, and the intercellular space (IS) was measured to find dilatation, a characteristic GERD finding., Results: About 30% (8/26) of LPR patients showed GERD-related symptoms, connecting LPR with the GERD group. Most of the LPR patients showed grossly normal endoscopic findings. On TEM, IS of control group (n = 15) was measured as 0.35 +/- 0.27 microm, whereas the LPR without GERD group (n = 18) and LPR with GERD group (n = 8) revealed a dilated IS of 0.61 +/- 0.47 microm and 0.95 +/- 0.44 microm, respectively. This difference was statistically significant compared to the control group (P < .05)., Conclusions: The mean IS of LPR was significantly increased, suggesting common pathogenesis between LPR and GERD.

Aim: To evaluate esophageal mucosal defense mechanisms at an epithelial level to establish if pantoprazole treatment can induce ultrastructural healing and improvement in the proliferation activity of the esophageal epithelium in gastroesophageal reflux disease (GERD)., Methods: This was a single-blinded study for pH-monitoring, and histological, ultrastructural and MIB1 immunostaining evaluation. Fifty eight patients with GERD were enrolled and underwent 24 h pH-monitoring and endoscopy. Patients were treated for 12 and 24 mo with pantoprazole. Esophageal specimens were taken for histological and ultrastructural evaluation, before and after the treatment., Results: With transmission electron microscopy, all patients with GERD showed ultrastructural signs of damage with dilation of intercellular spaces (DIS). After 3 mo of therapy the mean DIS values showed a significant reduction and the mean MIB1-LI values of GERD showed an increase in cell proliferation. A further 3 mo of therapy significantly increased cell proliferation only in the erosive esophagitis (ERD) group., Conclusion: Three months of pantoprazole therapy induced ultrastructural healing of mucosal damage in 89% and 93% of ERD and non-erosion patients, respectively. Moreover, long-term pantoprazole treatment may be helpful in increasing the capability for esophageal cell proliferation in GERD, particularly in ERD patients.

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.

Aim: To investigate the intercellular spaces between the most superficially located esophageal epithelial cells in patients with gastroesophageal reflux disease (GERD)., Methods: Eighteen patients with erosive esophagitis, 10 patients with non-erosive reflux disease (NERD), and 18 normal asymptomatic volunteers were enrolled. Biopsy specimens were obtained from the lower esophageal mucosa without ulcer or erosion. Scanning electron microscopy was employed to investigate the tightness of the superficial cellular attachment., Results: The intercellular space between the most superficially located epithelial cells in patients with erosive esophagitis or NERD was not different from that in asymptomatic healthy individuals., Conclusion: Widened luminal intercellular spaces of esophageal superficial epithelium are not responsible for the induction of reflux symptoms in patients with GERD.

Esophageal mucosal dilated intercellular spaces (DIS) are frequently observed in patients with nonerosive reflux disease (NERD) and patients with esophagitis. The specificity of DIS is questionable, as it is present in up to 30% of asymptomatic healthy subjects and in patients with other esophageal disorders. DIS occurs in parallel with a drop in potential difference, diminished transepithelial resistance, and increased esophageal mucosal permeability. These alterations arise with exposure to acid and pepsin during gastroesophageal reflux, but the exact pathway of damage to the intercellular junctions remains unclear and seems to be multifactorial. Other noxious contents of the refluxate, such as bile acids, are harmful and DIS can also be induced by acute psychological stress. DIS can be assessed quantitatively with electron microscopy (EM), but it is also recognizable with light microscopy (LM). DIS can disappear after treatment with proton pump inhibitors (PPI); however, this is not the case in all NERD patients. A recent study showed that patients with NERD who are refractory to PPI might still have DIS; and animal experiments showed that persistence of DIS might be due to esophageal mucosal exposure to bile acids and/or psychological stress. In conclusion, DIS is a frequent but nonspecific histological feature of NERD. It can be caused by acid reflux, but bile acids in the refluxate and/or psychological stress can modulate the development or persistence of DIS. Although a causal relationship between DIS and heartburn has been proposed, it still needs to be proven and the underlying mechanisms investigated before considering DIS as a target for treatment of NERD.

Dilated intercellular spaces (DIS) within esophageal epithelium (EE) is a histopathologic feature of non-erosive reflux disease and early lesion in acid-damaged rabbit EE associated with increased paracellular permeability. Its cause remains unknown, but the lesion's morphology suggests a significant fluid shift into the intercellular spaces (ICS). Since water follows osmotic forces and consequently ion movements, we explored the role of active (ion) transport and ion gradients in its pathogenesis. This was done by quantifying the effect of inhibited active transport and altered ion gradients on electrical resistance (R(T)) and ICS diameter in acid-exposed Ussing-chambered rabbit EE. Compared with normal Ringer, pH 7.5, 30 minutes of luminal HCl (100 mmol/L), pH 1.1, increased permeability (R(T): +5 +/- 4% vs-52 +/- 4%) and ICS diameter (0.25 +/- 0.01 microm vs 0.42 +/- 0.02 microm), but had no effect on cell morphology or diameter. Ouabain pretreatment significantly reduced active transport but had no effect on the acid-induced changes. However, negating the chloride gradient created by luminal HCl either by adding choline chloride, 100 mmol/L, serosally or by replacing luminal HCl, pH 1.1, with luminal H(2)SO(4), pH 1.1, prevented the development of DIS while maintaining the increase in permeability. DIS was also prevented in the presence of a 100 mmol/L (choline) chloride gradient by luminal exposure at neutral pH. DIS in HCl-damaged EE is caused by an H(+)-induced increase in epithelial permeability; this enables Cl(-) to diffuse along its gradient into the ICS, creating an osmotic force for water movement into and (hydrostatic) dilation of the ICS.

Telomeres are repetitive DNA sequences located at the ends of chromosomes. Telomeres are shortened by repeated cell divisions and by oxidative DNA damage, and cells with critically shortened telomeres cannot divide. We hypothesized that chronic gastroesophageal reflux disease (GERD)-induced injury of the esophageal squamous epithelium results in progressive telomeric shortening that eventually might interfere with mucosal healing. To address our hypothesis, we compared telomere length and telomerase activity in biopsy specimens of esophageal squamous epithelium from GERD patients and control patients. Endoscopic biopsies were taken from the esophageal squamous epithelium of 38 patients with GERD [10 long-segment Barrett's esophagus (LSBE), 15 short-segment (SSBE), 13 GERD without Barrett's esophagus] and 16 control patients without GERD. Telomere length was assessed using the terminal restriction fragment assay, and telomerase activity was studied by the PCR-based telomeric repeat amplification protocol assay. Patients with GERD had significantly shorter telomeres in the distal esophagus than controls [8.3 +/- 0.5 vs. 10.9 +/- 1.5 (SE) Kbp, P = 0.043]. Among the patients with GERD, telomere length in the distal esophagus did not differ significantly in those with and without Barrett's esophagus (LSBE 7.9 +/- 0.8, SSBE 8.6 +/- 0.9, GERD without BE 8.7 +/- 1.0 Kbp). No significant differences in telomerase activity in the distal esophagus were noted between patients with GERD and controls (4.0 +/- 0.39 vs. 5.2 +/- 0.53 RIUs). Telomeres in the squamous epithelium of the distal esophagus of patients who have GERD, with and without Barrett's esophagus, are significantly shorter than those of patients without GERD despite similar levels of telomerase activity.

Objective: To observe the changes of dilated intercellular space (DIS) of esophageal epithelium in different subtypes of gastroesophageal reflux disease (GERD) before and after esomeprazole treatment., Methods: Nineteen patients with GERD, 6 with erosive esophagitis (EE), 7 with NERD with abnormal acid exposure (NERD pH+), and 6 with NERD with normal acid exposure (NERD pH-), were treated with esomeprazole 40 mg daily for two months. During endoscopy before and after treatment, six biopsy specimens were taken from the apparently normal mucosa 3 - 5 cm above the dentate line in the esophagus to undergo HE staining and histological examination and transmission electron microscopy (TEM). Fifteen normal subjects were used as controls., Results: Two months after the treatment 5 cases (83.33%) in the EE group, 6 cases (85.57%) in the NERD pH+ group, and 5 cases (83.33%) in the NERD pH- group showed a complete recovery of DIS and complete disappearance of the symptom of heartburn. Two of the left three patients who showed incomplete recovery of DIS still had heartburn., Conclusion: A complete recovery of DIS 2 months after treatment of esomeprazole is always accompanied by resolution of heartburn symptom. No significant difference in complete recovery of DIS can be found among different GERD subgroups.

Background and Aims: A recent electron microscopy study suggested that dilated intercellular spaces (DIS) are specific for acid reflux-damaged esophageal epithelium. Electron microscopy is, however, expensive and difficult to apply to routine biopsies. The aims of this study are to establish a method for assessing DIS on light microscopy of esophageal biopsies and to estimate its association with current clinicopathological parameters of esophagitis., Materials and Methods: 21 patients with reflux symptoms were investigated. Light microscopy biopsies were assessed for DIS size by a semiquantitative method and computer-assisted, static morphometry. A DIS score accounting for DIS size and distribution was assigned to each patient and its association with 30 clinicopathological variables investigated by univariate and multivariate logistic regression., Results: Both the semiquantitative method and static morphometry identified 4 different classes of DIS size. The DIS score was significantly and independently associated with the esophageal symptoms score, the histological score of esophagitis and the relevant morphometry data., Conclusions: DIS may be efficiently assessed during light microscopy of routine esophageal biopsies. Since correlation with both the histology and the symptoms of esophagitis, the DIS score may be considered a novel parameter of esophagitis and is suggested for the routine evaluation of esophageal biopsies in patients with reflux disease., (Copyright 2001 S. Karger AG, Basel)

Background and Aims: The usefulness of histological diagnosis of gastroesophageal reflux disease (GERD) is limited by poor specificity or sensitivity of available diagnostic tools. Recently, ultrastructural morphometry showed interstitial space dilation (ISD) to be a reliable sign of reflux disease. Aims of this study were to (a) search for a light microscopy equivalent of ISD, (b) test its diagnostic value, and (c) look for a possible role of intercellular glycoconjugates in its genesis., Methods: Esophageal grasp biopsies were taken during endoscopy, 2-3 cm and 6-7 cm above the squamocolumnar junction, from patients under investigation for GERD symptoms. The biopsies were fixed in aldehyde solutions and embedded in resin for electron microscopy or in paraffin for routine histology, and the glycoconjugates underwent immunohistochemistry using 3-fucosyl-N-acetylactosamine antibodies., Results: Irregular intercellular space dilation was detected in the basal and prickle layers using both light and electron microscopy. Hematoxylin-eosin preparations showed ISD in 20 of 22 (90%) erosive esophagitis cases, 30 of 44 (68%) endoscopy negative GERD cases, and 1 of 12 (8%) controls, with good interobserver (K = 0.75) and bioptic site reproducibility. ISD correlated with loss or rearrangement of intercellular glycoconjugates of the overlying layers and with granulocyte (eosinophil and/or neutrophil) infiltration., Conclusions: Light microscopy ISD is a suitable index of GERD. Alterations of intercellular glycoconjugates are likely to have a role in the genesis of ISD and GERD.

Background & Aims: Dilated intercellular spaces are a sign of epithelial damage in acid-perfused rabbit esophagus, a change best identified by transmission electron microscopy. The aim of this study was to determine if this change is also a feature of acid damage to human esophageal epithelium., Methods: Endoscopic esophageal biopsy specimens from patients with (n = 11) and without (n = 13) recurrent heartburn were examined using transmission electron microscopy. Of 11 patients with heartburn, 6 had erosive esophagitis and 5 had normal-appearing mucosa on endoscopy; 13 controls had no symptoms or signs of esophageal disease. Using a computer, intercellular space diameter was measured from transmission electron microscopy photomicrographs of the specimen from each patient., Results: Intercellular space diameter was significantly greater in specimens from patients with heartburn than those from controls; this was true irrespective of whether the patient had erosive or nonerosive disease. Space diameters of > or = 2.4 microns were present in 8 of 11 patients with heartburn and in no controls., Conclusions: Dilated intercellular spaces are a feature of reflux damage to human esophageal epithelium. As a morphological marker of increased paracellular permeability, its presence in patients without endoscopic abnormalities may help explain their development of heartburn.

Few studies have examined the ultrastructural changes in mild reflux esophagitis. Endoscopic esophageal biopsies were obtained from 10 patients with reflux symptoms and mild endoscopic esophagitis (grade 0:3 patients, grade I: 7 patients) and 9 patients with erosive esophagitis (grade II-IV), at least 5 cm above the Z line. The biopsies were evaluated by light and transmission electron microscopy. Ultrastructural changes were present in one patient with grade 0, 7 with grade I and 9 with grade II-IV esophagitis. Four of the 10 patients with grade 0-I esophagitis and 6 of 9 with grade II-IV esophagitis had light microscopic abnormalities. The ultrastructural abnormalities in patients with mild esophagitis were seen in the cell membrane, cytoplasmic organelles, desmosomes, and nuclei of all the three layers of esophageal mucosa and the basal lamina. Ultrastructural studies by transmission electron microscopy on endoscopic pinch biopsies may be a sensitive research tool to study the pathogenesis of mild reflux esophagitis.

Background: There is a growing body of evidence to indicate that the gastric mucosa is protected against the back-diffusion of acid by a physical barrier comprising surface-active phospholipid (SAPL) otherwise known as gastric surfactant on account of its similarity to pulmonary surfactant in composition and behaviour., Aims: To determine whether this form of mucosal protection might extend into the oesophagus to offer some degree of protection against the reflux of gastric contents., Methods: Oesophageal epithelium was tested for the same hydrophobicity which is characteristically imparted to gastric mucosa by SAPL. A morphological study was also performed to visualise any barrier, purposely avoiding conventional fixatives for electron microscopy which destroy hydrophobic surfaces., Results: Oesophageal epithelium in the vicinity of the cardiac sphincter was found to be appreciably hydrophobic, although not as hydrophobic as gastric mucosa. This hydrophobicity was eliminated by bile salts selected as a known 'barrier breaker' and one which reacts with any lining of SAPL. The morphological study revealed much evidence of SAPL, especially that lining epithelial cells, while its source is probably the lamellar bodies also visualised., Conclusions: These findings indicate a physical barrier of oesophageal surfactant which could offer some degree of protection against gastro-oesophageal reflux but one which is particularly prone to attack by bile.