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Background: High-flow, heated, and humidified nasal oxygen therapy (HFNO) is frequently used in critical care and perioperative settings for a range of clinical applications. Much of the benefit of HFNO is attributed to generation of modest levels of positive airway pressure. Concern has been raised that this positive airway pressure may cause gastric insufflation, potentially increasing the risk of regurgitation and aspiration in an unprotected airway., Methods: A prospective, interventional, assessor-blinded study was undertaken to evaluate the effects of HFNO on gastric content and gastric distension in healthy fasted adult volunteers assessed by ultrasonography. The primary outcome was the volume of gastric secretions. The secondary outcomes were the incidence of gastric air insufflation and the distribution of gastric antral grades., Results: Sixty subjects were enrolled. No subject was found to have air gastric distension either at baseline or after treatment with HFNO. All subjects had either a Grade 0 or Grade 1 antrum, with similar distribution of antral grades and similar volume of gastric secretions before and after treatment with HFNO., Conclusions: There was no evidence that treatment with HFNO at flow rates of up to 70 L min -1 for 30 min resulted in gastric distension or an increase in gastric secretions in healthy individuals breathing spontaneously. The generalisability of these findings to subjects under anaesthesia and patients with incompetence of the lower oesophageal sphincter or impaired gastric emptying requires further investigation., Clinical Trial Registration: NCT03134937., (Copyright © 2020 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Background: Probiotics are live microorganisms that, when administered in adequate amounts, confer a health benefit on the host, are now accepted as suitable alternatives to antibiotics in the control of animal infections and improving animal production. Lactic acid bacteria (LAB) with remarkable functional properties have been evaluated in different studies as possible probiotic candidates. The purpose of this study was to isolate, characterize and assess the potentials of LAB from poultry gastrointestinal tract as potential poultry probiotics., Results: Potential LAB probiotics were isolated from broilers, characterized and evaluated for probiotic properties including antagonistic activity (against Escherichia coli, E. coli O157: H7, Enterococcus faecalis, Salmonella Typhimurium, S. Enteritidis and Listeria monocytogenes), survivability in simulated gastric juice, tolerance to phenol and bile salts, adhesion to ileum epithelial cells, auto and co-aggregation, hydrophobicity, α-glucosidase inhibitory activity, and antibiotic susceptibility tests. Most promising LAB strains with excellent probiotic potentials were identified by API 50 CHL and 16S rRNA sequencing as Lactobacillus reuteri I2, Pediococcus acidilactici I5, P. acidilactici I8, P. acidilactici c3, P. pentosaceus I13, and Enterococcus faecium c14. They inhibited all the pathogens tested with zones of inhibition ranging from 12.5 ± 0.71 to 20 ± 0 mm, and competitively excluded (P < 0.05) the pathogens examined while adhering to ileum epithelial cells with viable counts of 3.0 to 6.0 Log CFU/ml. The selected LAB strains also showed significant (P < 0.005) auto and co-aggregation abilities with α-glucosidase inhibitory activity ranging from 12.5 to 92.0%. The antibiotic susceptibility test showed 100.00% resistance of the LAB strains to oxacillin, with multiple antibiotic resistance indices above 0.5., Conclusion: The selected LAB strains are ideal probiotic candidates which can be applied in the field for the improvement of poultry performance and control of pathogens in poultry, hence curtailing further transmission to humans.

We evaluated whether the excluded stomach (ES) after Roux-en-Y gastric bypass (RYGB) can represent a premalignant environment. Twenty obese women were prospectively submitted to double-balloon enteroscopy (DBE) with gastric juice and biopsy collection, before and 3 months after RYGB. We then evaluated morphological and molecular changes by combining endoscopic and histopathological analyses with an integrated untargeted metabolomics and transcriptomics multiplatform. Preoperatively, 16 women already presented with gastric histopathological alterations and an increased pH (≥4.0). These gastric abnormalities worsened after RYGB. A 90-fold increase in the concentration of bile acids was found in ES fluid, which also contained other metabolites commonly found in the intestinal environment, urine, and faeces. In addition, 135 genes were differentially expressed in ES tissue. Combined analysis of metabolic and gene expression data suggested that RYGB promoted activation of biological processes involved in local inflammation, bacteria overgrowth, and cell proliferation sustained by genes involved in carcinogenesis. Accumulated fluid in the ES appears to behave as a potential premalignant environment due to worsening inflammation and changing gene expression patterns that are favorable to the development of cancer. Considering that ES may remain for the rest of the patient's life, long-term ES monitoring is therefore recommended for patients undergoing RYGB.

Background: Surgical patients are asked to fast for a sufficient duration to ensure that the amount of residual liquid in the stomach is within the safe range, thereby reducing the risk of gastric reflux perioperatively. The authors hypothesized that subjective hunger numerical rating scale (NRS) score could also help assess the process of gastric emptying and determine the amount of fluid remaining in the stomach., Methods: The current study consisted of healthy volunteers recruited by advertisement and mutual introduction. Participants were asked to rate their subjective hunger feeling every 30 min after oral administration of 8 mL/kg carbohydrate nutrient solution that contained 10% maltodextrin and 2.5% sucrose. Consecutively, the gastric residual fluid was measured by magnetic resonance imagining (MRI). The Spearman's correlation coefficient, the ROC curves and the stepwise regression were used to analyze the predictive value of NRS for the gastric emptying process., Results: The cohort consisted of 29 healthy volunteers enrolled in this study. The area under ROC curves estimated by the NRS score for the gastric residual volume of 2 mL/kg, 1 mL/kg, and 0.5 mL/kg were AUC 2.0  = 0.78, AUC 1.0  = 0.76, and AUC 0.5  = 0.72, respectively. The correlation coefficient between the NRS score and the residual liquid in the stomach was -0.57 (P < 0.01). The correlation coefficient between the increase of the NRS score and the decrease of gastric liquid residual volume was 0.46 (P < 0.01). The standardized estimate of NRS score for the residual volume was -0.18 (P < 0.01) and the standardized estimate of fasting time was -0.73 (P < 0.01)., Conclusions: The subjective hunger NRS score can not accurately predict the gastric residual volume, but it can provide a reference for clinicians to judge the gastric emptying process and it should be used as a second check after oral intake of clear fluids before surgery according to the new fasting protocol.

The pathogenesis of gastroesophageal reflux disease (GERD) is complex and involves changes in reflux exposure, epithelial resistance, and visceral sensitivity. The gastric refluxate is a noxious material that injures the esophagus and elicits symptoms. Esophageal exposure to gastric refluxate is the primary determinant of disease severity. This exposure arises via compromise of the anti-reflux barrier and reduced ability of the esophagus to clear and buffer the refluxate, leading to reflux disease. However, complications and symptoms also occur in the context of normal reflux burden, when there is either poor epithelial resistance or increased visceral sensitivity. Reflux therefore develops via alterations in the balance of aggressive and defensive forces., (Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Mixing fluid in a container at low Reynolds number--in an inertialess environment--is not a trivial task. Reciprocating motions merely lead to cycles of mixing and unmixing, so continuous rotation, as used in many technological applications, would appear to be necessary. However, there is another solution: movement of the walls in a cyclical fashion to introduce a geometric phase. We show using journal-bearing flow as a model that such geometric mixing is a general tool for using deformable boundaries that return to the same position to mix fluid at low Reynolds number. We then simulate a biological example: we show that mixing in the stomach functions because of the "belly phase," peristaltic movement of the walls in a cyclical fashion introduces a geometric phase that avoids unmixing.

Unlabelled: CF patients are often treated with proton pump inhibitors (PPIs) to reduce acidic gastro-esophageal reflux (GER) and bronchial aspiration of duodeno-gastric contents is common in CF. We have previously demonstrated that gastric juice (GJ) from patients "on" PPI can induce interleukin-8 (IL-8) production by bronchial epithelial cells in culture. We hypothesized that such effect would be more pronounced in CF patients known to have high inflammatory susceptibility. We aimed to evaluate the effect of GJ on IL-8 production by primary bronchial epithelial cells (PBEC), derived from a CF patient and a healthy subject., Methods: PBEC obtained from one donor (normal PBEC) and one receptor (CF-PBEC) for lung transplantation were stimulated with GJ from patients "off" and "on" PPI. IL-8 levels were measured in the supernatant., Results: GJ from patients "on" PPI provoked a significant higher IL-8 production compared to GJ from patients "off" PPI, both in normal PBEC [462 (200-1468) vs. 11 (4-28) pg/ml, p=0.0001] as in CF-PBEC [1468 (841-2449) vs. 85 (26-131) pg/ml, p<0.0001]. Exposure of the cells to GJ "off" PPI and "on" PPI provoked significantly higher IL-8 production in the CF-PBEC compared to the normal PBEC ["off" PPI 85 (26-131) vs. 11 (4-28) pg/ml, p=0.01; "on" PPI 1468 (841-2449) vs. 462 (200-1468) pg/ml, p=0.01]. Filtration (0.20 μm) of the GJ "on" PPI, to eliminate large particles and bacterial sub-products, resulted in a significant decrease of IL-8 production., Conclusion: Patients with CF, treated with PPIs, have GJ with high pH and high endotoxin levels. These patients often have GER and bronchial aspiration. The aspirated material (GJ "on" PPI) has a significantly enhanced inflammatory effect on CF bronchial epithelial cells in culture. As chronic PPI treatment in CF may result in a paradoxically increased inflammatory effect in the airways, alternative anti-reflux therapies should be considered in CF., (Copyright © 2013 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)

Background: Recent data suggest that acid suppressive medications may alter factors central to the pathophysiology of inflammatory bowel diseases (IBD), whether through shifts in the intestinal microbiome due to acid suppression or effects on immune function., Aim: To assess the relationship between the use of proton pump inhibitors (PPIs) or histamine2-receptor antagonists (H2Ra) and incidence of 'flares' (hospitalisation/surgery and change in medication)., Methods: We conducted a new user cohort study including individuals diagnosed with IBD in British Columbia using linked healthcare utilisation databases (available from July 1996 through April 2006). Propensity-score matched incidence rates during a 6-month follow-up period and rate ratios (RR) and 95% CI were calculated., Results: Among 16 151 IBD patients, 1307 Crohn's disease (CD) and 996 ulcerative colitis (UC) patients experienced a new use of PPIs, whereas 741 CD and 738 UC used H2Ra. All IBD subgroups were matched separately to an equal number of unexposed IBD patients. H2Ra use in CD doubled the risk of hospitalisation/surgery (RR = 1.94; 95%CI 1.24-3.10) and numerically less so in UC patients (RR = 1.11) with widely overlapping CIs (0.61-2.03). Proton pump inhibitors use was associated with medication change in UC (RR = 1.39; 95%CI 1.20-1.62), but without meaningfully, increased risk of hospitalisation/surgery for UC or CD patients. Extending follow-up showed persistence, but attenuation, of all effects., Conclusions: Initiation of PPIs or H2Ra may be associated with short-term changes in the course of IBD. Although confounding by indication was adjusted using propensity score matching, residual confounding may persist and findings need to be interpreted cautiously., (© 2012 Blackwell Publishing Ltd.)

Aim: To search the independent factors determining gastric juice acidity and to investigate the acidity of gastric juices in various benign and malignant upper gastrointestinal diseases., Methods: Fasting gastric juice acidity of 165 healthy subjects and 346 patients with esophageal ulcer (n = 21), gastric ulcer (n = 136), duodenal ulcer (n = 100) or gastric cancer (n = 89) were measured and compared. Additionally, gastric specimens were taken from the antrum and body for rapid urease test and histological examination., Results: Multivariate analysis revealed that bile stain of gastric juice, high acute inflammatory score of the corpus, and atrophy of the corpus were independent risk factors for the development of gastric hypoacidity with odds ratios of 3.1 (95% CI: 1.3-7.3), 3.1 (95% CI: 1.2-7.9) and 3.5 (95% CI: 1.3-9.2). Esophageal ulcer and duodenal ulcer patients had a lower pH level (1.9 and 2.1 vs 2.9, both P < 0.05) of gastric juices than healthy subjects. In contrast, gastric ulcer and gastric cancer patients had a higher pH level (3.4 and 6.6 vs 2.9, both P < 0.001) than healthy controls. Hypoacidity existed in 22%, 5%, 29%, 5% and 88% of healthy subjects, esophageal ulcer, gastric ulcer, duodenal ulcer and gastric cancer patients, respectively., Conclusion: Bile reflux, atrophy and dense neutrophil infiltrate of the corpus are three independent factors determining the acidity of gastric juice.

This study aimed to assess variations in the human gastrointestinal transit tolerance of Lactobacillus plantarum strain No. 14 after culture with glucose and with fructose. Transit tolerance was determined at 37 degrees C against simulated gastric juices at pH values of 2.5, 3.0, and 3.5, and against simulated small intestinal juices containing 0%, 0.2%, or 0.4% oxgall. The simulated gastrointestinal transit tolerance of Lactobacillus plantarum strain No. 14 varied with the carbon source. Hence we compared the amounts of exopolysaccharide from Lactobacillus plantarum strain No. 14 cultured in various carbon sources. The exopolysaccharide levels were 146.5+/-8.1 mg/l (culture) with glucose, and 20.1+/-17.0 mg/l (culture) with fructose. When exopolysaccharide was removed by centrifugation, the simulated gastric tolerance of Lactobacillus plantarum strain No. 14 cultured with glucose decreased markedly, but that with fructose did not decrease. These results suggest that the gastrointestinal transit tolerance of Lactobacillus plantarum strain No. 14 is related to exopolysaccharide contents.

Disorders of haemostasis and haemocoagulation are often seen in cancer patients as a part of the paraneoplastic syndrome. This study describes a novel compound that activates coagulation and also inhibits fibrinolytic system and fibrin degradation products in the gastric juice of 33 patients with gastric cancer. Similar, but less pronounced changes have been found in gastric juice of patients with gastric precancerosis. Procoagulant activity, induced by pathologically changed cells or monocytes, macrophages from tumor stroma, indicates the activation of local coagulation with the production of fibrin. It can be concluded that the local changes of coagulation and fibrinolysis may precede coagulopathies in cancer patients (Tab. 2, Ref. 15). Full Text (Free, PDF) www.bmj.sk.

Leptin is a hormone secreted by the gastric mucosa into the lumen of the stomach. It is present in its intact form in the intestine where it regulates nutrient absorption and intestinal mucosa integrity. We have identified the binding protein that protects leptin from the harsh conditions of the gastric juice. Immunoprecipitations and Western blot analyses demonstrated that leptin is present in the gastric mucosa and the gastric juice, bound to a protein corresponding to the extracellular domain of the leptin receptor. In the absence of this soluble receptor, leptin is rapidly degraded. Immunocytochemistry on rat gastric mucosa identified the cells and intracellular compartments involved in secretion of this complex. Leptin receptor extracellular domain and leptin are present along the rough endoplasmic reticulum-Golgi-granules secretory pathways and form a complex in the secretory granules of Chief and specific endocrine cells. The long-form membrane leptin receptor OB-Rb, the protease activator furin, and proprotein convertase 7 were found in Chief cell granules but not in those of endocrine cells. The shedding of the receptor occurs in the immature granules. It is concluded that in the immature secretory granules of Chief cells, furin activates proprotein convertase 7 that, in turn, cleaves the extracellular portion of membrane-bound leptin receptors. Leptin bound to its soluble receptor forms a complex that is resistant to the gastric juice. Endocrine cells, on the other hand, generate a soluble leptin receptor by mechanisms different from those of the exocrine cells.

The fed human stomach displays regular peristaltic contraction waves that originate in the proximal antrum and propagate to the pylorus. High-resolution concurrent manometry and magnetic resonance imaging (MRI) studies of the stomach suggest a primary function of antral contraction wave (ACW) activity unrelated to gastric emptying. Detailed evaluation is difficult, however, in vivo. Here we analyse the role of ACW activity on intragastric fluid motions, pressure, and mixing with computer simulation. A two-dimensional computer model of the stomach was developed with the 'lattice-Boltzmann' numerical method from the laws of physics, and stomach geometry modelled from MRI. Time changes in gastric volume were specified to match global physiological rates of nutrient liquid emptying. The simulations predicted two basic fluid motions: retrograde 'jets' through ACWs, and circulatory flow between ACWs, both of which contribute to mixing. A well-defined 'zone of mixing', confined to the antrum, was created by the ACWs, with mixing motions enhanced by multiple and narrower ACWs. The simulations also predicted contraction-induced peristaltic pressure waves in the distal antrum consistent with manometric measurements, but with a much lower pressure amplitude than manometric data, indicating that manometric pressure amplitudes reflect direct contact of the catheter with the gastric wall. We conclude that the ACWs are central to gastric mixing, and may also play an indirect role in gastric emptying through local alterations in common cavity pressure.

Objective: Diet is an area of major interest to those investigating the causes of cancer of the oesophagus in the Transkei. This study looked at the associations between intragastric epidermal growth factor level, diet and intragastric pH., Setting and Subjects: A dietary survey was co-ordinated with studies of gastric luminal epidermal growth factor and gastric fluid pH in 120 rural Transkeians., Results: Gastric fluid epidermal growth factor was associated with low dietary intake of animal products (p = 0.002) and vegetables (p = 0.026). There was no association with pH., Conclusion: A dietary subgroup has been identified in the Transkei population with high levels of epidermal growth factor in the upper gastrointestinal lumen. This adds to previously demonstrated diet-related changes in the upper gastrointestinal tract in Transkei. These changes may affect the disease pattern of the population.

Background & Aims: Gastroesophageal reflux typically occurs after meals. During dual gastric and esophageal pH monitoring, we observed that postprandial refluxate was often more acidic than the gastric contents. This study aimed to investigate this phenomenon., Methods: Dual gastric and esophageal pH tracings were analyzed from 40 dyspeptic patients. Dual pH electrode pull-through studies were performed in healthy volunteers to document regional variation in intragastric pH under both fasting and postprandial conditions. The squamocolumnar junction was identified using radio-opaque endoscopic clips. We also examined in vitro partitioning of gastric juice added to a homogenized fatty meal., Results: The dual pH traces confirmed that esophageal refluxate was frequently more acidic than the body of the stomach after meals but not during fasting. The pull-through studies showed a pocket of acid at the gastroesophageal junction that escaped the buffering effect of meals, remaining highly acidic (median pH 1.6) compared with the body of the stomach (pH 4.7; P < 0.001). This proximal acid pocket extended from the cardia across the squamocolumnar junction 1.8 cm into the distal esophagus. The in vitro studies showed that acidic gastric juice could partition on top of a homogenized fatty meal., Conclusions: After eating, highly acidic unbuffered gastric juice is present at the gastroesophageal squamocolumnar junction and is likely to contribute to the high prevalence of disease at this site.

The stability and bioavailability of the major antioxidants in garland (Chrysanthemum coronarium L.), chlorogenic acid, 3,5-dicaffeoylquinic acid and 4-succinyl-3,5-dicaffeoylquinic acid, were investigated together with caffeic acid. These compounds were stable in artificial digestive juice, but more than 90% of them disappeared from plasma within 30 min after intravenous injection into rats. When they were orally administered, only caffeic acid could be detected.

An important criterion to consider in the selection of strains for dietary adjuncts is the ability of the microorganisms to survive the severe conditions of acidity and bile concentrations usually found in the gastrointestinal tract. In the present work, we report the effects of digestions by artificial gastric and intestinal fluids on beta-galactosidase activity and survival of four strains of dairy propionibacteria previously selected by their bile tolerance and beta-galactosidase activity. The strains were exposed to artificial gastric juice at pH values between 2 and 7 and then subjected to artificial intestinal digestion. Both viability and beta-galactosidase activity were seriously affected at pH 2. Skim milk and Emmental cheese juice exerted a protective effect on the parameters tested. The trypsin present in the intestinal fluid inactivated the enzyme beta-galactosidase in strains of Propionibacterium freudenreichii but not in Propionibacterium acidipropionici. Moreover, the presence of bile salts enhanced the beta-galactosidase activity of these strains by permeabilization of the cells during the first hour of exposure. The intestinal transit rate confirmed the permanence of the bacteria in the intestine for long enough to be permeabilized. These results suggest that P. acidipropionici would be a good source of beta-galactosidase activity in the intestine. We also propose a practical and effective in vitro method as a tool of screening and selection of potential probiotic bacteria.

Background: The authors compared the lung injury in rabbits that occurred after tracheal instillation of human breast milk (HBM) acidified to pH 1.8 with hydrochloric acid (HCl), HBM at its native pH (7.0), and HBM acidified with gastric juice to pH 1.8 and 3.0., Methods: The alveolar-to-arterial oxygen tension gradient and dynamic compliance were recorded before and hourly for 4 h after intratracheal instillation of 0.8 ml/kg HBM acidified with HCI (pH 1.8), HBM at its native pH (7.0), HBM acidified with gastric juice (pH 1.8 or 3.0), or 5% dextrose solution acidified with gastric juice (pH 1.8) as a control in 30 adult rabbits. The circulating neutrophil count and phagocyte oxidant activity were determined before and 1 and 4 h after instillation., Results: The alveolar-to-arterial oxygen tension gradient increased and dynamic compliance decreased significantly in all groups after instillation of HBM compared with baseline values and those in the control group. The severity of the lung injury after instillation of HBM at all pH values (1.8, 3.0, and 7.0) and after acidification with gastric juice or HCl was similar. The circulating neutrophil count increased steadily for 4 h after instillation (P < 0.013), whereas spontaneous phagocyte oxidant burst activity peaked at 1 h (P < 0.007) and returned to baseline by 4 h after instillation., Conclusions: The severity of the lung injury after tracheal instillation of 0.8 ml/kg HBM in rabbits is similar at pH values between 1.8 and 7.0 after acidification with HCl or gastric juice. Tracheal instillation of HBM increases the circulating neutrophil count and phagocyte oxidant burst activity.

Irsogladine maleate (IM) has been used as a mucosal protective agent, whose action is partially explained as enhancement of mucosal blood flow, increase of cellular cyclic AMP and facilitation of gap-junctional intercellular communication. Effect of IM on rat gastric mucosal hydrophobicity, one of the mucosal barrier properties, was investigated, in comparison with that of 16,16-dimethyl prostaglandin E2 (dmPGE2). IM alone had no effect on mucosal hydrophobicity and mucosal phospholipids content. dmPGE2 alone did not change mucosal hydrophobicity significantly, but remarkably increased mucosal surface-active phospholipids. Intragastric administration of absolute ethanol significantly decreased gastric mucosal hydrophobicity and mucosal phospholipids content. IM could prevent the decrease in mucosal hydrophobicity by ethanol, maintaining the surface mucus gel layer and mucosal surface phospholipids almost as non-damaged control levels, whereas dmPGE2 also prevented the decrease in mucosal hydrophobicity by ethanol, with the surface epithelium being partially exfoliated and mucosal surface-active phospholipids showing remarkable enhancement. These results suggest that IM may preserve gastric mucosal hydrophobicity against ethanol, not through enhancement of mucosal phospholipids content like prostaglandin, but possibly through its reported stabilization action to the epithelial cell lining, which may preserve the surface epithelium with the mucous gel layer containing surface-active phospholipids, a possible origin of mucosal hydrophobicity.

The impairment of formation and maintenance of a formed fibrin clot contributes to the prolonged bleeding and high incidence of rebleeding in upper gastrointestinal haemorrhage. To investigate the basis for the use of drug therapy in gastric bleeding, this study used thrombelastography to determine the effects of pharmacological manipulation of gastric juice on coagulation and fibrinolysis. The thrombelastograph is a mechanical device that provides a visual assessment of all stages of coagulation and fibrinolysis. The effects of fresh and pharmacologically changed gastric juice was assessed after its addition to fresh whole blood in the thrombelastograph cuvette. Pharmacological manipulation was achieved through alkalisation or through addition of tranexamic acid, aprotinin, or sucralfate. Fresh gastric juice delayed clot formation, decreased maximum clot amplitude, and stimulated clot lysis. Alkalisation inhibited the lytic effects of fresh gastric juice and improved the induced abnormalities in coagulation. Tranexamic acid partially inhibited gastric juice induced clot lysis but did not exhibit a beneficial effect on coagulation. Sucralfate, and to a lesser extent aprotinin significantly inhibited fibrinolysis but exacerbated the detrimental effect of gastric juice on the parameters of coagulation. Alkalisation of gastric juice reduces the adverse effect on coagulation and fibrinolysis. Tranexamic acid, aprotinin, and sucralfate can all reduce or inhibit clot lysis, but the adverse effects on clot formation may outweigh any potential benefit in the treatment of gastrointestinal bleeding.

Preoperative anxiety may increase gastric fluid acidity and volume. To pursue this possibility we evaluated the relationship between peroral premedication, preoperative anxiety, and gastric content in 246 consecutive patients presenting for elective gynecologic surgery. All patients fasted overnight and received either flunitrazepam 1 mg, oxazepam 25 mg, or placebo with 20 mL of water on the morning of surgery in a randomized, double-blind fashion. The patients assessed relief of anxiety using a four-graded scale (excellent, good, fair, poor). Both flunitrazepam and oxazepam decreased anxiety (P less than 0.01) compared with placebo. However, no correlations between type of premedication or level of anxiety and gastric contents were found. The proportion of patients with gastric fluid volume greater than 25 mL and pH less than 2.5 was not significantly different in any of the groups studied. These results suggest that neither peroral benzodiazepine premedication nor preoperative anxiety have a clinically important impact on gastric content in patients presenting for elective gynecologic surgery.

Non-immunological defence mechanisms represent an important line of intestinal defence in addition to humoral and cellular immunity. This review summarises the evidence for the role of the non-immunological defence system. Protective factors that have been amply documented are gastric juice, intestinal motility, and intestinal flora. Components of pancreatic juice, lysozyme, and epithelial cell turnover may also be involved. Special attention is given to gastric acid, infection with Helicobacter pylori, and hypochlorhydria and their association with infectious diarrhoea. Epidemic hypochlorhydria is discussed since this increases sensitivity to intestinal infections in third world countries.

The surface thermodynamic effects of bile acids in the stomach were assessed in 48 subjects who had undergone gastric surgery for peptic ulcer disease and in 52 controls with medically healed ulcers. We derived values for surface tension of gastric mucosa from contact angle using a goniometer and measured the surface tension of gastric juice by the drop-weight method. Subjects with gastric surgery had higher median fasting bile acid concentrations than controls (1.2 vs. 0.1 mmol/L; P less than 0.0001), higher mean mucosal surface tension (51.9 vs. 47.9 mN/m; P less than 0.0001), and lower mean surface tension of gastric juice (43.2 vs. 51.7 mN/m; P less than 0.0001). Subjects who had had a Billroth II gastrectomy (n = 19) had higher bile acid concentrations (5.8 vs. 0.6 mmol/L; P less than 0.01), higher mucosal surface tension (53.7 vs. 50.3 mN/m; P less than 0.05), and lower gastric juice surface tension (41.3 vs. 47.1 mN/m; P less than 0.05) than those who had a vagotomy and drainage procedure (n = 17). Overall, intragastric bile acid concentration correlated directly with surface tension of gastric mucosa (r = 0.51, P less than 0.0001) and inversely with that of gastric juice (r = -0.60, P less than 0.0001). In conclusion, the interfacial energy barrier at the surface of the gastric mucosa is overcome in the presence of intragastric bile acids.

Gastric juice from patients with peptic ulcer disease and from patients with no upper gastrointestinal abnormality was studied in order to assess its effect on a formed fibrin clot. In both groups of patients gastric juice caused a marked increase in fibrinolysis as evidenced by a shortening of the euglobulin clot lysis time. This plasmin mediated fibrinolytic activity was found to be heat labile and only present in an acid environment. Addition of tranexamic acid or sucralfate to gastric juice almost completely reversed this effect, whereas pepstatin was only partially effective. It is probable that acid dependent proteases other than pepsin are responsible for the marked fibrinolysis. The ulcer healing agent sucralfate might be useful in those patients at risk of bleeding or rebleeding from active peptic ulcer disease.

Twenty-one patients underwent serial insulin testing, approximately 1 week, 1 year, 3 years, and 5 years after highly selective vagotomy (HSV) for duodenal ulcer (DU). They were thought to be representative of the much larger number of patients who have undergone HSV for DU in Leeds. The results obtained were compared with the responses to insulin of 40 other DU patients who were tested before HSV. Before operation, all tests were positive in the 1st hr after insulin ("early-positive") by Hollander's criteria and the mean peak acid response to insulin after subtraction of basal acid output (PAO1) was 33 mEq per hr. One week after HSV, all 21 tests were negative and mean PAOI was 0.05 mEq per hr. One year after HSV, 62% OF 21 tests were Hollander-positive and PAOI had increased significantly (P less than or equal to 0.001) to a mean of 2.3 mEq per hr. Three years after HSV, 15 of 17 tests (94%) were Hollander-positive and mean PAOI was 3.1 mEq per hr (0.1 greater than or equal to P greater than or equal 0.05, compared with PAOI at 1 year). Five years after HSV, 65% of 20 tests were positive and mean PAOI was 3.5 mEq per hr, a significant increase (P less than or equal 0.05) compared with PAOI at 1 year. Only 2 patients (10%) had consistently negative insulin tests over the 5-year period and neither of them was tested 3 years after operation. Thus, HSV was found to abolish consistently the acid response to insulin soon after operation, but on serial testing 90% of the patients eventually developed positive responses to insulin by Hollander's criteria. Most of the acid responses to insulin after HSV were small and the mean reduction in PAOI 5 years after compared with PAOI before operation is approximately 90%. The positive responses to insulin in the long term after HSV could be due to vagal nerve regeneration or to other causes. After a mean period of follow-up of 5 years (range 3 1/2 to 6 1/2 years), only 1 of the first 100 patients who were treated by HSV for DU in Leeds has so far developed recurrent ulceration. The findings of a positive response to insulin by Hollander's criteria more than 1 year after HSV appears to have no prognostic significance.

In five dogs gastric emptying of low, medium and high viscosity meals was measured via a duodenal cannula. The rate of emptying depended on the viscosity of the test meals: the time for half emptying was 4.5 +/- 2.2 min with the low viscosity liquid meal (1 centipoise), 28.9 +/- 9.5 min with the test meal of medium viscosity (10(5) centipoise), and 43 +/- 11.8 min with the test meal of high viscosity (10(6) centipoise). The emptying curves of the medium and high viscosity meals were sigmoid, whereas the curve representing the emptying of the low viscosity liquid meal followed an exponential pattern. Results indicate that the viscosity of the meal is an important factor for the rate of gastric emptying.

Oesophageal mucosal biopsies were incubated in 20, 0, and 0.2mM solutions of cholic, chenodeoxycholic, ursodeoxycholic, and deoxycholic bile acids. Both conjugated and unconjugated bile acids were studied at pH 1 and 7 singly and in combination. Observations were also made using 0.1 N hydrochloric acid and human gastric juice at pH 1-3 and 7-8. After incubation for up to 15 minutes the mucosa was examined under transmission electron microscopy. We concluded that high and moderate concentration of all the common bile acids damaged the oesophagus irrespective of the pH, that low concentrations of bile acids were damaging only at high acid levels, and that damage to the epithelium did not occur when the pH of the gastric juice had been raised.

1. [35S]sulphate was used to measure the apparent turnover of sulphate, sulphide and microbial-protein-S in the rumen contents of four sheep that were intraruminally infused with 10 g sodium sulphate/d alone, or together with 126 mg sodium molybdate (50 mg molybdenum). 2. Infusion of molybdate increased the concentration of sulphate in rumen fluid from 2.2 to 7.2 mug S/ml and decreased the rate of reduction of sulphate to sulphide by 50%. Although the rate of sulphide production was slower, the concentration of sulphide in the rumen is suggested to explain these changes. 3. In animals that were not infused with molybdate, only one-third of the S (3.0 g/d) that passed through the sulphate pool in rumen fluid was converted to sulphide, decreasing to one-sixth when molybdate was infused. 4. The turnover of S amino acids in microbial protein was not significantly affected by molybdate. Only 52-57% of the S amino acid content of microbial protein was synthesized de novo by way of the sulphide pool.

Forty patients with duodenal ulcer were randomly allocated to treatment with either tripotassium dicitrato bismuthate tablets or cimetidine for six weeks. Endoscopically confirmed healing of the ulcer occurred in 80% treated with tripotassium dicitrato bismuthate tablets and in 85% treated with cimetidine. Symptomatic improvement was also similar in the two groups. Treatment with cimetidine was associated with an increase in pH of gastric aspirate during treatment and increased numbers of bacteria were isolated from the gastric aspirate during treatment, while the pH and bacterial flora of gastric aspirate did not change during tripotassium dicitrato bismuthate treatment. Serum and urinary bismuth levels rose during treatment with tripotassium dicitrato bismuthate and urinary excretion remained raised two weeks after cessation of treatment. Tripotassium dicitrato bismuthate tablets appear to be as effective as cimetidine in the treatment of duodenal ulcer without the potentially undesirable effects of a reduction in gastric acid secretion.

Sodium polyacrylate (PANa) is a water-soluble, high-molecular compound, and its aqueous solution shows a very high viscosity and stringiness. In the present study, preventive effects of PANa on three kinds of esophageal lesions induced by gastric juice were examined in comparison with those of aceglutamide aluminum and sodium alginate. The influences of PANa on gastric contents were also studied. The preventive effect of PANa given intraesophageally on esophageal lesions induced by the intraesophageal application of gastric juice was more potent than aceglutamide aluminum and sodium alginate. Oral administration of PANa inhibited the formation of esophageal ulcer by pylorus ligation more markedly than aceglutamide aluminum, whereas sodium alginate had no effect in a high dose of 500 mg/kg. In preventing gastric ulcer which occurred simultaneously with the esophageal ulcer after the pylorus ligation, aceglutamide aluminum was most potent, and PANa was as potent as sodium alginate. Oral administration of PANa showed a more protective effect than aceglutamide aluminum on the esophageal ulceration induced by the simultaneous ligations of the pylorus and limiting ridge, whereas sodium alginate in a high dose of 500 mg/kg had little effect on the ulcer formation. PANa caused only a slight increase in the pH of gastric juice and a slight decrease in pepsin activity. From the results, it may be concluded that PANa showed an antiulcerogenic activity mainly due to its mucosa covering action against gastric juice.

The damaging effect of hydrochloric acid within the lumen of the stomach and duodenum should be diffuse, but chronic peptic ulcers are discrete and usually single. The search for localizing effects on acid attack, or localized defects in mucosal defense have so far been fruitless. If attacking forces increase, or mucosal defense diminishes to the point where ulceration occurs, mucosal breakdown should be progressive. In chronic peptic ulceration, however, the process usually seems to be self-limiting. The catastrophe theory of René Thom may describe the progressive change in the forces that leads to eventual breakdown in mucosal continuity. Possibly this catastrophe triggers off biofeedback mechanisms that hold in check further progress of the ulcer.

The ability of pig gastric mucus to retard diffusion of hydrogen and other small ions was examined. Mucus layered between gauze supports separating equimolar solutions of hydrochloric acid and sodium chloride markedly delayed the diffusion of hydrogen ions when compared with the gauze supports alone acting as a barrier. This observation was confirmed using an isotope technique. The diffusion coefficient for hydrogen ions through a known thickness of mucus was four times smaller than the diffusion coefficient through an equivalent thickness of unstirred solution. Mucus probably delays the trasfer of hydrogen ions across it by maintaining an unstirred layer of water and in part by immobilizing some water in its interstices making it unavailable for diffusion, a characteristic which is dependent on its viscosity. These obervations may be relevant to the ability of gastric mucus to protect the underlying mucosa from acid.

1. A study of ammonia and urea metabolism in sheep was made using isotope dilution techniques with (15NH4)2SO4,[15N]urea and [14C]urea in order to determine quantitatively the movements of urea-N and NH3-N throughout the body of normal, feeding sheep. 2. Single injections of 15N-labelled compounds were made into the rumen fluid NH3, caecal fluid NH3 and the blood urea pools, in order to estimate the rates of flux through, and the transfer of N between, these and other nitrogenous pools in the body. 51CrEDTA was injected into the rumen and caecum with (15NH4)2SO4 to allow estimation of fluid volumes and to provide an indication of mixing, and of times of transit of isotopes between different sampling sites in the digestive tract. 3. The sheep ate approximately 22 g lucerne chaff/h and the mean dietary N intake was 16-3 g/d. 4. The rate of flux of NH3 through the rumen NH3 pool was 15-0 g/d (i.e. 90% of the dietary N ingested; however, this amount also included N from plasma urea (1-1 g/d) and other endogenous sources including NH3 derived from caecal NH3 (0-4 g/d). 5. Only 40% of the N in isolated rumen bacteria was derived from NH3, indicating that a considerable proportion of their N requirements were obtained from compounds other than NH3 (e.g. peptides and amino acids). 6. There was evidence of recycling of N between nitrogenous pools in the rumen, probably through rumen NH3 leads to microbial N leads to NH3. 7. It was estimated that 5-3 g blood urea-N/d entered the digestive tract; 20% of this urea was degraded in the rumen, 25% in the caecum and the remainder was apparently degraded elsewhere; there was evidence of urea degradation in the large intestine posterior to the caecum and it is suggested that urea degradation and absorption of the resultant NH3 may occur in the ileum. 8. Of the 4-8 g N/d entering the caecal NH3 pool, 4-2 g N/d left and did not return and the difference (0-6 g N/d) was recycled, possibly through caecal NH3 leads to microbial N leads to NH3. 9. A large proportion of the NH3 entering the caecal NH3 pool (70% or 3-2 g N/d) was apparently derived from degradation of nitrogenous products, other than urea, including rumen microbial N (1-0 g N/d) passing undigested from the small intestine. 10. Less than half the NH3-N of caecal origin entering the rumen passed through the blood urea pool; the remainder was apparently transported as other nitrogenous compounds in the blood or body fluids. 11. The results of the three experiments were combined in a general three-pool, open-compartment model which formally recognizes an unlimited number of other unspecified, interconnected pools together comprising the whole-animal system. Rates of flux through, and transfer of N between these and other nitrogenous pools in the body were calculated by solving this model and the information derived has been applied to whole-animal models with a view to subsequently using these models in computer simulation studies.

Somatostatin, a hypothalamic peptide, suppresses hydrochloric acid-stimulated release of secretin, pancreatic flow rate, and bicarbonate and protein secretion in fasted, conscious dogs. It also reduces nonstimulated pancreatic exocrine secretion but does not affect basal secretin concentrations. Suppression of HCl-stimulated secretin release is complete, whereas pancreatic flow rate and bicarbonate and protein secretions are only partially inhibited. The action of somatostatin is rapid in onset and quickly reversible.

Histamine infusion studies were performed in 54 healthy persons, in 58 patients with duodenal ulcers and in 29 patients with gastric ulcers. The acid load entering the duodenum was estimated by measuring the loss of an intragastric marker, phenol red. The volume of duodenal juice that had refluxed into the stomach and which was aspirated with the gastric juice was estimated by the sodium content of the aspirate. The bicarbonate concentration of the refluxed duodenal juice was calculated from the relationship between neutralisation and total electrolyte concentration, since the reaction of one bicarbonate ion removes two ions from the resultant mixture. The mean bicarbonate concentration of the refluxed duodenal juice in the control group was 116,4 (+/- 9) mEq/1, and the individual bicarbonate concentrations showed the expected dependence on the magnitude of the intraduodenal acid load. The mean bicarbonate concentration in patients with duodenal ulcers was 84,6 (+/- 9) mEq/1, which was significantly lower than in healthy persons. In patients with duodenal ulcers and in those with gastric ulcers, the reflux bicarbonate concentrations were independent of acid load. These results confirm previous reports of an impaired pancreatic bicarbonate secretion in response to duodenal acid load in patients with duodenal ulcers, and indicate a similar response in patients with gastric ulcers.

We studied 211 unselected, healthy, adult patients scheduled to undergo elective ambulatory surgery to determine whether the volume or pH of gastric fluid at induction of anesthesia is correlated with the duration of the preoperative fluid fast. Patients were instructed that they must not eat any solid food after midnight but that they were permitted to drink 150 ml of tea, coffee, apple juice or water until 3 hours before their scheduled time of surgery. Patients with gastric disorders and those taking medications that affect gastric motility or secretion were excluded. No premedicant drugs were given. Following induction of general anesthesia the gastric fluid was aspirated through an orogastric tube, its volume recorded and its pH measured with a calibrated pH meter. The patients were retrospectively assigned to one of four groups according to the interval from last fluid ingestion until induction of anesthesia (less than 3 hours, 3 to 4.9 hours, 5 to 8 hours and nothing after midnight). The mean values and extremes for gastric fluid volume and pH were similar in the four groups. We conclude that healthy patients should be allowed to ingest fluid until 3 hours before elective ambulatory surgery.

Using flowing isotonic NaCl or flowing molar KCl electrodes, the magnitude of liquid junction potentials between the electrode tip and gastric juice was measured directly, and calculated from electrolyte concentrations in gastric juice according to standard formulas. Gastric transepithelial potential difference was obtained by subtracting the junction potential from the measured gastric potential difference. Junction potentials by direct experiment correlated closely with calculated values. The magnitude of the junction potential was shown to depend on the level of gastric acidity as well as on the nature of the flowing intraluminal electrode. However, transepithelial potential difference was always the same with the two electrode solutions. It is impossible to measure junction potentials with an intraluminal KCl agar electrode, but they must exist because these electrodes did not accurately measure transepithelial potential difference when gastric acidity was high. Pentagastrin caused a transient decline in transepithelial potential difference; this was not observed in patients with pernicious anemia. We conclude that accurate measurement of transepithelial potential difference must include correction for liquid junction potentials, which are sizable when gastric acidity is high. This can best be done with a flowing intraluminal electrode.

Four patients with erosive hemorrhagic gastroduodenitis were found to have high fibrinolytic activity of the gastric juice. No increase in the fibrinolytic activity could be demonstrated in the circulating blood, but the values found for fibrinogen, plasminogen and alpha2-macroglobulin were low. A high content of FDP was found in the serum. All patients had a markedly decreased content of factor XIII. Platelet count and other coagulation components were normal. These findings were interpreted as signs of local fibrinolysis in the diseased parts of the gastrointestinal canal. The bleeding stopped after oral and intravenous administration of a fibrinolytic inhibitor (AMCA Cyclokapron) and of factor XIII-containing concentrate. In bleeding from gastroduodenal ulcer and esophageal varices, no increase in gastric fibrinolytic activity was found. It is suggested that the high local fibrinolytic activity in the stomach in erosive gastritis together with the low content of factor XIII contributes substantially to the hemorrhage in this condition. These observations may lead to a revision of the treatment of such cases.