Does asymmetric dimethylarginine (ADMA) plasma concentration predict esophageal varices in patients with cirrhosis?

BACKGROUND: In previous studies elevated Asymmetric NG, NG - dimethylarginine (ADMA) plasma levels, an endogenous nitric oxide synthase inhibitor, correlated with the severity of hepatic venous pressure gradient measurement, both in peripheral and in hepatic veins. The aim of this study was to explore whether elevated ADMA plasma levels were able to predict the presence of esophageal varices (EV) and/or large EV in patients with cirrhosis. METHODS: 74 cirrhotic patients who had undergone elective upper gastrointestinal endoscopy in order to assess the presence of portal hypertension and predictors of EV and/or large EV. ADMA levels were assayed by an ELISA test (Immundiagnostik AG, Germany). RESULTS: 53 patients had EV (26/53 had large EV). Univariate analysis of low hemoglobin (p = 0.045), PT-INR (p = 0.003), albumin (p = 0.024), bilirubin (p = 0.036), Child-Pugh score (p = 0.026), and ascites (p = 0.036) predicted the presence of EV. Multivariate analysis predicted EV for only PT-INR. The presence of large EV was predicted with univariate analysis of ADMA plasma levels (p = 0.013), low hemoglobin (p < 0.001), PT-INR (p = 0.001), albumin (p = 0.001), bilirubin (p = 0.026), Child-Pugh score (p < 0.001), ascites (p = 0.004). Sensitivity, specificity, predictive positive and negative values of ADMA plasma level > 0.5 micromol/L(-1) in predicting large EV were 0.69 (95% CI 0.53 - 0.82), 0.51 (95% CI 0.40 - 0.62), 0.43 (95% CI 0.31 - 0.56), 0.76 (95% CI 0.62 - 0.86), while the area under the ROC curve was 0.65 (95% CI 0.51 - 0.79). CONCLUSIONS: ADMA plasma levels were increased in cirrhotics with more advanced liver failure but did not prove to be a useful clinical tool for predicting the presence of esophageal varices or large esophageal varices.

DPEJ placement in cases of PEG insertion failure.

BACKGROUND AND STUDY AIMS: PEG placement is routinely used for enteral feeding; in some cases PEG is not feasible or indicated due to technical difficulties, such as gastric herniation, organ interposition, or presence of gastroparesis. In these cases, surgical gastrostomy or jejunostomy are possible alternatives; more recently, direct percutaneous jejunostomy (DPEJ) has been proposed to avoid surgical intervention. The aim of the study was to evaluate the necessity, technical feasibility and outcome of DPEJ in a group of patients consecutively proposed for PEG placement. PATIENTS AND METHODS: In each patient proposed for PEG placement, an upper gastrointestinal endoscopy was performed, and then a pull traction removal gastrostomy tube (18-20 F) was inserted. When PEG was not feasible or contraindicated, a variable stiffness pediatric videocolonscope was used to reach the jejunum: then DPEJ was performed with the same technique and materials as PEG. In both groups enteral feeding was started 24h after the endoscopic procedure, using an enteral feeding pump and the same nutritional schedules. RESULTS: In a 1-year period 90 patients were proposed for PEG placement; PEG could not be performed for technical reasons in 8 (gastric herniation in 1; organ interposition in 7) and gastroparesis in 1. In one patient both PEG and DPEJ were not feasible for organ interposition. The duration of the endoscopic procedure was slightly longer in DPEJ (mean 20 min versus 15 min). No complications related to the endoscopic procedure were observed in both DPEJ and PEG patients. No nutritional complication were observed in the DPEJ group. CONCLUSION: In our experience, PEG was not feasible or contraindicated in about 10% of patients proposed for. In these patients, DPEJ was placed: the procedure resulted to be feasible and safe with the use of a pediatric videocolonscope to easily reach the jejunum. The insertion of DPEJ did not change the nutritional management of enteral feeding. However, long-term effects or complications remain to be evaluated in larger studies.

Probiotics: from research to consumer.

Intestinal microflora has metabolic, trophic and protective functions, and can be modified in pathological conditions and by the exogenous administration of probiotics. Probiotics are defined as living microorganisms which resist gastric, bile, and pancreatic secretions, attach to epithelial cells and colonize the human intestine. In the last twenty years research has been focused on the identification of the role of planktonic flora and adhesive bacteria in health and disease, and on the requisite of bacterial strains to become probiotic product which can be marketed. Probiotics can be commercialized either as nutritional supplements, pharmaceuticals or foods, but the marketing as a pharmaceutical product requires significant time, complex and costly research, and the demonstration of a well-defined therapeutic target. This review examines the sequential steps of research which, from the identification of a possible probiotic strain, lead to its production and marketing, summarizing the whole process existing behind its development, through its growth in laboratory, the studies performed to test its resistance to human secretions and stability, microencapsulation technologies, and safety tests.

Impact of referral for gastro-oesophageal reflux disease on the workload of an academic Gastroenterology Unit.

BACKGROUND: Gastro-oesophageal reflux disease is known to be a frequent cause of patients' referral to hospital gastroenterologists. AIM: To increase knowledge on referral for reflux disease, in an Italian academic setting. PATIENTS AND METHODS: The impact of gastro-oesophageal reflux disease on 1 year's workload, comprising upper endoscopy, outpatients' consultations in the general clinic, oesophageal pH monitoring and oesophageal manometry was retrospectively assessed. Appropriateness of oesophageal pH monitoring and oesophageal manometry was also evaluated. RESULTS: Endoscopy: Out of 2269 upper endoscopies reflux symptoms comprised 16.9% (n=386) of referrals; 19.1% only of these 386 patients had erosive oesophagitis at endoscopy and none had oesophagogastric malignancies (68% of the patients were >45 years). Consultations: Thirty-three percent out of 553 patients were referred for reflux symptoms. Upper endoscopy had already been performed before consultation in 64% of them. pH monitoring and oesophageal manometry: Two hundred and sixteen oesophageal pH monitorings and 160 oesophageal manometries were performed and 29% and 28%, respectively, were inappropriate, being performed in the diagnostic work-up of patients with typical reflux symptoms. CONCLUSIONS: At an academic Gastroenterology Unit, (a) gastro-oesophageal reflux disease is a frequent referral for upper endoscopy and consultations, (b) prevalence of oesophagitis is low, (c) consultation is preceded by endoscopy in the majority of patients and (d) oesophageal pH monitoring and oesophageal manometry are often inappropriately used.

Gastric involvement in a patient with secondary syphilis.

A 30-year-old man was referred because of a short lasting history of severe epigastric pain and early satiety, with remarkable weight loss. Physical examination was fully consistent with secondary syphilis and upper GI tract endoscopy revealed multiple gastric mucopurulent erosions and several nodular lesions ranging from 2 to 3 cm in diameter, with central crater, abruptly ending at the pyloric level. Appropriate antibiotic treatment obtained a dramatic improvement and complete reversal of cutaneous and gastric lesions.

Double-peaked high-pressure zone at the esophagogastric junction in controls and in patients with a hiatal hernia: a study using high-resolution manometry.

The lower esophageal high-pressure zone (HPZ) consists of the intrinsic lower esophageal sphincter (LES) and the diaphragmatic sphincter. In patients with a hiatal hernia these constituents are separated. We performed high-resolution manometry of the esophagogastric HPZ in six controls, six patients with a small hernia, and six patients with a large hernia. Prevalence of a double-peak pressure profile of the HPZ was noted. Pressures and distances between the peaks were assessed. Prevalence of the double-peak profile was similar between patients with a small hernia and controls, but patients with a large hernia showed a higher prevalence with inspiration (P < 0.05) than the others. The distance between the two peaks was larger in patients with a large hernia (P < 0.05). In conclusion, high-resolution manometry makes it possible to distinguish the diaphragmatic pressure component from the LES. Two pressure peaks can be found both in hernia patients and in healthy volunteers.

Relationship between motor function of the proximal stomach and transient lower oesophageal sphincter relaxation after morphine.

BACKGROUND: Morphine reduces the rate of transient lower oesophageal sphincter (LOS) relaxations but its site of action is presently unknown. There are no data available concerning its motor effects on the proximal stomach, an important site for triggering transient LOS relaxations. AIM: To evaluate the effect of morphine on the rate of transient LOS relaxations and motor function of the proximal stomach. SUBJECTS AND METHODS: In 19 healthy subjects, concurrent transient LOS relaxations with a sleeve sensor and motor function of the proximal stomach with a bag connected to an electronic barostat were recorded during pressure controlled (n = 9) and volume controlled (n = 10) gastric distensions after intravenous administration of placebo and morphine 100 microg/kg. RESULTS: During pressure controlled distensions, intrabag volume was markedly decreased by morphine (median 189 ml (interquartile range 101-448) v 404 (265-868) after placebo; p<0.01) as was the rate of transient LOS relaxations (0.5/30 minutes (0.4-2) v 2.5 (2-4); p<0.01). When intrabag volume was kept constant (525 ml (490-600)) (that is, in volume controlled distensions), the rate of transient LOS relaxations was not affected by morphine (2/30 minutes (2-3) v 2.5 (2-3)). Gastric contractions decreased after morphine similarly during pressure controlled and volume controlled distensions (8.5/30 minutes (4-10) v 15.5 (9.5-20.5), p<0.02; and 6.5 (0-24) v 19.5 (12-22), p<0.05). CONCLUSIONS: The effect of morphine on transient LOS relaxations is dependent on the decrease in volume of the proximal stomach. Our data suggest that pharmacological interventions which decrease fundal volume should result in control of transient LOS relaxation mediated gastro-oesophageal reflux.

An experimental model for the study of transient lower oesophageal sphincter relaxation and motor function of the proximal stomach in humans.

A simple and reliable experimental model would be useful in human research on new drugs which target transient lower oesophageal sphincter (LOS) relaxation. The aim was to investigate the effect of repeated distensions on the rate of transient LOS relaxation, LOS pressure and motor function of the proximal stomach. Twelve healthy subjects were studied with a multilumen manometric assembly incorporating a sleeve sensor for the LOS and a bag positioned in the proximal stomach and connected to a barostat. Intrabag volume was set at 75% of the threshold for gastric discomfort and maintained for two 30-min distension periods separated by a 45-min washout with the bag deflated. The studies lasted 145 +/- 2 min. The rate of transient LOS relaxations was similar during the two distensions, 3.5;2-4 vs 3;2.5-4 (median;interquartile range) and so was LOS pressure. Baseline intrabag pressure, as a measure of gastric tone, and the number of pressure waves, as a measure of phasic contractions, were also similar, 11.3;9.3-12.3 mmHg vs 10.8;9.3-12.5 mmHg and 16;13-28 mmHg vs 19;15-29 mmHg, respectively. Our model allows to perform 1-day studies which can assess two experimental conditions on transient LOS relaxations and motor function of the proximal stomach within an acceptable time span.

Effect of non-selective gamma-aminobutyric acid receptor stimulation on motor function of the lower oesophageal sphincter and gastro-oesophageal reflux in healthy human subjects.

BACKGROUND: Transient lower oesophageal sphincter relaxation and low lower oesophageal sphincter pressure are the main mechanisms of reflux. It has recently been shown that the stimulation of gamma-aminobutyric acid type B (GABAB) receptors by baclofen decreases the rate of transient lower oesophageal sphincter relaxation and increases the lower oesophageal sphincter pressure in healthy humans. Valproic acid increases synaptosomal GABA concentrations, thus affecting all types of GABA receptors. AIM: To evaluate the effect of valproic acid on transient lower oesophageal sphincter relaxation, lower oesophageal sphincter pressure and gastro-oesophageal reflux. METHODS: Thirteen healthy subjects underwent 2-h post-prandial oesophageal motility and pH monitoring on two separate occasions after the oral administration of 1 g valproic acid or placebo. RESULTS: Valproic acid increased the lower oesophageal sphincter pressure by 41% (14.0 +/- 2.1 mmHg vs. 9.9 +/- 2.0 mmHg after placebo, P<0.02), but did not affect the rate of transient lower oesophageal sphincter relaxation (7.9 +/- 1.0/h vs. 8.2 +/- 0.9/h after placebo), the number of reflux episodes or gastro-oesophageal reflux. CONCLUSIONS: Non-selective GABA receptor stimulation may be beneficial to reflux patients with low lower oesophageal sphincter pressure, but exerts a different modulation of transient lower oesophageal sphincter relaxation than the selective stimulation of GABAB receptors.

Review article: gastro-oesophageal reflux disease--pathophysiological issues of clinical relevance.

Gastro-oesophageal reflux disease is a multifactorial disorder in which the pathophysiological mechanisms are variably combined in different patients. Motor dysfunction of the lower oesophageal sphincter (LOS) and, possibly, the proximal stomach is a major cause of the increase in the number of reflux episodes. Transient LOS relaxation is the main mechanism of reflux in many patients with endoscopically negative disease, whereas a hypotensive LOS becomes relevant only in patients with oesophagitis. Alterations in primary and secondary peristalsis contribute to the increased oesophageal acid exposure by delaying clearance. The presence of a hiatus hernia, especially when voluminous and/or non-reducible, increases the number of reflux episodes by mechanically weakening the oesophago-gastric junction, and impairs oesophageal clearance. Hypersensitivity to acid is often present and contributes to the clinical manifestations of the disease, whereas oesophageal hypersensitivity, both to chemical and mechanical stimuli, plays a predominant role in a subset of patients. Increased concentrations of noxious compounds in the oesophageal refluxate may contribute to the development of anatomical lesions, but this is still a matter for debate. The clinical relevance of Helicobacter pylori infection and of mucosal defensive factors still needs to be fully elucidated.