An Interactive Web-Based Educational Tool Improves Detection and Delineation of Barrett's Esophagus-Related Neoplasia.

BACKGROUND & AIMS: Endoscopic detection of early Barrett's esophagus-related neoplasia (BORN) is a challenge. We aimed to develop a web-based teaching tool for improving detection and delineation of BORN. METHODS: We made high-definition digital videos during endoscopies of patients with BORN and non-dysplastic Barrett's esophagus. Three experts superimposed their delineations of BORN lesions on the videos using special tools. In phase one, 68 general endoscopists from 4 countries assessed 4 batches of 20 videos. After each batch, mandatory feedback compared the assessors' interpretations with those from experts. These data informed the selection of 25 videos for the phase 2 module, which was completed by 121 new assessors from 5 countries. A 5-video test batch was completed before and after scoring of the four 5-video training batches. Mandatory feedback was as in phase 1. Outcome measures were scores for detection, delineation, agreement delineation, and relative delineation of BORN. RESULTS: A linear mixed-effect model showed significant sequential improvement for all 4 outcomes over successive training batches in both phases. In phase 2, median detection rates of BORN in the test batch increased by 30% (P < .001) after training. From baseline to the end of the study, there were relative increases in scores of 46% for detection, 129% for delineation, 105% for agreement delineation, and 106% for relative delineation (all, P < .001). Scores improved independent of assessors' country of origin or level of endoscopic experience. CONCLUSIONS: We developed a web-based teaching tool for endoscopic recognition of BORN that is easily accessible, efficient, and increases detection and delineation of neoplastic lesions. Widespread use of this tool might improve management of Barrett's esophagus by general endoscopists.

Etiopathogenetic principles and peptic ulcer disease classification.

Ulceration corresponds to tissue loss, breaching the muscularis mucosae. When ulcers develop in the acid-peptic environment of the gastroduodenum, they are traditionally called peptic ulcer (PUD). Ulcers never develop spontaneously in a healthy gastroduodenal mucosa. Ulceration is the ultimate consequence of a disequilibrium between aggressive injurious factors and defensive mucosa-protective factors. The dominant aggressors are strong acid and high proteolytic (pepsin) activity in gastric secretions. The dominant defensors are the phospholipid surfactant layer, covering the mucus bicarbonate gel, the mucus bicarbonate layer covering the epithelium, the tight junctional structures between the epithelial cells, restricting proton permeability, and the epithelial trefoil peptides, contributing to healing after injury. Initially, acid-peptic aggression was considered the overwhelming cause of PUD, supported by the pioneering work of Schwartz, launching the dictum 'no acid, no ulcer'. This led to the universal therapy directed against intragastric acidity, also interfering with peptic activity when the pH was >4. The therapeutic sequence went from large doses of antacids to H(2)-receptor antagonists and finally to proton pump inhibitors (PPIs). The longer the intragastric pH was >3, the quicker ulcer healing was seen. Unfortunately, ulcers often recurred after stopping therapy, demanding maintenance therapy to keep the ulcers healed and to prevent the need for surgery (vagotomy, partial gastric resection). Later on, the emphasis gradually shifted to weakening/failing of the defensive factors, raising the vulnerability of the gastroduodenal mucosa to luminal secretions. Leading injurious mechanisms jeopardizing the mucosal integrity are numerous: infections, especially Helicobacter pylori, drug-induced injury, particularly acetylsalicylic acid (ASA) and non-steroidal anti-inflammatory drugs (NSAIDs), physicochemical and caustic injury, vascular disorders, interfering with perfusion, etc. Currently the leading cause of PUD is H. pylori infection. Standard triple eradication therapy is losing interest in favor of quadruple therapy (PPI, bismuth, tetracycline, metronidazole). H. pylori-induced PPI is rapidly disappearing in the Western world, in contrast to drug-induced ulcer disease and what is called idiopathic PUD. Partial prophylaxis of ASA/NSAID-induced ulceration is possible with PPI maintenance therapy, but novel ways to strengthen the mucosal defense are urgently awaited.

Diagnosis and management of non-erosive reflux disease--the Vevey NERD Consensus Group.

BACKGROUND/AIMS: Although considerable information exists regarding gastroesophageal reflux disease with erosions, much less is known of non-erosive reflux disease (NERD), the dominant form of reflux disease in the developed world. METHODS: An expert international group using the modified Delphi technique examined the quality of evidence and established levels of agreement relating to different aspects of NERD. Discussion focused on clinical presentation, assessment of clinical outcome, pathobiological mechanisms, and clinical strategies for diagnosis and management. RESULTS: Consensus was reached on 85 specific statements. NERD was defined as a condition with reflux symptoms in the absence of mucosal lesions or breaks detected by conventional endoscopy, and without prior effective acid-suppressive therapy. Evidence supporting this diagnosis included: responsiveness to acid suppression therapy, abnormal reflux monitoring or the identification of specific novel endoscopic and histological findings. Functional heartburn was considered a separate entity not related to acid reflux. Proton pump inhibitors are the definitive therapy for NERD, with efficacy best evaluated by validated quality-of-life instruments. Adjunctive antacids or H(2) receptor antagonists are ineffective, surgery seldom indicated. CONCLUSIONS: Little is known of the pathobiology of NERD. Further elucidation of the mechanisms of mucosal and visceral hypersensitivity is required to improve NERD management.

Metabolism of fibrinogen in cirrhosis of the liver.

The metabolism of human fibrinogen labeled with radioactive iodine was studied in 50 patients with documented cirrhosis of the liver and in 35 healthy control subjects. Results in cirrhotic subjects were the following: plasma volume 47 +/- 10 ml/kg; plasma fibrinogen concentration 250 +/- 102 mg/100 ml; total plasma fibrinogen pool 118 +/- 59 mg/kg, representing 0.73 +/- 0.10 of the total body pool; fibrinogen half-life 2.99 +/- 0.59 days; fractional catabolic rate 0.34 +/- 0.09 of the plasma pool per day; absolute catabolic rate 39 +/- 20 mg/kg per day; fractional transcapillary efflux rate 0.82 +/- 0.30 of the plasma pool per day. Results in the control subjects were the following: plasma volume 42 +/- 7 ml/kg; plasma fibrinogen concentration 284 +/- 71 mg/100 ml; total plasma fibrinogen pool 119 +/- 40 mg/kg, representing 0.72 +/- 0.07 of the total body pool; fibrinogen half-life 4.14 +/- 0.56 days; fractional catabolic rate 0.24 +/- 0.04 of the plasma pool per day; absolute catabolic rate 28 +/- 9 mg/kg per day; fractional transcapillary efflux rate 0.60 +/- 0.26 of the plasma pool per day.A significant difference between cirrhotics and controls was observed for plasma volume, fibrinogen half-life, fractional and total catabolic rates, and transcapillary efflux rate. During heparinization of 10 cirrhotic patients the fibrinogen half-life was prolonged from 3.15 +/- 0.69 to 4.59 +/- 0.79 days. This was associated with a rise in plasma fibrinogen in six out of eight patients. Heparinization did not influence the fibrinogen half-life in five control subjects. Inhibition of the fibrinolytic system in 17 patients resulted in prolongation of the plasma radioactivity half-life of more than 1 day in only three patients, an incidence comparable with that in five control subjects. These results strongly support the concept of accelerated fibrinogen consumption by a process of disseminated intravascular coagulation in cirrhosis of the liver.

Synthesis and transport of lipoprotein particles by intestinal absorptive cells in man.

The site of synthesis and some new details of lipoprotein particle transport have been demonstrated within the jejunal mucosa of man. In normal fasting volunteers, lipoprotein particles (88%, 150-650 A diameter) were visualized within the smooth endoplasmic reticulum and Golgi cisternae of absorptive cells covering the tips of jejunal villi. Electron microscopic observations suggested that these particles exited through the sides and bases of absorptive cells by reverse pinocytosis and then passed through the extracellular matrix of the lamina propria to enter lacteal lumina. When these lipid particles were isolated from fasting intestinal biopsies by preparative ultracentrifugation, their size distribution was similar to that of very low density (S(f) 20-400) lipoprotein (VLDL) particles in plasma. After a fatty meal, jejunal absorptive cells and extracts of their homogenates contained lipid particles of VLDL-size as well as chylomicrons of various sizes. The percentage of triglyceride in isolated intestinal lipid particles increased during fat absorption. Our interpretation of these data is that chylomicrons are probably derived from intestinal lipoprotein particles by addition of triglyceride.

Impaired drinking capacity in patients with functional dyspepsia: intragastric distribution and distal stomach volume.

The water drink test is a good tool to evoke dyspeptic symptoms. To what extent these symptoms are related to altered gastric distribution is not clear. Therefore, we determined gastric volumes after a drink test using SPECT. After a baseline scan 20 healthy volunteers (HV) and 18 patients with functional dyspepsia (FD) underwent a drink test (100 mL min(-1)) followed by five scans up to 2 h. Dyspeptic symptoms were scored before every scan. A Wilcoxon signed rank test (P < 0.05) and a mixed effects model were used for statistical analyses. Fasting volumes were significantly higher in FD compared to HV for total, proximal and distal stomach (P < 0.001). Functional dyspeptic patients ingested significantly less water (P < 0.001) and had an impaired filling of the distal part of the stomach (P = 0.001) after the drink test. In FD, bloating (prox. 80%, dist. 56%), pain (prox. 87%, dist. 62%) and fullness (prox. 80%, dist. 59%) were determined more by proximal stomach volume rather than distal stomach volume. These data suggest that drinking capacity is mainly determined by antral volume, with a reduced antral filling in FD compared to HV. The persisting symptoms of bloating, pain and fullness in FD are predominantly associated with proximal stomach volume.

Clinical and laboratory studies of the antacid and raft-forming properties of Rennie alginate suspension.

BACKGROUND: Acid pockets at the gastro-oesophageal junction escape buffering from meals in the stomach. Combining high-dose antacid with alginate may therefore be of benefit in gastro-oesophageal reflux disease. AIM: To characterize the antacid and raft-forming properties of Rennie alginate suspension (containing high-dose antacid and alginate; Bayer Consumer Care, Bladel, the Netherlands). METHODS: The in vitro acid-neutralizing capacity of Rennie algniate was compared with Gaviscon (Reckitt Benckiser, Slough, UK) by pH-recorded HCl titration. Alginate raft weight formed in vitro at different pH was used to evaluate the pH dependency of raft formation with each product. A double-blind, placebo-controlled, randomized crossover study also compared the antacid activity of Rennie alginate vs. placebo in vivo using continuous intragastric pH monitoring in 12 healthy fasting volunteers. RESULTS: Compared with Gaviscon, Rennie alginate had a higher acid-neutralizing capacity, greater maximum pH and longer duration of antacid activity in vitro. However, the two products produced comparable alginate rafts at each pH evaluated. In vivo, Rennie alginate provided rapid, effective and long-lasting acid neutralization, with an onset of action of <5 min, and duration of action of almost 90 min. CONCLUSIONS: The dual mode of action of Rennie alginate offers an effective treatment option for mild symptomatic gastro-oesophageal reflux disease particularly considering recent findings regarding 'acid pockets'.

Prevalence and management of abdominal cramping and pain: a multinational survey.

BACKGROUND: Though functional gastrointestinal complaints are recognised as being common throughout the world, there have been few comparative studies of prevalence. AIM: To compare the prevalence and management of abdominal cramping/pain in nine countries. METHODS: In a two-stage community survey, approximately 1000 subjects were interviewed in each of nine countries to establish the demographics of individuals with abdominal cramping/pain (stage 1) followed by market research-driven interviews with >or=200 sufferers per country (stage 2). RESULTS: 9042 subjects were interviewed in stage 1. Mexico (46%) and Brazil (43%) had the highest prevalence of abdominal cramping/pain; Japan the lowest (10%). Abdominal cramping/pain was more common in women (12-55%) than in men (7-38%). About 1717 subjects participated in stage 2; 65% were women and the average age at symptom onset was 29 years. The frequency of episodes differed between countries, being highest in the US (61% suffered at least once in a week). Sufferers in the US and Latin America reported a higher usage of medications (around 90%) than those in Europe (around 72%). In most countries over-the-counter drugs were principally used. Antispasmodic drugs were most popular in Latin America and Italy, antacids in Germany and the UK. Drug therapy decreased the duration of episodes (by up to 81% in Brazil). CONCLUSIONS: The community prevalence, severity, healthcare seeking and medication usage related to abdominal cramping/pain are high overall, but vary considerably between countries.

Placebo- and paracetamol-controlled study on the efficacy and tolerability of hyoscine butylbromide in the treatment of patients with recurrent crampy abdominal pain.

AIM: To compare the efficacy and tolerability of oral hyoscine butylbromide (hereafter hyoscine) 10 mg t.d.s., paracetamol 500 mg t.d.s. and their fixed combination against placebo in patients with recurrent crampy abdominal pain. METHODS: A total of 1637 patients were entered into a four-arm double-blind study. After a 1 week placebo run-in, they were randomized to 3 weeks of treatment with one of the four therapies with assessments after 1, 2 and 3 weeks. Pain intensity (Visual Analogue Scale) and pain frequency (Verbal Rating Scale) were self-assessed daily. RESULTS: Pain intensity on the Visual Analogue Scale decreased in all treatment groups; the adjusted mean changes from baseline were 2.3, 2.4 and 2.4 cm for the hyoscine, paracetamol and combination groups, respectively, compared with 1.9 cm for the placebo group (all P < 0.0001). The Verbal Rating Scale also showed a statistically significant decrease of 0.7, 0.7 and 0.7 in the hyoscine, paracetamol and combination groups compared with 0.5 in placebo (all P < 0.0001). All treatments were well tolerated: 16%, 14%, 17% and 11% of patients on hyoscine, paracetamol, combination and placebo reported at least one adverse event. CONCLUSIONS: Hyoscine, paracetamol and their fixed combination are effective in the treatment of recurrent crampy abdominal pain and well tolerated if used three times daily continuously for 3 weeks.

Review article: from gastrin to gastro-oesophageal reflux disease--a century of acid suppression.

To commemorate Edkins' discovery of gastrin in 1905, we review a century of progress in the physiology and pathobiology of gastrin and acid secretion especially as it pertains to clinical aspects of gastro-oesophageal reflux disease. Although initially ignored, Edkins' observations eventually led to the enthusiastic investigation of gastrin and acid regulation in peptic ulcer disease, culminating in important therapeutic advances in the management of acid peptic disease. Following the improved understanding of gastric secretory physiology, and the development of acid suppressants with increasing efficacy, the use of surgical intervention for peptic ulcer disease was almost eliminated. Surgery became obsolete with the discovery of Helicobacter pylori. Three other advances are also influencing modern practice: the gastrotoxicity of aspirin and non-steroidal anti-inflammatory drugs is now increasingly appreciated, the role of endoscopy in the diagnosis and therapy of upper gastrointestinal bleeding, and the use of intravenous acid-suppressive agents. The major issue for the future resides within the epidemic of gastro-oesophageal reflux disease. How to diagnose, categorize and treat this condition and how to identify and prevent neoplasia, are the challenges of the new century.

Possible role of nitric oxide in visceral hypersensitivity in patients with irritable bowel syndrome.

BACKGROUND: Visceral hypersensitivity is a consistent finding in a considerable proportion of patients with irritable bowel syndrome (IBS), and may provide a physiological basis for the development of IBS symptoms. In this study, we aimed to confirm the hypothesis that nitric oxide (NO) is involved in maintaining visceral hypersensitivity in IBS. Ten healthy volunteers (HV) and 12 IBS patients with documented hypersensitivity to rectal distension underwent a rectal barostat study. The effect of placebo and the specific NO synthase inhibitor NG -monomethyl-L-arginine (L-NMMA) on resting volume, rectal sensitivity to distension and rectal compliance was evaluated in a double-blind, randomized, cross-over fashion. NG -monomethyl-L-arginine did not alter resting volumes in HV or IBS patients. In HV, l-NMMA did not alter rectal sensory thresholds compared to placebo (45 +/- 3 and 46 +/- 3 mmHg, respectively). In contrast, L-NMMA significantly increased the threshold for discomfort/pain in IBS patients (placebo: 18 +/- 2, l-NMMA: 21 +/- 3 mmHg, P < 0.05). Rectal compliance was not affected by L-NMMA. Although NO does not seem to play a major role in normal rectal sensation or tone, we provide evidence that NO may be involved in the pathophysiology of visceral hypersensitivity in IBS.

The influence of the novel 5-HT1A agonist R137696 on the proximal stomach function in healthy volunteers.

As fundic dysaccommodation represents one of the pathophysiological mechanisms underlying functional dyspepsia, gastric relaxant agents may serve as a new treatment of this disorder. Previous studies have suggested the involvement of 5HT1 receptors in the control of gastric tone. Our aim was to study the effect of R137696, a novel 5HT1A agonist, on fundus sensorimotor function in healthy volunteers. The effect of single oral doses (1-2 mg) R137696 was evaluated in a double-blind, placebo-controlled manner on fasting fundic volume, visceral perception, distension-evoked symptoms and fundic compliance in 21 healthy male subjects. R137696 increased the proximal stomach volumes in a dose-dependent manner. Distention-evoked symptoms or distention and discomfort threshold were not altered by R137696. A logistic regression model, characterizing the relationships between the volume and the visual analogue scale score for dyspeptic symptoms (nausea, fullness, discomfort, pain and satiety) as a sigmoidal curve, revealed that R137696 had no effect on distension-induced discomfort, fullness, pain and satiety compared to placebo. R137696 relaxes the gastric fundus in fasting conditions but has no effect on distension-evoked dyspeptic symptoms in healthy volunteers.

Meta-analysis of the risk of gastric stump cancer: detection of high risk patient subsets for stomach cancer after remote partial gastrectomy for benign conditions.

Controversy about gastric cancer risk after partial gastrectomy exists, especially in the United States. Therefore, we performed a meta-analysis to determine overall relative risk and weighted mean relative risk for subsets of postgastrectomy patients, define possible high risk patients suitable for surveillance, and assess for publication bias which would overestimate risk. If 2 studies were excluded because of heterogeneity, overall relative risk (RR) for gastric stump cancer in 22 studies analyzed was 1.66 [95% confidence limits (CL), 1.54-1.79]. With these 2 studies included, the RR summarized with a random effects model to account for study heterogeneity was 1.46 (95% CL, 1.18-1.82). No obvious evidence of publication bias was detected. Patients 15 years or more postoperative had a weighted mean RR of 1.48 (95% CL, 1.31-1.67) and patients 5-14 years postoperative had a RR of 0.91 (95% CL, 0.71-1.17) (P = 0.026). Patients operated upon for gastric ulcer had a weighted mean RR of 2.12 (95% CL, 1.73-2.59) and patients with duodenal ulcers had a RR of 0.84 (95% CL, 0.66-1.05) (P = 0.001). The weighted mean RR for females was 1.79 (95% CL, 1.39-2.29) and for males 1.43 (95% CL, 1.27-1.62) (P = 0.074). For Billroth II gastrectomy the weighted mean RR was 1.60 (95% CL, 1.15-2.18) and for Billroth I gastrectomy 1.20 (95% CL, 1.01-1.42) (P = 0.220). Although differences in risk between subsets of postagastrectomy patients seen to exist, recommendations concerning endoscopic surveillance await further studies of cost-benefit analysis.

Simultaneous evaluation of a pancreas-specific antigen and a pancreatic cancer-associated antigen in pancreatic carcinoma.

A pancreas cancer-associated antigen (PCAA) and a pancreas-specific antigen (PaA) were simultaneously quantitated by enzyme-linked immunosorbent assays in serum specimens from 51 normal controls, 76 pancreatic cancers, 194 nonpancreatic cancers, and 22 benign pancreatic diseases. Primary immunological reagents used in the enzyme-linked immunosorbent assays were our polyclonal antibodies produced in rabbits against purified PCAA and PaA. Results revealed discordance of these two markers in pancreatic cancer, suggesting that the presence of these two biochemically and immunologically distinct pancreas proteins in patients' serum may reflect different biological aspects of cancer. The combination test resulted in a better sensitivity and specificity for pancreatic cancer, 90 and 85%, respectively, than either PCAA or PaA assay alone. This study demonstrated that the combination of serum PCAA and PaA tests yields an additive clinical value and may be a useful adjunctive aid for the immunodiagnosis of the pancreatic cancer.

An appraisal of the role of biliary phospholipases in the pathogenesis of gallstone disease.

Human bile contains proteins that influence nucleation of cholesterol. Recently, it has been suggested that activity of phospholipases in bile may play a role in this process. To study the influence of phospholipase on nucleation we have determined the effect of phospholipases A2, C and D on the nucleation time of model bile. Phospholipase C decreased the nucleation time, whereas phospholipase A2 inhibited nucleation. The phospholipases were effective only at relatively high concentrations. Phospholipase D was strongly inhibited in model bile and probably only influenced the nucleation time by an aspecific protein effect. The cleavage products of the different phospholipases were determined in native bile samples of 14 cholesterol gallstone patients, 6 patients without stones and 4 patients with pigment stones. In all samples, choline, phosphorylcholine and free fatty acids (FFA) could be detected. However, there was no significant difference between the three groups of patients. The rate of production of choline, phosphorylcholine and FFA was measured in bile incubated at 37 degrees C. Again, there was no significant difference between the three groups of patients. We conclude that phospholipase activity in bile does not play an important role in the pathogenesis of gallstone disease.

The validity of the cholesterol nucleation assay.

The validity of the cholesterol nucleation assay rests on the assumption that all cholesterol crystals are removed at the start of the assay so that de novo formation of crystals can be studied. In this paper we have tested the validity of this assumption. Cholesterol crystals were added to supersaturated model bile. Subsequently the mixtures were either filtered over a 0.22 micron filter or centrifuged at 37 degrees C for 2 h at 100,000 x g. After ultracentrifugation the isotropic interphase was collected. Using polarized light microscopy no crystals could be visualized in this fraction. However, the nucleation time of the isotropic interphase decreased from 6.8 +/- 1.1 days to 1.8 +/- 0.2 days (mean +/- S.E., P less than 0.01, n = 5) when 10-100 micrograms/ml crystals were added prior to centrifugation. Similar results were observed when instead of centrifugation the mixtures containing crystals were filtered. After filtration over a 0.22 micron filter no crystals could be detected in the filtrate. Yet the nucleation time of the filtrate decreased from 6.4 +/- 0.7 days to 3.1 +/- 0.5 days (mean +/- S.E.) when 10 micrograms/ml cholesterol crystals were added before filtration (n = 10, P less than 0.01). Since no cholesterol crystals could be detected at the start of the assay the reduction in nucleation time must have been brought about by cholesterol microcrystals that passed through the filter. Supplementation of cholesterol crystals to model bile did not accelerate the nucleation time when the samples were passed over a 0.02 micron filter, indicating that the size of the microcrystals was larger than 20 nm. The effect of addition of cholesterol crystals prior to filtration over a 0.22 micron filter was also tested in the crystal growth assay recently developed by Busch et al. ((1990) J. Lipid Res. 31, 1903-1909). Addition of crystals had only a minor effect on the assay. In conclusion, the reduced nucleation time of biles from gallstone patients is probably not only due to the presence of promoting or the absence of inhibiting proteins, but can be caused by the presence of small cholesterol crystals in these biles.

Purification and characterization of a human pancreas-specific antigen.

A pancreas-specific antigen was identified by immunologic techniques and purified from saline extract of human pancreas. The purified pancreas-specific antigen was shown to be homogeneous by polyacrylamide gel electrophoresis under both denaturing and non-denaturing conditions. It had a molecular weight of 44000 as estimated by gel filtration or sodium dodecyl sulfate-gel electrophoresis, and a sedimentation coefficient of 3.4 S as analyzed by sucrose gradient centrifugation. Pancreas-specific antigen possessed an isoelectric point of 4.9 and migrated to alpha-beta region upon immunoelectrophoresis. By colorimetric assay procedures, pancreas-specific antigen exhibited no enzyme activity, such as amylase, protease, esterase, lipase, acid phosphatase, alkaline phosphatase peroxidase, deoxyribonuclease or ribonuclease. Immunoreactivity of pancreas-specific antigen was sensitive to proteolytic enzymes, perchloric acid and high temperature (70 degrees C, 10 min); but insensitive to neuraminidase or beta-glucosidase. Immunohistochemical staining revealed that pancreas-specific antigen was located in acinar cells of human pancreas. In addition, a higher concentration of pancreas-specific antigen was detected in pancreatic juice than in the saline extract of pancreas. This newly identified pancreas-specific antigen, therefore, may be a useful marker protein in physiological studies of pancreas and pancreatic secretion.

Review article: drugs interfering with visceral sensitivity for the treatment of functional gastrointestinal disorders--the clinical evidence.

At present, the concept of visceral hypersensitivity provides the leading hypothesis regarding the generation of symptoms in functional gastrointestinal disorders. This paper discusses the current clinical evidence for drugs that have been proposed to interfere with visceral sensitivity in functional gastrointestinal disorders. Several possible pharmacological targets have been identified to reduce visceral pain and to reverse the processes underlying the persistence of visceral hypersensitivity. However, most of the available evidence comes from experimental animal models and cannot simply be extrapolated to patients with functional gastrointestinal disorders. In this review, we selected five drug classes that have been shown to exhibit visceral analgesic properties in experimental studies, and of which data were available regarding their clinical efficacy. These included opioid substances, serotonergic agents, antidepressants, somatostatin analogues and alpha(2)-adrenergic agonists. Although clinical trials show a limited benefit, in particular for serotonergic agents, the evidence illustrating that these effects result from normalization of visceral sensation is currently lacking. Therefore, we conclude that the concept of targeting visceral hypersensitivity as a treatment for functional gastrointestinal disorders is still controversial. Future evaluations require patient selection based on the presence of visceral hypersensitivity and application of compounds that exhibit 'true' viscerosensory effects.

Relationship between symptoms and hypersensitivity to rectal distension in patients with irritable bowel syndrome.

BACKGROUND: Visceral hypersensitivity is considered an important pathophysiological mechanism in irritable bowel syndrome, yet its relationship to symptoms is unclear. AIM: To detect possible associations between symptoms and the presence of hypersensitivity to rectal distension in patients with irritable bowel syndrome. METHODS: Ninety-two irritable bowel syndrome patients and 17 healthy volunteers underwent a rectal barostat study. The association between specific irritable bowel syndrome symptoms and the presence of hypersensitivity was examined using Area under the Receiver Operating Characteristic curves. RESULTS: Irritable bowel syndrome patients had significantly lower thresholds for discomfort/pain than healthy volunteers: 24 (18-30) and 30 (27-45) mmHg above minimal distending pressure, respectively. Forty-one patients (45%) showed hypersensitivity to rectal distension. Proportions of patients with different predominant bowel habits were similar in hypersensitive and normosensitive subgroups (diarrhoea predominant: 39 and 41%, respectively; alternating type: 27 and 28%, respectively; constipation predominant: 34 and 31%, respectively). Severe abdominal pain was more frequent in hypersensitive, compared with normosensitive patients (88% vs. 67%, P = 0.02), but none of the individual irritable bowel syndrome symptoms could accurately predict the presence of hypersensitivity, as assessed by Area under the Receiver Operating Characteristic curve analysis. CONCLUSIONS: Hypersensitive and normosensitive irritable bowel syndrome patients present with comparable, heterogeneous symptomatology. Therefore, selection based on clinical parameters is unlikely to discriminate individual irritable bowel syndrome patients with visceral hypersensitivity from those with normal visceral sensitivity.

Gastrin (G) cells and somatostatin (D) cells in patients with dyspeptic symptoms: Helicobacter pylori associated and non-associated gastritis.

BACKGROUND: Gastrin G cells and somatostatin D cells are important regulators of gastric acid secretion and alterations in their relative numbers may play a key role in gastroduodenal disease. AIM: To investigate the effect of Helicobacter pylori infection on the density of immunoreactive G and D cells in gastric antral and corpus biopsies from patients with dyspeptic complaints. METHODS: One hundred and twenty two patients with dyspeptic complaints had two antrum and two corpus biopsies taken during upper endoscopy. The severity of inflammation and the density of H pylori were evaluated semiquantitatively. In addition, the density and distribution of neuroendocrine cells, especially G and D cells, were examined using immunohistochemistry. Patients were divided into three groups, those with H pylori positive gastritis, H pylori negative gastritis, and histologically normal gastric mucosa. RESULTS: The number of immunoreactive G cells was significantly higher and the number of immunoreactive D cells lower in patients with H pylori positive gastritis compared with H pylori negative gastritis or histological normal gastric mucosa. The percentage of G cells as a percentage of mucosal endocrine cells was also raised and that of D cells was decreased. CONCLUSIONS: Helicobacter pylori infection produces alterations in the number of endocrine cells responsible for regulating acid secretion in relation to intragastric pH and feeding. The alterations correlate best with the severity of inflammation and not with H pylori density.