Simulations of dredged sediment spreading on a Posidonia oceanica meadow off the Ligurian coast, Northwestern Mediterranean.

The sandy deposits from dredging can have negative effects on the environment such as increase in suspended solids in the water column and their consequent transport. An experimental study was conducted to characterize water masses, dynamics, and sedimentation rates on the Ligurian continental shelf (Italy), where both a sand deposit, that could be used for beach nourishment, and a nearby Posidonia oceanica meadow coexist. The environmental plan provides a mathematical simulation of the sediment-dispersion to evaluate the possible impact on the meadow. It has been calculated that the dredging could double the concentration of suspended particles, but its scheduling will preclude a sediment accumulation. All the information obtained from this work will be used to study the environmental feasibility of the sand deposit exploitation and as starting point for drawing up the monitoring plan in case of dredging.

Essential hypertension and chronic viral hepatitis.

OBJECTIVE: Both arterial hypertension and chronic hepatitis are common disorders. The relationship between arterial pressure and liver cirrhosis has been extensively studied, but no studies are available in chronic hepatitis (CH). Recently, a few studies have reported that treatment with angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin-receptor blockers (ARBs), commonly used in arterial hypertension, reduce hepatic fibrosis in patients with viral CH and in nonalcoholic steatohepatitis. This study was aimed at comparing the evolution of post-viral CH in patients with/without concomitant essential hypertension. METHODS: Two sets of observations were carried out: (a) a cross-sectional cohort study of 95 patients with viral CH, to compare the severity of histological and biochemical data at diagnosis, in relation to pharmacologically treated essential hypertension, and (b) a retrospective study with the observation of 254 patients with CH of viral etiology, followed up from 2 to 20 years, to establish the natural history of viral CH in relation to treated essential hypertension. RESULTS: In the cross-sectional analysis, patients with treated hypertension had a significantly older age at diagnosis of CH (51.4 +/- 8.4 years vs. 46.2 +/- 12.2 in normotensive; P < 0.001) and histological evidence of less severe necro-inflammatory liver damage. ALT levels were also lower (109.8 +/- 62.5 U/L vs. 166.0+/-169.5 in normotensive; P < 0.001) as were endothelin-1 levels (0.74 +/- 0.97 vs. 1.77 +/- 1.51 fmol/mL; P < 0.001). The retrospective study confirmed an older age at diagnosis in patients with treated hypertension (48.7 +/- 9.8 vs. 41.9 +/- 11.8 years; P < 0.001) and lower death rates (2.2% vs. 11%; P < 0.05). CONCLUSIONS: The evolution of post-viral CH seems to be less severe in subjects with essential hypertension, possibly in relation to treatment with antihypertensive drugs.

Gastrokine 1 expression in patients with and without Helicobacter pylori infection.

BACKGROUND: To understand the molecular changes underlying Helicobacter pylori-related gastric diseases is mandatory to prevent gastric cancer. Proteomic technology is providing a rapid expansion of the basic knowledge, particularly in the discovery of new biomarkers involved in the tumourigenesis. AIM: To characterise changes in protein expression level of the gastric mucosa in H. pylori-infected patients. METHODS: The population enrolled comprised 41 dyspeptic patients. Proteins extracted from gastric mucosal specimens were analysed by 2-dimensional electrophoresis, sequenced by MALDI-TOF and identified by Edman's degradation. RESULTS: Twenty-one out of 41 patients had H. pylori infection of whom 17 had anti-CagA IgG antibodies. Several proteins were identified, of which Rho guanosine diphosphatase dissociation inhibitor alpha and heat shock protein 27 increased and glutathione transferase and antrum mucosa protein-18 decreased in H. pylori-positive in respect to H. pylori-negative patients. Interestingly, antrum mucosa protein-18, currently referred as gastrokine-1, showed two isoforms differing in the first N-terminal amino acid residue. Both gastrokine-1 isoforms were observed in the H. pylori-negative group whereas a lower expression or even absence of the gastrokine-1 basic isoform was found in a subgroup (7/21) of H. pylori-positive patients with moderate-severe gastritis. CONCLUSION: Our study demonstrated the presence of gastrokine-1 isoforms of which the basic isoform was reduced in a subset of patients with H. pylori infection.

Oesophageal acid exposure and altered neurocardiac function in patients with GERD and idiopathic cardiac dysrhythmias.

BACKGROUND: Oesophageal sensory stimuli alter neurocardiac function through autonomic reflexes. AIM: To evaluate in patients with idiopathic supraventricular cardiac dysrhythmias and gastro-oesophageal reflux disease (GERD) whether GE reflux alters neurocardiac function and the effect of acid suppression on cardiac symptoms. METHODS: Thirty-two patients (13 females and 19 males; age: 20-69 years) with dysrhythmias plus GERD, and nine patients (five females and four males; age: 43-58 years) with GERD only, underwent simultaneous 24-h pH-metry and ECG monitoring. Power spectrum analysis of heart rate variability (PSHRV) was obtained with both its low frequency (LF, sympathetic modulation) and high frequency (HF, vagal modulation) components. Hourly mean oesophageal pH and LF/HF ratio were correlated. A 3 months full-dosage PPI therapy (esomeprazole 40 mg/day) was prescribed. RESULTS: In 18 (56%) of the 32 patients with dysrhythmia and in none with GERD only, a significant (P < 0.05) correlation between oesophageal pH and LF/HF ratio (oesophagus-heart correlation) was observed. A significant reduction of cardiac symptoms after PPI therapy was observed only in these patients (13/16 vs. 4/11, P < 0.01). CONCLUSIONS: This study has identified a subgroup of dysrhythmic patients in whom the oesophageal acid stimulus elicited cardiac autonomic reflexes. In these patients acid suppression seems to improve GERD and cardiac symptoms.

Diagnostic accuracy of the serum profile of gastric mucosa in relation to histological and morphometric diagnosis of atrophy.

BACKGROUND: Histology is the gold standard for diagnosis of atrophy but is hampered by observer variation. A reliable method to overcome this issue is morphometric analysis of gastric mucosa. Serum pepsinogens and gastrin have been proposed in the diagnostic work-up of gastric atrophy although diagnostic accuracy of these tests is considered unsatisfactory. AIM: To evaluate the diagnostic accuracy of gastric serum profile in relation both to morphological and morphometric diagnosis of gastric atrophy. METHODS: Ninety-four dyspeptic out-patients underwent upper endoscopy and evaluation of serum levels of PGI, PGII and 17-gastrin. Diagnostic accuracy of gastric serum profile was tested by receiver operating characteristic curves and by evaluation of sensitivity and specificity in relation to both histology and morphometric analyses. RESULTS: As far as concern to histological evaluation, only PGI/PGII ratio showed an acceptable diagnostic accuracy in discrimination of gastric atrophy, while, when morphometric analysis was considered as reference, both serum PGI level and PGI/PGII ratio showed an excellent performance. However, both PGI and PGI/PGII ratio showed low sensitivity and high specificity. CONCLUSIONS: Serological gastric profile corresponds better with the morphometric diagnosis of atrophy, even if, because of the low sensitivity, today this could only be used as screening test of chronic atrophic gastritis.

Nutritional state and energy balance in cirrhotic patients with or without hypermetabolism. Multicentre prospective study by the 'Nutritional Problems in Gastroenterology' Section of the Italian Society of Gastroenterology (SIGE).

BACKGROUND AND AIMS: A total of 334 stable, compensated cirrhotic patients admitted to 10 Italian Gastroenterology Units were included in a prospective study to evaluate nutritional state and energy balance in liver cirrhosis. MATERIALS AND METHODS: Nutritional state and calorie intake were examined in the total population, while adequacy of calorie intake versus measured total energy expenditure was evaluated in a comparable subpopulation and in 40 matched controls, by computing the energy balance. RESULTS: Our data demonstrated that: (i) malnutrition was present in 25% of the total patients and significantly correlated with the Child's group (A=16%; B=25%; C=44%); (ii) the type of malnutrition is influenced by mBEE: normometabolic patients exhibit a significant (p<0.005) reduction of mid-arm fat area while both hypermetabolic and hypometabolic patients show a significant (p<0.005) decline in kg of free fat mass; (iii) normometabolic and hypometabolic patients have a negative energy balance, due to a high level of physical activity (127+/-14 kJ) in the first group and a reduced energy intake/kg body weight (102+/-12 kJ) in the second; (iv) hypermetabolic patients have a positive energy balance due to decreased daily physical activity/kg body weight (108+/-28 kJ); (v) malnourished and normometabolic patients eat a significantly (p<0.05) reduced percentage of protein whereas malnourished and hypermetabolic patients eat a significantly increased percentage of fat (p<0.05). CONCLUSION: Although multivariate regression analysis confirms that the Child-Pugh's score is a better independent predictor of malnutrition, the measure of REE, TEE, calorie intake and energy balance need to be routinely performed in cirrhotic patients, in order to recognise hypermetabolic and hypometabolic patients (approximately 30%) in whom the nutritional and metabolic parameters are indispensable as a basis for designing and prescribing personalised nutritional strategies that can treat muscle malnutrition and thus improve the morbidity and mortality rates.

An unusual case of ascites.

A 76-year-old woman with abdominal pain and diarrhoea developed ascites that did not respond to treatment. There were no signs of liver damage. Abdominal ultrasonography with colour Doppler revealed an arterial-like flow in the enlarged splenic vein. Using selective mesenteric arteriography, we were able to diagnose a shunt between the inferior mesenteric artery and the inferior mesenteric vein. This is an unusual case of ascites due to prehepatic portal hypertension secondary to an extrahepatic arterioportal fistula.

Is there a link between environmental factors and a genetic predisposition to cancer? A lesson from a familial cluster of gastric cancers.

To determine the prevalence of gastric precancerous lesions and mucosal genetic alterations in relatives of a cluster of familial gastric cancer (FGC), we studied a kindred spanning two generations. The founder, daughter and niece underwent surgery for gastric cancer (GC); a son and other two daughters of the founder, presented with chronic dyspepsia. In all subjects, gastric mucosa samples were analysed for pathological features, Helicobacter pylori infection, microsatellite (MIN) and chromosomal (CIN) instability. The overexpression of mp53 and c-myc, and cytoplasmic beta-catenin delocalisation were found in the 2 younger cancer patients. All GC and gastritis patients had normal E-cadherin expression and were MIN-negative. Aneuploidy characterised all GC cases, and mixed euploid and aneuploid cell populations were present in the gastric biopsies from two of three 'at-risk' relatives. These two subjects, one of whom had severe active gastritis, and gastric mp53 and c-myc expression, were CagA-positive H. pylori-infected. DNA aneuploidy, p53 and c-myc expression disappeared after H. pylori eradication. In this FGC cluster, genetic abnormalities were found in first-degree relatives (3 patients) only in presence of H. pylori infection (2 cases H. pylori-positive versus 1 case H. pylori-negative) supporting the hypothesis that, besides the influence of a genetic profile, FGC may be, at least partly, mediated by intrafamilial clustering of H. pylori infection.

Acid exposure and altered acid clearance in GERD patients treated for Helicobacter pylori infection.

BACKGROUND: After the eradication of Helicobacter pylori, an increased incidence of gastroesophageal reflux disease and acid gastric secretion have been reported. AIM: To evaluate the effect of Helicobacter pylori-eradication on proximal and distal gastroesophageal reflux and acid clearance in patients with gastroesophageal reflux disease. PATIENTS AND METHODS: Sixty-eight gastroesophageal reflux disease patients (age range 18-61 years) were studied by upper endoscopy. All underwent esophageal manometry and dual probe 24-h pH-metry. RESULTS: Percent of time at pH<4 was significantly increased in the proximal esophagus of Helicobacter pylori-eradicated patients compared to Helicobacter pylori-negative (2.4+/-0.5 vs. 1.0+/-0.2; p<0.01); no differences were found in the distal esophagus (14.0+/-3.7 vs. 9.0+/-1.4%, NS). The total number of reflux episodes was significantly higher in the proximal oesophagus of Helicobacter pylori-eradicated patients (37+/-3 vs. 22+/-3, p<0.05). In the distal esophagus, acid clearance was significantly longer, both during total time (1.4+/-0.2 vs. 0.8+/-0.7 min, p<0.01), and in the supine period (8.5+/-2.7 vs. 2.7+/-0.4 min, p<0.05). No differences were reported in the manometric parameters of the two groups of patients. CONCLUSION: In patients with gastroesophageal reflux disease, Helicobacter pylori eradication is associated with increased acid exposure of the proximal esophagus and delayed distal acid clearance.

Reflux oesophagitis in adult coeliac disease: beneficial effect of a gluten free diet.

BACKGROUND: Coeliac disease patients show a number of gastrointestinal motor abnormalities, including a decrease in lower oesophageal sphincter pressure. The prevalence of endoscopic oesophagitis in these subjects however is unknown. AIM: To evaluate whether untreated adult coeliac patients had an increased prevalence of reflux oesophagitis and, if so, to assess whether a gluten free diet exerted any beneficial effect on gastro-oesophageal reflux disease (GORD) symptoms. PATIENTS AND METHODS: We retrospectively studied 205 coeliac patients (females/males 153/52, median age 32 years) who underwent endoscopy for duodenal biopsy and 400 non-coeliac subjects (females/males 244/156, median age 37 years) referred for endoscopy for upper gastrointestinal symptoms. Each patient was given a questionnaire for evaluation of GORD symptoms prior to and 4-12 months after endoscopy. Coeliac patients were given a gluten free diet. Oesophagitis patients of both groups, following an eight week course of omeprazole, were re-evaluated for GORD symptoms at four month intervals up to one year. Significance of differences was assessed by Fisher's exact test. RESULTS: Oesophagitis was present in 39/205 (19%, 95% confidence interval (CI) 13.8-25.0%) coeliac patients and in 32/400 (8%, 95% CI 5.5-11.1%) dyspeptic subjects. At the one year follow up, GORD symptoms relapsed in 10/39 (25.6%, 95% CI 13-42.1%) coeliacs with oesophagitis and in 23/32 (71.8%, 95% CI 53.2-86.2%) non-coeliac subjects with oesophagitis. CONCLUSION: Coeliac patients have a high prevalence of reflux oesophagitis. That a gluten free diet significantly decreased the relapse rate of GORD symptoms suggests that coeliac disease may represent a risk factor for development of reflux oesophagitis.

Natural history of chronic viral hepatitis in southern Italy: epidemiological changes since the introduction of the anti-HCV test.

We investigated whether there are differences between the natural history of B and C chronic hepatitis in a southern Italian population, and whether the chronic viral hepatitis population was modified by the introduction of the anti-HCV test in 1989. We examined clinical charts of 1120 patients consecutively admitted to our division from January 1979 to December 1998 with the histological diagnosis of chronic viral hepatitis (304 from 1979 to 1988; 816 from 1989 to 1998). We found significant differences only in age at diagnosis (higher in the second decade, P = 0.001), and in aetiology (HBV decreased in the second decade, P < 0.0001). We were able to follow up 449 patients for 2-20 years (311 with HCV and 138 with HBV infection), and found that chronic HCV evolved to cirrhosis more frequently than did chronic HBV; but in both types time to development of cirrhosis and the incidence of death were similar. Our data confirm that a higher onset age of HBV and of HCV is frequently observed in those subjects who have a faster disease progression.

Molecular alteration of gastric carcinoma.

Gastric cancer is constituted by two histomorphological entities ''intestinal'' and ''diffuse'' that differ in epidemiology, pathogenesis, clinical outcome and genetic profile. Two distinct molecular pathways of genomic destabilization have been identified in gastric carcinogenesis: the microsatellite mutator phenotype (MMP) and a phenotype associated with chromosomal and intrachromosomal instability (CIN). The microsatellite mutator phenotype is caused by mismatch repair (MMR) deficiency and is associated with mutational inactivation; this condition is identified as microsatellite instability (MIN). CIN is characterized by chromosomal rearrangements and losses or gains of chromosomes, which in turn can induce oncogene activation and/or tumour-suppressor-gene inactivation. Mounting evidence suggests that MMP alterations, DNA aneuploidy and expression of the products of cancer-related genes are early markers of cell transformation, and may serve to identify the genetic pathway of gastric carcinoma. However, the lack of a clear genetic basis lends weight to the notion that gastric cancer may be affected by exposure to environmental factors. Helicobacter pylori is one of the most frequent infections worldwide and is the most important environmental risk factor associated with sporadic gastric cancer. Exposure of gastric epithelial cells to H. pylori results in the generation of reactive oxygen species and an increased level of inducible nitric oxide synthase that in turn may cause genetic alterations leading to cancer in a subset of subjects. In conclusion gastric cancer is the result of an interplay between genetic and environmental factors. The new technologies for the molecular analysis will be a useful tool to understand the individual's risk and settle novel biological therapeutic strategies.

Non-alcoholic fatty liver disease in an area of southern Italy: main clinical, histological, and pathophysiological aspects.

BACKGROUND/AIMS: Studies on non-alcoholic fatty liver disease (NAFLD) have included chronic liver damage attributed to various causes. Our investigation was held to observe the main clinical, histological, and pathophysiological aspects of NAFLD in patients not exposed to any known cause of chronic liver disease. METHODS: We evaluated, in 84 in-patients (male/female, 66/18; median age, 36 years), the clinical and biochemical characteristics of NAFLD, and particularly its association with diabetes, dyslipidemia, hyperinsulinemia and/or with the increase of parameters of oxidative stress (blood levels of malonyldialdehyde, 4-hydroxynonenal and total plasma antioxidant capacity). RESULTS: Ninety percent of patients had an increased body mass index (BMI), 35% had dyslipidemia, 40% had sub-clinical diabetes (only 3% had overt diabetes), 60% had hyperinsulinemia, and more than 90% had enhanced levels of lipid peroxidation markers. In 48 patients who had consented to liver biopsy, we found: 14 with simple steatosis, 32 with steatohepatitis, and two with cirrhosis. CONCLUSIONS: Our data indicate that in our country, NAFLD may occur in young males with an increased BMI, with or without hyperinsulinemia, dyslipidemia and diabetes, generally associated with disorders of redox status, and that it may be differentiated from steatosis to steatohepatitis or cirrhosis only with a liver biopsy.

Functional dyspepsia symptoms, gastric emptying and satiety provocative test: analysis of relationships.

BACKGROUND: The correlation between symptoms and observed impaired function in functional dyspepsia is still inconsistent. The aims of the study were to obtain a measure of satiety by a meal test; to verify whether this compares with severity of symptoms assessed using a reproducible questionnaire; and to correlate the parameters of satiety test and gastric emptying with all the dyspeptic symptoms. METHODS: Fifty-two functional dyspepsia patients reported their symptoms on a standardized questionnaire that considered belching, bloating, early satiety, epigastric pain and burning, nausea, postprandial fullness and vomiting. They were monitored for gastric emptying of a solid caloric meal using a radionuclide technique and underwent a test to quantify meal-induced satiety by a liquid caloric meal. RESULTS: The number of kilocalories ingested during the satiety test until the occurrence of maximum satiety in healthy subjects was 110% higher than in the dyspeptic group (mean +/- s(mean): 1110 +/- 23 versus 532 +/- 56; P < 0.01). We found a significant positive correlation between gastric emptying rate and kcal of the satiety test (P < 0.01; r = 0.428). Logistic regression showed a significant inverse association between severity of early satiety-coded as absent, mild, moderate or severe, kcal of meal test (P = 0.01), and gastric emptying lag phase (P = 0.03). Bloating was associated directly with t(1/2) of gastric emptying (P = 0.03) and inversely with lag phase (P = 0.02). CONCLUSIONS: The satiety test gives a fine numerical measure of satiety and confirms the results of a symptoms questionnaire. Our study showed an indirect correlation between severity of early satiety--as measured by the satiety test, and gastric emptying rate, as well as an association between bloating and delayed gastric emptying.

In vivo and in vitro studies of cytosolic phospholipase A2 expression in Helicobacter pylori infection.

Modifications of mucosal phospholipids have been detected in samples from patients with Helicobacter pylori-positive gastritis. These alterations appear secondary to increased phospholipase A2 activity (PLA2). The cytosolic form of this enzyme (cPLA2), normally involved in cellular signaling and growth, has been implicated in cancer pathogenesis. The aim of this study was to investigate cPLA2 expression and PLA2 activity in the gastric mucosae of patients with and without H. pylori infection. In gastric biopsies from 10 H. pylori-positive patients, cPLA2 levels, levels of mRNA as determined by reverse transcriptase PCR, levels of protein as determined by immunohistochemistry, and total PLA2 activity were higher than in 10 H. pylori-negative gastritis patients. To clarify whether H. pylori had a direct effect on the cellular expression of cPLA2, we studied cPLA2 expression in vitro with different human epithelial cell lines, one from a patient with larynx carcinoma (i.e., HEp-2 cells) and two from patients with gastric adenocarcinoma (i.e., AGS and MKN 28 cells), incubated with different H. pylori strains. The levels of cPLA2, mRNA, and protein expression were unchanged in Hep-2 cells independently of cellular adhesion or invasion of the bacteria. Moreover, no change in cPLA2 protein expression was observed in AGS or MKN 28 cells treated with wild-type H. pylori. In conclusion, our study shows increased cPLA2 expression and PLA2 activity in the gastric mucosae of patients with H. pylori infection and no change in epithelial cell lines exposed to H. pylori.

Interferon-alpha plus amantadine in chronic hepatitis C resistant to interferon alone: a pilot randomized study.

The optimal therapy for patients with chronic hepatitis C who have not responded to interferon (IFN) is still an unsolved issue. The aim of this study was to evaluate the efficacy and tolerability of a high dose of IFN-alpha2a plus amantadine for chronic hepatitis C patients who were non-responders to a previous course of IFN. Forty consecutive patients with chronic hepatitis C, genotype 1b, who had not responded to IFN-alpha, were randomized to receive: (i) IFN 4.5 MU daily plus amantadine 200 mg/day for 4 weeks and then IFN 6 MU thrice weekly plus amantadine 200 mg/day for an additional 5 months (group A) or (ii) IFN alone at the same dosage and duration (group B). After 1 month of therapy, normal alanine aminotransferase (ALT) values were observed in three of 21 (14.3%) patients in group A and in three of 19 (15.8%) in group B; serum hepatitis C virus (HCV)-RNA clearance was observed in one patient (4.8%) in group A and in six (31.6%) in group B. At the end of treatment, six patients (28.6%) in group A and three (15.8%) in group B had normal ALT levels; however, HCV-RNA in serum was detectable in all of them at levels comparable to the basal values; an ALT relapse occurred within 3 months of stopping therapy. The combination of daily IFN plus amantadine was ineffective in this setting.

Interactions between metabolic disorders (diabetes, gallstones, and dyslipidaemia) and the progression of chronic hepatitis C virus infection to cirrhosis and hepatocellular carcinoma. A cross-sectional multicentre survey.

BACKGROUND: Diabetes, gallstones and dyslipidaemia are widespread, metabolically related, disorders that can affect the liver, often in a clinically silent fashion. AIM: To investigate whether the presence of these disorders may worsen chronic viral disease by inducing additional liver damage, revealed by variations in serum increases of aminotransferase, alkaline phosphatase and gamma-glutamyl-transpeptidase activities. PATIENTS AND METHODS: This retrospective, cross-sectional study involved 1,195 patients with chronic hepatitis C virus infection: 47.2% chronic hepatitis, 45.2% cirrhosis, and 7.6% hepatocellular carcinoma. 14.9% of patients had enzymatic cholestasis, defined as combined increase of alkaline phosphatase and gamma-glutamyl-transpeptidase. A Log-linear statistical model was applied to the following variables: stages of liver disease, diabetes, cholelithiasis, hypertriglyceridaemia, hypercholesterolaemia, and enzymatic cholestasis. RESULTS: Log-linear analysis, applied to categorical variables, revealed, for the first time, a three-way interaction between the stages of chronic liver disease, diabetes, and enzymatic cholestasis. Two-way interactions demonstrated that liver disease stages correlated directly to the prevalence of cholelithiasis and inversely to hypercholesterolaemia. Irrespective of the liver disease stage, hypertriglyceridaemia correlated to hypercholesterolaemia. CONCLUSIONS: This study discloses a synergistic liver damaging effect of diabetes and hepatitis C virus. The three-way interaction obtained by our analysis suggests that diabetes is a risk factor for the progression of viral liver disease and that it contributes to disease evolution, at least in part, by induction of cholestasis.

The metabolism of nicotinamide in human liver cirrhosis: a study on N-methylnicotinamide and 2-pyridone-5-carboxamide production.

OBJECTIVES: Nicotinamide methylation followed by urinary excretion of N-methylnicotinamide increases in cirrhotic patients, despite the derangement of the overall methylation processes in liver disease. The rise in N-methylnicotinamide could depend, at least in part, on a reduced transformation of this molecule into 2-pyridone-5-carboxamide. The aim of this study was to investigate this hypothesis. METHODS: Serum and urinary levels (mean +/- SEM) of N-methylnicotinamide and urinary excretion of 2-pyridone-5-carboxamide were measured in 10 healthy controls and 10 patients with liver cirrhosis in basal conditions and after a nicotinamide oral load (1.5 mg/kg body weight). RESULTS: N-methylnicotinamide serum levels increased significantly (p < 0.01) in cirrhotic patients compared to controls, both as basal values (0.43 +/- 0.07 nmol/ml; 0.15 +/- 0.01) and as area under the curve 5 h after a nicotinamide load (cirrhotics: 562.4 +/- 50.5 nmol/ml x min; controls: 314.4 +/- 23.8). Twenty-four-hour urinary excretion of N-methylnicotinamide and 2-pyridone-5-carboxamide was also significantly (p < 0.05) increased in cirrhotic patients versus controls, both in basal conditions (N-methylnicotinamide: 82.0 +/- 8.4 micromol, 48.8 +/- 4.8; 2-pyridone-5-carboxamide: 129.3 +/- 23.0, 64.6 +/- 9.8) and after a nicotinamide oral load (N-methylnicotinamide: 290.1 +/- 23.1, 180.8 +/- 7.4; 2-pyridone-5-carboxamide: 694.7 +/- 32.5, 391.0 +/- 21.9). Moreover, 24 h N-methylnicotinamide/2-pyridone-5-carboxamide ratio was similar in patients and controls (basal: 0.78 +/- 0.39, 0.90 +/- 0.51; load: 0.42 +/- 0.11, 0.48 +/- 0.16). CONCLUSIONS: In cirrhotic patients nicotinamide methylation is increased, as shown by the rise in urinary N-methylnicotinamide and 2-pyridone-5-carboxamide that is concurrent and proportional (constant 24-h metabolite ratio). The hyperfunction of this methylating pathway might play a protective role against the toxic effect of intracellular accumulation of nicotinamide deriving from the catabolic state of cirrhosis.

Role of diaphragmatic crura and lower esophageal sphincter in gastroesophageal reflux disease: manometric and pH-metric study of small hiatal hernia.

The rapid pull-through (RPT) technique during esophageal manometry helps to identify various pressure profiles of hiatal hernia (HH), based on the presence of two high pressure zones: the diaphragmatic crura (DC) and the lower esophageal sphincter (LES). Our aim was to correlate different HH profiles with frequency of reflux episodes in patients with gastroesophageal reflux disease (GERD). Seventy-eight patients with GERD and HH underwent esophageal manometry with RPT and were grouped according to the prevalent pressure profile of HH. Twenty-four-hour pH-metry served to quantify traditional (TR) and nontraditional refluxes (drop of 1 pH unit with pH > 4 or pH < 4 and time < 5 sec) (NTR) during total, upright, and recumbent periods. The group with a prevalent "flat" HH profile, representing LES and DC impairment, had significantly more TRs in total time of reflux (P < 0.01) and in recumbent and upright periods (P < 0.05) compared to the group with a prevalence of the two pressure peaks, corresponding to LES and DC efficiency. However, the group with the flat profile had significantly more NTRs + TRs than the group with pressure peaks in total time (P < 0.01) and recumbent position (P < 0.001) but not in the upright position. Hiatal hernia predisposes to GERD, but only the associated impairment of the LES and diaphragmatic crura pressures represents a condition of high risk for gastroesophageal reflux events.

Effect of Helicobacter pylori infection on gastric cell proliferation and genomic instability in a paediatric population of southern Italy.

BACKGROUND: The incidence of gastric cancer is high in areas with a high prevalence of Helicobacter pylori infection. Cell transformation and tumour progression occur over a long period of time and markers of genomic instability usually precede morphological changes. AIM: To evaluate the effect of Helicobacter pylori infection on cell proliferation, DNA status and oncogene expression in children. PATIENTS AND METHODS: Morphometric and immunohistochemical techniques were used to analyse DNA content, p53 and c-myc oncogene expression and cell proliferation on gastric biopsies of 53 children (27 Helicobacter pylori-negative and 26 Helicobacter pylori-positive). RESULTS: Gastric mucosa was normal in 11% of Helicobacter pylori-positive and in 33% of Helicobacter pylori-negative subjects. Most children had chronic non-atrophic gastritis regardless of Helicobacter pylori infection, and only a minority of children affected by Helicobacter pylori had mild atrophic gastritis. Cell proliferation was significantly higher in children with Helicobacter pylori-positive gastritis than in those with Helicobacter pylori-negative gastritis. No metaplasia, dysplasia, p53 overexpression or altered DNA content was found in any child. Interestingly, 46% of children with and 29% without Helicobacter pylori infection had c-myc overexpression closely related to the cell proliferation rate. CONCLUSION: Helicobacter pylori infection in children may coexist with a normal gastric mucosa, and it is not associated with genomic instability markers in cases of chronic gastritis.