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Heat shock protein B (HspB) is one of the dominant proteins recognized by most Helicobacter pylori-infected persons and is being considered as potential candidates for subunit vaccines. In the present study we describe the generation of an antibody against HspB and its use in immunohistochemical assays on gastric biopsies. We have demonstrated that our rabbit polyclonal antibody against HspB did not recognize any protein in lysates from a lung human epithelial cell (H1299) line and did not cross-react with the other members of human heat shock proteins. Secondly, we have observed that in gastric biopsies, HspB immunostaining was present inside the cytoplasm of human epithelial cells with a particular localization in the apical portion of gastric epithelial cells other than in the extracellular spaces among gastric cells of human stomach. Finally, we have demonstrated a cytoplasmic HspB immunostaining in groups of neoplastic cells of MALT lymphoma. In conclusion, our observations suggest a possible involvement of HspB in the pathogenesis of H. pylori-related pathologies such as gastritis, ulcer and gastric cancer., ((c) 2008 Wiley-Liss, Inc.)

Background & Aims: The extensive infiltration of CD8(+) T cells in the intestinal mucosa of celiac disease (CD) patients is a hallmark of the disease. We identified a gliadin peptide (pA2) that is selectively recognized by CD8(+) T cells infiltrating intestinal mucosa of HLA-A2(+) CD patients. Herein, we investigated the phenotype, the tissue localization, and the effector mechanism of cells responsive to pA2 by using the organ culture of CD intestinal mucosa. The target of pA2-mediated cytotoxicity was also investigated by using the intestinal epithelial cell lines Caco2 and HT29, A2(+) and A2(-), respectively, as target cells., Methods: Jejunal biopsy specimens from CD patients were cultured in vitro with pA2, and cellular activation was evaluated by immunohistochemistry and cytofluorimetric analysis. Cytotoxicity of pA2-specific, intestinal CD8(+) T cells was assayed by granzyme-B and interferon-gamma release and by apoptosis of target cells., Results: pA2 challenge of A2(+) CD mucosa increased the percentage of CD8(+)CD25(+) and of CD80(+) cells in the lamina propria, the former mainly localized beneath the epithelium, as well as the number of terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling-positive cells (TUNEL(+)) in the epithelium. Intraepithelial CD3(+) cells and enterocyte expression of Fas were also increased. CD8(+)CD25(+) and CD8(+)FASL(+) T cells were significantly increased in cell preparations from biopsy specimens cultured with pA2. CD8(+) T-cell lines released both granzyme-B and interferon-gamma following recognition of pA2 when presented by Caco2 and not by HT29., Conclusions: These data indicate that gliadins contain peptides able to activate, through a TCR/HLA class I interaction, CD8-mediated response in intestinal CD mucosa and to induce the enterocyte apoptosis.

Background: Duodenal cancer and ampullary cancer are major causes of death after a prophylactic colectomy in patients with familial adenomatous polyposis (FAP). Forward-viewing endoscopy and side-viewing endoscopy are recommended in patients with FAP for surveillance of periampullary and duodenal polyposis. The study of polyps distal to the duodenum in FAP is limited. A capsule endoscopy (CE) allows visualization of the mucosa of the entire small bowel., Objective: The objective was to detect whether CE has clinical value or any utility for the surveillance of small-bowel polyps in patients with FAP and to evaluate whether there are genotypic factors that predict which patients are at a lower risk of small-bowel polyps., Setting: Two Italian tertiary-referral centers., Patients: Twenty-three patients with FAP who presented for a CE., Main Outcome Measurements: Patients with FAP were examined by CE to assess the location, size, and number of small-bowel polyps. Patient age at CE, sex, years of observation after surgery, type of surgery, duodenal adenomas, and colorectal cancer at surgery were analyzed. All patients were selected for mutation analysis, and the germline adenomatous polyposis coli (APC) gene mutation was detected., Results: Eleven of 23 patients with FAP had duodenal polyps. During CE, jejunal-ileal polyps were detected in 7 of 23 FAPs, with a total number of 15 polyps in the ileum. The presence of duodenal adenomas was the only clinical feature predictive of small-bowel polyps. Identification of the ampulla of Vater was not achieved with CE; duodenal polyps were only seen in 4 of 11 patients identified endoscopically, with an underestimation of polyp numbers. APC mutations between codons 499 and 805 were associated with the absence of small-bowel polyps., Conclusions: CE is useful and safe for the surveillance of jejunal-ileal polyps in selected patients with FAP. CE is not useful in the surveillance of the duodenum where the majority of small-bowel cancers occur.

Background & Aims: Celiac disease is characterized by activation of HLA-DQ2/DQ8-restricted intestinal gluten-specific CD4(+) T cells. In particular, gluten becomes a better T-cell antigen following deamidation catalyzed by tissue transglutaminase. To date, the only available therapy is represented by adherence to a gluten-free diet. Here, we examined a new enzyme strategy to preventively abolish gluten activity., Methods: Enzyme modifications of the immunodominant alpha-gliadin peptide p56-68 were analyzed by mass spectrometry, and peptide binding to HLA-DQ2 was simulated by modeling studies. Wheat flour was treated with microbial transglutaminase and lysine methyl ester; gliadin was subsequently extracted, digested, and deamidated. Gliadin-specific intestinal T-cell lines (iTCLs) were generated from biopsy specimens from 12 adult patients with celiac disease and challenged in vitro with different antigen preparations., Results: Tissue transglutaminase-mediated transamidation with lysine or lysine methyl ester of p56-68 or gliadin in alkaline conditions inhibited the interferon gamma expression in iTCLs; also, binding to DQ2 was reduced but not abolished, as suggested by in silico analysis. Lysine methyl ester was particularly effective in abrogating the activity of gliadin. Notably, a block in the response was observed when iTCLs were challenged with gliadin extracted from flour pretreated with microbial transglutaminase and lysine methyl ester., Conclusions: Transamidation of wheat flour with a food-grade enzyme and an appropriate amine donor can be used to block the T cell-mediated gliadin activity. Considering the crucial role of adaptive immunity in celiac disease, our findings highlight the potential of the proposed treatment to prevent cereal toxicity.

Celiac disease (CD) results from a permanent intolerance to dietary gluten and is due to a massive T cell-mediated immune response to gliadin, the main component of gluten. In this disease, the regulation of immune responses to dietary gliadin is altered. Herein, we investigated whether IL-10 could modulate anti-gliadin immune responses and whether gliadin-specific type 1 regulatory T (Tr1) cells could be isolated from the intestinal mucosa of CD patients in remission. Short-term T cell lines were generated from jejunal biopsies, either freshly processed or cultured ex vivo with gliadin in the presence or absence of IL-10. Ex vivo stimulation of CD biopsies with gliadin in the presence of IL-10 resulted in suppression of Ag-specific proliferation and cytokine production, indicating that pathogenic T cells are susceptible to IL-10-mediated immune regulation. T cell clones generated from intestinal T cell lines were tested for gliadin specificity by cytokine production and proliferative responses. The majority of gliadin-specific T cell clones had a Th0 cytokine production profile with secretion of IL-2, IL-4, IFN-gamma, and IL-10 and proliferated in response to gliadin. Tr1 cell clones were also isolated. These Tr1 cells were anergic, restricted by DQ2 (a CD-associated HLA), and produced IL-10 and IFN-gamma, but little or no IL-2 or IL-4 upon activation with gliadin or polyclonal stimuli. Importantly, gliadin-specific Tr1 cell clones suppressed proliferation of pathogenic Th0 cells. In conclusion, dietary Ag-specific Tr1 cells are present in the human intestinal mucosa, and strategies to boost their numbers and/or function may offer new therapeutic opportunities to restore gut homeostasis.

Objectives: Our objectives were to assess the beneficial and harmful effects of milk thistle (MT) or MT constituents versus placebo or no intervention in patients with alcoholic liver disease and/or hepatitis B and/or C liver diseases., Methods: Randomized clinical trials studying patients with alcoholic and/or hepatitis B or C liver diseases were included (December 2003). The randomized clinical trials were evaluated by components of methodological quality., Results: Thirteen randomized clinical trials assessed MT in 915 patients with alcoholic and/or hepatitis B or C liver diseases. The methodological quality was low: only 23% of the trials reported adequate allocation concealment and only 46% were considered double blind. MT versus placebo or no intervention for a median duration of 6 months had no significant effects on all-cause mortality (relative risk (RR) 0.78, 95% confidence interval (CI) 0.53-1.15), complications of liver disease, or liver histology. Liver-related mortality was significantly reduced by MT in all trials (RR 0.50, 95% CI 0.29-0.88), but not in high-quality trials (RR 0.57, 95% CI 0.28-1.19). MT was not associated with a significantly increased risk of adverse events., Conclusions: Based on high-quality trials, MT does not seem to significantly influence the course of patients with alcoholic and/or hepatitis B or C liver diseases. MT could potentially affect liver injury. Adequately conducted randomized clinical trials on MT versus placebo may be needed.

Helicobacter pylori is a spiral, gram-negative rod-shaped pathogen that attaches to gastric epithelial cells in the human stomach and is a causative agent of chronic active gastritis, peptic ulcer and neoplasia. H. pylori is one of the most common pathogens afflicting humans and is the major environmental factor in the development of gastric cancer increasing from 4 to 6 folds the risk of its development. Several specific virulence factors are implicated in the mechanism of H. pylori infection like the bacterial motility; the secretion of large amounts of urease; specific adhesins for the interaction between H. pylori and the gastric surface epithelium; the traslocation into gastric ephitelial cells of the cytotoxin-associated gene A (CagA), the vacuolating cytotoxin A (VacA) and the heat shock protein HspB. Adherence of H. pylori to the gastric epithelium and secretion of interleukins are believed to be an important step in the induction of active inflammation of the mucosal layer. Several studies have demonstrated that H. pylori infection induces gastric epithelial cell proliferation activating ERK and MAPK pathways and increase of mitosis and mutations. Therefore, H. pylori infection seems to increase apoptosis, implying increased gastric epithelial cell turnover. Recently, it has been shown that H. pylori-induced apoptosis in gastric epithelial cells is mediated via the CD95-receptor/ ligand system but that TRAIL also plays an important role in this regulation.

Goals: Therapy for active ulcerative colitis (UC) usually involves rectal formulations of corticosteroids (CS), which are characterized by the risk of systemic steroid-related adverse effects., Background: To compare the efficacy and safety of the topically acting CS beclomethasone dipropionate (BDP) versus mesalamine (5-ASA) in the treatment of active UC., Study: Patients with mild to moderate distal active UC were randomized to a 6-week treatment with BDP 3 mg enema o.d. or 5-ASA 1 g enema daily in a single-blind, multicenter, parallel-group, controlled study. The primary efficacy variable was the decrease in Disease Activity Index (DAI) score. Safety variables were adrenal function, monitoring of adverse events, vital signs, and laboratory parameters., Results: A total of 217 patients were enrolled and treated with BDP (n = 111) or 5-ASA (n = 106). A significant decrease in the DAI score (P < 0.05) was observed in both treatment groups, with a clinical remission rate of 36.7% in the BDP group and of 29.2% in the 5-ASA group. Both treatments were well tolerated. No changes from baseline in morning cortisol levels were observed in the BDP group., Conclusions: BDP administered as a rectal enema over a 6-week treatment period was efficacious and safe in patients with active UC, without interference with pituitary adrenal axis.

The bacterium Helicobacter pylori is linked to the appearance of several gastric diseases and in particular is associated with a progression to gastric cancer. Thistrun -1 bacterium colonizes the gastric mucosa directly interacting with epithelial cells. It is well known that H. pylori is associated with alterations in the gastric epithelial cell cycle, and apoptosis, higher levels of mononuclear and neutrophilic infiltrates, more severe atrophy and intestinal metaplasia. In last years, two mechanisms that interact with each other or not have been proposed: the hyperproliferation of gastric cells and oxidative damage of stomach mucosa. In particular, cell cycle alterations induce mitogenic signals and proto-oncogene expression that may trigger the development of cancer. Contemporary, H. pylori is able to induce polymorphonuclear and mononuclear cells that produce oxygen free radicals that could cause DNA damage to the adjacent cells leading to cancer development. Due to dangerous infection of this bacterium, the scientific community must point out its attention on the development of detection and prevention strategies.

Helicobacter pylori lives in the stomach lumen adhering and specifically interacting with gastric epithelial cells. H. pylori infection can cause a broad range of diseases. Although most infected individuals only develop a chronic inflammation of the stomach, some patients progress to chronic gastritis, duodenal ulceration, or, rarely, cancer. H. pylori is able to send and to receive signals from the gastric epithelium, allowing host and bacteria to become linked in a dynamic equilibrium. Several studies have demonstrated that H. pylori infection induces morphological changes of gastric epithelial cells other than cell proliferation, increase of mitosis and mutations. It has also been demonstrated that H. pylori may predispose to cancer by altering gastric epithelial cell turnover acting specifically on transcription factors. Although H. pylori is able to induce several host responses, it specifically perturbs the delicate balance of those factors that usually help to maintain cell homeostasis. The study of mechanisms of interaction between the bacterium and gastric cells will surely help to prevent the increase and diffusion of malignancies all over the world., (Copyright 2004 Wiley-Liss, Inc.)

Adenocarcinoma of the stomach is the second most common cause of cancer mortality in the world. The purpose of this study was to evaluate the potential role in carcinogenesis of two secreted Helicobacter pylori's proteins, CagA and HspB, both shown to increase the risk of gastric carcinoma in patients infected with H. pylori-positive strain. The effects of these two proteins on cell kinetics and the ability to selectively affect the expression of cell cycle-related proteins by transfection of a human gastric epithelial cell line (AGS) were analyzed. Using a genomic library of H. pylori, we isolated and cloned CagA and HspB. The effects of the overexpression of these proteins on cell growth were analyzed in AGS cells by immunoblots, proliferation assay, and flow cytometry. Coexpression of CagA and HspB in AGS cells in the first 48 h caused an increase of the level of E2F transcription factor, cyclin D3, and phosphorylated retinoblastoma protein, all involved in the G(1)-S checkpoint of the cell cycle. Consistently, an increase of cell proliferation, corresponding to an augment of the fraction of the cells in the S-G(2)-M phase of the cell cycle, was also demonstrated. Moreover, an increase of c-jun protein levels, but not of c-fos, was also found after coexpression of CagA and HspB. All these data suggest that CagA and HspB, independently from the bacterial infection, have a direct effect on the cell growth of the gastric cells acting on the G(1)-S checkpoint of the cell cycle.

Objective: Barrett's esophagus (BE) is a premalignant condition for which regular endoscopic follow-up is usually advised. We evaluated the incidence of esophageal adenocarcinoma (AC) in patients with BE and the impact of endoscopic surveillance on mortality from AC., Methods: A cohort of newly diagnosed BE patients was studied prospectively. Endoscopic and histological surveillance was recommended every 2 yr. Follow-up status was determined from hospital and registry office records and telephone calls to the patients., Results: From 1987 to 1997, BE was diagnosed in 177 patients. We excluded three with high-grade dysplasia (HGD) at the time of enrollment. Follow-up was complete in 166 patients (135 male, 31 female). The mean length of endoscopic follow-up was 5.5 yr (range 0.5-13.3). Low-grade dysplasia (LGD) was present initially in 16 patients (9.6%) and found during follow-up in another 24 patients. However, in 75% of cases, LGD was not confirmed on later biopsies. HGD was found during surveillance in three patients (1.8%), one with simultaneous AC; two with HGD developed AC later. AC was detected in five male patients during surveillance. The incidence of AC was 1/220 (5/1100) patient-years of total follow-up, or 1/183.6 (5/918) patient-years in subjects undergoing endoscopy. Four AC patients died, and one was alive with advanced-stage tumor. The mean number of endoscopies performed for surveillance, rather than for symptoms, was 2.4 (range 1-10) per patient. During the follow-up years the cohort had a total of 528 examinations and more than 4000 biopsies., Conclusions: The incidence of AC in BE is low, confirming recent data from the literature reporting an overestimation of cancer risk in these patients. In our patient cohort, surveillance involved a large expenditure of effort but did not prevent any cancer deaths. The benefit of surveillance remains uncertain.

Gastric microcirculatory disturbances are involved in the ethanol-induced gastric mucosal damage. In this study in humans we evaluated the time course of plasma and gastric mucosal endothelin-1 (ET-1) concentrations after intragastric ethanol administration; furthermore we determined the correlation among changes in gastric tissue endothelin-1 and microscopic and gross gastric hemorrhagic damage. ET-1 concentrations in plasma and gastric mucosa were measured by radioimmunoassay. The endoscopic appearance of the gastric mucosa was evaluated and scored on a scale of 0-5, and gastric biopsies for histological evaluation were obtained from the antral and the corpus mucosa just before and 30 min after 40% ethanol administration in seven healthy volunteers. Plasma ET-1 concentration increased as soon as 20 min after ethanol administration, reached a significant peak at 30 min (P < 0.01), and returned to near basal level within 120 min. Gastric mucosal ET-1 concentration significantly increased 30 min after ethanol administration in both the body (P < 0.05) and the antrum (P < 0.05) of the stomach; however the ET-1 increase was significantly higher in the body. Moreover, data obtained 30 min after ethanol administration showed a significant correlation between gastric mucosal ET-1 levels and gross hemorrhagic damage (r = 0.84). A significant correlation was also observed between antral gastric mucosal ET-1 and microscopic lesions (r = 0.70). We conclude that 40% ethanol, given orally, stimulates the release of gastric mucosal endothelin-1 and causes a rapid and time-dependent increase of ET-1 plasma level in humans. The increased plasma and gastric tissue endothelin-1 concentration may play a role in ethanol-induced gastric hemorrhagic injury in humans.

Objectives: The objectives were to assess the beneficial and harmful effects of anabolic-androgenic steroids for alcoholic liver disease., Methods: The Cochrane Hepato-Biliary Group Controlled Trials Register, The Cochrane Library, MEDLINE, EMBASE, and full text searches were combined. Only randomized clinical trials studying patients with alcoholic liver disease were included. Interventions encompassed anabolic-androgenic steroids at any dose or duration versus placebos or no intervention. The statistical package (RevMan and MetaView) provided by The Cochrane Collaboration was used., Results: Five randomized clinical trials (including mainly men with alcoholic hepatitis and/or cirrhosis) were identified. Only one trial was assessed as adequate regarding all methodological quality components. Anabolic-androgenic steroids versus placebos or no intervention demonstrated no significant effects on mortality (relative risk [RR] = 0.96, 95% CI = 0.72-1.28), liver-related mortality (RR = 0.83, 95% CI = 0.60-1.15), complications to the liver disease (RR = 1.25, 95% CI = 0.74-2.10), liver histology, and a number of other outcome measures. Anabolic-androgenic steroids were not associated with a significantly increased risk of nonserious adverse events, but with the seldom occurrence of serious adverse events (RR = 4.54,95% CI = 0.57-36.30)., Conclusions: This systematic review could not demonstrate any significant beneficial effects of anabolic-androgenic steroids on any clinically important outcomes of patients with alcoholic liver disease.

Aims: To evaluate long-term efficacy of intrasphincteric injection of botulinum toxin in untreated achalasia patients; to analyse whether age can be a predictor of response; and to verify whether any objective measurements correlate with symptom relief, Materials and Methods: A total of 37 patients (mean age 61.4+/-17.5 years) were enrolled, all of whom injected endoscopically with 100 U of botulinum toxin. Symptom score, oesophageal manometry and oesophageal radionuclide emptying were assessed prior to treatment and 4 weeks, 3 months and 1 year after botulinum toxin. In the case of failure or relapse (symptom score >2), treatment was repeated., Results: All but 6 patients (83.7%) were in clinical remission one month after botulinum toxin. At 12 months, mean symptom score was 0.9+/-0.5 (p<0.05 vs basal); mean lower oesophageal sphincter pressure was 22.0+/-6.3 (p<0.05 vs basal), and 10-min radionuclide retention was 14.0%+/-7.2 (p<0.05 vs basal). Of the 35 patients followed, 12 (34.3%) had a relapse and were re-treated; 4 out of 12 did not respond after re-treatment. Efficacy of first injection of botulinum toxin lasted for a mean period of 15.6 months (range 2-30). Up to day 31 (83.7%) patients were still in remission. We observed a trend towards a better response to botulinum toxin treatment in patients over 50 years (p=0.053). Moreover no correlation was found between any objective achalasia measurements and symptom relief (r coefficient between 0.1 and 0.5), Conclusions: Results show that: 1) one or two intrasphincteric injections of botulinum toxin result in clinical and objective improvement in about 84% of achalasia patients and are not associated with serious side-effects; 2) patients over 50 years showed better benefit than younger patients; 3) no correlation was found between any objective measurements and symptom relief.

Barrett's esophagus (BE) is an acquired disorder due to chronic gastroesophageal reflux. Environmental factors seem to play an important role in the pathogenesis of BE, especially in Western society. A multicenter case-control study was carried out between February 1995 and April 1999 in 8 Italian Departments of Gastroenterology gathered in a study group (GOSPE), in order to analyze the influence of some individual characteristics and life-style habits on the occurrence of BE. Three groups of patients were studied: 149 patients with BE, 143 patients with esophagitis (E) and 308 hospital controls (C) with acute, non-neoplastic, non-gastroenterological conditions. The diagnosis of BE was based on endoscopy and histology. E was defined by the Savary classification (grade I-III). Data collection was performed by using a questionnaire that focused on smoking, coffee and alcohol consumption, medical history, drugs history, gastroesophageal reflux disease (GERD) symptoms (heartburn, regurgitation) and socio-economic status. Multivariate analysis showed that the frequency of weekly GERD symptoms was significantly associated with both BE and E (p<0.0001), such as the presence of hiatal hernia (p< or =0.001). Ulcer was significantly associated with BE (p=0.001). Among patients with E, the risk was directly related to spirits consumption (p=0.03). Patients with GERD symptoms that lasted more than 13 years were more likely to have BE than E (p=0.01). In conclusion, results from our study point out that long-standing GERD symptoms, hiatal hernia and possibly alcohol consumption are risk factors in the development of the BE and E., (Copyright 2002 Wiley-Liss, Inc.)

Background: Some conditions characterized by a loss (anatomical or functional) of parietal cells of the gastric antrum, containing an alcohol-dehydrogenase, may reduce the first pass metabolism of ethanol at that level and, simultaneously, raise its bioavailability. The observation that the first pass metabolism was drastically suppressed after gastrectomy would appear to suggest that the latter condition represents a risk for the development of liver damage in patients who continue to consume alcohol even in a non relevant amount., Methods: Consecutively enrolled in the study were 304 individuals of both sexes aged between 45 and 70 years of whom 114 gastrectomized and 190 pair-matched control subjects all submitted to an Upper Gastrointestinal Endoscopy for whatever disturbance. All the patients were diagnosed as having liver disease with routine clinical and instrumental means. Information was collected concerning the mean daily alcohol intake, both before and after the operation., Results: The overall prevalence of hepatic lesions was shown to be higher in the gastrectomized than in the control group (42.1% vs 25.8%, p = 0.005). Moreover, referring only to alcohol-related hepatic lesions (steatosis, steato-fibrosis and cirrhosis), the prevalence was higher in the gastrectomized patients than in the controls (29.8% vs 17.9%, p = 0.02). As far as concerns alcohol consumption, the gastrectomized group had consumed 71 g/day and the control group 39 g/day alcohol per person (p < 0.05) in a similar period of time (35 and 33 years, respectively). Also the non alcohol-related liver damage (especially the viral type) was slightly higher in the gastrectomized patients (gastrectomized 12.3% vs control 7.9%, p = ns). Accordingly, the percentage of serum markers of viral infection was higher in this group (HBs Ag: gastrectomized 3.9% vs control 2.2%, p = ns; anti-HCV: gastrectomized 13.5% vs control 5.0%, p = 0.03). Finally, to test the eventual damaging effects of gastrectomy alone (excluding ethanol and/or viral infection), two groups of patients with a medium to low alcoholic negative assumption (30-60 g ethanol/day) and no signs of viral infection (HBsAg and anti-HCV negative) were extrapolated. In these two selected groups, the prevalence of alcoholic-related hepatic lesions were not statistically different (28 gastrectomized 20.3% vs 44 control 18.4%)., Conclusions: In conclusion, data emerging from investigations on the population under study indicate that the alcohol and viral infection appear to play a more important role in determining hepatic lesions than gastroresection.

Although the pathogenic role of gastroesophageal reflux in Barrett's esophagus is widely accepted, the pattern of gastric and esophageal pH profile of patients with Barrett's esophagus is not well documented. Moreover, the observation that a columnar-lined esophagus can also develop after gastrectomy implies that chronic irritation of the lower esophagus by duodenal juice can be as harmful as acid reflux. To test this hypothesis, we simultaneously monitored gastric and esophageal pH in 19 patients with endoscopically and histologically proven Barrett's esophagus, in 35 with slight-to-moderate esophagitis and in 10 healthy subjects. The gastroesophageal reflux pattern in both Barrett's esophagus and esophagitis was characterized by mainly acid refluxes. Esophageal acid exposure (% time pH < 4) was 39.4 in patients with Barrett's esophagus, 14.6 in patients with esophagitis (P < 0.05), and 3.1 in healthy subjects (P < 0.05). Seven of 19 patients with Barrett's esophagus and 7 of 35 with esophagitis had evidence of alkaline reflux too; but pure alkaline refluxes accounted for only 1.9% of total time in Barrett's esophagus and 0.3% in esophagitis patients. In conclusion, these results confirm the high prevalence and severity of acid reflux in patients with Barrett's esophagus and show that the reflux of pure alkaline material into the esophagus is a rare event in both Barrett's esophagus and esophagitis patients.

Liver affects the release and clearance of many hormones, but the interactions between gastrointestinal peptides and liver function are obscure. Aim of this study was to evaluate plasma concentrations of gastrointestinal peptides during acute hepatic cytonecrosis and during liver regeneration in man. The study was performed in ten patients with viral hepatitis (8 virus A, 2 virus B) in the acute phase (alanine transaminase = 3073 +/- 739 U/L; mean +/- SEM), and at days 7, 45 and 52 after the initial evaluation, during clinical and biochemical recovery (52nd day, alanine transaminase = 77 +/- 26). Plasma concentrations of the following hormones were evaluated by radioimmunoassay: glucagon, insulin, gastrin, vasoactive intestinal peptide, bombesin, neurotensin, cholecystokinin, secretin and motilin. Only serum bombesin and cholecystokinin were significantly (p < 0.01) increased in the acute phase of hepatitis (bombesin: 138 +/- 21 pg/ml; cholecystokinin: 57 +/- 7 pg/ml); they returned to normal values during convalescence (bombesin: 60 +/- 8; cholecystokinin: 31 +/- 4). During hepatocellular necrosis, plasma concentrations of cholecystokinin and bombesin, which are both cellular growth factors and regulatory signals of food introduction and satiety state, were increased by 83% and 130%, respectively. Increase of these hormones may cause the dyspepsia and lack of appetite that characterizes the initial phase of acute viral hepatitis.

We report a case of pleuropericarditis in a 23-yr-old woman with ulcerative colitis (UC) treated with 5-aminosalicylic acid (5-ASA). In our case we exclude a possible 5-ASA hypersensitivity in view of the longterm complication free treatment and the successful resolution of the case without withdrawal of 5-ASA. A 5-ASA induced lupus-like syndrome was also ruled out by immunoserological investigations. Infectious and endocrinologic causes of pleuropericarditis were also excluded. In conclusion pleuropericarditis must be considered a systemic complication of inflammatory bowel disease (IBD) if adverse reaction to 5-ASA and sulfasalazine as well as other possible pathogenetic factors have been ruled out.

In a long-term study (27 months) of patients affected by C-virus active hepatitis we have evaluated the effect of decreasing the dose of interferon by 50% and by 75% with respect to the initial efficacious dose (6 MU tiw). Sixty patients received recombinant interferon alpha-2b(r-IFN- alpha-2b) 6 MU tiw for two months followed by 3 MU for seven months (Group A), and 60 patients received r-IFN alpha-2b 6 MU tiw for two months followed by 1.5 MU for seven months (Group B). Three patients in group B failed to return to follow-up and were not considered in subsequent evaluations. Side effects such as to cause suspension of treatment occurred only during the first two months of the study at 6 MU of interferon (3 patients in group A and 6 in group B). During the two months at 6 MU, transaminase values returned to normal in 94 patients (80%). At the end of follow-up, 49 of these patients (42% of the 117 patients examined; or 48.3% in group A and 35.1% in group B) had normal transaminase levels. In no case did the anti-HCV test become negative. On a reduced dose of interferon, relapses occurred more frequently in group B (21.4%) than in group A (9.6%), but the difference was not significant. No difference between responders and non-responders, including relapsing patients, was observed in relation to gender, age, presence of cirrhosis, presence of B-virus antibodies and initial levels of serum transaminase.

We describe the case of a 42 year old woman with abdominal pain, ascites, and splenomegaly after having taken dihydroergotamine continuously for three months due to frequent hemicranic episodes. The celiac-mesenteric angiography demonstrated diffuse thrombosis of splenic, superior mesenteric and portal veins. No surgical intervention was possible. We believe that it is possible that dihydroerogotamine, a hydrogenated derivative of ergotamine, inasmuch as it is capable of causing peripheral vasoconstriction, intimal lesions, arterial and venous thrombi, was also the cause of our patient's portal thrombosis. We therefore suggest the minimum effective amount of the drug be utilized to achieve the relief of cephalalgia.

The management of gastro-oesophageal reflux still presents a considerable problem mostly because of its multifactorial pathogenesis. In this study, we tested the response to treatment with famotidine for 8 weeks in patients with reflux oesophagitis, taking into consideration, however, only cases with pathological gastro-oesophageal reflux of the acidic type. All the patients participating in the multicentre study underwent gastro-oesophageal 24-hr pH-metry. The results show a good response to the H2 antagonist treatment with regards to both symptomatology (improvement/healing in 98% of cases, asymptomatic in 68%) and the endoscopic and histological picture. In fact, endoscopy showed complete remission of the lesions in 60% of cases and an improvement in 21%. The histological picture of oesophagitis improved in 64% of cases, 36% of which were completely healed, with no modifications in the remaining 36%. These data, which are globally better than those reported in the literature, can probably be attributed to the original selection of patients treated by means of prolonged gastro-oesophageal pH-metry, who had exclusively pathological gastro-oesophageal reflux of the acidic type. For these patients the use of the H2 antagonist drug is more appropriate even as monotherapy, than it is for those patients who have combined or isolated alkaline gastrooesophageal reflux.

A new method to evaluate lymphocyte response to mitogens is proposed. The method is based on the observation in fluorescence of the stimulated cells after their supravital staining on slides prestained with acridine orange in alcoholic solution. The results are expressed as Blast Index (IB). The method is very practical, easy to reproduce and shows a good correlation with 3H-thymidine uptake.