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Background and Aims: Decompensated‐cirrhosis encompasses several stages with different prognosis, such as bleeding, ascites and bleeding‐plus‐ascites. Development of further‐decompensation worsens survival, while non‐selective β‐blockers (NSBBs) can modify the risk. However, how this applies to each stage is uncertain. We aimed to investigate, in each stage of decompensated‐cirrhosis, the influence of further‐decompensation on mortality and whether changes in portal‐pressure (HVPG) under NSBBs influence these outcomes. Methods: Patients with variceal bleeding were consecutively included differentiating those with bleeding‐alone from those who also had ascites. Patients with ascites and high‐risk varices referred for primary‐prophylaxis were also investigated. A baseline haemodynamic study was performed and was repeated after 1‐3‐months under NSBBs. Outcomes were investigated by competing‐risk. Results: Totally 103 patients had bleeding‐alone, 186 bleeding‐plus‐ascites and 187 ascites‐alone. Mean follow‐up was 32‐months (IQR, 12–60). Patients with bleeding‐plus‐ascites had higher HVPG and were more hyperdynamic than patients with ascites‐alone and these than those with bleeding‐alone. At each stage, the mortality risk was more than twice in patients developing further‐decompensation vs. those without (p <.001). In each stage, HVPG‐decrease under NSBBs showed better discrimination to predict further‐decompensation than the baseline MELD, Child–Pugh or HVPG, by time‐dependent ROC‐curves (c‐statistic >70%). At each stage, patients without HVPG‐decreases, either ≥10% or ≥20% from the baseline, had higher risk of further‐decompensation (sHR from 2.43 to 6.73, p <.01) and worse survival. Conclusions: In each stage of decompensated cirrhosis, mortality risk significantly and very markedly increase with further‐decompensation. HVPG‐non‐response to NSBBs may adequately stratify the risk of further decompensation and death, in each stage. This suggests potential benefit with pre‐emptive therapies in HVPG‐non‐responders at each‐stage. [ABSTRACT FROM AUTHOR]

Homeostasis constitutes a key concept in physiology and refers to self‐regulating processes that maintain internal stability when adjusting to changing external conditions. It diminishes internal entropy constituting a driving force behind evolution. Natural selection might act on homeostatic regulatory mechanisms and control mechanisms including homeodynamics, allostasis, hormesis and homeorhesis, where different stable stationary states are reached. Regeneration is under homeostatic control through hormesis. Damage to tissues initiates a response to restore the impaired equilibrium caused by mild stress using cell proliferation, cell differentiation and cell death to recover structure and function. Repair is a homeorhetic change leading to a new stable stationary state with decreased functionality and fibrotic scarring without reconstruction of the 3‐D pattern. Mechanisms determining entrance of the tissue or organ to regeneration or repair include the balance between innate and adaptive immune cells in relation to cell plasticity and stromal stem cell responses, and redox balance. The regenerative and reparative capacities vary in different species, distinct tissues and organs, and at different stages of development including ageing. Many cell signals and pathways play crucial roles determining regeneration or repair by regulating protein synthesis, cellular growth, inflammation, proliferation, autophagy, lysosomal function, metabolism and metalloproteinase cell signalling. Attempts to favour the entrance of damaged tissues to regeneration in those with low proliferative rates have been made; however, there are evolutionary constraint mechanisms leading to poor proliferation of stem cells in unfavourable environments or tumour development. More research is required to better understand the regulatory processes of these mechanisms. [ABSTRACT FROM AUTHOR]

Background and Aim: This study aimed to determine safety and risk factors for adverse events (AEs) of endoscopic ultrasound‐guided gallbladder drainage (EUS‐GBD) with long‐term indwell of lumen‐apposing metal stents (LAMS). Methods: This study is a multicenter prospective observational study on consecutive high surgical‐risk patients requiring gallbladder drainage who underwent EUS‐GBD with LAMS over 12 months. Centralized telephone follow‐up interviews were conducted every 3 months for 1 year. Patients were censored at LAMS removal, cholecystectomy, or death. AE‐free survival was determined using log–rank tests. Cumulative risks were estimated using life‐table analysis. Results: Eighty‐two patients were included (53.7% male, median [interquartile range] age of 84.6 [76.5–89.8] years, and 85.4% with acute cholecystitis). Technical success was achieved in 79 (96.3%), and clinical success in 73 (89%). No patient was lost to follow‐up; 45 patients (54.9%) completed 1‐year follow‐up with in situ LAMS. Median (interquartile range) LAMS indwell time was 364 (47–367) days. Overall, 12 (14.6%) patients presented 14 AEs, including 5 (6.1%) recurrent biliary events (3 acute cholangitis, 1 mild acute pancreatitis, and 1 acute cholecystitis). Patients with pancreatobiliary malignancy had an increased risk of recurrent biliary events (33% vs 1.5%, P = 0.001). The overall 1‐year cumulative risk of recurrent biliary events was 9.7% (4.1–21.8%). The 1‐year risk of AEs and of severe AEs was 18.8% (11–31.2%) and 7.9% (3.3–18.2%), respectively. Pancreatobiliary malignancy was the single risk factor for recurrent biliary events; LAMS misdeployment was the strongest risk factor for AEs. Conclusions: Long‐term LAMS indwell does not increase the risk of delayed AEs following EUS‐GBD. [ABSTRACT FROM AUTHOR]

Despite diffusion tensor imaging (DTI) evidence for widespread fractional anisotropy (FA) reductions in the brain white matter of patients with bipolar disorder, questions remain regarding the specificity and sensitivity of FA abnormalities as opposed to other diffusion metrics in the disorder. We conducted a whole‐brain voxel‐based multicompartment diffusion MRI study on 316 participants (i.e., 158 patients and 158 matched healthy controls) employing four diffusion metrics: the mean diffusivity (MD) and FA estimated from DTI, and the intra‐axonal signal fraction (IASF) and microscopic axonal parallel diffusivity (Dpar) derived from the spherical mean technique. Our findings provide novel evidence about widespread abnormalities in other diffusion metrics in BD. An extensive overlap between the FA and IASF results suggests that the lower FA in patients may be caused by a reduced intra‐axonal volume fraction or a higher macromolecular content in the intra‐axonal water. We also found a diffuse alteration in MD involving white and grey matter tissue and more localised changes in Dpar. A Machine Learning analysis revealed that FA, followed by IASF, were the most helpful metric for the automatic diagnosis of BD patients, reaching an accuracy of 72%. Number of mood episodes, age of onset/duration of illness, psychotic symptoms, and current treatment with lithium, antipsychotics, antidepressants, and antiepileptics were all significantly associated with microstructure abnormalities. Lithium treatment was associated with less microstructure abnormality. [ABSTRACT FROM AUTHOR]

Background: Recent data suggests an association between blood hyperviscosity and both propensity for thrombosis and disease severity in patients with COVID‐19. This raises the possibility that increased viscosity may contribute to endothelial damage and multiorgan failure in COVID‐19, and that therapeutic plasma exchange (TPE) to decrease viscosity may improve patient outcomes. Here we sought to share our experience using TPE in the first 6 patients treated for COVID‐19‐associated hyperviscosity. Study Design and Methods: Six critically ill COVID‐19 patients with plasma viscosity levels ranging from 2.6 to 4.2 centipoise (cP; normal range, 1.4‐1.8 cP) underwent daily TPE for 2‐3 treatments. Results: TPE decreased plasma viscosity in all six patients (Pre‐TPE median 3.75 cP, range 2.6‐4.2 cP; Post‐TPE median 1.6 cP, range 1.5‐1.9 cP). TPE also decreased fibrinogen levels in all five patients for whom results were available (Pre‐TPE median 739 mg/dL, range 601‐1188 mg/dL; Post‐TPE median 359 mg/dL, range 235‐461 mg/dL); D‐dimer levels in all six patients (Pre‐TPE median 5921 ng/mL, range 1134‐60 000 ng/mL; Post‐TPE median 4893 ng/mL, range 620‐7518 ng/mL); and CRP levels in five of six patients (Pre‐TPE median 292 mg/L, range 136‐329 mg/L; Post‐TPE median 84 mg/L, range 31‐211 mg/L). While the two sickest patients died, significant improvement in clinical status was observed in four of six patients shortly after TPE. Conclusions: This series demonstrates the utility of TPE to rapidly correct increased blood viscosity in patients with COVID‐19‐associated hyperviscosity. Large randomized trials are needed to determine whether TPE may improve clinical outcomes for patients with COVID‐19. [ABSTRACT FROM AUTHOR]

Adenovirus infection is commonly associated with self‐limited respiratory and gastrointestinal illnesses. However, infection in immunocompromised individuals, such as transplant recipients, can cause severe life‐threatening illness including pneumonitis, hemorrhagic cystitis, nephritis, hepatitis, and enterocolitis. In orthotopic liver transplant recipients, adenovirus viremia can cause hepatitis leading to marked transaminitis, allograft loss, and death. Although hepatic abscesses mediated by adenovirus have been described in other immunosuppressed patient populations, it has very rarely been described in liver transplant recipients. Here, we report two adult cases of hepatic abscesses following liver transplantation secondary to adenovirus infection and describe the successful treatment of these patients. Adenovirus should be considered as an uncommon etiology of hepatic abscess and unexplained fevers in adults following liver transplantation. [ABSTRACT FROM AUTHOR]

Background and Aim: Frailty is increasingly recognized as a major prognostic factor in cirrhosis in addition to conventional liver insufficiency scores. The aim was to compare the prevalence and characteristics of frailty between patients with cirrhosis and controls, and to analyse its prognostic value. Methods: We included outpatients with cirrhosis and age‐ and gender‐matched non‐cirrhotic controls. Frailty was defined according to the Fried frailty criteria. In patients with cirrhosis, we analysed the ability of the degree of frailty to predict a composite endpoint, consisting of hospitalization, admission to a long‐term care centre, falls or death. Results: We included 135 patients with cirrhosis and 135 controls. The prevalence of frailty was higher among patients with cirrhosis: 35 (25.9%) frail, 74 (54.8%) pre‐frail and 26 (19.2%) robust vs 14 (10.4%) frail, 67 (49.6%) pre‐frail and 54 (40%) robust (P <.001) in controls. This difference was mainly as a result of decreased muscle strength in patients with cirrhosis. During follow‐up, frail patients with cirrhosis showed a higher probability of composite endpoint, hospitalization and falls than pre‐frail and robust cirrhotic patients but mortality was similar. MELD‐Na score and frailty were independent predictive factors for hospitalization, frailty for falls, and MELD‐Na score and albumin for survival. Vitamin D deficiency and increased cystatin C were associated with frailty. Conclusions: Frailty was more frequent in outpatients with cirrhosis than in controls, mainly because of a decrease in muscle strength, and it could be a predictive factor for hospitalization and falls in these patients. [ABSTRACT FROM AUTHOR]

Background: The Joint Commission lists improving staff communication (handoffs) as part of several National Safety Goals. In this study, we developed an electronic web‐based charting system for clinical pathology handoffs, which primarily consist of transfusion medicine calls, and evaluated the advantages over a paper‐based handwritten call log. Materials and Methods: A secure online web browser application using Research Electronic Data Capture (REDCap) was designed to document on‐call pathology resident consults. A year after implementation, an online survey was administered to our pathology residents in order to evaluate and compare the usability of the electronic application (e‐consults) to the previous handwritten call log, which was a notebook where trainees hand wrote different components of the consult. Results: The REDCap web‐based application includes discrete fields for patients' information, requesting physician contact, type of consult, action items for follow‐up and faculty responses, as well as other information. These components have eventually progressed to be an online consult call catalog. With approximately 1079 consults per year, transfusion medicine‐related calls account for ~90% of the encounters, while clinical chemistry, microbiology and immunology calls constitute the remainder. The overall response rate of the survey was 96% (29 of 30 participants). Of the 16 respondents who experienced both call log systems, 100% responded that REDCap was an improvement over the handwritten call log (P < 0·0001). Conclusion: E‐consult documentation entered into a web‐based application was a user‐friendly, secure clinical information access and effective handoff system as compared to a paper‐based handwritten call log. [ABSTRACT FROM AUTHOR]

Background: Ventricular tachycardia (VT) is one of the main predictors of mortality in Chagas cardiomyopathy (CC). Although the substrate of sustained and nonsustained‐VT (NS‐VT) seems to be the same, little is known about the distribution of late enhancement (LE). Our aim was to compare the clinical findings and the amount and patterns of LE in Chagas disease according to the presence and type of VT. Methods and Results: Magnetic resonance imaging was performed in 54 Chagas seropositive patients: 8 indeterminate and 46 with CC of whom 15 were without VT, 13 with NS‐VT, and 18 with sustained‐VT (S‐VT). There were 31 males (57%), mean age was 55.9 ± 12.2 years. LE was found in 87% of all patients and in 50%, 80%, and 100% of the indeterminate, without VT and VT groups, respectively. The percentage of LE increased progressively in the indeterminate, CC without VT, and CC with VT groups; without a significant difference between NS‐VT and S‐VT (0.93%, 15.2%, 23.2%, and 21.4%, respectively). The amount of LE increased with the functional class. LE in the basal and mid lateral wall was more frequent in VT, without difference between S‐VT and NS‐VT. The only predictor of VT was the percentage of LE, odds ratio (OR), 6.2; (95% confidence interval [CI], 3.7‐28.4; P = .01) with a cutoff of Odds Ratio 17.1%. Conclusions: The amount of LE increases in relation to the clinical stage of the disease and its functional class in Chagas seropositive patients. The amount of LE was the main predictor of VT, without difference between S‐VT and NS‐VT. [ABSTRACT FROM AUTHOR]

Background and Aim: Chronic Helicobacter pylori infection causes gastric mucosal inflammation as an important antecedent of gastric cancer. We aimed to evaluate associations of blood markers of inflammation with gastric intestinal metaplasia and dysplasia in H. pylori‐infected individuals. Methods: We compared pre‐treatment serum levels of immune‐related and inflammation‐related markers between 99 individuals with intestinal metaplasia or dysplasia and 75 control individuals with non‐atrophic gastritis within an H. pylori eradication trial in Mexico. Serum levels of 28 markers measured with Luminex bead‐based assays were categorized in tertiles as low (T1), middle (T2), and high (T3). Logistic regression models were used to calculate age‐adjusted and sex‐adjusted odds ratios and 95% confidence intervals. All statistical tests were two‐sided, and significance values were adjusted for multiple comparisons using false discovery rate methods. Results: Five markers were nominally associated (Ptrend < 0.05) with the presence of advanced premalignant gastric lesions. Adjusted odds ratios (95% confidence interval) of T2 and T3 versus T1 were 4.09 (1.65–10.17) and 3.08 (1.23–7.68) for CCL3/MIP1A, 3.21 (1.33–7.75) and 2.69 (1.10–6.57) for CCL20/MIP3A levels, 1.79 (0.77–4.18) and 2.39 (1.02–5.60) for IL‐1β, 1.34 (0.56–3.19) and 3.02 (1.29–7.12) for IL‐4, and 1.07 (0.44–2.59) and 3.07 (1.32–7.14) for IL‐5, respectively. Two (IL‐4 and IL‐5) of the five markers had false discovery rate adjusted Ptrend < 0.2. Conclusions: Our results suggest that certain Th2 and other cytokines may have a role in promoting carcinogenesis in the setting of H. pylori infection. Additional research is needed to replicate these findings, extend to pre‐diagnostic samples, and elucidate the underlying mechanisms. [ABSTRACT FROM AUTHOR]

Background: Patients with achalasia develop a well‐defined obstructive pattern of pressure in response to a rapid drink challenge test (RDC). Our aim was to determine if successful treatment of achalasia can revert the obstructive pattern of pressure in response to the RDC, and if this simple test could be useful in the follow‐up of patients with achalasia. Methods: In 26 healthy controls and 103 patients with achalasia, pressure responses to a RDC were prospectively analysed using high resolution esophageal manometry in two consecutive protocols: (a) Development study: one RDC was performed in 20 healthy controls, 63 patients with nontreated achalasia, and 21 patients with previously treated achalasia; (b) Validation study: two RDC were performed before, and 8‐12 weeks after treatment, in 19 patients with nontreated, newly diagnosed achalasia. Key Results: In the development study no healthy control, 19% of patients with previously treated achalasia and 96% of patients with nontreated achalasia developed an obstructive pressure pattern during the RDC (P < 0.001). In the validation study, 100% of patients had an obstructive pressure pattern before treatment, that reverted to a nonobstructive pattern in 89% of patients after treatment (P < 0.001). The obstructive pressure pattern during the RDC correlated with clinical symptoms (Eckardt score > 3; P < 0.001), and with the height of the water column retained after the RDC, as assessed by impedance (P = 0.015). Conclusions & Inferences: The RDC may objectively assess treatment outcome in patients with achalasia, and can be recommended in the evaluation of achalasia. [ABSTRACT FROM AUTHOR]

Abstract: Background & Aims: Norfloxacin administration is useful in preventing bacterial infections in cirrhosis but associated to the generation of resistant species. Rifaximin is known to reach high concentrations in the intestinal lumen without generating relevant resistance in the intestinal flora. Our aim was to compare the effect of Norfloxacin and Rifaximin on intestinal flora composition, bacterial translocation and survival in cirrhotic rats. Methods: Cirrhosis was induced in rats by oral administration of CCl4. Animals were divided into three groups: only CCl4 (group I, n = 10); CCl4 + Norfloxacin (group II, n = 17) and CCl4 + Rifaximin (group III, n = 14). Gut bacterial composition, bacterial translocation and cytokine levels were measured. Results: Forty‐one rats were finally included. The incidence of viable and non‐viable bacterial translocation was significantly reduced in animals receiving Norfloxacin; Rifaximin also decreased the incidence of viable and non‐viable bacterial translocation, but did not reach statistical significance. Serum TNF‐α levels were significantly lower in antibiotic groups. Norfloxacin modified intestinal microbiota, depleting significantly more pathobionts than Rifaximin. Conclusion: Norfloxacin is more effective than Rifaximin in preventing bacterial translocation in rats with cirrhosis probably because of its capacity to reduce pathobionts from intestinal microbiota. [ABSTRACT FROM AUTHOR]

Background We have shown that a galactooligosaccharide prebiotic administration ( HOST-G904) initially increased intestinal gas production and this increase declined back to baseline after 2 week administration. Our aim was to determine the mechanism of microbiota adaptation; i.e., to determine whether the net reduction is due to decreased overall production or increased gas consumption. Methods In 10 healthy subjects, intestinal gas production and intraluminal disposal was measured before, at the beginning and after 2 week of HOST-G904 prebiotic administration. Anal gas was collected for 4 hour after a probe meal. Paired studies were performed without and with high-rate infusion of exogenous gas (24 mL/min) into the jejunum to wash-out the endogenous gas produced by bacterial fermentation. The exogenous gas infused was labeled (5% SF6) to calculate the proportion of endogenous gas evacuated. Key Results The volume of intestinal gas produced i.e., endogenous gas washed-out, increased by 37% at the beginning of HOST-G904 administration ( P=.049 vs preadministration) and decreased down to preadministration level after 2 week administration ( P=.030 vs early administration). The proportion of gas eliminated from the lumen before reaching the anus tended to increase after 2-week administration (87±3% vs 78±5% preadministration; P=.098). Conclusions & Inferences Adaptation to regular consumption of HOST-G904 prebiotic involves a shift in microbiota metabolism toward low-gas producing pathways, with a non-significant increase in gas-consuming activity. Hence, regular consumption of HOST-G904 regulates intestinal gas metabolism: less gas is produced and a somewhat larger proportion of it is consumed. [ABSTRACT FROM AUTHOR]

Background Prebiotics have been shown to reduce abdominal symptoms in patients with functional gut disorders, despite that they are fermented by colonic bacteria and may induce gas-related symptoms. Aim To investigate changes in the metabolic activity of gut microbiota induced by a recognised prebiotic. Methods Healthy subjects ( n = 20) were given a prebiotic (2.8 g/day HOST-G904, HOST Therabiomics, Jersey, Channel Islands) for 3 weeks. During 3-day periods immediately before, at the beginning and at the end of the administration subjects were put on a standard diet (low fibre diet supplemented with one portion of high fibre foods) and the following outcomes were measured: (i) number of daytime gas evacuations for 2 days by means of an event marker; (ii) volume of gas evacuated via a rectal tube during 4 h after a test meal; and (iii) microbiota composition by faecal Illumina MiSeq sequencing. Results At the beginning of administration, HOST-G904 significantly increased the number of daily anal gas evacuations (18 ± 2 vs. 12 ± 1 pre-administration; P < 0.001) and the volume of gas evacuated after the test meal (236 ± 23 mL vs. 160 ± 17 mL pre-administration; P = 0.006). However, after 3 weeks of administration, these effects diminished (11 ± 2 daily evacuations, 169 ± 23 mL gas evacuation). At day 21, relative abundance of butyrate producers (Lachnospiraceae) correlated inversely with the volume of gas evacuated ( r = −0.52; P = 0.02). Conclusion The availability of substrates induces an adaptation of the colonic microbiota activity in bacterial metabolism, which produces less gas and associated issues. Clinical trials.gov NCT02618239. [ABSTRACT FROM AUTHOR]

Background Despite inoculation into blood culture bottles, ascitic fluid culture is negative in 50% of cases of spontaneous bacterial peritonitis (SBP). Aim To determine whether 16S rDNA gene detection by real-time polymerase chain reaction (PCR) and sequencing increases the efficacy of culture in microbiological diagnosis of spontaneous bacterial peritonitis. Methods We prospectively included 55 consecutive spontaneous bacterial peritonitis episodes in cirrhotic patients, 20 cirrhotic patients with sterile ascites and 27 patients with neoplasic ascites. Ascitic fluid was inoculated into blood culture bottles at the bedside and tested for bacterial DNA by real-time PCR and sequencing of 16S rDNA gene. Results Bacterial DNA was detected in 23 / 25 (92%) culture-positive SBP, 16 / 30 (53%) culture-negative SBP (P = 0.002 with respect to culture-positive SBP), 12 / 20 (60%) sterile ascites (P = 0.01 with respect to culture-positive SBP) and 0 / 27 neoplasic ascites (P < 0.001 with respect to other groups). Sequencing identified to genus or species level 12 culture-positive SBP, six culture-negative SBP and six sterile ascites. In the remaining cases with positive PCR, sequencing did not yield a definitive bacterial identification. Conclusions Bacterial DNA was not detected in almost half the culture-negative spontaneous bacterial peritonitis episodes. Methodology used in the present study did not always allow identification of amplified bacterial DNA. [ABSTRACT FROM AUTHOR]

Aliment Pharmacol Ther 31, 1192–1199 Background Toll-like receptor (TLR) 4 genetic polymorphisms, mainly D299G, have been associated with increased predisposition to infection in several populations. Aim To retrospectively analyse the relationship between the presence of the TLR4 D299G polymorphism and the incidence of bacterial infections in cirrhotic patients. Methods We included 111 consecutive cirrhotic patients hospitalized with ascites and we determined the presence of the TLR4 D299G polymorphism by PCR–RFLP (polymerase chain reaction–restriction fragment length polymorphism) and its relationship with the incidence of previous bacterial infections. Results Ten out of 111 (9%) cirrhotic patients presented with the TLR4 D299G polymorphism. The mean follow-up from first decompensation of cirrhosis until current admission was longer in D299G polymorphism patients than in wild-type patients (53.8 ± 40.7 vs. 35.4 ± 48.3 months, P = 0.03). D299G polymorphism patients showed a trend towards a higher incidence of history of previous infections (80% vs. 56.4%, P = 0.19), as well as a higher number of infections (2.8 ± 2.3 vs. 1.0 ± 1.3, P = 0.01) and bacteriaemias (0.4 ± 1.0 vs. 0.04 ± 0.2, P = 0.02) per patient than wild-type patients. Conclusions Toll-like receptor 4 D299G polymorphism could influence not only the predisposition to bacterial infections but also the evolution of the disease in cirrhotic patients. Further prospective studies in larger series of patients are warranted. [ABSTRACT FROM AUTHOR]

Background Hospital mortality in patients with spontaneous bacterial peritonitis ( SBP) is high despite albumin treatment, particularly in those with worse liver and/or renal function. Aim To determine the independent predictive factors of in-hospital mortality and to create and validate a predictive model of mortality in patients with SBP. Methods We analysed all cirrhotic patients with high-risk SBP (serum urea ≥11 mmol/L and/or serum bilirubin ≥68 μmol/L) between 2001 and 2011. We developed a predictive model of in-hospital mortality and validated this in a different cohort. Results We included 118 high-risk SBP episodes treated with antibiotics and albumin. In-hospital mortality was 33/118 (28%). The independent predictive factors of in-hospital mortality at SBP diagnosis were serum urea, blood leucocyte count, Child-Pugh score and mean arterial pressure. A predictive model including these four variables showed a discrimination accuracy ( AUC) of 0.850, 95% CI 0.777-0.922. A cut-off point of 0.245 showed a sensitivity of 0.85 and specificity of 0.75. The in-hospital mortality was 28/49 (57.1%) in patients with a model value ≥0.245, and 5/69 (7.2%) in patients with a model value <0.245 ( P < 0.001). The validation series included 161 patients with an in-hospital mortality of 40/161 (24.8%), 30/77 (39.0%) in patients with a model value ≥0.245, and 10/84 (11.9%) in those with a model value <0.245 ( P < 0.001). Conclusions We developed and validated a predictive model of mortality that includes serum urea, blood leucocyte count, Child-Pugh score and mean arterial pressure in high-risk patients with spontaneous bacterial peritonitis. These findings may help to identify patients who would benefit from additional therapeutic strategies. [ABSTRACT FROM AUTHOR]

The intracellular N-terminal domain of the nucleoside and drug transporter human concentrative nucleoside transporter (hCNT)3 was used as bait in a glutathione S-transferase pull-down approach, to identify hCNT3 protein partners, using human colon homogenates as a prey source. Galectin (Gal)-4 was identified as a potential hCNT3 partner in the colon. The biochemical validation of the Gal-4-hCNT3 interaction was verified by targeted pull-down assays and coimmunoprecipitation experiments in HT-29 cells, which endogenously express hCNT3 and Gal-4. Furthermore, Gal-4 was shown to colocalize with hCNT3 in HT-29 cells. The biologic significance of this interaction was obtained from experiments in which Gal-4 was knocked down, showing that this protein is a regulator of hCNT3 trafficking and retention at the cell membrane, reducing its plasma membrane location by 70%. Conversely, the addition of Gal-4 increased hCNT3 location at the plasma membrane by 77%, thereby demonstrating that this lectin modulates hCNT3 function in colonic cells. The integrity of this partnership may be clinically relevant, because hCNT3 may be responsible for the translocation of thiopurines, such as 6-mercaptopurine, a front-line treatment in inflammatory bowel disease. The expression of Gal-4 and hCNT3 proteins is not impaired in inflamed colon from patients with Crohn's disease, thereby anticipating the integrity of this system for drug targeting. [ABSTRACT FROM AUTHOR]

Background As mean transit time in the colon is longer than the interval between meals, several consecutive meal loads accumulate, and contribute to colonic biomass. Our aim was to determine the summation effect of fermentable food residues on intestinal gas production. Methods In eight healthy subjects, the volume of endogenous intestinal gas produced in the intestine over a 4-h period was measured by means of a wash-out technique, using an exogenous gas infusion into the jejunum (24 mL/min) and collection of the effluent via a rectal Foley catheter. The exogenous gas infused was labeled (5% SF6) to calculate the proportion of endogenous intestinal gas evacuated. In each subject, four experiments were performed ≥1 week apart combining a 1-day high- or low-flatulogenic diet with a test meal or fast. Key Results Basal conditions: on the low-flatulogenic diet, intestinal gas production during fasting over the 4-h study period was 609 ± 63 mL. Effect of diet: during fasting, intestinal gas production on the high-flatulogenic diet was 370 ± 146 mL greater than on the low-flatulogenic diet ( p = 0.040). Effect of test meal: on the low-flatulogenic diet, intestinal gas production after the test meal was 681 ± 114 mL greater than during fasting ( p = 0.001); a similar effect was observed on the high-flatulogenic diet (599 ± 174 mL more intestinal gas production after the test meal than during fasting; p = 0.021). Conclusions & Inferences Our data demonstrate temporal summation effects of food residues on intestinal gas production. Hence, intestinal gas production depends on pre-existing and on recent colonic loads of fermentable foodstuffs. [ABSTRACT FROM AUTHOR]

Background & Aims Probiotics can prevent pathological bacterial translocation in cirrhosis by modulating intestinal microbiota and improving gut barrier and immune disturbances. To evaluate the effect of probiotic VSL#3 on bacterial translocation, intestinal microbiota, gut barrier and inflammatory response in rats with experimental cirrhosis. Methods Forty-six Sprague-Dawley rats with CCl4-induced cirrhosis were randomized into two groups: VSL#3 group ( n = 22) that received VSL#3 in drinking water, and water group ( n = 24) that received water only. Treatment began at week 6 of cirrhosis induction and continued until laparotomy, performed 1 week after development of ascites or at week 20. A control group included 11 healthy rats. At this study end, we evaluated bacterial translocation, intestinal flora, intestinal barrier (ileal claudin-2 and 4, β-defensin-1, occludin and malondialdehyde as index of oxidative damage) and serum cytokines. Results Mortality during this study was similar in the VSL#3 group (10/22, 45%) and the water group (10/24, 42%) ( P = 1). The incidence of bacterial translocation was 1/12 (8%) in the VSL#3 group, 7/14 (50%) in the water group ( P = 0.03 vs. VSL#3 group) and 0/11 in the control group ( P = 0.008 vs. water group). The concentration of ileal and caecal enterobacteria and enterococci was similar in the two groups of cirrhotic rats. The ileal occludin concentration was higher and ileal malondialdehyde and serum levels of TNF-α were lower in the VSL#3 group than in the water group ( P < 0.05). Conclusions VSL#3 decreases bacterial translocation, the pro-inflammatory state and ileal oxidative damage and increases ileal occludin expression in rats with experimental cirrhosis. [ABSTRACT FROM AUTHOR]

BackgroundInteraction between gut flora and the intestinal barrier may involve changes in permeability. MethodsRats with a colonic segment excluded from faecal transit were surgically prepared. Matched groups were either kept on luminal antibiotics to prevent colonization of the segment or recolonized with mixed rat flora. Permeability to low-dose trinitrobenzenesulphonic acid (TNBS) or trinitrophenol (TNP), and mucosal injury by the compounds at a high dose were tested in antibiotic and recolonized rats (the compounds differ in water solubility but share a common antigenic domain). ResultsLumen to blood clearance of the hydrophilic probe (TNBS) was faster in recolonized than in antibiotic rats. The hydrophobic compound TNP was absorbed at faster rates than TNBS, but there was no difference between antibiotic and recolonized rats. Instillation of TNBS at a high dose induced mucosal release of inflammatory mediators and tissue myeloperoxidase accumulation in recolonized rats but not in antibiotic rats. Large necrotic lesions with submucosal involvement after TNBS were only observed in recolonized rats. In contrast, TNP induced mucosal inflammation and large lesions with submucosal necrosis both in recolonized and in antibiotic rats. ConclusionColonizing bacteria may increase intestinal permeability to hydrophilic compounds and render the mucosa susceptible to injury. [ABSTRACT FROM AUTHOR]

Background & Aims Combined therapy with endoscopic variceal ligation ( EVL) and β-blockers ± isosorbide mononitrate ( ISMN) is currently recommended to prevent variceal rebleeding. However, the role of this combined therapy has been challenged by some studies. We performed a systematic review to assess the value of combined therapy with EVL and β-blockers ± ISMN as compared with each treatment alone to prevent rebleeding. Methods Databases, references and meeting abstracts were searched to retrieve randomized trials comparing combined therapy with EVL and β-blockers ± ISMN vs either treatment alone, to prevent variceal rebleeding in cirrhosis. Random-effects model was used for meta-analysis. Results We identified five studies comparing EVL alone or combined with drugs, including a total of 476 patients. Combination therapy reduced overall rebleeding [risk ratios (RR) = 0.44, 95% confidence interval (CI) = 0.28-0.69], and showed a trend towards lower mortality (RR = 0.58, 95% CI = 0.33-1.03), without increasing complications. We identified four trials comparing drugs alone or associated with EVL, including 409 patients. All used β-blockers plus ISMN. Variceal rebleeding decreased with combined therapy ( P < 0.01) but rebleeding from oesophageal ulcers increased ( P = 0.01). Overall, there was a trend towards lower rebleeding (RR = 0.76, 95% CI = 0.58-1.00) without effect on mortality (RR = 1.24, 95% CI = 0.90-1.70). Conclusions The addition of drug therapy to EVL improves the efficacy of EVL alone. However, the addition of EVL to β-blockers and ISMN achieves a non-significant decrease of rebleeding with no effect on mortality. Although combination therapy with EVL plus β-blockers ± ISMN is adequate to prevent rebleeding, β-blockers + ISMN alone may be a valid alternative. [ABSTRACT FROM AUTHOR]

Background Diets rich in fermentable residues increase intestinal gas production. Our aim was to demonstrate the potential effects of diet on gas-related symptoms. Methods The effect of a low-flatulogenic test diet (restricted to foodstuffs low in fermentable residues; n = 15) was compared to that of a balanced control diet ( Mediterranean type; n = 15) in 30 patients complaining of flatulence and other abdominal symptoms using a randomized parallel design. The following outcomes were measured daily: number of anal gas evacuations by an event marker, severity of gas-related symptoms by 0-10 scales, and sensation of digestive comfort by a −5 (unpleasant) to +5 (pleasant) scale. Measurements were taken pretreatment for 3 days on their habitual diet and for 7 days during the treatment phase. Key Results No pretreatment differences were detected between patients allocated to the control or test diets. The test diet significantly reduced the number of gas evacuations (by 54 ± 10%; p = 0.002 vs basal diet) whereas the control diet had a lesser effect (reduction by 28 ± 9%; p = 0.059 vs basal diet; p = 0.089 vs test diet). Compared to the control diet, the test diet significantly reduced flatulence (by 48 ± 7% vs 27 ± 8%, respectively; p = 0.018), abdominal distension (by 48 ± 4% vs 22 ± 12%, respectively; p = 0.038), and enhanced digestive well-being (by 149 ± 18% vs 58 ± 22%, respectively; p = 0.006). Conclusions & Inferences In patients with gas-related symptoms, a low-flatulogenic diet produces immediate beneficial effects with digestive, cognitive, and emotive dimensions. The number of gas evacuations is an objective biological marker of response to dietary treatment. [ABSTRACT FROM AUTHOR]

Background Although incrimination of the intestinal microbiota in the pathogenesis of IBD is widely accepted, few data are available about the role of specific bacteria. Potentially, Faecalibacterium prausnitzii, bacteria with anti-inflammatory properties, might be deficient in ulcerative colitis ( UC). Aim To quantify F. prausnitzii in the faecal microbiota of UC patients in remission and determine its relationship with relapse. Methods A cross-sectional study included 116 UC patients in remission, 29 first-degree relatives and 31 healthy controls. A subset of eighteen patients, recruited during the first month of remission, underwent a 1-year follow-up. Total bacteria and F. prausnitzii were measured by quantitative Real Time PCR ( qPCR, copies/g). Calprotectin was determined as inflammatory index (μg/g). Results We found that F. prausnitzii was reduced in patients (median, IQR: 1.4 × 108, 5.1 × 107-4.5 × 108) and relatives (1.7 × 108, 9.3 × 107-5.1 × 108) vs. controls (6.5 × 108, 3.7 × 108-1.6 × 109, P < 0.0001). Moreover, low counts of F. prausnitzii were associated with less than 12 months of remission (8.0 × 107, 2.0 × 107-3.5 × 108 vs. 2.1 × 108, 1.0 × 108-7.9 × 108, P < 0.001) and more than 1 relapse/year (8.0 × 107, 3.2 × 107-3.8 × 108 vs. 1.9 × 108, 6.8 × 107-6.0 × 108, P < 0.01). When patients were followed up, F. prausnitzii increased steadily until reaching similar levels to those of controls if remission persisted (2.9 × 108, 9.3 × 106-1.2 × 109; calprotectin: 76, 19-212), whereas it remained low if patients relapsed (2.2 × 108, 1.4 × 106-3.3 × 108; calprotectin: 1760, 844-3662 P < 0.05 vs. controls). Conclusions Defective gut colonisation by F. prausnitzii occurred in UC patients during remission and in their unaffected relatives. The recovery of the F. prausnitzii population after relapse is associated with maintenance of clinical remission. [ABSTRACT FROM AUTHOR]

Background The microbial community of the human gut - the enteric microbiota - plays a critical role in functions that sustain health and is a positive asset in host defenses. In recent years, our understanding of this so-called human 'super organism' has advanced, following characterization of fecal metagenomes which identified three core bacterial enterotypes, and based on basic and clinical research into the impact and consequences of microbiota biodiversity and change on gastrointestinal disorders and diseases. Purpose This article considers current knowledge and future perspectives on the make-up and function of human gut microbiota, with a particular focus on altered microbiota and gastrointestinal disorders, nutritional influences on the gut microbiota, and the consequences for gastrointestinal health, as well as improved understanding of gut-microbiota-brain communication. [ABSTRACT FROM AUTHOR]

Transforming growth factor β (TGF-β) is known to play a key role in intestinal fibrosis; however, the underlying mechanisms are not well understood. TGF-β signal transduction is through TGF-β receptors, including the TGF-β type 1 receptor. Most cell types contain a TGF-β type 1 receptor form known as activin receptor-like kinase 5 (ALK5), which propagates the signal to the nucleus through the phosphorylation of Smad2 and Smad3 proteins. Therefore, we assessed the effect of the disruption of TGF-β/ALK5/Smad signalling by an ALK5 inhibitor (SD-208) in two experimental animal models of intestinal fibrosis: anaerobic bacteria- and trinitrobenzensulphonic acid-induced colitis. In addition, isolated myofibroblasts were pretreated with SD-208 and exposed to recombinant TGF-β1. Finally, myofibroblasts were transfected with ALK5, Smad2, and Smad3-specific siRNA. Up-regulation of ALK5 and TIMP-1, phosphorylation of Smad2 and Smad3 proteins, and increased intestinal wall collagen deposition were found in both experimental animal models. These effects were decreased by SD-208. TGF-β1 treatment also induced phosphorylation of Smad2 and Smad3 and up-regulation of ALK5 protein, TIMP-1, and α2 type 1 collagen gene expression in isolated myofibroblasts. Again these effects were inhibited by SD-208. Also, ALK5, Smad2, and Smad3 siRNA abolished the induction of TIMP-1 and α2 type 1 collagen. Our findings provide evidence that the TGF-β/ALK5/Smad pathway participates in the pathogenesis of experimental intestinal fibrosis. These data show promise for the development of an effective therapeutic intervention in this condition. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Hyponatraemia is common in patients with advanced cirrhosis and is associated with remarkable changes in brain cells, particularly a reduction in myoinositol and other intracellular organic osmolytes related to the hypo-osmolality of the extracellular fluid. It has been recently suggested that hyponatraemia may be an important factor associated with the development of overt hepatic encephalopathy (HE). To test this hypothesis, we retrospectively analysed the incidence and predictive factors of overt HE using a database of 70 patients with cirrhosis included in a prospective study comparing transjugular intrahepatic portosystemic shunts (TIPS) vs large-volume paracentesis in the management of refractory of ascites. Variables used in the analysis included age, sex, previous history of HE, treatment assignment (TIPS vs large volume paracentesis plus albumin), treatment with diuretics, serum bilirubin, serum creatinine and serum sodium concentration. Laboratory parameters were measured at entry, at 1 month and every 3 months during follow-up and at the time of development of HE in patients who developed this complication. During a mean follow-up of 10 months, 50 patients (71%) developed 117 episodes of HE. In the whole population of patients, the occurrence of HE was independently associated with serum hyponatraemia, serum bilirubin and serum creatinine. In conclusion, in patients with refractory ascites, the occurrence of HE is related to the impairment of liver and renal function and presence of hyponatraemia. [ABSTRACT FROM AUTHOR]

Background Acute intestinal toxicity is a frequent complication that may lead to interruption of treatment in patients undergoing pelvic radiotherapy. Reliable, non-invasive biological markers to evidence their severity are not yet available. Aim To test faecal DNA and calprotectin as potential biomarkers of intestinal toxicity caused by pelvic radiotherapy. Methods Patients were categorized according to the location of the cancer as nonrectal ( n = 25) and rectal ( n = 27). Four stool samples were collected at weeks w0, w3, w5 (end of radiotherapy) and w7. Faecal DNA was determined by quantitative PCR and calprotectin by ELISA. Intestinal toxicity was scored according to the Common Toxicity Criteria. Results In the nonrectal group, acute diarrhoea toxicity was present in 80% of patients, faecal DNA increased 10-fold during radiotherapy (1.5 × 103 copies/mg dry weight, 9.5 × 102–8.8 × 103 at w0, median and interquartile range vs. 1.3 × 104, 1.9 × 103–3.9 × 104 at w5, P < 0.01), but was not recovered at w7 (3.4 × 103, 1.5 × 103–4.1 × 104) and calprotectin doubled during treatment at w3 and w5. No significant changes in faecal markers were found in the rectal group. Conclusion Faecal excretion of human DNA and calprotectin increased during pelvic radiotherapy treatment, and may be a good objective biomarker of intestinal damage in nonrectal cancer patients. [ABSTRACT FROM AUTHOR]

The article presents a study which examines the relation between lifetime consumption of alcohol and the prevalent mutations in the codon 12 of the K-ras oncogene in patients with pancreatic ductal adenocarcinoma (PDA). Using logistic regression, the researchers compared the PDA cases with mutated and wild-type K-ras tumors. The results indicate a weak association between alcohol consumption with an increased risk of having a K-ras mutated PDA, although mutated cases were observed moderately in heavy drinkers.

Background Hepatic venous pressure gradient (HVPG) monitoring of therapy to prevent variceal rebleeding provides strong prognostic information. Treatment of nonresponders to β-blockers ± nitrates has not been clarified. Aim To assess the value of HVPG-guided therapy using nadolol + prazosin in nonresponders to nadolol + isosorbide-5-mononitrate (ISMN) compared with a control group treated with nadolol + ligation. Methods Cirrhotic patients with variceal bleeding were randomized to HVPG-guided therapy ( n = 30) or nadolol + ligation ( n = 29). A Baseline haemodynamic study was performed and repeated within 1 month. In the guided-therapy group, nonresponders to nadolol + ISMN received nadolol and carefully titrated prazosin and had a third haemodynamic study. Results Nadolol + prazosin decreased HVPG in nonresponders to nadolol + ISMN ( P < 0.001). Finally, 74% of patients were responders in the guided-therapy group vs. 32% in the nadolol + ligation group ( P < 0.01). The probability of rebleeding was lower in responders than in nonresponders in the guided therapy group ( P < 0.01), but not in the nadolol + ligation group ( P = 0.41). In all, 57% of nonresponders rebled in the guided-therapy group and 20% in the nadolol + ligation group ( P = 0.05). The incidence of complications was similar. Conclusions In patients treated to prevent variceal rebleeding, the association of nadolol and prazosin effectively rescued nonresponders to nadolol and ISMN, improving the haemodynamic response observed in controls receiving nadolol and endoscopic variceal ligation. Our results also suggest that ligation may rescue nonresponders. [ABSTRACT FROM AUTHOR]

Background Acute liver injury of uncertain aetiology is often drug related and quantitative information about the associated risk is scarce. Aim To estimate the risk of acute liver injury associated with the use of drugs. Methods In a population survey study, 126 cases of acute liver injury were prospectively assembled from January 1993 to December 1999, in patients over 15 years of age, in 12 hospitals in Barcelona (Spain). We estimated the relative risk for each drug as the ratio between the incidence of acute liver injury among the exposed population to the drug and the incidence of acute liver injury among those not exposed to it. Drug consumption data were used to estimate the exposed population. Results Isoniazid, pyrazinamide, rifampicin, amoxicillin with clavulanic acid, erythromicin, chlorpromazine, nimesulide, and ticlopidine presented the highest risk (point relative risk > 25). Amoxicillin, metoclopramide, captopril and enalapril, furosemide, hydrochlorothiazide, fluoxetine, paroxetine, diazepam, alprazolam, lorazepam, metamizole, low-dose acetylsalicylic acid and salbutamol showed the lowest risk (point relative risk < 5). Conclusions This study provides a risk estimation of serious liver disease for various drugs that will be useful in its diagnosis and management, and when comparing with the drug therapeutic benefit in each indication. Some observed associations would be worth specific studies. [ABSTRACT FROM AUTHOR]

Background Inulin and oligofructose promote selective growth of saccharolytic bacteria with low inflammatory potential. Objective To test the effect of oligofructose-enriched inulin in patients with active ulcerative colitis. Design Prospective, randomized, placebo controlled pilot trial. Eligible patients had been previously in remission with mesalazine as maintenance therapy or no drug, and presented with a relapse of mild to moderate activity. They were treated with mesalazine (3 g/day) and randomly allocated to receive either oligofructose-enriched inulin (12 g/day, p.o., n = 10) or placebo (12 g/day of maltodextrin, p.o., n = 9) for 2 week. Primary endpoint was the anti-inflammatory effect as determined by reduction of calprotectin and human DNA in faeces. Results Rachmilewitz score decreased in both groups, reaching statistical significance at day 14 ( P < 0.05). Oligofructose-enriched inulin was well-tolerated and dyspeptic symptoms scale decreased significantly with active treatment but not with placebo. At day 7, an early significant reduction of calprotectin was observed in the group receiving oligofructose-enriched inulin (day 0: 4377 ± 659 µg/g; day 7: 1033 ± 393 µg/g, P < 0.05) but not in the placebo group (day 0: 5834 ± 1563 µg/g; day 7: 4084 ± 1395 µg/g, n.s.). Changes in faecal concentration of human DNA were not significant. Conclusion In active ulcerative colitis, dietary supplementation with oligofructose-enriched inulin is well tolerated and is associated with early reduction in faecal calprotectin. [ABSTRACT FROM AUTHOR]

The principal defense of the human host against a Mycobacterium tuberculosis infection is the formation of granulomas, organized collections of activated macrophages, including epithelioid and multinucleated giant cells, surrounded by lymphocytes. This granuloma can sequester and contain the bacteria preventing active disease, and if the granuloma is maintained, these bacteria may remain latent for a person's lifetime. Secretion of a variety of chemoattractant cytokines following phagocytosis of the bacilli by the macrophage is critical not only to the formation of the granuloma but also to its maintenance. To investigate this process of early granuloma formation, we developed an in vitro model composed entirely of human cells. Combining blood lymphocytes and autologous macrophages from healthy purified protein derivative skin test-negative individuals and mycobacteria resulted in the formation of small, rounded aggregate structures. Microscopic examination found macrophage-specific CD68+ epithelioid macrophages and small round CD3+ lymphocytes that in complex resembled small granulomas seen in clinical pathology specimens. Acid-fast staining bacteria were observed between and possibly within the cells composing the granulomas. Supernatants from the infected cells collected at 24 and 48 h and 5 and 9 days after infection were analyzed by a multiplexed cytokine bead-based assay using the Luminex 100 and were found to contain interleukin (IL)-6, IL-8, interferon-γ and tumor necrosis factor-α, cytokines known to be involved in human granuloma formation, in quantities from two-fold to 7000-fold higher than supernatants from uninfected control cells. In addition, chemotaxis assays demonstrated that the same supernatants attracted significantly more human peripheral blood mononuclear cells than those of uninfected cells (P<0.001). This model may provide insight into the earliest stages of granuloma formation in those newly infected.Immunology and Cell Biology (2007) 85, 160–168. doi:10.1038/sj.icb.7100019; published online 2 January 2007 [ABSTRACT FROM AUTHOR]

Immunization with defined antigens is generally less effective at inducing host protection against experimental infection with Schistosoma mansoni than vaccination with attenuated infective cercariae. We predicted that quantitative and/or qualitative differences existed between the immune responses generated to attenuated cercariae and those induced by defined antigens. Thus, we compared immune responses typically associated with protection in the murine model between animals vaccinated with attenuated cercariae and mice immunized with DNA encoding Sm23, a schistosome integral membrane protein that has previously been shown to confer protection. Mice vaccinated three times with attenuated cercariae demonstrated higher levels of protection than Sm23-vaccinated animals but spleen cells from Sm23 DNA vaccinated mice produced significantly higher levels of schistosome antigen-specific IFN-γ. Both vaccines induced similar levels of Sm23-specific antibody and post-challenge dermal inflammation. However, the pulmonary inflammatory responses following challenge were much less pronounced in DNA immunized animals compared to those receiving irradiated cercariae. Thus, although Sm23 DNA vaccination effectively induced parasite-specific IFN-γ and antibody responses, it failed to evoke other critical responses needed for optimal vaccine efficacy. [ABSTRACT FROM AUTHOR]

Background: Active gastritis, gastric mucosal atrophy and intestinal metaplasia are lesions associated with Helicobacter pylori infection. Atrophy and intestinal metaplasia are only seen in adults.Objectives: We describe pediatric patients with atrophy and metaplasia, and compare the inflammatory response in these patients to controls.Methods: As part of a multicenter study of pediatric H. pylori infection, gastric biopsy specimens obtained during diagnostic upper endoscopy of 19 H. pylori-infected children and 45 uninfected controls were reviewed and graded by using the updated Sydney system. The inflammatory response was characterized using immunohistochemistry for T lymphocytes, B lymphocytes, and macrophages, and TUNEL assay for apoptosis.Results: Histology of H. pylori-infected and control biopsy specimens showed active gastritis in 32% and 2% respectively (P = 0.002). Mild intestinal metaplasia was found in 4 H. pylori-infected children, in two of whom it appeared to be accompanied by atrophy. Specimens from patients with H. pylori infection contained increased numbers of B lymphocytes in lymphoid nodules, and apoptosis in the superficial epithelium and inflammatory cells. T lymphocytes and macrophages appeared in similar numbers in specimens from controls and infected patients.Conclusions: We describe intestinal metaplasia associated with H. pylori infection in children. Since atrophy usually precedes intestinal metaplasia in adults, we suggest that atrophy exists in children. High numbers of B lymphocytes and apoptosis in the surface epithelium are seen in patients with H. pylori infection and may be related to the development of atrophy and intestinal metaplasia. [ABSTRACT FROM AUTHOR]

SUMMARY: BACKGROUND Active gastritis, gastric mucosal atrophy and intestinal metaplasia are lesions associated with Helicobacter pylori infection. Atrophy and intestinal metaplasia are only seen in adults.OBJECTIVES We describe pediatric patients with atrophy and metaplasia, and compare the inflammatory response in these patients to controls.METHODS As part of a multicenter study of pediatric H. pylori infection, gastric biopsy specimens obtained during diagnostic upper endoscopy of 19 H. pylori-infected children and 45 uninfected controls were reviewed and graded by using the updated Sydney system. The inflammatory response was characterized using immunohistochemistry for T lymphocytes, B lymphocytes, and macrophages, and TUNEL assay for apoptosis.RESULTS Histology of H. pylori-infected and control biopsy specimens showed active gastritis in 32% and 2% respectively (P = 0.002). Mild intestinal metaplasia was found in 4 H. pylori-infected children, in two of whom it appeared to be accompanied by atrophy. Specimens from patients with H. pylori infection contained increased numbers of B lymphocytes in lymphoid nodules, and apoptosis in the superficial epithelium and inflammatory cells. T lymphocytes and macrophages appeared in similar numbers in specimens from controls and infected patients.CONCLUSIONS We describe intestinal metaplasia associated with H. pylori infection in children. Since atrophy usually precedes intestinal metaplasia in adults, we suggest that atrophy exists in children. High numbers of B lymphocytes and apoptosis in the surface epithelium are seen in patients with H. pylori infection and may be related to the development of atrophy and intestinal metaplasia. [ABSTRACT FROM AUTHOR]

ABSTRACT- In vitro studies were carried out on isolated rat hepatocytes to examine further the proposed cytoprotective actions of prostaglandins (PG) using carbon tetrachloride (CCl4) as the toxic agent. Isolated hepatocytes, prepared by collagenase, were cultured in Leibowitz-15 medium. Following preincubation, CCl4(300 or 150 μg/ml) was added to the hepatocytes. Treatment with Indomethacin (INDO), 16, 16-dimethyl-PGE2(PGE2) and prostacyclin (PGI2) was assayed in the cultures. Cell damage was measured by lactic dehydrogenase (LDH) release. 6-keto-PGF1α was measured in the supernatant by direct radioimmunoassay. The results showed PGI2 (30.0 ng/ml) treatment 30 min after CCl4(300 μg/ml) addition to be highly protective (p<0.001 versus CCl4 control). PGE2(3 ng/ml) showed similar protection (p<0.001). INDO (2 μg/ml) following CCl4(150 μg/ml) demonstrated increased cell death (p<0.001). INDO (0.5 μg/ml) reduced 6-keto-PGF1α production (p<0.05). Low dose ethanol (1.5 μg/ ml) increased 6-keto-PGF1α production (p<0.05). Ethanol (1.5 μg/ml), added to stimulate endogenous PG production, was cytoprotective when added prior to CCl4 (p<0.01). This protection was suppressed by INDO. Ethanol added after CCl4 was not protective. We conclude that exogenously added PGI2and PGE2 are cytoprotective in this in vitro model and that endogenous PG production may play a protective role in the initial stages of cellular damage. [ABSTRACT FROM AUTHOR]