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Background: There is little known about stem cells in human non-neoplastic and neoplastic esophageal epithelia. We have demonstrated expression of linker threonine-phosphorylated Smad2/3 (pSmad2/3L-Thr), suggesting presence of stem-like cells in mouse esophageal epithelium, and identified presence of pSmad2/3L-Thr-positive cells that might function as cancer stem cells in mouse model of colorectal carcinoma. Aims: We explore whether pSmad2/3L-Thr can be used as a biomarker for stem cells of human esophageal epithelia and/or neoplasms. Methods: We have used esophageal tissues from inpatients undergoing endoscopic submucosal dissection and performed double immunofluorescent staining of pSmad2/3L-Thr and Ki67, CDK4, p63, Sox2, CK14, p53, ALDH1, CD44 or D2-40 after which the sections were stained with hematoxylin and eosin. Results: pSmad2/3L-Thr-positive cells showed immunohistochemical co-localization with CDK4, p63, CD44 and Sox2 in the basal and parabasal layers of non-neoplastic esophageal epithelia. In esophageal neoplasms, they showed immunohistochemical co-localization with p53, CDK4, ALDH1 and CD44. There was a significant increase in the percentage of pSmad2/3L-Thr-positive cells in the p53-positive neoplastic cell population with development of esophageal neoplasia. pSmad2/3L-Thr-positive cells localized to the lower section of low-grade intraepithelial neoplasia and were observed up to the upper section in carcinoma in situ. In invasive squamous cell carcinoma, they were scattered throughout the tumor with disappearance of polarity and were found in intraepithelial primary lesions and sites of submucosal and vessel invasion. Conclusions: We determined significant expression of pSmad2/3L-Thr in human esophageal non-neoplastic and neoplastic epithelia, indicating that these are epithelial stem-like cells and cancer stem cells, respectively, that correlate with developing esophageal neoplasms. [ABSTRACT FROM AUTHOR]

Background: Racial/ethnic disparities in prognosis have been reported in patients with hepatocellular carcinoma (HCC); however, few studies have evaluated racial/ethnic disparities in the context of insurance status.Aims: Characterize racial/ethnic and insurance status in early tumor detection, receipt of curative therapy and overall survival in a multicenter diverse cohort of HCC patients from the USA.Study: We included patients with HCC diagnosed between June 2012 and May 2013 at four centers in the USA. Generalized linear mixed effects models were used to compare early tumor detection (defined using Milan Criteria) and curative treatment receipt (liver transplantation, surgical resection, or local ablation) as a function of patient race/ethnicity and insurance status. A multivariable frailty survival model was used to compare risk of death between patient groups.Results: Of 379 HCC patients (52.8% non-Hispanic White, 19.5% Hispanic White, 19.8% Black), 46.4% and 48.0% were found at an early stage and underwent curative therapy, respectively, and median overall survival of the cohort was 25.7 months. Early detection of HCC was associated with gastroenterology subspecialty care and receipt of HCC surveillance but not race/ethnicity or insurance status in adjusted models. However, commercial insurance was significantly associated with higher odds of curative treatment receipt, which in turn was the strongest correlate for overall survival. After adjusting for health system and insurance status, race/ethnicity was not associated with curative treatment receipt or overall survival.Conclusions: Insurance status and access to gastroenterology subspecialty care may be important drivers of racial/ethnic disparities in prognosis among HCC patients. [ABSTRACT FROM AUTHOR]

Background and Aims: Direct oral anticoagulants (DOAC) are important new anticoagulant therapies that are not well studied in patients with chronic liver disease. The aim of this study was to compare rates of bleeding in cirrhosis patients treated with DOAC (factor Xa inhibitors: rivaroxaban and apixaban) to those in cirrhosis patients treated with traditional anticoagulation (warfarin and low molecular weight heparin).Methods: We identified a total of 39 patients with cirrhosis who received anticoagulation therapy over a 3-year period (20 DOAC and 19 traditional anticoagulation) from a research database. Medical records were reviewed to obtain clinical data to compare between the groups.Results: Clinical characteristics between the two groups were similar. There were three documented bleeding events in the traditional anticoagulation group and four bleeding events in the DOAC group (p = 0.9). There were two major bleeding events in the traditional anticoagulation group and one major bleeding event in the DOAC group. There were no documented reports of drug-induced liver injury during this study period. Among all patients, no significant predictors of bleeding were identified using univariate regression and Cox proportional hazard modeling.Conclusions: This is the first clinical study evaluating the use of DOAC in patients with cirrhosis. DOAC display similar safety characteristics when compared to traditional anticoagulation in patients with cirrhosis and are potentially attractive agents for anticoagulation therapy. Larger studies are now needed to better understand the safety and efficacy of these agents in cirrhosis. [ABSTRACT FROM AUTHOR]

Background: Few studies have shown that host interleukin-28B ( IL28B) genetic polymorphisms are associated with insulin resistance in patients with chronic hepatitis C virus (HCV) infection. However, the clinical relevance of this relationship is unclear. Aims: We examined the association between IL28B genotype for rs12980275 and risk of type 2 diabetes and diabetes-related complications. Methods: We used a cross-sectional study of prospectively recruited male veterans with chronic HCV. We employed logistic regression analysis and adjusted for patients' age, race, body mass index, and hepatic fibrosis. Results: A total of 528 participants were recruited (mean age 59.1 years; 38.5 % African-American; 40.3 % advanced fibrosis). Of these, 36.1 % were homozygous for favorable AA allele for rs12980275, 49.0 % were heterozygous (AG), and 14.0 % were homozygous for the unfavorable allele (GG). Prevalence of diabetes was significantly lower in patients with both favorable alleles (AA) than that with at least one unfavorable IL28B G allele (21.1 vs. 30.2 %, p = 0.02). Similarly, patients who were homozygous for the favorable alleles had lower prevalence of diabetes-related complications than patients with any unfavorable IL28B allele (5.7 vs. 12.2 %, p = 0.01). This association did not change after adjusting for sociodemographic characteristics, body mass index, and stage of hepatic fibrosis (adjusted OR 0.56, 95 % CI 0.35-0.89; OR 0.47, 95 % CI 0.23-0.96). Conclusions: Patients who have favorable AA IL28B alleles have a lower prevalence of diabetes and related complications compared with patients with unfavorable IL28B rs12980275 genotype. IL28B genotype information may be used to counsel HCV patients regarding their individualized risk of diabetes and diabetes-related complications. [ABSTRACT FROM AUTHOR]

Background: The hepatitis C virus (HCV) antibody test alone does not distinguish current from resolved infections. Aim: The study aimed to describe the percentage of current HCV infection, defined by HCV RNA positivity, among those tested positive for anti-HCV, and to examine characteristics of those with current infection. Methods: Using nationally representative data from the 2003 to 2010 National Health and Nutrition Examination Surveys, descriptive analyses and regressions were performed on data from anti-HCV-positive adults aged ≥40 years. Results: Of 13,909 participants examined, 304 were anti-HCV-positive. Of these, 238 or 75.3 % [95 % confidence interval (CI) 67.5-81.8 %] had detectable viral RNA. The percentage of current, unresolved HCV infection was highest among non-Hispanic Blacks (91.1 %) and lowest among those with a college education (57.3 %). In multivariate analyses, non-Hispanic Blacks were more likely to have current HCV infection compared to non-Hispanic Whites (adjusted odds ratio 3.9, 95 % CI 1.6-9.2). Among persons with current HCV infection, most had elevated alanine aminotransferase (56.5 %) or aspartate aminotransferase (71.8 %) levels, but only 35.3 % reported having been diagnosed with any abnormal liver conditions. Excessive alcohol drinking was reported by 27.3 % of participants with current HCV infection. Conclusions: Among adults aged ≥40 years who had ever been infected with HCV, approximately three-quarters had current, unresolved HCV infection. Non-Hispanic Blacks were more likely to have current infection than non-Hispanic Whites. The majority of those with current infection had abnormal liver function tests but had not received appropriate diagnoses. Many currently infected persons would benefit from lifestyle modifications to avoid the multiplicative effect of alcohol on HCV infection. [ABSTRACT FROM AUTHOR]

Background and Aim: Hepatitis C virus (HCV) is an important cause of hepatocellular carcinoma (HCC) in Asians; however, it is often overlooked due to the high prevalence of hepatitis B virus in Asians. This study examines HCV-related HCC in Asians. Methods: We conducted a retrospective cohort study of 792 consecutive Asian ( n = 220) and non-Asian ( n = 572) patients with HCV-related HCC identified at Stanford University Medical Center using International Classification of Diseases-9 diagnosis between July 1996 and June 2012. Results: Asian patients were much older [66 (38-88) vs. 56 (31-87) years, P < 0.0001] and more likely to be female (33 vs. 19 %, P < 0.0001). A larger proportion of Asians were diagnosed with HCC within 2 years of HCV diagnosis (35 vs. 20 %, P = 0.001). Asian patients were more likely to undergo palliative therapy (46 vs. 28 %) and less likely to be listed for liver transplantation (20 vs. 48 %, P < 0.001), despite similar rates of meeting Milan criteria (52 vs. 58 %, P = 0.16). Overall, there was a trend for higher median survival rates in Asians (30 vs. 21 months, P = 0.091). Asians had higher long-term survival with palliative therapy only (5-year survival: 28 vs. 10 %, P < 0.0001); however, survival was similar among patients listed for liver transplantation. Conclusions: There were distinct differences in clinical presentations of Asian and non-Asian patients with HCV-related HCC. Asians with HCV-related HCC are less likely to undergo liver transplantation and more likely to have delayed HCV diagnosis. Improved strategies in HCV screening in Asians are needed, as it may lead to earlier diagnosis and treatment of HCV infection and possible prevention of HCC development. [ABSTRACT FROM AUTHOR]

Background/Aims: Among individuals without human immunodeficiency virus (HIV), African Americans have lower spontaneous clearance of hepatitis C virus (HCV) than Caucasians, and women have higher clearance than men. Few studies report racial/ethnic differences in acute HCV in HIV infected, or Hispanic women. We examined racial/ethnic differences in spontaneous HCV clearance in a population of HCV mono- and co-infected women. Methods: We conducted a cross sectional study of HCV seropositive women (897 HIV infected and 168 HIV uninfected) followed in the US multicenter, NIH-funded Women's Interagency HIV Study (WIHS), to determine the association of race/ethnicity with spontaneous HCV clearance, as defined by undetectable HCV RNA at study entry. Results: Among HIV and HCV seropositive women, 18.7 % were HCV RNA negative, 60.9 % were African American, 19.3 % Hispanic and 17.7 % Caucasian. HIV infected African American women were less likely to spontaneously clear HCV than Hispanic (OR 0.59, 95 % CI 0.38-0.93, p = 0.022) or Caucasian women (OR 0.57, 95 % CI 0.36-0.93, p = 0.023). Among HIV uninfected women, African Americans had less HCV clearance than Hispanics (OR 0.18, 95 % CI 0.07-0.48, p = 0.001) or Caucasians (OR 0.26, 95 % CI 0.09-0.79, p = 0.017). There were no significant differences in HCV clearance between Hispanics and Caucasians, among either HIV infected (OR 0.97, 95 % CI 0.57-1.66, p = 0.91) or uninfected (OR 1.45, 95 % CI 0.56-3.8, p = 0.45) women. Conclusions: African Americans were less likely to spontaneously clear HCV than Hispanics or Caucasians, regardless of HIV status. No significant differences in spontaneous HCV clearance were observed between Caucasian and Hispanic women. Future studies incorporating IL28B genotype may further explain these observed racial/ethnic differences in spontaneous HCV clearance. [ABSTRACT FROM AUTHOR]

Background: Given the significant side-effects and healthcare costs associated with telaprevir- or boceprevir-combination therapy, identifying patients likely to respond to dual therapy peg-interferon (Peg-IFN)/ribavirin is highly desirable. Since the perception of how large the pool of patients who may achieve rapid virologic response (RVR) is vaguely ascertained, we searched the literature for this information. Methods: Studies on patients treated with Peg-IFN/ribavirin were identified by searching MEDLINE and analyzed by meta-analysis. The primary end point was weighted estimates of RVR. The influence on race/ethnicity, baseline viremia, type of Peg-IFN, ribavirin dosage, and significant hepatic fibrosis on the results was evaluated. Results: Across 38 studies on 13,219 patients, the fraction of RVR patients was 19.6 %. The only baseline factor influencing RVR was race/ethnicity, with higher rates in Asian (26.7 %) and Caucasian patients (22.5 %). Of the 1,735 RVR patients, 85.1 % attained sustained virologic response (SVR). In these, SVR was influenced by ribavirin dose (86.8 vs. 72.8 % for high or low), type of Peg-IFN (91.8 % for alpha-2b vs. 82.9 % for alpha-2a), and treatment duration (91.7 % for 48 weeks vs. 79.4 % for 24 weeks). Conclusions: One fifth to one fourth of hepatitis C virus genotype 1 (HCV-1) patients can be safely treated with dual therapy of Peg-IFN/ribavirin, and may be spared from cost and inconvenience of regimens considering the addition of HCV protease inhibitors. [ABSTRACT FROM AUTHOR]

Hepatitis C virus infection is a major public health concern. Approximately 4 million people are reported to be infected with the virus in the United States, and the annual death rate due to HCV-associated decompensated liver failure or hepatocellular carcinoma is estimated to be approximately 18,000 within the next decade. Therapeutic success, as measured by a sustained virologic response, is approximately 50 % in G1 patients with pegylated-interferon/ribavirin-based therapies. Independent studies have reported significant variation in response rates depending on the ethnicity or race of the patient, though the underlying reasons are not well understood. Historically, ethnic populations have been underrepresented in most large clinical trials of HCV therapies, even though these populations have disproportionately high rates of HCV infection. Recent clinical trials have investigated genetic variations in key biological pathways that may underlie the mechanisms responsible for the different rates of HCV clearance and treatment outcomes in ethnic populations treated with pegylated-interferon/ribavirin. However, as novel direct-acting antiviral drugs are added to, and eventually replace, existing treatment regimens, the role of the innate immune response in determining treatment outcomes will diminish. Socioeconomic and biological factors can impact rates of HCV infection, disease progression, and treatment outcomes in minority populations. Improved access to health care, novel antiviral treatments, and a better understanding of the host factors that contribute to disparities in treatment outcomes are expected to result in optimized treatment paradigms that directly target the virus, leading to improved outcomes for all patients. [ABSTRACT FROM AUTHOR]

Background: Single-nucleotide polymorphisms (SNPs) in the IL28B and PNPLA3 gene regions have been associated with hepatic steatosis in genotype 1 (G1) chronic HCV infection but their clinical impacts remain to be determined. Aim: We sought to validate these associations and to explore their impact on treatment response to peginterferon and ribavirin therapy. Methods: A total of 972 G1 HCV-infected Caucasian patients were genotyped for the SNPs rs12979860 (IL28B) and rs2896019 ( PNPLA3). Multivariable analysis tested IL28B and PNPLA3 for association with the presence of any steatosis (>0 %); clinically significant steatosis (>5 %); steatosis severity (grade 0-3/4); and the interacting associations of the SNPs and hepatic steatosis to sustained viral response (SVR). Results: IL28B and PNPLA3 polymorphisms were associated with the presence of any steatosis (rs12979860, p = 1.87 × 10; rs2896019, p = 7.56 × 10); clinically significant steatosis (rs12979860, p = 1.82 × 10; rs2896019, p = 1.27 × 10); and steatosis severity (rs12979860, p = 2.05 × 10; rs2896019, p = 2.62 × 10). Obesity, hypertriglyceridemia, hyperglycemia, liver fibrosis, and liver inflammation were all independently associated with worse steatosis. Hepatic steatosis was associated with lower SVR, and this effect was attenuated by IL28B. PNPLA3 had no independent association with SVR. Conclusions: IL28B and PNPLA3 are associated with hepatic steatosis prevalence and severity in Caucasians with G1 HCV, suggesting differing potential genetic risk pathways to steatosis. IL28B attenuates the association between steatosis and SVR. Remediable metabolic risk factors remain important, independently of these polymorphisms, and remain key therapeutic goals to achieve better outcomes for patients with HCV-associated hepatic steatosis. [ABSTRACT FROM AUTHOR]

Background and Aims: The standard treatment regimen for chronic HCV genotype 3 (HCV-G3) hepatitis consists of PEGylated interferon-α (IFN-α) and ribavirin at varying doses ranging from 400 to 1,200 mg and results in response rates of 80%. However, this therapy has substantial side-effects including anemia, is teratogenic, and costly. To reduce the side-effects of therapy, the role of monotherapy consisting of only IFN-α was investigated.Methods: A retrospective analysis of individual therapy courses of HCV-G3-infected patients who were treated with IFN-α(2a) monotherapy or a combination therapy with attention to the treatment outcome and the presence of IL28B rs12979860 and IL28B rs8099917 single-nucleotide polymorphism genotypes was performed. Conventional prognostic features in each case were assessed as well.Results: In the study, 15/30 (50%) of patients treated with IFN-α(2a) monotherapy and 32/36 (89%) treated with combination therapy achieved a sustained virological response (SVR). In addition, 7/11 (64%) of those treated initially with monotherapy and subsequently with combination therapy achieved an SVR. An "ultra-rapid" virological response occurring within 2 weeks of initiation of therapy (p = 0.005), young age (<40; p < 0.001) and low initial γ-GT/ALT-ratio (p = 0.03) were associated with a SVR to IFN-α(2a) monotherapy. An SVR in those treated with combination therapy was found to be associated with a rapid virological response (RVR) (p = 0.03). The absence of histologic steatosis was associated with SVR in all patient groups (p = 0.01). Therapy duration (24 vs. 48 weeks) did not affect the SVR in either group. As expected, combination therapy resulted in more hematological side-effects than did monotherapy.Conclusions: An "ultra-rapid" virological response, young age, low initial γ-GT/ALT-ratio and absence of steatosis were each associated with an SVR in those receiving IFN-α(2a) monotherapy. Therefore, monotherapy in these patients should still be discussed independently of the existence of the IL28B polymorphisms. [ABSTRACT FROM AUTHOR]

Background: With only a third of Latinos achieving sustained virologic response (SVR), there is a need for enhanced HCV treatment. Amantadine has been proposed to improve response rates in addition to standard therapy with peginterferon alpha and ribavirin. Our objective is to evaluate whether triple therapy with amantadine improves SVR rates in this special population.Method: Treatment-naïve Latino subjects with HCV genotype 1 infection were randomized to receive peginterferon alpha-2a plus weight-based ribavirin for 48 weeks (double therapy) or the same regimen plus amantadine 200 mg daily (triple therapy). The primary endpoint was SVR. Predictors of liver fibrosis using APRI and Forns indices were also evaluated.Results: We enrolled 124 patients with chronic hepatitis C genotype 1. Sixty-three received conventional therapy and 61 patients had triple therapy with amantadine. SVR at week 72 was achieved in 25 patients (39.7%) vs. 26 patients (42.6%) in the double and triple regimen, respectively (p=0.561). After multivariate analysis, advanced fibrosis, obesity, and low pretreatment ALT levels were associated with non-response in both groups (p=0.0234, p=0.0012, p=0.0249, respectively). APRI values delimited an area under the ROC curve (AUROC) of 0.724 and Forns index with AUROC of 0.733. There was no difference between both indices in predicting significant fibrosis (Knodell index: F3-F4).Conclusion: Our study demonstrates that the addition of amantadine to standard treatment of chronic HCV does not improve SVR rates in Latino patients with genotype 1. Further research to improve response rates in this special population is needed. [ABSTRACT FROM AUTHOR]

The first metabolite of ethanol, acetaldehyde, has the ability to form adducts with proteins and alter their function. It has been shown that acetaldehyde reacts with various proteins of the blood coagulation pathway and, subsequently, produces a prolongation of the clotting time. This study evaluated the function of clotting proteins from the extrinsic coagulation pathway (factor VII) and the intrinsic coagulation pathway (factor IX) when preincubated with acetaldehyde as compared to a control and compared to preincubation with ethanol. Prior to use in a clotting assay, incubation times with acetaldehyde, ethanol, and the control were the same for both factors VII and IX. An automatic fibrometer measured the clotting times. Factor VII preincubated with acetaldehyde prolonged the clotting time. However, factor IX preincubated with acetaldehyde actually decreased the clotting time. Of interest, both factors VII and IX preincubated with acetaldehyde produced statistically significant results when compared to the control and ethanol. This experiment indicates that acetaldehyde, in forming an adduct with proteins of the blood coagulation pathway, may induce a conformational change of factors VII and IX so as to either increase or decrease the clotting time. Therefore, it is possible that some of the deranged coagulation in alcohol abusers may be a final net result of the interaction of acetaldehyde and proteins of the coagulation pathway. [ABSTRACT FROM AUTHOR]

Activated factor X (FXa) is a trypsinlike serine protease involved in the cascade of blood coagulation. The monocyte chemoattractant protein-1 (MCP-1) may be important in the pathophysiology of liver ischemia-reperfusion injury. We investigated the effects of a selective FXa inhibitor, DX-9065a, on MCP-1 expression after ischemia-reperfusion in the rat liver. Liver ischemia was induced in rats by occluding the portal vein for 30 min. DX-9065a was injected intravenously 5 min before vascular clamping. Serum concentrations of MCP-1 were measured by enzyme-linked immunosorbent assay. The levels of MCP-1 mRNA in the liver after reperfusion were determined by northern blot analysis. In vitro MCP-1 production by peritoneal macrophages in response to alpha-thrombin was examined. Serum concentrations of MCP-1 increased and peaked at 6 hr after reperfusion. However, pretreatment of animals with DX-9065a resulted in significantly smaller increases in the serum concentration of MCP-1 after reperfusion in a dose-dependent manner. Pretreatment with DX-9065a significantly reduced MCP-1 mRNA levels in the liver after ischemia-reperfusion. In vitro MCP-1 production by peritoneal macrophages was enhanced by alpha-thrombin. In addition, DX-9065a significantly reduced tissue factor mRNA levels in peripheral monocytes after ischemia-reperfusion, compared to untreated animals. In conclusion, a selective inhibitor of FXa, DX-9065a, limited MCP-1 production after ischemia-reperfusion of the rat liver. [ABSTRACT FROM AUTHOR]

The colocolonic inhibitory reflex is characterized by inhibition of proximal colonic motility induced by distal colonic distension. The aim of this study was to investigate the underlying neural mechanisms of this reflex, in vivo, using an isolated loop of canine colon. In five beagle dogs, motility was recorded from an exteriorized colonic loop via a serosal strain gauge connected to a digital data logger and chart recorder. Inflation of a balloon in the distal colon resulted in inhibition of motility in the isolated loop. Inhibition of motor activity persisted following injection of propranolol (100 microg/kg intravenously), a beta-adrenoceptor antagonist, but was abolished following administration of the alpha2-adrenoceptor antagonist yohimbine (200 microg/kg intravenously). This study confirms that the colocolonic inhibitory reflex is mediated via the extrinsic nerves to the colon. As the reflex was abolished by alpha2-, but not beta-adrenoceptor blockade, this indicates that the reflex pathway involves alpha2-adrenoceptors. [ABSTRACT FROM AUTHOR]

An abnormal immune response may play apathogenic role in ulcerative colitis (UC). Animalmodels suggest that T-cell regulation may be of centralimportance in the inflammatory process. Our aims werethe characterization of the phenotype andfunctional status of circulating T-cells in ulcerativecolitis patients and to determine if activation-inducedcell death in CD4+ and CD8+lymphocytes in patients differs from healthy controls.Forty-eight patients (24 women and 24 men) fulfillingthe histopathological, clinical, and immunologicalcriteria for UC were studied. T-cell phenotype andfunction were studied in blood lymphocytes from patientswith ulcerative colitis and healthy donors by flowcytometric analysis, as well as [3H]thymidineincorporation. There were no significant differences in the percentage of T-cell subpopulations(CD3, CD4, CD8) and NK cells in the different groups.The percentage of cells in growth phase S+G2Mat two and three days of phytohemagglutinin (PHA) stimulation was significantly decreased in UCpatients, but the percentage of CD4+ andCD8+ cells in UC patients that showedapoptosis was not significantly different than that inthe control group. Proliferative responses to IL-4 also suggested that a reducedresponsiveness to this cytokine may be involved in UC.In conclusion, the impaired proliferative response toPHA of T lymphocytes from UC patients is not associated with an in vitro increase in theapoptotic response in CD4+ or CD8+cells. A reduced IL-4 response may be involved in thispeculiar mitogenic response. These changes may be pathogenic or a favorable adaptivemechanism. [ABSTRACT FROM AUTHOR]

The aims of the study were to assess the agreement between data from personal interviews and medical records on selected medical conditions, to evaluate the validity of each source of information, and to estimate the prevalence of these conditions in pancreatobiliary pathology. Between 1992 and 1995, 602 patients with pancreatobiliary diseases were included in the PANKRAS II Study. Information from interview and medical records was available in 88% of cases. The agreement between both data sources was poor only for cholecystitis and mental disorders. The validity of both sources of information was high or acceptable for all conditions except for cholecystitis. Prevalence of past medical conditions was similar to that reported previously and varied according to diagnosis, gender, age, educational level, and hospital of admission. Research aimed at assessing the prevalence of less common diseases should consider subject- and health-related factors in collecting information. [ABSTRACT FROM AUTHOR]

Several reports have confirmed that the cooperative interaction between cAMP- and Ca2+-mediated transduction pathways may contribute to the stimulatory or inhibitory regulation of Cl- secretion in intestinal epithelium. Saccharomyces boulardii has been shown to inhibit cholera toxin-induced secretion in rat jejunum. We have identified a 120-kDa protein in medium conditioned by Saccharomyces boulardii that reduces cholera toxin-induced cAMP in intestinal cells. The present study evaluated the effect of medium conditioned by Saccharomyces boulardii on cAMP- and Ca2+-mediated Cl- secretion in T84 cells. Experiments performed with cAMP agonists revealed that 1 hr of preincubation of cells with medium conditioned by Saccharomyces boulardii was necessary to elicit a 40-50% reduction in receptor (cholera toxin, prostaglandin E2, and vasoactive intestinal polypeptide) and nonreceptor (forskolin) mediated cAMP synthesis and 125I efflux. Secretion induced by carbachol was inhibited when cells were pretreated for 1 hr with medium conditioned by Saccharomyces boulardii despite the absence of inhibition of Ins (1,4,5)P3. From this study we conclude that Saccharomyces boulardii exerts an inhibitory effect in vitro on Cl- secretion mediated through both cAMP- and Ca2+-mediated signaling pathways. [ABSTRACT FROM AUTHOR]

Reactive oxygen species (ROS) are implicated in the pathogenesis of chemically induced gastric mucosal injury. We have investigated the effects of ethanol, hydrochloric acid (HCl), and sodium hydroxide (NaOH) on: (1) enhanced production of ROS including superoxide anion and hydroxyl radicals, (2) modulation of intracellular oxidized states by laser scanning confocal microscopy, and (3) DNA fragmentation, indices of oxidative tissue, and DNA damage in a primary culture of normal human gastric mucosal cells (GC), which were isolated and cultured from Helicobacter pylori-negative endoscopic biopsies from human subjects. The induction of ROS and DNA damage in these cells following exposure to ethanol (15%), HCl (150 mM) and NaOH (150 mM) were assessed by cytochrome c reduction (superoxide anion production), HPLC detection for enhanced production of hydroxyl radicals, changes in intracellular oxidized states by laser scanning confocal microscopy, and DNA damage by quantitating DNA fragmentation. Furthermore, the protective ability of bismuth subsalicylate (BSS) was assessed at concentrations of 25, 50, and 100 mg/liter. Incubation of GC with ethanol, HCI, and NaOH increased superoxide anion production by approximately 8.0-, 6.1-and 7.1-fold and increased hydroxyl radical production by 13.3-, 9.6-, and 8.9-fold, respectively, compared to the untreated gastric cells. Incubation of GC with ethanol, HCl, and NaOH increased DNA fragmentation by approximately 6.7-, 4.3-, and 4.8-fold, respectively. Approximately 20.3-, 17.5-, and 13.1-fold increases in fluorescence intensities were observed following incubation of gastric cells with ethanol, HCl, and NaOH, respectively, demonstrating dramatic changes in the intracellular oxidized states of GC following exposure to these necrotizing agents. Preincubation of GC with 25, 50, and 100 mg/liter of BSS decreased ethanol-induced increases in intracellular oxidized states in these cells by 36%, 56%, and 66%, respectively, demonstrating a concentration-dependent protective ability by BSS. Similar results were observed with respect to BSS in terms of superoxide anion and hydroxyl radical production, and DNA damage. The present study demonstrates that ethanol, HCl, and NaOH induce oxidative stress and DNA damage in GC and that BSS can significantly attenuate gastric injury by scavenging these ROS. [ABSTRACT FROM AUTHOR]

We investigated the effects of 16,16-dimethyl prostaglandin E2 on the production of tumor necrosis factor-alpha and interleukin-1beta in human monocytes stimulated with Helicobacter pylori. Monocytes isolated from human peripheral blood were incubated for 24 hr with the extract of H. pylori diluted 1:100 to 1:100,000 by volume, a combination of the extract and 16,16-dimethyl prostaglandin E2, or a vehicle alone. The extract stimulated the production of tumor necrosis factor-alpha and interleukin-1beta and the expression of their messenger RNA in a dose-dependent manner. 16,16-Dimethyl prostaglandin E2 inhibited the production of these cytokines and their messenger RNA in the presence of H. pylori at doses higher than 10(-6) M, predominantly with tumor necrosis factor-alpha. These data suggest that antiinflammatory effects of prostaglandins on gastric mucosa are in part related to their effects on inhibition of production of proinflammatory cytokines by monocytes. [ABSTRACT FROM AUTHOR]

Adequate nutritional support can enhance theprotective action of growth hormone in radiation-inducedmucositis. Our aim is to address the evolutionarypattern of radiation injury to the small intestine of rats fed a high-protein diet and treatedwith growth hormone before irradiation. Male Wistar ratswere fed a high-protein diet and killed two, four orseven days after irradiation. Animals were given either growth hormone or saline. Thecombination of growth hormone and high-protein dietreduced mortality, increased mucosal height and cryptproliferation, and reduced apoptosis from day 2 to day7 after irradiation. Bacterial translocation wasincreased in rats fed the high-protein formula.Insulin-like growth factor was reduced by radiation andfurther reduced by the high-protein diet. Thecombination of growth hormone and high-protein dietprotects from the damage caused by radiation to thebowel and accelerates its recovery. This effect does notseem to be mediated through insulin-like growth factor levels. [ABSTRACT FROM AUTHOR]

Noninvasive tests for Helicobacter pylori are increasingly used. Recently, an enzyme immunoassay for H. pylori detection in feces has been put on the market. Aim of this multicenter study was to evaluate the usefulness of this novel test as a predictor of H. pylori status in the pretreatment setting. Three hundred consecutive patients were enrolled. None of the patients had received any eradicating treatment in the last 12 months, and all underwent gastroscopy with biopsies of the antrum and body for histology (H) and rapid urease test (RUT). H. pylori status was defined positive (or negative) if both H and RUT were positive (or negative). When H and RUT gave conflicting results, the patients were classified as H. pylori-indeterminate. A stool specimen was collected for each patient and tested by using a novel enzyme immunoassay for H. pylori detection (HpSAT). Sensitivity, specificity, and diagnostic accuracy of the test were calculated, as was the cost of each assay. H. pylori status was positive in 159 patients, negative in 131, and indeterminate in 10. HpSAT gave evaluable results (positive or negative) in 293 patients, and doubtful results in 7 (2.3%). Sensitivity, specificity, and diagnostic accuracy of HpSAT were 96.8%, 89.7%, and 93.6% respectively. Considering the H. pylori-indeterminate patients as positive, the percentages were 95.8%, 98.7%, and 93.2% respectively. The cost for each assay was about US $27. These results suggest that HpSAT is a noninvasive, simple, reliable, fast, and cheap method for evaluating H. pylori status in the pretreatment setting. [ABSTRACT FROM AUTHOR]

Ambulatory 24-hr esophageal pH monitoring is considered the gold standard for diagnosing gastroesophageal reflux disease (GERD). The current approach is to encourage patients to pursue their everyday activity in order to obtain near-physiological recordings. However, the effect of the test itself on reflux-provoking activities has never been evaluated. Thus, the aim of our study was to assess daily food consumption, habits, symptoms, sleep, and perceived experience of patients undergoing pH testing as compared to an off test (normal) day. Patients reported type and time spent in each activity pursued, food ingested and length of each meal, habits, frequency and severity of GERD and other related symptoms, sleep disturbances, side effects, and overall perceived experience during pH testing and four weeks later, during a normal day. Fifty-four patients enrolled. pH testing significantly reduced time spent being active, number of meals and cups of coffee consumed, and frequency of GERD symptoms. Almost half of the patients reported having dysphagia during the test. Most patients experienced side effects and stated that the test bothered them most of the time. In conclusion, pH testing has a significant effect on decreasing reflux-provoking activities-patients tend to assume a more sedentary lifestyle. This may influence the reliability of the test as a physiologic measure of acid reflux. [ABSTRACT FROM AUTHOR]

Glutathione plays a role in gastric mucosalprotection and the glutathione level is elevated in someforms of gastritis. We studied the relevance ofglutathione for the penetration ofN-methyl-N-nitro-N-nitrosoguanidine in the glandular mucosa of the stomach. MaleWistar rats were treated with glutathione (0.5 mmol/kgintravenously), N-acetylcysteine (0.5 mmol/kgintravenously), or L-buthionine-[S,R,]-sulfoximine (BSO, 2 mmol/kg intraperitonealy), before the gastricmucosa was exposed toN-[3H]methyl-N-nitro-N-nitrosoguanidine for10 min. Penetration of the carcinogen was evaluated bylight microscopic identification of cells labeled with bromodeoxyuridine andN-[3H]methyl-N-nitro-N-nitrosoguanidine(double-labeled cells). Thiol substances were quantifiedby reversed-phase ion-pair liquid chromatography and fluorescence detection. The percentagedouble-labeled cells was higher in antrum mucosa (11.7± 3.1%) than in corpus mucosa (1.1 ± 0.2%)(P < 0.05). Total glutathione level was 1853 ±101 nmol/g in antrum and 1560 ± 76 nmol/g in corpusmucosa. BSO administration reduced the amount ofglutathione in antrum to 495 ± 14 nmol/g (P <0.05) and reduced the percentage double-labeled cells inantrum mucosa to 6.1 ± 1.3% (P < 0.05). Apositive correlation was found between the percentage ofdouble-labeled cells in the antrum mucosa and the totalamount of glutathione (r = 0.451, P = 0.002), and the amount of reduced glutathione (r = 0.449,P = 0.002). Glutathione modulation effects thepenetration ofN-[3H]methyl-N-nitro-N-nitrosoguanidine inthe antrum but not in the corpus mucosa. Thiols do not explain the different penetrationof carcinogen in antrum and corpus mucosa. [ABSTRACT FROM AUTHOR]

The protective effects of the proton pump inhibitor lansoprazole on gastric mucosal damage induced by ethanol-HCl or hemorrhagic shock were investigated in the present study. The morphometric analysis of gastric histological sections revealed that lansoprazole dose-dependently reduced mucosal injury evoked by ethanol-HCl (ED50 = 24.3 micromol/kg) or hemorrhagic shock (ED50 = 38.9 micromol/kg), these effects being associated with marked increments of Alcian blue recovery from gastric bound mucus (ED50 = 31.4 micromol/kg and 27.6 micromol/kg, respectively). In addition, lansoprazole inhibited gastric acid secretion from pylorus-ligated rats (ED50 = 9.8 micromol/kg). Further experiments, performed on rats with ethanol-HCl-induced gastric injury, indicated that the protective effects of lansoprazole were not modified by L-365,260, suramin, N(G)-nitro-L-arginine, or systemic ablation of capsaicin-sensitive sensory nerves, whereas they were partly blocked by indomethacin and fully prevented by N-ethyl-maleimide. In addition, lansoprazole did not modify somatostatin concentrations in gastric mucosa. The present results provide evidence that lansoprazole prevents the necrotic damage of gastric mucosa induced by ethanol-HCl or hemorrhagic shock. According to the rank order of ED50 values, these effects appear to depend mainly on the enhancement of the gastric mucus barrier rather than on the reduction of acid secretion. It is also proposed that an increased production of prostaglandins, as well as an increased availability of sulfhydryl compounds at level of gastric mucosa may account for the gastroprotective effects of lansoprazole. [ABSTRACT FROM AUTHOR]

Intramural injection of peptidoglycan-polysaccharide (PG-PS) induces acute enterocolitis that spontaneously relapses in Lewis but not Fischer rats. Interleukin-1 (IL-1) and tumor-necrosis factor-alpha (TNF-alpha) induce prostaglandin E2 (PGE2) secretion, which inhibits secretion of these cytokines by macrophages, suggesting an inhibitory feedback mechanism. We postulate that Lewis rat susceptibility to relapse is due to an imbalance between protective prostaglandins and cytokines. Female Fischer and Lewis rats were injected with PG-PS (37.5 microg/g) or human serum albumin intramurally. Tissue IL-1alpha and PGE2 immunoreactivities and myeloperoxidase (MPO) activity were determined. Relapsing rats had lower PGE2 and PGE2:IL-1alpha ratios than nonrelapsing rats (P < 0.05). In Fischer rats, 2 mg/kg/day indomethacin potentiated cecal MPO and IL-1alpha concentrations above PG-PS alone (P < 0.05). Misoprostol treatment blocked PG-PS-induced IL-1alpha and MPO and inhibited the potentiating effect of indomethacin on MPO and IL-1alpha (P < 0.05). In conclusion, increased endogenous PG may be protective against relapsing inflammation in PG-PS induced enterocolitis, at least partially via inhibition of proinflammatory cytokines. An imbalance between protective prostaglandins and proinflammatory cytokines may be involved in the pathogenesis of chronic relapsing inflammation in genetically susceptible hosts. [ABSTRACT FROM AUTHOR]

An impaired oxidation of butyrate has beensuggested as a causative factor of ulcerative colitisand, moreover, agents present in colonic luminalcontents impair butyrate oxidation in both rat and human colonocytes. To evaluate the overall effect offeces on the production of CO2 and ketonebodies from butyrate oxidation in rat colonocytes, fecalhomogenates from 10 healthy subjects and 10 patients with quiescent and 10 patients with activeulcerative colitis were sterile filtrated and added torat colonocytes incubated with 2, 4, and 10 mmol/literof stock butyrate, respectively. Addition of fecal filtrate from healthy subjects and patientswith quiescent and active ulcerative colitis tocolonocytes incubated with 2, 4, and 10 mmol/liter ofstock butyrate, respectively, tended to decrease theproduction of CO2 from butyrate oxidation,whereas ketogenesis was unaffected. The decrease inCO2 production was not explained by thesimultaneous addition of fecal short-chain fatty acids(SCFAs). However, a difference in the ability todecrease CO2 production was not found betweenfiltrates from healthy subjects and patients withquiescent and active ulcerative colitis. In conclusion, feces from healthy subjects and patients withquiescent and active ulcerative colitis containinhibitor(s) of the production of CO2 frombutyrate oxidation in colonocytes. However, a specific inhibitory effect of feces from patients withulcerative colitis on the production of CO2could not be identified. [ABSTRACT FROM AUTHOR]

The effects on gastric pH of a single administration of 200 mg cimetidine (Tagamet HB) were compared to multiple doses of a liquid antacid (Mylanta) using a pH microelectrode. Gastric pH was monitored for 8 hr in 20 normal fasting volunteers in a crossover design to compare Tagamet HB (two 100-mg tablets administered as a single dose) with Mylanta Suspension, an initial 17.5-ml dose of antacid with additional doses given when gastric pH fell below 3.5. Both treatments increased the pH above 3.5 during the first hour following treatment, with Mylanta being more effective than Tagamet HB. Interestingly, to sustain the reduction in acidity during this 1-hr interval, a mean of 2.45 doses of antacid were administered. Although multiple doses of Mylanta kept the pH above 3.5 (for at least 25% of the time) for the first 4 hr, the single administration of 200 mg of Tagamet HB maintained gastric pH above 3.5 (greater than 25% of time) for the full 8 hr of the study. Compared to Mylanta, the percent of time gastric pH was >3.5 was significantly higher with Tagamet HB during the 3rd to 8th hour after dosing. This study demonstrates that 200 mg of cimetidine administered as Tagamet HB is significantly more effective and has a much longer duration of action in raising gastric pH >3.5 than six doses of Mylanta. [ABSTRACT FROM AUTHOR]

Granulocyte elastase (GE) is a powerful proteolytic enzyme that is released by PMNs when degranulated in infectious processes. The aim of this study was to measure GE in ascites and plasma of cirrhotic patients with spontaneous bacterial peritonitis (SBP). We studied 29 cirrhotic patients, 17 of them having SBP (group A). Twelve patients with noninfected ascites formed the control group (group B). At the time of diagnosis of SBP, GE levels in ascites (183.17 +/- 86.11 microg/liter) and plasma (114.6 +/- 35.99 microg/liter) were higher in group A than in group B (27.41 +/- 11.54 microg/liter, P < 0.00001 and 82.54 +/- 20.52 microg/liter, P = 0.01, respectively). Levels of GE in ascites had a high value for discriminating between patients with and without SBP. In the patients who responded to the initial antibiotic treatment, these values significantly decreased in ascites (67.69 +/- 54.22 microg/liter, P = 0.003) and plasma (67 +/- 22.39 microg/liter, P = 0.01) 48 hr after therapy was started, in parallel with the decrease of PMN in ascites. In patients who did not respond, the production of GE remained elevated. Patients who developed renal insufficiency following SBP had more marked elevation of GE in plasma (144.8 +/- 33.43 microg/liter) than those with normal renal function (99.5 +/- 27.53 microg/liter, P = 0.02). These results suggest that the measurement of GE may be helpful for the diagnosis of SBP in patients with cirrhosis and for assessing the efficacy of therapy. In addition, the release of GE into plasma may contribute to the impairment of renal function that follows SBP in some patients. [ABSTRACT FROM AUTHOR]

We assessed the sensitivities of several methods for detecting Helicobacter pylori (culture, histology, rapid urease test, and serology), and evaluated the H. pylori positivity considering the degree of atrophy in the background mucosa in 202 gastric cancer patients and 101 controls. The positivity of H. pylori determined by culture (81%) was significantly higher than that determined by serology (62%) in gastric cancer patients (P < 0.001). The positivities of H. pylori determined by biopsy and/or serology in intestinal (84%) and diffuse (95%) types of gastric cancer were higher than that observed in controls (54%) (P < 0.001). Intestinal-type gastric cancer tended to occur in the atrophic mucosa, in which H. pylori positivity was not different from that in controls after adjusting for the degree of atrophy, whereas diffuse-type gastric cancer was observed more often in the nonatrophic mucosa, in which H. pylori positivity was higher than that in controls even after adjusting for the degree of atrophy. [ABSTRACT FROM AUTHOR]

Somatic activating mutations at codon 12 of the K-ras gene are present in the majority of exocrine pancreatic cancers and occur early in tumorgenesis. The aim of this study was to test the feasibility of using a mutated K-ras gene from the serum as a potential tumor marker for detection of exocrine pancreatic carcinoma. Codon 12 K-ras mutations were examined in DNA extracted from the sera of 20 patients with pancreatic carcinomas, six patients with chronic pancreatitis, and five healthy individuals. K-ras gene mutations at codon 12 were detected in the sera of 14 of 20 patients with pancreatic carcinoma and in none of the six patients with chronic pancreatitis, or in the five healthy controls. Elevation of either CA19-9 or K-ras mutation was detected in 19/20 patients. These results suggest that K-ras abnormalities in serum could be used as a potential tumor marker in patients with a pancreatic lesion. The absence of K-ras mutations in serum and presence of CA19-9 in the normal range make the diagnosis of pancreatic cancer unlikely. [ABSTRACT FROM AUTHOR]

Gestational maturation of gastrointestinalmotility is a key factor in readiness of the pretermneonates for enteral nutrition. Since gastric motilitymainly depends on the electrical activity of the smooth muscle cells, it was of interest to investigatethe developmental aspects of electrical activity of thestomach. The latter was recorded weekly throughcutaneous electrogastrography in 27 preterm infants (aged 29-34 weeks of gestation). Recordingswere done for 1 hr before and 1 hr after meal. Theelectrogastrographic variables measured were: percentageof normal gastric rhythm, i.e., 2-4 cpm; percentage of tachygastria (>4 cpm); the fed-to-fastingratio of the dominant electrogastrographic power; andthe instability coefficient of the dominant frequency.Data were compared with those measured in 10 full-term infants. Peaks of normal electricalactivity (2-4 cpm) were present in most of therecordings at all the gestational ages; however,percentages of both normal electrical rhythm andtachygastria in preterm infants were similar to thosemeasured in full-term infants (mean ± SD) (normalrhythm; fasting: 70.2 ± 3.8, fed: 72.2 ±5.0; tachygastria: fasting: 24.6 ± 4.0, fed: 19.1± 3.5) by 35 weeks of gestation (normal rhythm; fasting:67.5 ± 2.0, fed: 69.6 ± 4.4; tachygastria:fasting: 27.1 ± 4.0, fed: 25.6 ± 4.1). Thecoefficient of instability of the dominant frequency inpreterm infants was also similar to the value measuredin full-term infants by 35 weeks of gestation, whereasthe EGG power showed a significant increase in thepostprandial state at all the gestational ages. We conclude that a maturation pattern of theelectrical activity of the stomach can be detected bymeans of a noninvasive tool such as cutaneouselectrogastrography: a normal electrical rhythm can bedetected at very early gestational ages; however, thisactivity becomes dominant at around the 35 weeks ofgestational age. In preterm infants developmentalchanges of gastric electrical activity are a function of advancing postnatal age. [ABSTRACT FROM AUTHOR]

We have demonstrated that in rats subjected topartial hepatectomy (PH), the regenerating liver had anenhanced metabolism of ethanol, which largely dependedon the route and timing of ethanol administration. Therefore, the influence of the administrationroute and timing for ethanol-induced deleterious effectson the regenerating rat liver was evaluated in animalssubjected to 70% PH. Remnant liver showed moderate fatty infiltration, extended distortion ofhepatocellular structure, and high mitotic index.Intragastric ethanol administration (1.5 g/kg bodyweight) considerably reduced the PH-induced changes inliver structures. Ethanol treatment also decreasedliver thymidine kinase activity, serum albumin, andglucose levels. Intraperitoneal administration of thesame ethanol dose to PH rats promoted lesser alterations on liver regeneration. Independently of itsadministration route, ethanol abruptly shortened aPH-induced selective increase in serum enzymeactivities. These data suggest that the inhibitoryeffect of a low dose of ethanol on PH-induced liverregeneration is dependent on the timing and route ofadministration. [ABSTRACT FROM AUTHOR]

The role of oxidative stress in the regulation of intestinal epithelial proliferation was examined by evaluating the effect of H2O2 and xanthine oxidase + xanthine (XO + X) on [3H]thymidine incorporation into DNA in Caco-2 cells. DNA synthesis was highest 4 and 5 days after seeding, while it declined rapidly between 5 and 12 days. Pretreatment for 0.5-24 h with H2O2 or XO + X reduced DNA synthesis on 4- to 6-day-old, but not on 7- to 20-day-old cells. The effect of XO + X on DNA synthesis was significantly reduced by catalase, superoxide dismutase, and ferric chloride, but pretreatment with deferoxamine potentiated XO + X-induced inhibition of DNA synthesis. Coadministration of epidermal growth factor (EGF) for 24 hr reduced the H2O2 and XO + X-induced inhibition of DNA synthesis; this effect of EGF was not observed up to 8 hr. Results show that O2- and H2O2 rapidly inhibit DNA synthesis in Caco-2 cells and that EGF restores DNA synthesis in oxidant-treated cells. [ABSTRACT FROM AUTHOR]

Five patients with gastroesophageal reflux disease (GERD), who also had chronic functional diarrhea and postprandial urgency, unexpectedly noted rapid relief of their diarrhea and urgency when they took lansoprazole for their heartburn. To determine if this surprising result was not fortuitous, all 20 patients seen during the next six months for chronic diarrhea and postprandial urgency due to irritable bowel syndrome (IBS) or functional diarrhea were treated with inhibitors of gastric secretion: 14 with proton-pump inhibitors and 6 with H2 blockers. All patients had rapid, marked improvement. Usually within three days, their symptoms abated and they usually had one to three formed stools per day. Relief continued during the one to six months they were followed on therapy. Five patients stopped therapy, had recurrent diarrhea, and rapid relief upon resuming therapy. Thus, inhibition of gastric secretion effectively controls the diarrhea and postprandial urgency associated with IBS or functional diarrhea, probably by diminishing the gastrocolic or gastroenteric reflex. [ABSTRACT FROM AUTHOR]

The small intestine's large capacity for glucose absorption and for adaptation seems to contradict the reported importance of carbohydrate malabsorption in short bowel (SB) patients. The aim of the present study was to investigate the occurrence of malabsorption in these patients ingesting realistic amounts of carbohydrates. We performed a dose-response study [ingestion of increasing amounts of glucose and complex carbohydrates (boiled rice and wheat bread), and the nonabsorbable disaccharide lactulose] in SB patients with an intact colon. The hydrogen (H2) -breath test and changes in serum acetate were used to evaluate colonic fermentation and, thus, indirectly, the lack of small intestinal carbohydrate assimilation. Blood glucose and plasma insulin were measured to evaluate absorption. Plasma concentrations of the ileal brake hormones--glucagon-like peptide-1 (GLP-1) and peptide tyrosine tyrosine (PYY)--were measured to test whether release of these hormones was related to colonic fermentation. Significant amounts of 25 g and 50 g glucose, and of the bread and rice meals were fermented rather than absorbed, as judged by the increases in end-expiratory H2. Serum acetate concentrations were significantly higher in SB patients than in healthy controls. The orocecal transit times of all test meals ranged from 15 to 120 min. GLP-1 and PYY releases in SB patients were significantly higher than in healthy volunteers. They were mutually parallel and paralleled the increase in insulin. They were not related to ongoing fermentation or to intraluminal carbohydrate content per se, but most probably to absorption of glucose in the distal bowel. In conclusion, well-adapted SB patients had pronounced small intestinal malabsorption of carbohydrate, even after ingestion of small amounts of easily absorbable carbohydrates. A fast small intestinal spreading of carbohydrates, once in the small intestine, and a spill-over to the colon seem to explain the data best. [ABSTRACT FROM AUTHOR]

The participation of xanthine-xanthine oxidase and neutrophils in the development of acute gastric mucosal lesions was examined in rats injected once with compound 48/80, a mast cell degranulator. Gastric mucosal lesions appeared 0.5 hr after compound 48/80 injection and developed at 3 hr. The formation of gastric mucosal lesions at 0.5 hr after compound 48/80 injection was prevented by pretreatment with anti-neutrophil antiserum and NPC 14686, an antiinflammatory agent, but not with allopurinol, a xanthine oxidase inhibitor. The development of gastric mucosal lesions at 3 hr after compound 48/80 injection was prevented by pretreatment with anti-neutrophil antiserum, NPC 14686, or allopurinol. Increases in the activities of gastric mucosal xanthine oxidase and myeloperoxidase, an index of neutrophil infiltration, and the content of lipid peroxide occurred 0.5 hr after compound 48/80 injection, and these increases were enhanced at 3 hr. The increases in gastric mucosal myeloperoxidase activity and lipid peroxide content at 0.5 hr after compound 48/80 injection were attenuated by pretreatment with anti-neutrophil antiserum and NPC 14686, while only the increase in gastric mucosal xanthine oxidase activity at the same time point was arrested by allopurinol pretreatment. The increases in gastric mucosal xanthine oxidase and myeloperoxidase activities and lipid peroxide content at 3 hr after compound 48/80 treatment were attenuated by pretreatment with anti-neutrophil antiserum, NPC 14686, or allopurinol. When compound 48/80-injected rats were treated with allopurinol at 0.5 hr after compound 48/80 injection, the progression of gastric mucosal lesions at 3 hr after the injection was almost completely prevented with inhibition of the increases in gastric mucosal xanthine oxidase and myeloperoxidase activities and lipid peroxide content. These results indicate that in rats with a single compound 48/80 treatment neutrophils infiltrated into the gastric mucosa participated in the development of acute gastric mucosal lesions and that the xanthine-xanthine oxidase system in the gastric mucosa participated in the progression rather than the formation of the gastric mucosal lesions. [ABSTRACT FROM AUTHOR]

In our clinical experience, postprandialsymptomatic hypoglycemic (PSH) patients with H. pylorigastritis showed a substantial improvement in theirhypoglycemic symptoms after the eradication of H.pylori. Therefore, in this study we have investigatedwhether H. pylori gastritis may contribute to theoccurrence of PSH. For this purpose, we have evaluatedthe following parameters in 12 PSH patients with H. pylori gastritis before and one month afterthe eradication therapy: (1) the number and severity ofPSH attacks that occurred in a one-month period using a30-day diary, (2) the total symptom score following a mixed meal using a visual analog scalequestionnaire (VASQ), and (3) the glucose and insulinresponses to the mixed meal. After the eradication of H.pylori, the serum insulin responses at 30 and 60 min decreased (P < 0.001 in both), whereasthe plasma glucose levels at 150, 180 and 210 minincreased significantly (P < 0.001 for 180 min and P< 0.01 in others) following the mixed meal. The number and severity score of PSH attacks thatoccurred in a one-month period and the area under curvefor symptom score in VASQ decreased significantly (P< 0.001 in all). These results suggest that H. pylori gastritis may contribute to theoccurrence of PSH. [ABSTRACT FROM AUTHOR]

Ischemic colitis is a serious complication ofaortic surgery. The condition continues to be difficultto diagnose at an early stage. This study monitors thebiochemical changes in systemic and selective inferior mesenteric vein (IMV) blood samplingduring aortic surgery and compares the reproducibilityof this method to intraoperative colonic pulse oximetryin a series of 18 patients undergoing infrarenal aortic aneurysm repair. Base excess, pH,pCO2, and lactate were altered by aorticcross-clamping but returned to normal within 48 hr. IMVinorganic phosphate levels were higher than systemic values, suggesting improved sensitivity withselective sampling. BB isoenzymes of creatine kinaseremained normal in all patients. Pulse oximetry signalswere inconsistently obtained from the colon. This study establishes the physiological changes inIMV biochemistry during aortic surgery. Unlikeintraoperative pulse oximetry, selective IMV samplingprovides reproducible measurements of colonic perfusion. This simple and safe technique warrants furtherassessment of its accuracy at diagnosing ischemiccolitis. [ABSTRACT FROM AUTHOR]

Self-expanding metal stents are being used more commonly to prevent biliary tract obstruction. Silicone-covered self-expanding metal stents (Wallstent, Schneider, Inc.) have been developed to prevent tumor ingrowth. Biofilm formation and occlusion material in silicone-covered self-expanding metal stents compared to standard polyethylene stents were examined in an in vitro model. Matched pairs of polyethylene and silicone-covered metal stents were perfused with infected bile for 8, 12, and 16 weeks at a rate of 0.5 cc/min at 37 degrees C. Two reservoirs fitted with silicone-covered metal stents had ampicillin/sulbactam added and were perfused for 16 weeks. The stents were then analyzed by scanning electron microscopy and light microscopy for biofilm formation and presence of occlusion material. The two ampicillin/sulbactam-treated stents showed no biofilm formation. Biofilm was seen on all of the remaining stents. There was a difference in occlusion thickness between the 8- and 16-week polyethylene stents, and no difference between the biofilm thickness at 8, 12, or 16 weeks in the silicone-covered metal stents. Silicone-covered self-expanding metal stents will likely extend patency rates in malignant obstructive jaundice by providing a larger lumen for bile flow and allowing cyclical antibiotics to prevent bacterial biofilm formation. [ABSTRACT FROM AUTHOR]

Trypsin and chymotrypsin readily bind to human erythrocyte ghosts and to resealed right-side-out ghosts, but not to intact erythrocytes, as followed with [3H]trypsin and [3H]chymotrypsin and with cold proteases in a caseinolytic assay. The proteases freely reacted with casein in the presence of intact cells. Trypsin activated trypsinogen over an 8-hr time course at a faster rate in the presence of erythrocytes than in the absence thereof, after a slight initial delay. Trypsinogen did not bind to intact erythrocytes, thereby behaving comparably to trypsin. These results suggest that different microenvironments exist about the erythrocyte ghosts and the intact erythrocytes, thereby permitting the proteases to bind to the former but not to the latter. Hence, in the absence of considerable ghosts in circulating blood, which may mask the binding site of the proteases, the proteases may be more readily accessible for interaction with circulating serpins, leading to inactivation of the proteases and protection from their degradative potential. The presence of the serpins in circulating blood may assist in the control of the degradative power of the pancreatic proteases in pancreatitis and may negatively modulate such processes as thrombosis, activation of the complement system, and vascular remodeling. [ABSTRACT FROM AUTHOR]