Metabolomic comparison of postprandial distress syndrome patients with and without duodenal eosinophilia.

OBJECTIVE: In functional dyspepsia patients, duodenal mucosal eosinophilia has been associated with early satiety but is not present in all patients suggesting varied pathways to symptom generation. The objective of the current study was to explore metabolic differences comparing those with duodenal mucosal eosinophilia to those without eosinophilia. METHODS: This study was conducted utilizing an existing biorepository. Patients had plasma samples obtained at the time of endoscopy. All had undergone endoscopy for dyspepsia and reported early satiety. Two groups were identified including those with peak duodenal mucosal eosinophil densities above 30/high power field (N = 28) and those below 30 (N = 16). The fasting plasma samples were analyzed by liquid chromatography/high-resolution mass spectrometry. Significant differences between groups were determined. RESULTS: The eosinophilia group demonstrated significant elevations in several gamma-glutamyl amino acids. The eosinophilia group had elevations of metabolites associated with oxidative stress including glutathione metabolites (cysteinlyglycine and cys-gly oxidized), and metabolites related to nitric oxide synthesis (arginine, citrulline, ornithine, and dimethylarginine). Eosinophilia was also associated with alterations in lipid metabolism including several long-chain acylcarnitine conjugated fatty acids. Carnitine levels were lower in the eosinophilia group. Lastly, vanillymandelate, a derivative of norepinephrine and epinephrine was elevated in the eosinophilia group. CONCLUSIONS: In patients with dyspepsia and early satiety, duodenal mucosal eosinophilia is associated with metabolites levels which are consistent with increased oxidative stress and alterations in lipid metabolism. Eosinophilia was also associated with lower carnitine levels. These alterations may contribute to pathophysiology and represent therapeutic targets.

[Lemmel's syndrome: report of a case]. / Síndrome de Lemmel: reporte de un caso.

Lemmel's syndrome is a very rare condition as a cause of obstructive jaundice secondary to the presence of a duodenal diverticulum. We report a case, a 68-year-old female patient with a cholestatic pattern, biliary tract dilatation, who underwent ERCP, with a juxtapapillary diverticulum compressing the distal bile duct, which was sphincterotomy.

Association between an increase in blood urea nitrogen at 24 hours and worse outcomes in acute nonvariceal upper GI bleeding.

BACKGROUND AND AIMS: An increase in blood urea nitrogen (BUN) at 24 hours is a solitary and significant predictor of mortality in patients with acute pancreatitis, which may predict worse outcomes in the similarly resuscitation-requiring condition of acute nonvariceal upper GI bleeding (UGIB). The aim of our study was to assess whether an increase in BUN at 24 hours is predictive of worse clinical outcomes in acute nonvariceal UGIB. METHODS: A retrospective cohort study including patients admitted to an academic hospital from 2004 to 2014 was conducted. An increase in BUN was defined as an increase in BUN at 24 hours of hospitalization compared with BUN at presentation. The primary outcome was a composite of inpatient death, inpatient rebleeding, need for surgical or radiologic intervention, or endoscopic reintervention. Associations between BUN change and outcomes were assessed via the Pearson χ2 test and the Fisher exact test and via logistic regression for adjusted analyses. RESULTS: There were 357 patients included in the analysis with a mean age of 64 years; 54% were men. The mean change in BUN was -10.1 mg/dL (standard deviation, 12.7 mg/dL). Patients with an increased BUN (n = 37 [10%]) were significantly more likely to experience the composite outcome (22% vs 9%, P = .014), including an increased risk of inpatient death (8% vs 1%, P = .004), compared with patients with a decreased or unchanged BUN (n = 320 [90%]). In a logistic regression model adjusting for the AIMS65 score, an increase in BUN was independently associated with an increased risk for the composite outcome (odds ratio, 2.75; P = .026). CONCLUSION: Increasing BUN at 24 hours likely reflects under resuscitation and is a predictor of worse outcomes in patients with acute nonvariceal UGIB.

Relationship of time to presentation after onset of upper GI bleeding with patient characteristics and outcomes: a prospective study.

BACKGROUND AND AIMS: We performed a prospective multi-national study of patients presenting to the emergency department with upper GI bleeding (UGIB) and assessed the relationship of time to presentation after onset of UGIB symptoms with patient characteristics and outcomes. METHODS: Consecutive patients presenting with overt UGIB (red-blood emesis, coffee-ground emesis, and/or melena) from March 2014 to March 2015 at 6 hospitals were included. Multiple predefined patient characteristics and outcomes were collected. Rapid presentation was defined as ≤6 hours. RESULTS: Among 2944 patients, 1068 (36%) presented within 6 hours and 576 (20%) beyond 48 hours. Significant independent factors associated with presentation ≤6 hours versus >6 hours on logistic regression included melena (odds ratio [OR], 0.22; 95% CI, 0.18-0.28), hemoglobin ≤80 g/L (OR, 0.47; 95% CI, 0.36-0.61), altered mental status (OR, 2.06; 95% CI, 1.55-2.73), albumin ≤30 g/L (OR, 1.43; 95% CI, 1.14-1.78), and red-blood emesis (OR, 1.29; 95% CI, 1.06-1.59). Patients presenting ≤6 hours versus >6 hours required transfusion less often (286 [27%] vs 791 [42%]; difference, -15%; 95% CI, -19% to -12%) because of a smaller proportion with low hemoglobin levels, but were similar with regard to hemostatic intervention (189 [18%] vs 371 [20%]), 30-day mortality (80 [7%] vs 121 [6%]), and hospital days (5.0 ± 0.2 vs 5.0 ± 0.2). CONCLUSIONS: Patients with melena alone delay their presentation to the hospital. A delayed presentation is associated with a decreased hemoglobin level and increases the likelihood of transfusion. Other outcomes are similar with rapid versus delayed presentation. Time to presentation should not be used as an indicator for poor outcome. Patients with delayed presentation should be managed with the same degree of care as those with rapid presentation.

Gastrointestinal bleeding in adult patients with Henoch-Schönlein purpura.

We investigated the clinical and endoscopic features of gastrointestinal lesions in adults with Henoch-Schönlein purpura (HSP) causing gastrointestinal bleeding. The study included 24 adult HSP patients with gastrointestinal hemorrhage who underwent both upper gastrointestinal endoscopy and colonoscopy. The controls were 27 adult HSP patients without gastrointestinal hemorrhage. Patients with gastrointestinal bleeding showed higher frequencies of purpura on the upper extremities and trunk, and of elevated serum C-reactive protein (CRP). The rate of concurrent lesions in both the upper and lower gastrointestinal tracts was 91.7 %. The second portion of duodenum and terminal ileum were most frequently and severely involved. Leukocytoclastic vasculitis was detected in severe lesions and was significantly associated with mucosal ischemic changes. Most lesions (95.7 %) dramatically improved after corticosteroid therapy. This study suggests that both upper and lower gastrointestinal examinations are necessary for proper evaluation of gastrointestinal bleeding in patients with HSP.

Classification of intestinal lymphangiectasia with protein-losing enteropathy: white villi type and non-white villi type.

BACKGROUND/AIMS: We classified intestinal lymphangiectasia (IL) into two categories, the white and non-white villi types, and evaluated their clinical characteristics and therapeutic responses. METHODS: Of the 988 patients who underwent double-balloon enteroscopy, 14 consecutive patients (7 men and 7 women, median age at onset 34 years) were enrolled with immunohistochemically confirmed IL with protein-losing enteropathy. RESULTS: Enteroscopically the white villi type (n = 8) showed white plaques and white-tipped villi were scattered in the small bowel, while non-white villi type (n = 6) showed that apparently normal but under more detailed observation, low and round villi with a normal color were diffused. The serum albumin levels and fecal α1-antitrypsin clearance before treatment were significantly worse in the non-white villi type (p = 0.017 and 0.039, respectively), whereas the serum immunoglobulin A and M levels were significantly lower in the white villi type (p = 0.010 and 0.046, respectively). At gastroscopy, a non-cirrhotic snakeskin appearance was significantly observed in the non-white villi type (p = 0.015). The corticosteroid response was better in the non-white villi type (p = 0.015). CONCLUSION: Two distinct subgroups were found in IL. This classification was useful in pathophysiological clustering and in predicting the therapeutic response.

[IgE-antibodies to Helicobacter pylori in children with gastroduodenal diseases and concomitant of allergy].

In children with chronic gastritis/gastroduodenitis (CG/CGD), ulcerative and erosive processes of mucous and associated allergic diseases IgM, IgA, IgG, and IgE to the H. pylori were determined by ELISA in the blood serum. IgM-antibodies to H. pylori were found in isolated cases and did not present a diagnostic significance. IgG-antibodies were detected in all children in the same percentage (40-50%), pointing indirectly to the widespread contamination by H. pylori. IgA-antibodies to H. pylori with high frequency (83% and 57%) were found in the blood serum of children with the diseases of gastroduodenal zone without allergies, while in children with allergic pathology they were found by 3-4 times less (20%). IgE antibodies to H. pylori were determined in a high percentage of cases in healthy children (86%) and allergic children (75%), while children without allergy IgE antibodies were detected in the 54-65% of cases. In this study, the detection of IgE antibodies to H. pylori has allowed to increase the frequency of the diagnosis of helicobacteriosis cases in children with gastropathology by 16% in general and in the group of children with allergic diseases this increase amounted to 27.3%. Moreover, children with antihelicobacterial IgE antibodies in a large percentage of cases (92-94%) revealed a positive urease activity. Detection of serum IgE-antibodies to H. pylori in combination with other antibodies isotypes in children increases the diagnostic significance of determination of H. pylori infection and may be recommended when applying serodiagnosis H. pylori in children's practice, especially in children with allergic pathology.

[To the problem of evaluation of public health: screening for gastroduodenal pathology on the example of atrophic gastritis in mass medical examination of the population].

Assessment of health status of the population - the most important issue in preventive medicine. The objective of this work - to determine the possibility of nonendoscopic screening for gastroduodenal pathology, by the example of atrophic gastritis, in mass medical examinations of working residents in Moscow. Minimally invasive diagnostic test system GastroPanel ("Biohit", Finland) has been used. It allows with the ELISA method to determine both serum indicators of the function of the stomach -pepsinogen 1, gastrin 17 and the presence of H. pylori infection. 758 persons have been examined. The performed study confirms the possibility with the use of a set of mentioned indicators to identify individuals suspected for the presence of gastroduodenal disorders, especially atrophic gastritis, recognized as a precancerous condition. The use in preventive medicine complex diagnostic system, firstly, will make assessment of the health of the population more correct, increase the effectiveness of preventive measures and quality of life, and secondly, will contribute to the diagnosis of diseases of the stomach and duodenum in the early stages.

[Population association features of interleukine gene polymorphism in khakases with gastroduodenal diseases].

AIM: To investigate association of polymorphisms of IL-1 genes and antagonist of IL-2 receptor (IL1Ra). MATERIAL AND METHODS: Patients with chronic gastritis and ulcer were examined using the method of restriction analysis. RESULTS: It was found that CCILbeta and R4/R4IL1Ra are most prevalent allel variants in khakas population. CONCLUSION: It is expedient to define population risk and protective genotypes of development of ulcer associated with Helicobacter pylori in khakases.

Effects of passage through the digestive tract on incretin secretion: Before and after birth.

AIMS/INTRODUCTION: It was reported that fetuses secrete endogenous incretin; however, the stimulants of fetal incretin secretion are not fully understood. To investigate the association between the passage of amniotic fluid through the intestinal tract and fetal secretion of incretin, we analyzed umbilical cord incretin levels of infants with duodenum atresia. MATERIALS AND METHODS: Infants born from July 2017 to July 2019 (infants with duodenum atresia and normal term or preterm infants) were enrolled. We measured and compared the concentrations of glucagon-like peptide-1 (GLP-1) and gastric inhibitory peptide/glucose-dependent insulinotropic polypeptide (GIP) in the umbilical vein and preprandial blood samples after birth. RESULTS: A total of 98 infants (47 term, 46 preterm and 5 with duodenum atresia) were included. In patients with duodenum atresia, umbilical vein GLP-1 and GIP levels were the same as those in normal infants. In postnatal samples, there were positive correlations between the amount of enteral feeding and preprandial serum concentrations of GLP-1 (r = 0.47) or GIP (r = 0.49). CONCLUSIONS: Our results show that enteral feeding is important for secretion of GLP-1 and GIP in postnatal infants, whereas the passage of amniotic fluid is not important for fetal secretion of GLP-1 and GIP. The effect of ingested material passing through the digestive tract on incretin secretion might change before and after birth. Other factors might stimulate secretion of GLP-1 and GIP during the fetal period.

[Etiology and pathogenesis of duodenal mucosa lesion in chronic pancreatitis].

AIM: To measure content of neuromediators (acetylcholine-Ach, serotonin-5-NT) and gastrointestinal hormones (cholecystokinine-CCK and secretin) in the blood serum of patients with chronic pancreatitis (CP); to study protective properties of the mucus in the duodenum in CP. MATERIAL AND METHODS: CCK and secretin concentrations were estimated by enzyme immunoassay, Ach and 5-NT were measured biochemically basally and after standard meal in 65 CP patients and in the control group. Proteolytic activity of the mucus was assessed by Anson's method. An inhibitory property of the mucus was studied by residual proteolytic activity of pepsine after its incubation with mucus. RESULTS: In AP patients the response of biologically active substrates to standard meal changed: 5-NT concentration rose from 0.40 +/- 0.07 to 0.55 +/- 0.05 mcg/ml (p < 0.05) while Ach dropped from 1.7 +/- 0.3 to 1.6 +/- 0.3 mmol/l (p > 0.05). BP patients responded to the standard meal with 5-HT concentration rise from 0.28 +/- 0.04 to 0.43 +/- 0.05 mcg/ml (p < 0.05), Ach changed insignificantly (from 1.5 +/- 0.12 to 1.45 +/- 0.21 mmol/l, p > 0.05, reselectively). CCK after standard meal significantly rose both in AP and BP. AP and BP patients had strong direct correlation between concentrations of 5-HT and CCK (r = 0.875439) and weak negative correlation with Ach level (r = -0.2209). In AP and BP patients secretin level weakly negatively correlated both with 5-NT and Ach levels (r = -0.4839 and r = -0.33207, respectively). Reduction of secretin secretion diminished secretion of bicarbonates and mucus with simultaneous change in the quality of mucous gel. CONCLUSION: In CP of various etiology there are changes in the level and proportions of neuromediators and hormones causing alterations in the regulation system. These disorders correlate with disturbances in pancreatic excretory function and destructive tissue changes. Bicarbonates secretion decreases and changes quality of the secreted mucus.

[Typical changes in the electrophoretic mobility of red blood cells and their phospholipid composition in different diseases].

Changes in the electrophoretic mobility of red blood cells and their phospholipid composition were studied in patients with psoriasis and duodenal peptic ulcer. A relationship of the electrophoretic mobility of red blood cells to their phospholipids spectrum was established in the above diseases. The paper shows the same change in the electrophoretic mobility of red blood cells and a change in the fractions of phosphotidylethanolamine, sphingomyelin, lysophosphotidylcholine of the erythrocytic membranes.

Detection of α-defensin in eosinophils in helminth-infected mouse model.

α-defensin is a potent antimicrobial peptide secreted from intestinal mucosal epithelial cells, such as Paneth cells, and affects not only bacteria but also parasites and fungi. Recently, human eosinophils have also been shown to produce α-defensin, but no studies have been done on other animals. In this study, we attempted to detect α-defensin protein in mouse eosinophils infiltrating the intestinal mucosa during a helminth infection using Zamboni fixation and immunohistochemistry. Most of the eosinophils infiltrating the intestinal mucosa during helminth infection were positive for α-defensin. The expression level of α-defensin mRNA was 50 fold that in the control. Meanwhile, the number of Paneth cells was doubled, and their α-defensin fluorescence intensity was increased. These results suggested that eosinophils are also important producers of α-defensin, such as Paneth cells in mice, and that α-defensin produced from eosinophils might be involved in defensive mechanisms against helminths. Moreover, the experimental system used in this study is a good model to study the generation of α-defensin by eosinophils.

Activation of epithelial proliferation induced by Eimeria acervulina infection in the duodenum may be associated with cholesterol metabolism.

Cell proliferation in the intestine is commonly occurred during infection and inflammation to replace damaged enterocytes, and cholesterol as an essential constituent of cell membrane, is required for cell proliferation and growth. Here we found that coccidium-challenged (CC) chickens showed severe damages in intestinal structure, a significant increase of cell proliferation, and an activation of genes expression involved in the innate immune response. Compared to control (CON), CC chickens showed a marked decrease of cholesterol (Tch) level in the circulating system, but a significant increase in local duodenum epithelium. Increase of LDLR protein combined with a significant decrease of CYP27A1 protein expression in duodenum epithelium may contribute to intestinal cholesterol accumulation in CC chickens. Moreover, we found miRNAs targeting to CYP27A1 gene participating in post-transcriptional regulation. Hence, these results provide a new insight for the intervention of epithelial proliferation and cholesterol metabolism in the gastrointestinal tracts.

Hepatocyte growth factor predicts survival and relates to inflammation and intima media thickness in end-stage renal disease.

Hepatocyte growth factor (HGF) is a pleiotropic cytokine involved in tissue protection and repair in the endothelium and various organ systems. The serum concentration of this protein is markedly increased in patients with chronic renal diseases, but the clinical and pathophysiological correlates of this substance in renal failure are scarcely understood. Serum HGF, lipid, albumin, hemoglobin, C-reactive protein (CRP), and immunoglobulin G (IgG) were measured in fasting conditions in a cohort of 244 dialysis patients. In addition, the relationship between HGF and severity of carotid atherosclerosis was studied in a subgroup of 105 patients. The entire cohort was followed up for a median of 31 months (interquartile range, 21 to 34 months). Serum HGF level was directly related to duration of dialysis treatment, CRP level, age, IgG level, and hemoglobin level and inversely related to systolic and diastolic arterial blood pressure. In a multiple regression model, only duration of dialysis treatment (r = 0.38), age (r = 0.26), hemoglobin level (r = 0.17), IgG level (r = 0.15), and CRP level (r = 0.14) were independent correlates of serum HGF level (R = 0.54; P < 0.0001), suggesting that increased levels of serum HGF may be the expression of a chronic inflammatory process. HGF levels were greater in hemodialysis than continuous ambulatory peritoneal dialysis patients, independent of the type of dialysis membrane, and slightly increased in patients seropositive for hepatitis C virus. In the subgroup of patients who underwent echo color Doppler studies, serum HGF level was an independent correlate of intima media thickness (IMT; partial r = 0.23; P = 0.02). In the entire cohort, increased HGF levels predicted shorter survival in a multivariate Cox regression model. These results support the hypothesis that in patients with chronic renal failure, increased serum HGF level is linked to an inflammatory state. The relationships between HGF level and survival and IMT suggest that this cytokine might be a marker of a process that has a major impact in the high mortality and morbidity of the dialysis population.

Relationship of Helicobacter pylori infection to several malignant and non-malignant gastrointestinal diseases.

The importance of the Helicobacter pylori infection was investigated as a risk factor for several gastrointestinal diseases. In this study 203 patients with gastric cancer, 61 with peptic ulcus, 60 with gastritis and 100 asymptomatic control subjects were investigated. Serum samples were examined for IgC antibodies to H. pylori by enzyme linked immunoassay - tissue samples were stained for H. pylori by Wartin-Stary technique and by Giemsa for routine histopathology. H. pylori seropositivity was 58.1% in gastric cancer, 54% in peptic ulcus, 63.3% in gastritis and 27% in asymptomatic control group. There was a 10.1% discordance between the serum and tumor determinants in the seropositive group and 11.3% of discordance in the seronegative group. The frequency of H. pylori seropositivity was lowest in cardia tumors (22.7%) and highest in antral tumors (65.5%, p=0.00002). H. pylori seropositivity was 29% in diffuse type of histology, 35% in mixed type and 79% in the intestinal type (p=0.00000). In the gastric cancer patients the frequent use of salty food (p=0.00001, OR=6.4), excessive salt, pickled food (p=0.0000, OR=24.92) and proteins (p=0.003, OR=0.45) were more significant than asymptomatic volunteers. In gastric cancer patients the frequent use of salty and pickled food were relevantly associated with H. pylori infection (p=0.001). It was concluded that H. pylori infection could play a role in the pathogenesis of non-malignant gastrointestinal diseases which may be the precursor of carcinoma. However, other contributing factors to carcinogenesis must be investigated.

Low molecular weight protein of Helicobacter pylori and its relation to gastroduodenal diseases.

BACKGROUND/AIMS: In Taiwan, CagA and VacA cannot be used as markers to evaluate the risk of developing serious gastroduodenal pathogenesis in the hosts. Recent research suggests that the low molecular weight proteins, 35kDa and 19kDa, in Helicobacter pylori may be related to duodenal ulcers and gastric MALToma (mucosa-associated lymphoid tissue lymphoma) respectively. The aims of this study were to examine the sero-prevalence of antibodies against specific Helicobacter pylori antigen in patients with different gastroduodenal diseases and further to find possible virulence factor(s) associated with the development of clinically relevant disease in Helicobacter pylori-infected subjects in Taiwan. METHODOLOGY: Sera were obtained from 108 patients, of which 22 had gastric adenocarcinoma, 31 had non-ulcer dyspepsia and 65 had peptic ulcer disease. The sera were analyzed for specific Helicobacter pylori antigen by using one commercial kit (HelicoBlot 2.0, Genelabs Diagnostic, Singapore, HB2.0). Helicobacter pylori infection was confirmed when the culture was positive or when any two of the other three tests (biopsy CLO test, histology and 13C-urea breath test) were positive. RESULTS: The data showed a high prevalence of CagA and VacA proteins [CagA(+): gastric adenocarcinoma--88.1%, non-ulcer dyspepsia--87.1%, peptic ulcer disease--91%; VacA(+): gastric adenocarcinoma--78.6%, non-ulcer dyspepsia--58.1%, peptic ulcer disease--71.4%] in Taiwan. This is similar to the findings in other Chinese and Taiwanese studies. No significant difference was found among the three groups (P > 0.05) for any Helicobacter pylori protein. We found that antibody responses to the 26.5-kDa and 116-kDa (CagA) antigens were most prevalent in the peptic ulcer disease group. Consequently, we analyzed two special phenotypes, which have simultaneous presence in bands at 116 and 26.5kDa. The phenotype [116-kDa (+) and 26.5kDa(+)] predicted the risk of peptic ulcer disease with 76.7% sensitivity and 62% specificity. CONCLUSIONS: We confirm the universal prevalence of CagA and VacA-positive Helicobacter pylori infection in Taiwan independent of disease. Although we did not find any single specific Helicobacter pylori protein which could act as an indicator of clinical outcome, we found a possible marker of peptic ulcer disease which may be acceptable. This is the phenotype with simultaneous presence in bands at 116kDa and 26.5kDa protein. Our report differs from some previous reports from other regions. This may reflect differences of race and geography.