Laparoscopic Conversion of One Anastomosis Gastric Bypass to Roux-en-Y Gastric Bypass for Chronic Bile Reflux.

PubMed

Facchiano, Enrico; Leuratti, Luca; Veltri, Marco; Lucchese, Marcello

2016-03-01

One anastomosis gastric bypass (OAGB) demonstrated similar results to traditional Roux-en-Y procedures. A possible concern is how to manage a chronic bile reflux when medical therapy results ineffective. Revision of the gastro-jejunal anastomosis, obtaining a Roux-en-Y reconstruction, has already been proposed, but technical details have not been elucidated yet. This video shows how to revise a 200-cm OAGB to treat chronic bile reflux, by converting the procedure to Roux-en-Y, having a short gastric pouch and a long efferent limb. A 51-year-old patient complained of recurrent heartburns 2 months after OAGB. A gastroscopy witnessed the presence of a 6-cm long gastric pouch with pouchitis and bile reflux in esophagus. Specific medications were ineffective. He underwent a revisional laparoscopic procedure. The efferent limb was measured and consisted of 650 cm. The afferent limb was then divided next to the previous gastro-jejunal anastomosis and a jejuno-jejunal anastomosis was performed distally at 70 cm on the alimentary limb. Total operative time was 50 min. The postoperative stay was uneventful and the patient was discharged in postoperative day four. At 6 months follow-up he is still free of medications without symptoms. The ideal scenario for the presented technique is the finding of a long efferent limb, in order to fashion a Roux-en-Y limb without the risk of postoperative malabsorption. To reach this goal, we suggest the measurement of the whole small bowel intra-operatively, in order to assess the length of the common channel left in place.

Gastritis

MedlinePlus

... Less common causes are: Autoimmune disorders (such as pernicious anemia) Backflow of bile into the stomach (bile reflux) ... causing bleeding from the lining of the stomach, symptoms may include: Black stools Vomiting blood ... Complete blood count (CBC) to check for anemia or low blood count Examination of the stomach ...

Comparative evaluation of intragastric bile acids and hepatobiliary scintigraphy in the diagnosis of duodenogastric reflux.

PubMed

Chen, Teng-Fei; Yadav, Praveen K; Wu, Rui-Jin; Yu, Wei-Hua; Liu, Chang-Qin; Lin, Hui; Liu, Zhan-Ju

2013-01-01

To assess the diagnostic value of a combination of intragastric bile acids and hepatobiliary scintigraphy in the detection of duodenogastric reflux (DGR). The study contained 99 patients with DGR and 70 healthy volunteers who made up the control group. The diagnosis was based on the combination of several objective arguments: a long history of gastric symptoms (i.e., nausea, epigastric pain, and/or bilious vomiting) poorly responsive to medical treatment, gastroesophageal reflux symptoms unresponsive to proton-pump inhibitors, gastritis on upper gastrointestinal (GI) endoscopy and/or at histology, presence of a bilious gastric lake at > 1 upper GI endoscopy, pathologic 24-h intragastric bile monitoring with the Bilitec device. Gastric juice was aspirated in the GI endoscopy and total bile acid (TBA), total bilirubin (TBIL) and direct bilirubin (DBIL) were tested in the clinical laboratory. Continuous data of gastric juice were compared between each group using the independent-samples Mann-Whitney U-test and their relationship was analysed by Spearman's rank correlation test and Fisher's linear discriminant analysis. Histopathology of DGR patients and 23 patients with chronic atrophic gastritis was compared by clinical pathologists. Using the Independent-samples Mann-Whitney U-test, DGR index (DGRi) was calculated in 28 patients of DGR group and 19 persons of control group who were subjected to hepatobiliary scintigraphy. Receiver operating characteristic curve was made to determine the sensitivity and specificity of these two methods in the diagnosis of DGR. The group of patients with DGR showed a statistically higher prevalence of epigastric pain in comparison with control group. There was no significant difference between the histology of gastric mucosa with atrophic gastritis and duodenogastric reflux. The bile acid levels of DGR patients were significantly higher than the control values (Z: TBA: -8.916, DBIL: -3.914, TBIL: -6.197, all P < 0.001). Two of three in the DGR group have a significantly associated with each other (r: TBA/DBIL: 0.362, TBA/TBIL: 0.470, DBIL/TBIL: 0.737, all P < 0.001). The Fisher's discriminant function is followed: Con: Y = 0.002TBA + 0.048DBIL + 0.032TBIL - 0.986; Reflux: Y = 0.012TBA + 0.076DBIL + 0.089TBIL - 2.614. Eighty-four point zero five percent of original grouped cases were correctly classified by this method. With respect to the DGR group, DGRi were higher than those in the control group with statistically significant differences (Z = -5.224, P < 0.001). Twenty eight patients (59.6%) were deemed to be duodenogastric reflux positive by endoscopy, as compared to 37 patients (78.7%) by hepatobiliary scintigraphy. The integrated use of intragastric bile acid examination and scintigraphy can greatly improve the sensitivity and specificity of the diagnosis of DGR.

Deoxycholic acid promotes development of gastroesophageal reflux disease and Barrett's oesophagus by modulating integrin-αv trafficking.

PubMed

Prichard, David O; Byrne, Anne Marie; Murphy, James O; Reynolds, John V; O'Sullivan, Jacintha; Feighery, Ronan; Doyle, Brendan; Eldin, Osama Sharaf; Finn, Stephen P; Maguire, Aoife; Duff, Deirdre; Kelleher, Dermot P; Long, Aideen

2017-12-01

The fundamental mechanisms underlying erosive oesophagitis and subsequent development of Barrett's oesophagus (BO) are poorly understood. Here, we investigated the contribution of specific components of the gastric refluxate on adhesion molecules involved in epithelial barrier maintenance. Cell line models of squamous epithelium (HET-1A) and BO (QH) were used to examine the effects of bile acids on cell adhesion to extracellular matrix proteins (Collagen, laminin, vitronectin, fibronectin) and expression of integrin ligands (α 3 , α 4, α 5 , α 6 and α ν ). Experimental findings were validated in human explant oesophageal biopsies, a rat model of gastroesophageal reflux disease (GORD) and in patient tissue microarrays. The bile acid deoxycholic acid (DCA) specifically reduced adhesion of HET-1A cells to vitronectin and reduced cell-surface expression of integrin-α ν via effects on endocytic recycling processes. Increased expression of integrin-α v was observed in ulcerated tissue in a rat model of GORD and in oesophagitis and Barrett's intestinal metaplasia patient tissue compared to normal squamous epithelium. Increased expression of integrin-α ν was observed in QH BO cells compared to HET-1A cells. QH cells were resistant to DCA-mediated loss of adhesion and reduction in cell-surface expression of integrin-α ν . We demonstrated that a specific component of the gastric refluxate, DCA, affects the epithelial barrier through modulation of integrin α ν expression, providing a novel mechanism for bile acid-mediated erosion of oesophageal squamous epithelium and promotion of BO. Strategies aimed at preventing bile acid-mediated erosion should be considered in the clinical management of patients with GORD. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

A Fiber Optic System For The Detection Of Entero-Gastric Reflux

NASA Astrophysics Data System (ADS)

Falciai, R.; Baldini, F.; Conforti, G.; Cosi, F.; Scheggi, A. M...; Bechi, P.

1989-01-01

The study and the development of an optical fiber sensor for entero-gastric and non-acid gastro-esophageal reflux is described. The working principle, based on the spectrophotometric properties of the bile, which constitutes the main part of the reflux, differs from the traditional measurement method, based on pH monitoring. The measuring apparatus is described as well as experimental "in vitro" and preliminary "in vivo" tests are reported.

Comparative evaluation of intragastric bile acids and hepatobiliary scintigraphy in the diagnosis of duodenogastric reflux

PubMed Central

Chen, Teng-Fei; Yadav, Praveen K; Wu, Rui-Jin; Yu, Wei-Hua; Liu, Chang-Qin; Lin, Hui; Liu, Zhan-Ju

2013-01-01

AIM: To assess the diagnostic value of a combination of intragastric bile acids and hepatobiliary scintigraphy in the detection of duodenogastric reflux (DGR). METHODS: The study contained 99 patients with DGR and 70 healthy volunteers who made up the control group. The diagnosis was based on the combination of several objective arguments: a long history of gastric symptoms (i.e., nausea, epigastric pain, and/or bilious vomiting) poorly responsive to medical treatment, gastroesophageal reflux symptoms unresponsive to proton-pump inhibitors, gastritis on upper gastrointestinal (GI) endoscopy and/or at histology, presence of a bilious gastric lake at > 1 upper GI endoscopy, pathologic 24-h intragastric bile monitoring with the Bilitec device. Gastric juice was aspirated in the GI endoscopy and total bile acid (TBA), total bilirubin (TBIL) and direct bilirubin (DBIL) were tested in the clinical laboratory. Continuous data of gastric juice were compared between each group using the independent-samples Mann-Whitney U-test and their relationship was analysed by Spearman’s rank correlation test and Fisher’s linear discriminant analysis. Histopathology of DGR patients and 23 patients with chronic atrophic gastritis was compared by clinical pathologists. Using the Independent-samples Mann-Whitney U-test, DGR index (DGRi) was calculated in 28 patients of DGR group and 19 persons of control group who were subjected to hepatobiliary scintigraphy. Receiver operating characteristic curve was made to determine the sensitivity and specificity of these two methods in the diagnosis of DGR. RESULTS: The group of patients with DGR showed a statistically higher prevalence of epigastric pain in comparison with control group. There was no significant difference between the histology of gastric mucosa with atrophic gastritis and duodenogastric reflux. The bile acid levels of DGR patients were significantly higher than the control values (Z: TBA: -8.916, DBIL: -3.914, TBIL: -6.197, all P < 0.001). Two of three in the DGR group have a significantly associated with each other (r: TBA/DBIL: 0.362, TBA/TBIL: 0.470, DBIL/TBIL: 0.737, all P < 0.001). The Fisher’s discriminant function is followed: Con: Y = 0.002TBA + 0.048DBIL + 0.032TBIL - 0.986; Reflux: Y = 0.012TBA + 0.076DBIL + 0.089TBIL - 2.614. Eighty-four point zero five percent of original grouped cases were correctly classified by this method. With respect to the DGR group, DGRi were higher than those in the control group with statistically significant differences (Z = -5.224, P < 0.001). Twenty eight patients (59.6%) were deemed to be duodenogastric reflux positive by endoscopy, as compared to 37 patients (78.7%) by hepatobiliary scintigraphy. CONCLUSION: The integrated use of intragastric bile acid examination and scintigraphy can greatly improve the sensitivity and specificity of the diagnosis of DGR. PMID:23599645

Elevated bile amylase level without pancreaticobiliary maljunction is a risk factor for gallbladder carcinoma.

PubMed

Fujimoto, Takaaki; Ohtsuka, Takao; Nakashima, Yohei; Gotoh, Yoshitaka; Date, Kenjiro; Mori, Yasuhisa; Sadakari, Yoshihiko; Takahata, Shunichi; Oda, Yoshinao; Nakamura, Masafumi

2017-02-01

Elevated bile amylase level in patients with pancreaticobiliary maljunction (PBM) or high confluence of pancreaticobiliary ducts (HCPBD) is well known as a risk factor for gallbladder carcinoma (GBC) development. However, the effects of occult pancreaticobiliary reflux (OPR), a condition characterized by high bile amylase level in the presence of an anatomically normal pancreaticobiliary junction, on GBC development remain unclear. The aim of this study was to assess the relationship between OPR and GBC. Clinicopathological data of 52 patients who were preoperatively diagnosed with gallbladder (GB) tumor (22 malignant, 30 benign) were retrospectively reviewed. All of the patients underwent preoperative endoscopic retrograde cholangiopancreatography to evaluate pancreaticobiliary junction morphology and bile amylase level. The relationship between the histological diagnosis of GB lesions, and pancreaticobiliary junction morphology and bile amylase level were investigated. Pancreaticobiliary maljunction, HCPBD, and normal pancreaticobiliary junction (NPJ) were identified in 12, nine, and 31 patients, respectively. The rates of GBC in patients with PBM, HCPBD, and NPJ were 58% (7/12), 67% (6/9), and 29% (9/31), respectively. Of the 31 patients with NPJ, 22 had OPR and nine of these had GBC. None of the patients with NPJ and normal bile amylase level had GBC. Additionally, among patients with NPJ, bile amylase level was significantly higher in patients with GBC than in patients with benign tumors. Occult pancreaticobiliary reflux, like PBM and HCPBD, is a risk factor for GBC development. © 2017 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

A novel mechanism of acid and bile acid-induced DNA damage involving Na+/H+ exchanger: implication for Barrett's oesophagus.

PubMed

Goldman, Aaron; Shahidullah, Mohammad; Goldman, David; Khailova, Ludmila; Watts, George; Delamere, Nicholas; Dvorak, Katerina

2010-12-01

Barrett's oesophagus is a premalignant disease associated with oesophageal adenocarcinoma. The major goal of this study was to determine the mechanism responsible for bile acid-induced alteration in intracellular pH (pH(i)) and its effect on DNA damage in cells derived from normal oesophagus (HET1A) or Barrett's oesophagus (CP-A). Cells were exposed to bile acid cocktail (BA) and/or acid in the presence/absence of inhibitors of nitric oxide synthase (NOS) or sodium-hydrogen exchanger (NHE). Nitric oxide (NO), pH(i) and DNA damage were measured by fluorescent imaging and comet assay. Expression of NHE1 and NOS in cultured cells and biopsies from Barrett's oesophagus or normal squamous epithelium was determined by RT-PCR, immunoblotting or immunohistochemistry. A dose dependent decrease in pH(i) was observed in CP-A cells exposed to BA. This effect of BA is the consequence of NOS activation and increased NO production, which leads to NHE inhibition. Exposure of oesophageal cells to acid in combination with BA synergistically decreased pH(i). The decrease was more pronounced in CP-A cells and resulted in >2-fold increase in DNA damage compared to acid treatment alone. Examination of biopsies and cell lines revealed robust expression of NHE1 in Barrett's oesophagus but an absence of NHE1 in normal epithelium. The results of this study identify a new mechanism of bile acid-induced DNA damage. We found that bile acids present in the refluxate activate immediately all three isoforms of NOS, which leads to an increased NO production and NHE inhibition. This consequently results in increased intracellular acidification and DNA damage, which may lead to mutations and cancer progression. Therefore, we propose that in addition to gastric reflux, bile reflux should be controlled in patients with Barrett's oesophagus.

Pathophysiology of gastro-esophageal reflux disease: a role for mucosa integrity?

PubMed

Farré, R

2013-10-01

Gastro-esophageal reflux disease (GERD) is very prevalent and has a high burden on health security system costs. Nevertheless, pathophysiology is complex and not well-understood. Several mechanisms have been proposed: decreased salivation, impaired esophageal clearance, decreased lower esophageal sphincter pressure resting tone, presence of hiatal hernia, increased number of transient lower esophageal sphincter relaxations (TLESRs), increased acid, and pepsin secretion, pyloric incompetence provoking duodeno-gastro-esophageal reflux of bile acids and trypsin. Independent of the relevance of each mechanism, the ultimate phenomenon is that mucosal epithelium is exposed for a longer time to agents as acid and pepsin or is in contact to luminal agents not commonly present in gastric refluxate as trypsin or bile acids. This leads to a visible damage of the epithelium (erosive esophagitis -EE) or impairing mucosal integrity without any sign of macroscopic alteration as occurs in non-erosive reflux disease (NERD). Luminal factors are not the only responsible for such impairment; more recent data indicate that endogenous factors may also play a role. This review will update the most recent findings on the putative pathophysiological mechanisms and specially will focus on the role of esophageal mucosal integrity in GERD. Methodologies used for the evaluation of mucosal integrity, its relevance in EE and NERD, its involvement in symptoms perception and the effect of luminal and endogenous factors will be discussed. © 2013 John Wiley & Sons Ltd.

Relation between bile acid reflux into the stomach and the risk of atrophic gastritis and intestinal metaplasia: a multicenter study of 2283 cases.

PubMed

Matsuhisa, Takeshi; Arakawa, Tetsuo; Watanabe, Tetsuo; Tokutomi, Tadashi; Sakurai, Kouichi; Okamura, Seisuke; Chono, Shinji; Kamada, Tomoari; Sugiyama, Atsushi; Fujimura, Yoshinori; Matsuzawa, Kenji; Ito, Masanori; Yasuda, Mitsugu; Ota, Hiroyoshi; Haruma, Ken

2013-09-01

The relationship between bile acid reflux into the stomach and the risk of atrophic gastritis and intestinal metaplasia is still not well understood. Towards obtaining a better understanding, concentrations of bile acids were measured. This study was carried out with the participation of 14 facilities in Japan, and 2283 samples were collected. The subjects with bile acid concentrations equal to or higher than the limit of detection were divided into four groups of equal size (group A: 0-25%, group B: 26-50%, group C: 51-75%, and group D: 76-100%). Thus, including the control group, there were five groups in total. The odds that the control group would develop atrophic gastritis and intestinal metaplasia was set as 1,and the odds ratios (OR) in groups A, B, C and D were calculated based on the odds in the control group. Regarding the development of atrophic gastritis, no increased risk was observed in either the Helicobacter pylori (H. pylori)-positive or -negative cases. The OR for the development of intestinal metaplasia were significantly higher, for both cases with and without H. pylori infection, in group D. High concentrations of bile acid seem to be associated with an elevated risk of intestinal metaplasia. © 2013 The Authors. Digestive Endoscopy © 2013 Japan Gastroenterological Endoscopy Society.

A Novel Roux-en-Y Reconstruction Involving the Use of Two Circular Staplers after Distal Subtotal Gastrectomy for Gastric Cancer.

PubMed

Hur, Hoon; Ahn, Chang Wook; Byun, Cheul Su; Shin, Ho Jung; Kim, Young Bae; Son, Sang-Yong; Han, Sang-Uk

2017-09-01

Although Roux-en-Y (R-Y) reconstruction after distal gastrectomy has several advantages, such as prevention of bile reflux into the remnant stomach, it is rarely used because of the technical difficulty. This prospective randomized clinical trial aimed to show the efficacy of a novel method of R-Y reconstruction involving the use of 2 circular staplers by comparing this novel method to Billroth-I (B-I) reconstruction. A total of 118 patients were randomly allocated into the R-Y (59 patients) and B-I reconstruction (59 patients) groups. R-Y anastomosis was performed using two circular staplers and no hand sewing. The primary end-point of this clinical trial was the reflux of bile into the remnant stomach evaluated using endoscopic and histological findings at 6 months after surgery. No significant differences in clinicopathological findings were observed between the 2 groups. Although anastomosis time was significantly longer for the patients of the R-Y group (P<0.001), no difference was detected between the 2 groups in terms of the total surgery duration (P=0.112). Endoscopic findings showed a significant reduction of bile reflux in the remnant stomach in the R-Y group (P<0.001), and the histological findings showed that reflux gastritis was more significant in the B-I group than in the R-Y group (P=0.026). The results of this randomized controlled clinical trial showed that compared with B-I reconstruction, R-Y reconstruction using circular staplers is a safe and feasible procedure. This clinical trial study was registered at www.ClinicalTrials.gov (registration No. NCT01142271).

Respiratory Pathogens Adopt a Chronic Lifestyle in Response to Bile

PubMed Central

Reen, F. Jerry; Woods, David F.; Mooij, Marlies J.; Adams, Claire; O'Gara, Fergal

2012-01-01

Chronic respiratory infections are a major cause of morbidity and mortality, most particularly in Cystic Fibrosis (CF) patients. The recent finding that gastro-esophageal reflux (GER) frequently occurs in CF patients led us to investigate the impact of bile on the behaviour of Pseudomonas aeruginosa and other CF-associated respiratory pathogens. Bile increased biofilm formation, Type Six Secretion, and quorum sensing in P. aeruginosa, all of which are associated with the switch from acute to persistent infection. Furthermore, bile negatively influenced Type Three Secretion and swarming motility in P. aeruginosa, phenotypes associated with acute infection. Bile also modulated biofilm formation in a range of other CF-associated respiratory pathogens, including Burkholderia cepacia and Staphylococcus aureus. Therefore, our results suggest that GER-derived bile may be a host determinant contributing to chronic respiratory infection. PMID:23049911

Effects of bile acids on human airway epithelial cells: implications for aerodigestive diseases.

PubMed

Aldhahrani, Adil; Verdon, Bernard; Ward, Chris; Pearson, Jeffery

2017-01-01

Gastro-oesophageal reflux and aspiration have been associated with chronic and end-stage lung disease and with allograft injury following lung transplantation. This raises the possibility that bile acids may cause lung injury by damaging airway epithelium. The aim of this study was to investigate the effect of bile acid challenge using the immortalised human bronchial epithelial cell line (BEAS-2B). The immortalised human bronchial epithelial cell line (BEAS-2B) was cultured. A 48-h challenge evaluated the effect of individual primary and secondary bile acids. Post-challenge concentrations of interleukin (IL)-8, IL-6 and granulocyte-macrophage colony-stimulating factor were measured using commercial ELISA kits. The viability of the BEAS-2B cells was measured using CellTiter-Blue and MTT assays. Lithocholic acid, deoxycholic acid, chenodeoxycholic acid and cholic acid were successfully used to stimulate cultured BEAS-2B cells at different concentrations. A concentration of lithocholic acid above 10 μmol·L -1 causes cell death, whereas deoxycholic acid, chenodeoxycholic acid and cholic acid above 30 μmol·L -1 was required for cell death. Challenge with bile acids at physiological levels also led to a significant increase in the release of IL-8 and IL6 from BEAS-2B. Aspiration of bile acids could potentially cause cell damage, cell death and inflammation in vivo . This is relevant to an integrated gastrointestinal and lung physiological paradigm of chronic lung disease, where reflux and aspiration are described in both chronic lung diseases and allograft injury.

Bile acids induce necrosis in pancreatic stellate cells dependent on calcium entry and sodium-driven bile uptake.

PubMed

Ferdek, Pawel E; Jakubowska, Monika A; Gerasimenko, Julia V; Gerasimenko, Oleg V; Petersen, Ole H

2016-11-01

Acute biliary pancreatitis is a sudden and severe condition initiated by bile reflux into the pancreas. Bile acids are known to induce Ca 2+ signals and necrosis in isolated pancreatic acinar cells but the effects of bile acids on stellate cells are unexplored. Here we show that cholate and taurocholate elicit more dramatic Ca 2+ signals and necrosis in stellate cells compared to the adjacent acinar cells in pancreatic lobules; whereas taurolithocholic acid 3-sulfate primarily affects acinar cells. Ca 2+ signals and necrosis are strongly dependent on extracellular Ca 2+ as well as Na + ; and Na + -dependent transport plays an important role in the overall bile acid uptake in pancreatic stellate cells. Bile acid-mediated pancreatic damage can be further escalated by bradykinin-induced signals in stellate cells and thus killing of stellate cells by bile acids might have important implications in acute biliary pancreatitis. Acute biliary pancreatitis, caused by bile reflux into the pancreas, is a serious condition characterised by premature activation of digestive enzymes within acinar cells, followed by necrosis and inflammation. Bile acids are known to induce pathological Ca 2+ signals and necrosis in acinar cells. However, bile acid-elicited signalling events in stellate cells remain unexplored. This is the first study to demonstrate the pathophysiological effects of bile acids on stellate cells in two experimental models: ex vivo (mouse pancreatic lobules) and in vitro (human cells). Sodium cholate and taurocholate induced cytosolic Ca 2+ elevations in stellate cells, larger than those elicited simultaneously in the neighbouring acinar cells. In contrast, taurolithocholic acid 3-sulfate (TLC-S), known to induce Ca 2+ oscillations in acinar cells, had only minor effects on stellate cells in lobules. The dependence of the Ca 2+ signals on extracellular Na + and the presence of sodium-taurocholate cotransporting polypeptide (NTCP) indicate a Na + -dependent bile acid uptake mechanism in stellate cells. Bile acid treatment caused necrosis predominantly in stellate cells, which was abolished by removal of extracellular Ca 2+ and significantly reduced in the absence of Na + , showing that bile-dependent cell death was a downstream event of Ca 2+ signals. Finally, combined application of TLC-S and the inflammatory mediator bradykinin caused more extensive necrosis in both stellate and acinar cells than TLC-S alone. Our findings shed new light on the mechanism by which bile acids promote pancreatic pathology. This involves not only signalling in acinar cells but also in stellate cells. © 2016 The Authors The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.

Detection of endogenous DNA adducts, O-carboxymethyl-2'-deoxyguanosine and 3-ethanesulfonic acid-2'-deoxycytidine, in the rat stomach after duodenal reflux.

PubMed

Terasaki, Masaru; Totsuka, Yukari; Nishimura, Koichi; Mukaisho, Ken-Ichi; Chen, Kuan-Hao; Hattori, Takanori; Takamura-Enya, Takeji; Sugimura, Takashi; Wakabayashi, Keiji

2008-09-01

The endogenous DNA adducts O(6)-carboxymethyl-deoxyguanosine (O(6)-CM-dG) and 3-ethanesulfonic acid-deoxycytidine (3-ESA-dC) are produced from N-nitroso bile acid conjugates, such as N-nitrosoglycocholic acid (NO-GCA) and N-nitrosotaurocholic acid (NO-TCA), respectively. Formation of these DNA adducts in vivo was here analyzed by 32P-postlabeling in the glandular stomach of rats subjected to duodenal content reflux surgery. In this model, all duodenal contents, including bile acid conjugates, flow back from the jejunum into the gastric corpus. The levels of O(6)-CM-dG found at 4 and 8 weeks after surgery were 40.9 +/- 9.4 and 56.3 +/- 3.2 per 10(8) nucleotides, respectively, whereas the sham operation groups had values of 5.8 +/- 2.3 and 5.9 +/- 0.5 per 10(8) nucleotides. Moreover, adduct spots corresponding to 3-ESA-dC were detected in both duodenal reflux and sham operation groups and levels in the duodenal reflux groups were around four-fold elevated at 11.2 +/- 1.0 and 8.9 +/- 1.0 per 10(8) nucleotides after 4 and 8 weeks, respectively. When the duodenal reflux animals were treated with a nitrite trapping agent, thiazolidine- 4-carboxylic acid (thioproline, TPRO), the levels of O(6)-CM-dG and 3-ESA-dC were reduced to the same levels as in the sham operation animals. These observations suggest that NO-TCA and NO-GCA are formed by nitrosation of glycocholic acid and taurocholic acid, respectively, and these nitroso compounds produce DNA adducts in the glandular stomach of rats subjected to duodenal content reflux surgery.

Pancreaticobiliary maljunction and biliary cancer.

PubMed

Kamisawa, Terumi; Kuruma, Sawako; Tabata, Taku; Chiba, Kazuro; Iwasaki, Susumu; Koizumi, Satomi; Kurata, Masanao; Honda, Goro; Itoi, Takao

2015-03-01

Pancreaticobiliary maljunction (PBM) is a congenital malformation in which the pancreatic and bile ducts join anatomically outside the duodenal wall. Japanese clinical practice guidelines on how to deal with PBM were made in 2012, representing a world first. According to the 2013 revision to the diagnostic criteria for PBM, in addition to direct cholangiography, diagnosis can be made by magnetic resonance cholangiopancreatography (MRCP), 3-dimensional drip infusion cholangiography computed tomography, endoscopic ultrasonography (US), or multiplanar reconstruction images by multidetector row computed tomography. In PBM, the common channel is so long that sphincter action does not affect the pancreaticobiliary junction, and pancreatic juice frequently refluxes into the biliary tract. Persistence of refluxed pancreatic juice injures epithelium of the biliary tract and promotes cancer development, resulting in higher rates of carcinogenesis in the biliary tract. In a nationwide survey, biliary cancer was detected in 21.6% of adult patients with congenital biliary dilatation (bile duct cancer, 32.1% vs. gallbladder cancer, 62.3%) and in 42.4% of PBM patients without biliary dilatation (bile duct cancer, 7.3% vs. gallbladder cancer, 88.1%). Pathophysiological conditions due to pancreatobiliary reflux occur in patients with high confluence of pancreaticobiliary ducts, a common channel ≥6 mm long, and occlusion of communication during contraction of the sphincter. Once the diagnosis of PBM is established, immediate prophylactic surgery is recommended. However, the surgical strategy for PBM without biliary dilatation remains controversial. To detect PBM without biliary dilatation early, MRCP is recommended for patients showing gallbladder wall thickening on screening US under suspicion of PBM.

Bile acids induce necrosis in pancreatic stellate cells dependent on calcium entry and sodium‐driven bile uptake

PubMed Central

Jakubowska, Monika A.; Gerasimenko, Julia V.; Gerasimenko, Oleg V.; Petersen, Ole H.

2016-01-01

Key points Acute biliary pancreatitis is a sudden and severe condition initiated by bile reflux into the pancreas.Bile acids are known to induce Ca2+ signals and necrosis in isolated pancreatic acinar cells but the effects of bile acids on stellate cells are unexplored.Here we show that cholate and taurocholate elicit more dramatic Ca2+ signals and necrosis in stellate cells compared to the adjacent acinar cells in pancreatic lobules; whereas taurolithocholic acid 3‐sulfate primarily affects acinar cells.Ca2+ signals and necrosis are strongly dependent on extracellular Ca2+ as well as Na+; and Na+‐dependent transport plays an important role in the overall bile acid uptake in pancreatic stellate cells.Bile acid‐mediated pancreatic damage can be further escalated by bradykinin‐induced signals in stellate cells and thus killing of stellate cells by bile acids might have important implications in acute biliary pancreatitis. Abstract Acute biliary pancreatitis, caused by bile reflux into the pancreas, is a serious condition characterised by premature activation of digestive enzymes within acinar cells, followed by necrosis and inflammation. Bile acids are known to induce pathological Ca2+ signals and necrosis in acinar cells. However, bile acid‐elicited signalling events in stellate cells remain unexplored. This is the first study to demonstrate the pathophysiological effects of bile acids on stellate cells in two experimental models: ex vivo (mouse pancreatic lobules) and in vitro (human cells). Sodium cholate and taurocholate induced cytosolic Ca2+ elevations in stellate cells, larger than those elicited simultaneously in the neighbouring acinar cells. In contrast, taurolithocholic acid 3‐sulfate (TLC‐S), known to induce Ca2+ oscillations in acinar cells, had only minor effects on stellate cells in lobules. The dependence of the Ca2+ signals on extracellular Na+ and the presence of sodium–taurocholate cotransporting polypeptide (NTCP) indicate a Na+‐dependent bile acid uptake mechanism in stellate cells. Bile acid treatment caused necrosis predominantly in stellate cells, which was abolished by removal of extracellular Ca2+ and significantly reduced in the absence of Na+, showing that bile‐dependent cell death was a downstream event of Ca2+ signals. Finally, combined application of TLC‐S and the inflammatory mediator bradykinin caused more extensive necrosis in both stellate and acinar cells than TLC‐S alone. Our findings shed new light on the mechanism by which bile acids promote pancreatic pathology. This involves not only signalling in acinar cells but also in stellate cells. PMID:27406326

Bile acid regulates c-Jun expression through the orphan nuclear receptor SHP induction in gastric cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Park, Won Il; Park, Min Jung; An, Jin Kwang

2008-05-02

Bile reflux is considered to be one of the most important causative factors in gastric carcinogenesis, due to the attendant inflammatory changes in the gastric mucosa. In this study, we have assessed the molecular mechanisms inherent to the contribution of bile acid to the transcriptional regulation of inflammatory-related genes. In this study, we demonstrated that bile acid induced the expression of the SHP orphan nuclear receptor at the transcriptional level via c-Jun activation. Bile acid also enhanced the protein interaction of NF-{kappa}B and SHP, thereby resulting in an increase in c-Jun expression and the production of the inflammatory cytokine, TNF{alpha}.more » These results indicate that bile acid performs a critical function in the regulation of the induction of inflammatory-related genes in gastric cells, and that bile acid-mediated gene expression provides a pre-clue for the development of gastric cellular malformation.« less

Chemoprevention of esophageal adenocarcinoma in a rat model by ursodeoxycholic acid.

PubMed

Ojima, Eisuke; Fujimura, Takashi; Oyama, Katsunobu; Tsukada, Tomoya; Kinoshita, Jun; Miyashita, Tomoharu; Tajima, Hidehiro; Fushida, Sachio; Harada, Shin-ichi; Mukaisho, Ken-ichi; Hattori, Takanori; Ohta, Tetsuo

2015-08-01

Reflux of bile acid into the esophagus induces esophagitis, inflammation-stimulated hyperplasia, metaplasia such as Barrett's esophagus (BE), and esophageal adenocarcinoma (EAC). Caudal-type homeobox 2 (Cdx2) via nuclear factor (NF)-κB induced by bile acid is an important factor in the development of BE and EAC. In colorectal cancer, experimental data suggest a chemopreventive effect of ursodeoxycholic acid (UDCA). We hypothesized that UDCA may protect against the esophageal inflammation-metaplasia-carcinoma sequence by decreasing the overall proportion of the toxic bile acids. Wistar male rats that underwent a duodenoesophageal reflux procedure were divided into two groups. One group was given commercial chow (control group), and the other was given experimental chow containing UDCA (UDCA group). The animals were killed at 40 weeks after surgery, and their bile and esophagus were examined. In the UDCA group, the esophagitis was milder and the incidence of BE was significantly lower (p < 0.05) than in the control group, and EAC was not observed (p < 0.05). In analysis of the compartment of bile acid, UDCA was markedly increased in the UDCA group compared with the control group (32.7 ± 11.4 vs. 0.82 ± 0.33 mmol/L, p < 0.05) and cholic acid was decreased (32.7 ± 4.05 vs. 60.9 ± 8.26 mmol/L, p < 0.05). Expression intensity of Cdx2 and NF-κB was greater in the control group than in the UDCA group (p < 0.05). UDCA may be a chemopreventive agent against EAC by varying the bile acid composition.

Laparoscopic Conversion of One Anastomosis Gastric Bypass to a Standard Roux-en-Y Gastric Bypass.

PubMed

Amor, Imed Ben; Petrucciani, Niccolo; Kassir, Radwan; Al Munifi, Abdullah; Piche, Thierry; Debs, Tarek; Gugenheim, Jean

2017-05-01

One anastomosis gastric bypass (OAGB) demonstrated results similar to traditional Roux-en-Y procedures [1-3], in terms of weight loss and resolution of obesity-related comorbidities. The main controversy regarding OAGB is the concern for an association between biliary alkaline gastritis and esophageal or gastric cancer raised by some studies [4]. We present the case of a 51-year-old woman with a BMI of 41 kg/m2 who underwent a laparoscopic OAGB in 2014. One year later, she consulted for recurrent heartburns. An upper GI endoscopy showed pouchitis and bile reflux in the esophagus. Medical treatment of gastroesophageal reflux disease was ineffective. We decided to convert the OAGB to a Roux-en-Y gastric bypass (RYGB). In this video, we show how to revise an OAGB to treat chronic bile reflux, by converting the procedure to a standard RYGB. The intervention starts by restoring the normal anatomy of the small bowel, with the resection of the gastrojejunal anastomosis, which was located at 250-cm du Treitz's ligament. Then, the gastric pouch is created. A standard Roux-en-Y gastric bypass is performed. The resection of the gastrojejunal anastomosis allows fashioning the Roux-en-Y limb with the classical measures. This technique allows a conversion to a standard RYGB and is effective in treating the biliary reflux.

Proton pump inhibitor-refractory gastroesophageal reflux disease: challenges and solutions

PubMed Central

Mermelstein, Joseph; Chait Mermelstein, Alanna; Chait, Maxwell M

2018-01-01

A significant percentage of patients with gastroesophageal reflux disease (GERD) will not respond to proton pump inhibitor (PPI) therapy. The causes of PPI-refractory GERD are numerous and diverse, and include adherence, persistent acid, functional disorders, nonacid reflux, and PPI bioavailability. The evaluation should start with a symptom assessment and may progress to imaging, endoscopy, and monitoring of esophageal pH, impedance, and bilirubin. There are a variety of pharmacologic and procedural interventions that should be selected based on the underlying mechanism of PPI failure. Pharmacologic treatments can include antacids, prokinetics, alginates, bile acid binders, reflux inhibitors, and antidepressants. Procedural options include laparoscopic fundoplication and LINX as well as endoscopic procedures, such as transoral incisionless fundoplication and Stretta. Several alternative and complementary treatments of possible benefit also exist. PMID:29606884

The diagnostic value of gastroesophageal reflux disease (GERD) symptoms and detection of pepsin and bile acids in bronchoalveolar lavage fluid and exhaled breath condensate for identifying lung transplantation patients with GERD-induced aspiration.

PubMed

Reder, Nicholas P; Davis, Christopher S; Kovacs, Elizabeth J; Fisichella, P Marco

2014-06-01

Gastroesophageal reflux disease (GERD) is thought to lead to aspiration and bronchiolitis obliterans syndrome after lung transplantation. Unfortunately, the identification of patients with GERD who aspirate still lacks clear diagnostic indicators. The authors hypothesized that symptoms of GERD and detection of pepsin and bile acids in the bronchoalveolar lavage fluid (BAL) and exhaled breath condensate (EBC) are effective for identifying lung transplantation patients with GERD-induced aspiration. From November 2009 to November 2010, 85 lung transplantation patients undergoing surveillance bronchoscopy were prospectively enrolled. For these patients, self-reported symptoms of GERD were correlated with levels of pepsin and bile acids in BAL and EBC and with GERD status assessed by 24-h pH monitoring. The sensitivity and specificity of pepsin and bile acids in BAL and EBC also were compared with the presence of GERD in 24-h pH monitoring. The typical symptoms of GERD (heartburn and regurgitation) had modest sensitivity and specificity for detecting GERD and aspiration. The atypical symptoms of GERD (aspiration and bronchitis) showed better identification of aspiration as measured by detection of pepsin and bile acids in BAL. The sensitivity and specificity of pepsin in BAL compared with GERD by 24-h pH monitoring were respectively 60 and 45 %, whereas the sensitivity and specificity of bile acids in BAL were 67 and 80 %. These data indicate that the measurement of pepsin and bile acids in BAL can provide additional data for identifying lung transplantation patients at risk for GERD-induced aspiration compared with symptoms or 24-h pH monitoring alone. These results support a diagnostic role for detecting markers of aspiration in BAL, but this must be validated in larger studies.

Role of bile acids in carcinogenesis of pancreatic cancer: An old topic with new perspective

PubMed Central

Feng, Hui-Yi; Chen, Yang-Chao

2016-01-01

The role of bile acids in colorectal cancer has been well documented, but their role in pancreatic cancer remains unclear. In this review, we examined the risk factors of pancreatic cancer. We found that bile acids are associated with most of these factors. Alcohol intake, smoking, and a high-fat diet all lead to high secretion of bile acids, and bile acid metabolic dysfunction is a causal factor of gallstones. An increase in secretion of bile acids, in addition to a long common channel, may result in bile acid reflux into the pancreatic duct and to the epithelial cells or acinar cells, from which pancreatic adenocarcinoma is derived. The final pathophysiological process is pancreatitis, which promotes dedifferentiation of acinar cells into progenitor duct-like cells. Interestingly, bile acids act as regulatory molecules in metabolism, affecting adipose tissue distribution, insulin sensitivity and triglyceride metabolism. As a result, bile acids are associated with three risk factors of pancreatic cancer: obesity, diabetes and hypertriglyceridemia. In the second part of this review, we summarize several studies showing that bile acids act as cancer promoters in gastrointestinal cancer. However, more question are raised than have been solved, and further oncological and physiological experiments are needed to confirm the role of bile acids in pancreatic cancer carcinogenesis. PMID:27672269

Bile sensor: from the lab to the market

NASA Astrophysics Data System (ADS)

Baldini, Francesco

1999-12-01

In 1988 the idea of measuring bile in the stomach and in the oesophagus via optical fibers was conceived and patented in collaboration with physicians from the University of Florence. The working principle is based on the spectrophotometric properties of the bile which contains some pigments with definite absorption properties. Bilirubin is the main pigment and it is characterized by an absorption peak in the blue region: therefore it is possible to detect optically the bile in the stomach by optically detecting bilirubin. The possibility of measuring bile reflux directly measuring the presence of bile represented a winning aspect in comparison with the traditional techniques (pH-metry, cholescintigraphy, bile acid assessment in aspirates); on the contrary the new technique had to overcome the traditional 'cultural' barriers constituted by the conservative attitude of clinicians concerning any innovative technology. The realization of the first laboratory prototype demonstrates the feasibility and validity of the proposed optical method. Then many years were necessary to arrive at the definitive and marketable product. The history of Bilitec 2000 is described, with the purpose to stress how a laboratory prototype is still very far from the market.

Gastroesophageal reflux and lung disease.

PubMed

Meyer, Keith C

2015-08-01

Gastroesophageal reflux (GER) can cause respiratory symptoms and may trigger, drive and/or worsen airway disorders, interstitial lung diseases and lung allograft dysfunction. Whether lifestyle changes and acid suppression alone can counter and prevent the adverse effects of GER on the respiratory tract remains unclear. Recent data suggest that antireflux surgery may be more effective in preventing lung disease progression in patients with idiopathic pulmonary fibrosis or lung transplant recipients who have evidence of allograft dysfunction associated with the presence of excessive GER. Additional research and clinical trials are needed to determine the role of GER in various lung disorders and identify which interventions are most efficacious in preventing the respiratory consequences of gastroesophageal reflux disease. In addition, measuring biomarkers that indicate that gastric refluxate has been aspirated into the lower respiratory tract (e.g., pepsin and bile acid concentrations in bronchoalveolar lavage fluid) may prove helpful in both diagnosis and therapeutic decision making.

Trypsin level in gallbladder bile and ductitis and width of the cystic duct.

PubMed

Vracko, J; Wiechel, K L

2000-01-01

The change from laparotomy to laparoscopy for cholecystectomy has raised the question of how to manage concomitant bile duct stones. The present-day interest--and controversy--has focused on a transcystic approach reported to be feasible in 66-96% of cases, but without explaining the necessary prerequisite: the widening of the cystic duct. The cystic duct, wide mainly in patients with bile duct stones, has been reported to be highly variable: from strictured to very wide. The present study aims at comparing the trypsin level in the gallbladder bile and the cystic duct morphology and width in patients with and without bile duct stones. A prospective series of 63 gallstone patients, 30 with and 33 without bile duct stones (controls), underwent cholecystectomy and bile duct clearance. The study includes the trypsin level in the gallbladder bile, the width and morphology of the cystic duct, and the size of the gallstones. The patients with bile duct stones had, in contrast to the controls, higher trypsin levels in the gallbladder bile (P < 0.001) and wider cystic ducts (P < 0.001) with more pronounced signs of chronic ductitis. The obtained results strongly suggest that the increased trypsin level, a sign of reflux of pancreatic juice, caused changes in the cystic duct that facilitate gallstone migration, which also ought to render a transcystic stone extraction feasible.

Comparison Between Billroth-II with Braun and Roux-en-Y Reconstruction After Laparoscopic Distal Gastrectomy.

PubMed

In Choi, Chang; Baek, Dong Hoon; Lee, Si Hak; Hwang, Sun Hwi; Kim, Dae Hwan; Kim, Kwang Ha; Jeon, Tae Yong; Kim, Dong Heon

2016-06-01

This study aims to compare the effectiveness of Billroth-II with Braun and Roux-en-Y reconstruction after laparoscopic distal gastrectomy. From April 2010 to August 2012, 66 patients underwent laparoscopic distal gastrectomy (Billroth-II with Braun reconstruction, 26; Roux-en-Y, 40). The patients' data were collected prospectively and reviewed retrospectively. The mean operation and reconstruction times were statistically shorter for Billroth-II with Braun reconstruction than Roux-en-Y (198.1 ± 33.0 vs. 242.3 ± 58.1 min, p = 0.001). One case of postoperative stricture was observed in each group. One case each of intra-abdominal abscess and delayed gastric emptying occurred in the Billroth-II with Braun group. At 1 year postoperatively, gastric residue and reflux esophagitis were not significantly different between the groups. Gastritis and bile reflux were more frequently observed in the Billroth-II with Braun group (p = 0.004 and p < 0.001, respectively). At 2 years postoperatively, gastric residue was not significantly different, but gastritis, bile reflux, and esophagitis were more frequent in the Billroth-II with Braun group (p = 0.029, p < 0.001, and p = 0.036, respectively). The postoperative effectiveness of Roux-en-Y reconstruction may be superior to Billroth-II with Braun reconstruction after laparoscopic distal gastrectomy.

Toll-like Receptor 2 Signalling and the Lysosomal Machinery in Barrett's Esophagus.

PubMed

Verbeek, Romy E; Siersema, Peter D; Vleggaar, Frank P; Ten Kate, Fiebo J; Posthuma, George; Souza, Rhonda F; de Haan, Judith; van Baal, Jantine W P M

2016-09-01

Inflammation plays an important role in the development of esophageal adenocarcinoma and its metaplastic precursor lesion, Barrett's esophagus. Toll-like receptor (TLR) 2 signalling and lysosomal function have been linked to inflammation-associated carcinogenesis. We examined the expression of TLR2 in the esophagus and the effect of long-term TLR2 activation on morphological changes and expression of factors involved in lysosomal function in a Barrett's esophagus epithelium cell line. TLR2 expression in normal squamous esophagus, reflux esophagitis, Barrett's esophagus and esophageal adenocarcinoma biopsies was assessed with Q-RT-PCR, in situ hybridization and immunohistochemistry. Barrett's esophagus epithelium cells (BAR-T) were incubated with acid and bile salts in the presence or absence of the TLR2 agonist Pam3CSK4 for a period up to 4 weeks. Morphological changes were assessed with electron microscopy, while Q-RT-PCR was used to determine the expression of lysosomal enzymes (Cathepsin B and C) and factors involved in endocytosis (LAMP-1 and M6PR) and autophagy (LC3 and Rab7). TLR2 was expressed in normal squamous esophagus, reflux esophagitis, Barrett's esophagus but was most prominent in esophageal adenocarcinoma. Long-term TLR2 activation in acid and bile salts exposed BAR-T cells resulted in more and larger lysosomes, more mitochondria and increased expression of LAMP-1, M6PR, Cathepsin B and C when compared to BAR-T cells incubated with acid and bile salts but no TLR2 agonist. Factors associated with autophagy (LC3 and Rab7) expression remained largely unchanged. Activation of TLR2 in acid and bile salts exposed Barrett epithelium cells resulted in an increased number of mitochondria and lysosomes and increased expression of lysosomal enzymes and factors involved in endocytosis.

Rate of duodenal-biliary reflux increases in patients with recurrent common bile duct stones: evidence from barium meal examination.

PubMed

Zhang, Rongchun; Luo, Hui; Pan, Yanglin; Zhao, Lina; Dong, Junqiang; Liu, Zhiguo; Wang, Xiangping; Tao, Qin; Lu, Guohua; Guo, Xuegang

2015-10-01

Stone recurrence is a common late adverse event after ERCP in patients with common bile duct stones (CBDS). Duodenal-biliary reflux (DBR) is considered a major cause of CBDS recurrence. However, specific evidence is still lacking. To investigate the DBR rate in patients with recurrent CBDS after ERCP. A prospective case-control study. A tertiary center. During follow-up, patients with a history of either recurrent CBDS (recurrence group) or nonrecurrent CBDS (control group) were invited to participate in the study. All patients had previously undergone successful CBDS removal by ERCP. Patients in the control group were matched with the recurrence group by age and gender in a 1:1 ratio. Patients with gallbladder stones, hepatolithiasis, remnant CBDS, CBD strictures, or stents were excluded. Standard barium meal examination, MRCP, and enhanced abdominal CT. DBR. Thirty-two patients with a history of recurrent CBDS and 32 matched control subjects were enrolled. Baseline characteristics and parameters regarding the first ERCP were comparable between the 2 groups. The DBR rate was significantly higher in the recurrent than in the control group (68.8% vs 15.6%, P < .001). Multivariate analysis indicated that DBR (OR, 9.59; 95% CI, 2.65-34.76) and acute distal CBD angulation (OR, 5.48; 95% CI, 1.52-19.78) were independent factors associated with CBDS recurrence. DBR rates in patients with no, single, or multiple recurrences were 15.6%, 60.9%, and 88.9%, respectively (P < .001). Intrahepatic bile duct reflux was more common in patients with multiple recurrences. Small sample size. DBR is correlated with CBDS recurrence in patients who had previously undergone ERCP. DBR and acute distal CBD angulation are 2 independent risk factors related to stone recurrence. ( NCT02329977.) Copyright © 2015 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.

Utilization of wireless pH monitoring technologies: a summary of the proceedings from the esophageal diagnostic working group.

PubMed

Richter, J E; Pandolfino, J E; Vela, M F; Kahrilas, P J; Lacy, B E; Ganz, R; Dengler, W; Oelschlager, B K; Peters, J; DeVault, K R; Fass, R; Gyawali, C P; Conklin, J; DeMeester, T

2013-01-01

Gastroesophageal reflux disease (GERD) can be difficult to diagnose - symptoms alone are often not enough, and thus, objective testing is often required. GERD is a manifestation of pathologic levels of reflux into the esophagus of acidic, nonacidic, and/or bilious gastric content. However, in our current evidence-based knowledge approach, we only have reasonable outcome data in regards to acid reflux, as this particular type of refluxate predictably causes symptoms and mucosal damage, which improves with medical or surgical therapy. While there are data suggesting that nonacid reflux may be responsible for ongoing symptoms despite acid suppression in some patients, outcome data about this issue are limited. Therefore, this working group believes that it is essential to confirm the presence of acid reflux in patients with 'refractory' GERD symptoms or extraesophageal symptoms thought to be caused by gastroesophageal reflux before an escalation of antireflux therapy is considered. If patients do not have pathologic acid reflux off antisecretory therapy, they are unlikely to have clinically significant nonacid or bile reflux. Patients who do not have pathologic acid gastroesophageal reflux parameters on ambulatory pH monitoring then: (i) could attempt to discontinue antisecretory medications like proton pump inhibitors and H2-receptor antagonists (which are expensive and which carry risks - i.e. C. diff, etc.); (ii) may undergo further evaluation for other causes of their esophageal symptoms (e.g. functional heartburn or chest pain, eosinophilic esophagitis, gastroparesis, achalasia, other esophageal motor disorders); and (iii) can be referred to an ear, nose, and throat/pulmonary/allergy physician for assessment of non-GERD causes of their extraesophageal symptoms. © 2012 Copyright the Authors. Journal compilation © 2012, Wiley Periodicals, Inc. and the International Society for Diseases of the Esophagus.

The spectrum of motor function abnormalities in gastroesophageal reflux disease and Barrett's esophagus.

PubMed

Ang, D; Blondeau, K; Sifrim, D; Tack, J

2009-01-01

Barrett's esophagus has traditionally been regarded as the most severe end of the spectrum of gastroesophageal reflux disease and is of great clinical importance in view of the association with esophageal adenocarcinoma. Studies have documented high levels of esophageal acid exposure in Barrett's esophagus. Various pathogenetic mechanisms underlie this phenomenon. These include abnormalities in esophageal peristalsis, defective lower esophageal sphincter pressures, gastric dysmotility and bile reflux. Whilst these factors provide evidence for an acquired cause of Barrett's esophagus, an underlying genetic predisposition cannot be ruled out. Although the past decade has brought about many new discoveries in the pathogenesis of Barrett's esophagus, it has also added further controversy to this complex disorder. A detailed analysis of the gastrointestinal motor abnormalities occurring in Barrett's esophagus follows, with a review of the currently available literature and an update on this condition that continues to be of interest to the gastroenterologist.

Management of Gastroesophageal Reflux Disease.

PubMed

Gyawali, C Prakash; Fass, Ronnie

2018-01-01

Management of gastroesophageal reflux disease (GERD) commonly starts with an empiric trial of proton pump inhibitor (PPI) therapy and complementary lifestyle measures, for patients without alarm symptoms. Optimization of therapy (improving compliance and timing of PPI doses), or increasing PPI dosage to twice daily in select circumstances, can reduce persistent symptoms. Patients with continued symptoms can be evaluated with endoscopy and tests of esophageal physiology, to better determine their disease phenotype and optimize treatment. Laparoscopic fundoplication, magnetic sphincter augmentation, and endoscopic therapies can benefit patients with well-characterized GERD. Patients with functional diseases that overlap with or mimic GERD can also be treated with neuromodulators (primarily antidepressants), or psychological interventions (psychotherapy, hypnotherapy, cognitive and behavioral therapy). Future approaches to treatment of GERD include potassium-competitive acid blockers, reflux-reducing agents, bile acid binders, injection of inert substances into the esophagogastric junction, and electrical stimulation of the lower esophageal sphincter. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

Clinical Study of Ursodeoxycholic Acid in Barrett’s Esophagus Patients

PubMed Central

Banerjee, Bhaskar; Shaheen, Nicholas J.; Martinez, Jessica A.; Hsu, Chiu-Hsieh; Trowers, Eugene; Gibson, Blake A.; Della’Zanna, Gary; Richmond, Ellen; Chow, H-H. Sherry

2016-01-01

Prior research strongly implicates gastric acid and bile acids, two major components of the gastroesophageal refluxate, in the development of Barrett’s esophagus (BE) and its pathogenesis. Ursodeoxycholic acid (UDCA), a hydrophilic bile acid, has been shown to protect esophageal cells against oxidative stress induced by cytotoxic bile acids. We conducted a pilot clinical study to evaluate the clinical activity of UDCA in patients with BE. Twenty-nine BE patients received UDCA treatment at a daily dose of 13–15 mg/kg/day for six months. The clinical activity of UDCA was assessed by evaluating changes in gastric bile acid composition and markers of oxidative DNA damage (8-hydroxydeoxyguanosine, 8OHdG), cell proliferation (Ki67), and apoptosis (cleaved caspase 3, CC3) in BE epithelium. The bile acid concentrations in gastric fluid were measured by liquid chromatography-mass spectrometry. At baseline, UDCA (sum of unchanged and glycine/taurine conjugates) accounted for 18.2% of total gastric bile acids. Post UDCA intervention, UDCA increased significantly to account for 93.39% of total gastric bile acids (p<0.0001). The expression of markers of oxidative DNA damage, cell proliferation, and apoptosis was assessed in the BE biopsies by immunohistochemistry. The selected tissue biomarkers were unchanged after 6 months of UDCA intervention. We conclude that high dose UDCA supplementation for six months resulted in favorable changes in gastric bile acid composition but did not modulate selected markers of oxidative DNA damage, cell proliferation, and apoptosis in the BE epithelium. PMID:26908564

Inhibition of NF-κB prevents the acidic bile-induced oncogenic mRNA phenotype, in human hypopharyngeal cells

PubMed Central

Vageli, Dimitra P.; Doukas, Sotirios G.; Sasaki, Clarence T.

2018-01-01

Bile-containing gastro-duodenal reflux has been clinically considered an independent risk factor in hypopharyngeal carcinogenesis. We recently showed that the chronic effect of acidic bile, at pH 4.0, selectively induces NF-κB activation and accelerates the transcriptional levels of genes, linked to head and neck cancer, in normal hypopharyngeal epithelial cells. Here, we hypothesize that NF-κB inhibition is capable of preventing the acidic bile-induced and cancer-related mRNA phenotype, in treated normal human hypopharyngeal cells. In this setting we used BAY 11-7082, a specific and well documented pharmacologic inhibitor of NF-κB, and we observed that BAY 11-7082 effectively inhibits the acidic bile-induced gene expression profiling of the NF-κB signaling pathway (down-regulation of 72 out of 84 analyzed genes). NF-κB inhibition significantly prevents the acidic bile-induced transcriptional activation of NF-κB transcriptional factors, RELA (p65) and c-REL, as well as genes related to and commonly found in established HNSCC cell lines. These include anti-apoptotic bcl-2, oncogenic STAT3, EGFR, ∆Np63, TNF-α and WNT5A, as well as cytokines IL-1β and IL-6. Our findings are consistent with our hypothesis demonstrating that NF-κB inhibition effectively prevents the acidic bile-induced cancer-related mRNA phenotype in normal human hypopharyngeal epithelial cells supporting an understanding that NF-κB may be a critical link between acidic bile and early preneoplastic events in this setting. PMID:29464041

Alcohol and acute pancreatitis. An experimental study in the rat.

PubMed

Jalovaara, P; Apaja, M

1978-01-01

The effect of chronic alcohol pretreatment and various pancreatobiliary secretions on the severity of experimental pancreatitis was studied in the rat. 95 rats were pretreated with ethanol (20% w/v, 1.1 ml/100 g body weight) five times weekly for 10 to 12 weeks by gastric intubation. 88 rats served as controls. Pancreatic lesions were produced by retograde injection of different pancreatobiliary secretions into the pancreatic ducts. The secretions were collected from both normal and chronically alcohol-fed rats, and each was used for induction of experimental pancreatitis in the control and alcohol pretreated rats. Bile obtained from normal rats was no more toxic to the pancreas than 0.9% saline solution, while bile obtained from the chronically alcohol-fed rats caused significantly more serious lesions to the pancreas than did normal rat bile. Bile-pancreatic juice (mixture of secretions at papilla of Vater) of normal and chronically alcohol-fed rats was as toxic as the bile of the alcohol-fed rats. Alcohol pretreatment had no significant effect on the severity of pancreatitis when control and alcohol-fed groups separately or the whole material according to pretreatment was examined. These results suggest that the metabolic effects of ethanol on the pancreas as such do not sensitize the pancreas to acute pancreatitis. An exogenous mechanism is required. The reflux of toxic alcoholic bile into the pancreas might act as an induction factor in acute alcohol pancreatitis.

Etiological involvement of Helicobacter pylori in "reflux" gastritis after gastrectomy.

PubMed

Nagahata, Y; Kawakita, N; Azumi, Y; Numata, N; Yano, M; Saitoh, Y

1996-10-01

"Reflux" gastritis after gastrectomy is associated with various symptoms that are often detrimental to the patients' quality of life. However, prevention of the reflux does not always bring relief from the symptoms of gastritis. Helicobacter pylori (H. pylori) is now considered one of the most important pathogenetic factors in gastritis. The association between H. pylori infection and reflux gastritis after gastrectomy was investigated in the present study. In total, 115 patients who had undergone gastrectomy were entered in this study. Five biopsy specimens from the gastric remnant were taken during upper GI endoscopy. One specimen was examined pathohistologically, and the remaining four were examined for H. pylori infection. The histological degree of gastritis was determined according to the score system of Rauws et al. Forty-six patients (40%) demonstrated H. pylori infection in their stomachs. The prevalence of the infection was significantly higher in patients with conventional gastrectomy than in those with subtotal gastrectomy. The prevalence of H. pylori infection was significantly lower in patients who had undergone gastrectomy more than 4 yr ago. The histological gastritis score in patients with H. pylori infection was significantly higher than in those without H. pylori infection. Furthermore, the eradication of H. pylori in patients with both serious gastritis symptoms and no bile reflux improved the symptoms and significantly decreased the histological gastritis score. The results suggest that H. pylori is a factor in the pathogenesis of reflux gastritis after gastrectomy.

Clinical curative effect of electroacupuncture combined with zhizhukuanzhong capsules for treating gastroesophageal reflux disease.

PubMed

Zhang, Chaoxian; Guo, Like; Guo, Xiaofeng; Guo, Xiaohe; Li, Guangyan

2012-09-01

To study the clinical curative effect, safety and mechanism of action of electroacupuncture combined with Zhizhukuanzhong capsules (ZZKZC) in treating gastroesophageal reflux disease (GERD). A total of 480 patients with confirmed GERD were randomly divided into four groups: the electroacupuncture group, the ZZKZC group, the combined therapy group, and the control group, with 120 cases in each group. Each case in the electroacupuncture group was treated with electroacupuncture on Zusanli (ST 36), Zhongwan (CV 12), Neiguan (PC 6),Taichong (LR 3) and Gongsun (SP 4) once daily for 6 weeks. Each case in the ZZKZC group was treated with oral administration of 1.29 g ZZKZC three times daily. The combined therapy group had electroacupuncture and ZZKZC. The control group was given oral administration of 5 mg mosapride three times and 20 mg pantoprazole twice daily. The 24-hour intraesophageal total number of reflux episodes with pH <4 (or bilirubin absorbance > or = 0.14), the number of long-term (> or = 5 min) reflux episodes, the percentage of upright time, the percentage of supine time, the percentage of total time of pH <4 (or bilirubin absorbance > or = 0.14), endoscopic grading score, symptom score, quality of life score, and adverse reactions were observed before treatment, at the end of treatment and 54 weeks after treatment in the four groups. The 24-hour intraesophageal pH and bile reflux, endoscopic grading score and symptom score were all significantly decreased at the end of treatment in every group, while the scores of 8 dimensions of quality of life were all increased compared with those before treatment (P<0.01). All of these indices were better in the combined therapy group than those in the other groups (P<0.05). These indices did not significantly deteriorate in the combined therapy group and electroacupuncture group 54 weeks after treatment compared with the end of treatment (P>0.05); however, these indices all significantly deteriorated in the ZZKZC and control groups (P>0.05). The short and long-term total efficacy rates in the combined therapy group showed significant superiority to those in the other groups (P<0.05 or P<0.01). No serious adverse reactions were found in the four groups. Electroacupuncture and ZZKZC play an important role in inhibiting intraesophageal acid and bile reflux, decreasing the endoscopic grading score, and alleviating the symptoms of gastroesophageal reflux to improve the quality of life. However, the effect of combined treatment is more effective, with better security and long-term efficacy, and therefore, this combination treatment is appropriate for clinical use.

Radiosynthesis of N-¹¹C-Methyl-Taurine-Conjugated Bile Acids and Biodistribution Studies in Pigs by PET/CT.

PubMed

Schacht, Anna Christina; Sørensen, Michael; Munk, Ole Lajord; Frisch, Kim

2016-04-01

During cholestasis, accumulation of conjugated bile acids may occur in the liver and lead to hepatocellular damage. Inspired by our recent development of N-(11)C-methyl-glycocholic acid-that is, (11)C-cholylsarcosine-a tracer for PET of the endogenous glycine conjugate of cholic acid, we report here a radiosynthesis of N-(11)C-methyl-taurine-conjugated bile acids and biodistribution studies in pigs by PET/CT. A radiosynthesis of N-(11)C-methyl-taurine-conjugated bile acids was developed and used to prepare N-(11)C-methyl-taurine conjugates derived from cholic, chenodeoxycholic, deoxycholic, ursodeoxycholic, and lithocholic acid. The lipophilicity of these new tracers was determined by reversed-phase thin-layer chromatography. The effect of lipophilicity and structure on the biodistribution was investigated in pigs by PET/CT using the tracers derived from cholic acid (3α-OH, 7α-OH, 12α-OH), ursodeoxycholic acid (3α-OH, 7β-OH), and lithocholic acid (3α-OH). The radiosyntheses of the N-(11)C-methyl-taurine-conjugated bile acids proceeded with radiochemical yields of 61% (decay-corrected) or greater and radiochemical purities greater than 99%. PET/CT in pigs revealed that the tracers were rapidly taken up by the liver and secreted into bile. There was no detectable radioactivity in urine. Significant reflux of N-(11)C-methyl-taurolithocholic acid into the stomach was observed. We have successfully developed a radiosynthesis of N-(11)C-methyl-taurine-conjugated bile acids. These tracers behave in a manner similar to endogenous taurine-conjugated bile acids in vivo and are thus promising for functional PET of patients with cholestatic diseases. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Clinical Study of Ursodeoxycholic Acid in Barrett's Esophagus Patients.

PubMed

Banerjee, Bhaskar; Shaheen, Nicholas J; Martinez, Jessica A; Hsu, Chiu-Hsieh; Trowers, Eugene; Gibson, Blake A; Della'Zanna, Gary; Richmond, Ellen; Chow, H-H Sherry

2016-07-01

Prior research strongly implicates gastric acid and bile acids, two major components of the gastroesophageal refluxate, in the development of Barrett's esophagus and its pathogenesis. Ursodeoxycholic acid (UDCA), a hydrophilic bile acid, has been shown to protect esophageal cells against oxidative stress induced by cytotoxic bile acids. We conducted a pilot clinical study to evaluate the clinical activity of UDCA in patients with Barrett's esophagus. Twenty-nine patients with Barrett's esophagus received UDCA treatment at a daily dose of 13 to 15 mg/kg/day for 6 months. The clinical activity of UDCA was assessed by evaluating changes in gastric bile acid composition and markers of oxidative DNA damage (8-hydroxydeoxyguanosine), cell proliferation (Ki67), and apoptosis (cleaved caspase-3) in Barrett's esophagus epithelium. The bile acid concentrations in gastric fluid were measured by liquid chromatography/mass spectrometry. At baseline, UDCA (sum of unchanged and glycine/taurine conjugates) accounted for 18.2% of total gastric bile acids. After UDCA intervention, UDCA increased significantly to account for 93.4% of total gastric bile acids (P < 0.0001). The expression of markers of oxidative DNA damage, cell proliferation, and apoptosis was assessed in the Barrett's esophagus biopsies by IHC. The selected tissue biomarkers were unchanged after 6 months of UDCA intervention. We conclude that high-dose UDCA supplementation for 6 months resulted in favorable changes in gastric bile acid composition but did not modulate selected markers of oxidative DNA damage, cell proliferation, and apoptosis in the Barrett's esophagus epithelium. Cancer Prev Res; 9(7); 528-33. ©2016 AACRSee related article by Brian J. Reid, p. 512. ©2016 American Association for Cancer Research.

Smaller-diameter circular stapler has an advantage in Billroth I stapled anastomosis after laparoscopy-assisted distal gastrectomy.

PubMed

Kim, Min-Kyoon; Park, Joong-Min; Choi, Yoo-Shin; Chi, Kyong-Choun

2012-04-01

Billroth I gastroduodenostomy using a circular stapler is the most preferred reconstruction method after laparoscopy-assisted distal gastrectomy (LADG). The optimal stapler size for this procedure has not yet been proposed. Sixty-five patients who underwent LADG and stapled anastomosis with a 25-mm stapler (25-mm group) and a 29-mm stapler (29-mm group) were enrolled in this study. Clinical data and gastroscopic findings at 6 and 12 months after surgery were retrospectively reviewed. Postoperative complications and postprandial symptoms were similar in both groups. Gastroscopically, food materials remained more frequently in the remnant stomach in the 25-mm group than in the 29-mm group at 6 months after surgery (P=.041). Gastritis and bile reflux were observed more frequently in the 29-mm group than in the 25-mm group (P=.012 and P=.015, respectively). All these differences in the gastroscopic findings between the two groups decreased at 12 months after surgery except for reflux esophagitis, which was observed more frequently in the 29-mm group (P=.002). The length of the incision was smaller in the 25-mm group than in the 29-mm group (4.39 cm versus 4.95 cm, P=.009). A small-diameter stapler is a risk factor for gastric stasis in the early postoperative period, whereas a large-diameter stapler is a risk factor for gastritis and bile reflux in the early postoperative period and for esophagitis in the late postoperative period. Thus, a small-diameter circular stapler has more advantages over a large-diameter circular stapler. It also enables a reliable anastomosis through a smaller incision and easy handling of the stapler during anastomosis.

MicroRNA-196a & microRNA-101 expression in Barrett's oesophagus in patients with medically and surgically treated gastro-oesophageal reflux

PubMed Central

2011-01-01

Background Proton pump inhibitor (PPI) medication and surgical fundoplication are used for the control of gastro-oesophageal reflux in patients with Barrett's oesophagus, but differ in their effectiveness for both acid and bile reflux. This might impact on the inflammatory processes that are associated with progression of Barrett's oesophagus to cancer, and this may be evident in the gene expression profile and microRNA expression pattern in Barrett's oesophagus mucosa. We hypothesised that two miRNAs with inflammatory and oncogenic roles, miR-101 and miR-196a, are differentially expressed in Barrett's oesophagus epithelium in patients with reflux treated medically vs. surgically. Findings Mucosal tissue was obtained at endoscopy from patients with Barrett's oesophagus whose reflux was controlled by proton pump inhibitor (PPI) therapy (n = 20) or by fundoplication (n = 19). RNA was extracted and the expression of miR-101 and miR-196a was measured using real-time reverse transcription - polymerase chain reaction. There were no significant differences in miR-101 and miR-196a expression in Barrett's oesophagus epithelium in patients treated by PPI vs. fundoplication (p = 0.768 and 0.211 respectively). Secondary analysis showed a correlation between miR-196a expression and Barrett's oesophagus segment length (p = 0.014). Conclusion The method of reflux treatment did not influence the expression of miR-101 and miR-196a in Barrett's oesophagus. This data does not provide support to the hypothesis that surgical treatment of reflux better prevents cancer development in Barrett's oesophagus. The association between miR-196a expression and Barrett's oesophagus length is consistent with a tumour promoting role for miR-196a in Barrett's oesophagus. PMID:21352563

Characterization of basal hepatic bile flow and the effects of intravenous cholecystokinin on the liver, sphincter, and gallbladder in patients with sphincter of Oddi spasm.

PubMed

Krishnamurthy, Gerbail T; Krishnamurthy, Shakuntala; Watson, Randy D

2004-01-01

The major objectives of this project were to establish the pattern of basal hepatic bile flow and the effects of intravenous administration of cholecystokinin on the liver, sphincter of Oddi, and gallbladder, and to identify reliable parameters for the diagnosis of sphincter of Oddi spasm (SOS). Eight women with clinically suspected sphincter of Oddi spasm (SOS group), ten control subjects (control group), and ten patients who had recently received an opioid (opioid group) were selected for quantitative cholescintigraphy with cholecystokinin. Each patient was studied with 111-185 MBq (3-5 mCi) technetium-99m mebrofenin after 6-8 h of fasting. Hepatic phase images were obtained for 60 min, followed by gallbladder phase images for 30 min. During the gallbladder phase, 10 ng/kg octapeptide of cholecystokinin (CCK-8) was infused over 3 min through an infusion pump. Hepatic extraction fraction, excretion half-time, basal hepatic bile flow into the gallbladder, gallbladder ejection fraction, and post-CCK-8 paradoxical filling (>30% of basal counts) were identified. Seven of the patients with SOS were treated with antispasmodics (calcium channel blockers), and one underwent endoscopic sphincterotomy. Mean (+/-SD) hepatic bile entry into the gallbladder (versus GI tract) was widely variable: it was lower in SOS patients (32%+/-31%) than in controls (61%+/-36%) and the opioid group (61%+/-25%), but the difference was not statistically significant. Hepatic extraction fraction, excretion half-time, and pattern of bile flow through both intrahepatic and extrahepatic ducts were normal in all three groups. Gallbladder mean ejection fraction was 9%+/-4% in the opioid group; this was significantly lower (P<0.0001) than the values in the control group (54%+/-18%) and the SOS group (48%+/-29%). Almost all of the bile emptied from the gallbladder refluxed into intrahepatic ducts; it reentered the gallbladder after cessation of CCK-8 infusion (paradoxical gallbladder filling) in all eight patients with SOS, but in none of the patients in the other two groups. Mean paradoxical filling was 204% (+/-193%) in the SOS group and less than 5% (P<0.05) in both the control and the opioid group. After treatment, six of the SOS patients had complete pain relief and one, partial pain relief. The basal tonus of the sphincter is variable in patients with SOS, and allows relatively more of the hepatic bile to enter the GI tract than the gallbladder. Due to simultaneous contraction of the sphincter and gallbladder in response to CCK-8, most of the bile emptied from the gallbladder refluxes into intrahepatic ducts, and reenters the gallbladder immediately after cessation of hormone infusion. The characteristic features of gallbladder filling, emptying, and paradoxical refilling with cholecystokinin provide objective parameters for noninvasive diagnosis of SOS by quantitative cholescintigraphy.

Update on radionuclide imaging in hepatobiliary disease. [/sup 99m/Tc-labelled acetanilide iminodracetic acid analogues

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rosenthall, L.

1981-05-01

The recent introduction of technetium Tc 99m-labeled acetanilide iminodiacetic acid (/sup 99m/Tc-IDA) analogues has facilitated the clincal study of the bile flow pathways. A variety of /sup 99m/Tc-IDA derivaties are under investigation. Basically all are metabolized by the hepatocyte and immediately thereafter excreted unconjugated into the biliary tract. Of the various derivatives tested, e.g., dimethyl (lidofenin), diethyl, paraisopropyl (iprofenin), parabutyl (butilfenin), and diisopropyl (disofenin), the last named is the best universal agent at this time. By serial liver imaging the patency of the cystic duct and the integrity of altered cholangiointestinal anatomy can be assessed, leakage of bile and gastricmore » reflux can be disclosed, and medical and surgical jaundice can be distinguished.« less

Expression of protease-activated-receptor 2 (PAR-2) in human esophageal mucosa.

PubMed

Inci, Kamuran; Edebo, Anders; Olbe, Lars; Casselbrant, Anna

2009-01-01

The role of duodenal reflux in gastroesophageal reflux disease (GERD) containing bile salts and pancreatic enzymes (with special attention to trypsin) is still under discussion. Proteinase-activated receptors (PARs) are a novel family and PAR-2 is a unique member of this family because it is activated by trypsin. The aim of the present study was to examine the presence and the position of the PAR-2 receptor in human esophageal mucosa in different subgroups of GERD. Distal biopsies taken from healthy controls, patients with erosive reflux disease (ERD), patients with specialized intestinal metaplasia (SIM) and adenocarcinoma were analyzed for the PAR-2 receptor with reverse-transcription polymerase chain reaction (RT-PCR), Western blotting and immunohistochemistry. Gene transcripts for the PAR-2 receptor were found in all groups, with increased levels in SIM patients compared to controls. However, this visual pattern was not seen for the protein expression of the PAR-2 receptor showing no apparent quantitative differences between the groups. Immunohistochemistry revealed distinct staining for the PAR-2 receptor in the luminal part of the esophageal epithelium. The localization of the PAR-2 receptor indicates that the receptor can be cleaved and activated by trypsin in duodenogastric esophageal refluxate. The data thus suggest that the trypsin-PAR-2 pathway may be involved in the pathogenesis of GERD.

The bile acid deoxycholic acid has a non-linear dose response for DNA damage and possibly NF-kappaB activation in oesophageal cells, with a mechanism of action involving ROS.

PubMed

Jenkins, G J S; Cronin, J; Alhamdani, A; Rawat, N; D'Souza, F; Thomas, T; Eltahir, Z; Griffiths, A P; Baxter, J N

2008-09-01

Deoxycholic acid (DCA) is a secondary bile acid implicated in various cancers of the gastrointestinal (GI) tract. In oesophageal adenocarcinoma, DCA is believed to contribute to carcinogenesis during reflux where stomach contents enter the lower oesophagus. It is imperative that we understand the mechanisms whereby oesophageal carcinogens function in order that therapeutic options may be developed. We have previously shown that DCA can damage chromosomes and does so through its generation of reactive oxygen species (ROS). We show here, after detailed experiments, that DCA appears to have a non-linear dose response for DNA damage. DCA induces DNA damage (as measured by the micronucleus assay) at doses of 100 microM and higher in oesophageal OE33 cells, but fails to induce such DNA damage below this cut-off dose. We also show that in terms of NF-kappaB activation (as measured by up-regulation of two NF-kappaB target genes) by DCA, a similar dose response is observed. This dose-response data may be important clinically as DCA exposure to the oesophagus may be used as a way to identify the 10% of Barrett's oesophagus patients currently progressing to cancer from the 90% of patients who do not progress. Only quantitative studies measuring DCA concentrations in refluxates correlated with histological progression will answer this question. We further show here that ROS are behind DCAs ability to activate NF-kappaB as antioxidants (epigallocatechin gallate, resveratrol and vitamin C) abrogate DCAs ability to up-regulate NF-kappaB-controlled genes. In conclusion, low doses of DCA appear to be less biologically significant in vitro. If this were to be confirmed in vivo, it might suggest that reflux patients with low DCA concentrations may be at a lower risk of cancer progression compared to patients with high levels of DCA in their refluxate. Either way, antioxidant supplementation may possibly help prevent the deleterious effects of DCA in the whole GI tract.

Treatment of reflux gastritis: double blind comparison between clebopride and domperidone. A preliminary report.

PubMed

Angelini, G; Castagnini, A; Rizzoli, R; Pasini, A F; Lavarini, E; Brocco, G; Scuro, L A

1990-02-01

Altered gastro-duodenal motility seems to be a major factor of alkaline gastritis. Therefore prokinetic drugs have been extensively used for the treatment of this disease. Aim of this study has been to compare the effects of domperidone with those of a more recent drug of the orthopramide class, clebopride. Thirty patients affected by reflux gastritis have been randomly allocated to one of the two treatments. Clinical symptoms, endoscopic and histologic appearance of gastric mucosa, gastric pH and bile acid concentration in gastric juice have been evaluated before and after a four week course of therapy. A statistically significant improvement was observed for the clinical symptoms in the subjects treated with clebopride. Even if no statistical difference has been pointed out for the other parameters between and within the two groups, a slight trend in favour of clebopride was observed. It is concluded that clebopride is at least as effective as domperidone for the treatment of reflux gastritis but that more prolonged studies and different administration schedules are requested for a better evaluation.

The evolution of a valved hepatoduodenal intestinal conduit.

PubMed

Kaufman, B H; Luck, S R; Raffensperger, J G

1981-06-01

Ascending cholangitis remains among the most serious complications following operations for biliary disorders. The bacterial count of refluxing intestinal contents can be reduced by using an enteric conduit from the biliary tract to the relatively sterile duodenum. A valvular conduit prohibits reflux of intestinal contents and permits unobstructed antegrade flow of bile. This can be created by intussuscepting approximately 1 cm of intestine in the midportion of the conduit. During the last 3 yr, valvular conduits were created in 11 patients. Seven of these children were treated for biliary atresia, and 4 had operations for choledochal duct cysts. There have been no deaths or morbidity resulting from the use of the valvular conduits. The postoperative courses in these patients indicate that the use of an intussusception valve may be beneficial in the prevention of ascending cholangitis.

Malignant biliary obstruction complicated by ascites: Closure of the transhepatic tract with cyanoacrylate glue after placement of an endoprosthesis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cekirge, Saruhan; Akhan, Okan; Ozmen, Mustafa

1997-05-15

A new technique using cyanoacrylate glue is suggested for closing the transparenchymal tract following metallic endoprosthesis placement in a patient with malignant biliary obstruction complicated by ascites. With this technique, complications related to bile reflux through the transparenchymal tract would be avoided after transhepatic endoprosthesis placement in patients who have ascites. This technique would also be useful for avoiding bleeding following transhepatic portal venous puncture.

A valved hepatic portoduodenal intestinal conduit for biliary atresia.

PubMed

Tanaka, K; Shirahase, I; Utsunomiya, H; Katayama, T; Uemoto, S; Asonuma, K; Inomata, Y; Ozawa, K

1991-03-01

Forty-six consecutive patients with biliary atresia were operated on at our institution during the 11-year period between 1978 and 1989. Their ages at operation ranged from 18 to 153 days (mean, 59 days). After dissecting the porta hepatis structures by Kasai operation, a biliointestinal anastomosis was constructed with a valved hepatic portoduodenal intestinal conduit in all cases. The intestinal valve is an intussuscepted muscular valve. Valvular function was examined radiologically. The upper gastrointestinal series demonstrated no reflux of contrast material into the conduit proximal to the valve and liver scintigraphy demonstrated that radioactive isotope drained readily into the duodenum through the valve. Thirty-nine of the forty-six patients (85%) had bile drainage after initial operation. At present 30 patients (65%) are alive without jaundice, 6 (13%) are alive with jaundice, and 10 (22%) are dead. The 5-year jaundice-free survival rate was 64%. Cholangitis occurred in 9 of 39 patients (23%) who had obtained apparent bile drainage: 5 had tractable cholangitis and 4 had refractory cholangitis. Reoperation restored bile flow in 2 of 8 patients who abruptly ceased to have bile drainage without cholangitis. In conclusion, with a valved hepatic portoduodenal intestinal conduit, the incidence of cholangitis was decreased, its medical control became easier, and the survival rate was improved.

Pepsin and bile acid concentrations in sputum of mustard gas exposed patients.

PubMed

Karbasi, Ashraf; Goosheh, Hassan; Aliannejad, Rasoul; Saber, Hamid; Salehi, Maryam; Jafari, Mahvash; Imani, Saber; Saburi, Amin; Ghanei, Mostafa

2013-01-01

Gastro-esophageal reflux has been suggested to be associated with several pulmonary complications such as asthma, and post-transplant bronchiolitis obliterans (BO). Pepsin or bile salts in the sputum is shown to be an optimal molecular marker of gastric contents macro/micro aspiration. In this study, we investigated sputum pepsin as a marker of micro-aspiration in sulfur mustard (SM) exposed cases compared to healthy controls. In a case controlled study, 26 cases with BO and 12 matched healthy controls were recruited and all cases were symptomatic and their exposure to SM was previously documented during Iran-Iraq conflict. Pepsin levels in sputum and total bile acids were measured using enzymatic assay. The severity of respiratory disorder was categorized based upon the spirometric values. The average concentration of pepsin in sputum was higher in the case group (0.29 ± 0.23) compared with healthy subjects (0.13 ± 0.07; P ± 0.003). Moreover, the average concentration of bile acids in the sputum cases was not significantly different in comparison to the controls ( P = 0.5). Higher pepsin concentrations in sputum of SM exposed patients compared with healthy control subjects indicate the occurrence of significantly more gastric micro-aspiration in SM exposed patients.

Pepsin and Bile Acid Concentrations in Sputum of Mustard Gas Exposed Patients

PubMed Central

Karbasi, Ashraf; Goosheh, Hassan; Aliannejad, Rasoul; Saber, Hamid; Salehi, Maryam; Jafari, Mahvash; Imani, Saber; Saburi, Amin; Ghanei, Mostafa

2013-01-01

Background/Aim: Gastro-esophageal reflux has been suggested to be associated with several pulmonary complications such as asthma, and post-transplant bronchiolitis obliterans (BO). Pepsin or bile salts in the sputum is shown to be an optimal molecular marker of gastric contents macro/micro aspiration. In this study, we investigated sputum pepsin as a marker of micro-aspiration in sulfur mustard (SM) exposed cases compared to healthy controls. Materials and Methods: In a case controlled study, 26 cases with BO and 12 matched healthy controls were recruited and all cases were symptomatic and their exposure to SM was previously documented during Iran-Iraq conflict. Pepsin levels in sputum and total bile acids were measured using enzymatic assay. The severity of respiratory disorder was categorized based upon the spirometric values. Result: The average concentration of pepsin in sputum was higher in the case group (0.29 ± 0.23) compared with healthy subjects (0.13 ± 0.07; P ± 0.003). Moreover, the average concentration of bile acids in the sputum cases was not significantly different in comparison to the controls (P = 0.5). Conclusion: Higher pepsin concentrations in sputum of SM exposed patients compared with healthy control subjects indicate the occurrence of significantly more gastric micro-aspiration in SM exposed patients. PMID:23680709

Cough reflex sensitization from esophagus and nose

PubMed Central

Hennel, Michal; Brozmanova, Mariana; Kollarik, Marian

2015-01-01

The diseases of the esophagus and nose are among the major factors contributing to chronic cough although their role in different patient populations is debated. Studies in animal models and in humans show that afferent C-fiber activators applied on esophageal or nasal mucosa do not initiate cough, but enhance cough induced by inhaled irritants. These results are consistent with the hypothesis that activation of esophageal and nasal C-fibers contribute to cough reflex hypersensitivity observed in chronic cough patients with gastroesophageal reflux disease (GERD) and chronic rhinitis, respectively. The afferent nerves mediating cough sensitization from the esophagus are probably the neural crest-derived vagal jugular C-fibers. In addition to their responsiveness to high concentration of acid typical for gastroesophageal reflux (pH<5), esophageal C-fibers also express receptors for activation by weakly acidic reflux such as receptors highly sensitive to acid and receptors for bile acids. The nature of sensory pathways from the nose and their activators relevant for cough sensitization are less understood. Increased cough reflex sensitivity was also reported in many patients with GERD or rhinitis who do not complain of cough indicating that additional endogenous or exogenous factors may be required to develop chronic coughing in these diseases. PMID:26498387

Reflux-Associated Cholecystopathy: Analysis of 76 Gallbladders From Patients With Supra-Oddi Union of the Pancreatic Duct and Common Bile Duct (Pancreatobiliary Maljunction) Elucidates a Specific Diagnostic Pattern of Mucosal Hyperplasia as a Prelude to Carcinoma.

PubMed

Muraki, Takashi; Memis, Bahar; Reid, Michelle D; Uehara, Takeshi; Ito, Tetsuya; Hasebe, Osamu; Okaniwa, Shinji; Horigome, Naoto; Hisa, Takeshi; Mittal, Pardeep; Freedman, Alexa; Maithel, Shishir; Sarmiento, Juan M; Krasinskas, Alyssa; Koshiol, Jill; Adsay, Volkan

2017-09-01

Pancreaticobiliary maljunction (PBM) is the anomalous union of the main pancreatic duct and common bile duct outside the Oddi-sphincter, allowing the reflux of pancreatic juice to the gallbladder. There is only limited awareness and understanding of the pathologic correlates of this condition, mostly from Japan; this entity is largely unrecognized in the West. In this study, 76 gallbladders from patients with PBM (64 from Japan; 12 from the United States) were analyzed and contrasted with 66 from non-PBM patients. These were predominantly females (54 vs. 22), mean age, 53 (range: 14 to 81). Cholelithiasis was uncommon (16% vs. 80% in non-PBM, P<0.01) whereas cholesterolosis was more common (49% vs. 29%, P=0.02) suggesting an altered chemical milieu. There was a distinctive diffuse mucosal hyperplasia (82% vs. 42%, P<0.01) with markedly elongated folds (mean: 1.1 vs. 0.7 mm, P<0.01) composed of compact villoglandular proliferation, often showing broad-based pushing into muscle, accompanied by prominent and more complex Rokitansky-Aschoff sinus formation (2.0 vs. 1.0/cm, P<0.01) at the base. At the tips, this villiform hyperplasia displayed frequent horizontal bridging of the folds (68% vs. 47%, P=0.01), bulbous dilatation (52% vs. 21%, P<0.01) as well as deposition of a peculiar amyloid-like hyaline material (56% vs. 15%, P<0.01). Despite paucity of inflammation and gallstones, findings attributed to mucosal injury were common including: pyloric gland metaplasia (70% vs. 48%, P=0.01) and intestinal metaplasia (24% vs. 6%, P<0.01). Invasive gallbladder carcinoma was present in 22 (29%) of the cases with 6 of these (27%) arising in association with intracholecystic papillary tubular neoplasm. Five cases had bile duct carcinoma at the time of cholecystectomy and 1 developed it 4 years after. In conclusion, gallbladders with patients with PBM display a distinctive pattern of mucosal hyperplasia with distinguishing features, which in constellation render it a microscopically diagnosable specific entity. We propose to refer to this entity as "reflux-associated cholecystopathy." Recognition of the pathologic characteristics of this entity is important so that investigation for, as well as treatment and prevention of, PBM-associated complications (biliary tract cancers and pancreatitis) can be instituted. This group also offers a distinct model of carcinogenesis (chemical rather than inflammatory) in the gallbladder for cancer researchers to scrutinize.

GERD related micro-aspiration in chronic mustard-induced pulmonary disorder.

PubMed

Aliannejad, Rasoul; Hashemi-Bajgani, Seyed-Mehdi; Karbasi, Asharaf; Jafari, Mahvash; Aslani, Jafar; Salehi, Maryam; Ghanei, Mostafa

2012-08-01

Bronchiolitis obliterans (BO) is the main pulmonary involvement resulting from sulfur mustard (SM) gas exposure that was used against Iranian civilians and military forces during the Iran-Iraq war. The present study aimed to investigate the prevalence of gastro-esophageal reflux (GER) and gastric micro-aspiration in SM gas injured patients with chronic pulmonary diseases and recurrent episodes of exacerbations. This cross-sectional study was done at Baqiyatallah University of Medical Sciences, Tehran, Iran. Gastric micro-aspiration and GER were assessed in the enrolled patients by assessing bile acids, pepsin and trypsin in their bronchoalveolar lavage fluid. Our result showed that bile acids were found to be high in 21.4% patients, and low in 53.6% of patients. Only in 16% patients, no bile was detected in the BALF. Trypsin and pepsin were detected in BAL fluid of all patients. Most of BO patients after exposure to SM suffer GER, while none the etiologic factors of GER in post lung transplant BO are present. It would be hypothesized that GER per se could be considered as an aggregative factor for exacerbations in patients. Further studies will provide more advances to better understanding of pathophysiological mechanism regarding GER and BO and treatment.

Hepatic immunohistochemical localization of the tight junction protein ZO-1 in rat models of cholestasis.

PubMed Central

Anderson, J. M.; Glade, J. L.; Stevenson, B. R.; Boyer, J. L.; Mooseker, M. S.

1989-01-01

Structural alterations in hepatocyte tight junctions accompanying cholestasis were investigated using immunolocalization of ZO-1, the first known protein component of the tight junction. Disruption in the paracellular barrier function of the tight junction has been proposed to allow reflux of bile into the blood. Cholestasis was induced in 210 to 235 g male Sprague-Dawley rats either by five consecutive daily subcutaneous injections of 17-alpha-ethinyl estradiol (0.5 mg/kg/d in propylene glycol) or ligation of the common bile duct for 72 hours. The structural organization of the tight junction was assessed in each model by indirect immunofluorescent and immunoperoxidase staining for ZO-1 on frozen sections of liver and compared with controls. In control, sham-operated, and estradiol-injected animals, ZO-1 localizes in a uniform continuous manner along the margins of the canaliculi. In contrast, bile duct ligation results in the appearance of numerous discontinuities in ZO-1 staining accompanied by dilation or collapse of the lumenal space. Tissue content of the ZO-1 protein, as determined by quantitative immunoblotting, was unaffected in either cholestatic model compared with controls. These findings indicate that the molecular organization of the tight junction can be assessed from immunostaining patterns of ZO-1 in frozen sections of cholestatic livers. Under these experimental conditions, the organization of the tight junction at the level of the ZO-1 protein is altered by bile duct obstruction but not by ethinyl estradiol. Images Figure 1 Figure 2 PMID:2719075

GERD related micro-aspiration in chronic mustard-induced pulmonary disorder

PubMed Central

Aliannejad, Rasoul; Hashemi-Bajgani, Seyed-Mehdi; Karbasi, Asharaf; Jafari, Mahvash; Aslani, Jafar; Salehi, Maryam; Ghanei, Mostafa

2012-01-01

Background and Aim: Bronchiolitis obliterans (BO) is the main pulmonary involvement resulting from sulfur mustard (SM) gas exposure that was used against Iranian civilians and military forces during the Iran-Iraq war. The present study aimed to investigate the prevalence of gastro-esophageal reflux (GER) and gastric micro-aspiration in SM gas injured patients with chronic pulmonary diseases and recurrent episodes of exacerbations. Materials and Methods: This cross-sectional study was done at Baqiyatallah University of Medical Sciences, Tehran, Iran. Gastric micro-aspiration and GER were assessed in the enrolled patients by assessing bile acids, pepsin and trypsin in their bronchoalveolar lavage fluid. Results: Our result showed that bile acids were found to be high in 21.4% patients, and low in 53.6% of patients. Only in 16% patients, no bile was detected in the BALF. Trypsin and pepsin were detected in BAL fluid of all patients. Conclusion: Most of BO patients after exposure to SM suffer GER, while none the etiologic factors of GER in post lung transplant BO are present. It would be hypothesized that GER per se could be considered as an aggregative factor for exacerbations in patients. Further studies will provide more advances to better understanding of pathophysiological mechanism regarding GER and BO and treatment. PMID:23798946

Successful treatment of recurrent cholangitis by constructing a hepaticojejunostomy with long Roux-en-Y limb in a long-term surviving patient after a Whipple procedure for pancreatic adenocarcinoma.

PubMed

Tsalis, Konstantinos; Antoniou, Nikolaos; Koukouritaki, Zambia; Patridas, Dimitrios; Sakkas, Leonidas; Kyziridis, Dimitrios; Lazaridis, Charalampos

2014-08-20

Female, 74. Recurrent cholangitis. -. -. -. Gastroenterology and Hepatology. Unusual clinical course. Cholangitis may result from biliary obstruction (e.g., biliary or anastomotic stenosis, or foreign bodies) or occur in the presence of normal biliary drainage. Although reflux of intestinal contents into the biliary tree after hepaticojejunostomy appears to be a rare complication, it is important to emphasize that there are few available surgical therapeutic techniques. A 74-year-old woman presented to our hospital after 17 years of episodes of cholangitis. The patient had undergone a pancreatoduodenectomy (Whipple procedure) 18 years earlier due to pancreatic adenocarcinoma. The reconstruction was achieved through the sequential placement of pancreatic, biliary, and retrocolic gastric anastomosis into the same jejunal loop. The postoperative course was uneventful and the patient received adjuvant chemotherapy. Approximately 6 months after the initial operation, the patient started having episodes of cholangitis. Over the next 17 years she experienced several febrile episodes presumed to be secondary to cholangitis. A computing tomography (CT) scan of the abdomen revealed intrahepatic bile ducts partially filled with orally administered contrast material (Gastrografin). Magnetic resonance cholangiopancreatography (MRCP) showed dilatation of the left intrahepatic bile ducts. A percutaneous transhepatic cholangiography showed that the bilioenteric anastomosis was normal, without stenosis. Based on these findings, a diagnosis of a short loop between the hepaticojejunostomy and the gastrojejunostomy permitting the reflux of intestinal juice into the biliary tree was made. During the re-operation, a new hepaticojejunal anastomosis in a 100-cm long Roux-en-Y loop was performed to prevent the reflux of the intestinal fluid into the biliary tree. The patient was discharged on postoperative day 10. One year after the second procedure, the patient enjoys good health and has been free of fever and abdominal pain and has not received any antibiotic therapy. Lengthening the efferent Roux-en-Y limb should be considered as a therapeutic option when treating a patient with recurrent episodes of cholangitis after hepaticojejunostomy.

Should peri-gastrectomy gastric acidity be our focus among gastric cancer patients?

PubMed

Huang, Lei; Xu, A-Man; Li, Tuan-Jie; Han, Wen-Xiu; Xu, Jing

2014-06-14

To investigate the necessity and correctness of acid suppression pre- and post-gastrectomy among gastric carcinoma (GC) patients. From June 2011 to April 2013, 99 patients who were diagnosed with GC or adenocarcinoma of the gastroesophageal junction (type II or III) and needed surgical management were enrolled. They all underwent gastrectomy by the same operators [35 undergoing total gastrectomy (TG) plus Roux-en-Y reconstruction, 34 distal gastrectomy (DG) plus Billroth I reconstruction, and 30 proximal gastrectomy (PG) plus gastroesophagostomy]. We collected and analyzed their gastrointestinal juice and tissues from the pre-operational day to the 5(th) day post-operation, and 6 mo post-surgery. Gastric pH was detected with a precise acidity meter. Gastric juice contents including potassium, sodium and bicarbonate ions, urea nitrogen, direct and indirect bilirubin, and bile acid were detected using Automatic Biochemical Analyzer. Data regarding tumor size, histological type, tumor penetration and tumor-node-metastasis (TNM) stage were obtained from the pathological records. Reflux symptoms pre- and 6 mo post-gastrectomy were evaluated by reflux disease questionnaire (RDQ) and gastroesophageal reflux disease questionnaire (GERD-Q). SPSS 16.0 was applied to analyze the data. Before surgery, gastric pH was higher than the threshold of hypoacidity (4.25 ± 1.45 vs 3.5, P = 0.000), and significantly affected by age, tumor size and differentiation grade, and potassium and bicarbonate ions; advanced malignancies were accompanied with higher pH compared with early ones (4.49 ± 1.31 vs 3.66 ± 1.61, P = 0.008). After operation, gastric pH in all groups was of weak-acidity and significantly higher than that pre-gastrectomy; on days 3-5, comparisons of gastric pH were similar between the 3 groups. Six months later, gastric pH was comparable to that on days 3-5; older patients were accompanied with higher total bilirubin level, indicating more serious reflux (r = 0.238, P = 0.018); the TG and PG groups had higher RDQ (TG vs DG: 15.80 ± 5.06 vs 12.26 ± 2.14, P = 0.000; PG vs DG: 15.37 ± 3.49 vs 12.26 ± 2.14, P = 0.000) and GERD-Q scores (TG vs DG: 10.54 ± 3.16 vs 9.15 ± 2.27, P = 0.039; PG vs DG: 11.00 ± 2.07 vs 9.15 ± 2.27, P = 0.001) compared with the DG group; all gastric juice contents except potassium ion significantly rose; reflux symptom was significantly associated with patient's body mass index, direct and indirect bilirubin, and total bile acid, while pH played no role. Acidity is not an important factor causing unfitness among GC patients. There is no need to further alkalify gastrointestinal juice both pre- and post-gastrectomy.

Pancreatogenic choledocholithiasis in common bile duct stump after Roux-en-Y hepaticojejunostomy

PubMed Central

Jiang, Yuan-Hui; Zhang, An-Hong; Zhou, Shao-Jun

2017-01-01

Abstract Rationale: Choledocholithiasis in common bile duct (CBD) stump after Roux-en-Y hepaticojejunostomy (RYHJ) is incredibly rare and its pathophysiology is poorly understood. Patient concerns: A 79-year-old woman was admitted to our hospital with upper abdominal pain radiating through to the back in November 2016. Diagnoses: Abdominal computed tomography (CT) scan and magnetic resonance cholangiopancreatography (MRCP) revealed filling defects in CBD stump, chronic pancreatitis, and dilatation of CBD stump and main pancreatic duct (MPD). Interventions: During the endoscopic retrograde cholangiopancreatography (ERCP), cannulation proceeded easily from MPD to CBD through a variant pancreatic duct, and then white crushed stones extracted from the CBD stump. Elemental analysis and infrared spectrophotometry demonstrated that the main constituent of the calculi was calcium carbonate. Outcomes: After a therapeutic ERCP, the patient's symptoms disappeared, and a 9-month follow-up indicated no remaining stones or lithiasis relapse. Lessons: This type of choledocholithiasis in CBD stump after RYHJ has never been reported before. We nominated it as “pancreatogenic choledocholithiasis,” and pancreatobiliary reflux caused by a variant pancreatic duct may be the main cause. PMID:29145338

Predictive Factors of Biliary Tract Cancer in Anomalous Union of the Pancreaticobiliary Duct

PubMed Central

Park, Jin-Seok; Song, Tae Jun; Park, Tae Young; Oh, Dongwook; Lee, Hyun Kyo; Park, Do Hyun; Lee, Sang Soo; Seo, Dong Wan; Lee, Sung Koo; Kim, Myung-Hwan

2016-01-01

Abstract The assessment of malignancies associated with anomalous union of the pancreaticobiliary duct (AUPBD) is essential for the design of appropriate treatment strategies. The aim of the present study is to measure the incidence of AUPBD-related pancreaticobiliary malignancy and to identify predictive factors. This retrospective cohort study included cases of 229 patients with AUPBD between January 1999 and December 2013. The impact of bile duct dilatation on the incidence of AUPBD-related pancreaticobiliary disease was measured, and predictive factors were evaluated. Among 229 patients with AUPBD, 152 had common bile duct dilatation (≥10 mm) (dilated group) and 77 did not (<10 mm) (nondilated group). Intrahepatic cholangiocarcinoma occurred more frequently in the nondilated group than in the dilated group (3.9% vs 0%; P < 0.05). By contrast, no significant difference in the incidence of extrahepatic cholangiocarcinoma was observed between the 2 groups (1.3% vs 3.9%; P = 0.271). By univariate analysis, age, type of AUPBD, and the level of pancreatic enzymes refluxed in the bile duct were associated with occurrence of biliary tract cancers. In multivariate analysis, age ≥45 years (odds ratio [OR] 1.042, 95% confidence interval [CI] 1.011–1.073, P < 0.05), P-C type (OR 3.327, 95% CI 1.031–10.740, P < 0.05), and a high level of biliary lipase (OR 4.132, 95% CI 1.420–12.021, P < 0.05) showed a significant association with AUPBD-related biliary tract cancer. Intrahepatic cholangiocarcinoma may occur more frequently in AUPBD patients without bile duct dilatation. Age ≥45 years, P-C type, and biliary lipase level ≥45,000 IU/L are significantly associated with AUPBD-related biliary tract cancer. PMID:27196455

Bile salt receptor TGR5 is highly expressed in esophageal adenocarcinoma and precancerous lesions with significantly worse overall survival and gender differences

PubMed Central

Pang, Chunhong; LaLonde, Amy; Godfrey, Tony E; Que, Jianwen; Sun, Jun; Wu, Tong Tong; Zhou, Zhongren

2017-01-01

Bile acid reflux in the esophagus plays an important role in the carcinogenesis of esophageal adenocarcinoma (EAC). The G-protein coupled bile acid receptor (TGR5) has been associated with the development of gastrointestinal cancer. However, little is known regarding the role of TGR5 in esophageal carcinoma and precancerous lesions. We analyzed genomic DNA from 116 EACs for copy number aberrations via Affymetrix SNP6.0 microarrays. The TGR5 gene locus was amplified in 12.7% (14/116) of the EACs. The TGR5 protein expression was also assessed using immunohistochemistry from tissue microarrays, including Barrett’s esophagus (BE), low-(LGD) and high-grade dysplasia (HGD), columnar cell metaplasia (CM), squamous epithelium (SE), EAC and squamous cell carcinoma. The TGR5 protein was highly expressed in 71% of EAC (75/106), 100% of HGD (11/11), 72% of LGD (13/18), 66% of BE (23/35), 84% of CM (52/62), and 36% of SE (30/83). The patients with high expression of TGR5 exhibited significantly worse overall survival compared to the patients with nonhigh expression. TGR5 high expression was significantly increased in the males compared to the females in all cases with an odds ratio of 1.9 times. The vitamin D receptor (VDR) was significantly correlated with TGR5 expression. Our findings indicated that TGR5 may play an important role in the development and prognosis of EAC through a bile acid ligand. Gender differences in TGR5 and VDR expression may explain why males have a higher incidence of EAC compared to females. PMID:28223834

Response of cricopharyngeus muscle to esophageal stimulation by mechanical distension and acid and bile perfusion.

PubMed

Chernichenko, Natalya; Woo, Jeong-Soo; Hundal, Jagdeep S; Sasaki, Clarence T

2011-02-01

The aim of this study was to identify the response of the cricopharyngeus muscle (CPM) to esophageal stimulation by intraluminal mechanical distension and intraluminal acid and bile perfusion. In 3 adult pigs, electromyographic (EMG) activity of the CPM was recorded at baseline and after esophageal stimulation at 3 levels: proximal, middle, and distal. The esophagus was stimulated with 20-mL balloon distension and intraluminal perfusion of 40 mL 0.1N hydrochloric acid, taurocholic acid (pH 1.5), and chenodeoxycholic acid (pH 7.4) at the rate of 40 mL/min. The EMG spike density was defined as peak-to-peak spikes greater than 10 microV averaged over 10-ms intervals. In all 3 animals, the spike density at baseline was 0. The spike densities increased after proximal and middle distensions to 15.2 +/- 1.5 and 5.1 +/- 1.2 spikes per 10 ms, respectively. No change in CPM EMG activity occurred after distal distension. The spike density following intraluminal perfusion with hydrochloric acid at the distal level was 10.1 +/- 1.1 spikes per 10 ms. No significant change in CPM EMG activity occurred after acid perfusion at the middle and proximal levels. No change in CPM EMG activity occurred after intraluminal esophageal perfusion with either taurocholic acid or chenodeoxycholic acid. Proximal esophageal distension, as well as distal intraluminal acid perfusion, appeared to be important mechanisms in generation of CPM activity. Bile acids, on the other hand, failed to evoke such CPM activity. The data suggest that transpyloric refluxate may not be significant enough to evoke the CPM protective sphincteric function, thereby placing supraesophageal structures at risk of bile injury.

What is the best reconstruction method after distal gastrectomy for gastric cancer?

PubMed

Lee, Moon-Soo; Ahn, Sang-Hoon; Lee, Ju-Hee; Park, Do Joong; Lee, Hyuk-Joon; Kim, Hyung-Ho; Yang, Han-Kwang; Kim, Nayoung; Lee, Won Woo

2012-06-01

We performed this prospective randomized study to evaluate what is the best reconstruction method after distal gastrectomy for gastric cancer. One hundred fifty-nine patients who underwent laparoscopy-assisted or open gastrectomy for gastric cancer were analyzed from March 2006 to August 2007. Billroth I (B-I) anastomosis, Billroth II (B-II) with Braun anastomosis, and Roux-en-Y (R-Y) anastomosis were applied randomly. Additionally, the patients were divided into two groups based on treatment type: laparoscopic and open operation. Endoscopy and hepatobiliary scans were performed to investigate gastric stasis and enterogastric reflux. The Gastrointestinal Quality of Life Index (GIQLI) was used to evaluate postoperative quality of life, and the hematologic test was used to assess nutritional aspect. Endoscopy revealed that reflux after the R-Y anastomosis procedure was significantly less frequent than after the other anastomosis types at 12 months. Comparison of the GIQLI and the nutritional parameters between the reconstruction types revealed that there were no differences, but a significantly higher GIQLI score was observed in the laparoscopic group immediately following the procedure (P = 0.042). R-Y anastomosis is superior to B-I and B-II with Braun anastomosis in terms of frequency of bile reflux, despite the fact that there is no difference in the postoperative quality-of-life index and nutritional status between reconstructive procedures. The laparoscopic approach is the better option than open surgery in terms of QOL in the immediate postoperative period.

Bilious Vomiting Syndrome in Dogs: Retrospective Study of 20 Cases (2002-2012).

PubMed

Ferguson, Leah; Wennogle, Sara A; Webb, Craig B

2016-01-01

Bilious vomiting syndrome (BVS) is a condition historically associated with early morning vomiting of bile, but it is otherwise poorly characterized. The vomiting is thought to result from a reflux of duodenal fluid into the gastric lumen causing mucosal irritation. Medical records from Colorado State University Veterinary Teaching Hospital (CSUVTH) were searched for "canine" and "bilious vomiting syndrome" between 2002 and 2012. Visual inspection confirmed a diagnosis of BVS during the case history. The diagnosis remained BVS for the duration of the dog's contact with the hospital in 17 cases. Therapy involved frequent feedings, late evening meals, gastric acid reducers, prokinetics, and gastroprotectants. Twelve dogs improved with therapy. Five dogs did not improve or were lost to follow-up. The diagnosis of BVS was supplanted in three cases with gastric adenocarcinoma, dietary indiscretion, and hepatopathy. The patient most likely given a diagnosis of BVS would be a young, mixed-breed, castrated male dog with a chronic history of vomiting bile. Response to therapy suggests abnormal gastrointestinal motility, local gastritis, gastric pH, or stimulation of the emetic center may be important factors in BVS. Dogs diagnosed with BVS rarely received a diagnostic evaluation sufficient to qualify it as a diagnosis of exclusion.

Ambulatory combined pH, bile and manometric monitoring of the oesophagus in asymptomatic healthy volunteers.

PubMed

Freedman, Jacob; Lindqvist, Madeleine; Melcher, Anders; Granström, Lars; Näslund, Erik

2004-11-01

With the development of sophisticated equipment ambulatory studies of oesophageal motor function, pH and bilirubin have gained in popularity. The aim of the study was to present reference values for combined 24 h pH, bilirubin and manometric measurements of the oesophagus. Twenty-six (15 male) healthy volunteers without symptoms of gastro-oesophageal reflux underwent a 24-h ambulatory oesophageal combined three-channel pressure, acid and bilirubin detection. The subjects were studied for a median of 20 h (16-22). The median per cent time with pH < 4 for the whole measured time was 3.1 (0.8-14; 5 and 95 percentiles). Bile was detected for a median of 0.05% (0.0-8.5; 5 and 95 percentiles) of the time. Eighty-one per cent of the contractions were peristaltic, 55% of which were complete. Of these, 53% had a pressure over 30 mmHg at all three pressure points, giving an efficient peristalsis in a median of 29% (13-46; 5 and 95 percentiles) of all registered contractile patterns. No difference between the genders could be observed. This study provides normative data for ambulatory oesophageal manometry, pH and bilirubin studies that can be used for comparing with patients with disease.

Novel biliary self-expanding metal stents: indications and applications.

PubMed

Blero, Daniel; Huberty, Vincent; Devière, Jacques

2015-03-01

Endoscopic insertion of a self-expanding metal stent (SEMS) through a malignant common bile duct stricture is the first line of palliation for malignant jaundice. Patency of these stents remains a major concern. SEMS dysfunction can result from tumor ingrowth, overgrowth and/or clogging. Initial SEMS modifications involved covering the central part of the stent in order to reduce ingrowth and ultimately increase patency. Fully covered stents became available shortly after reports of their use in human patients. The potential removability and radial strength of SEMS have led to evaluation of their use in new indications including benign biliary strictures, post sphincterotomy bleeding and perforation. Other aspects of development include the addition of features such as anti-reflux valves, drug elution and spontaneous biodegradability. These aspects and their clinical implications are reviewed and discussed.

[Surgical silicone prostheses in the treatment of biliary tract cancers: long prostheses or short prostheses? Results apropos of 500 cases].

PubMed

Kron, B

1992-10-01

The interest of surgical prostheses in the palliative treatment of biliary tract cancer is well established, on the basis of their good tolerance, the more than 15 year follow up experience and the number of patients operated upon. After exeresis, they allow re-establishment of continuity, either by use of a prosthesis in Y when the right and let ducts can be dissected, or by using two prostheses, a multiperforated long prosthesis reimplanted in the duodenum and a short prosthesis reimplanted in the common bile duct without attaining the sphincter of Oddi. Of the 1000 cases treated, 500 were the object of a statistical analysis, 46 being operated upon by the author, in 60% of cases for biliary tract cancer, either primary or as an extension from the gallbladder. One-third of the patients had advanced lesions and a short survival of less than 3 months. Two-thirds a median survival of 9 months. In 10%, a radical exeresis was performed with survival of more than one year without recurrence of jaundice. Failure of treatment with persistence of jaundice was due to advanced disease for which surgery is unsatisfactory. Essential complications were premature bile leaks (5%) without serious consequences if sufficient drainage was maintained, since it stopped spontaneously, and angiocholitis (6%), the result of territory exclusion or reflux. Recurrence of jaundice was related to extension of the neoplasm to the secondary bile ducts, and to hepatic metastases. Obstruction of the prosthesis before two months was rare (6%) and was preceded by angiocholitis. In the absence of recurrence of the cancer the prosthesis can be replaced surgically without difficulty.

Characterization of squamous esophageal cells resistant to bile acids at acidic pH: implication for Barrett's esophagus pathogenesis

PubMed Central

Goldman, Aaron; Chen, Hwu Dau Rw; Roesly, Heather B.; Hill, Kimberly A.; Tome, Margaret E.; Dvorak, Bohuslav; Bernstein, Harris

2011-01-01

Barrett's esophagus (BE) is a premalignant condition, where normal squamous epithelium is replaced by intestinal epithelium. BE is associated with an increased risk of developing esophageal adenocarcinoma (EAC). However, the BE cell of origin is not clear. We hypothesize that BE tissue originates from esophageal squamous cells, which can differentiate to columnar cells as a result of repeated exposure to gastric acid and bile acids, two components of refluxate implicated in BE pathology. To test this hypothesis, we repeatedly exposed squamous esophageal HET1A cells to 0.2 mM bile acid (BA) cocktail at pH 5.5 and developed an HET1AR-resistant cell line. These cells are able to survive and proliferate after repeated 2-h treatments with BA at pH 5.5. HET1AR cells are resistant to acidification and express markers of columnar differentiation, villin, CDX2, and cytokeratin 8/18. HET1AR cells have increased amounts of reactive oxygen species, concomitant with a decreased level and activity of manganese superoxide dismutase compared with parental cells. Furthermore, HET1AR cells express proteins and activate signaling pathways associated with inflammation, cell survival, and tumorigenesis that are thought to contribute to BE and EAC development. These include STAT3, NF-κB, epidermal growth factor receptor (EGFR), cyclooxygenase-2, interleukin-6, phosphorylated mammalian target of rapamycin (p-mTOR), and Mcl-1. The expression of prosurvival and inflammatory proteins and resistance to cell death could be partially modified by inhibition of STAT3 signaling. In summary, our study shows that long-term exposure of squamous cells to BA at acidic pH causes the cells to display the same characteristics and markers as BE. PMID:21127259

The In Vitro Effect of Acidic-Pepsin on Nuclear Factor KappaB Activation and Its Related Oncogenic Effect on Normal Human Hypopharyngeal Cells

PubMed Central

Sasaki, Clarence T.; Toman, Julia; Vageli, Dimitra

2016-01-01

Background Extra-esophageal carcinogenesis has been widely discussed in relation to the chronic effects of laryngopharyngeal reflux and most prominently with pepsin historically central to this discussion. With refluxate known to include gastric (pepsin) and duodenal (bile) fluids, we recently demonstrated the mechanistic role of NF-κB in mediating the preneoplastic effects of acidic-bile. However, the role of pepsin in promoting hypopharyngeal premalignant events remains historically unclear. Here, we investigate the in vitro effect of acidic-pepsin on the NF-κB oncogenic pathway to better define its potential role in hypopharyngeal neoplasia. Methods Human hypopharyngeal primary cells (HHPC) and keratinocytes (HHK) were repetitively exposed to physiologic pepsin concentrations (0.1 mg/ml) at pH 4.0, 5.0 and 7.0. Cellular localization of phospho-NF-κB and bcl-2 was determined using immunofluorescence and western blotting. NF-κB transcriptional activity was tested by luc reporter and qPCR. Analysis of DNA content of pepsin treated HHK and HHPC was performed using Fluorescence-activated-cell sorting assay. To explore a possible dose related effect, pepsin concentration was reduced from 0.1 to 0.05 and 0.01 mg/ml. Results At physiologic concentration, acidic-pepsin (0.1 mg/ml at pH 4.0) is lethal to most normal hypopharyngeal cells. However, in surviving cells, no NF-κB transcriptional activity is noted. Acidic-pepsin fails to activate the NF-κB or bcl-2, TNF-α, EGFR, STAT3, and wnt5α but increases the Tp53 mRNAs, in both HHPC and HHK. Weakly acidic-pepsin (pH 5.0) and neutral-pepsin (pH 7.0) induce mild activation of NF-κB with increase in TNF-α mRNAs, without oncogenic transcriptional activity. Lower concentrations of pepsin at varying pH do not produce NF-κB activity or transcriptional activation of the analyzed genes. Conclusion Our findings in vitro do not support the role of acidic-pepsin in NF-κB related hypopharyngeal carcinogenesis. PMID:27973541

[Longterm controls after endoscopic papillotomy [EPT] (author's transl)].

PubMed

Burmeister, W; Wurbs, D; Hagenmüller, F; Classen, M

1980-10-01

In 117 patients who have undergone endoscopic papillotomy (EPT) long term controls have been done. 51 were controlled in the hospital and 66 did answer a questionnaire. The mean time interval to the EPT was mean = 21.6 months. Nine out of every ten patients had no complaints. One third had minimal changes of laboratory dates, which can easily be explained by second diseases. With nearly no exception there was a large orifice to the common bile duct at the upper brim of the papilla. There was no bilioduodenal pressure gradient in 75%. Duodenobiliary reflux could be demonstrated in 25% and aerobilia in 65%. Although there was a massive bacteriobilia in all cases, no signs of cholangitis could be found in any patient. As a result, no unfavourable effects of the EPT became obvious during this follow-up study.

Cdx genes, inflammation, and the pathogenesis of intestinal metaplasia

PubMed Central

Stairs, Doug B.; Kong, Jianping; Lynch, John P.

2018-01-01

Intestinal metaplasia is a biologically interesting and clinically relevant condition in which one differentiated type of epithelium is replaced by another that is morphologically similar to normal intestinal epithelium. Two classic examples of this are gastric intestinal metaplasia and Barrett’s esophagus. In both, a chronic inflammatory microenvironment, provoked either by Helicobacter pylori infection of the stomach or acid and bile reflux into the esophagus, precedes the metaplasia. The Caudal-related homeodomain transcription factors Cdx1 and Cdx2 are critical regulators of the normal intetinal epithelial cell phenotype. Ectopic expression of Cdx1 and Cdx2 occurs in both gastric intestinal metaplasia as well as in Barrett’s esophagus. This expression precedes the onset of the metaplasia and implies a causal role for these factors in this process. We will review the observations regarding the role of chronic inflammation and the Cdx transcription factors in the pathogenesis of gastric intestinal metaplasia and Barrett’s esophagus. PMID:21075347

In Vivo Cancer Biomarkers of Esophageal Neoplasia

PubMed Central

Lu, Shaoying; Wang, Thomas D

2011-01-01

Summary The emergence of in vivo cancer biomarkers is promising tool for early detection, risk stratification, and therapeutic intervention in the esophagus, where adenocarcinoma is increasing at a rate that is faster than any other in industrialized nations. Exciting advances in target identification, probe development, and optical instrumentation are creating tremendous new opportunities for advancing techniques of molecular imaging. Progress in these areas is being made with small animal models of esophageal cancer using surgical approaches to induce reflux of acid and bile, and these findings are beginning to be evaluated in the clinic. Further identification of relevant targets, characterization of specific probes, and development of endoscopic imaging technologies are needed to further this direction in the field of molecular medicine. In the future, new methods that use in vivo cancer biomarkers for the early detection of neoplastic changes in the setting of Barrett's esophagus will become available. PMID:19126962

Analysis of the Protective Biochemical and Pathologic Effects of Aminoguanidine on an Experimental Aspiration Pneumonitis Model Induced by Bile Acids

PubMed Central

Karli, Rifat; Alacam, Hasan; Duran, Latif; Alici, Omer; Kati, Celal; Karli, Arzu; Guzel, Ahmet

2012-01-01

Background Gastroesophageal reflux (GER) is a common clinical pathology detected in childhood. Bile acids (BAs) are present in reflux and cause various pathologies in the esophagus, the larynx, and the lungs. Objective We aimed to show if aminoguanidine (AG) contributes to the biochemical and histopathologic treatment of experimental aspiration pneumonitis induced by BAs. Methods Twenty-eight female Sprague Dawley rats were used. There were 4 groups in the study: (1) group aspirated with 0.9% saline (n = 7), (2) group aspirated with 0.9% saline and treated with AG (n = 7), (3) group aspirated with a solution of 10 mg/kg taurocholic acid and 5 mg/kg taurochenodeoxycholate (n = 7), and (4) group aspirated with BA and treated with AG (n = 7). The saline and BA solutions were administered as 1 mL/kg intratracheally. The AG was administered intraperitoneally twice a day at a 150 mg/kg dose for 7 days. The different histopathologic and biochemical parameters were analyzed. Results Clara cell protein 16 and malondialdehyde levels were found to be significantly higher in the BA group than in the group where saline was administered; however, they were significantly lower in the BA + AG group than in the BA group. The total superoxide dismutase activity decreased significantly in the BA group compared with the group where saline was administered. A significant increase in superoxide dismutase activity was observed in the BA + AG group when compared with the group where only BA was administered. When the group where BA was administered solely was compared with the group where saline was administered, peribronchial inflammatory cell infiltration, alveolar septal infiltration, alveolar histiocytes, interstitial fibrosis, and granuloma were significantly higher in the BA group than in the saline group. When the BA + AG group was compared with the BA group, peribronchial inflammatory cell infiltration, alveolar septal infiltration, alveolar histiocytes, interstitial fibrosis, and granuloma were found to be significantly lower. Conclusions Oxidant stress increases and antioxidant capacity decreases in pneumonitis induced by BAs. AG administration as an antioxidant helps in recovery, both biochemically and histopathologically. Consequently, AG seems to be an alternative that should be considered in a conservative approach to treating aspiration pneumonitis. PMID:24653522

Bile acids at neutral and acidic pH induce apoptosis and gene cleavages in nasopharyngeal epithelial cells: implications in chromosome rearrangement.

PubMed

Tan, Sang-Nee; Sim, Sai-Peng

2018-04-12

Chronic rhinosinusitis (CRS) increases the risk of developing nasopharyngeal carcinoma (NPC) while nasopharyngeal reflux is known to be one of the major aetiological factors of CRS. Bile acid (BA), the component of gastric duodenal contents, has been recognised as a carcinogen. BA-induced apoptosis was suggested to be involved in human malignancies. Cells have the potential and tendency to survive apoptosis. However, cells that evade apoptosis upon erroneous DNA repair may carry chromosome rearrangements. Apoptotic nuclease, caspase-activated deoxyribonuclease (CAD) has been implicated in mediating translocation in leukaemia. We hypothesised that BA-induced apoptosis may cause chromosome breaks mediated by CAD leading to chromosome rearrangement in NPC. This study targeted the AF9 gene located at 9p22 because 9p22 is one of the most common deletion sites in NPC. We tested the ability of BA at neutral and acidic pH in inducing phosphatidylserine (PS) externalisation, reactive oxygen species (ROS) production, mitochondrial membrane potential (MMP) disruption, and caspase 3/7 activity in normal nasopharyngeal epithelial (NP69) and NPC (TWO4) cells. Inverse-PCR (IPCR) was employed to detect AF9 gene cleavages. To investigate the role of CAD in mediating these cleavages, caspase inhibition was performed. IPCR bands representing AF9 cleaved fragments were sequenced. BA-treated cells showed higher levels of PS externalisation, ROS production, MMP loss and caspase 3/7 activity than untreated control cells. The effect of BA in the induction of these intracellular events was enhanced by acid. BA at neutral and acidic pH also induced significant cleavage of the AF9 gene. These BA-induced gene cleavages were inhibited by Z-DEVD-FMK, a caspase-3 inhibitor. Intriguingly, a few chromosome breaks were identified within the AF9 region that was previously reported to participate in reciprocal translocation between the mixed lineage leukaemia (MLL) and AF9 genes in an acute lymphoblastic leukaemia (ALL) patient. These findings suggest a role for BA-induced apoptosis in mediating chromosome rearrangements in NPC. In addition, CAD may be a key player in chromosome cleavages mediated by BA-induced apoptosis. Persistent exposure of sinonasal tract to gastric duodenal refluxate may increase genomic instability in surviving cells.

Exposure to gastric juice may not cause adenocarcinogenesis of the esophagus

PubMed Central

Cheng, Peng; Li, Jian-Sheng; Zhang, Lian-Feng; Chen, Yong-Zhong; Gong, Jun

2013-01-01

AIM: To determine the effects of gastric juice on the development of esophageal adenocarcinoma (EAC). METHODS: A animal model of duodenogastroesophageal reflux was established in Sprague-Dawley rats undergoing esophagoduodenostomy. The development of EAC and forestomach adenocarcinoma was investigated 40 wk after the treatment. Intraluminal pH and bile of the forestomach were measured. RESULTS: There were no significant differences in pH (t = 0.117, P = 0.925) or bile (χ2 = 0.036, P = 0.85) in the forestomach before and 40 wk after esophagoduodenostomy. There were also no significant differences between the model and controls during esophagoduodenostomy or 40 wk after esophagoduodenostomy. The incidence of intestinal metaplasia (88%) and intestinal metaplasia with dysplasia and adenocarcinoma (28%) in the esophagus in the model was higher than in the controls 40 wk after surgery (χ2 = 43.06, P < 0.001 and χ2 = 9.33, P = 0.002, respectively) and in the forestomach in the model (χ2 = 32.05, P < 0.001 and χ2 = 8.14, P = 0.004, respectively). The incidence rates of inflammation in the esophagus and forestomach were 100% and 96%, respectively (χ2 = 1.02, P = 0.31) in the model, which was higher than in the esophageal control (6.8%) (χ2 = 42.70, P < 0.001). CONCLUSION: Gastric juice exposure may not cause intestinal metaplasia with dysplasia or adenocarcinoma of the forestomach and may not be related to EAC. PMID:23613638

Development and intra-institutional and inter-institutional validation of a comprehensive new hepatobiliary software: Part 1--Liver and gallbladder function.

PubMed

Krishnamurthy, Gerbail T; Krishnamurthy, Shakuntala; Gambhir, Sanjiv Sam; Rodrigues, Cesar; Rosenberg, Jarrett; Schiepers, Christiaan; Buxton-Thomas, Muriel

2009-12-01

To develop a software tool for quantification of liver and gallbladder function, and to assess the repeatability and reproducibility of measurements made with it. The software tool developed with the JAVA programming language uses the JAVA2 Standard Edition framework. After manual selection of the regions of interest on a 99mTc hepatic iminodiacetic acid study, the program calculates differential hepatic bile flow, basal duodeno-gastric bile reflux (B-DGBR), hepatic extraction fraction (HEF) of both the lobes with deconvolutional analysis and excretion half-time with nonlinear least squares fit. Gallbladder ejection fraction, ejection period (EP), ejection rate (ER), and postcholecystokinin (CCK) DGBR are calculated after stimulation with CCK-8. To assess intra-observer repeatability and intra-observer reproducibility, measurements from 10 normal participants were analyzed twice by three nuclear medicine technologists at the primary center. To assess inter-site reproducibility, measurements from a superset of 24 normal participants were also assessed once by three observers at the primary center and single observer at three other sites. For the 24 control participants, mean+/-SD of hepatic bile flow into gallbladder was 63.87+/-28.7%, HEF of the right lobe 100+/-0%, left lobe 99.43+2.63%, excretion half-time of the right lobe 21.50+6.98 min, left lobe 28.3+/-11.3 min. Basal DGBR was 1.2+/-1.0%. Gallbladder ejection fraction was 80+/-11%, EP 15.0+/-3.0 min, ER 5.8+/-1.6%/min, and DGBR-CCK 1.3+/-2.3%. Left and right lobe HEF was virtually identical across readers. All measures showed high repeatability except for gallbladder bile flow, basal DGBR, and EP, which exhibited marginal repeatability. Ejection fraction exhibited high reproducibility. There was high concordance among the three primary center observers except for basal DGBR, EP, and ER. Concordance between the primary site and one of the other sites was high, one was fair, and one was poor. New United States Food and Drug Administration-approved personal computer-based Krishnamurthy Hepato-Biliary Software for quantification of the liver and gallbladder function shows promise for consistently repeatable and reproducible results both within and between institutions, and may help to promote universal standardization of data acquisition and analysis in nuclear hepatology.

The MUC4 membrane-bound mucin regulates esophageal cancer cell proliferation and migration properties: Implication for S100A4 protein.

PubMed

Bruyère, Emilie; Jonckheere, Nicolas; Frénois, Frédéric; Mariette, Christophe; Van Seuningen, Isabelle

2011-09-23

MUC4 is a membrane-bound mucin known to participate in tumor progression. It has been shown that MUC4 pattern of expression is modified during esophageal carcinogenesis, with a progressive increase from metaplastic lesions to adenocarcinoma. The principal cause of development of esophageal adenocarcinoma is the gastro-esophageal reflux, and MUC4 was previously shown to be upregulated by several bile acids present in reflux. In this report, our aim was thus to determine whether MUC4 plays a role in biological properties of human esophageal cancer cells. For that stable MUC4-deficient cancer cell lines (shMUC4 cells) were established using a shRNA approach. In vitro (proliferation, migration and invasion) and in vivo (tumor growth following subcutaneous xenografts in SCID mice) biological properties of shMUC4 cells were analyzed. Our results show that shMUC4 cells were less proliferative, had decreased migration properties and did not express S100A4 protein when compared with MUC4 expressing cells. Absence of MUC4 did not impair shMUC4 invasiveness. Subcutaneous xenografts showed a significant decrease in tumor size when cells did not express MUC4. Altogether, these data indicate that MUC4 plays a key role in proliferative and migrating properties of esophageal cancer cells as well as is a tumor growth promoter. MUC4 mucin appears thus as a good therapeutic target to slow-down esophageal tumor progression. Copyright © 2011 Elsevier Inc. All rights reserved.

Long-term comparison of boomerang-shaped jejunal interposition and Billroth-I reconstruction after distal gastrectomy.

PubMed

Sasaki, Kinro; Miyachi, Kazuhito; Yoda, Norihito; Onodera, Shinichi; Satomura, Hitoshi; Otsuka, Kichiro; Nakajima, Masanobu; Yamaguchi, Satoru; Sunagawa, Masakatsu; Kato, Hiroyuki

2015-05-01

Billroth-I (BI) is a simple, physiological method of reconstruction following distal gastrectomy. In actuality, postoperative QOL is by no means favorable due to the high incidence of post-gastrectomy syndrome. The aim of this study is to assess the safety and efficacy of boomerang-shaped jejunal interposition (BJI) after distal gastrectomy. Sixty-six patients with early gastric cancer underwent the BI procedure (n = 33) or BJI (n = 33) after distal gastrectomy, following which they were compared for 5 years. Tumor characteristics, operative details, postoperative complications and complaints, number of meals, and body weight were analyzed. Patients were followed up by endoscopy every 12 months. There were no significant differences in the incidence of postoperative complications. The incidence of heartburn (30 vs. 0 %, P = 0.0009) and oral bitterness (33 vs. 6 %, P = 0.0112) were significantly lower in the BJI cases. Endoscopic findings revealed significantly lower incidences of reflux esophagitis (24 vs. 0 %, P = 0.0051) and remnant gastritis (70 vs. 3 %, P < 0.0001) in the BJI group. The incidence of food stasis was low in both groups (12 vs. 15 %). In the BJI group, 30 patients (90 %) were eating 3 meals/day within 12 months, whereas in the BI group, 16 patients (48 %) were still eating 5 meals/day at 12 months or later. BJI is as safe as BI, but is better in terms of improvement in bile reflux and food intake without stasis. This procedure, therefore, appears to be a useful method for reconstruction after distal gastrectomy.

Aberrant Epithelial-Mesenchymal Hedgehog Signaling Characterizes Barrett's Metaplasia

PubMed Central

Wang, David H.; Clemons, Nicholas J.; Miyashita, Tomoharu; Dupuy, Adam J.; Zhang, Wei; Szczepny, Anette; Corcoran-Schwartz, Ian M.; Wilburn, Daniel L.; Montgomery, Elizabeth A.; Wang, Jean S.; Jenkins, Nancy A.; Copeland, Neal A.; Harmon, John W.; Phillips, Wayne A.; Watkins, D. Neil

2010-01-01

Background & Aims The molecular mechanism underlying epithelial metaplasia in Barrett's esophagus remains unknown. Recognizing that Hedgehog signaling is required for early esophageal development, we sought to determine if the Hedgehog pathway is reactivated in Barrett's esophagus, and if genes downstream of the pathway could promote columnar differentiation of esophageal epithelium. Methods Immunohistochemistry, immunofluorescence, and quantitative real-time PCR were used to analyze clinical specimens, human esophageal cell lines, and mouse esophagi. Human esophageal squamous epithelial (HET-1A) and adenocarcinoma (OE33) cells were subjected to acid treatment and used in transfection experiments. Swiss Webster mice were used in a surgical model of bile reflux injury. An in vivo transplant culture system was created using esophageal epithelium from Sonic hedgehog transgenic mice. Results Marked upregulation of Hedgehog ligand expression, which can be induced by acid or bile exposure, occurs frequently in Barrett's epithelium and is associated with stromal expression of the Hedgehog target genes PTCH1 and BMP4. BMP4 signaling induces expression of SOX9, an intestinal crypt transcription factor, which is highly expressed in Barrett's epithelium. We further show that expression of DMBT1, the human homologue of the columnar cell factor Hensin, occurs in Barrett's epithelium and is induced by SOX9. Finally, transgenic expression of Sonic hedgehog in mouse esophageal epithelium induces expression of stromal Bmp4, epithelial Sox9 and columnar cytokeratins. Conclusions Epithelial Hedgehog ligand expression may contribute to the initiation of Barrett's esophagus through induction of stromal BMP4, which triggers reprogramming of esophageal epithelium in favor of a columnar phenotype. PMID:20138038

Characteristics of symptomatic reflux episodes in Japanese proton pump inhibitor-refractory non-erosive reflux disease patients.

PubMed

Nakagawa, Kenichiro; Koike, Tomoyuki; Iijima, Katsunori; Saito, Masahiro; Kikuchi, Hiroki; Hatta, Waku; Ara, Nobuyuki; Uno, Kaname; Asano, Naoki; Shimosegawa, Tooru

2015-12-21

To clarify the pathogenesis of gastroesophageal reflux disease symptoms in non-erosive reflux disease (NERD) patients. Thirty-five NERD patients with persistent symptoms, despite taking rabeprazole 10 mg twice daily for at least 8 wk, were included in this study. All patients underwent 24 h combined impedance - pH on rabeprazole. The symptom index (SI) was considered to be positive if ≥ 50%, and proximal reflux episodes were determined when reflux reached 15 cm above the proximal margin of the lower esophageal sphincter. In 14 (40%) SI-positive patients, with liquid weakly acid reflux, the occurrence rate of reflux symptoms was significantly more frequent in proximal reflux episodes (46.7%) than in distal ones (5.7%) (P < 0.001). With liquid acid reflux, there were no significant differences in the occurrence rate of reflux symptoms between proximal reflux episodes (38.5%) and distal ones (20.5%) (NS). With mixed liquid-gas weakly acid reflux, the occurrence rate of reflux symptoms in proximal reflux episodes was significantly more frequent (31.0%) than in distal reflux ones (3.3%) (P < 0.001). With mixed liquid-gas acid reflux, there were no significant differences in the occurrence rate of reflux symptoms between proximal reflux episodes (29.4%) and distal ones (14.3%) (NS). The proximal extent of weakly acidic liquid and mixed liquid-gas reflux is a major factor associated with reflux perception in SI-positive patients on proton pump inhibitor therapy.

Characteristics of symptomatic reflux episodes in Japanese proton pump inhibitor-refractory non-erosive reflux disease patients

PubMed Central

Nakagawa, Kenichiro; Koike, Tomoyuki; Iijima, Katsunori; Saito, Masahiro; Kikuchi, Hiroki; Hatta, Waku; Ara, Nobuyuki; Uno, Kaname; Asano, Naoki; Shimosegawa, Tooru

2015-01-01

AIM: To clarify the pathogenesis of gastroesophageal reflux disease symptoms in non-erosive reflux disease (NERD) patients. METHODS: Thirty-five NERD patients with persistent symptoms, despite taking rabeprazole 10 mg twice daily for at least 8 wk, were included in this study. All patients underwent 24 h combined impedance - pH on rabeprazole. The symptom index (SI) was considered to be positive if ≥ 50%, and proximal reflux episodes were determined when reflux reached 15 cm above the proximal margin of the lower esophageal sphincter. RESULTS: In 14 (40%) SI-positive patients, with liquid weakly acid reflux, the occurrence rate of reflux symptoms was significantly more frequent in proximal reflux episodes (46.7%) than in distal ones (5.7%) (P < 0.001). With liquid acid reflux, there were no significant differences in the occurrence rate of reflux symptoms between proximal reflux episodes (38.5%) and distal ones (20.5%) (NS). With mixed liquid-gas weakly acid reflux, the occurrence rate of reflux symptoms in proximal reflux episodes was significantly more frequent (31.0%) than in distal reflux ones (3.3%) (P < 0.001). With mixed liquid-gas acid reflux, there were no significant differences in the occurrence rate of reflux symptoms between proximal reflux episodes (29.4%) and distal ones (14.3%) (NS). CONCLUSION: The proximal extent of weakly acidic liquid and mixed liquid-gas reflux is a major factor associated with reflux perception in SI-positive patients on proton pump inhibitor therapy. PMID:26715820

Mucin expression in reactive gastropathy: an immunohistochemical analysis.

PubMed

Mino-Kenudson, Mari; Tomita, Shigeki; Lauwers, Gregory Y

2007-01-01

Reactive gastropathy is the second most common diagnosis made on gastric biopsies. Increased epithelial proliferation and modifications of epithelial cytokeratin profile, distinct from those of Helicobacter pylori gastritis, have been previously reported. However, the evaluation of mucins, important components of the protective mucosal mucous layer, has not been reported. To investigate alterations of membrane and secreted mucins in reactive gastropathy of various etiologies using antibodies against mucin glycoproteins. Thirty-eight gastric biopsies diagnosed as reactive gastropathy, related to nonsteroidal anti-inflammatory drugs (n = 18) or bile reflux (n = 6) or of indeterminate etiology (n = 14), were evaluated using antibodies to MUC1, MUC5AC, MUC6, and MUC2. All cases were confirmed to be negative for H. pylori. The biopsies were classified in 3 groups based on the severity of cytoarchitectural changes (mild, moderate, and severe). Mucin expression and its distribution were recorded and the results correlated with the cytoarchitectural alterations and etiologies. Loss of MUC1, either patchy or complete, was noted in 67% of the cases. Aberrant expression of MUC5AC in pyloric glands was observed in 81% of the cases, and aberrant expression of MUC6 in the upper foveolar epithelium was diffusely seen in 14% of the cases. Aberrant expression of MUC2 in non-goblet cells was observed in a single case. Aberrant expression of MUC6 was less extensive in the nonsteroidal anti-inflammatory drugs group than in other 2 groups (P = .03). Concurrently, the diffuse distribution of aberrant MUC6 expression was seen only in the cases of severe gastropathy (P = .09). There was no correlation between modifications in expression of other mucins and either the etiologies or the severity of cytoarchitectural changes. Expressions of membrane (MUC1) and secreted (MUC5AC, MUC6) mucins are frequently modified in reactive gastropathy. The alteration of MUC1, which is involved in cell adhesion and polarity, may play a role in the development of the serrated profile of reactive gastropathy. Milder modifications of the secreted mucins may be explained by the reactive/regenerative nature of the process. Importantly, theses changes are different from the increase in MUC6 and reduction of MUC5AC expression reported in H. pylori gastritis, underlying their mechanistic differences. It is worth noting that similar alterations of mucin expression are shared by various etiologies, that is, nonsteroidal anti-inflammatory drugs and bile reflux, consistent with the nonspecific nature of reactive gastropathy.

Nocturnal Gastroesophageal Reflux Revisited by Impedance-pH Monitoring

PubMed Central

Blondeau, Kathleen; Mertens, Veerle; Tack, Jan; Sifrim, Daniel

2011-01-01

Background/Aims Impedance-pH monitoring allows detailed characterization of gastroesophageal reflux and esophageal activity associated with reflux. We assessed the characteristics of nocturnal reflux and esophageal activity preceding and following reflux. Methods Impedance-pH tracings from 11 healthy subjects and 76 patients with gastroesophageal reflux disease off acid-suppressive therapy were analyzed. Characteristics of nocturnal supine reflux, time distribution and esophageal activity seen on impedance at 2 minute intervals preceding and following reflux were described. Results Patients had more nocturnal reflux events than healthy subjects (8 [4-12] vs 2 [1-5], P = 0.002), with lower proportion of weakly acidic reflux (57% [35-78] vs 80% [60-100], P = 0.044). Nocturnal reflux was mainly liquid (80%) and reached the proximal esophagus more often in patients (6% vs 0%, P = 0.047). Acid reflux predominated in the first 2 hours (66%) and weakly acidic reflux in the last 3 hours (70%) of the night. Most nocturnal reflux was preceded by aboral flows and cleared by short lasting volume clearance. In patients, prolonged chemical clearance was associated with less esophageal activity. Conclusions Nocturnal weakly acidic reflux is as common as acid reflux in patients with gastroesophageal reflux disease, and predominates later in the night. Impedance-pH can predict prolonged chemical clearance after nocturnal acid reflux. PMID:21602991

Role of Acid and Weakly Acidic Reflux in Gastroesophageal Reflux Disease Off Proton Pump Inhibitor Therapy

PubMed Central

Sung, Hea Jung; Moon, Sung Jin; Kim, Jin Su; Lim, Chul Hyun; Park, Jae Myung; Lee, In Seok; Kim, Sang Woo; Choi, Myung-Gye

2012-01-01

Background/Aims Available data about reflux patterns and symptom determinants in the gastroesophageal reflux disease (GERD) subtypes off proton pump inhibitor (PPI) therapy are lacking. We aimed to evaluate reflux patterns and determinants of symptom perception in patients with GERD off PPI therapy by impedance-pH monitoring. Methods We retrospectively reviewed the impedance-pH data in patients diagnosed as GERD based on results of impedance-pH monitoring, endoscopy and/or typical symptoms. The characteristics of acid and weakly acidic reflux were evaluated. Symptomatic and asymptomatic reflux were compared according to GERD subtypes and individual symptoms. Results Forty-two patients (22 males, mean age 46 years) were diagnosed as GERD (17 erosive reflux disease, 9 pH(+) non-erosive reflux disease [NERD], 9 hypersensitive esophagus and 7 symptomatic NERD). A total of 1,725 reflux episodes were detected (855 acid [50%], 857 weakly acidic [50%] and 13 weakly alkaline reflux [< 1%]). Acid reflux was more frequently symptomatic and bolus clearance was longer compared with weakly acidic reflux. In terms of globus, weakly acidic reflux was more symptomatic. Symptomatic reflux was more frequently acid and mixed reflux; these associations were more pronounced in erosive reflux disease and symptomatic NERD. The perception of regurgitation was related to acid reflux, while that of globus was more related to weakly acidic reflux. Conclusions In patients not taking PPI, acid reflux was more frequently symptomatic and had longer bolus clearance. Symptomatic reflux was more frequently acid and mixed type; however, weakly acidic reflux was associated more with globus. These data suggest a role for impedance-pH data in the evaluation of globus. PMID:22837877

Role of Acid and weakly acidic reflux in gastroesophageal reflux disease off proton pump inhibitor therapy.

PubMed

Sung, Hea Jung; Cho, Yu Kyung; Moon, Sung Jin; Kim, Jin Su; Lim, Chul Hyun; Park, Jae Myung; Lee, In Seok; Kim, Sang Woo; Choi, Myung-Gye

2012-07-01

Available data about reflux patterns and symptom determinants in the gastroesophageal reflux disease (GERD) subtypes off proton pump inhibitor (PPI) therapy are lacking. We aimed to evaluate reflux patterns and determinants of symptom perception in patients with GERD off PPI therapy by impedance-pH monitoring. We retrospectively reviewed the impedance-pH data in patients diagnosed as GERD based on results of impedance-pH monitoring, endoscopy and/or typical symptoms. The characteristics of acid and weakly acidic reflux were evaluated. Symptomatic and asymptomatic reflux were compared according to GERD subtypes and individual symptoms. Forty-two patients (22 males, mean age 46 years) were diagnosed as GERD (17 erosive reflux disease, 9 pH(+) non-erosive reflux disease [NERD], 9 hypersensitive esophagus and 7 symptomatic NERD). A total of 1,725 reflux episodes were detected (855 acid [50%], 857 weakly acidic [50%] and 13 weakly alkaline reflux [< 1%]). Acid reflux was more frequently symptomatic and bolus clearance was longer compared with weakly acidic reflux. In terms of globus, weakly acidic reflux was more symptomatic. Symptomatic reflux was more frequently acid and mixed reflux; these associations were more pronounced in erosive reflux disease and symptomatic NERD. The perception of regurgitation was related to acid reflux, while that of globus was more related to weakly acidic reflux. In patients not taking PPI, acid reflux was more frequently symptomatic and had longer bolus clearance. Symptomatic reflux was more frequently acid and mixed type; however, weakly acidic reflux was associated more with globus. These data suggest a role for impedance-pH data in the evaluation of globus.

Vesicoureteral reflux in the primate IV: does reflux harm the kidney

DOE Office of Scientific and Technical Information (OSTI.GOV)

Roberts, J.A.; Fischman, N.H.; Thomas, R.

1982-09-01

It has been said that vesicoureteral reflux causes renal scarring because of intrarenal reflux. We studied reflux in the monkey because of its similarity to man, especially in regard to the incidence of vesicoureteral reflux and chronic pyelonephritis. High pressure moderate grade reflux was produced and renal function followed by means of quantitative renal camera studies using /sup 131/I hippuran. There was no change in renal function from sterile reflux even when intrarenal reflux occurred. When, however, infection was introduced, renal function decreased. We concluded that sterile moderate vesicoureteral or intrarenal reflux does not harm the kidney.

Clinical characteristics and psychosocial impact of different reflux time in gastroesophageal reflux disease patients.

PubMed

Chen, Jiann-Hwa; Wen, Shu-Hui; Hsu, Ching-Sheng; Yi, Chih-Hsun; Liu, Tso-Tsai; Chen, Chien-Lin; Wang, Chia-Chi

2017-02-01

Gastroesophageal reflux disease (GERD) is an emerging disease, and can impair quality of life and sleep. This study aimed to investigate whether GERD patients with different timings of reflux symptoms have different clinical characteristics. This study prospectively enrolled individuals who underwent upper gastrointestinal endoscopy during a health checkup. Each participant completed all questionnaires including Reflux Disease Questionnaire, Nighttime GERD questionnaire, Pittsburg Sleep Quality Index, Taiwanese Depression Questionnaire, and State-Trait Anxiety Inventory. Combined reflux was defined as the timing of reflux symptoms occurring at both daytime and nighttime. A total of 2604 participants were enrolled. Of them, 651 symptomatic GERD patients, according to the Reflux Disease Questionnaire score, were recruited for final analysis. Of them, 224 (34.4%) had erosive esophagitis on endoscopy. According to the timing of reflux symptoms, 184 (28.3%) were assigned to the daytime reflux group, 71 (10.9%) to the nighttime reflux group, and 396 (60.8%) to the combined reflux group. In post hoc analysis, the combined reflux group had a significantly higher Reflux Disease Questionnaire score than the daytime reflux group (p < 0.0001). Combined and nighttime reflux groups had higher body mass index and longer duration (> 12 years) of education than the daytime reflux group (p < 0.05). There was no difference in Pittsburg Sleep Quality Index, Taiwanese Depression Questionnaire, and State-Trait Anxiety Inventory scores among three groups. GERD patients with combined daytime and nighttime reflux of have more troublesome symptoms than those with daytime reflux. GERD patients with different timings of reflux symptoms have different clinical characteristics in terms of body mass index and duration of education, but not in terms of esophageal inflammation, quality of sleep, and psychosocial status. Copyright © 2016. Published by Elsevier B.V.

Majority of symptoms in esophageal reflux PPI non-responders are not related to reflux

PubMed Central

Roman, Sabine; Keefer, Laurie; Imam, Hala; Korrapati, Praneet; Mogni, Benjamin; Eident, Kate; Friesen, Laurel; Kahrilas, Peter J; Martinovich, Zoran; Pandolfino, John

2015-01-01

Background Genesis of persistent gastro-esophageal reflux symptoms despite proton pump inhibitor (PPI) therapy is not fully understood. We aimed at determining reflux patterns on 24-h pH-impedance monitoring performed on PPI and correlating impedance patterns and symptom occurrence in PPI non-responders. Methods 78 PPI non-responder patients underwent 24-h pH-impedance monitoring on PPI. Reflux impedance characterization included gastric and supragastric belches and proximal extent of reflux. Symptoms were considered associated with reflux if occurring within 5 min after a reflux event. Patients were classified into 3 groups: persistent acid reflux (acid esophageal exposure (AET) >5% of time), reflux sensitivity (AET<5%, symptom index (SI) ≥50%), and functional symptoms (AET<5%, SI<50%). Dominant impedance pattern was determined for each patient. Key results 7 patients (9%) had persistent acid reflux, 28 (36%) reflux sensitivity and 43 (55%) functional symptoms. A total of 4,296 reflux events were identified (median per patient 45 (range 4–221)). Although liquid reflux was the most common pattern in all groups, patients with reflux sensitivity and functional symptoms had much more variability in their pattern profile with a large proportion being associated with gastric and supra-gastric belching. Only 417 reflux events (9.7%) were associated with symptoms. Reflux with a supragastric component and proximal extent were more likely to be associated with symptoms. Conclusions & Inferences The impedance reflux profile in PPI non-responders was heterogeneous and the majority of reflux events were not associated with symptoms. Thus, the treatment of PPI non-responders should focus on mechanisms beyond reflux, such as visceral hypersensitivity and hypervigilance. PMID:26337396

Acid reflux episodes sensitize the esophagus to perception of weakly acidic and mixed reflux in non-erosive reflux disease patients.

PubMed

Emerenziani, S; Ribolsi, M; Guarino, M P L; Balestrieri, P; Altomare, A; Rescio, M P; Cicala, M

2014-01-01

Non-erosive reflux disease (NERD) patients are more sensitive than erosive esophagitis patients to weakly acidic reflux and to the presence of gas in the refluxate. Intra-esophageal acid perfusion sensitizes esophageal receptors to mechanical and chemical stimuli. To establish whether acid sensitization plays a role in the perception of weakly acidic and mixed reflux episodes, 29 NERD patients, responders and 14 non-responders to proton pump inhibitors (PPIs), underwent pH-impedance monitoring. Non-responders repeated the study while on PPIs. To assess the effect of acid exposure on symptom perception, the time period with pH below 4 was measured in 15- and 30-minute time-windows preceding the onset of each reflux episode. Considering weakly acidic and mixed refluxes, both in responder and non-responder patients (off PPIs), the symptomatic refluxes were preceded by a significantly higher cumulative acid exposure than the asymptomatic refluxes. In all patients, following acid reflux, the percentage of symptomatic weakly acidic reflux episodes was significantly higher than that of asymptomatic refluxes. Non-responder patients, off-treatment, were characterized by a lower proportion of weakly acidic reflux and mixed reflux episodes. In the non-responder patients on PPI, only mixed and weakly symptomatic reflux episodes were preceded by a higher cumulative acid exposure. In NERD patients, spontaneous acid reflux enhances subsequent reflux perception, regardless of acidity or liquid/mixed composition of episodes; in non-responder patients on PPIs, only the perception of mixed and weakly acidic reflux episodes seems to be mediated by a preceding acid exposure. © 2013 John Wiley & Sons Ltd.

Comparison of Characteristics According to Reflux Type in Patients With Laryngopharyngeal Reflux.

PubMed

Lee, Jun Seok; Jung, Ah Ra; Park, Jung Min; Park, Myung Jin; Lee, Young Chan; Eun, Young-Gyu

2018-06-01

To analyze laryngopharyngeal reflux (LPR) as an acidic, nonacidic, or mixed type according to 24-hour multi-channel intraluminal impedance (MII) pH monitoring and the clinical characteristics of each type. Ninety patients were prospectively enrolled in this study. All patients underwent 24-hour MII pH monitoring as a diagnostic tool. Eighty-three patients were diagnosed with LPR. The patients were classified into three groups according to the pH of the hypopharyngeal probe: the acid reflux group, nonacid reflux group, and mixed reflux group. Subjective symptoms and objective findings were evaluated based on patients' responses to the Short Form 12 Survey (SF-12), LPR health-related quality of life (LPR-HRQOL), reflux symptom index, and reflux finding score. The results of each group were compared. As a result, 34 patients were classified into the nonacid reflux group and 49 into the mixed reflux group. There were no patients classified as having acid reflux alone. There was no significant difference between the two groups when comparing the reflux symptom index, reflux finding score, LPR-HRQOL, or the mental component score of the SF-12. However, the physical component score of the SF-12 was higher in the nonacid reflux group ( P =0.018). The DeMeester composite score ( P =0.015) and total number of LPR events ( P =0.001) were lower in the nonacid reflux group than in the mixed reflux group. In conclusion, no LPR patient had only acid reflux. The nonacid reflux LPR patients showed similar clinical characteristics and findings compared to the mixed reflux group, but exhibited significantly fewer LPR episodes.

Durable Flap-Valve Mitigation of Duodenogastric Reflux,  Remnant Gastritis and Dumping Syndrome Following Billroth I Reconstruction.

PubMed

Hoya, Yoshiyuki; Taki, Tetsuya; Watanabe, Atsushi; Nakayoshi, Tomoko; Okamoto, Tomoyoshi; Mitsumori, Norio; Yanaga, Katsuhiko

2016-04-01

We have reported the short-term results of pylorus reconstruction gastrectomy (PRG) that prevents duodenogastric reflux (DGR) and remnant gastritis after distal gastrectomy. We herein report the long-term results of the PRG. PRG was performed in 37 patients (age 31 to 86 [mean 67.8 ± 12.3] years, male:female = 22:15) with gastric cancer from June 2006 through December 2013. We examined the long-term outcome in 28 patients (age 41 to 86 [mean 67.0 ± 10.7] years, male:female = 18:10) that passed over 3 years after surgery (LTR 44.1 ± 11.7 months), and compared with their short-term result after the operation (STR 13.1 ± 6.9 months). The adverse events of gastric surgery evaluated in this study consisted of the degree of remnant gastritis, the presence of dumping syndrome, and degree of weight loss (%). There was no difference in the degree of DGR and remnant gastritis by gastroscopic finding between LTR and STR after PRG (P = 0.21). Statistically, there was no difference in the bile acid concentration of remnant gastric juice between LTR and STR (108.4 ± 254.1 vs. 94.0 ± 208.6 μmol/L, P = 0.33), and weight loss of LTR was the same as that of STR (5.67 ± 7.08 vs. 4.59 ± 5.63%, P = 0.34). There were few morphological changes in the reconstructed pylorus by the long-term course, but 2 patients showed mild atrophy. The form of reconstructed pylorus and the effect that reduces side effects of Billroth I seem to last for a long time.

Short-term outcomes and nutritional status after laparoscopic subtotal gastrectomy with a very small remnant stomach for cStage I proximal gastric carcinoma.

PubMed

Furukawa, Haruna; Kurokawa, Yukinori; Takiguchi, Shuji; Tanaka, Koji; Miyazaki, Yasuhiro; Makino, Tomoki; Takahashi, Tsuyoshi; Yamasaki, Makoto; Nakajima, Kiyokazu; Mori, Masaki; Doki, Yuichiro

2018-05-01

Total or proximal gastrectomy is usually performed for early proximal gastric carcinoma, but the optimal type of gastrectomy is still unknown. We evaluated short-term outcomes and nutritional status after laparoscopic subtotal gastrectomy (LsTG) in comparison with laparoscopic total gastrectomy (LTG) and laparoscopic proximal gastrectomy (LPG). We analyzed 113 patients who underwent LsTG (n = 38), LTG (n = 48), or LPG (n = 27) for cStage I gastric cancer located in the upper third of the stomach. Postoperative morbidities, nutritional status including body weight, serum albumin, hemoglobin, the prognostic nutritional index (PNI), and endoscopic findings at 1 year after surgery were compared between LsTG and both LTG and LPG. Operation time and intraoperative blood loss were similar among the three groups. The incidence of postoperative morbidities was lower in LsTG than in LTG. The degree of body weight loss was significantly smaller in LsTG than in LTG at 6 and 12 months. At 12 months, LsTG resulted in better serum albumin and PNI than LPG, and better hemoglobin than LTG. Endoscopic examination demonstrated that one LsTG patient and two LPG patients had reflux esophagitis. Remnant gastritis was observed more frequently in LPG than in LsTG. No LsTG patient had bile reflux, although it was observed in four LPG patients. LsTG with a very small remnant stomach had favorable short-term outcomes and nutritional status compared with LTG and LPG, so it may be a better treatment option for cStage I proximal gastric carcinoma.

The utility of ambulatory pH monitoring in patients presenting with chronic cough and asthma

PubMed Central

AlHabib, KF; Vedal, S; Champion, P; FitzGerald, JM

2007-01-01

OBJECTIVE: To evaluate the prevalence of gastroesophageal reflux disease (GERD) in patients presenting with asthma and chronic cough. PATIENTS AND METHODS: The charts of 358 consecutive patients who were referred for ambulatory gastroesophageal pH monitoring to the Lung Centre in Vancouver, British Columbia, were reviewed, and the data of 108 (30%) patients with asthma and 134 (37%) patients with chronic cough were analyzed. The maintenance treatment for GERD was discontinued before patients underwent the pH monitoring study. One hundred eighteen (33%) patients were excluded. RESULTS: Reflux episodes identified reflux events as the percentage of time where the pH was less than four. For asthma patients, 70 (64.8%) had distal total reflux, 50 (46.3%) had distal upright reflux, 41 (38.3%) had distal supine reflux and 73 (67.6%) had other distal refluxes. Proximal total reflux in asthmatic patients was present in 56 (52%), proximal upright reflux in 55 (51%) and proximal supine reflux in 56 (52%) patients. For chronic cough patients, 70 (52.6%) had distal total reflux, 59 (44.4%) had distal upright reflux, 45 (34.4%) had distal supine reflux and 75 (56%) patients had other distal refluxes. In chronic cough patients, proximal total reflux was present in 70 (52%), proximal upright reflux in 80 (60%) and proximal supine reflux in 59 (44%). Presenting respiratory and/or reflux symptoms were absent in approximately 25% of patients with asthma and reflux, and in approximately 50% of patients with chronic cough and reflux. During pH monitoring, symptoms did not differ significantly between those with and without distal reflux in both study groups, except for more significant heartburn in patients with chronic cough and reflux (RR 2.0). CONCLUSIONS: The data of the present study support the observation that there is a high prevalence of GERD in patients with asthma or chronic cough. The use of different pH parameters for detecting acid reflux during 24 h ambulatory pH monitoring, such as proximal esophageal acid measurement, should be considered as part of the routine interpretation of such testing. A low threshold for diagnosing GERD in patients with asthma or chronic cough is essential, because respiratory and/or reflux symptoms can be absent or atypical in some of these patients. PMID:17377644

Pathophysiology of Gastroesophageal Reflux Disease.

PubMed

Tack, Jan; Pandolfino, John E

2018-01-01

The pathogenesis of gastroesophageal reflux disease (GERD) is complex and involves changes in reflux exposure, epithelial resistance, and visceral sensitivity. The gastric refluxate is a noxious material that injures the esophagus and elicits symptoms. Esophageal exposure to gastric refluxate is the primary determinant of disease severity. This exposure arises via compromise of the anti-reflux barrier and reduced ability of the esophagus to clear and buffer the refluxate, leading to reflux disease. However, complications and symptoms also occur in the context of normal reflux burden, when there is either poor epithelial resistance or increased visceral sensitivity. Reflux therefore develops via alterations in the balance of aggressive and defensive forces. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

Reflux in Infants

MedlinePlus

What are reflux (GER) and GERD? The esophagus is the tube that carries food from your mouth to your stomach. If your baby has reflux, his or ... into the esophagus. Another name for reflux is gastroesophageal reflux (GER). GERD stands for gastroesophageal reflux disease. It ...

Reflux in Children

MedlinePlus

What are reflux (GER) and GERD? The esophagus is the tube that carries food from your mouth to your stomach. If your child has reflux, his or ... into the esophagus. Another name for reflux is gastroesophageal reflux (GER). GERD stands for gastroesophageal reflux disease. It ...

Gastroesophageal reflux disease in children with chronic otitis media with effusion.

PubMed

Yüksel, Fatih; Doğan, Mansur; Karataş, Duran; Yüce, Salim; Şentürk, Mehmet; Külahli, Ismail

2013-03-01

We aimed to evaluate a possible relation between gastroesophageal reflux disease and middle ear effusion in children. Children who came to ear, nose, and throat (ENT) department with the symptoms of hearing loss or aural fullness and diagnosed as OME by examination and tympanometry were included into the study. Children were reviewed gastroesophageal reflux disease symptoms including the following: (a) airway symptoms: stridor, frequent cough, recurrent croup, wheezing, nasal congestion, obstructive apnea, hoarseness, and throat clearing; (b) feeding symptoms: frequent emesis, dysphagia, choking: gagging, sore throat, halitosis, food refusal, regurgitation, pyrosis, irritability, failure to thrive, and anemia. Diagnosis is made with at least one positive test of radionuclide gastroesophageal scintigraphy or 24 h pH probe in the patients with reflux. ENT findings were also examined between gastroesophageal reflux disease positive and gastroesophageal reflux disease negative groups. Approximately 39 (54.9%) of 71 children had at least 1 positive test for gastroesophageal reflux disease. Between the gastroesophageal reflux disease-positive and gastroesophageal reflux disease-negative groups, symptoms of reflux were not significantly different. Two pooled variables were created: airway complex (stridor, frequent cough, throat clearing), and feeding complex (irritability, pyrosis, failure to thrive). Percentage of positive symptom complexes were no statistically different between gastroesophageal reflux disease-positive and gastroesophageal reflux disease-negative groups (>0.05). Ear, nose, and throat disorders (including rhinitis/sinusitis, adenoid hypertrophy, tonsillitis/pharyngitis, and laryngitis) were more frequent in gastroesophageal reflux disease-positive group. Tonsillitis/pharyngitis was significantly different between the gastroesophageal reflux disease positive and gastroesophageal reflux disease-negative groups. Upper respiratory tract infections were seen more frequently in gastroesophageal reflux disease positive group. Children who present with gastroesophageal reflux disease symptoms are more likely to have a positive gastroesophageal reflux disease test. However, no concordance may be found between the complaints and gastroesophageal reflux disease findings. For this reason, a decision about gastroesophageal reflux disease should not only be made by looking to complaints; diagnostic tests must also be performed.

Motor disorders of the oesophagus in gastro-oesophageal reflux.

PubMed Central

Mahony, M J; Migliavacca, M; Spitz, L; Milla, P J

1988-01-01

Mechanisms of gastro-oesophageal reflux were studied by oesophageal manometry and pH monitoring in 33 children: nine controls, 15 with gastro-oesophageal reflux alone, and nine with reflux oesophagitis. A total of 122 episodes of reflux were analysed in detail: 82 (67%) were synchronous with swallowing and 40 (33%) asynchronous. Infants with trivial symptoms had gastro-oesophageal reflux synchronous with swallowing, whereas those with serious symptoms had slower acid clearance and asynchronous reflux. There were significant differences in lower oesophageal sphincter pressure and amplitude of oesophageal contractions between controls and patients with both gastro-oesophageal reflux and reflux oesophagitis. In reflux oesophagitis there was a decrease in lower oesophageal sphincter pressure and the contractions had a bizarre waveform suggesting a neuropathic process. PMID:3202640

High Prevalence of Laryngopharyngeal Reflux Disease in Patients With Lumbar Kyphosis.

PubMed

Matsuzaki, Hiroumi; Makiyama, Kiyoshi; Hoshino, Masahiro; Oshima, Takeshi

2016-11-01

To evaluate the relationship between laryngopharyngeal reflux disease and presence of lumbar kyphosis. A cross-sectional study. We included 20 patients with lumbar kyphosis and 31 control subjects. A diagnosis of laryngopharyngeal reflux disease and gastroesophageal reflux disease was made if the Reflux Symptom Index score was ≥13 and if the Frequency Scale for the Symptoms of Gastroesophageal Reflux Disease was ≥8, respectively. We compared the prevalence of the two reflux diseases, frequent reflux symptoms, and demographic factors between the two groups. There was no significant difference in demographic factors between the two groups. Five (25%) of 20 patients with lumbar kyphosis had a Reflux Symptom Index ≥13 compared with one (3.2%) of 31 controls. Seven (35.0%) of 20 patients had a Frequency Scale for the Symptoms of Gastroesophageal Reflux Disease ≥8 compared with three (9.7%) of 31 controls. A comparison of the prevalence of laryngopharyngeal reflux disease and gastroesophageal reflux disease showed a significant difference between patients with kyphosis and controls (P value = 0.029 and 0.036, respectively). In Reflux Symptom Index, heartburn, hoarseness, and a swallowing problem were significantly frequent symptoms in the kyphosis group compared with the control group. The prevalence of laryngopharyngeal reflux disease and gastroesophageal reflux disease was significantly higher in patients with lumbar kyphosis than in controls. Therefore, otolaryngologists and orthopedic surgeons should be aware that patients with lumbar kyphosis are likely to have gastroesophageal reflux disease and also laryngopharyngeal reflux disease. Copyright © 2016 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

Optimal treatment of laryngopharyngeal reflux disease

PubMed Central

Martinucci, Irene; Savarino, Edoardo; Nacci, Andrea; Romeo, Salvatore Osvaldo; Bellini, Massimo; Savarino, Vincenzo; Fattori, Bruno; Marchi, Santino

2013-01-01

Laryngopharyngeal reflux is defined as the reflux of gastric content into larynx and pharynx. A large number of data suggest the growing prevalence of laryngopharyngeal symptoms in patients with gastroesophageal reflux disease. However, laryngopharyngeal reflux is a multifactorial syndrome and gastroesophageal reflux disease is not the only cause involved in its pathogenesis. Current critical issues in diagnosing laryngopharyngeal reflux are many nonspecific laryngeal symptoms and signs, and poor sensitivity and specificity of all currently available diagnostic tests. Although it is a pragmatic clinical strategy to start with empiric trials of proton pump inhibitors, many patients with suspected laryngopharyngeal reflux have persistent symptoms despite maximal acid suppression therapy. Overall, there are scant conflicting results to assess the effect of reflux treatments (including dietary and lifestyle modification, medical treatment, antireflux surgery) on laryngopharyngeal reflux. The present review is aimed at critically discussing the current treatment options in patients with laryngopharyngeal reflux, and provides a perspective on the development of new therapies. PMID:24179671

Quantifying saphenous reflux.

PubMed

Raju, Seshadri; Ward, Mark; Jones, Tamekia L

2015-01-01

Quantification of reflux is desirable in advanced chronic venous disease as clinical features are based on its adverse impact on ambulatory venous pressure (AMVP). Prior clinical observation suggests that reflux in a saphenous vein > 5 mm is likely significant. On the basis of normal calf pump mechanics, we hypothesized that a reflux volume ≥ 30 mL was necessary to upset pump equilibrium. Venous laboratory data in 119 limbs with isolated saphenous reflux were analyzed. Reflux volume was calculated by duplex ultrasound (area × velocity × duration). The relationship of reflux volume to saphenous size, calf pump function (air plethysmography, AMVP), flow resistance (Poiseuille equation), and clinical severity were examined. Saphenous size had a bimodal relationship to reflux volume. Reflux volume of ≥ 30 mL occurred mostly (97% of limbs) with saphenous size of ≥ 5.5 mm, but 51% of saphenous veins >5.5 mm had reflux volumes <30 mL. This is because saphenous veins invariably carried less than their maximum reflux potential indicated by their size (Poiseuille equation). Variable additional focal resistance across refluxive valve cusps and narrower re-entry perforators is not taken into account when only saphenous truncal size is used for resistance calculation. Furthermore, the association of AMVP with reflux was found not to be based on a set (≥ 30 mL) threshold but was variable, depending on existing calf pump mechanics, compensatory in some (12% of limbs) and aggravating reflux effects in others (26%). Calf pump abnormalities were found in 70% of refluxive limbs and in 44% (n = 16) of contralateral limbs without any reflux. Reflux volume was significantly higher overall in limbs with ulcer (C6), but the range overlapped with lesser clinical classes. Seven of 14 limbs with active ulcers had reflux volume >30 mL; six of seven limbs with active ulcers and reflux volume of <30 mL had calf pump abnormalities that would be poorly tolerant of reflux even at these smaller volumes. Saphenous size alone cannot be used as an indicator of significant reflux. More than two thirds of the limbs with isolated saphenous reflux have calf pump abnormalities, which also occurred without reflux in the opposite limb--a novel finding. This means that in addition to quantification of reflux volume, calf pump assessment such as with air plethysmography and AMVP is desirable in clinical classes 3 and higher for proper assessment. Copyright © 2015 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

The effect of dietary carbohydrate on gastroesophageal reflux disease.

PubMed

Wu, Keng-Liang; Kuo, Chung-Mou; Yao, Chih-Chien; Tai, Wei-Chen; Chuah, Seng-Kee; Lim, Chee-Sang; Chiu, Yi-Chun

2018-01-12

Acid changes in gastroesophageal reflux with vary component in the food have less been studied, especially carbohydrate. We plan to clarify the effect of different carbohydrate density on low esophageal acid and reflux symptoms of patients with gastroesophgeal reflux disease. Twelve patients (52 ± 12 years old; five female) with gastroesophageal reflux disease were recruited for the prospective crossover study. Each patient was invited for panendoscope, manometry and 24 h pH monitor. The two formulated liquid meal, test meal A: 500 ml liquid meal (containing 84.8 g carbohydrate) and B: same volume liquid meal (but 178.8 g carbohydrate) were randomized supplied as lunch or dinner. Reflux symptoms were recorded. There are significant statistic differences in more Johnson-DeMeester score (p = 0.019), total reflux time (%) (p = 0.028), number of reflux periods (p = 0.026) and longest reflux (p = 0.015) after high carbohydrate diet than low carbohydrate. Total reflux time and number of long reflux periods more than 5 min are significant more after high carbohydrate diet. More acid reflux symptoms are found after high carbohydrate diet. High carbohydrate diet could induce more acid reflux in low esophagus and more reflux symptoms in patients with gastroesophageal reflux disease. Copyright © 2018. Published by Elsevier B.V.

Lower pH values of weakly acidic refluxes as determinants of heartburn perception in gastroesophageal reflux disease patients with normal esophageal acid exposure.

PubMed

de Bortoli, N; Martinucci, I; Savarino, E; Franchi, R; Bertani, L; Russo, S; Ceccarelli, L; Costa, F; Bellini, M; Blandizzi, C; Savarino, V; Marchi, S

2016-01-01

Multichannel impedance pH monitoring has shown that weakly acidic refluxes are able to generate heartburn. However, data on the role of different pH values, ranging between 4 and 7, in the generation of them are lacking. The aim of this study was to evaluate whether different pH values of weakly acidic refluxes play a differential role in provoking reflux symptoms in endoscopy-negative patients with physiological esophageal acid exposure time and positive symptom index and symptom association probability for weakly acidic refluxes. One hundred and forty-three consecutive patients with gastroesophageal reflux disease, nonresponders to proton pump inhibitors (PPIs), were allowed a washout from PPIs before undergoing: upper endoscopy, esophageal manometry, and multichannel impedance pH monitoring. In patients with both symptom index and symptom association probability positive for weakly acidic reflux, each weakly acidic reflux was evaluated considering exact pH value, extension, physical characteristics, and correlation with heartburn. Forty-five patients with normal acid exposure time and positive symptom association probability for weakly acidic reflux were identified. The number of refluxes not heartburn related was higher than those heartburn related. In all distal and proximal liquid refluxes, as well as in distal mixed refluxes, the mean pH value of reflux events associated with heartburn was significantly lower than that not associated. This condition was not confirmed for proximal mixed refluxes. Overall, a low pH of weakly acidic reflux represents a determinant factor in provoking heartburn. This observation contributes to better understand the pathophysiology of symptoms generated by weakly acidic refluxes, paving the way toward the search for different therapeutic approaches to this peculiar condition of esophageal hypersensitivity. © 2014 International Society for Diseases of the Esophagus.

Acid Secretion and Its Relationship to Esophageal Reflux Symptom in Patients with Subtotal Gastrectomy.

PubMed

Oh, Hyun Jin; Choi, Myung-Gyu; Park, Jae Myung; Song, Kyo Young; Yoo, Han Mo

2018-03-01

Esophageal reflux symptom has been reported as common in patients with subtotal gastrectomy. Management of postoperative esophageal reflux symptom is not satisfactory. The aim of this study is to investigate prevalence of esophageal reflux symptom after subtotal gastrectomy and assess factors affecting esophageal reflux symptom in subtotal gastrectomy patients. We prospectively enrolled 100 consecutive patients with subtotal gastrectomy who were regularly followed up by endoscopic examination. Acid secretory capacity was assessed by measuring messenger RNA (mRNA) expression of H + /K + -adenosine triphosphatase (ATPase) via real-time polymerase chain reaction (PCR) in biopsy specimens. In total, 47 % of patients had typical esophageal reflux symptom, where heartburn or regurgitation was experienced at least weekly. Age, sex, body mass index, and type of reconstruction did not differ between esophageal reflux and non-esophageal-reflux groups. The esophageal reflux group had longer duration from time of operation until study (median 5.0 versus 3.6 years; P = 0.017). Hill grade for gastroesophageal (GE) flap valve was higher in the esophageal reflux group than in the non-esophageal-reflux group (P = 0.027). H + /K + -ATPase mRNA expression was higher in the esophageal reflux group than in the non-esophageal-reflux group [3967.6 (± 7583.7) versus 896.2 (± 1456.0); P = 0.006]. Multivariate analysis revealed that postoperative duration, H + /K + -ATPase mRNA expression level, and GE flap valve disruption were significantly associated with esophageal reflux symptom development. Esophageal reflux symptom is common in patients after subtotal gastrectomy, possibly because of anti-reflux-barrier impairment and preservation of acid secretory capacity following surgery. Optimal acid suppression may be helpful in managing postoperative esophageal reflux symptom.

Regional oesophageal sensitivity to acid and weakly acidic reflux in patients with non-erosive reflux disease.

PubMed

Emerenziani, S; Ribolsi, M; Sifrim, D; Blondeau, K; Cicala, M

2009-03-01

The mechanisms underlying symptoms in non-erosive reflux disease (NERD) remain to be elucidated. Non-erosive reflux disease patients appear to be more sensitive to intraluminal stimula than erosive patients, the proximal oesophagus being the most sensitive. In order to assess regional oesophageal changes in reflux acidity and sensitivity to reflux, according either to the acidity or the composition of the refluxate, combined multiple pH and multiple pH-impedance (pH-MII) was performed in 16 NERD patients. According to multiple pH-metry, 29% and 12% of reflux events reached the middle and proximal oesophagus respectively, and 35% and 19% according to conventional pH-MII (P < 0.05). The per-individual analysis confirmed the difference between the two techniques. According to combined distal and proximal pH-MII, approximately 30% of distal acid reflux became weakly acidic at the proximal oesophagus. In all patients, the frequency of symptomatic refluxes, both acid and weakly acidic, was significantly higher at the proximal, compared with distal oesophagus (25 +/- 8%vs 11 +/- 2% for acid reflux and 27 +/- 8%vs 8 +/- 2% for weakly acidic reflux; P < 0.05). Compared with multiple pH-metry, pH-MII shows a higher sensitivity in the detection of proximal reflux. As approximately 30% of acid reflux becomes weakly acidic along the oesophageal body, to better characterize proximal reflux, in clinical practice, combined proximal pH-impedance monitoring should be used. In NERD patients, the proximal oesophagus seems to be more sensitive to both acid and weakly acidic reflux.

Reflux and GERD (in Children)

MedlinePlus

... Pediatric Gastroenterology and Nutrition Nurses Print Share Reflux GERD Reflux occurs during or after a meal when ... tube connecting the mouth to the stomach). Reflux & GERD The Difference Between Reflux and GERD in Kids ...

“A New Reconstructive Method after Pancreaticoduodenectomy: the Triple Roux on a “P” Loop. Rationale and Radionuclide Scanning Evaluatlon.”

PubMed Central

Cariati, Erminio

1996-01-01

We propose a method of reconstruction after pancreaticoduodenectomy consisting of a double Roux en Y on the same jejunal loop without interruption of the mesentery and a third anatomical Roux en Y to reconstitute the alimentary tract. The construction of the double Roux en Y draining pancreas and bile ducts separately, requires a linear Stapler 3-4 centimeters from the biliary anastomosis. In this way, by employing the same loop without mesenteric interruption, two functional excluded loops will be ’obtained. The rationale of the suggested model is based on the separation of biliary and pancreatic secretions. This makes it possible to avoid a stagnant cul-de-sac coinciding with the pancreaticojejunal anastomosis and to obtain in the case of leakage, a pure biliary and/or pancreatic fistula as far as is possible. 99mTc HIDA scans demonstrated the efficiency, of the biliopancreatic limbs of the reconstruction, showing normal emptying time for the gastric remnant and the absence of radionuclide stagnation or any alkaline enterogastric reflux. PMID:8809583

Outcomes of targeted treatment for vesicoureteral reflux in children with nonneurogenic lower urinary tract dysfunction.

PubMed

Fast, Angela M; Nees, Shannon N; Van Batavia, Jason P; Combs, Andrew J; Glassberg, Kenneth I

2013-09-01

There is a known association between nonneurogenic lower urinary tract conditions and vesicoureteral reflux. Whether reflux is secondary to the lower urinary tract condition or coincidental is controversial. We determined the rate of reflux resolution in patients with lower urinary tract dysfunction using targeted treatment for the underlying condition. Patients diagnosed and treated for a lower urinary tract condition who had concomitant vesicoureteral reflux at or near the time of diagnosis were included. Patients underwent targeted treatment and antibiotic prophylaxis, and reflux was monitored with voiding cystourethrography or videourodynamics. Vesicoureteral reflux was identified in 58 ureters in 36 females and 5 males with a mean age of 6.2 years. After a mean of 3.1 years of treatment reflux resolved with targeted treatment in 26 of 58 ureters (45%). All of these patients had a history of urinary tract infections before starting targeted treatment. Resolution rates of vesicoureteral reflux were similar for all reflux grades. Resolution or significant improvement of reflux was greater in the ureters of patients with dysfunctional voiding (70%) compared to those with idiopathic detrusor overactivity disorder (38%) or detrusor underutilization (40%). Vesicoureteral reflux associated with lower urinary tract conditions resolved with targeted treatment and antibiotic prophylaxis in 45% of ureters. Unlike the resolution rates reported in patients with reflux without a coexisting lower urinary tract condition, we found that there were no differences in resolution rates among grades I to V reflux in patients with lower urinary tract conditions. Patients with dysfunctional voiding had the most improvement and greatest resolution of reflux. Additionally grade V reflux resolved in some patients. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Temporal associations between coughing or wheezing and acid reflux in asthmatics

PubMed Central

Avidan, B; Sonnenberg, A; Schnell, T; Sontag, S

2001-01-01

BACKGROUND AND AIMS—The pulmonary symptoms of patients with lung disease may be ascribed to gastro-oesophageal reflux although a causal relationship between acid reflux and coughing or wheezing has not been proved. Does cough cause reflux or does reflux cause cough? The aim of this study was to evaluate 24 hour oesophageal pH tracings of asthmatics with gastro-oesophageal reflux to determine the temporal association between acid reflux and coughing or wheezing.
METHODS—The oesophageal tracings of 128 asthmatics from the outpatient clinics who underwent oesophagogastroduodenoscopy, oesophageal manometry, and 24 hour oesophageal pH monitoring were analysed. Three possible temporal relationships between the occurrence of acid reflux and the occurrence of coughs or wheezes were evaluated: (1) pulmonary symptoms preceding reflux; (2) reflux preceding pulmonary symptoms; and (3) unrelated occurrence of both events.
RESULTS—Of 128 asthmatics, 53 recorded five or more coughs and 19 recorded three or more wheezes during the 24 hour recording period. Mean acid contact time was similar in asthmatics with and without pulmonary symptoms (12.2 (1.2)% v 10.4 (0.6)%). Of all coughs and wheezes, 46% and 48%, respectively, were associated with acid reflux. For the individual asthmatic, the likelihood of reflux induced coughing increased as the number of coughs increased.
CONCLUSIONS—Half of all coughs and wheezes in asthmatics are associated with acid reflux into the oesophagus. While an occasional coughing episode can lead to reflux, it is rather the reflux episode in the vast majority of instances that leads to cough.


Keywords: asthma; gastro-oesophageal reflux disease; erosive oesophagitis; oesophageal pH monitoring; lung disease; pulmonary symptoms PMID:11709509

The Efficacy of the Upright Position on Gastro-Esophageal Reflux and Reflux-Related Respiratory Symptoms in Infants With Chronic Respiratory Symptoms

PubMed Central

Jung, Woo Jin; Yang, Hyeon Jong; Min, Taek Ki; Jeon, You Hoon; Lee, Hae Won; Lee, Jun Sung

2012-01-01

Purpose Gastro-esophageal reflux (GER), particularly non-acid reflux, is common in infants and is a known cause of chronic respiratory symptoms in infancy. Recent guidelines recommended empirical acid suppression therapy and the head-up position in patients with suspected GER. However, the efficacy of the upright position in relieving GER and reflux-related respiratory symptoms in infants is unclear. We conducted this study to investigate the efficacy of the upright position on GER and reflux-related respiratory symptoms in infants with chronic respiratory symptoms. Methods Thirty-two infants (21 male; median age, 5 months; range, 0 to 19 months) with unexplained chronic respiratory symptoms underwent multi-channel intraluminal esophageal impedance and pH monitoring. We retrospectively compared the frequencies of GER and reflux-related symptoms according to body position. Results A mean of 3.30 episodes of reflux per hour was detected. Overall, refluxes were more frequent during the postprandial period than the emptying period (3.77 vs. 2.79 episodes/hour, respectively; P=0.01). Although there was no significant difference in the total refluxes per hour between the upright and recumbent positions (6.12 vs. 3.77 episodes, P=0.10), reflux-related respiratory symptoms per reflux were significantly fewer in infants kept in an upright position than in a recumbent position during the postprandial period (3.07% vs. 14.75%, P=0.016). Non-acid reflux was the predominant type of reflux in infants, regardless of body position or meal time. Conclusions The upright position may reduce reflux-related respiratory symptoms, rather than reflux frequency. Thus, it may be a useful non-pharmacological treatment for infantile GER disease resistant to acid suppressants. PMID:22211166

The efficacy of the upright position on gastro-esophageal reflux and reflux-related respiratory symptoms in infants with chronic respiratory symptoms.

PubMed

Jung, Woo Jin; Yang, Hyeon Jong; Min, Taek Ki; Jeon, You Hoon; Lee, Hae Won; Lee, Jun Sung; Pyun, Bok Yang

2012-01-01

Gastro-esophageal reflux (GER), particularly non-acid reflux, is common in infants and is a known cause of chronic respiratory symptoms in infancy. Recent guidelines recommended empirical acid suppression therapy and the head-up position in patients with suspected GER. However, the efficacy of the upright position in relieving GER and reflux-related respiratory symptoms in infants is unclear. We conducted this study to investigate the efficacy of the upright position on GER and reflux-related respiratory symptoms in infants with chronic respiratory symptoms. Thirty-two infants (21 male; median age, 5 months; range, 0 to 19 months) with unexplained chronic respiratory symptoms underwent multi-channel intraluminal esophageal impedance and pH monitoring. We retrospectively compared the frequencies of GER and reflux-related symptoms according to body position. A mean of 3.30 episodes of reflux per hour was detected. Overall, refluxes were more frequent during the postprandial period than the emptying period (3.77 vs. 2.79 episodes/hour, respectively; P=0.01). Although there was no significant difference in the total refluxes per hour between the upright and recumbent positions (6.12 vs. 3.77 episodes, P=0.10), reflux-related respiratory symptoms per reflux were significantly fewer in infants kept in an upright position than in a recumbent position during the postprandial period (3.07% vs. 14.75%, P=0.016). Non-acid reflux was the predominant type of reflux in infants, regardless of body position or meal time. The upright position may reduce reflux-related respiratory symptoms, rather than reflux frequency. Thus, it may be a useful non-pharmacological treatment for infantile GER disease resistant to acid suppressants.

Which drugs are risk factors for the development of gastroesophageal reflux disease?

PubMed

Mungan, Zeynel; Pınarbaşı Şimşek, Binnur

2017-12-01

Gastroesophageal reflux disease (GERD), which is common in many communities, is associated with structural factors, eating habits, and the use of certain drugs. The use of such drugs can lead to the emergence of GERD and can also exacerbate existing reflux symptoms. These drugs can contribute to GERD by directly causing mucosal damage, by reducing lower esophageal sphincter pressure (LESP), or by affecting esophagogastric motility. In this article, we report our investigation of the relationships between GERD and medications within the scope of the "Turkish GERD Consensus Group." For the medication groups for which sufficient data were obtained (Figure 1), a systematic literature review in English was conducted using the keywords "gastroesophageal reflux" [MeSH Terms] and "anti-inflammatory agents, non-steroidal" [MeSH Terms], "gastroesophageal reflux" [MeSH Terms] and "acetylsalicylic acid" [MeSH Terms], "gastroesophageal reflux" [All Fields] and "estrogenic agents" [All Fields], "gastroesophageal reflux" [All Fields] and "progesterones" [All Fields], "gastroesophageal reflux" [All Fields] and "hormone replacement therapy" [All Fields], "gastroesophageal reflux" [MeSH Terms] and "diphosphonates" [MeSH Terms] OR "diphosphonates" [All Fields], "calcium channel blockers" [MeSH Terms] and "gastroesophageal reflux" [MeSH Terms], "gastroesophageal reflux" [MeSH Terms] and "nitrates" [MeSH Terms], "gastroesophageal reflux" [MeSH Terms] and "antidepressive agents" [MeSH Terms], "gastroesophageal reflux" [MeSH Terms] and "benzodiazepines" [MeSH Terms] and "hypnotic drugs" [MeSH Terms], "gastroesophageal reflux" [MeSH Terms] and "cholinergic antagonists" [MeSH Terms], "gastroesophageal reflux" [MeSH Terms] and "theophylline" [MeSH Terms], and "gastroesophageal reflux [MeSH Terms] AND "anti-asthmatic agents" [MeSH Terms]. The studies were analyzed and the results are presented here.

Oesophageal mucosal intercellular space diameter and reflux pattern in childhood erosive and non-erosive reflux disease.

PubMed

Mancini, Valentina; Ribolsi, Mentore; Gentile, Massimo; de'Angelis, Gianluigi; Bizzarri, Barbara; Lindley, Keith J; Cucchiara, Salvatore; Cicala, Michele; Borrelli, Osvaldo

2012-12-01

We sought to compare intercellular space diameter in children with non-erosive and erosive reflux disease, and a control group. We also aimed to characterize the reflux pattern in erosive and non-erosive reflux disease patients, and to explore the relationship between intercellular space diameter values and reflux parameters. Twenty-four children with non-erosive reflux disease, 20 with erosive reflux disease, and 10 controls were prospectively studied. All patients and controls underwent upper endoscopy. Biopsies were taken at 2-3 cm above the Z-line, and intercellular space diameter was measured using transmission electron microscopy. Non-erosive and erosive reflux disease patients underwent impedance-pH monitoring. Mean intercellular space diameter values were significantly higher in both non-erosive (0.9 ± 0.2 μm) and erosive reflux disease (1 ± 0.2 μm) compared to controls (0.5 ± 0.2 μm, p<0.01). No difference was found between the two patient groups. Acid exposure time, the number of acid, weakly acidic and weakly alkaline reflux events did not differ between the two patient groups. No difference was found in the mean intercellular space diameter between non-erosive reflux disease children with and without abnormal acid exposure time (1 ± 0.3 vs. 0.9 ± 0.2 μm). No correlation was found between any reflux parameter and intercellular space diameter values. Dilated intercellular space diameter seems to be a useful and objective marker of oesophageal damage in paediatric gastro-oesophageal reflux disease, regardless of acid exposure. In childhood, different gastro-oesophageal reflux disease phenotypes cannot be discriminated on the basis of reflux pattern. Copyright © 2012 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

[Impact of reflux on the kidney].

PubMed

Mollard, P; Louis, D; Basset, T

1984-03-01

Description of the reflux nephropathy. Pyelonephritis lesions are undoubtedly linked to the vesico-ureteric reflux. The role of the intra-renal reflux ( Hodson ) and the Big Bang Theory ( Ransley ) are discussed as the data from animal experiments. The role of the sterile reflux and of the segmental hypoplasia is relatively less important. The actual management of vesico-ureteric reflux treatment is questioned.

COMBINED 24-HOURS ESOPHAGEAL PH MONITORING AND MULTICHANNEL INTRALUMINAL IMPEDANCE FOR COMPARISON OF GASTROESOPHAGEAL REFLUX IN CHILDREN WITH TYPICAL VERSUS ATYPICAL SYMPTOMS OF GASTROESOPHAGEAL REFLUX DISEASE.

PubMed

Dehghani, Seyed Mohsen; Taghavi, Seyed Alireza; Javaherizadeh, Hazhir; Nasri, Maryam

2016-01-01

- Gastroesophageal reflux disease is the most common esophageal disorder in pediatrics. - The aim of this study was to compare reflux parameters of typical and atypical symptoms of gastroesophageal reflux disease using 24-hour esophageal pH monitoring and multichannel intraluminal impedance in pediatric population. - In this prospective study, 43 patients aged less than 18 year with suspected gastroesophageal reflux disease were enrolled. The patients were divided into two groups based on the main presenting symptoms (typical versus atypical). Twenty four-hour pH monitoring and multichannel intraluminal impedance were performed in all the patients for comparing these two group regarding association of symptoms and reflux. Number of refluxes, pH related reflux, total reflux time, reflux more than 5 minutes, longest time of the reflux, lowest pH at reflux, reflux index were recorded and compared. Data comparison was done using SPSS. - The mean age of the patients was 5.7±3.4 years and 65.1% were male. Out of 43 patients 24 cases had typical symptoms and 19 had atypical symptoms. The mean reflux events detected by multichannel intraluminal impedance was more than mean reflux events detected by pH monitoring (308.4±115.8 vs 69.7±66.6) with P value of 0.037, which is statistically significant. The mean symptom index and symptom association probability were 35.01% ± 20.78% and 86.42% ± 25.79%, respectively in multichannel intraluminal impedance versus 12.73% ± 12.48% and 45.16% ± 42.29% in pH monitoring (P value <0.001). Number of acid reflux was 46.26±47.16 and 30.9±22.09 for atypical and typical symptoms respectively. The mean symptom index was 18.12% ± 13.101% and 8.30% ± 10.301% in atypical and typical symptoms respectively (P=0.034). Bolus clearance was longer in atypical symptoms compared typical symptoms(P<0.05). - Symptom index was significantly higher in atypical symptoms compared to typical symptoms. Higher number of acid reflux was found in children with atypical symptoms of reflux. Longer duration of bolus clearance was found in group with atypical symptoms of reflux.

Utility of Water Siphon Maneuver for Eliciting Gastroesophageal Reflux During Barium Esophagography: Correlation With Histologic Findings.

PubMed

Dane, B; Doshi, A; Khan, A; Megibow, A

2018-06-12

The objective of this study is to evaluate whether the water siphon maneuver improves detection of gastroesophageal (GE) reflux during barium esophagography compared with observation for spontaneous reflux only. Histopathologic analysis is the reference standard. This retrospective study assessed 87 outpatients who underwent both barium esophagography and upper endoscopy-guided biopsy within a 30-day interval. The water siphon maneuver was routinely performed when spontaneous GE reflux was not observed during the fluoroscopic study. Radiology reports were reviewed for mentions of the presence of reflux and the circumstances in which it was observed (as a spontaneous occurrence or as a result of the water siphon maneuver). Pathology reports from subsequent endoscopic biopsies were reviewed to identify histologic changes of reflux disease. The sensitivity, specificity, and accuracy of esophagography, observation for spontaneous reflux, and the water siphon maneuver were calculated and then compared using a McNemar test. Of the 87 patients, 57 (65.5%) had GE reflux diagnosed on the basis of histologic changes noted on endoscopy, and 30 (34.5%) did not. A total of 57 patients (65.5%) showed reflux during esophagography, 41 (71.9%) of whom had reflux diagnosed by the water siphon maneuver, and 16 (28.1%) had reflux diagnosed on the basis of observation of spontaneous reflux. Forty-four patients had reflux diagnosed on the basis of both a barium study and histologic findings; 13 patients had reflux noted on esophagography but had negative histologic findings. The overall sensitivity, specificity, and accuracy of esophagography for reflux were 77.2%, 56.7%, and 70.1%, respectively. Spontaneous reflux alone had a sensitivity, specificity, and accuracy of 21.1%, 86.7%, and 43.7%, respectively. The water siphon maneuver showed a sensitivity of 71.1%, a specificity of 65.4%, and accuracy of 69.0%. The differences in the sensitivity, specificity, and accuracy of the water siphon maneuver versus observation of spontaneous reflux were statistically significant (p ≤ 0.004). A properly performed and interpreted water siphon maneuver significantly increases the sensitivity and accuracy for GE reflux during esophagography, compared with observation for spontaneous reflux alone. The water siphon maneuver is a simple addition to barium esophagography that improves sensitivity and accuracy for the diagnosis of GE reflux compared with observation alone.

Gastroesophageal Reflux Disease and Aerodigestive Disorders.

PubMed

Maqbool, Asim; Ryan, Matthew J

2018-03-01

This relationship between gastroesophageal reflux and airway disorders is complex, possibly bidirectional, and not clearly defined. The tools used to investigate gastroesophageal reflux are mostly informative about involvement of gastroesophageal reflux within the gastrointestinal tract, although they are often utilized to study the relationship between gastroesophageal reflux and airway issues with are suspected to occur in relation to reflux. These modalities often lack specificity for reflux-related airway disorders. Co-incidence of gastroesophageal reflux and airway disorders does not necessarily infer causality. While much of our focus has been on managing acidity, controlling refluxate is an area that has not been traditionally aggressively pursued. Our management approach is based on some of the evidence presented, but also often from a lack of adequate study to provide further guidance. Copyright © 2018 Mosby, Inc. All rights reserved.

Food and Gastroesophageal Reflux Disease.

PubMed

Surdea-Blaga, Teodora; Negrutiu, Dana E; Palage, Mariana; Dumitrascu, Dan L

2017-05-15

Gastroesophageal reflux disease is a chronic condition with a high prevalence in western countries. Transient lower esophageal sphincter relaxation episodes and a decreased lower esophageal sphincter pressure are the main mechanisms involved. Currently used drugs are efficient on reflux symptoms, but only as long as they are administered, because they do not modify the reflux barrier. Certain nutrients or foods are generally considered to increase the frequency of gastroesophageal reflux symptoms, therefore physicians recommend changes in diet and some patients avoid bothering foods. This review summarizes current knowledge regarding food and gastroesophageal reflux. For example, fat intake increases the perception of reflux symptoms. Regular coffee and chocolate induce gastroesophageal reflux and increase the lower esophageal exposure to acid. Spicy foods might induce heartburn, but the exact mechanism is not known. Beer and wine induce gastroesophageal reflux, mainly in the first hour after intake. For other foods, like fried food or carbonated beverages data on gastroesophageal reflux is scarce. Similarly, there is few data about the type of diet and gastroesophageal reflux. Mediterranean diet and a very low carbohydrate diet protect against reflux. Regarding diet-related practices, consistent data showed that a "short-meal-to-sleep interval" favors reflux episodes, therefore some authors recommend that dinner should be at least four hours before bedtime. All these recommendations should consider patient's weight, because several meta-analysis showed a positive association between increased body mass index and gastroesophageal reflux disease. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Reflux and GERD in Infants

MedlinePlus

... Gastroenterology and Nutrition Nurses Print Share Reflux and GERD : Reflux and GERD in Infants Reflux and GERD in Infants It’s not uncommon for a baby ... happy, healthy childhood. Quick Facts about Reflux and GERD in Infants The majority of infants do not ...

Relationship between gastro-oesophageal reflux and airway diseases: the airway reflux paradigm.

PubMed

Pacheco-Galván, Adalberto; Hart, Simon P; Morice, Alyn H

2011-04-01

Our understanding of the relationship between gastro-oesophageal reflux and respiratory disease has recently undergone important changes. The previous paradigm of airway reflux as synonymous with the classic gastro-oesophageal reflux disease (GORD) causing heartburn has been overturned. Numerous epidemiological studies have shown a highly significant association of the acid, liquid, and gaseous reflux of GORD with conditions such as laryngeal diseases, chronic rhinosinusitis, treatment resistant asthma, COPD and even idiopathic pulmonary fibrosis. However, it has become clear from studies on cough hypersensitivity syndrome that much reflux of importance in the airways has been missed, since it is either non- or weakly acid and gaseous in composition. The evidence for such a relationship relies on the clinical history pointing to symptom associations with known precipitants of reflux. The tools for the diagnosis of extra-oesophageal reflux, in contrast to the oesophageal reflux of GORD, lack sensitivity and reproducibility. Unfortunately, methodology for detecting such reflux is only just becoming available and much additional work is required to properly delineate its role. Copyright © 2011 SEPAR. Published by Elsevier Espana. All rights reserved.

Vesicoureteral reflux in asymptomatic siblings of patients with known reflux: radionuclide cystography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Van den Abbeele, A.D.; Treves, S.T.; Lebowitz, R.L.

1987-01-01

The familial nature of vesicoureteral reflux among siblings of patients with vesicoureteral reflux has been reported to be from 8% to 32%. These included both symptomatic and asymptomatic siblings. The incidence of vesicoureteral reflux in asymptomatic siblings, however, has not been studied extensively. Sixty asymptomatic siblings of patients known to have vesicoureteral reflux were studied with radionuclide voiding cystography. Their ages ranged from 2 months to 15 years (mean, 4.2 years). Vesicoureteral reflux was detected in 27 of 60 (45%) of the siblings. Vesicoureteral reflux was unilateral in 15 and bilateral in 12 of the siblings. Radionuclide cystography is moremore » sensitive than radiographic cystography and results in a very low radiation dose to the patient. The gonadal dose with radionuclide cystography is only 1.0 to 2.0 mrads. Because of these features, radionuclide cystography is a nearly ideal technique for the diagnosis of vesicoureteral reflux in siblings of patients with known vesicoureteral reflux. All siblings (symptomatic or asymptomatic) of patients with known vesicoureteral reflux should have a screening radionuclide cystography.« less

A study to evaluate patterns of superficial venous reflux in patients with primary chronic venous disease.

PubMed

Qureshi, Mahim I; Gohel, Manj; Wing, Louise; MacDonald, Andrew; Lim, Chung S; Ellis, Mary; Franklin, Ian J; Davies, Alun H

2015-08-01

This study assessed patterns of superficial reflux in patients with primary chronic venous disease. Retrospective review of all patient venous duplex ultrasonography reports at one institution between 2000 and 2009. Legs with secondary, deep or no superficial reflux were excluded. In total, 8654 limbs were scanned; 2559 legs from 2053 patients (mean age 52.3 years) were included for analysis. Great saphenous vein reflux predominated (68%), followed by combined great saphenous vein/small saphenous vein reflux (20%) and small saphenous vein reflux (7%). The majority of legs with competent saphenofemoral junction had below-knee great saphenous vein reflux (53%); incompetent saphenofemoral junction was associated with combined above and below-knee great saphenous vein reflux (72%). Isolated small saphenous vein reflux was associated with saphenopopliteal junction incompetence (61%), although the majority of all small saphenous vein reflux limbs had a competent saphenopopliteal junction (57%). Superficial venous reflux does not necessarily originate from a saphenous junction. Large prospective studies with interval duplex ultrasonography are required to unravel the natural history of primary chronic venous disease. © The Author(s) 2014.

Twenty-four-hour esophageal impedance-pH monitoring in healthy preterm neonates: rate and characteristics of acid, weakly acidic, and weakly alkaline gastroesophageal reflux.

PubMed

López-Alonso, Manuel; Moya, Maria Jose; Cabo, Jose Antonio; Ribas, Juan; del Carmen Macías, Maria; Silny, Jiry; Sifrim, Daniel

2006-08-01

Gastroesophageal reflux is a physiologic process and is considered pathologic (gastroesophageal reflux disease) when it causes symptoms or results in complications. It is common in preterm infants and occurs in healthy neonates. Twenty-four-hour pH monitoring commonly is used in children for diagnosis of gastroesophageal reflux disease, and abnormal reflux is considered with detection of increased esophageal acid exposure. However, in neonates, relatively few gastroesophageal reflux episodes cause esophageal acidification to pH < 4. Premature infants receive frequent feeds, which can induce a weaker acid secretory response than that observed in older infants and adults. As a consequence, gastric pH may be > 4 for prolonged periods, and reflux of gastric contents might be less acidic or even alkaline. Esophageal impedance monitoring can detect weakly acidic and even alkaline gastroesophageal reflux. The role of weakly acidic reflux in the pathophysiology of gastroesophageal reflux disease in preterm infants is not clear. To date, studies that have used impedance-pH in neonates assessed the association between nonacid reflux and cardiorespiratory symptoms, but no impedance data from healthy preterm neonates have been available to determine whether those symptomatic neonates had an increased number of weakly acidic reflux episodes or increased reactivity to a physiologic number of reflux events. Our aim with this study was to provide impedance-pH values for acid, weakly acidic, and weakly alkaline reflux from healthy preterm neonates. Esophageal impedance was recorded for 24 hours in 21 asymptomatic preterm neonates by replacing the conventional feeding tube with a specially designed feeding tube that included 9 impedance electrodes (8 French). All neonates were asymptomatic, with spontaneous breathing. Reflux monitoring was performed after comprehensive explanation and on receipt of written parental consent. Esophageal and gastric pH were monitored using a separate parallel pediatric catheter (6 French). According to the corresponding pH change, impedance-detected reflux was classified as acid, weakly acidic, and weakly alkaline. For each infant, the total number of reflux events, the acid exposure and bolus exposure times at 2 cm above the respiratory inversion point, and average proximal extent of reflux were calculated. Twenty-six preterm neonates were recruited into this study. A preliminary analysis was performed, and tracings were classified according to their quality and the presence of technical artifacts (spontaneous pH and impedance drifts, esophageal probe migration, and dysfunction of 1 or more impedance channels). Five studies were excluded because of 1 or more technical artifacts; a total of 21 neonates represent the final cohort included. At birth, the infants had a median postmenstrual age of 32 weeks, and the measurements were performed at a median age of 12 days. The total recording time was 23.7 +/- 2 hours. Gastric pH was higher than 4 during 69.3 +/- 20.4% of the recording time. The median number of reflux events in 24 hours was 71, 25.4% (range: 0%-53.1%) of which were acid, 72.9% (range: 45.3%-98.0%) were weakly acidic, and 0% (range: 0%-8.1%) were weakly alkaline. Compared with fasting periods, feeding periods tended to be associated with a higher number of total reflux events per hour. The acidity of reflux, however, was significantly different: during fasting, the number of acid reflux episodes per hour was higher, whereas during feeding, the number of weakly acidic reflux episodes was increased. Most reflux events were only liquid, whereas gas was present either mixed with liquid or pure only in 7.7% of all reflux episodes detected. The proximal esophageal segments were reached in 90% of reflux episodes. Reflux-related acid exposure (pH drops associated with impedance-detected reflux) was 1.66% (range: 0%-6.43%), whereas total acid exposure (associated and not associated with reflux detected by impedance) was 5.59% (range: 0.04%-20.69%). There was no relationship between the number or acidity of reflux events and anthropometric parameters such as weight and gestational age. We present the first study using 24-hour impedance-pH recordings in asymptomatic premature neonates. Previous studies that used pH-metry suggested that neonatal cardiorespiratory symptoms could be related to acid gastroesophageal reflux. However, pH-metry could not detect accurately weakly acidic or nonacid reflux. Our healthy premature neonates had approximately 70 reflux events in 24 hours, 25% of which were acid, 73% were weakly acidic, and 2% were weakly alkaline. The number of reflux events per hour (2-3 per hour) was slightly lower than that described in premature neonates with cardiorespiratory events (4 per hour). We confirmed that weakly acidic reflux is more prevalent than acid reflux, particularly so during the feeding periods. In contrast, similar to healthy adults, weakly alkaline reflux was very rare. We confirmed findings from previous studies in which most reflux events were pure liquid during both fasting and during postprandial periods and gas reflux was very rare. As in neonates with cardiorespiratory symptoms, the majority of reflux events in asymptomatic preterms reached the proximal esophagus or pharynx, and there were no differences between acid and weakly acidic reflux. The lack of differences between asymptomatic and diseased infants contravenes the hypothesis for macro- or microaspiration but does not exclude hypersensitivity to reflux as a cause for respiratory symptoms. The acid exposure that was related to reflux events and detected by impedance was significantly lower than the total acid exposure during 24 hours. Increased acid exposure could be attributable to pH-only reflux events or, less frequently, to slow drifts of pH from baselines at approximately 5 to values < 4. These changes were not accompanied by a typical impedance pattern of reflux but by slow drifts in impedance in 1 or 2 channels. Our findings confirm the need for the use of impedance together with pH-metry for diagnosis of all gastroesophageal reflux events. The relationship between gastroesophageal reflux and cardiorespiratory events in neonates and older infants has been studied extensively. The current evidence for such a relationship is controversial. This study provides values of impedance-pH monitoring for acid, weakly acidic, and weakly alkaline reflux from healthy preterm neonates that can be used for comparison when evaluating gastroesophageal reflux in preterm infants with a cardiorespiratory disease.

[Congenital bladder diverticula and vesicoureteral reflux].

PubMed

Garat, José María; Angerri, Oriol; Caffaratti, Jorge; Moscatiello, Pietro

2008-03-01

To analyze our series of primary congenital diverticula (PCD) and their association with vesicoureteral reflux. We have taken care of 23 children with PCD. Eleven of them had big diverticula (> 2 cm) and twelve small. In the first group, 4 children had vesicoureteral reflux and 5 in the second group. In group A, ureteral reimplantation was performed at the time of diverticulum excision. Nor diverticula neither refluxes were operated in group B. We analyze separately results in both groups. Group A: Patients were operated including diverticulum excision. There were not recurrences except in one case with Ehler-Danlos Syndrome. No reimplanted ureter showed postoperative reflux. Nevertheless, one case with multiple bladder diverticula without reflux presented reflux after the excision of several diverticula without reimplantation. Group B: Small diverticula did not undergo surgery Spontaneous outcome of reflux was similar to that of the general population without diverticula. Bladder diverticula are frequently associated with vesicoureteral reflux. The presence of reflux is not an absolute condition for surgical or endoscopic treatment. When diverticula are big in size (Group A) the indication for surgery comes from recurrent infection or voiding disorders, not from reflux. If they undergo surgery, ureteral reimplantation is performed in the case they had reflux or for technical reasons like bladder wall weakness. When diverticula are small (Group B) the presence of reflux does not condition treatment, being the rate of spontaneous resolution similar to the general population.

Correlation of Gastroesophageal reflux disease Assessment Symptom Questionnaire to impedance-pH measurements in children.

PubMed

Prachuapthunyachart, Sittichoke; Jarasvaraparn, Chaowapong; Gremse, David A

2017-01-01

Esophageal multichannel intraluminal impedance-pH monitoring has become one of the preferred tests to correlate observed reflux-like behaviors with esophageal reflux events. The Gastroesophageal reflux disease Assessment Symptom Questionnaire is a validated tool used to distinguish infants with gastroesophageal reflux disease from healthy children. The aim of this study was to determine whether the Gastroesophageal reflux disease Assessment Symptom Questionnaire composite symptom scores and individual symptom scores correlate with outcomes in esophageal multichannel intraluminal impedance-pH monitoring. A total of 26 patients with gastroesophageal reflux disease-associated symptoms, aged 0-2 years, for whom both esophageal multichannel intraluminal impedance-pH monitoring and Gastroesophageal reflux disease Assessment Symptom Questionnaire survey results were available were included in the study. Gastroesophageal reflux disease Assessment Symptom Questionnaire score data were collected from a 7-day recall of parent's responses about the frequency and severity of gastroesophageal reflux disease symptoms, which determined the individual symptom scores. The composite symptom scores is the sum of all individual symptom scores. Multichannel intraluminal impedance-pH study results were compared to Gastroesophageal reflux disease Assessment Symptom Questionnaire data using Pearson correlation. Among 26 patients, a total number of 2817 (1700 acid and 1117 non-acid) reflux episodes and 845 clinical reflux behaviors were recorded. There were significant correlations between the reflux index and the individual symptom scores for coughing/gagging/choking (r 2 = 0.2842, p = 0.005), the impedance score and individual symptom scores for coughing/gagging/choking (r 2 = 0.2482, p = 0.009), the reflux symptom index for acid reflux-related coughing/gagging/choking and the individual symptom scores for coughing/gagging/choking (r 2 = 0.1900, p = 0.026), the impedance score and individual symptom scores for vomiting (r 2 = 0.1569, p = 0.045), and the impedance score and the composite symptom scores (r 2 = 0.2916, p = 0.004). However, there were no significant correlations between fussiness, irritability, or abdominal pain-related multichannel intraluminal impedance-pH results and the individual symptom scores for abdominal pain. The impedance scores from multichannel intraluminal impedance-pH studies correlate with coughing/gagging/choking and vomiting in infants with gastroesophageal reflux disease. There are no significant correlations among the reflux index and impedance score versus the Gastroesophageal reflux disease Assessment Symptom Questionnaire scores for abdominal pain. We conclude that in infants with gastroesophageal reflux disease, multichannel intraluminal impedance-pH studies are more likely to demonstrate an association between gastroesophageal reflux disease and symptoms of coughing, gagging, or choking compared to an association between gastroesophageal reflux disease and pain in infants.

Correlation of Gastroesophageal reflux disease Assessment Symptom Questionnaire to impedance-pH measurements in children

PubMed Central

Prachuapthunyachart, Sittichoke; Jarasvaraparn, Chaowapong; Gremse, David A

2017-01-01

Background: Esophageal multichannel intraluminal impedance-pH monitoring has become one of the preferred tests to correlate observed reflux-like behaviors with esophageal reflux events. The Gastroesophageal reflux disease Assessment Symptom Questionnaire is a validated tool used to distinguish infants with gastroesophageal reflux disease from healthy children. The aim of this study was to determine whether the Gastroesophageal reflux disease Assessment Symptom Questionnaire composite symptom scores and individual symptom scores correlate with outcomes in esophageal multichannel intraluminal impedance-pH monitoring. Methods: A total of 26 patients with gastroesophageal reflux disease–associated symptoms, aged 0–2 years, for whom both esophageal multichannel intraluminal impedance-pH monitoring and Gastroesophageal reflux disease Assessment Symptom Questionnaire survey results were available were included in the study. Gastroesophageal reflux disease Assessment Symptom Questionnaire score data were collected from a 7-day recall of parent’s responses about the frequency and severity of gastroesophageal reflux disease symptoms, which determined the individual symptom scores. The composite symptom scores is the sum of all individual symptom scores. Multichannel intraluminal impedance-pH study results were compared to Gastroesophageal reflux disease Assessment Symptom Questionnaire data using Pearson correlation. Results: Among 26 patients, a total number of 2817 (1700 acid and 1117 non-acid) reflux episodes and 845 clinical reflux behaviors were recorded. There were significant correlations between the reflux index and the individual symptom scores for coughing/gagging/choking (r2 = 0.2842, p = 0.005), the impedance score and individual symptom scores for coughing/gagging/choking (r2 = 0.2482, p = 0.009), the reflux symptom index for acid reflux-related coughing/gagging/choking and the individual symptom scores for coughing/gagging/choking (r2 = 0.1900, p = 0.026), the impedance score and individual symptom scores for vomiting (r2 = 0.1569, p = 0.045), and the impedance score and the composite symptom scores (r2 = 0.2916, p = 0.004). However, there were no significant correlations between fussiness, irritability, or abdominal pain–related multichannel intraluminal impedance-pH results and the individual symptom scores for abdominal pain. Conclusion: The impedance scores from multichannel intraluminal impedance-pH studies correlate with coughing/gagging/choking and vomiting in infants with gastroesophageal reflux disease. There are no significant correlations among the reflux index and impedance score versus the Gastroesophageal reflux disease Assessment Symptom Questionnaire scores for abdominal pain. We conclude that in infants with gastroesophageal reflux disease, multichannel intraluminal impedance-pH studies are more likely to demonstrate an association between gastroesophageal reflux disease and symptoms of coughing, gagging, or choking compared to an association between gastroesophageal reflux disease and pain in infants. PMID:29276590

Determinants of reflux-induced chronic cough.

PubMed

Herregods, Thomas V K; Pauwels, Ans; Jafari, Jafar; Sifrim, Daniel; Bredenoord, Albert J; Tack, Jan; Smout, André J P M

2017-12-01

Gastro-oesophageal reflux is considered to be an important contributing factor in chronic unexplained cough. It remains unclear why some reflux episodes in the same patient causes cough while others do not. To understand more about the mechanism by which reflux induces cough, we aimed to identify factors which are important in triggering cough. In this multicentre study, 49 patients with reflux-associated chronic cough were analysed using 24-hour pH-impedance-pressure monitoring. The characteristics of reflux episodes that were followed by cough were compared with reflux episodes not associated with cough. The majority (72.4%) of the reflux episodes were acidic (pH<4). Compared with reflux episodes that were not followed by cough, reflux episodes that were followed by a cough burst were associated with a higher proximal extent (p=0.0001), a higher volume clearance time (p=0.002) and a higher acid burden in the preceding 15 min window (p=0.019) and higher reflux burden in the preceding 30 min window (p=0.044). No significant difference was found between the two groups when looking at the nadir pH, the pH drop, the acid clearance time or the percentage of reflux episodes which were acidic. The presence of a larger volume of refluxate and oesophageal exposure to reflux for a longer period of time seems to play an important role in inducing cough, while the acidity of the refluxate seems to be less relevant. This helps explain the observation that most patients with chronic cough tend not to benefit from acid inhibitory treatment. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Pre-lung transplant measures of reflux on impedance are superior to pH testing alone in predicting early allograft injury

PubMed Central

Lo, Wai-Kit; Burakoff, Robert; Goldberg, Hilary J; Feldman, Natan; Chan, Walter W

2015-01-01

AIM: To evaluate pre-lung transplant acid reflux on pH-testing vs corresponding bolus reflux on multichannel intraluminal impedance (MII) to predict early allograft injury. METHODS: This was a retrospective cohort study of lung transplant recipients who underwent pre-transplant combined MII-pH-testing at a tertiary care center from January 2007 to November 2012. Patients with pre-transplant fundoplication were excluded. Time-to-event analysis was performed using a Cox proportional hazards model to assess associations between measures of reflux on MII-pH testing and early allograft injury. Area under the receiver operating characteristic (ROC) curve (c-statistic) of the Cox model was calculated to assess the predictive value of each reflux parameter for early allograft injury. Six pH-testing parameters and their corresponding MII measures were specified a priori. The pH parameters were upright, recumbent, and overall acid reflux exposure; elevated acid reflux exposure; total acid reflux episodes; and acid clearance time. The corresponding MII measures were upright, recumbent, and overall bolus reflux exposure; elevated bolus reflux exposure; total bolus reflux episodes; and bolus clearance time. RESULTS: Thirty-two subjects (47% men, mean age: 55 years old) met the inclusion criteria of the study. Idiopathic pulmonary fibrosis (46.9%) represented the most common pulmonary diagnosis leading to transplantation. Baseline demographics, pre-transplant cardiopulmonary function, number of lungs transplanted (unilateral vs bilateral), and post-transplant proton pump inhibitor use were similar between reflux severity groups. The area under the ROC curve, or c-statistic, of each acid reflux parameter on pre-transplant pH-testing was lower than its bolus reflux counterpart on MII in the prediction of early allograft injury. In addition, the development of early allograft injury was significantly associated with three pre-transplant MII measures of bolus reflux: overall reflux exposure (HR = 1.18, 95%CI: 1.01-1.36, P = 0.03), recumbent reflux exposure (HR = 1.25, 95%CI: 1.04-1.50, P = 0.01) and bolus clearance (HR = 1.09, 95%CI: 1.01-1.17, P = 0.02), but not with any pH-testing parameter measuring acid reflux alone. CONCLUSION: Pre-transplant MII measures of bolus reflux perform better than their pH-testing counterparts in predicting early allograft injury post-lung transplantation. PMID:26290637

Pathological bolus exposure may define gastro-esophageal reflux better than pathological acid exposure in patients with globus.

PubMed

Sinn, Dong Hyun; Kim, Beom Jin; Son, Hee Jung; Kim, Jae J; Rhee, Jong Chul; Rhee, Poong-Lyul

2012-01-01

Conventionally, pathological acid exposure (PAE), defined by acid reflux only, is used to identify gastro-esophageal reflux disease (GERD). However, weak acid reflux or non-acid reflux also induces reflux symptoms. Defining abnormal reflux based on all reflux episodes may better identify GERD and would be more useful among patients with atypical GERD symptoms, such as globus. Impedance-pHmetry results of 31 globus patients, off acid suppressants, were analysed. A median of 24 episodes of reflux were observed. Of the reflux episodes, 54% were non-acid reflux and 50% reached the proximal extent. PAE was observed in 6 patients (19%). For 5 patients (16%) without PAE, there was evidence of increased bolus exposure compared to normal controls (an intraesophageal bolus exposure for more than 1.4% of the recording time, defined as pathological bolus exposure, PBE). When GERD was defined by PAE or esophagitis, the prevalence of GERD was 29%. When GERD was defined by PBE, PAE or esophagitis, the prevalence was 42%. PBE identified 13% of the patients who otherwise would have been missed. A significant proportion of patients without PAE had evidence of PBE. PBE may be a more useful definition for identifying patients with abnormal increase in reflux in patients with globus. Further studies are warranted.

[Analysis on replacement of traditional Chinese medicine bear bile with bile acids based on drug properties].

PubMed

Yuan, Bin; Ren, Ying-Long; Ma, Li; Gu, Hao; Wang, Yun; Qiao, Yan-Jiang

2014-02-01

To discuss the rationality of the clinical replacement of traditional Chinese medicine (TCM) bear bile with bile acid constituents, and analyze the difference between these constituents and bear bile in drug properties. Summarizing the drug properties of bear bile by reference to medical literatures for drug properties of TCM bear bile and Science of Traditional Chinese Medicine (China Press of Traditional Chinese Medicine, 2007). Analyzing and summarizing the pharmacological effects of main bile acid constituents according to relevant literatures for studies on pharmacological effects of main bile acid constituents in CNKI database. Predicating the drug properties of these bile acid constituents by using the drug property predication model established by the study group according the pharmacological effects of main bile acid constituents in the paper, and compare the prediction results with the drug properties of bear bile. Bile acid constituents in bear bile were mostly cold in property, bitter in taste, and the combination of their drug properties could reflect the combined drug properties of bear bile. All of these bile acid constituents in bear bile could show part of effects of bear bile. Attention shall be given to regulate the medication scheme in clinical application according to actual conditions.

Bile Acid Metabolism in Liver Pathobiology

PubMed Central

Chiang, John Y. L.; Ferrell, Jessica M.

2018-01-01

Bile acids facilitate intestinal nutrient absorption and biliary cholesterol secretion to maintain bile acid homeostasis, which is essential for protecting liver and other tissues and cells from cholesterol and bile acid toxicity. Bile acid metabolism is tightly regulated by bile acid synthesis in the liver and bile acid biotransformation in the intestine. Bile acids are endogenous ligands that activate a complex network of nuclear receptor farnesoid X receptor and membrane G protein-coupled bile acid receptor-1 to regulate hepatic lipid and glucose metabolic homeostasis and energy metabolism. The gut-to-liver axis plays a critical role in the regulation of enterohepatic circulation of bile acids, bile acid pool size, and bile acid composition. Bile acids control gut bacteria overgrowth, and gut bacteria metabolize bile acids to regulate host metabolism. Alteration of bile acid metabolism by high-fat diets, sleep disruption, alcohol, and drugs reshapes gut microbiome and causes dysbiosis, obesity, and metabolic disorders. Gender differences in bile acid metabolism, FXR signaling, and gut microbiota have been linked to higher prevalence of fatty liver disease and hepatocellular carcinoma in males. Alteration of bile acid homeostasis contributes to cholestatic liver diseases, inflammatory diseases in the digestive system, obesity, and diabetes. Bile acid-activated receptors are potential therapeutic targets for developing drugs to treat metabolic disorders. PMID:29325602

Systematic review: relationships between sleep and gastro-oesophageal reflux.

PubMed

Dent, J; Holloway, R H; Eastwood, P R

2013-10-01

Gastro-oesophageal reflux disease (GERD) adversely impacts on sleep, but the mechanism remains unclear. To review the literature concerning gastro-oesophageal reflux during the sleep period, with particular reference to the sleep/awake state at reflux onset. Studies identified by systematic literature searches were assessed. Overall patterns of reflux during the sleep period show consistently that oesophageal acid clearance is slower, and reflux frequency and oesophageal acid exposure are higher in patients with GERD than in healthy individuals. Of the 17 mechanistic studies identified by the searches, 15 reported that a minority of reflux episodes occurred during stable sleep, but the prevailing sleep state at the onset of reflux in these studies remains unclear owing to insufficient temporal resolution of recording or analysis methods. Two studies, in healthy individuals and patients with GERD, analysed sleep and pH with adequate resolution for temporal alignment of sleep state and the onset of reflux: all 232 sleep period reflux episodes evaluated occurred during arousals from sleep lasting less than 15 s or during longer duration awakenings. Six mechanistic studies found that transient lower oesophageal sphincter relaxations were the most common mechanism of sleep period reflux. Contrary to the prevailing view, subjective impairment of sleep in GERD is unlikely to be due to the occurrence of reflux during stable sleep, but could result from slow clearance of acid reflux that occurs during arousals or awakenings from sleep. Definitive studies are needed on the sleep/awake state at reflux onset across the full GERD spectrum. © 2013 John Wiley & Sons Ltd.

Prevalence and demographic determinants of gastroesophageal reflux disease (GERD) in the Turkish general population: a population-based cross-sectional study.

PubMed

Mungan, Zeynel

2012-08-01

We aimed to establish the prevalence and demographic determinants of gastroesophageal reflux disease in the Turkish general population using the Turkish version of the gastroesophageal reflux disease questionnaire. A total of 8143 volunteers (mean age: 38.5 (13.3) years; 52.3% males) were included in this cross-sectional questionnaire study conducted via face-to-face administration of the questionnaire forms including items on sociodemographic features, past history of gastric disorders, gastroesophageal reflux disease, the influence of reflux symptoms on patients' lives, physician visits, diagnostic tests, and reflux medications. A past history of gastric symptoms was reported in half of the population. More female participants (p<0.001) had a past history of gastric symptoms that yielded a previous diagnosis of gastroesophageal reflux disease in 19.1% of the population. The likelihood of gastroesophageal reflux disease was low in the majority (75.3%) of the subjects evaluated. Gastroesophageal reflux disease with an inconveniencing or disrupting impact on the patient's life was present in 17.9% and 6.8% of the population. Total gastroesophageal reflux disease-questionnaire scores and reflux prevalence were higher in older age groups (p<0.001). Females were more likely to have gastroesophageal reflux disease prevalence based on reflux symptoms. The impact of gastroesophageal reflux disease on sleep and psychological/emotional well-being was more pronounced in older and female patients, whereas the impact on eating/drinking behaviors and physical-social activities was more marked among females independent of their age (p<0.001). Reflux prevalence was higher in subjects from East Anatolia, Central Anatolia, Mediterranean, and Black Sea regions of Turkey (p<0.001 for each). Prevalence and demographic determinants of gastroesophageal reflux disease are compatible with the profile of the disease in the other Western populations, with a predilection for females and older individuals.

Liquid-containing Refluxes and Acid Refluxes May Be Less Frequent in the Japanese Population Than in Other Populations: Normal Values of 24-hour Esophageal Impedance and pH Monitoring

PubMed Central

Kawamura, Osamu; Kohata, Yukie; Kawami, Noriyuki; Iida, Hiroshi; Kawada, Akiyo; Hosaka, Hiroko; Shimoyama, Yasuyuki; Kuribayashi, Shiko; Fujiwara, Yasuhiro; Iwakiri, Katsuhiko; Inamori, Masahiko; Kusano, Motoyasu; Hongo, Micho

2016-01-01

Background/Aims Twenty-four-hour esophageal impedance and pH monitoring allows detection of all types of reflux episodes and is considered the best technique for identifying gastroesophageal refluxes. However, normative data for the Japanese population are lacking. This multicenter study aimed to establish the normal range of 24-hour esophageal impedance and pH data both in the distal and the proximal esophagus in Japanese subjects. Methods Forty-two healthy volunteers (25 men and 17 women) with a mean ± standard deviation age of 33.3 ± 12.4 years (range: 22–72 years) underwent a combined 24-hour esophageal impedance and pH monitoring. According to the physical and pH properties, distal or proximal esophageal reflux events were categorized. Results Median 45 reflux events occurred in 24 hours, and the 95th percentile was 85 events. Unlike previous reports, liquid-containing reflux events are median 25/24 hours with the 95th percentile of 62/24 hours. Acidic reflux events were median 11/24 hours with the 95th percentile of 39/24 hours. Non-acidic gas reflux events were median 15/24 hours with the 95th percentile of 39/24 hours. Proximal reflux events accounted for 80% of the total reflux events and were mainly non-acidic gas refluxes. About 19% of liquid and mixed refluxes reached the proximal esophagus. Conclusions Unlike previous studies, liquid-containing and acidic reflux events may be less frequent in the Japanese population. Non-acidic gas reflux events may be frequent and a cause of frequent proximal reflux events. This study provides important normative data for 24-hour impedance and pH monitoring in both the distal and the proximal esophagus in the Japanese population. PMID:27247103

Mechanisms of acid reflux and how refluxed Acid extends proximally in patients with non-erosive reflux disease.

PubMed

Sano, Hirohito; Iwakiri, Katsuhiko; Kawami, Noriyuki; Tanaka, Yuriko; Sakamoto, Choitsu

2014-01-01

The mechanisms that cause acid reflux in patients with non-erosive reflux disease (NERD), including those that determine how acid extends proximally, are not yet clear. Concurrent esophageal manometry and pH monitoring were performed for 3 h after a meal in 13 patients with NERD, 12 with mild reflux esophagitis (RE), and 13 healthy subjects (HS). Transient lower esophageal sphincter (LES) relaxation (TLESR) was the major mechanism of acid reflux in all three groups. LES pressure did not differ between the groups. At 2 cm above the LES, there were no differences between the three groups in the number of TLESR-related acid reflux episodes, rate of TLESRs and rate of acid reflux during TLESR. However, at 7 cm above the LES, the rate of acid reflux during TLESRs was significantly higher in patients with NERD (mean ± SEM 42.3 ± 4.8) than in those with mild RE (28.0 ± 3.8) and HS (10.8 ± 2.5). TLESRs are the sole motor events underlying acid reflux episodes in patients with NERD. Acid extends proximally more readily in patients with NERD than in HS and those with mild RE.

Pharyngeal pH alone is not reliable for the detection of pharyngeal reflux events: A study with oesophageal and pharyngeal pH-impedance monitoring

PubMed Central

Desjardin, Marie; Roman, Sabine; des Varannes, Stanislas Bruley; Gourcerol, Guillaume; Coffin, Benoit; Ropert, Alain; Mion, François

2013-01-01

Background Pharyngeal pH probes and pH-impedance catheters have been developed for the diagnosis of laryngo-pharyngeal reflux. Objective To determine the reliability of pharyngeal pH alone for the detection of pharyngeal reflux events. Methods 24-h pH-impedance recordings performed in 45 healthy subjects with a bifurcated probe for detection of pharyngeal and oesophageal reflux events were reviewed. Pharyngeal pH drops to below 4 and 5 were analysed for the simultaneous occurrence of pharyngeal reflux, gastro-oesophageal reflux, and swallows, according to impedance patterns. Results Only 7.0% of pharyngeal pH drops to below 5 identified with impedance corresponded to pharyngeal reflux, while 92.6% were related to swallows and 10.2 and 13.3% were associated with proximal and distal gastro-oesophageal reflux events, respectively. Of pharyngeal pH drops to below 4, 13.2% were related to pharyngeal reflux, 87.5% were related to swallows, and 18.1 and 21.5% were associated with proximal and distal gastro-oesophageal reflux events, respectively. Conclusions This study demonstrates that pharyngeal pH alone is not reliable for the detection of pharyngeal reflux and that adding distal oesophageal pH analysis is not helpful. The only reliable analysis should take into account impedance patterns demonstrating the presence of pharyngeal reflux event preceded by a distal and proximal reflux event within the oesophagus. PMID:24917995

Bile acid patterns in commercially available oxgall powders used for the evaluation of the bile tolerance ability of potential probiotics

PubMed Central

Hu, Peng-Li; Yuan, Ya-Hong; Yue, Tian-Li

2018-01-01

This study aimed to analyze the bile acid patterns in commercially available oxgall powders used for evaluation of the bile tolerance ability of probiotic bacteria. Qxgall powders purchased from Sigma-Aldrich, Oxoid and BD Difco were dissolved in distilled water, and analyzed. Conjugated bile acids were profiled by ion-pair high-performance liquid chromatography (HPLC), free bile acids were detected as their p-bromophenacyl ester derivatives using reversed-phase HPLC after extraction with acetic ether, and total bile acids were analyzed by enzymatic-colorimetric assay. The results showed that 9 individual bile acids (i.e., taurocholic acid, glycocholic acid, taurodeoxycholic acid, glycodeoxycholic acid, taurochenodeoxycholic acid, glycochenodeoxycholic acid, cholic acid, chenodeoxycholic acid, deoxycholic acid) were present in each of the oxgall powders tested. The content of total bile acid among the three oxgall powders was similar; however, the relative contents of the individual bile acids among these oxgall powders were significantly different (P < 0.001). The oxgall powder from Sigma-Aldrich was closer to human bile in the ratios of glycine-conjugated bile acids to taurine-conjugated bile acids, dihydroxy bile acids to trihydroxy bile acids, and free bile acids to conjugated bile acids than the other powders were. It was concluded that the oxgall powder from Sigma-Aldrich should be used instead of those from Oxoid and BD Difco to evaluate the bile tolerance ability of probiotic bacteria as human bile model. PMID:29494656

Association of canalicular membrane enzymes with bile acid micelles and lipid aggregates in human and rat bile.

PubMed

Accatino, L; Pizarro, M; Solís, N; Koenig, C S

1995-01-18

This study was undertaken to gain insights into the characteristics of the polymolecular association between canalicular membrane enzymes, bile acids, cholesterol and phospholipids in bile and into the celular mechanisms whereby the enzymes are secreted into bile. With this purpose, we studied the distribution of bile acids, cholesterol, phospholipids, proteins and representative canalicular membrane enzymes (alkaline phosphatase, 5'-nucleotidase and gamma-glutamyl transpeptidase), which can be considered specific marker constituents, in bile fractions enriched in phospholipid-cholesterol lamellar structures (multilamellar and unilamellar vesicles) and bile acid-mixed micelles. These fractions were isolated by ultracentrifugation from human hepatic bile, normal rat bile and bile of rats treated with diosgenin, a steroid that induces a marked increase in biliary cholesterol secretion, and were characterized by density, lipid composition and transmission electron microscopy. These studies demonstrate that alkaline phosphatase, 5'-nucleotidase and gamma-glutamyl transpeptidase are secreted into both human and rat bile where they are preferentially associated with bile acid-mixed micelles, suggesting a role for bile acids in both release of these enzymes and lipids from the canalicular membrane and solubilization in bile. In addition, heterogeneous association of these enzymes with nonmicellar, lamellar structures in human and rat bile is consistent with the hypothesis that processes independent of the detergent effects of bile acids might also result in the release of specific intrinsic membrane proteins into bile.

Hemodynamic and clinical impact of ultrasound-derived venous reflux parameters.

PubMed

Neglén, Peter; Egger, John F; Olivier, Jake; Raju, Seshadri

2004-08-01

This study was undertaken to assess which ultrasound-derived parameter was superior for measuring venous reflux quantitatively and to evaluate the importance of popliteal vein valve reflux. A retrospective analysis was performed of 244 refluxive limbs in 182 patients who underwent ultrasound scanning, venous pressure measurement, air plethysmography, and clinical classification of severity according to the CEAP score. Reflux time (RT, s), peak reflux velocity (PRV, m/s), time of average rate of reflux (TAF, mL/min), absolute displaced volume retrogradely (ADV, mL) were compared to clinical class, ambulatory venous pressure (% drop), venous filling time (s), and venous filling index (mL/s) using nonparametric statistical tests. A P value of <.05 was considered significant. Limbs were divided into 3 groups: (A) axial great saphenous vein reflux only (n = 68); (B) axial deep reflux including popliteal vein incompetence with or without concomitant gastrocnemius or great or small saphenous vein reflux (all ultrasound reflux parameters of each refluxive vein added at the knee level) (n = 79); and (C) all limbs with popliteal vein reflux (the ultrasound data of the refluxive popliteal vein exclusively was used in comparison regardless of concomitant associated reflux) (n = 103). Limbs were also stratified into limbs with skin changes and ulcer (C-class 4-6) and those without (C-class 1-3) and subsequently compared. No meaningful significant correlation was found between RT and the clinical and hemodynamic results in groups A and B. The PRV and TAF correlated significantly with the hemodynamic parameters. The PRV and TAF and clinical severity trended towards correlation in group A (P =.0554 and P =.0998, respectively), but was significantly correlated in group B. The poor hemodynamic condition in the subset of C-class 4-6 limbs in groups A and B was reflected in a greater PRV, TAF, and ADV in this subset as compared with the limbs in C-class 1-3. RT was not significantly different in the subsets of limbs, further suggesting that RT is not related to hemodynamic or clinical state of the limbs. No meaningful correlations were found in group C. Although the hemodynamic data were significantly poorer in the subset of limbs with C-class 4-6 than in C-class 1-3, the ultrasound-derived parameters were not significantly different. The duration of valve reflux time (or valve closure time) cannot be used to quantify severity of reflux and is purely a qualitative measurement. The PRV and the rate of reflux appeared to better reflect the magnitude of venous incompetence. In the presence of axial reflux, it appeared logical and physiologically correct to sum up these reflux parameters for each venous segment crossing the knee. The popliteal valve reflux (the "gatekeeper" function) was not in itself an important determinant of venous hemodynamics and clinical severity. Additional reflux in other venous segments must be taken into account.

Bile salt tolerance of Lactococcus lactis is enhanced by expression of bile salt hydrolase thereby producing less bile acid in the cells.

PubMed

Bi, Jie; Liu, Song; Du, Guocheng; Chen, Jian

2016-04-01

Changes of bile salt tolerance, morphology and amount of bile acid within cells were studied to evaluate the exact effects of bile salt hydrolase (BSH) on bile salt tolerance of microorganism. The effect of BSHs on the bile salt tolerance of Lactococcus lactis was examined by expressing two BSHs (BSH1 and BSH2). Growth of L. lactis expressing BSH1 or BSH2 was better under bile salt stress compared to wild-type L. lactis. As indicated by transmission electron microscopy, bile acids released by the action of BSH induced the formation of micelles around the membrane surface of cells subject to conjugated bile salt stress. A similar micelle containing bile acid was observed in the cytoplasm by liquid chromatography-mass spectrometry. BSH1 produced fewer bile acid micelles in the cytoplasm and achieved better cell growth of L. lactis compared to BSH2. Expression of BSH improved bile salt tolerance of L. lactis but excessive production by BSH of bile acid micelles in the cytoplasm inhibited cell growth.

COMPLEX EVOLUTION OF BILE SALTS IN BIRDS

PubMed Central

Hagey, Lee R.; Vidal, Nicolas; Hofmann, Alan F.; Krasowski, Matthew D.

2010-01-01

Bile salts are the major end-metabolites of cholesterol and are important in lipid digestion and shaping of the gut microflora. There have been limited studies of bile-salt variation in birds. The purpose of our study was to determine bile-salt variation among birds and relate this variation to current avian phylogenies and hypotheses on the evolution of bile salt pathways. We determined the biliary bile-salt composition of 405 phylogenetically diverse bird species, including 7 paleognath species. Bile salt profiles were generally stable within bird families. Complex bile-salt profiles were more common in omnivores and herbivores than in carnivores. The structural variation of bile salts in birds is extensive and comparable to that seen in surveys of bile salts in reptiles and mammals. Birds produce many of the bile salts found throughout nonavian vertebrates and some previously uncharacterized bile salts. One difference between birds and other vertebrates is extensive hydroxylation of carbon-16 of bile salts in bird species. Comparison of our data set of bird bile salts with that of other vertebrates, especially reptiles, allowed us to infer evolutionary changes in the bile salt synthetic pathway. PMID:21113274

Correlation between chemical components of billary calculi and bile & sera and bile of gallstone patients.

PubMed

Chandran, Prasheeda; Garg, Pradeep; Pundir, Chandra S

2005-07-01

Total cholesterol, total bilirubin, calcium, oxalate, inorganic phosphate, magnesium, iron, copper, sodium and potassium were analyzed quantitatively in gallstones, bile of gall bladder and sera of 200 patients of cholelithiasis (52 cholesterol, 76 mixed and 72 pigment stone patients) and their contents were correlated between calculi and bile and sera and bile in these three type of stone patients. A significant positive correlation was observed between total cholesterol, total bilirubin of calculi and bile, copper of bile and sera of cholesterol stone patients, copper of calculi and bile, total bilirubin, oxalate, magnesium, potassium of sera and bile of pigment stone patients and oxalate and iron of stone and bile, total bilirubin, oxalate, sodium of sera and bile of mixed stone patients. A significant negative correlation was found between magnesium of serum and bile of cholesterol stone patients, oxalate of calculi and bile of pigment stone patients and magnesium of serum and bile of mixed stone patients.

Vesicoureteral Reflux Index: Predicting Primary Vesicoureteral Reflux Resolution in Children Diagnosed after Age 24 Months.

PubMed

Garcia-Roig, Michael; Ridley, Derrick E; McCracken, Courtney; Arlen, Angela M; Cooper, Christopher S; Kirsch, Andrew J

2017-04-01

The Vesicoureteral Reflux Index is a validated tool that reliably predicts spontaneous resolution of reflux or at least 2 grades of improvement for patients diagnosed before age 24 months. We evaluated the Vesicoureteral Reflux Index in children older than 2 years. Patients younger than 18 years who were diagnosed with primary vesicoureteral reflux after age 24 months and had undergone 2 or more voiding cystourethrograms were identified. Disease severity was scored using the Vesicoureteral Reflux Index, a 6-point scale based on gender, reflux grade, ureteral abnormalities and reflux timing. Proportional subdistribution hazard models for competing risks identified variables associated with resolution/improvement at different time points. A total of 21 males and 250 females met inclusion criteria. Mean ± SD age was 4.0 ± 2.1 years and patients had a median vesicoureteral reflux grade of 2. The Vesicoureteral Reflux Index score improved by 1 point in 1 patient (100%), 2 points in 25 (67.6%), 3 points in 48 (37%), 4 points in 18 (21.4%) and 5 to 6 points in 4 (18.2%). Female gender (p = 0.005) and vesicoureteral reflux timing (late filling, p = 0.002; early/mid filling, p <0.001) independently predicted nonresolution. Median resolution time based on Vesicoureteral Reflux Index score was 2 months or less in 15.6% of patients (95% CI 11.0-13.8), 3 months in 34.7% (95% CI 25.4-44.1), 4 months in 55.9% (95% CI 40.1 to infinity) and 5 months or more in 30.3% (95% CI 29.5 to infinity). High grade (IV or V) reflux was not associated with resolution at any point. Ureteral abnormalities were associated with lack of resolution in the first 12 to 18 months (HR 0.29, 95% CI 0.29-0.80) but not in later followup. Vesicoureteral Reflux Index scores of 3, 4 and 5 were significantly associated with lack of resolution/improvement compared to scores of 2 or less (p = 0.031). The Vesicoureteral Reflux Index reliably predicts primary vesicoureteral reflux improvement/resolution in children diagnosed after age 24 months. Spontaneous resolution/improvement is less likely as Vesicoureteral Reflux Index score and time from diagnosis increase. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Clinical and polysomnographic predictors of laryngopharyngeal reflux in obstructive sleep apnea syndrome.

PubMed

Caparroz, Fábio Azevedo; Campanholo, Milena de Almeida Torres; Regina, Caroline Gomez; Park, Sung Woo; Haddad, Leonardo; Gregório, Luís Carlos; Haddad, Fernanda Louise Martinho

2018-04-14

Obstructive sleep apnea syndrome and laryngopharyngeal reflux are diseases with a high prevalence in the overall population; however, it remains unclear whether they are diseases with the same risk factors present in the same populations or if there is any association between them. To evaluate and determine the prevalence of laryngopharyngeal reflux in patients with moderate and severe obstructive apnea syndrome and also to determine its predictive factors. Historical cohort, cross-sectional study of patients aged 18-70 years, referred to a tertiary service Otorhinolaryngology outpatient clinic with a polysomnographic diagnosis of moderate or severe obstructive sleep apnea syndrome. The reflux symptom index questionnaire and the reflux finding score at indirect videolaryngoscopy were applied to the assessed population, considering the inclusion and exclusion criteria. Fifty-six patients were evaluated, of which 64.3% had a positive laryngopharyngeal reflux (positive reflux symptom index and/or positive endolaryngeal reflux finding score). Body mass index was a predictor of reflux presence in this group of patients with moderate to severe obstructive sleep apnea syndrome. In patients with positive score for endoscopic findings and reflux symptom index (12.3%), there was a trend toward significance for a higher mean apnea-hypopnea index and a higher percentage of sleep time with oxyhemoglobin saturation below 90% (p=0.05). The prevalence of laryngopharyngeal reflux was higher in this group of patients with moderate to severe obstructive sleep apnea syndrome, and the body mass index was a predictor of laryngopharyngeal reflux in these patients. There was a trend toward greater oxyhemoglobin desaturation in patients with a positive score for reflux symptoms index (RSI) and reflux finding score (RFS). Copyright © 2018 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. All rights reserved.

Acid and non-acid reflux in patients refractory to proton pump inhibitor therapy: is gastroparesis a factor?

PubMed

Tavakkoli, Anna; Sayed, Bisma A; Talley, Nicholas J; Moshiree, Baharak

2013-10-07

To determine whether an increased number and duration of non-acid reflux events as measured using the multichannel intraluminal impedance pH (MII-pH) is linked to gastroparesis (GP). A case control study was conducted in which 42 patients undergoing clinical evaluation for continued symptoms of gastroesophageal reflux disease (both typical and atypical symptoms) despite acid suppression therapy. MII-pH technology was used over 24 h to detect reflux episodes and record patients' symptoms. Parameters evaluated in patients with documented GP and controls without GP by scintigraphy included total, upright, and supine number of acid and non-acid reflux episodes (pH < 4 and pH > 4, respectively), the duration of acid and non-acid reflux in a 24-h period, and the number of reflux episodes lasting longer than 5 min. No statistical difference was seen between the patients with GP and controls with respect to the total number or duration of acid reflux events, total number and duration of non-acid reflux events or the duration of longest reflux episodes. The number of non-acid reflux episodes with a pH > 7 was higher in subjects with GP than in controls. In addition, acid reflux episodes were more prolonged (lasting longer than 5 min) in the GP patients than in controls; however, these values did not reach statistical significance. Thirty-five patients had recorded symptoms during the 24 h study and of the 35 subjects, only 9% (n = 3) had a positive symptom association probability (SAP) for acid/non-acid reflux and 91% had a negative SAP. The evaluation of patients with a documented history of GP did not show an association between GP and more frequent episodes of non-acid reflux based on MII-pH testing.

Sleeve gastrectomy with anti-reflux procedures

PubMed Central

Santoro, Sergio; Lacombe, Arnaldo; de Aquino, Caio Gustavo Gaspar; Malzoni, Carlos Eduardo

2014-01-01

Objective Sleeve gastrectomy is the fastest growing surgical procedure to treat obesity in the world but it may cause or worsen gastroesophageal reflux disease. This article originally aimed to describe the addition of anti-reflux procedures (removal of periesophageal fats pads, hiatoplasty, a small plication and fixation of the gastric remnant in position) to the usual sleeve gastrectomy and to report early and late results. Methods Eighty-eight obese patients that also presented symptoms of gastroesophageal reflux disease were submitted to sleeve gastrectomy with anti-reflux procedures. Fifty of them were also submitted to a transit bipartition. The weight loss of these patients was compared to consecutive 360 patients previously submitted to the usual sleeve gastrectomy and to 1,140 submitted to sleeve gastrectomy + transit bipartition. Gastroesophageal reflux disease symptoms were specifically inquired in all anti-reflux sleeve gastrectomy patients and compared to the results of the same questionnaire applied to 50 sleeve gastrectomy patients and 60 sleeve gastrectomy + transit bipartition patients that also presented preoperative symptoms of gastroesophageal reflux disease. Results In terms of weight loss, excess of body mass index loss percentage after anti-reflux sleeve gastrectomy is not inferior to the usual sleeve gastrectomy and anti-reflux sleeve gastrectomy + transit bipartition is not inferior to sleeve gastrectomy + transit bipartition. Anti-reflux sleeve gastrectomy did not add morbidity but significantly diminished gastroesophageal reflux disease symptoms and the use of proton pump inhibitors to treat this condition. Conclusion The addition of anti-reflux procedures, such as hiatoplasty and cardioplication, to the usual sleeve gastrectomy did not add morbidity neither worsened the weight loss but significantly reduced the occurrence of gastroesophageal reflux disease symptoms as well as the use of proton pump inhibitors. PMID:25295447

Determinants of perception of heartburn and regurgitation

PubMed Central

Bredenoord, A J; Weusten, B L A M; Curvers, W L; Timmer, R; Smout, A J P M

2006-01-01

Background and aim It is not known why some reflux episodes evoke symptoms and others do not. We investigated the determinants of perception of gastro‐oesophageal reflux. Methods In 32 patients with symptoms suggestive of gastro‐oesophageal reflux, 24 hour ambulatory pH and impedance monitoring was performed after cessation of acid suppressive therapy. In the 20 patients who had at least one symptomatic reflux episode, characteristics of symptomatic and asymptomatic reflux episodes were compared. Results A total of 1807 reflux episodes were detected, 203 of which were symptomatic. Compared with asymptomatic episodes, symptomatic episodes were associated with a larger pH drop (p<0.001), lower nadir pH (p<0.05), and higher proximal extent (p<0.005). Symptomatic reflux episodes had a longer volume and acid clearance time (p<0.05 and p<0.002). Symptomatic episodes were preceded by a higher oesophageal cumulative acid exposure time (p<0.05). The proximal extent of episodes preceding regurgitation was larger than those preceding heartburn; 14.8% of the symptomatic reflux episodes were weakly acidic. In total, 426 pure gas reflux episodes occurred, of which 12 were symptomatic. Symptomatic pure gas reflux was more frequently accompanied by a pH drop than asymptomatic gas reflux (p<0.05). Conclusions Heartburn and regurgitation are more likely to be evoked when the pH drop is large, proximal extent of the refluxate is high, and volume and acid clearance is delayed. Sensitisation of the oesophagus occurs by preceding acid exposure. Weakly acidic reflux is responsible for only a minority of symptoms in patients off therapy. Pure gas reflux associated with a pH drop (“acid vapour”) can be perceived as heartburn and regurgitation. PMID:16120760

Sonographic measurement of abdominal esophageal length as a diagnostic tool in gastroesophageal reflux disease in infants.

PubMed

Dehdashti, Hamid; Dehdashtian, Masoud; Rahim, Fakher; Payvasteh, Mehrdad

2011-01-01

This study was conducted to provide sonographic measurements of the abdominal esophagus length in neonates and infants with and without gastroesophageal reflux disease (GERD) and to investigate its diagnostic value. GERD severity was also evaluated and correlated with esophageal length. It is a prospective case-control study. This prospective case-control study comprised 235 neonates and infants (120 without reflux and 115 with reflux). There were 40 children without reflux in each of three age categories: less than 1 month, 1-6 months, and 6-12 months. Of the children with reflux, 40 were less than 1 month old; 37, 1-6 months; and 38, 6-12 months. The abdominal esophagus was measured from its entrance into the diaphragm to the base of gastric folds in fed infants. GERD was sonographically diagnosed and confirmed by a barium meal. The number of refluxes during a 10-min period were recorded. Neonates and infants with reflux had a significantly shorter abdominal esophagus than subjects without reflux: the mean difference in neonates, 4.65 mm; 1-6 months, 4.57 mm; 6-12 months, 3.61 mm. Children with severe reflux had a shorter esophagus compared with those with mild and moderate reflux only in the neonate group. Therefore, thinking of GERD and carefully looking for its symptoms is necessary to avoid unnecessary utilization of healthcare resources in children with severe reflux.

The effect of decaffeination of coffee on gastro-oesophageal reflux in patients with reflux disease.

PubMed

Pehl, C; Pfeiffer, A; Wendl, B; Kaess, H

1997-06-01

Patients with reflux disease often complain of heartburn after ingestion of coffee. Induction of gastro-oesophageal reflux has been demonstrated by pH-metry following the intake of coffee in healthy volunteers. The reflux was reduced when the coffee had undergone a decaffeination process. The aim of this study was to investigate the effect of decaffeination of coffee on reflux in patients with reflux disease. Seventeen reflux patients underwent two osesophageal 3-h pH measurements. The patients received, in a double-blind study design in a randomized order, 300 mL of either regular or decaffeinated coffee together with a standardized breakfast. The fraction time oesophageal pH < 4 was calculated during the three postprandial hours. For regular coffee the fraction time was calculated to a median of 17.9% with a range of 0.7-56.6%. The fraction time was significantly reduced to 3.1% (0-49.9%) after ingestion of decaffeinated coffee. The amount of gastro-oesophageal reflux induced by the intake of regular coffee in patients with reflux disease can be reduce by the decaffeination of coffee.

Vesicoureteral Reflux Index: 2-Institution Analysis and Validation.

PubMed

Arlen, Angela M; Garcia-Roig, Michael; Weiss, Aaron D; Leong, Traci; Cooper, Christopher S; Kirsch, Andrew J

2016-04-01

The vesicoureteral reflux index is a novel tool designed to predict spontaneous reflux resolution in infants younger than 2 years. We performed a multi-institutional validation study to confirm the discriminatory power of the vesicoureteral reflux index to predict the vesicoureteral reflux resolution rate in young children. We identified patients diagnosed with primary vesicoureteral reflux before age 24 months who had 2 or more voiding cystourethrograms available. Demographics, vesicoureteral reflux grade and timing, ureteral anomalies and radiographic outcomes were evaluated. The C-index was estimated for time to event model assessment. A total of 219 girls and 150 boys met study inclusion criteria. Mean ± SD age at diagnosis was 4.7 ± 4.9 months. Of the patients 101 (27.4%) had early to mid filling, 214 (58%) had late filling and 54 (14.6%) had voiding only vesicoureteral reflux. High grade reflux was present in 87 patients (23.6%) and ureteral anomalies were observed in 50 (13.6%). A vesicoureteral reflux index of 1, 2, 3, 4 and 5 or greater showed an improvement/resolution rate of 88.2%, 77.3%, 62.3%, 32.1% and 14.3%, respectively. On time to event analysis children with filling phase vesicoureteral reflux (p <0.001), grade 4-5 reflux (p <0.001) and ureteral anomalies (p = 0.003) had significantly longer median time to resolution. Median time to spontaneous resolution was 12.6, 12.7, 15.1, 25.6 and 31 months or greater for a vesicoureteral reflux index of 1, 2, 3, 4 and 5 or greater, respectively (C-index 0.305, 95% CI 0.252-0.357). During the study period 65 patients (17.6%) underwent surgical intervention. The vesicoureteral reflux index is a simple tool that reliably predicts significant improvement and spontaneous resolution of primary reflux in patients diagnosed at younger than 2 years. The index provides valuable prognostic information, facilitating individualized patient care. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Risk factors, treatment and impact on outcomes of bile leakage after hemihepatectomy.

PubMed

Zheng, Si-Ming; Li, Hong; Li, Gen-Cong; Yu, Dan-Song; Ying, Dong-Jian; Zhang, Bin; Lu, Cai-De; Zhou, Xin-Hua

2017-07-01

Risk factors for bile leakage after hemihepatectomy are unknown. A prospectively maintained database review identified patients undergoing hemihepatectomy between 1 January 2009 and 30 September 2014. Patients were divided into B/C and non-B/C bile leakage groups. Risk factors for bile leakage were predicted and assessments of their impact on patients were made. Bile leakage occurred in 91 of the 297 patients (30.6%); 64 cases were classified as grade B bile leakage (21.5%) and three cases as grade C bile leakage (1.0%). Multivariate analysis confirmed that elevated preoperative alanine transaminase (ALT), positive bile culture during surgery, hilar bile duct plasty, bilioenteric anastomosis and laparoscopic surgery were risk factors for B/C grade bile leakage (P < 0.05). Percutaneous transhepatic biliary drainage (PTBD) and endoscopic nasobiliary drainage (ENBD) were protective factors for B/C grade bile leakage (P < 0.05). PTBD, ENBD and Kehr's T-tube drainage could reduce the drainage volume and duration of drainage after bile leakage (P < 0.05). The incidence of wound infection, abdominal infection, major complications and the Clavien classification system score in the B/C bile leakage group were higher than those in the non-B/C bile leakage group (P < 0.05). Patients in the B/C bile leakage group also required prolonged hospitalization (P < 0.05). The mortality of two groups was similar (P > 0.05). Patient with elevated preoperative ALT, positive bile cultures during surgery, hilar bile duct plasty, bilioenteric anastomosis and laparoscopic surgery are more likely to complicate bile leakage. We should use biliary drainage such as preoperative PTBD, ENBD or intraoperative Kehr's T-tube drainage to reduce and treat bile leakage in patients with high risk of bile leakage. © 2015 Royal Australasian College of Surgeons.

[Knowledge and practice of Brazilian pediatricians concerning gastroesophageal reflux disease in infants].

PubMed

Soares, Ana Cristina Fontenele; de Freitas, Carla Lima; de Morais, Mauro Batista

2015-01-01

To assess the knowledge and practice of pediatricians about infants with physiological reflux and gastroesophageal reflux disease. 140 pediatricians were interviewed during two scientific events in 2009 and 2010. The questions referred to two clinical cases of infants. One with symptoms of infant regurgitation (physiological reflux) and another with gastroesophageal reflux disease. Among 140 pediatricians, 11.4% (n=16) and 62.1% (n=87) would require investigation tests, respectively for infant regurgitation (physiological reflux) and gastroesophageal reflux disease. A series of upper gastrointestinal exams would be the first requested with a higher frequency. Medication would be prescribed by 18.6% (n=26) in the case of physiological reflux and 87.1% (n=122) in the case of gastroesophageal reflux disease. Prokinetic drugs would be prescribed more frequently than gastric acid secretion inhibitors. Sleeping position would be recommended by 94.2% (n=132) and 92.9% (n=130) of the respondents, respectively for the case of physiological reflux and gastroesophageal reflux disease; however, about half of the respondents would recommend the prone position. Only 10 (7.1%) of the pediatricians would exclude the cow's milk protein from the infants' diet. Approaches different from the international guidelines are often considered appropriate, especially when recommending a different position other than the supine and prescription of medication. In turn, the interviews enable us to infer the right capacity of the pediatricians to distinguish physiologic reflux and gastroesophageal reflux disease correctly. Copyright © 2014 Associação de Pediatria de São Paulo. Publicado por Elsevier Editora Ltda. All rights reserved.

Differentiation of various traditional Chinese medicines derived from animal bile and gallstone: simultaneous determination of bile acids by liquid chromatography coupled with triple quadrupole mass spectrometry.

PubMed

Qiao, Xue; Ye, Min; Pan, De-lin; Miao, Wen-juan; Xiang, Cheng; Han, Jian; Guo, De-an

2011-01-07

Animal biles and gallstones are popularly used in traditional Chinese medicines, and bile acids are their major bioactive constituents. Some of these medicines, like cow-bezoar, are very expensive, and may be adulterated or even replaced by less expensive but similar species. Due to poor ultraviolet absorbance and structural similarity of bile acids, effective technology for species differentiation and quality control of bile-based Chinese medicines is still lacking. In this study, a rapid and reliable method was established for the simultaneous qualitative and quantitative analysis of 18 bile acids, including 6 free steroids (cholic acid, chenodeoxycholic acid, deoxycholic acid, lithocholic acid, hyodeoxycholic acid, and ursodeoxycholic acid) and their corresponding glycine conjugates and taurine conjugates, by using liquid chromatography coupled with tandem mass spectrometry (LC/MS/MS). This method was used to analyze six bile-based Chinese medicines: bear bile, cattle bile, pig bile, snake bile, cow-bezoar, and artificial cow-bezoar. Samples were separated on an Atlantis dC₁₈ column and were eluted with methanol-acetonitrile-water containing ammonium acetate. The mass spectrometer was monitored in the negative electrospray ionization mode. Total ion currents of the samples were compared for species differentiation, and the contents of bile acids were determined by monitoring specific ion pairs in a selected reaction monitoring program. All 18 bile acids showed good linearity (r² > 0.993) in a wide dynamic range of up to 2000-fold, using dehydrocholic acid as the internal standard. Different animal biles could be explicitly distinguished by their major characteristic bile acids: tauroursodeoxycholic acid and taurochenodeoxycholic acid for bear bile, glycocholic acid, cholic acid and taurocholic acid for cattle bile, glycohyodeoxycholic acid and glycochenodeoxycholic acid for pig bile, and taurocholic acid for snake bile. Furthermore, cattle bile, cow-bezoar, and artificial cow-bezoar could be differentiated by the existence of hyodeoxycholic acid and the ratio of cholic acid to deoxycholic acid. This study provided bile acid profiles of bile-based Chinese medicines for the first time, which could be used for their quality control. Copyright © 2010 Elsevier B.V. All rights reserved.

Physiological and molecular biochemical mechanisms of bile formation

PubMed Central

Reshetnyak, Vasiliy Ivanovich

2013-01-01

This review considers the physiological and molecular biochemical mechanisms of bile formation. The composition of bile and structure of a bile canaliculus, biosynthesis and conjugation of bile acids, bile phospholipids, formation of bile micellar structures, and enterohepatic circulation of bile acids are described. In general, the review focuses on the molecular physiology of the transporting systems of the hepatocyte sinusoidal and apical membranes. Knowledge of physiological and biochemical basis of bile formation has implications for understanding the mechanisms of development of pathological processes, associated with diseases of the liver and biliary tract. PMID:24259965

Vesicoureteral reflux (image)

MedlinePlus

... in the bladder wall, which can cause vesicoureteral reflux. Vesicoureteral reflux is a condition that allows urine to go ... and kidneys causing repeated urinary tract infections. The reflux of urine exposes the ureters and kidney to ...

Improvements of deep vein reflux following radiofrequency ablation for saphenous vein incompetence.

PubMed

Kim, Suh Min; Jung, In Mok; Chung, Jung Kee

2017-02-01

Objectives The aim of this study was to describe the changes of deep vein reflux after radiofrequency ablation for great saphenous vein incompetence. Method The data on 139 limbs which were treated with radiofrequency ablation for great saphenous vein incompetence were prospectively collected and reviewed. Results Deep vein reflux was present in 43 of 139 limbs (30.9%). There were no significant differences in the rate of successful closure, the incidence of procedure-related complications, and the improvements of symptoms and quality of life between the limbs with or without deep vein reflux. With a mean follow-up of 5.9 months, the peak reflux velocity and duration of reflux were improved in all limbs with deep vein reflux and it was completely corrected in 13 limbs (30.2%) after radiofrequency ablation. Conclusions The presence of deep vein reflux does not affect the treatment outcomes of radiofrequency ablation for great saphenous vein incompetence and is improved in all patients. Deep vein reflux is not a barrier to performing radiofrequency ablation.

New insights into bile acid malabsorption.

PubMed

Johnston, Ian; Nolan, Jonathan; Pattni, Sanjeev S; Walters, Julian R F

2011-10-01

Bile acid malabsorption occurs when there is impaired absorption of bile acids in the terminal ileum, so interrupting the normal enterohepatic circulation. The excess bile acids in the colon cause diarrhea, and treatment with bile acid sequestrants is beneficial. The condition can be diagnosed with difficulty by measuring fecal bile acids, or more easily by retention of selenohomocholyltaurine (SeHCAT), where this is available. Chronic diarrhea caused by primary bile acid diarrhea appears to be common, but is under-recognized where SeHCAT testing is not performed. Measuring excessive bile acid synthesis with 7α-hydroxy-4-cholesten-3-one may be an alternative means of diagnosis. It appears that there is no absorption defect in primary bile acid diarrhea but, instead, an overproduction of bile acids. Fibroblast growth factor 19 (FGF19) inhibits hepatic bile acid synthesis. Defective production of FGF19 from the ileum may be the cause of primary bile acid diarrhea.

Gastro-oesophageal reflux monitoring: review and consensus report on detection and definitions of acid, non-acid, and gas reflux

PubMed Central

Sifrim, D; Castell, D; Dent, J; Kahrilas, P J

2004-01-01

To date, most concepts on the frequency of gastro-oesophageal reflux episodes and the efficiency of the antireflux barrier have been based on inferences derived from measurement of oesophageal pH. The development of intraluminal impedance monitoring has highlighted the fact that pH monitoring does not detect all gastro-oesophageal reflux events when little or no acid is present in the refluxate, even if special pH tracing analysis criteria are used. In November 2002, a workshop took place at which 11 specialists in the field of gastro-oesophageal reflux disease discussed and criticised all currently available techniques for measurement of reflux. Here, a summary of their conclusions and recommendations of how to achieve the best results from the various techniques now available for reflux measurement is presented. PMID:15194656

Adaptation and Preadaptation of Salmonella enterica to Bile

PubMed Central

Hernández, Sara B.; Cota, Ignacio; Ducret, Adrien; Aussel, Laurent; Casadesús, Josep

2012-01-01

Bile possesses antibacterial activity because bile salts disrupt membranes, denature proteins, and damage DNA. This study describes mechanisms employed by the bacterium Salmonella enterica to survive bile. Sublethal concentrations of the bile salt sodium deoxycholate (DOC) adapt Salmonella to survive lethal concentrations of bile. Adaptation seems to be associated to multiple changes in gene expression, which include upregulation of the RpoS-dependent general stress response and other stress responses. The crucial role of the general stress response in adaptation to bile is supported by the observation that RpoS− mutants are bile-sensitive. While adaptation to bile involves a response by the bacterial population, individual cells can become bile-resistant without adaptation: plating of a non-adapted S. enterica culture on medium containing a lethal concentration of bile yields bile-resistant colonies at frequencies between 10−6 and 10−7 per cell and generation. Fluctuation analysis indicates that such colonies derive from bile-resistant cells present in the previous culture. A fraction of such isolates are stable, indicating that bile resistance can be acquired by mutation. Full genome sequencing of bile-resistant mutants shows that alteration of the lipopolysaccharide transport machinery is a frequent cause of mutational bile resistance. However, selection on lethal concentrations of bile also provides bile-resistant isolates that are not mutants. We propose that such isolates derive from rare cells whose physiological state permitted survival upon encountering bile. This view is supported by single cell analysis of gene expression using a microscope fluidic system: batch cultures of Salmonella contain cells that activate stress response genes in the absence of DOC. This phenomenon underscores the existence of phenotypic heterogeneity in clonal populations of bacteria and may illustrate the adaptive value of gene expression fluctuations. PMID:22275872

Bile acid metabolism and signaling in cholestasis, inflammation and cancer

PubMed Central

Apte, Udayan

2015-01-01

Bile acids are synthesized from cholesterol in the liver. Some cytochrome P450 (CYP) enzymes play key roles in bile acid synthesis. Bile acids are physiological detergent molecules, so are highly cytotoxic. They undergo enterohepatic circulation and play important roles in generating bile flow and facilitating biliary secretion of endogenous metabolites and xenobiotics and intestinal absorption of dietary fats and lipid soluble vitamins. Bile acid synthesis, transport and pool size are therefore tightly regulated under physiological conditions. In cholestasis, impaired bile flow leads to accumulation of bile acids in the liver, causing hepatocyte and biliary injury and inflammation. Chronic cholestasis is associated with fibrosis, cirrhosis and eventually liver failure. Chronic cholestasis also increases the risk of developing hepatocellular or cholangiocellular carcinomas. Extensive research in the last two decades has shown that bile acids act as signaling molecules that regulate various cellular processes. The bile acid-activated nuclear receptors are ligand-activated transcriptional factors that play critical roles in the regulation of bile acid, drug and xenobiotic metabolism. In cholestasis, these bile acid-activated receptors regulate a network of genes involved in bile acid synthesis, conjugation, transport and metabolism to alleviate bile acid-induced inflammation and injury. Additionally, bile acids are known to regulate cell growth and proliferation, and altered bile acid levels in diseased conditions have been implicated in liver injury/regeneration and tumorigenesis. We will cover the mechanisms that regulate bile acid homeostasis and detoxification during cholestasis, and the roles of bile acids in the initiation and regulation of hepatic inflammation, regeneration and carcinogenesis. PMID:26233910

Factors Affecting the Prevalence of Gastro-oesophageal Reflux in Childhood Corrosive Oesophageal Strictures.

PubMed

Iskit, Serdar H; Ozçelik, Zerrin; Alkan, Murat; Türker, Selcan; Zorludemir, Unal

2014-06-01

Gastro-oesophageal reflux may accompany the corrosive oesophageal damage caused by the ingestion of corrosive substances and affect its treatment. The factors that affect the development of reflux in these cases and their effects on treatment still remain unclear. Our aim is to investigate the prevalence of gastro-oesophageal reflux in children with corrosive oesophageal strictures, the risk factors affecting this prevalence and the effects of gastro-oesophageal reflux on treatment. Case-control study. We enrolled 52 patients with oesophageal stricture due to corrosive substance ingestion who were referred to our clinic between 2003 and 2010. Groups, which were determined according to the presence of gastro-oesophageal reflux (GER), were compared with each other in terms of clinical findings, results of examination methods, characteristics of the stricture and success of the treatment. The total number of patients in our study was 52; 30 of them were male and 22 of them were female. The mean age of our study population was 4.2±2.88 years. Thirty-three patients had gastrooesophageal reflux (63.5%). Patients who had strictures caused by the ingestion of alkali substances were 1.6-times more likely to have reflux. There were no differences between patients with or without reflux in terms of number and localisation of strictures. Mean distance of stricture was longer in patients with reflux (3.7±1.8 cm) than in patients without (2.2±1.0 cm) (p<0.005). Only one patient among 17 who had a long stricture (≥4 cm) did not suffer from reflux. Patients with long stricture were 1.9-times more likely to have reflux. Dilatation treatment was successful in 69.6% of patients with reflux and in 78.9% of patients without. The mean treatment period was 8.41±6.1 months in patients with reflux and 8.21±8.4 months in the other group. There was no significant difference between groups in terms of frequency of dilatation and dilator diameters (p>0.05). Corrosive oesophageal stricture was usually accompanied by gastro-oesophageal reflux and the length of stricture is an important risk factor. Negative effects of reflux over dilatation treatment have not yet been demonstrated in the short-term. Nevertheless, this frequent rate of reflux may eventually increase the risk of oesophagitis and Barrett's oesophagus; therefore, we suggest that these effects should be prospectively evaluated in a large number of patients and these patients should be followed-up routinely in terms of the long-term effects of reflux.

[Vesicorenal reflux. Morphological diagnosis and indications for anti-reflux plasty].

PubMed

Stark, R; Brühl, P

1975-09-25

The importance of reflux-pyelonephritis in children and adults is discussed. Important leading-symptoms are the incontinence after the age of four besides the cystoureteritis, which is resistant to all kinds of therapy. Following the discussion of the etiopathogenesis of the reflux and its consequences, the symptomatic of the reflux is described in detail and a diagnostic program is given. Extended urological diagnosis includes intravenous urography with preceeding x-ray-examination, reflux cystogram and cystourethrogram during urination. An essential emprovement of these diagnostic measures for the recording of the vesicoureteral reflux is the recording by the 100-mm-cutfilm-camera. Indications for surgical measures and the operative proceeding are discussed.

Bile Routing Modification Reproduces Key Features of Gastric Bypass in Rat.

PubMed

Goncalves, Daisy; Barataud, Aude; De Vadder, Filipe; Vinera, Jennifer; Zitoun, Carine; Duchampt, Adeline; Mithieux, Gilles

2015-12-01

To evaluate the role of bile routing modification on the beneficial effects of gastric bypass surgery on glucose and energy metabolism. Gastric bypass surgery (GBP) promotes early improvements in glucose and energy homeostasis in obese diabetic patients. A suggested mechanism associates a decrease in hepatic glucose production to an enhanced intestinal gluconeogenesis. Moreover, plasma bile acids are elevated after GBP and bile acids are inhibitors of gluconeogenesis. In male Sprague-Dawley rats, we performed bile diversions from the bile duct to the midjejunum or the mid-ileum to match the modified bile delivery in the gut occurring in GBP. Body weight, food intake, glucose tolerance, insulin sensitivity, and food preference were analyzed. The expression of gluconeogenesis genes was evaluated in both the liver and the intestine. Bile diversions mimicking GBP promote an increase in plasma bile acids and a marked improvement in glucose control. Bile bioavailability modification is causal because a bile acid sequestrant suppresses the beneficial effects of bile diversions on glucose control. In agreement with the inhibitory role of bile acids on gluconeogenesis, bile diversions promote a blunting in hepatic glucose production, whereas intestinal gluconeogenesis is increased in the gut segments devoid of bile. In rats fed a high-fat-high-sucrose diet, bile diversions improve glucose control and dramatically decrease food intake because of an acquired disinterest in fatty food. This study shows that bile routing modification is a key mechanistic feature in the beneficial outcomes of GBP.

Bile Routing Modification Reproduces Key Features of Gastric Bypass in Rat

PubMed Central

Goncalves, Daisy; Barataud, Aude; De Vadder, Filipe; Vinera, Jennifer; Zitoun, Carine; Duchampt, Adeline; Mithieux, Gilles

2015-01-01

STRUCTURED ABSTRACT Objective To evaluate the role of bile routing modification on the beneficial effects of gastric bypass surgery on glucose and energy metabolism. Summary background data Gastric bypass surgery (GBP) promotes early improvements in glucose and energy homeostasis in obese diabetic patients. A suggested mechanism associates a decrease in hepatic glucose production (HGP) to an enhanced intestinal gluconeogenesis (IGN). Moreover, plasma bile acids are elevated after GBP and bile acids are inhibitors of gluconeogenesis. Methods In male Sprague-Dawley rats, we performed bile diversions from the bile duct to the mid-jejunum or the mid-ileum to match the modified bile delivery in the gut occurring in GBP. Body weight, food intake, glucose tolerance, insulin sensitivity and food preference were analyzed. The expression of gluconeogenesis genes was evaluated in both the liver and the intestine. Results Bile diversions mimicking GBP promote an increase in plasma bile acids and a marked improvement in glucose control. Bile bioavailability modification is causal since a bile acid sequestrant suppresses the beneficial effects of bile diversions on glucose control. In agreement with the inhibitory role of bile acids on gluconeogenesis, bile diversions promote a blunting in HGP, whereas IGN is increased in the gut segments devoid of bile. In rats fed a high fat-high sucrose diet, bile diversions improve glucose control and dramatically decrease food intake due to an acquired disinterest in fatty food. Conclusion This study shows that bile routing modification is a key mechanistic feature in the beneficial outcomes of GBP. PMID:25575265

Gastro-pharyngeal reflux and total laryngectomy. Increasing knowledge about its management.

PubMed

Mannelli, Giuditta; Santoro, Roberto; Segala, Francesco; Surrenti, Elisabetta; Gallo, Oreste

Investigate the incidence, the degree and the effect of gastro-pharyngeal reflux (GPR) in laryngectomised patients. Behavioral and 24-hour pH- and impedance-monitoring data were prospectively analyzed for 25 laryngectomised patients with no previous history of GER in outpateints' setting. Reflux detected was characterized as either acid, weakly acidic or nonacid. Proximal reflux was found at 15cm above the LES. 40% of patients presented a pathological number of reflux episodes in the upright position (p<0.0001); 9 of them presented a pathologic bolus exposure time. Bolus exposure at the proximal sphincter was one fourth-fold lower than 5cm above the LES (p=0.3593). There was a prevalence of acid reflux at both sphincters (p<0.0001); liquid reflux was prevalent at the LES (p=0.003) and mixed reflux at the UES (p=0.0001). Median REs was higher than time acid exposure (p=0.0013). Pre- and post-surgical reflux investigation could identify preexisting reflux severity and screen potential high-risk cancer patients for postoperative complications. This might allow the early onset of acid suppressive therapy in presence of pathologic findings in high-complication risk cancer patients. Copyright © 2017 Elsevier Inc. All rights reserved.

Lack of correlation between extended pH monitoring and scintigraphy in the evaluation of infants with gastroesophageal reflux

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tolia, V.; Calhoun, J.A.; Kuhns, L.R.

1990-05-01

Sixty-nine infants younger than 1 year of age, with symptoms of persistent vomiting, recurrent choking, apnea, persistent cough, or stridor, were evaluated for gastroesophageal reflux. All infants underwent extended intraesophageal pH monitoring for 16 to 24 hours as well as gastroesophageal scintigraphy with technetium 99m sulfur colloid to study the correlation between the two tests. Forty-eight infants exhibited reflux with extended pH monitoring whereas 46 infants showed reflux with scintigraphy. However, the diagnosis of reflux in individual patients by extended pH monitoring corresponded poorly with the diagnosis of reflux in the same patients by scintigraphy. Similarly, no correlation was observedmore » between extended pH monitoring and scintigraphy results, whether expressed as percent gastric emptying or as gastroesophageal reflux ratio. We conclude that extended pH monitoring and scintigraphy measure different pathophysiologic phenomena and detect reflux under different conditions. The ability of these tests to detect reflux may be complementary and they may be of greatest value when used together to enhance the sensitivity and specificity of the diagnostic evaluation. Extended pH monitoring and scintigraphy should not be used interchangeably to monitor gastroesophageal reflux.« less

Evolution of substrate specificity for the bile salt transporter ASBT (SLC10A2)[S

PubMed Central

Lionarons, Daniël A.; Boyer, James L.; Cai, Shi-Ying

2012-01-01

The apical Na+-dependent bile salt transporter (ASBT/SLC10A2) is essential for maintaining the enterohepatic circulation of bile salts. It is not known when Slc10a2 evolved as a bile salt transporter or how it adapted to substantial changes in bile salt structure during evolution. We characterized ASBT orthologs from two primitive vertebrates, the lamprey that utilizes early 5α-bile alcohols and the skate that utilizes structurally different 5β-bile alcohols, and compared substrate specificity with ASBT from humans who utilize modern 5β-bile acids. Everted gut sacs of skate but not the more primitive lamprey transported 3H-taurocholic acid (TCA), a modern 5β-bile acid. However, molecular cloning identified ASBT orthologs from both species. Cell-based assays using recombinant ASBT/Asbt's indicate that lamprey Asbt has high affinity for 5α-bile alcohols, low affinity for 5β-bile alcohols, and lacks affinity for TCA, whereas skate Asbt showed high affinity for 5α- and 5β-bile alcohols but low affinity for TCA. In contrast, human ASBT demonstrated high affinity for all three bile salt types. These findings suggest that ASBT evolved from the earliest vertebrates by gaining affinity for modern bile salts while retaining affinity for older bile salts. Also, our results indicate that the bile salt enterohepatic circulation is conserved throughout vertebrate evolution. PMID:22669917

Evaluation of prenatal hydronephrosis: novel criteria for predicting vesicoureteral reflux on ultrasonography.

PubMed

Lee, Nora G; Rushton, H Gil; Peters, Craig A; Groves, Danja S; Pohl, Hans G

2014-09-01

Radiographic evaluation for prenatal hydronephrosis often includes voiding cystourethrography to ascertain whether vesicoureteral reflux is present. We sought to determine whether use of voiding cystourethrography could be limited to those patients at greatest risk for vesicoureteral reflux. We hypothesized that vesicoureteral reflux could be predicted by findings on renal/bladder ultrasonography of hydroureter, renal dysmorphia and/or duplication. We reviewed the records of patients with prenatal hydronephrosis who underwent initial postnatal ultrasonography and voiding cystourethrography during a 3-year period. The presence of vesicoureteral reflux on voiding cystourethrogram was correlated to ultrasound findings, including hydronephrosis grade, presence of hydroureter, renal dysmorphia or duplication, with ultrasound considered positive for any of the latter 3 findings. Of 262 patients 47 (18%) had vesicoureteral reflux. Ultrasound was positive in 24 of 29 patients (83%) with high grade reflux and 12 of 18 (67%) with low grade reflux. If ultrasonography showed any of the 3 positive findings, the odds ratio of detecting vesicoureteral reflux was 8.07 (95% CI 3.86, 16.87). Using these criteria, among all cases of prenatal hydronephrosis 5 (2%) with high grade vesicoureteral reflux and 6 (2%) with low grade reflux would have been missed. Among the 47 cases of reflux overall 5 of 29 high grade (17%) and 6 of 18 low grade cases (33%) would have been missed. By using ultrasonography criteria of hydroureter, duplication and renal dysmorphia for patients with prenatal hydronephrosis, vesicoureteral reflux can be detected more specifically. Using our criteria, 165 of 262 voiding cystourethrograms (63%) could have been avoided in patients with prenatal hydronephrosis during a 3-year period. Reducing these evaluations may decrease risks regarding radiation exposure, family anxiety and health care costs. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

The diagnosis of gastro-esophageal reflux disease cannot be made with barium esophagograms.

PubMed

Saleh, C M G; Smout, A J P M; Bredenoord, A J

2015-02-01

For over 50 years, barium studies have been used to diagnose gastro-esophageal reflux disease (GERD), but the value of this test is controversial. Our study aimed to determine if barium esophagograms can be used to diagnose GERD. Barium esophagograms and pH-impedance measurement were performed in 20 subjects with reflux symptoms. pH-impedance measurements were used as gold standard for the diagnosis of GERD. Gastro-esophageal reflux measured with the barium study was defined as a positive outcome. 50% of patients presented gastro-esophageal reflux on the barium esophagogram. No significant differences were observed in acid exposure time between subjects with (median: 7.4%; interquartile range, IQR: 8.4%) or without reflux at barium esophagography (median: 5.95%; IQR: 13.05%; p > 0.05). Nor did we find differences in median proximal extent of reflux measured with impedance monitoring between patients with a positive (median: 6.7%; IQR: 1.95%) and negative barium study (median: 7.1%; IQR: 0.68%; p > 0.05). Patients with reflux on barium esophagogram did not have a positive symptom association probability more often than those who did not have reflux at barium esophagography. Lastly, there were no differences in numbers of acid, weakly acidic or total reflux episodes between those with positive or negative barium esophagogram (p > 0.05). No correlations were found between the maximum proximal extent of gastro-esophageal reflux during esophagography and pH-impedance parameters. Presence or absence of gastro-esophageal reflux during barium esophagography does not correlate with incidence or extent of reflux observed during 24-h pH-impedance monitoring and is not of value for the diagnosis of GERD. © 2014 John Wiley & Sons Ltd.

Acid Rather Than Nonacid Reflux Burden Is a Predictor of Tooth Erosion.

PubMed

Ganesh, Meenakshi; Hertzberg, Anne; Nurko, Samuel; Needleman, Howard; Rosen, Rachel

2016-02-01

The relation between tooth erosion (TE) and gastroesophageal reflux in children has not been clearly established, and there are no studies to determine the relation with refluxate height, nonacid reflux, and erosions. The aim of this study was to determine the relation between TE and acid and nonacid gastroesophageal refluxes measured using combined pH and multichannel intraluminal impedance (pH-MII). We conducted a prospective cohort study of children presenting for pH-MII testing. Once informed consent was obtained, patients completed questionnaires about their reflux symptoms and diet, and then underwent pH-MII catheter placement and a dental examination. The Keels-Coffield erosion index was used to score the extent and severity of TE. Reflux parameters of patients with and without TE were compared using Student t test and correlations were performed using Spearman correlations. A total of 27 patients participated in the study, all of whom were on acid suppression at the time of pH-MII testing. Of the 27 patients, 10 (37%) had TE. There were significant positive correlations between acid reflux episodes (r = 0.44, P = 0.02), the percentage of time that acid reflux was present in the distal esophagus (r = 0.44, P = 0.02), and reflux index (r = 0.54, P = 0.004) with the number of TE in a given patient. The percentage of time that acid reflux was present in the proximal esophagus was positively correlated with the number of teeth erosions per patient with borderline significance (r = 0.38, P = 0.05). There was a positive correlation between acid reflux parameters and TE. Acid, rather than nonacid reflux, seems to have a significant role in the pathogenesis of TE.

Different effects of dietary factors on reflux esophagitis and non-erosive reflux disease in 11,690 Korean subjects.

PubMed

Nam, Su Youn; Park, Bum Joon; Cho, Yeong-Ah; Ryu, Kum Hei; Choi, Il Ju; Park, Sohee; Kim, Young-Woo

2017-07-01

Although dietary factors seem to be associated with gastroesophageal reflux symptoms, their effects on reflux esophagitis and non-erosive reflux disease (NERD) are unclear. We evaluate dietary effects on NERD and reflux esophagitis. A total of 11,690 health check-up persons completed questionnaires for reflux symptoms and 3-day recordings for dietary intake and underwent esophagogastroduodenoscopy from 2004 to 2008. Multiple logistic regression with odds ratio (OR) and 95% confidence interval (CI) was used to evaluate the relationship of dietary components with NERD or reflux esophagitis. Prevalence of NERD and reflux esophagitis was 7.7 and 7.2%, respectively. In adjusted analysis, highest quartile of beans (OR 0.78, 95% CI 0.64-0.95), 3rd quartile of vegetables (OR 0.74, 95% CI 0.60-0.91), 4th quartile of fruit (OR 0.78, 95% CI 0.64-0.95), 4th quartile of egg (OR 0.78, 95% CI 0.64-0.96), and 3rd quartile of fish (OR 0.80, 95% CI 0.66-0.98), and 4th quartile of milk (OR 0.78, 95% CI 0.65-0.94) reduced NERD. Reflux esophagitis had no association with food groups, whereas it was related with men, absence of H. pylori, hiatal hernia, BMI, and total energy intake. Furthermore, dietary effect on NERD was similar in men and women, whereas highest tertile of potato (OR 1.91) and milk (OR 1.87) increased reflux esophagitis only in women. While many food groups affected NERD, reflux esophagitis was associated with BMI and total energy intake rather than dietary component. These results may suggest different approaches toward dietary management of NERD and reflux esophagitis.

Quantitative assessment of reflux in commercially available needle-free IV connectors.

PubMed

Hull, Garret J; Moureau, Nancy L; Sengupta, Shramik

2018-01-01

Blood reflux is caused by changes in pressure within intravascular catheters upon connection or disconnection of a syringe or intravenous tubing from a needle-free connector (NFC). Changes in pressure, differing with each brand of NFC, may result in fluid movement and blood reflux that can contribute to intraluminal catheter occlusions and increase the potential for central-line associated bloodstream infections (CLABSI). In this study, 14 NFC brands representing each of the four market-categories of NFCs were selected for evaluation of fluid movement occurring during connection and disconnection of a syringe. Study objectives were to 1) theoretically estimate amount of blood reflux volume in microliters (μL) permitted by each NFC based on exact component measurements, and 2) experimentally measure NFC volume of fluid movement for disconnection reflux of negative, neutral and anti-reflux NFC and fluid movement for connection reflux of positive displacement NFC. The results demonstrated fluid movement/reflux volumes of 9.73 μL to 50.34 μL for negative displacement, 3.60 μL to 10.80 μL for neutral displacement, and 0.02 μL to 1.73 μL for pressure-activated anti-reflux NFC. Separate experiment was performed measuring connection reflux of 18.23 μL to 38.83 μL for positive displacement NFC connectors. This study revealed significant differences in reflux volumes for fluid displacement based on NFC design. While more research is needed on effects of blood reflux in catheters and NFCs, results highlight the need to consider NFCs based on performance of individual connector designs, rather than manufacturer designation of positive, negative and neutral marketing categories for NFCs without anti-reflux mechanisms.

Vegetal and Animal Food Proteins Have a Different Impact in the First Postprandial Hour of Impedance-pH Analysis in Patients with Heartburn

PubMed Central

Guidi, Giada; Savarino, Edoardo V.; Frazzoni, Marzio; Tolone, Salvatore; Frazzoni, Leonardo; Fuccio, Lorenzo; Bertani, Lorenzo; Bodini, Giorgia; Ceccarelli, Linda; Marchi, Santino; de Bortoli, Nicola

2018-01-01

Background and Aims By means of 24 h impedance-pH monitoring, we aimed to evaluate the effect of two different meals with a bromatological balanced composition: one with a prevailing component of animal proteins and the other with vegetable proteins. Patients and Methods We enrolled 165 patients with heartburn and negative endoscopy, who underwent impedance-pH monitoring off therapy. Patients were allocated to receive a Mediterranean diet with a total caloric intake of about 1694 kcal, divided into two meals: one with a prevailing component of animal proteins and the other with vegetable proteins. We evaluated the total reflux number, acid exposure time (AET), and symptom-reflux association with impedance-pH analysis. Moreover, during the first postprandial hour (at lunch and dinner), we evaluated the total reflux number, number of acid and weakly acidic refluxes, AET, and presence of symptoms. Results The male/female ratio was 80/85. Mean age was 51.9 ± 12.1 years. Impedance-pH analysis showed that 55/165 patients had pathological AET or a number of refluxes (nonerosive reflux disease (NERD)), 49/165 had normal AET and a number of refluxes but positive symptom-reflux association (hypersensitive esophagus (HE)), and 61/165 had normal AET and a number of refluxes with negative symptom-reflux association (functional heartburn (FH)). The overall first postprandial hour analysis showed a higher total reflux number, acid reflux number, and AET after the animal protein meal than after the vegetable protein meal. Moreover, more symptoms were reported after the animal protein meal. Similar results have been observed in the three different subcategories of patients (NERD, HE, and FH). Conclusions Vegetable proteins are associated with a lower number of refluxes, particularly acid refluxes, and with a reduced number of symptoms during the first postprandial hour. This is a pilot study and future investigations are warranted to confirm these results. PMID:29849599

Pediatric Vesicoureteral Reflux Guidelines Panel Summary Report: Clinical Practice Guidelines for Screening Siblings of Children With Vesicoureteral Reflux and Neonates/Infants With Prenatal Hydronephrosis.

PubMed

Skoog, Steven J; Peters, Craig A; Arant, Billy S; Copp, Hillary L; Elder, Jack S; Hudson, R Guy; Khoury, Antoine E; Lorenzo, Armando J; Pohl, Hans G; Shapiro, Ellen; Snodgrass, Warren T; Diaz, Mireya

2010-09-01

The American Urological Association established the Vesicoureteral Reflux Guideline Update Committee in July 2005 to update the management of primary vesicoureteral reflux in children guideline. The Panel defined the task into 5 topics pertaining to specific vesicoureteral reflux management issues, which correspond to the management of 3 distinct index patients and the screening of 2 distinct index patients. This report summarizes the existing evidence pertaining to screening of siblings and offspring of index patients with vesicoureteral reflux and infants with prenatal hydronephrosis. From this evidence clinical practice guidelines are developed to manage the clinical scenarios insofar as the data permit. The Panel searched the MEDLINE(R) database from 1994 to 2008 for all relevant articles dealing with the 5 chosen guideline topics. The database was reviewed and each abstract segregated into a specific topic area. Exclusions were case reports, basic science, secondary reflux, review articles and not relevant. The extracted article to be accepted should have assessed a cohort of children, clearly stating the number of children undergoing screening for vesicoureteral reflux. Vesicoureteral reflux should have been diagnosed with a cystogram and renal outcomes assessed by nuclear scintigraphy. The screening articles were extracted into data tables developed to evaluate epidemiological factors, patient and renal outcomes, and results of treatment. The reporting of meta-analysis of observational studies elaborated by the MOOSE group was followed. The extracted data were analyzed and formulated into evidence-based recommendations regarding the screening of siblings and offspring in index cases with vesicoureteral reflux and infants with prenatal hydronephrosis. In screened populations the prevalence of vesicoureteral reflux is 27.4% in siblings and 35.7% in offspring. Prevalence decreases at a rate of 1 screened person every 3 months of age. The prevalence is the same in males and females. Bilateral reflux prevalence is similar to unilateral reflux. Grade I-II reflux is estimated to be present in 16.7% and grade III-V reflux in 9.8% of screened patients. The estimate for renal cortical abnormalities overall is 19.3%, with 27.8% having renal damage in cohorts of symptomatic and asymptomatic children combined. In asymptomatic siblings only the rate of renal damage is 14.4%. There are presently no randomized, controlled trials of treated vs untreated screened siblings with vesicoureteral reflux to evaluate health outcomes as spontaneous resolution, decreased rates of urinary infection, pyelonephritis or renal scarring. In screened populations with prenatal hydronephrosis the prevalence of vesicoureteral reflux is 16.2%. Reflux in the contralateral nondilated kidney accounted for a mean of 25.2% of detected cases for a mean prevalence of 4.1%. In patients with a normal postnatal renal ultrasound the prevalence of reflux is 17%. The prenatal anteroposterior renal pelvic diameter was not predictive of reflux prevalence. A diameter of 4 mm is associated with a 10% to 20% prevalence of vesicoureteral reflux. The prevalence of reflux is statistically significantly greater in females (23%) than males (16%) (p=0.022). Reflux grade distribution is approximately a third each for grades I-II, III and IV-V. The estimate of renal damage in screened infants without infection is 21.8%. When stratified by reflux grade renal damage was estimated to be present in 6.2% grade I-III and 47.9% grade IV-V (p <0.0001). The risk of urinary tract infection in patients with and without prenatal hydronephrosis and vesicoureteral reflux could not be determined. The incidence of reported urinary tract infection in patients with reflux was 4.2%. The meta-analysis provided meaningful information regarding screening for vesicoureteral reflux. However, the lack of randomized clinical trials for screened patients to assess clinical health outcomes has made evidence-based guideline recommendations difficult. Consequently, screening guidelines are based on present practice, risk assessment, meta-analysis results and Panel consensus. 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

[Update on gastroesophageal reflux disease].

PubMed

Serra Pueyo, Jordi

2014-02-01

Gastroesophageal reflux disease is a highly frequent disorder classically characterized by the presence of heartburn and/or acid regurgitation that improves with drug therapy that reduces acid content in the stomach. However, especially in patients with non-erosive disease, response to proton pump inhibitors is unsatisfactory in approximately 1 out of 3 patients, and consequently, in these patients, it is important to establish a definitive diagnosis and an alternative therapeutic strategy. In the last few years, advances have been made in knowledge of the physiopathology of reflux, such as identification of the role of the acid pocket in producing reflux, technological advances that allow differentiation among acid reflux, non-acid reflux and slightly acid reflux, and advances in the treatment of reflux with drugs that attempt to act on the barrier function of the esophagogastric junction. Copyright © 2013 Elsevier España, S.L. and AEEH y AEG. All rights reserved.

Reflux Hypersensitivity: A New Functional Esophageal Disorder.

PubMed

Yamasaki, Takahisa; Fass, Ronnie

2017-10-30

Reflux hypersensitivity, recently introduced by Rome IV as a new functional esophageal disorder, is currently considered as the presence of typical heartburn symptoms in patients with normal upper endoscopy and esophageal biopsies, normal esophageal pH test and with evidence of a close correlation between patients' heartburn and reflux events. Reflux hypersensitivity is very common and together with functional heartburn accounts for more than 90% of the heartburn patients who failed treatment with proton pump inhibitor twice daily. In addition, reflux hypersensitivity affects primarily young to middle aged women, commonly overlaps with another functional gastrointestinal disorders, and is often associated with some type of psychological comorbidity. Diagnosis is made by using endoscopy with esophageal biopsies, pH-impedance, and high-resolution esophageal manometry. Reflux hypersensitivity is primarily treated with esophageal neuromodulators, such as tricyclic anti-depressants and selective serotonin reuptake inhibitors among others. Surgical anti-reflux management may also play an important role in the treatment of reflux hypersensitivity.

The Role of Sleep in the Modulation of Gastroesophageal Reflux and Symptoms in NICU Neonates.

PubMed

Qureshi, Aslam; Malkar, Manish; Splaingard, Mark; Khuhro, Abdul; Jadcherla, Sudarshan

2015-09-01

Newborns sleep about 80% of the time. Gastroesophageal reflux disease is prevalent in about 10% of neonatal intensive care unit infants. Concurrent polysomnography and pH-impedance studies clarify the relationship of gastroesophageal reflux with sleep. To characterize spatiotemporal and chemical characteristics of impedance-positive gastroesophageal reflux and define symptom associations in sleep and wake states in symptomatic neonates. We hypothesized that frequency of impedance-positive gastroesophageal reflux events and their association with cardiorespiratory symptoms is greater during sleep. Eighteen neonates underwent concurrent polysomnography with a pH-impedance study. Impedance-positive gastroesophageal reflux events (weakly acidic or acidic) were categorized between sleep versus wake states: Symptom Index = number of symptoms with gastroesophageal reflux/total symptoms*100; Symptom Sensitivity Index = number of gastroesophageal reflux with symptoms/total gastroesophageal reflux*100; Symptom Association Probability = [(1 - probability of observed association between reflux and symptoms)*100]). We analyzed 317 gastroesophageal reflux events during 116 hours of polysomnography. During wake versus sleep, respectively, the median (interquartile range) frequency of impedance-positive gastroesophageal reflux was 4.9 (3.1-5.8) versus 1.4 (0.7-1.7) events/hour (P < 0.001) and the proximal migration was 2.6 (0.8-3.3) versus 0.2 (0.0-0.9) events/hour (P < 0.001). The Symptom Index for cardiorespiratory symptoms for impedance-positive events was 22.5 (0-55.3) versus 6.1 (0-13), P = 0.04, whereas the Symptom Sensitivity Index was 9.1 (0-23.1) versus 18.4 (0-50), P = 0.04, although Symptom Association Probability was similar (P = 0.68). Contrary to our hypothesis, frequency of gastroesophageal reflux in sleep is lower; however, spatiotemporal and chemical characteristics of gastroesophageal reflux and symptom-generation mechanisms are distinct. For cardiorespiratory symptoms during sleep, a lower Symptom Index entails evaluation for etiologies other than gastroesophageal reflux disease, a higher Symptom Sensitivity Index implies heightened esophageal sensitivity, and similar Symptom Association Probability indicates other mechanistic possibilities. Copyright © 2015 Elsevier Inc. All rights reserved.

Substitutes for Bear Bile for the Treatment of Liver Diseases: Research Progress and Future Perspective

PubMed Central

Li, Sha; Tan, Hor Yue; Wang, Ning; Hong, Ming; Li, Lei; Cheung, Fan; Feng, Yibin

2016-01-01

Bear bile has been a well-known Chinese medicine for thousands of years. Because of the endangered species protection, the concept on substitutes for bear bile was proposed decades ago. Based on their chemical composition and pharmacologic actions, artificial bear bile, bile from other animals, synthetic compounds, and medicinal plants may be the promising candidates to replace bear bile for the similar therapeutic purpose. Accumulating research evidence has indicated that these potential substitutes for bear bile have displayed the same therapeutic effects as bear bile. However, stopping the use of bear bile is a challenging task. In this review, we extensively searched PubMed and CNKI for literatures, focusing on comparative studies between bear bile and its substitutes for the treatment of liver diseases. Recent research progress in potential substitutes for bear bile in the last decade is summarized, and a strategy for the use of substitutes for bear bile is discussed carefully. PMID:27087822

After Superficial Ablation for Superficial Reflux Associated with Primary Deep Axial Reflux, Can Variable Outcomes be Caused by Deep Venous Valve Anomalies?

PubMed

Maleti, O; Lugli, M; Perrin, M

2017-02-01

To identify which deep anatomical anomalies can explain variable hemodynamic outcomes in patients with superficial reflux associated with primary deep axial reflux who underwent isolated superficial vein ablation without improvement. This is a retrospective study of deep venous valve anomalies in patients who underwent superficial vein ablation for superficial and associated deep reflux. A group of 21 patients who were diagnosed with saphenous reflux associated with primary deep axial reflux, were submitted to great saphenous vein ablation. In 17 patients the deep reflux was not abolished. In this subgroup, surgical exploration of the deep valve was carried out using venotomy for possible valve repair. Among the 17 subgroup patients, four post-thrombotic lesions were discovered intra-operatively in four patients; they underwent different surgical procedures. In 13 of the subgroup patients, primary valve incompetence was confirmed intra-operatively. In 11 cases the leaflets were asymmetrical and in only two were they symmetrical. After valvuloplasty, deep reflux was abolished in all 13 patients. Clinical improvement was obtained in 12/13 patients (92%). It is noteworthy that abolition of deep reflux was associated with significant improvement in air plethysmography data as well as with improvement in clinical status measured on CEAP class, VCSS and the SF-36 questionnaire. Failure to correct deep axial reflux by superficial ablation in patients with superficial and associated primary deep axial reflux may be related to asymmetry in the leaflets of the incompetent deep venous valve. Copyright © 2016 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

Gastro-oesophageal reflux. Part 1: smoking and alcohol reduction.

PubMed

Al Talalwah, Narmeen; Woodward, Sue

Gastro-oesophageal reflux disease (GORD) is defined as an abnormal reflux of the stomach contents into the oesophagus, which provokes symptoms and impairs the quality of life. GORD has a high prevalence and incurs costs to the healthcare system. This is the first paper in a series of three exploring the conservative, medical and surgical treatment of GORD. This first paper presents a review of the effect of smoking and alcohol on reflux symptoms and the impact of smoking and alcohol reduction on symptoms of GORD. A search for English language studies on adults was conducted using three databases, MEDLINE, Embase and the Cochrane Central Register of Controlled Trials (CENTRAL). Eleven relevant studies were included in the review. The effect of alcohol on the stimulation of reflux has been debated over the years in different studies. Some studies state that alcohol consumption induces reflux and moderate amounts exacerbate nocturnal gastro-oesophageal heartburn reflux. However, other studies have found no association between alcohol consumption and reflux. Most reflux occurs during smoking because nicotine causes the lower oesophageal sphincter to relax, which increases the risk of reflux. Similarly, the number of cigarettes smoked is associated with the risk of reflux. Nurses need to be aware of the effect of smoking and alcohol on reflux to provide evidence-based advice to empower patients to change their lifestyle, which results in increased therapeutic compliance and a better clinical status. There is no evidence that reducing alcohol consumption decreases symptoms and only limited evidence on the effectiveness of smoking cessation. Further research into the effectiveness of these lifestyle modifications is therefore required.

Diet affects reflux in a rural African community.

PubMed

Ndebia, E J; Sammon, A M; Umapathy, E; Iputo, J E

2017-01-01

Reflux in this region of South Africa is known to be more frequent and less acidic than in other countries. We investigated the relationship between reflux and diet. We recruited 57 healthy participants. We carried out ambulant oesophageal pH-impedance monitoring for 24 hours. We used software and visual review to analyse data and to identify episodes of reflux and rapid alkaline rises in the stomach. A usual pattern diet questionnaire provided data on frequency of consumption of common foods. Associations between reflux, gastric pH and dietary components were sought using analysis of variance, and regression analyses. Diet was strongly based on maize. Protein was principally from milk, eggs, chicken and beans. Fat was principally from cooking oil. Fruit and vegetables were consumed moderately frequently. Milk consumption was associated with an increase in total reflux (P = .022), weakly acid reflux (P = 0.015) and supine reflux (P = 0.001), and a decrease in the time that gastric pH was higher than 4 (P = 0.030). Fat was associated with an increase in acid reflux (P = 0.046) and a decrease in time that gastric pH was higher than 4 (P = 0.005). Fruit consumption was associated with increases in liquid-only refluxes(P = 0.007), and upright refluxes (P = 0.048). Maize meal was associated with a reduction in rapid alkaline rises in the gastric lumen (P = 0.015). Diet significantly affects reflux in this community. What is normal in apparently healthy people in various parts of the world differs significantly. © Acta Gastro-Enterologica Belgica.

New bulking agent for the treatment of vesicoureteral reflux: Polymethylmethacrylate/dextranomer.

PubMed

Kim, Sang Woon; Lee, Yong Seung; Im, Young Jae; Han, Sang Won

2018-05-01

The aim of this study was to report preliminary results of endoscopic treatment of vesicoureteral reflux in children with a single injection of a new bulking agent, cross-linked dextran and polymethylmethacrylate mixture. We performed a single-center, single surgeon, prospective, off-label study using polymethylmethacrylate/dextranomer to treat vesicoureteral reflux. All patients underwent endoscopic injection, followed by renal ultrasound and voiding cystourethrogram at 3 months postoperatively to identify de novo or worsening hydronephrosis and vesicoureteral reflux correction (to Grade 0 or I). Eighteen patients underwent injection of polymethylmethacrylate/dextranomer at our institution between April 2013 and December 2013. Ten were males and eight were females, with a median age of 58 months (range, 6 months to 5 years). Vesicoureteral reflux was unilateral in three patients and bilateral in 15, for a total of 33 renal refluxing units. Vesicoureteral reflux was Grade I in one renal refluxing unit, Grade II in 12, Grade III in 16, and Grade IV in four. Mean injected volume was 0.86 mL. Reflux was corrected in 23 renal refluxing units (69.7%) according to the 3-month voiding cystourethrogram. Complications included urinary retention in one patient. Mild pyelectasis was noted in one patient at 3 months, which spontaneously resolved 3 months later. Our short-term data show that polymethylmethacrylate/dextranomer injection can be used to treat vesicoureteral reflux with comparable efficacy to other substances currently used and a low rate of complications. Long-term follow-up is required to confirm the usefulness of this material in treating vesicoureteral reflux.

Bile Formation and Secretion

PubMed Central

Boyer, James L.

2014-01-01

Bile is a unique and vital aqueous secretion of the liver that is formed by the hepatocyte and modified down stream by absorptive and secretory properties of the bile duct epithelium. Approximately 5% of bile consists of organic and inorganic solutes of considerable complexity. The bile-secretory unit consists of a canalicular network which is formed by the apical membrane of adjacent hepatocytes and sealed by tight junctions. The bile canaliculi (~1 μm in diameter) conduct the flow of bile countercurrent to the direction of portal blood flow and connect with the canal of Hering and bile ducts which progressively increase in diameter and complexity prior to the entry of bile into the gallbladder, common bile duct, and intestine. Canalicular bile secretion is determined by both bile salt-dependent and independent transport systems which are localized at the apical membrane of the hepatocyte and largely consist of a series of adenosine triphosphate-binding cassette transport proteins that function as export pumps for bile salts and other organic solutes. These transporters create osmotic gradients within the bile canalicular lumen that provide the driving force for movement of fluid into the lumen via aquaporins. Species vary with respect to the relative amounts of bile salt-dependent and independent canalicular flow and cholangiocyte secretion which is highly regulated by hormones, second messengers, and signal transduction pathways. Most determinants of bile secretion are now characterized at the molecular level in animal models and in man. Genetic mutations serve to illuminate many of their functions. PMID:23897680

Interactions between gut bacteria and bile in health and disease.

PubMed

Long, Sarah L; Gahan, Cormac G M; Joyce, Susan A

2017-08-01

Bile acids are synthesized from cholesterol in the liver and released into the intestine to aid the digestion of dietary lipids. The host enzymes that contribute to bile acid synthesis in the liver and the regulatory pathways that influence the composition of the total bile acid pool in the host have been well established. In addition, the gut microbiota provides unique contributions to the diversity of bile acids in the bile acid pool. Gut microbial enzymes contribute significantly to bile acid metabolism through deconjugation and dehydroxylation reactions to generate unconjugated bile acids and secondary bile acids. These microbial enzymes (which include bile salt hydrolase (BSH) and bile acid-inducible (BAI) enzymes) are essential for bile acid homeostasis in the host and represent a vital contribution of the gut microbiome to host health. Perturbation of the gut microbiota in disease states may therefore significantly influence bile acid signatures in the host, especially in the context of gastrointestinal or systemic disease. Given that bile acids are ligands for host cell receptors (including the FXR, TGR5 and Vitamin D Receptor) alterations to microbial enzymes and associated changes to bile acid signatures have significant consequences for the host. In this review we examine the contribution of microbial enzymes to the process of bile acid metabolism in the host and discuss the implications for microbe-host signalling in the context of C. difficile infection, inflammatory bowel disease and other disease states. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effect of acid suppression therapy on gastroesophageal reflux and cough in idiopathic pulmonary fibrosis: an intervention study.

PubMed

Kilduff, Claire E; Counter, Melanie J; Thomas, Gareth A; Harrison, Nicholas K; Hope-Gill, Benjamin D

2014-01-01

Chronic cough affects more than 70 percent of patients with Idiopathic Pulmonary Fibrosis and causes significant morbidity. Gastroesophageal reflux is the cause of some cases of chronic cough; and also has a postulated role in the aetiology of Idiopathic Pulmonary Fibrosis. A high prevalence of acid; and more recently non-acid, reflux has been observed in Idiopathic Pulmonary Fibrosis cohorts. Therefore, gastroesophageal reflux may be implicated in the pathogenesis of cough in Idiopathic Pulmonary Fibrosis. Eighteen subjects with Idiopathic Pulmonary Fibrosis underwent 24-hour oesophageal impedance and cough count monitoring after the careful exclusion of causes of chronic cough other than gastroesophageal reflux. All 18 were then treated with high dose acid suppression therapies. Fourteen subjects underwent repeat 24-hour oesophageal impedance and cough count monitoring after eight weeks. Total reflux and acid reflux frequencies were within the normal range in the majority of this cohort. The frequencies of non-acid and proximal reflux events were above the normal range. Following high dose acid suppression therapy there was a significant decrease in the number of acid reflux events (p = 0.02), but an increase in the number of non-acid reflux events (p = 0.01). There was no change in cough frequency (p = 0.70). This study confirms that non-acid reflux is prevalent; and that proximal oesophageal reflux occurs in the majority, of subjects with Idiopathic Pulmonary Fibrosis. It is the first study to investigate the effect of acid suppression therapy on gastroesophageal reflux and cough in patients with Idiopathic Pulmonary Fibrosis. The observation that cough frequency does not improve despite verifiable reductions in oesophageal acid exposure challenges the role of acid reflux in Idiopathic Pulmonary Fibrosis associated cough. The finding that non-acid reflux is increased following the use of acid suppression therapies cautions against the widespread use of acid suppression in patients with Idiopathic Pulmonary Fibrosis given the potential role for non-acid reflux in the pathogenesis of cough and Idiopathic Pulmonary Fibrosis itself. The study was registered with the Cardiff and Vale University Local Health Board Research and Development Committee (09/CMC/4619) and the South East Wales Ethics Committee (09/WSE04/57).

Effect of acid suppression therapy on gastroesophageal reflux and cough in idiopathic pulmonary fibrosis: an intervention study

PubMed Central

2014-01-01

Background Chronic cough affects more than 70 percent of patients with Idiopathic Pulmonary Fibrosis and causes significant morbidity. Gastroesophageal reflux is the cause of some cases of chronic cough; and also has a postulated role in the aetiology of Idiopathic Pulmonary Fibrosis. A high prevalence of acid; and more recently non-acid, reflux has been observed in Idiopathic Pulmonary Fibrosis cohorts. Therefore, gastroesophageal reflux may be implicated in the pathogenesis of cough in Idiopathic Pulmonary Fibrosis. Methods Eighteen subjects with Idiopathic Pulmonary Fibrosis underwent 24-hour oesophageal impedance and cough count monitoring after the careful exclusion of causes of chronic cough other than gastroesophageal reflux. All 18 were then treated with high dose acid suppression therapies. Fourteen subjects underwent repeat 24-hour oesophageal impedance and cough count monitoring after eight weeks. Results Total reflux and acid reflux frequencies were within the normal range in the majority of this cohort. The frequencies of non-acid and proximal reflux events were above the normal range. Following high dose acid suppression therapy there was a significant decrease in the number of acid reflux events (p = 0.02), but an increase in the number of non-acid reflux events (p = 0.01). There was no change in cough frequency (p = 0.70). Conclusions This study confirms that non-acid reflux is prevalent; and that proximal oesophageal reflux occurs in the majority, of subjects with Idiopathic Pulmonary Fibrosis. It is the first study to investigate the effect of acid suppression therapy on gastroesophageal reflux and cough in patients with Idiopathic Pulmonary Fibrosis. The observation that cough frequency does not improve despite verifiable reductions in oesophageal acid exposure challenges the role of acid reflux in Idiopathic Pulmonary Fibrosis associated cough. The finding that non-acid reflux is increased following the use of acid suppression therapies cautions against the widespread use of acid suppression in patients with Idiopathic Pulmonary Fibrosis given the potential role for non-acid reflux in the pathogenesis of cough and Idiopathic Pulmonary Fibrosis itself. Study registration The study was registered with the Cardiff and Vale University Local Health Board Research and Development Committee (09/CMC/4619) and the South East Wales Ethics Committee (09/WSE04/57). PMID:24876887

Correlation of obstructive sleep apnoea and laryngopharyngeal reflux: phmetry study.

PubMed

Elhennawi, D M; Ahmed, M R; Abou-Halawa, A S

2016-12-01

To study the correlation of obstructive sleep apnoea (OSA) and laryngopharyngeal reflux (LPR). A descriptive study. Suez Canal University Hospital, Ismailia, Egypt. 62 patients with polysomnography confirmed OSA. Patients were evaluated with ambulatory 24-h double channel pH monitoring. Mean reflux symptom index in the study group was 9 ± 5.5, and it was > 13 in all patients with severe OSA. Signs of LPR reflux were present in 34 (55%) patients. Abnormal reflux was detected in the distal oesophagus in 41 patients (66%) and in the proximal oesophagus in 21 patients (34%). Patients with severe OSA had significantly higher nocturnal LPR reflux episodes compared to patients with mild disease (P < .05). Number of reflux episodes and total duration of reflux during sleep are significantly correlated to degree of OSA (P < .05). No difference was found in relation to age or sex. Daytime reflux was not related to the degree of obstructive sleep apnoea (P > .05). LPR is common in patients with OSA. Patients with severe OSA have significantly higher nocturnal LPR. This should be considered when treating this group of patients. © 2016 John Wiley & Sons Ltd.

[Gastric and duodenal secretory and motor-evacuatory activity in patients with gastroesophageal reflux disease associated with different types of reflux].

PubMed

Dzhulay, G S; Sekareva, E V

2016-01-01

To estimate esophageal and gastric pH values on an empty stomach and after stimulation of gastric secretion and gastric and duodenal motor-evacuatory activity in patients with gastroesophageal reflux disease (GERD) associated with pathological refluxes, such as gastroesophageal reflux (GER) and duodenogastroesophageal reflux (DGER). The observational cross-sectional study was conducted to investigate and compare the parameters of intraesophageal and intragastric pH metry and peripheral electrogastroenterography in 103 GERD patients with endoscopically positive distal reflux esophagitis in GER and DGER. The patients with GERD developed pathological esophageal refluxes (both GER and DGER) in various degrees of impaired gastric production, from anacidity to hyperacidity. The patients with predominant DGER were found to have gastric hyperacidity and normal acidity slightly less frequently than those with predominant GER. The patients with GERD developing in the presence of predominant GER had moderate gastric stasis with discoordinated antroduodenal propulsion resulting from hypomotor dyskinesia of the stomach and duodenum. When DGER was predominant in the patients with GERD, the signs of gastric stasis and duodenal hyperkinesia were concurrent with discoordinated antroduodenal and duodenojejunal propulsion. The specific features of the esophagogastroduodenal secretory and motor evacuatory disorders found create conditions for the pathological refluxes into the esophagus, which differ in the composition of refluxate.

Role of altered esophageal intraluminal baseline impedance levels in patients with gatroesophageal reflux disease refractory to proton pump inhibitors

PubMed Central

Jiang, Liuqin; Ye, Bixing; Lin, Lin; Wang, Ying; Wang, Meifeng

2016-01-01

Abstract Numerous studies have investigated utility of esophageal intraluminal baseline impedance levels (BILs) in gastroesophageal reflux disease (GERD). However, effect of BILs in refractory GERD (RGERD) has not been well investigated. The aim of this study is to evaluate role of BILs in RGERD patients. Total 62 subjects with refractory gastroesophageal reflux symptoms underwent 24-hour impedance-pH monitoring and gastroendoscopy. Distal BILs in acid reflux type were significantly lower than those in nonacid reflux type and functional heartburn (FH) group. Distal BILs of reflux esophagitis (RE) patients were lower than those of nonerosive reflux disease (NERD) patients, while there were no statistical significance between 2 groups. Patients with severe esophagitis had lower distal BILs than those with mild esophagitis and NERD patients, and patients with severe esophagitis in acid reflux type had the lowest distal BILs. Distal BILs were significantly negatively correlated with DeMeester score, episodes of acid reflux, and acid exposure time, but no correlated with episodes of nonacid reflux. Characteristics of BILs in RGERD patients were similar with those in GERD patients, but might be more complicated. Evaluating BILs in RGERD patients could achieve a better understanding of pathophysiology in RGERD. PMID:27537561

Physiological analysis of the effects of rikkunshito on acid and non-acid gastroesophageal reflux using pH-multichannel intraluminal impedance monitoring.

PubMed

Kawahara, Hisayoshi; Tazuke, Yuko; Soh, Hideki; Yoneda, Akihiro; Fukuzawa, Masahiro

2014-09-01

To clarify the effects of rikkunshito on acid reflux, non-acid reflux, and esophageal clearance in patients with gastroesophageal reflux disease (GERD). We enrolled seven patients with vomiting and/or stridor (median 6 years; 1 month-17 years), with a percent total time of esophageal pH <4.0 (reflux index) over 4.0%. Rikkunshito (TJ-43; Tsumura Co, Tokyo, Japan) was given in three divided doses before meals. We retrospectively investigated its efficacy using pH-multichannel intraluminal impedance before and 7 (6-10) days after starting treatment. Statistical analyses were conducted using Wilcoxon signed-rank test. In the pH analyses alone, the median number of acid reflux episodes >5 min (14 versus 10, p = 0.046) and median acid-clearance time (184 versus 134 s, p = 0.03) decreased significantly, although median decrease in reflux index did not reach significance (16.0 versus 17.9%, p = 0.06). In the combined impedance and pH analyses, the median number (36 versus 36, p = 0.03) and median duration (1.9 versus 1.1%, p = 0.046) of acid reflux decreased significantly; non-acid reflux and bolus clearance time did not change. Rikkunshito effectively reduced acid reflux, but not esophageal clearance, in patients with GERD.

High incidence of vesicoureteric reflux in asymptomatic siblings of children with known reflux

DOE Office of Scientific and Technical Information (OSTI.GOV)

Treves, S.T.; Van den Abbeele, A.D.; Davis, R.T.

1985-05-01

A significant occurrence of vesicoureteric reflux in siblings of children with reflux has been previously suggested. The purpose of this study was to evaluate the incidence of vesicoureteric reflux in asymptomatic siblings of children with vesicoureteric reflux using radionuclide voiding cystography (RNC). A random group of 52 siblings was studied. Their ages were from 2 mos. to 13 yrs. (mean 4 yrs.). Seventy-one percent were female and 29% male, RNC was performed with the patients supine, and Tc-99m pertechnetate (2mCi/1) was infused into the bladder by catheter. A computerized gamma camera recorded the filling and voiding phase of the studymore » at 1 frame/5 sec. Reflux was detected in 40% of the patients. It was bilateral in 17% and unilateral in 23% of the patients. Reflux was identified to the renal pelves in half of the patients. In two of these patients Tc-99m DMSA scans were obtained which revealed significant renal scarring. This study demonstrates the high incidence of reflux of various degrees in these asymptomatic siblings on high risk of developing significant renal disease. Identification and proper treatment of asymptomatic children with vesicoureteric reflux may help prevent the development of renal damage.« less

Effect of proton pump inhibitor (PPI) treatment in obstructive sleep apnea syndrome: an esophageal impedance-pHmetry study.

PubMed

Ermis, Fatih; Akyuz, Filiz; Arici, Serpil; Uyanikoglu, Ahmet; Yakar, Fatih; Pinarbasi, Binnur; Demir, Kadir; Ozdil, Sadakat; Besisik, Fatih; Kaymakoglu, Sabahattin; Boztas, Gungor; Cuhadaroglu, Caglar; Mungan, Zeynel

2011-01-01

There is an increasing interest for a link between gastroesophageal reflux (GER) and obstructive sleep apnea syndrome (OSAS). There is no study in the literature which examines the relationship between OSAS and esophageal functions in adults with impedance. We first evaluated the role of reflux in OSAS with simultaneous polysomnography and impedance-pHmetry and then investigated whether the effect of proton pump inhibitor (PPI) treatment changes in these parameters. Twenty two OSAS patients who had applied to sleep laboratory between September 2007 and May 2008 were consecutively enrolled to the study. Twenty four hours esophageal impedance study was performed during polysomnographic recording. At least 50% of all apneas in patients must proceed with a reflux event in 2 minute intervals in order to be considered reflux related apnea patient. Pathologic reflux episodes were determined in 20 patients (8 were weakly acidic, 12 were acidic). Reflux dependent apnea was found in 6 patients. There was endoscopically esophagitis in all reflux related apnea patients. There was a negative correlation between initial mean SaO2 and gas reflux events at night (p=0.004, r =-0.588) and mixed reflux events at night (p=0.02, r=0.493). There was a statistically significant regression of AHI (apnea hypopnea index) after 3-months PPI treatment (p=0.012). Reflux may trigger apnea in some of the OSAS patients. Therefore, each OSAS patient must be inquired about esophageal and extraesophageal symptoms of reflux.

Influence of gastric emptying on gastro-esophageal reflux: a combined pH-impedance study.

PubMed

Gourcerol, G; Benanni, Y; Boueyre, E; Leroi, A M; Ducrotte, P

2013-10-01

The involvement of delayed gastric emptying (GE) in the pathophysiology of gastro-esophageal reflux disease (GERD) remains debated and has been to date only assessed using esophageal pH-metry that only detects acidic reflux. We therefore investigated whether delay in GE could impact on liquid, mixed, and gas reflux detected using combined esophageal pH-impedance recording. Thirty consecutive patients were explored with GE and esophageal pH-impedance measurement in the workup of typical symptoms of GERD. Gastric emptying was assessed using the (13) C-octanoic acid breath test and an ambulatory esophageal pH-impedance recording was performed off proton pump inhibitors (PPIs) for 24 h. Gastric emptying was normal in 17 patients and delayed in 13 patients. Delay in GE increased the daily number of liquid/mixed reflux events detected by combined esophageal pH-impedance monitoring, but had no effect of esophageal acid exposure or gas reflux. This translated in increased number of postprandial reflux events, with a longer bolus clearance time and increased esophageal proximal extension. In patient with delayed GE, symptomatic reflux had a higher proximal extension and a longer bolus clearance time compared to symptomatic reflux events from patients with normal GE. Delay in GE increases daily and postprandial liquid/mixed reflux events. Reflux characteristics differently trigger symptoms in patients with normal and delayed GE, and may impact on the therapeutic strategy. © 2013 John Wiley & Sons Ltd.

The association between gastroesophageal flap valve function and gastroesophageal reflux symptoms.

PubMed

Keskin, O; Kalkan, Ç; Yaman, A; Tüzün, A; Soykan, I

2017-01-01

Upper gastrointestinal endoscopic examination is usually the first step in the evaluation of patients with suspected gastroesopageal reflux disease. The primary aim of this study was to investigate the association between gastroesophageal flap valve function (GEFV) and gastroesophapgeal reflux symptoms in patients undergoing routine upper endoscopy. Patients and methods: 1507 patients were included into the study and the GEFV graded I to IV as follows: Hill I-II: normal GEFV, and Hill III-IV: abnormal GEFV. Patients in abnormal GEFV group had a higher incidence of reflux symptoms compared to normal GEFV group (53.4% vs 47.4% for heartburn p=0.03 and 53.2% vs 42.4% for regurgitation, p<0.01). In abnormal GEFV patients, esophagitis was more common compared to those with normal GEFV (32.6% vs 11.1%, p<0.01). Presence of heartburn and regurgitation (n =556) correlated with Hill III-IV grades (n = 184/556), (sensitivity: 33%, p = 0.003). In contrast, 24.6% (157/638) of patients without reflux symptoms were in abnormal GEFV group. In patients undergoing endoscopy because of reflux symptoms, Grade III-IV valve was detected more commonly in patients with reflux symptoms compared to patients without reflux symptoms (p = 0.01). Patients with abnormal valves (Hill grades III and IV) but without reflux symptoms, esophagitis and hiatal hernia should be evaluated individually by means of the presence of gastroesophageal reflux disease which means that GEFV is not a good indicator of reflux disease. © Acta Gastro-Enterologica Belgica.

Effects of taurodihydrofusidate, a bile salt analogue, on bile formation and biliary lipid secretion in the rhesus monkey.

PubMed Central

Beaudoin, M; Carey, M C; Small, D M

1975-01-01

Bile salts play a major role in bile formation and biliary lipid secretion. Sodium taurodihydrofusidate (TDHF), a derivative of the antibiotic fusidic acid, closely resembles bile salts in terms of structure, micellar characteristics, and capacity ot solubilize otherwise insolbule lipids. We have therefore studied the biliary secretion of this bile salt analogue and its influence on bile formation and biliary lipid secretion in primates. Alert, unanesthetized female rhesus monkeys prepared with a total biliary fistula were allowed to reach a steady bile salt secretion rate before each study. In three animals (group I),[14C]TDHF was infused intravenously. Most of the compound was secreted rapidly in bile chemically unchanged. The biliary secretion of this drug produced a twofold increase in bile flow; however, the bile salt output was markedly reduced during the infusion. In spite of this reduction, the phospholipid output remained essentially unchanged whereas the cholesterol output increased almost twofold. In five other animals (group II), the effect of TDHF on the bile salt secretion was further investigated by an intravenous infusion of [14C]taurocholate followed by a combined infusion of [14C]taurocholate and TDHF. When TDHF was added to the infusate, a reduction in the [14C]taurocholate output and a progressive rise in the plasma [14C]taurocholate concentration were observed in each animal. An analysis of the data in both groups indicates that (a) the most likely explanation to account for the decreased bile salt output is that the bile salt analogue, TDHF, interfered with bile salt secretion into the biliary canaliculi; (b) TDHF induces a greater secretion of biliary water than was observed with bile salts, an effect consistent with a stimulation of the bile salt-independent canalicular flow; (c) at similar 3alpha-hydroxysteroid secretion rates TDHF caused a significant increase in cholesterol secretion compared to that induced by bile salt. This finding suggests that TDHF affects cholesterol metabolism or secretion in a way distinct from bile salts. Thus, the solubilization of biliary lipids in mixed micelles, although essential, is only one of the factors which determine their secretion into bile. PMID:811689

Interactions among genetic variants in apoptosis pathway genes, reflux symptoms, body mass index, and smoking indicate two distinct etiologic patterns of esophageal adenocarcinoma.

PubMed

Zhai, Rihong; Chen, Feng; Liu, Geoffrey; Su, Li; Kulke, Matthew H; Asomaning, Kofi; Lin, Xihong; Heist, Rebecca S; Nishioka, Norman S; Sheu, Chau-Chyun; Wain, John C; Christiani, David C

2010-05-10

Apoptosis pathway, gastroesophageal reflux symptoms (reflux), higher body mass index (BMI), and tobacco smoking have been individually associated with esophageal adenocarcinoma (EA) development. However, how multiple factors jointly affect EA risk remains unclear. In total, 305 patients with EA and 339 age- and sex-matched controls were studied. High-order interactions among reflux, BMI, smoking, and functional polymorphisms in five apoptotic genes (FAS, FASL, IL1B, TP53BP, and BAT3) were investigated by entropy-based multifactor dimensionality reduction (MDR), classification and regression tree (CART), and traditional logistic regression (LR) models. In LR analysis, reflux, BMI, and smoking were significantly associated with EA risk, with reflux as the strongest individual factor. No individual single nucleotide polymorphism was associated with EA susceptibility. However, there was a two-way interaction between IL1B + 3954C>T and reflux (P = .008). In both CART and MDR analyses, reflux was also the strongest individual factor for EA risk. In individuals with reflux symptoms, CART analysis indicated that strongest interaction was among variant genotypes of IL1B + 3954C>T and BAT3S625P, higher BMI, and smoking (odds ratio [OR], 5.76; 95% CI, 2.48 to 13.38), a finding independently found using MDR analysis. In contrast, for participants without reflux symptoms, the strongest interaction was found between higher BMI and smoking (OR, 3.27; 95% CI, 1.88 to 5.68), also echoed by entropy-based MDR analysis. Although a history of reflux is an important risk for EA, multifactor interactions also play important roles in EA risk. Gene-environment interaction patterns differ between patients with and without reflux symptoms.

Acid Rather than Non-Acid Reflux Burden is a Predictor of Tooth Erosion

PubMed Central

Ganesh, Meenakshi; Hertzberg, Anne; Nurko, Samuel; Needleman, Howard; Rosen, Rachel

2015-01-01

Objectives The relationship between tooth erosion (TE) and gastroesophageal reflux (GER) in children has not been clearly established and there are no studies to determine the relationship with refluxate height, non-acid reflux and erosions. The aim of this study was to determine the relationship between TE and acid and non-acid GER measured using combined pH and multichannel intraluminal impedance (pH-MII). Methods We conducted a prospective cohort study of children presenting for pH-MII testing. Once consented, patients completed questionnaires about their reflux symptoms and diet, and then underwent pH-MII catheter placement and a dental examination. The Keels-Coffield erosion index was used to score extent and severity of TE. Reflux parameters of patients with and without TE were compared using Student's t test. Results Twenty-seven patients participated in the study, all of whom were on acid suppression at the time of pH-MII testing. Ten out of 27 patients (37%) had TE. There were significant positive correlations between acid reflux episodes (r=0.44, p=0.02), the % time that acid reflux was present in the distal esophagus (r=0.44, p=0.02), and reflux index (r=0.54, p=0.004) with number of TE in a given patient. The % time that acid reflux was present in the proximal esophagus was positively correlated with the number of teeth erosions per patient with borderline significance (r=0.38, p=0.05). Conclusions There was a positive correlation between acid reflux parameters and TE. Acid, rather than non-acid reflux, seems to have a significant role in the pathogenesis of TE. PMID:26230904

A study with pharyngeal and esophageal 24-hour pH-impedance monitoring in patients with laryngopharyngeal symptoms refractory to proton pump inhibitors.

PubMed

Dulery, C; Lechot, A; Roman, S; Bastier, P-L; Stoll, D; de Gabory, L; Zerbib, F

2017-01-01

The role of gastroesophageal reflux in chronic laryngeal symptoms is difficult to establish. The aim of this study was to characterize pharyngeal and esophageal pH-impedance reflux patterns in a group of patients with suspected laryngopharyngeal reflux and to determine predictive factors of response to proton pump inhibitors. Patients with chronic pharyngolaryngeal symptoms were evaluated with a symptom score questionnaire, laryngoscopy, and 24-hour pharyngeal and esophageal pH-impedance monitoring at baseline and after 8-week treatment with esomeprazole 40 mg b.i.d. Response to treatment was defined by a diminution of more than 50% of the score for the primary symptom. Reflux patterns and baseline impedance values were compared to those obtained in 46 healthy subjects. Twenty-four patients were included (17 women, median age 54 years), all previously refractory to antisecretory therapy. Symptom scores were 46 (32-62) and 40 (27-76) off and on therapy, respectively (P=.1). There was no significant difference between patients and controls for pH-impedance reflux parameters and baseline values off and on therapy in distal and proximal esophagus and in the pharynx. Median numbers of pharyngeal reflux were 0 and 0 off and on therapy, respectively. Only two patients were responders to treatment, both with excessive distal reflux but no pharyngeal reflux. Only one patient had abnormal pharyngeal reflux but did not respond to proton pump inhibitors. Patients with suspected laryngopharyngeal reflux refractory to therapy do not exhibit abnormal pharyngeal or esophageal pH-impedance reflux. In these patients, laryngopharyngeal reflux is unlikely. © 2016 John Wiley & Sons Ltd.

Esophageal Body Motility for Clinical Assessment in Patients with Refractory Gastroesophageal Reflux Symptoms

PubMed Central

Jiang, Liuqin; Ye, Bixing; Wang, Ying; Wang, Meifeng; Lin, Lin

2017-01-01

Background/Aims Little data exists about esophageal body dysmotility and reflux patterns in refractory gastroesophageal reflux disease (RGERD) patients off therapy. We aimed to evaluate effects of esophageal body dysmotility on reflux parameters in RGERD patients by combining impedance-pH monitoring and high-resolution manometry (HRM). Methods We retrospectively reviewed the impedance-pH data and HRM metrics in patients with refractory gastroesophageal reflux symptoms. Impedance-pH monitoring and manometric data were compared between 2 groups: ineffective esophageal motility (IEM) and normal motility. Results Forty-eight patients (30 males, mean age 54.5 years) were included (16 erosive esophagitis, 24 non-erosive reflux disease, and 8 functional heartburn), amongst which 24 subjects showed IEM, and others had normal motility. Number of patients who had a large break in the IEM group was significantly higher than that of normal motility patients. IEM group had more patients with weakly acid reflux and long term acid reflux than the normal group (P = 0.008, P = 0.004, respectively). There was no statistical difference in baseine impedance levels from z4 to z6 between the 2 groups (2911 ± 1160 Ω vs 3604 ± 1232 Ω, 2766 ± 1254 Ω vs 3752 ± 1439 Ω, 2349 ± 1131 Ω vs 3038 ± 1254 Ω, all P > 0.05). Acid exposure time, numbers of long term acid reflux and weakly acid reflux showed strong negative correlation with esophageal body motility and/or lower esophageal sphincter function. Conclusions IEM was associated more with acid exposure, abnormal weakly acid reflux, and long term acid reflux in RGERD patients. These data suggested the role of esophageal body dysmotility in the pathophysiological mechanisms of RGERD patients. PMID:27599539

Esophageal Body Motility for Clinical Assessment in Patients with Refractory Gastroesophageal Reflux Symptoms.

PubMed

Jiang, Liuqin; Ye, Bixing; Wang, Ying; Wang, Meifeng; Lin, Lin

2017-01-30

Little data exists about esophageal body dysmotility and reflux patterns in refractory gastroesophageal reflux disease (RGERD) patients off therapy. We aimed to evaluate effects of esophageal body dysmotility on reflux parameters in RGERD patients by combining impedance-pH monitoring and high-resolution manometry (HRM). We retrospectively reviewed the impedance-pH data and HRM metrics in patients with refractory gastroesophageal reflux symptoms. Impedance-pH monitoring and manometric data were compared between 2 groups: ineffective esophageal motility (IEM) and normal motility. Forty-eight patients (30 males, mean age 54.5 years) were included (16 erosive esophagitis, 24 non-erosive reflux disease, and 8 functional heartburn), amongst which 24 subjects showed IEM, and others had normal motility. Number of patients who had a large break in the IEM group was significantly higher than that of normal motility patients. IEM group had more patients with weakly acid reflux and long term acid reflux than the normal group ( P = 0.008, P = 0.004, respectively). There was no statistical difference in baseine impedance levels from z4 to z6 between the 2 groups (2911 ± 1160 Ω vs 3604 ± 1232 Ω, 2766 ± 1254 Ω vs 3752 ± 1439 Ω, 2349 ± 1131 Ω vs 3038 ± 1254 Ω, all P > 0.05). Acid exposure time, numbers of long term acid reflux and weakly acid reflux showed strong negative correlation with esophageal body motility and/or lower esophageal sphincter function. IEM was associated more with acid exposure, abnormal weakly acid reflux, and long term acid reflux in RGERD patients. These data suggested the role of esophageal body dysmotility in the pathophysiological mechanisms of RGERD patients.

Supraesophageal Reflux: Correlation of Position and Occurrence of Acid Reflux-Effect of Head-of-Bed Elevation on Supine Reflux.

PubMed

Scott, David R; Simon, Ronald A

2015-01-01

Supraesophageal reflux of gastric contents can contribute to perennial nasopharyngitis, cough, and asthma. However, effective treatment strategies for supraesophageal reflux disease (SERD) remain inadequately defined. The purpose of this study is to assess the prevalence and timing of SERD and to investigate the efficacy of head-of-bed elevation in its treatment. A retrospective chart review of patients seen at Scripps Clinic Division of Allergy, Asthma and Immunology was performed who had undergone overnight nasopharyngeal pH monitoring with a commercially available nasopharyngeal pH-monitoring device, Dx-pH Measurement System from Restech, San Diego, Calif. Subjects with reflux were classified based on the position of reflux as either supine only, upright only, or both supine and upright. In a subset of subjects with supine-only reflux, pH monitoring was compared before and after elevating the head of bed 6 inches. Adequate nasopharyngeal pH-monitoring data were obtained for 235 patients. Reflux was detected in 113 (48%) patients. The pattern of reflux observed was 62 (55%) supine only, 4 (4%) upright only, and 47 (42%) upright and supine. Sequential overnight nasopharyngeal pH monitoring before and after head-of-bed elevation was obtained in 13 individuals with supine-only reflux. Ten subjects demonstrated significant improvement, 8 of whom demonstrated complete resolution of supine reflux with 6 inches of head-of-bed elevation. This study provides new evidence that SERD frequently occurs in the supine position and that 6 inches of head-of-bed elevation is effective in reducing supine SERD. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Is the Impedance Baseline Helpful in the Evaluation of Globus Patients?

PubMed Central

Chun, Yeon Joo; Choi, Myung-Gyu; Kim, Hyung Hun; Cho, Yu Kyung; Ku, AeKyeong

2015-01-01

Background/Aims Gastroesophageal reflux disease (GERD) has been suggested to be responsible for 23–68% of globus cases. The impedance baseline (IB) acquired by 24-hour multichannel intraluminal impedance monitoring has been proven to represent esophageal mucosal integrity. We aimed to investigate whether the IB is helpful for evaluating globus patients. Methods Twenty-four-hour multichannel intraluminal impedance pH tracings (MII-pH) were evaluated in globus patients. Differences in the IB between the acid reflux, non-acid reflux, and no reflux groups were analyzed. Receiver operating characteristic (ROC) curves were obtained to determine the optimal measurement point from the lower esophageal sphincter (LES). Results A total of 62 patients were analyzed. MII-pH showed that acid reflux, non-acid reflux, and no reflux were present in 13, 5, and 44 patients, respectively. The acid reflux group had a significantly lower IB than the other groups at a location 3 cm from the LES. ROC curve analysis revealed that placement at a position 3 cm from the LES resulted in moderate diagnostic accuracy (area under the curve = 0.88). When we set 2500 Ω as the cut-off value for acid reflux at a position 3 cm from the LES, the additional diagnostic yield for acid reflux was increased by 19.4% compared with that obtained by MII-pH. Conclusions IB is complementary to pH findings enabling identification of a subset of patients with co-existing acid reflux. Catheter placement at a location 3 cm from the LES and a cut-off value of 2500 Ω may be reasonable criteria for estimating acid reflux. PMID:26130634

The clinical value of pharyngeal pH monitoring using a double-probe, triple-sensor catheter in patients with laryngopharyngeal reflux.

PubMed

Muderris, Togay; Gokcan, M Kursat; Yorulmaz, Irfan

2009-02-01

To determine the clinical value of pharyngeal pH monitoring for the diagnosis of laryngopharyngeal reflux (LPR) by using a double-probe, triple-sensor catheter in patients with symptoms of LPR. Prospective review of pH values recorded at the pharyngeal sensor, with the sensor placed in the proximal esophagus in patients with suspected LPR. Tertiary care university hospital. Thirty-three consecutive patients with symptoms of LPR. A pH test result was considered abnormal if a single reflux episode was detected in the hypopharynx and if, in the proximal esophagus, the total percentage of time the pH value was below 4 was 1.0% or higher. Data obtained from sensors were compared to determine the validity of pharyngeal sensor. Correlation between patients' reflux finding scores, reflux finding indexes, and reflux episodes were analyzed. Of 33 patients, 17 had more than 1 reflux episode detected by the pharyngeal sensor and 19 had pathological reflux detected by the proximal esophageal sensor. Four patients who had pharyngeal reflux had a normal esophageal acid exposure time, and 6 patients who had pathological reflux detected by the proximal esophageal sensor did not experienced any pharyngeal reflux episode. Four patients would have had a false-negative test result and 6 subjects would have had a false-positive test result if a hypopharyngeal pH sensor was not implemented. The adjustable, bifurcated, triple-sensor pH probe allows identifying true hypopharyngeal reflux episodes. If single-probe, double-sensor pH monitoring is to be performed, the proximal probe should be placed in the pharynx, not in the upper esophagus.

Gastro-esophageal reflux time parameters and esophagitis in children

DOE Office of Scientific and Technical Information (OSTI.GOV)

Baulieu, F.; Baulieu, J.; Maurage, C.

1985-05-01

The aim of this work was to study the correlation between the reflux timing and the presence of esophagitis, an inconstant but serious complication of gastro-esophageal reflux (GER). The hypothesis was that reflux occurring late after meal can be incriminated more than early reflux in esophagitis genesis. 32 children with GER (mean age = 10.5 months, 2 to 30 months) had esophagoscopy and scintigraphy in the same week. The children were classified in two groups according to esophagoscopy: group 1 (n = 18) no esophagitis, group 2 (n = 14) esophaqgitis. The scintigraphy involved the ingestion of 0.5 mCi Tc-99mmore » sulfur colloid milk mixture, followed by esophageal and gastric activity recording (one image per minute for 1 hour). The reflux was assessed from contrast enhanced images and esophageal time activity curves. Reflux intensity was quantitated by reflux index (Re). Mean reflux time was calculated as the mean esophageal activity peaks time (t-bar). Finally a composite parameter was calculated as the mean reflux time weighted by the relative intensity of each reflux peak (t-barw). Re was not found to be different between the two groups. t-bar was significantly higher in group 2: t-bar = 29.6 +- 3.0 mn (mean +- SD) than in group 1: t-bar = 24.5 +- 6.8 mn; rho <0.02. The difference between the two groups was enhanced by intensity weighting: group 1: t-barw = 16.6 +- 6.3 mn, group 2: t-barw = 33.5 +- 7.1 mn rho <0.001. t-barw value was not correlated to esophagitis grade. These results suggest that late reflux is more likely responsible of esophagitis.« less

Reflux parameters as modified by laparoscopic fundoplication in 40 patients with heartburn/regurgitation persisting despite PPI therapy: a study using impedance-pH monitoring.

PubMed

Frazzoni, Marzio; Conigliaro, Rita; Melotti, Gianluigi

2011-04-01

Patients with typical reflux symptoms (heartburn/regurgitation) persisting despite proton pump inhibitor (PPI) therapy are not uncommon. Impedance-pH monitoring detects gastroesophageal reflux at all pH levels and may establish if ongoing symptoms on PPI therapy are associated with acid/nonacid reflux. Laparoscopic fundoplication is a therapeutic option in such patients but reflux parameters on PPI therapy and after intervention and their relationship with symptom persistence/remission have been scarcely studied. The aim of this study was to assess reflux parameters and their relationship with symptoms before and after laparoscopic fundoplication, on and off PPI therapy, respectively, in patients with PPI-unresponsive heartburn/regurgitation and with a positive symptom-reflux association and/or abnormal reflux parameters detected on PPI therapy. Impedance-pH monitoring was performed on high-dose PPI therapy and 3 months after laparoscopic fundoplication, off PPI therapy, in 40 patients with PPI-unresponsive heartburn/regurgitation. Symptoms were scored by a validated questionnaire. Esophageal acid exposure time as well as the number of total and proximal reflux events and of acid and weakly acidic refluxes decreased significantly after surgery: normal values were found in 100, 77, 95, 92 and 65% of cases, respectively. Weakly alkaline refluxes increased significantly postoperatively but neither before nor after intervention were associated with symptoms. All patients reported total/subtotal remission of heartburn/regurgitation 3 months after surgery. Laparoscopic fundoplication improves acid and weakly acidic reflux parameters when compared with PPI therapy. This improvement justifies the very high post-surgical symptom remission rate that we observed. Prolonged follow-up is warranted but our findings strongly support the surgical option in PPI failures.

Relationship between sleep and acid gastro-oesophageal reflux in neonates.

PubMed

Ammari, Mohamed; Djeddi, Djamal; Léké, André; Delanaud, Stéphane; Stéphan-Blanchard, Erwan; Bach, Véronique; Telliez, Frédéric

2012-02-01

The aim of the present study was to investigate the impact of gastro-oesophageal acid reflux on sleep in neonates and, reciprocally, the influence of wakefulness (W) and sleep stages on the characteristics of the reflux (including the retrograde bolus migration of oesophageal acid contents). The pH and multichannel intraluminal impedance were measured during nocturnal polysomnography in 25 infants hospitalised for suspicion of gastro-oesophageal reflux. Two groups were constituted according to whether or not the infants displayed gastro-oesophageal reflux (i.e. a reflux group and a control group). There were no differences between the reflux and control groups in terms of sleep duration, sleep structure and sleep state change frequency. Vigilance states significantly influenced the gastro-oesophageal reflux pattern: the occurrence of gastro-oesophageal reflux episodes was greater during W (59 ± 32%) and active sleep (AS; 35 ± 30%) than during quiet sleep (QS; 6 ± 11%), whereas the mean duration of gastro-oesophageal reflux episodes was higher in QS than in W and AS. The percentage of retrograde bolus migrations of distal oesophageal acid content was significantly higher in AS (62 ± 26%) than in W (42 ± 26%) and QS (4.5 ± 9%). In neonates, gastro-oesophageal reflux occurred more frequently during W, whereas the physiological changes associated with sleep state increase the physiopathological impact of the gastro-oesophageal reflux. The duration of oesophagus-acid contact was greater during sleep; AS facilitated the retrograde migration of oesophageal acid content, and QS was characterised by the risk of prolonged acid mucosal contact. © 2011 European Sleep Research Society.

Bile Duct Cancer (Cholangiocarcinoma) Symptoms, Tests, Prognosis, and Stages (PDQ®)—Patient Version

Cancer.gov

Bile duct cancer, or cholangiocarcinoma, is rare. Bile ducts are tubes that carry bile between the liver, gallbladder, and small intestine. Bile duct cancer can occur in the intrahepatic, perihilar (Klatskin tumor), or distal extrahepatic area. Learn about tests to diagnose and the stages of bile duct cancer.

Analyses of bile from gallbladders of Arius platystomus, Arius tenuispinis, Pomadasys commersonni and Kishinoella tonggol.

PubMed

Hassan, Amir; Ahmed, Mansoor; Rasheed, Munawwer; Mansoor, Najia; Khan, Rafeeq Alam; Kamal, Mustafa; Rashid, Mohammad Abdur

2015-07-01

Bile from gallbladders of Arius platystomus (Singhara), Arius tenuispinis (Khagga), Pomadasys commersonni (Holoola) and Kishinoella tonggol (Dawan) were derivatised and analysed by GC-MS for identification of bile acids and bile alcohols. Cholic acid and Chenodeoxycholic acid were found as major bile acids in Arius platystomus, Arius tenuispinis and Pomadasys commersonni. Other bile acids identified in Arius platystomus were allochenodeoxycholic acid, allodeoxycholic acid, 3α,7α,12α-trihydroxy-24-methyl-5β-cholestane-26-oic acid, and 3α,7α,12α, 24-tetrahydroxy-5α-cholestane-26-oic acid. Cholesterol was found as major bile alcohol in Arius platystomus, Arius tenuispinis and Pomadasys commersonni. Cholic acid was the major bile acid identified in the bile of Kishinoella tonggol while other bile acids included 3α,7α,12α-tridydroxy-5α-cholestanoic acid and 3α,7α,12α-tridydroxy-5β-cholestanoic acid. Bile alcohol 5β-cyprinol was present in significant amounts with 5β-cholestane-3α,7α,12α,24-tetrol being the other contributors in the bile of Kishinoella tonggol.

Altered intestinal bile salt biotransformation in a cystic fibrosis (Cftr-/-) mouse model with hepato-biliary pathology.

PubMed

Bodewes, Frank A J A; van der Wulp, Mariëtte Y M; Beharry, Satti; Doktorova, Marcela; Havinga, Rick; Boverhof, Renze; James Phillips, M; Durie, Peter R; Verkade, Henkjan J

2015-07-01

Cftr(-/-tm1Unc) mice develop progressive hepato-biliary pathology. We hypothesize that this liver pathology is related to alterations in biliary bile hydrophobicity and bile salt metabolism in Cftr(-/-tm1Unc) mice. We determined bile production, biliary and fecal bile salt- and lipid compositions and fecal bacterial composition of C57BL/6J Cftr(-/-tm1Unc) and control mice. We found no differences between the total biliary bile salt or lipid concentrations of Cftr(-/-) and controls. Compared to controls, Cftr(-/-) mice had a ~30% higher bile production and a low bile hydrophobicity, related to a ~7 fold higher concentration of the choleretic and hydrophilic bile salt ursocholate. These findings coexisted with a significantly smaller quantity of fecal Bacteroides bacteria. Liver pathology in Cftr(-/-tm1Unc) is not related to increased bile hydrophobicity. Cftr(-/-) mice do however display a biliary phenotype characterized by increased bile production and decreased biliary hydrophobicity. Our findings suggest Cftr dependent, alterations in intestinal bacterial biotransformation of bile salts. Copyright © 2014. Published by Elsevier B.V.

Gastro-oesophageal reflux and cough.

PubMed

Abdulqawi, Rayid; Houghton, Lesley A; Smith, Jaclyn A

2013-05-01

Gastro-oesophageal reflux, either singly or in association with postnasal drip and/or asthma is considered to be a cause of chronic cough. The amount and nature of gastro-oesophageal reflux however is often normal with acid suppression having very little, if any therapeutic effect in these patients. This review examines the challenges posed when exploring the reflux-cough link, and discusses the merits and limitations of the proposed mechanisms of reflux leading to cough.

The MUC4 membrane-bound mucin regulates esophageal cancer cell proliferation and migration properties: Implication for S100A4 protein

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bruyere, Emilie; Jonckheere, Nicolas; Frenois, Frederic

2011-09-23

Highlights: {yields} Loss of MUC4 reduces proliferation of esophageal cancer cells. {yields} MUC4 inhibition impairs migration of esophageal cancer cells but not their invasion. {yields} Loss of MUC4 significantly reduces in vivo tumor growth. {yields} Decrease of S100A4 induced by MUC4 inhibition impairs proliferation and migration. -- Abstract: MUC4 is a membrane-bound mucin known to participate in tumor progression. It has been shown that MUC4 pattern of expression is modified during esophageal carcinogenesis, with a progressive increase from metaplastic lesions to adenocarcinoma. The principal cause of development of esophageal adenocarcinoma is the gastro-esophageal reflux, and MUC4 was previously shown tomore » be upregulated by several bile acids present in reflux. In this report, our aim was thus to determine whether MUC4 plays a role in biological properties of human esophageal cancer cells. For that stable MUC4-deficient cancer cell lines (shMUC4 cells) were established using a shRNA approach. In vitro (proliferation, migration and invasion) and in vivo (tumor growth following subcutaneous xenografts in SCID mice) biological properties of shMUC4 cells were analyzed. Our results show that shMUC4 cells were less proliferative, had decreased migration properties and did not express S100A4 protein when compared with MUC4 expressing cells. Absence of MUC4 did not impair shMUC4 invasiveness. Subcutaneous xenografts showed a significant decrease in tumor size when cells did not express MUC4. Altogether, these data indicate that MUC4 plays a key role in proliferative and migrating properties of esophageal cancer cells as well as is a tumor growth promoter. MUC4 mucin appears thus as a good therapeutic target to slow-down esophageal tumor progression.« less

Composition of gallbladder bile in healthy individuals and patients with gallstone disease from north and South India.

PubMed

Jayanthi, V; Sarika, S; Varghese, Joy; Vaithiswaran, V; Sharma, Malay; Reddy, Mettu Srinivas; Srinivasan, Vijaya; Reddy, G M M; Rela, Mohamed; Kalkura, S

2016-09-01

Gallstones (GS) in south India (SI) are predominantly pure pigment or mixed, while in North India (NI), these are either pure cholesterol or mixed. While cholesterol rich gallbladder (GB) bile predicts cholesterol GS, constituent of bile in primary pigment GS is not known. We compared the composition of GB bile from healthy liver donors and patients with GS from north and south India. Gallbladder bile from healthy liver donors from north (10) and south India (8) served as controls. Cases were patients from north (21) and south India (17) who underwent cholecystectomy for GS disease. Gallbladder bile from both cases and controls was analyzed for cholesterol, lecithin (phospholipid), and bile salts. Gallstones were classified as cholesterol, mixed, and pigment based on morphology and biochemical analysis. The median cholesterol concentration in control bile from north was significantly high compared to south (p<0.001) with no difference in lecithin and bile salts (p NS). Except for one sample each from north and south, the cholesterol solubility of controls was within the critical micellar zone. Mixed GS were most frequent in north India (61.9 %) while pigment GS dominated in south (61.9 %). The median cholesterol concentration in bile samples of cholecystectomy patients from north India was significantly high GS (p < 0.00001) with significant lowering of bile salts and lecithin (p < 0.00001). In south India, patients with mixed GS had high cholesterol content in bile compared to controls and patients with pigment GS; bile in latter had significantly higher concentration of bile salt compared to controls and mixed GS. The ternary plot confirmed the composition of GB bile from north and south India. Gallbladder bile in controls and patients with GS from north India had significantly high cholesterol concentration. In south India, patients with mixed GS had cholesterol rich bile while pigment GS had higher concentrations of bile salts.

Influence of exercise testing in gastroesophageal reflux in patients with gastroesophageal reflux disease.

PubMed

Mendes-Filho, Antonio Moreira; Moraes-Filho, Joaquim Prado Pinto; Nasi, Ary; Eisig, Jaime Natan; Rodrigues, Tomas Navarro; Barbutti, Ricardo Correa; Campos, Josemberg Marins; Chinzon, Decio

2014-01-01

Gastroesophageal reflux disease is a worldwide prevalent condition that exhibits a large variety of signs and symptoms of esophageal or extra-esophageal nature and can be related to the esophagic adenocarcinoma. In the last few years, greater importance has been given to the influence of physical exercises on it. Some recent investigations, though showing conflicting results, point to an exacerbation of gastroesophageal reflux during physical exercises. To evaluate the influence of physical activities in patients presenting with erosive and non erosive disease by ergometric stress testing and influence of the lower esophageal sphincter tonus and body mass index during this situation. Twenty-nine patients with erosive disease (group I) and 10 patients with non-erosive disease (group II) were prospectively evaluated. All the patients were submitted to clinical evaluation, followed by upper digestive endoscopy, manometry and 24 h esophageal pH monitoring. An ergometric testing was performed 1 h before removing the esophageal pH probe. During the ergometric stress testing, the following variables were analyzed: test efficacy, maximum oxygen uptake, acid reflux duration, gastroesophageal reflux symptoms, influence of the lower esophageal sphincter tonus and influence of body mass index in the occurrence of gastroesophageal reflux during these physical stress. Maximum oxigen consumption or VO 2 max, showed significant correlation when it was 70% or higher only in the erosive disease group, evaluating the patients with or without acid reflux during the ergometric testing (p=0,032). The other considered variables didn't show significant correlations between gastroesophageal reflux and physical activity (p>0,05). 1) Highly intensive physical activity can predispose the occurrence of gastroesophageal reflux episodes in gastroesophageal reflux disease patients with erosive disease; 2) light or short sessions of physical activity have no influence on reflux, regardless of body mass index; 3) the lower esophageal sphincter tonus does not influence the occurrence of reflux disease episodes during exercise testing.

A Mixed-Methods Study of Patient Views on Reflux Symptoms and Medication Routines.

PubMed

Pisegna, Jessica M; Yang, Sky; Purcell, Audrey; Rubio, Alix

2017-05-01

Gastroesophageal reflux disease is a chronic disorder often accompanied by laryngopharyngeal reflux. Speech-language pathologists are tasked with treating these patients with voice, dysphagia, and/or reflux therapy. This study investigated patient-reported reasons for reduced compliance with recommended reflux treatment and the top symptoms in patients with reflux, dysphagia, and voice symptoms. This study used a cross-sectional qualitative and quantitative mixed-methods design to identify and describe patients' reflux symptoms and reflux medication routines. Fifty-one patients completed a face-to-face, semistructured interview, a questionnaire, and the Reflux Symptom Index (RSI). Interview transcripts were coded by authors for concepts in two cycles. During the 51 interviews, the top four reported symptoms were heartburn (n = 17), mucous (n = 11), dysphagia, and globus (n = 10). Further, 62.7% (n = 32/51) described an incorrect routine in taking their proton pump inhibitor (PPI): taking it with other pills, taking it with food/drink, and uncertainty about which pill is for reflux. RSI scores were moderately correlated with patient-reported reflux severity (r = 0.62, P < 0.0001, r 2  = 0.34). Correct compliance with PPI timing was not enough to significantly lower RSI scores more than those who did not comply (an average RSI of 20.0 vs. 25.9, P = 0.1252). Literature has not described the most relevant reflux-related symptoms and why PPI compliance is notoriously poor, from the patients' perspective. The results of this study confirm that PPI compliance is poor, and the reasons for poor compliance could have been prevented with patient education. Even when PPI compliance was adequate, symptoms like globus, mucous, voice dysfunction, and dysphagia persisted. Other interventions such as evidence-based diet and behavioral changes should be a part of voice/dysphagia/reflux therapy. Copyright © 2017 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

Post-prandial reflux suppression by a raft-forming alginate (Gaviscon Advance) compared to a simple antacid documented by magnetic resonance imaging and pH-impedance monitoring: mechanistic assessment in healthy volunteers and randomised, controlled, double-blind study in reflux patients.

PubMed

Sweis, R; Kaufman, E; Anggiansah, A; Wong, T; Dettmar, P; Fried, M; Schwizer, W; Avvari, R K; Pal, A; Fox, M

2013-06-01

Alginates form a raft above the gastric contents, which may suppress gastro-oesophageal reflux; however, inconsistent effects have been reported in mechanistic and clinical studies. To visualise reflux suppression by an alginate-antacid [Gaviscon Advance (GA), Reckitt Benckiser, UK] compared with a nonraft-forming antacid using magnetic resonance imaging (MRI), and to determine the feasibility of pH-impedance monitoring for assessment of reflux suppression by alginates. Two studies were performed: (i) GA and antacid (Alucol, Wander Ltd, Switzerland) were visualised in the stomach after ingestion in 12 healthy volunteers over 30 min after a meal by MRI, with reflux events documented by manometry. (ii) A randomised controlled, double-blind cross-over trial of post-prandial reflux suppression documented by pH-impedance in 20 patients randomised to GA or antacid (Milk of Magnesia; Boots, UK) after two meals taken 24 h apart. MRI visualized a "mass" of GA form at the oesophago-gastric junction (OGJ); simple antacid sank to the distal stomach. The number of post-prandial common cavity reflux events was less with GA than antacid [median 2 (0-5) vs. 5 (1-11); P < 0.035]. Distal reflux events and acid exposure measured by pH-impedance were similar after GA and antacid. There was a trend to reduced proximal reflux events with GA compared with antacid [10.5 (8.9) vs. 13.9 (8.3); P = 0.070]. Gaviscon Advance forms a 'mass' close to the OGJ and significantly suppresses reflux compared with a nonraft-forming antacid. Standard pH-impedance monitoring is suitable for clinical studies of GA in gastro-oesophageal reflux disease patients where proximal reflux is the primary outcome. © 2013 Blackwell Publishing Ltd.

INFLUENCE OF EXERCISE TESTING IN GASTROESOPHAGEAL REFLUX IN PATIENTS WITH GASTROESOPHAGEAL REFLUX DISEASE

PubMed Central

MENDES-FILHO, Antonio Moreira; MORAES-FILHO, Joaquim Prado Pinto; NASI, Ary; EISIG, Jaime Natan; RODRIGUES, Tomas Navarro; BARBUTTI, Ricardo Correa; CAMPOS, Josemberg Marins; CHINZON, Décio

2014-01-01

Background Gastroesophageal reflux disease is a worldwide prevalent condition that exhibits a large variety of signs and symptoms of esophageal or extra-esophageal nature and can be related to the esophagic adenocarcinoma. In the last few years, greater importance has been given to the influence of physical exercises on it. Some recent investigations, though showing conflicting results, point to an exacerbation of gastroesophageal reflux during physical exercises. Aim To evaluate the influence of physical activities in patients presenting with erosive and non erosive disease by ergometric stress testing and influence of the lower esophageal sphincter tonus and body mass index during this situation. Methods Twenty-nine patients with erosive disease (group I) and 10 patients with non-erosive disease (group II) were prospectively evaluated. All the patients were submitted to clinical evaluation, followed by upper digestive endoscopy, manometry and 24 h esophageal pH monitoring. An ergometric testing was performed 1 h before removing the esophageal pH probe. During the ergometric stress testing, the following variables were analyzed: test efficacy, maximum oxygen uptake, acid reflux duration, gastroesophageal reflux symptoms, influence of the lower esophageal sphincter tonus and influence of body mass index in the occurrence of gastroesophageal reflux during these physical stress. Results Maximum oxigen consumption or VO 2 max, showed significant correlation when it was 70% or higher only in the erosive disease group, evaluating the patients with or without acid reflux during the ergometric testing (p=0,032). The other considered variables didn't show significant correlations between gastroesophageal reflux and physical activity (p>0,05). Conclusions 1) Highly intensive physical activity can predispose the occurrence of gastroesophageal reflux episodes in gastroesophageal reflux disease patients with erosive disease; 2) light or short sessions of physical activity have no influence on reflux, regardless of body mass index; 3) the lower esophageal sphincter tonus does not influence the occurrence of reflux disease episodes during exercise testing. PMID:24676289

Impact of Gut Microbiota-Mediated Bile Acid Metabolism on the Solubilization Capacity of Bile Salt Micelles and Drug Solubility.

PubMed

Enright, Elaine F; Joyce, Susan A; Gahan, Cormac G M; Griffin, Brendan T

2017-04-03

In recent years, the gut microbiome has gained increasing appreciation as a determinant of the health status of the human host. Bile salts that are secreted into the intestine may be biotransformed by enzymes produced by the gut bacteria. To date, bile acid research at the host-microbe interface has primarily been directed toward effects on host metabolism. The aim of this work was to investigate the effect of changes in gut microbial bile acid metabolism on the solubilization capacity of bile salt micelles and consequently intraluminal drug solubility. First, the impact of bile acid metabolism, mediated in vivo by the microbial enzymes bile salt hydrolase (BSH) and 7α-dehydroxylase, on drug solubility was assessed by comparing the solubilization capacity of (a) conjugated vs deconjugated and (b) primary vs secondary bile salts. A series of poorly water-soluble drugs (PWSDs) were selected as model solutes on the basis of an increased tendency to associate with bile micelles. Subsequently, PWSD solubility and dissolution was evaluated in conventional biorelevant simulated intestinal fluid containing host-derived bile acids, as well as in media modified to contain microbial bile acid metabolites. The findings suggest that deconjugation of the bile acid steroidal core, as dictated by BSH activity, influences micellar solubilization capacity for some PWSDs; however, these differences appear to be relatively minor. In contrast, the extent of bile acid hydroxylation, regulated by microbial 7α-dehydroxylase, was found to significantly affect the solubilization capacity of bile salt micelles for all nine drugs studied (p < 0.05). Subsequent investigations in biorelevant media containing either the trihydroxy bile salt sodium taurocholate (TCA) or the dihydroxy bile salt sodium taurodeoxycholate (TDCA) revealed altered drug solubility and dissolution. Observed differences in biorelevant media appeared to be both drug- and amphiphile (bile salt/lecithin) concentration-dependent. Our studies herein indicate that bile acid modifications occurring at the host-microbe interface could lead to alterations in the capacity of intestinal bile salt micelles to solubilize drugs, providing impetus to consider the gut microbiota in the drug absorption process. In the clinical setting, disruption of the gut microbial ecosystem, through disease or antibiotic treatment, could transform the bile acid pool with potential implications for drug absorption and bioavailability.

Reflux Hypersensitivity: A New Functional Esophageal Disorder

PubMed Central

Yamasaki, Takahisa; Fass, Ronnie

2017-01-01

Reflux hypersensitivity, recently introduced by Rome IV as a new functional esophageal disorder, is currently considered as the presence of typical heartburn symptoms in patients with normal upper endoscopy and esophageal biopsies, normal esophageal pH test and with evidence of a close correlation between patients’ heartburn and reflux events. Reflux hypersensitivity is very common and together with functional heartburn accounts for more than 90% of the heartburn patients who failed treatment with proton pump inhibitor twice daily. In addition, reflux hypersensitivity affects primarily young to middle aged women, commonly overlaps with another functional gastrointestinal disorders, and is often associated with some type of psychological comorbidity. Diagnosis is made by using endoscopy with esophageal biopsies, pH-impedance, and high-resolution esophageal manometry. Reflux hypersensitivity is primarily treated with esophageal neuromodulators, such as tricyclic anti-depressants and selective serotonin reuptake inhibitors among others. Surgical anti-reflux management may also play an important role in the treatment of reflux hypersensitivity. PMID:28992673

Respiratory disease and the oesophagus: reflux, reflexes and microaspiration.

PubMed

Houghton, Lesley A; Lee, Augustine S; Badri, Huda; DeVault, Kenneth R; Smith, Jaclyn A

2016-08-01

Gastro-oesophageal reflux is associated with a wide range of respiratory disorders, including asthma, isolated chronic cough, idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease and cystic fibrosis. Reflux can be substantial and reach the proximal margins of the oesophagus in some individuals with specific pulmonary diseases, suggesting that this association is more than a coincidence. Proximal oesophageal reflux in particular has led to concern that microaspiration might have an important, possibly even causal, role in respiratory disease. Interestingly, reflux is not always accompanied by typical reflux symptoms, such as heartburn and/or regurgitation, leading many clinicians to empirically treat for possible gastro-oesophageal reflux. Indeed, costs associated with use of acid suppressants in pulmonary disease far outweigh those in typical GERD, despite little evidence of therapeutic benefit in clinical trials. This Review comprehensively examines the possible mechanisms that might link pulmonary disease and oesophageal reflux, highlighting the gaps in current knowledge and limitations of previous research, and helping to shed light on the frequent failure of antireflux treatments in pulmonary disease.

PP-16 WEAK ACID REFLUX A TRIGGER FOR RECURRENT RESPIRATORY DISEASES IN CHILDREN.

PubMed

Kostovski, Aco; Zdraveska, Nikolina

2015-10-01

The main advantage of multichannel intraluminar impedance (MII) compared with pH monitoring is its ability to detect both acid and non-acid gastroesophageal reflux (GER) and to determine the characteristics of reflux (liquid or gas). To compare the value of pH monitoring and MII for diagnosis of GER in children who present with refractory respiratory symptoms. A prospective study that included 37 patients, aged 4.25 ± 3.15 years, using combined MII-pH monitoring was performed. Patients were referred for investigation because of suspected GER as the etiology of recurrent respiratory diseases, including recurrent obstructive bronchitis, recurrent pneumonia, laryngitis, and chronic cough. We analyzed the percentage of time during which the pH was less than 4, the numeric and percentile values of acid, weak acid, and non-acid reflux episodes, and the values of liquid and mixed reflux. Diagnostic values were determined separately for pH monitoring and MII using Fisher's exact test. Reflux was detected in 31 patients. pH monitoring was positive in 20 patients (% time during which pH <4 was 17.72 ± 12.06) and negative in 17 patients (2.93% ± 1.67). Both pH and MII were positive in 19 patients: in 11 patients, MII was positive and pH was negative, and in 6 patients, both were negative. Fisher's exact test showed significant statistical difference and superiority of MII in diagnosing GER (p = 0.033). Out of 30 patients with MII-positive results, 15 had both acid and weak acid reflux episodes, 3 had only acid reflux, 8 had weak acid reflux, and 3 had non-acid reflux. Sixteen patients had mixed (liquid and gas) reflux, and 14 had both liquid and mixed reflux. This study suggests that significant numbers of GER include weak acid reflux that cannot be detected by pH probes alone. The weak acid reflux could be a trigger for recurrent respiratory symptoms. Combining pH with MII monitoring is a valuable diagnostic method for diagnosing GER in children.

Predictive factors for outcomes of patients undergoing endoscopic therapy for bile leak after hepatobiliary surgery.

PubMed

Yabe, Shuntaro; Kato, Hironari; Mizukawa, Sho; Akimoto, Yutaka; Uchida, Daisuke; Seki, Hiroyuki; Tomoda, Takeshi; Matsumoto, Kazuyuki; Yamamoto, Naoki; Horiguchi, Shigeru; Tsutsumi, Koichiro; Okada, Hiroyuki

2017-05-01

Endoscopic procedures are used as first-line treatment for bile leak after hepatobiliary surgery. Advances have been made in endoscopic techniques and devices, but few reports have described the effectiveness of endoscopic procedures and the management principles based on severity of bile leak. We evaluated the effectiveness of an endoscopic procedure for the treatment of bile leak after hepatobiliary surgery. Fifty-eight patients underwent an endoscopic procedure for suspected bile leak after hepatobiliary surgery; the presence of bile leak on endoscopic retrograde cholangiopancreatography (ERCP) was evaluated retrospectively. Two groups were created based on bile leak severity at ERCP. We defined success as follows: technical, successful placement of the plastic stent at the intended bile duct; clinical, improvement in symptoms of bile leak; and eventual, disappearance of bile leak at ERCP. We evaluated several factors that influenced the success of the endoscopic procedure and the differences between bile leak severity. Success rates were as follows: technical, 90%; clinical, 79%; and eventual, 71%. Median interval between first endoscopic procedure and achievement of eventual success was 135 days (IQR, 86-257 days). Bile leak severity was the only independent factor associated with eventual success (P = 0.01). Endoscopic therapy is safe and effective for postoperative bile leak. Bile leak severity is the most important factor influencing successful endoscopic therapy. © 2016 Japan Gastroenterological Endoscopy Society.

Esophageal abnormalities in gastroesophageal reflux disease.

PubMed

Levine, Marc S; Carucci, Laura R

2018-06-01

Fluoroscopic esophagography is a widely available, safe, and inexpensive test for detecting gastroesophageal reflux disease. In this article, we review the technique for performing a high-quality esophagram, including upright, double-contrast views of the esophagus and cardia with high-density barium; prone, single-contrast views of the esophagus with low-density barium; and evaluation of gastroesophageal reflux. We then discuss the radiographic findings associated with gastroesophageal reflux disease, including esophageal dysmotility, reflux esophagitis, peptic strictures, and Barrett's esophagus. Finally, we consider the differential diagnosis for the various radiographic findings associated with this condition. When carefully performed and interpreted, the esophagram is a useful test for evaluating gastroesophageal reflux disease and its complications.

Refractory chronic cough due to gastroesophageal reflux: Definition, mechanism and management

PubMed Central

Lv, Han-Jing; Qiu, Zhong-Min

2015-01-01

Refractory chronic cough due to gastroesophageal reflux is a troublesome condition unresponsive to the standard medical anti-reflux therapy. Its underlying mechanisms may include incomplete acid suppression, non-acid reflux, transient lower esophageal sphincter relaxations and esophageal hypersensitivity. The diagnosis of this disorder depends on both the findings of multi-channel intraluminal impedance-pH monitoring and the subsequent intensified anti-reflux therapy. The strategies of pharmacological treatment for refractory chronic cough due to reflux include the optimization of proton pump inhibitors and add-on therapies with histamine H2 receptor antagonists, baclofen and gabapentin. However, the further study is needed to satisfy its management. PMID:26413488

Dental erosions and other extra-oesophageal symptoms of gastro-oesophageal reflux disease: Evidence, treatment response and areas of uncertainty.

PubMed

Pauwels, Ans

2015-04-01

Extra-oesophageal symptoms of gastro-oesophageal reflux disease (GORD) are often studied, but remain a subject of debate. It has been clearly shown that there is a relationship between the extra-oesophageal symptoms chronic cough, asthma, laryngitis and dental erosion and GORD. Literature is abundant concerning reflux-related cough and reflux-related asthma, but much less is known about reflux-related dental erosions. The prevalence of dental erosion in GORD and vice versa, the prevalence of GORD in patients with dental erosion is high but the exact mechanism of reflux-induced tooth wear erosion is still under review.

Dental erosions and other extra-oesophageal symptoms of gastro-oesophageal reflux disease: Evidence, treatment response and areas of uncertainty

PubMed Central

2015-01-01

Extra-oesophageal symptoms of gastro-oesophageal reflux disease (GORD) are often studied, but remain a subject of debate. It has been clearly shown that there is a relationship between the extra-oesophageal symptoms chronic cough, asthma, laryngitis and dental erosion and GORD. Literature is abundant concerning reflux-related cough and reflux-related asthma, but much less is known about reflux-related dental erosions. The prevalence of dental erosion in GORD and vice versa, the prevalence of GORD in patients with dental erosion is high but the exact mechanism of reflux-induced tooth wear erosion is still under review. PMID:25922676

Reflux oesophagitis and Helicobacter pylori infection in elderly patients.

PubMed Central

Liston, R.; Pitt, M. A.; Banerjee, A. K.

1996-01-01

Helicobacter pylori is associated with gastritis, peptic ulcers and gastric malignancies. Little attention has been paid to the possibility that it may also have a role in the pathogenesis of reflux oesophagitis. This is especially true in elderly patients who have life-long infection and provide an ideal group to study the mucosal changes associated with the organism. The aim of this study was to determine if H pylori is associated with reflux oesophagitis in elderly patients. Consecutive gastroscopy patients were recruited. Multiple biopsies were taken from oesophagus, stomach, antrum and duodenum for histology and rapid urease tests. Patients also had IgG ELISA antibodies and 13C-urea breath tests performed. Patients with macroscopic or microscopic evidence of reflux oesophagitis were compared to patients with macroscopically normal upper gastrointestinal tracts and no microscopic evidence of reflux. A total of 114 patients were recruited, average age 78.9 years (+/- 5.4). There were 37 refluxers and 33 non-refluxers. We found no evidence for an association between the presence of H pylori and reflux oesophagitis in elderly patients. The high prevalence of H pylori in patients with reflux oesophagitis can be explained by the presence of incidental gastritis. PMID:8733530

[Underlying Mechanisms and Management of Refractory Gastroesophageal Reflux Disease].

PubMed

Lee, Kwang Jae

2015-08-01

The prevalence of gastroesophageal reflux disease (GERD) in South Korea has increased over the past 10 years. Patients with erosive reflux disease (ERD) shows better response to proton pump inhibitors (PPIs) than those with non-erosive reflux disease (NERD). NERD is a heterogeneous condition, showing pathological gastroesophageal reflux or esophageal hypersensitivity to reflux contents. NERD patients with pathological gastroesophageal reflux or hypersensitivity to acid may respond to PPIs. However, many patients with esophageal hypersensitivity to nonacid or functional heartburn do not respond to PPIs. Therefore, careful history and investigations are required when managing patients with refractory GERD who show poor response to conventional dose PPIs. Combined pH-impedance studies and a PPI diagnostic trial are recommended to reveal underlying mechanisms of refractory symptoms. For those with ongoing reflux-related symptoms, split dose administration, change to long-acting PPIs or PPIs less influenced by CYP2C19 genotypes, increasing dose of PPIs, and the addition of alginate preparations, prokinetics, selective serotonin reuptake inhibitors, or tricyclic antidepressants can be considered. Pain modulators, selective serotonin reuptake inhibitors, or tricyclic antidepressants are more likely to be effective for those with reflux-unrelated symptoms. Surgery or endoscopic per oral fundoplication may be effective in selected patients.

The feasibility and advantages of billroth-I reconstruction in distal gastric cancers following resection.

PubMed

Ganesh, M S; Reddy, K G; Venkata Subbareddy, D S

2012-01-01

Gastric carcinomas are common malignancies in southern India and distal stomach remains the commonest site in low socio economic groups. Surgery still remains an important modality of treatment to achieve local control and also relieve obstructive symptoms. In this study we investigated the feasibility of performing a gastrectomy and billroth-1 type of anastomosis in a rural cancer center setting, with parameters like adequacy of margins, ease of anastomosis and its functional results were analysed. Eight patients presenting to a rurally based cancer center underwent a distal gastrectomy and billroth-1 type of anastomosis for continuity restoration. All the patients had adequate proximal and distal marg. The surgical time varied between-hrs. The anastomosis was constructed without any tension on bowel ends in all patients. The average time to start oral feeds varied between- None of the patients showed symptoms of bile reflux nor dumping. The average hospital stay varied between. Billroth-1 anastomosis is a physiologically more natural way of restoring continuity following a gastrectomy and it is a procedure which would be technically more simpler and decrease per and post operative complications and allow speedier post operative recovery following surgery on distal gastric cancers.

Acute pancreatitis with saw palmetto use: a case report.

PubMed

Bruminhent, Jackrapong; Carrera, Perliveh; Li, Zhongzhen; Amankona, Raymond; Roberts, Ingram M

2011-08-25

Saw palmetto is a phytotherapeutic agent commercially marketed for the treatment of benign prostatic hyperplasia. Evidence suggests that saw palmetto is a safe product, and mild gastrointestinal adverse effects have been reported with its use. We report a case of acute pancreatitis, possibly secondary to the use of saw palmetto. A 61-year-old Caucasian man with a history of benign prostatic hyperplasia and gastroesophageal reflux disease developed epigastric pain associated with nausea 36 hours prior to presentation. He denied drinking alcohol prior to the development of his symptoms. His home medications included saw palmetto, lansoprazole and multivitamins. Laboratory results revealed elevated lipase and amylase levels. An abdominal ultrasound demonstrated a nondilated common bile duct, without choledocholithiasis. Computed tomography of his abdomen showed the pancreatic tail with peripancreatic inflammatory changes, consistent with acute pancreatitis. Our patient's condition improved with intravenous fluids and pain management. On the fourth day of hospitalization his pancreatic enzymes were within normal limits: he was discharged home and advised to avoid taking saw palmetto. It is our opinion that a relationship between saw palmetto and the onset of acute pancreatitis is plausible, and prescribers and users of saw palmetto should be alert to the possibility of such adverse reactions.

Haemorrhoids are associated with internal iliac vein reflux in up to one-third of women presenting with varicose veins associated with pelvic vein reflux.

PubMed

Holdstock, J M; Dos Santos, S J; Harrison, C C; Price, B A; Whiteley, M S

2015-03-01

To determine the prevalence of haemorrhoids in women with pelvic vein reflux, identify which pelvic veins are associated with haemorrhoids and assess if extent of pelvic vein reflux influences the prevalence of haemorrhoids. Females presenting with leg varicose veins undergo duplex ultrasonography to assess all sources of venous reflux. Those with significant reflux arising from the pelvis are offered transvaginal duplex ultrasound (TVS) to evaluate reflux in the ovarian veins and internal Iliac veins and associated pelvic varices in the adnexa, vulvar/labial veins and haemorrhoids. Patterns and severity of reflux were evaluated. Between January 2010 and December 2012, 419 female patients with leg or vulvar varicose vein patterns arising from the pelvis underwent TVS. Haemorrhoids were identified on TVS via direct tributaries from the internal Iliac veins in 152/419 patients (36.3%) and absent in 267/419 (63.7%). The prevalence of the condition increased with the number of pelvic trunks involved. There is a strong association between haemorrhoids and internal Iliac vein reflux. Untreated reflux may be a cause of subsequent symptomatic haemorrhoids. Treatment with methods proven to work in conditions caused by pelvic vein incompetence, such as pelvic vein embolisation and foam sclerotherapy, could be considered. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Esophageal chemical clearance and baseline impedance values in patients with chronic autoimmune atrophic gastritis and gastro-esophageal reflux disease.

PubMed

Tenca, Andrea; de Bortoli, Nicola; Mauro, Aurelio; Frazzoni, Marzio; Savarino, Edoardo; Massironi, Sara; Russo, Salvatore; Bertani, Lorenzo; Marchi, Santino; Penagini, Roberto

2017-09-01

The factors influencing new markers of gastro-esophageal reflux disease detected by impedance-pH monitoring - mean nocturnal baseline impedance (MNBI) and post-reflux swallow-induced peristaltic wave (PSPW) index - need to be evaluated. To compare endoscopy-negative heartburn with chronic autoimmune atrophic gastritis (CAAG). 24 patients with CAAG, 25 with non-erosive reflux disease (NERD) and 25 with functional heartburn (FH) were included. In all patients the main impedance-pH monitoring parameters were calculated. CAAG and NERD patients had a number of reflux events (non-acid ones being more common among the former group) which was higher than that found in FH (p<0.001). MNBI decreased progressively in FH (>3000Ohm), CAAG (>2000Ohm) and NERD (<1000Ohm) patients (p=0.0046). The PSPW index was similar between CAAG and NERD patients but significantly lower in comparison to FH (p<0.0001). Patients with CAAG have evidence of non-acid reflux based on the high number of reflux events and confirmed by low values of MNBI and PSPW index. MNBI is a strong marker of acid/non-acid reflux-induced mucosal damage, whereas the PSPW index can reliably discriminate patients with reflux from those with FH, independently of the acidity of refluxate. Copyright © 2017 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Do laryngoscopic findings reflect the characteristics of reflux in patients with laryngopharyngeal reflux?

PubMed

Lee, Y C; Kwon, O E; Park, J M; Eun, Y G

2018-02-01

To analyse the association between 24-hour multichannel intraluminal impedance-pH (24-h MII-pH) parameters and each item of the reflux finding score (RFS) to determine whether the laryngoscopic findings of the RFS could reflect the characteristics of reflux in patients with laryngopharyngeal reflux (LPR). Prospective cohort study. Tertiary care referral medical centre. Patients complaining of LPR symptoms were evaluated via a 24-hour MII-pH. Among them, 99 patients whose LPR was confirmed via 24-hour MII-pH were enrolled in this study. Correlations between RFS ratings and 24-hour MII-pH parameters were evaluated and compared between patients with or without each laryngoscopic finding used in the RFS. Subglottic oedema had a statistically significant positive correlation with number of non-acid LPR and non-acid full column reflux events. Ventricular obliteration and posterior commissure hypertrophy showed a significant correlation with non-acid exposure time and total reflux exposure time. We also found a significant correlation between granuloma/granulation score and number of acid LPR events. The numbers of non-acid LPR and full column reflux events in patients with subglottic oedema were significantly higher than those without subglottic oedema. Among the laryngoscopic findings used in the RFS, subglottic oedema is specific for non-acid reflux episodes, and granuloma/granulation is specific for acid reflux episodes. © 2017 John Wiley & Sons Ltd.

Evaluating outcomes of endoscopic full-thickness plication for gastroesophageal reflux disease (GERD) with impedance monitoring.

PubMed

von Renteln, Daniel; Schmidt, Arthur; Riecken, Bettina; Caca, Karel

2010-05-01

Endoscopic full-thickness plication allows transmural suturing at the gastroesophageal junction to recreate the antireflux barrier. Multichannel intraluminal impedance monitoring (MII) can be used to detect nonacid or weakly acidic reflux, acidic swallows, and esophageal clearance time. This study used MII to evaluate the outcome of endoscopic full-thickness plication. In this study, 12 subsequent patients requiring maintenance proton pump inhibitor therapy underwent endoscopic full-thickness plication for treatment of gastroesophageal reflux disease. With patients off medication, MII was performed before and 6-months after endoscopic full-thickness plication. The total median number of reflux episodes was significantly reduced from 105 to 64 (p = 0.016). The median number of acid reflux episodes decreased from 73 to 43 (p = 0.016). Nonacid reflux episodes decreased from 23 to 21 (p = 0.306). The median bolus clearance time was 12 s before treatment and 11 s at 6 months (p = 0.798). The median acid exposure time was reduced from 6.8% to 3.4% (p = 0.008), and the DeMeester scores were reduced from 19 to 12 (p = 0.008). Endoscopic full-thickness plication significantly reduced total reflux episodes, acid reflux episodes, and total reflux exposure time. The DeMeester scores and total acid exposure time for the distal esophagus were significantly improved. No significant changes in nonacid reflux episodes and median bolus clearance time were encountered.

Nonalcoholic Fatty Liver Disease Is Associated with Increased Risk of Reflux Esophagitis.

PubMed

Yang, Hyo-Joon; Chang, Yoosoo; Park, Soo-Kyung; Jung, Yoon Suk; Park, Jung Ho; Park, Dong Il; Cho, Yong Kyun; Ryu, Seungho; Sohn, Chong Il

2017-12-01

Reflux esophagitis is associated with obesity and metabolic syndrome; however, the relationship between nonalcoholic fatty liver disease (NAFLD) and reflux esophagitis is unclear. We examined the association between NAFLD and the development of reflux esophagitis. Our cohort consisted of 117,377 Korean adults without reflux esophagitis at baseline who underwent a health checkup program including upper endoscopy between 2002 and 2014 and were followed annually or biennially until December 2014. NAFLD was defined as hepatic steatosis on ultrasonography in the absence of excessive alcohol use or any other identifiable cause. Over 520,843.2 person-years of follow-up, 22,500 participants developed reflux esophagitis (incidence density, 43.2 per 1000 person-years). In models adjusted for age and sex, the adjusted hazard ratio (aHR) (95% confidence interval [CI]) for incident reflux esophagitis in subjects with NAFLD compared to those without was 1.16 (1.13-1.20). After further adjustment for confounders of center, year of visit, smoking status, alcohol intake, regular exercise, education level, and body mass index, the association between NAFLD and incident reflux esophagitis was attenuated, but remained significant (aHR 1.06; 95% CI 1.02-1.10). In this large cohort of Korean men and women, participants with NAFLD exhibited increased incidence of reflux esophagitis independent of possible confounders, suggesting that NAFLD contributes to the development of reflux esophagitis.

Comparison of barium swallow and ultrasound in diagnosis of gastro-oesophageal reflux in children.

PubMed Central

Naik, D R; Bolia, A; Moore, D J

1985-01-01

Fifty one infants and older children with suspected gastro-oesophageal reflux entered a study comparing the diagnostic accuracy of a standard barium swallow examination with that of ultrasound scanning. All children were examined by both techniques. In 40 cases there was unequivocal agreement between the examinations. Of the remaining patients, four had definite reflux by ultrasonic criteria but showed no evidence of reflux on barium swallow examination, four had positive findings on ultrasound but showed only minimal reflux on barium swallow, and one showed minimal reflux on ultrasound but had a negative barium meal result. In two children the ultrasound study was inconclusive. Ultrasound has an important role in the diagnosis and follow up of patients under the age of 5 years with gastro-oesophageal reflux. Images FIG 1 FIG 2 PMID:3924317

Association Between Nocturnal Acid Reflux and Sleep Disturbance in Patients With Gastroesophageal Reflux Disease.

PubMed

Hung, Jui-Sheng; Lei, Wei-Yi; Yi, Chih-Hsun; Liu, Tso-Tsai; Chen, Chien-Lin

2016-08-01

This study was conducted to investigate whether there is a direct association between subjective sleep quality and esophageal acid reflux in patients with gastroesophageal reflux disease. We enrolled patients with classic reflux symptoms for endoscopy and ambulatory pH monitoring. The severity of esophageal mucosal injury was assessed by upper endoscopy. Distal esophageal acid exposure was determined by ambulatory 24-hour pH monitoring. Sleep disturbance was assessed by using the Pittsburgh Sleep Quality Index. In total, 103 patients (53 patients without sleep dysfunction and 50 patients with sleep dysfunction) were studied. Erosive esophagitis was found more in patients with sleep disturbance than in those without sleep disturbance (45% versus 31%, P = 0.04). Abnormal esophageal pH was found more in patients with dysfunction (22%) than in patients without sleep dysfunction (5.7%, P = 0.03). Recumbent acid contact time (%) was greater in patients with sleep disturbance than in those without sleep disturbance (3.7 ± 2.4 versus 1.9 ± 0.9, P = 0.04). Sleep quality score positively correlated with acid contact time (r = 0.32, P = 0.02), prolonged reflux events (r = 0.45, P = 0.008) and longer reflux event (r = 0.28, P = 0.03) during recumbent period. Patients with gastroesophageal reflux disease along with sleep dysfunction are characterized with greater nocturnal acid reflux and more erosive esophagitis. Our study suggests that increased nocturnal acid reflux may play a role in inducing sleep disturbance in patients with gastroesophageal reflux disease. Copyright © 2016 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

Does Cholecystectomy Increase the Esophageal Alkaline Reflux? Evaluation by Impedance-pH Technique.

PubMed

Uyanikoglu, Ahmet; Akyuz, Filiz; Ermis, Fatih; Arici, Serpil; Bas, Gurhan; Cakirca, Mustafa; Baran, Bulent; Mungan, Zeynel

2012-04-01

The aim of this study is to investigate the reflux patterns in patients with galbladder stone and the change of reflux patterns after cholecystectomy in such patients. Fourteen patients with cholecystolithiasis and a control group including 10 healthy control subjects were enrolled in this prospective study. Demographical findings, reflux symptom score scale and 24-hour impedance pH values of the 14 cholecystolithiasis cases and the control group were evaluated. The impedance pH study was repeated 3 months after cholecystectomy. Age, gender, and BMI were not different between the two groups. Total and supine weakly alkaline reflux time (%) (1.0 vs 22.5, P = 0.028; 201.85 vs 9.65, P = 0.012), the longest episodes of total, upright and supine weakly alkaline reflux mediums (11 vs 2, P = 0.025; 8.5 vs 1.0, P = 0.035; 3 vs 0, P = 0.027), total and supine weakly alkaline reflux time in minutes (287.35 vs 75.10, P = 0.022; 62.5 vs 1.4, P = 0.017), the number of alkaline reflux episodes (162.5 vs 72.5, P = 0.022) were decreased with statistical significance. No statistically significant difference was found in the comparison of symptoms between the subjects in the control group and the patients with cholecystolithiasis, in preoperative, postoperative and postcholecystectomy status. Significant reflux symptoms did not occur after cholecystectomy. Post cholecystectomy weakly alkaline reflux was decreased, but it was determined that acid reflux increased after cholecystectomy by impedance pH-metry in the study group.

Clinical and pH-metric characteristics of gastro-oesophageal reflux secondary to cows' milk protein allergy.

PubMed Central

Cavataio, F; Iacono, G; Montalto, G; Soresi, M; Tumminello, M; Carroccio, A

1996-01-01

AIMS: The primary aim was to assess whether there were differences in symptoms, laboratory data, and oesophageal pH-metry between infants with primary gastro-oesophageal reflux and those with reflux secondary to cows' milk protein allergy (CMPA). PATIENTS AND METHODS: 96 infants (mean(SD) age 7.8(2.0) months) with either primary gastro-oesophageal reflux, reflux with CMPA, CMPA only, or none of these (controls) were studied. Symptoms, immunochemical data, and oesophageal pH were compared between the four groups and the effect of a cows' milk protein-free diet on the severity of symptoms was also assessed. RESULTS: 14 out of 47(30%) infants with gastro-oesophageal reflux had CMPA. These infants had similar symptoms to those with primary gastro-oesophageal reflux but higher concentrations of total IgE and circulating eosinophils (p < 0.005) and IgG anti-beta lactoglobulin (p < 0.003). A progressive constant reduction in oesophageal pH at the end of a feed, which continued up to the next feed, was seen in 12 out of 14 patients with gastro-oesophageal reflux secondary to CMPA and in 24 of 25 infants with CMPA only. No infants with primary gastro-oesophageal reflux and none of the controls had this pattern. A cows' milk protein-free diet was associated with a significant improvement in symptoms only in infants with gastro-oesophageal reflux with CMPA. CONCLUSION: A characteristic oesophageal pH pattern is useful in distinguishing infants with gastro-oesophageal reflux associated with CMPA. PMID:8813871

Endoscopic management of bile leakage after liver transplantation.

PubMed

Oh, Dong-Wook; Lee, Sung Koo; Song, Tae Jun; Park, Do Hyun; Lee, Sang Soo; Seo, Dong-Wan; Kim, Myung-Hwan

2015-05-23

Endoscopic retrograde cholangiopancreatography (ERCP) can be an effective treatment for bile leakage after liver transplantation. We evaluated the efficacy of endoscopic treatment in liver transplantation in patients who developed bile leaks. Forty-two patients who developed bile leaks after liver transplantation were included in the study. If a bile leak was observed on ERCP, a sphincterotomy was performed, and a nasobiliary catheter was then inserted. If a bile leak was accompanied by a bile duct stricture, either the stricture was dilated with balloons, followed by nasobiliary catheter insertion across the bile duct stricture, or endoscopic retrograde biliary drainage was performed. In the bile leakage alone group (22 patients), endoscopic treatment was technically successful in 19 (86.4%) and clinically successful in 17 (77.3%) cases. Among the 20 patients with bile leaks with bile duct strictures, endoscopic treatment was technically successful in 13 (65.0%) and clinically successful in 10 (50.0%) cases. Among the 42 patients who underwent ERCP, technical success was achieved in 32 (76.2%) cases and clinical success was achieved in 27 (64.3%) cases. ERCP is an effective and safe therapeutic modality for bile leaks after liver transplantation. ERCP should be considered as an initial therapeutic modality in post-liver transplantation patients.

Steam cooking significantly improves in vitro bile acid binding of collard greens, kale, mustard greens, broccoli, green bell pepper, and cabbage.

PubMed

Kahlon, Talwinder Singh; Chiu, Mei-Chen M; Chapman, Mary H

2008-06-01

Bile acid binding capacity has been related to the cholesterol-lowering potential of foods and food fractions. Lowered recirculation of bile acids results in utilization of cholesterol to synthesize bile acid and reduced fat absorption. Secondary bile acids have been associated with increased risk of cancer. Bile acid binding potential has been related to lowering the risk of heart disease and that of cancer. Previously, we have reported bile acid binding by several uncooked vegetables. However, most vegetables are consumed after cooking. How cooking would influence in vitro bile acid binding of various vegetables was investigated using a mixture of bile acids secreted in human bile under physiological conditions. Eight replicate incubations were conducted for each treatment simulating gastric and intestinal digestion, which included a substrate only, a bile acid mixture only, and 6 with substrate and bile acid mixture. Cholestyramine (a cholesterol-lowering, bile acid binding drug) was the positive control treatment and cellulose was the negative control. Relative to cholestyramine, in vitro bile acid binding on dry matter basis was for the collard greens, kale, and mustard greens, 13%; broccoli, 10%; Brussels sprouts and spinach, 8%; green bell pepper, 7%; and cabbage, 5%. These results point to the significantly different (P < or = .05) health-promoting potential of collard greens = kale = mustard greens > broccoli > Brussels sprouts = spinach = green bell pepper > cabbage as indicated by their bile acid binding on dry matter basis. Steam cooking significantly improved the in vitro bile acid binding of collard greens, kale, mustard greens, broccoli, green bell pepper, and cabbage compared with previously observed bile acid binding values for these vegetables raw (uncooked). Inclusion of steam-cooked collard greens, kale, mustard greens, broccoli, green bell pepper, and cabbage in our daily diet as health-promoting vegetables should be emphasized. These green/leafy vegetables, when consumed regularly after steam cooking, would lower the risk of cardiovascular disease and cancer, advance human nutrition research, and improve public health.

Non-Newtonian flow of pathological bile in the biliary system: experimental investigation and CFD simulations

NASA Astrophysics Data System (ADS)

Kuchumov, Alex G.; Gilev, Valeriy; Popov, Vitaliy; Samartsev, Vladimir; Gavrilov, Vasiliy

2014-02-01

The paper presents an experimental study of pathological human bile taken from the gallbladder and bile ducts. The flow dependences were obtained for different types of bile from patients with the same pathology, but of different age and sex. The parameters of the Casson's and Carreau's equations were found for bile samples. Results on the hysteretic bile behavior at loading-unloading tests are also presented, which proved that the pathologic bile is a non-Newtonian thixotropic liquid. The viscosity of the gallbladder bile was shown to be higher compared to the duct bile. It was found that at higher shear stress the pathological bile behaves like Newtonian fluid, which is explained by reorientation of structural components. Moreover, some pathological bile flow in the biliary system CFD simulations were performed. The velocity and pressure distributions as well as flow rates in the biliary segments during the gallbladder refilling and emptying phases are obtained. The results of CFD simulations can be used for surgeons to assess the patient's condition and choose an adequate treatment.

Diversity of bile salts in fish and amphibians: evolution of a complex biochemical pathway.

PubMed

Hagey, Lee R; Møller, Peter R; Hofmann, Alan F; Krasowski, Matthew D

2010-01-01

Bile salts are the major end metabolites of cholesterol and are also important in lipid and protein digestion, as well as shaping of the gut microflora. Previous studies had demonstrated variation of bile salt structures across vertebrate species. We greatly extend prior surveys of bile salt variation in fish and amphibians, particularly in analysis of the biliary bile salts of Agnatha and Chondrichthyes. While there is significant structural variation of bile salts across all fish orders, bile salt profiles are generally stable within orders of fish and do not correlate with differences in diet. This large data set allowed us to infer evolutionary changes in the bile salt synthetic pathway. The hypothesized ancestral bile salt synthetic pathway, likely exemplified in extant hagfish, is simpler and much shorter than the pathway of most teleost fish and terrestrial vertebrates. Thus, the bile salt synthetic pathway has become longer and more complex throughout vertebrate evolution. Analysis of the evolution of bile salt synthetic pathways provides a rich model system for the molecular evolution of a complex biochemical pathway in vertebrates.

Physiology of bile secretion.

PubMed

Esteller, Alejandro

2008-10-07

The formation of bile depends on the structural and functional integrity of the bile-secretory apparatus and its impairment, in different situations, results in the syndrome of cholestasis. The structural bases that permit bile secretion as well as various aspects related with its composition and flow rate in physiological conditions will first be reviewed. Canalicular bile is produced by polarized hepatocytes that hold transporters in their basolateral (sinusoidal) and apical (canalicular) plasma membrane. This review summarizes recent data on the molecular determinants of this primary bile formation. The major function of the biliary tree is modification of canalicular bile by secretory and reabsorptive processes in bile-duct epithelial cells (cholangiocytes) as bile passes through bile ducts. The mechanisms of fluid and solute transport in cholangiocytes will also be discussed. In contrast to hepatocytes where secretion is constant and poorly controlled, cholangiocyte secretion is regulated by hormones and nerves. A short section dedicated to these regulatory mechanisms of bile secretion has been included. The aim of this revision was to set the bases for other reviews in this series that will be devoted to specific issues related with biliary physiology and pathology.

Reflux and Voice Disorders: Have We Established Causality?

PubMed Central

Schneider, G. Todd; Vaezi, Michael F.; Francis, David O.

2017-01-01

A trend of attributing abnormal voice changes to reflux has gained momentum among medical professionals over the last few decades. Evidence supporting the connection between reflux and voice and the use of anti-reflux medication in patients with dysphonia is conflicting and deserves careful examination. In the current health care environment, it is important that medical decisions be based on science rather than anecdote and practice patterns. The goal of this review is to investigate the evidence linking reflux and voice changes. Specifically, this association will be examined in the context of the Bradford-Hill criteria to determine what evidence exists for a causal relationship between this exposure (reflux) and outcome (voice change). PMID:28163985

Bile resistance in Lactococcus lactis strains varies with cellular fatty acid composition: analysis by using different growth media.

PubMed

Kimoto-Nira, Hiromi; Kobayashi, Miho; Nomura, Masaru; Sasaki, Keisuke; Suzuki, Chise

2009-05-31

Bile resistance is one of the basic characteristics of probiotic bacteria. The aim of this study was to investigate the characteristics of bile resistance in lactococci by studying the relationship between bile resistance and cellular fatty acid composition in lactococcci grown on different media. We determined the bile resistance of 14 strains in lactose-free M17 medium supplemented with either glucose only (GM17) or lactose only (LM17). Gas chromatographic analyses of free lipids extracted from the tested strains were used for determining their fatty acid composition. A correlation analysis of all strains grown in both media revealed significant positive correlations between bile resistance and relative contents of hexadecanoic acid and octadecenoic acid, and negative correlations between bile resistance and relative contents of hexadecenoic acid and C-19 cyclopropane fatty acid. It is also a fact that the fatty acids associated with bile resistance depended on species, strain, and/or growth medium. In L. lactis subsp. cremoris strains grown in GM17 medium, the bile-resistant strains had significantly more octadecenoic acid than the bile-sensitive strains. In LM17 medium, bile-resistant strains had significantly more octadecenoic acid and significantly less C-19 cyclopropane fatty acid than the bile-sensitive strains. In L. lactis subsp. lactis strains, bile resistances of some of the tested strains were altered by growth medium. Some strains were resistant to bile in GM17 medium but sensitive to bile in LM17 medium. Some strains were resistant in both media tested. The strains grown in GM17 medium had significantly more hexadecanoic acid and octadecenoic acid, and significantly less tetradecanoic acid, octadecadienoic acid and C-19 cyclopropane fatty acid than the strains grown in LM17 medium. In conclusion, the fatty acid compositions of the bile-resistant lactococci differed from those of the bile-sensitive ones. More importantly, our data suggest that altering their fatty acid composition (i.e. increased hexadecanoic acid and octadecenoic acid and decreased hexadecenoic acid and C-19 cyclopropane fatty acid) by changing growth conditions may be a useful way to enhance their bile resistance in lactococci.

Bile Duct Exploration

MedlinePlus

... Patients & Visitors Health Library Institutes & Departments Home / Health Library / Diagnostics & Testing / Bile Duct Exploration Advertising Policy Bile Duct Exploration Common bile duct exploration is ...

Esophageal Impedance Monitoring for Gastroesophageal Reflux

PubMed Central

Mousa, Hayat M.; Rosen, Rachel; Woodley, Frederick W.; Orsi, Marina; Armas, Daneila; Faure, Christophe; Fortunato, John; O'Connor, Judith; Skaggs, Beth; Nurko, Samuel

2014-01-01

Dual pH-multichannel intraluminal impedance (pH-MII) is a sensitive tool for evaluating overall gastroesophageal reflux disease, and particularly for permitting detection of nonacid reflux events. pH-MII technology is especially useful in the postprandial period or at other times when gastric contents are nonacidic. pH-MII was recently recognized by the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition as being superior to pH monitoring alone for evaluation of the temporal relation between symptoms and gastroesophageal reflux. In children, pHMII is useful to correlate symptoms with reflux (particularly nonacid reflux), to quantify reflux during tube feedings and the postprandial period, and to assess efficacy of antireflux therapy. This clinical review is simply an evidence-based overview addressing the indications, limitations, and recommended protocol for the clinical use of pH-MII in children. PMID:21240010

Respiratory and laryngeal symptoms secondary to gastro-oesophageal reflux

PubMed Central

Rafferty, G; Mainie, I; McGarvey, L P A

2011-01-01

Gastro-oesophageal reflux may cause a range of laryngeal and respiratory symptoms. Mechanisms responsible include the proximal migration of gastric refluxate beyond the upper oesophageal sphincter causing direct irritation of the larynx and lower airway. Alternatively, refluxate entering the distal oesophagus alone may stimulate oesophageal sensory nerves and indirectly activate airway reflexes such as cough and bronchospasm. Recognising reflux as a cause for these extraoesophageal symptoms can be difficult as many patients do not have typical oesophageal symptoms (eg, heartburn) and clinical findings on laryngoscopy are not very specific. Acid suppression remains an effective treatment in the majority of patients but there is growing appreciation of the need to consider and treat non-acid and volume reflux. New opinions about the role of existing medical and surgical (laparoscopic techniques) treatment are emerging and a number of novel anti-reflux treatments are under development. PMID:28839612

Normal or increased bile acid uptake in isolated mucosa from patients with bile acid malabsorption.

PubMed

Bajor, Antal; Kilander, Anders; Fae, Anita; Gälman, Cecilia; Jonsson, Olof; Ohman, Lena; Rudling, Mats; Sjövall, Henrik; Stotzer, Per-Ove; Ung, Kjell-Arne

2006-04-01

Bile acid malabsorption as reflected by an abnormal Se-labelled homocholic acid-taurine (SeHCAT) test is associated with diarrhoea, but the mechanisms and cause-and-effect relations are unclear. Primarily, to determine whether there is a reduced active bile acid uptake in the terminal ileum in patients with bile acid malabsorption. Secondarily, to study the linkage between bile acid malabsorption and hepatic bile acid synthesis. Ileal biopsies were taken from patients with diarrhoea and from controls with normal bowel habits. Maximal active bile acid uptake was assessed in ileal biopsies using a previously validated technique based on uptake of C-labelled taurocholate. To monitor the hepatic synthesis, 7alpha-hydroxy-4-cholesten-3-one, a bile acid precursor, was assayed in blood. The SeHCAT-retention test was used to diagnose bile acid malabsorption. The taurocholate uptake in specimens from diarrhoea patients was higher compared with the controls [median, 7.7 (n=53) vs 6.1 micromol/g per min (n=17)] (P<0.01) but no difference was seen between those with bile acid malabsorption (n=18) versus diarrhoea with a normal SeHCAT test (n=23). The SeHCAT values and 7alpha-hydroxy-4-cholesten-3-one were inversely correlated. The data do not support bile acid malabsorption being due to a reduced active bile acid uptake capacity in the terminal ileum.

3 alpha-Hydroxylated bile acid profiles in clinically normal cats, cats with severe hepatic lipidosis, and cats with complete extrahepatic bile duct occlusion.

PubMed

Center, S A; Thompson, M; Guida, L

1993-05-01

Concentrations of 3 alpha-hydroxylated bile acids were measured in serum and urine of clinically normal (healthy) cats (n = 6), cats with severe hepatic lipidosis (n = 9), and cats with complete bile duct occlusion (n = 4). Bile acid concentrations were measured by use of a gradient flow high-performance liquid chromatography procedure with an acetonitrile and ammonium phosphate mobile phase and an in-line postanalytic column containing 3 alpha-hydroxy-steroid dehydrogenase and a fluorescence detector. Specific identification of all bile acid peaks was not completed; unidentified moieties were represented in terms of their elution time (in minutes). Significant differences in serum and urine bile acid concentrations, quantitative and proportional, were determined among groups of cats. Cats with hepatic lipidosis and bile duct occlusion had significantly (P > or = 0.05) greater total serum and urine bile acids concentrations than did healthy cats. The proportion of hydrophobic bile acids in serum, those eluting at > or = 400 minutes, was 1.9% for healthy cats, 3.3% for cats with lipidosis, and 5.4% for bile duct-obstructed cats. Both groups of ill cats had a broader spectrum of unidentified late-eluting serum bile acids than did healthy cats; the largest spectrum developed in bile duct-occluded cats.(ABSTRACT TRUNCATED AT 250 WORDS)

The bile acid composition of crane gallbladder bile

USGS Publications Warehouse

Serafin, J.A.

1983-01-01

1. The biliary bile acids of the whooping crane (Grus americana) and the Florida sandhill crane (G. canadensis pratensis) have been examined.2. Cholic acid (CA), chenodeoxycholic acid (CDOCA) and lithocholic acid were found in bile from both species of these North American cranes.3. CDOCA and CA were the primary bile acids in both species, together constituting 70% or more of the bile acids by weight.4. The primary bile acids of cranes appear to be the same as those that have been identified in other avian species.

Usefulness of echocystography in the study of vesicoureteral reflux.

PubMed

Escape, I; Martínez, J; Bastart, F; Solduga, C; Sala, P

2001-02-01

The aim of our study was to assess the usefulness of contrast-enhanced sonography in detecting and staging vesicoureteral reflux in pediatric patients. Forty-nine children between birth and 5 years of age were studied for vesicoureteral reflux. Echocystography with the use of an endovesical signal enhancer was performed first, followed immediately by conventional voiding cystourethrography. The findings obtained by echocystography and voiding cystourethrography were consistent in 89 (90.8%) of 98 ureterorenal units (a ureterorenal unit is 1 kidney with its own ureter). Reflux was demonstrated by voiding cystourethrography in 13 cases; in 9 of these cases diagnosis had also been made by echocystography. Five cases of reflux detected by echocystography were not identified by voiding cystourethrography. With voiding cystourethrography as the standard of reference, sensitivity was 69%; specificity, 94%; positive predictive value, 64%; and negative predictive value, 95%. In conclusion, echocystography is a useful tool for the diagnosis of vesicoureteral reflux. Its ability to detect reflux is similar to that of cystography in cases of high-grade reflux, and it may be an appropriate complementary technique to voiding cystourethrography, because it avoids exposure to radiation.

Use of intermediate guide catheters as an adjunct in extracranial embolization to avoid onyx reflux into the anastomotic vasculature. A technical note.

PubMed

Puri, Ajit S; Kühn, Anna L; Hou, Samuel Y; Wakhloo, Ajay K

2014-01-01

Onyx is a non-adhesive polymer used for embolization of arteriovenous malformations and dural arteriovenous fistulas (DAVFs). The limiting factor for Onyx embolization is usually the amount of microcatheter reflux, which can be safely tolerated. The dual microcatheter technique, compliant balloon use proximally and the use of the dual lumen Scepter balloon have been described to prevent and limit proximal Onyx reflux. We describe the use the Navien 058 intermediate guide catheter to accept the Onyx reflux in its lumen and possibly also serve as a mechanical barrier to avoid reflux into the anastomotic channel connecting the occipital artery to the vertebral artery during DAVF embolization via the occipital artery. Complete embolization of the DAVF was achieved using the lumen of the Navien catheter to accept aggressive Onyx reflux. Complete cure of the DAVF was obtained with Onyx cast filling the entire venous pouch. Besides providing distal access support, intermediate guide catheters can also prevent embolic material reflux by accepting reflux into the lumen and providing a mechanical barrier.

Use of Intermediate Guide Catheters as an Adjunct in Extracranial Embolization to Avoid Onyx Reflux into the Anastomotic Vasculature

PubMed Central

Puri, Ajit S; Kühn, Anna L; Hou, Samuel Y; Wakhloo, Ajay K

2014-01-01

Summary Onyx is a non-adhesive polymer used for embolization of arteriovenous malformations and dural arteriovenous fistulas (DAVFs). The limiting factor for Onyx embolization is usually the amount of microcatheter reflux, which can be safely tolerated. The dual microcatheter technique, compliant balloon use proximally and the use of the dual lumen Scepter balloon have been described to prevent and limit proximal Onyx reflux. We describe the use the Navien 058 intermediate guide catheter to accept the Onyx reflux in its lumen and possibly also serve as a mechanical barrier to avoid reflux into the anastomotic channel connecting the occipital artery to the vertebral artery during DAVF embolization via the occipital artery. Complete embolization of the DAVF was achieved using the lumen of the Navien catheter to accept aggressive Onyx reflux. Complete cure of the DAVF was obtained with Onyx cast filling the entire venous pouch. Besides providing distal access support, intermediate guide catheters can also prevent embolic material reflux by accepting reflux into the lumen and providing a mechanical barrier. PMID:25207904

Quantifying Laryngopharyngeal Reflux in Singers: Perceptual and Objective Findings

PubMed Central

Lewis, Vicki M.

2017-01-01

This study examines the relationship between laryngopharyngeal reflux (LPR) symptoms and oropharyngeal pH levels in singers. We hypothesized that reported symptoms would correlate with objective measures of pH levels from the oropharynx, including the number and total duration of reflux episodes. Twenty professional/semiprofessional singers completed the Reflux Symptom Index (RSI) and underwent oropharyngeal pH monitoring. Mild, moderate, or severe pH exposure was recorded during oropharyngeal pH monitoring. Correlations were performed to examine potential relationships between reflux symptoms and duration of LPR episodes. Symptom severity did not correlate with pH levels; however, we found a number of covariances of interest. Large sample sizes are necessary to determine if true correlations exist. Our results suggest that singers may exhibit enhanced sensitivity to LPR and may therefore manifest symptoms, even in response to subtle changes in pH. This study emphasizes the importance of sensitive and objective measures of reflux severity as well as consideration of the cumulative time of reflux exposure in addition to the number of reflux episodes. PMID:29098155

[Clinical and laboratory characteristics of patients with pathologic chronic gastroesophageal reflux].

PubMed

Csendes, A; Burdiles, P; Maluenda, F; Cortés, C; Korn, O; Rojas, J; Tepper, P; Huertas, C; Sagastume, H; Puente, G; Quezada, F; Csendes, P

1998-07-01

Sixty percent of adults has typical symptoms of gastroesophageal reflux in Chile. To report the clinical and laboratory features of patients with gastroesophageal reflux. Five hundred thirty-four patients (255 male) with gastroesophageal reflux were included in a prospective protocol that included clinical analysis, manometry and endoscopy in all patients, barium swallow in 427, scintigraphy in 195, acid reflux test in 359, 24 h pH in 175, and differential potential of gastroesophageal mucosa in 73 patients. There was no correlation between the severity of symptoms and the endoscopical severity. Patients with Barret esophagus were 12 years older, were male in a greater proportion and had a higher proportion of manometrically incompetent sphincters than patients with esophageal reflux but without esophagitis or with erosive esophagitis. Severity of acid reflux, measured with 24 h pH monitoring was proportional to the endoscopical damage of the mucosa. There was a close relationship between the mucosal change limit determined with differential potentials and with endoscopy. No short esophagi were found. Patients with symptoms of gastroesophageal reflux must be assessed using several objective measures to determine the severity of their pathological alterations.

Fetal bile salt metabolism

PubMed Central

Smallwood, R. A.; Lester, R.; Piasecki, G. J.; Klein, P. D.; Greco, R.; Jackson, B. T.

1972-01-01

Bile salt metabolism was studied in fetal dogs 1 wk before term. The size and distribution of the fetal bile salt pool were measured, and individual bile salts were identified. The hepatic excretion of endogenous bile salts was studied in bile fistula fetuses, and the capacity of this excretory mechanism was investigated by the i.v. infusion of a load of sodium taurocholate-14C up to 20 times the endogenous pool size. The total fetal bile salt pool was 30.9±2.7 μmoles, of which two-thirds was in the fetal gallbladder. Expressed on a body weight basis, this was equal to approximately one-half the estimated pool size in the adult dog (119.2±11.3 vs. 247.5±33.1 μmoles/kg body wt). Measurable quantities of bile salt were found in small bowel (6.0±1.8 μmoles), large bowel (1.1±0.3 μmoles), liver (1.2±0.5 μmoles), and plasma (0.1±0.03 μmoles). Plasma bile salt levels were significantly greater in fetal than in maternal plasma (1.01±0.24 μg/ml vs. 0.36±0.06 μg/ml; P < 0.05). Fetal hepatic bile salt excretion showed a fall over the period of study from 2.04±0.34 to 0.30±0.07 μmoles/hr. The maximal endogenous bile salt concentration in fetal hepatic bile was 18.7±1.5 μmoles/ml. The concentration in fetal gallbladder bile was 73.9±8.6 μmoles/ml; and, in those studies in which hepatic and gallbladder bile could be compared directly, the gallbladder appeared to concentrate bile four- to fivefold. Taurocholate, taurochenodeoxycholate, and taurodeoxycholate were present in fetal bile, but no free bile salts were identified. The presence of deoxycholate was confirmed by thin-layer chromatography and gas liquid chromatography, and the absence of microorganisms in fetal gut suggests that it was probably transferred from the maternal circulation. After infusion of a taurocholate load, fetal hepatic bile salt excretion increased 30-fold, so that 85-95% of the dose was excreted by the fetal liver during the period of observation. Placental transfer accounted for less than 5% of the dose. Fetal bile volume increased 15-fold on average, while bile salt concentrations increased two- to threefold. It is concluded that bile salt is taken up, conjugated, and excreted by the fetal liver with remarkable efficiency. The excreted material is either stored and concentrated in the fetal gallbladder or released into the intestine and reabsorbed to be reexcreted in bile. PMID:5063379

Mucin and phospholipids determine viscosity of gallbladder bile in patients with gallstones

PubMed Central

Jüngst, Dieter; Niemeyer, Anna; Müller, Iris; Zündt, Benedikta; Meyer, Günther; Wilhelmi, Martin; del Pozo, Reginald

2001-01-01

AIM: An increased viscosity of gallbladder bile has been considered an important factor in the pathogenesis of gallstone disease. Besides lipids and proteins, mucin has been suggested to affect the viscosity of bile. To further clarify these issues we compared mucin, protein and the lipid componEnts of hepatic and gallbladder bile and its viscosity in patients with gallstones. METHODS: Viscosity of bile (mPa.s) was measured using rotation viscosimetry in regard to the non Newtonian property of bile at low shear rates. RESULTS: Biliary viscosity was markedly higher in gallbladder bile of patients with cholesterol (5.00 ± 0.60 mPa.s, mean ± SEM, n = 28) and mixed stones (3.50 ± 0.68 mPa.s; n = 8) compared to hepatic bile (0.92 ± 0.06 mPa.s, n = 6). A positive correlation between mucin and viscosity was found in gallbladder biles (r = 0. 65; P < 0.001) but not in hepatic biles. The addition of physiologic and supraphysiologic amounts of mucin to gallbladder bile resulted in a dose dependent non linear increase of its viscosity. A positive correlation was determined between phospholipid concentration and viscosity (r = 0.34, P < 0.005) in gallbladder biles. However, no correlation was found between total protein or the other lipid concentrations and viscosity in both gallbladder and hepatic biles. CONCLUSION: The viscosity of gallbladder bile is markedly higher than that of hepatic bile in patients with gallstones. The concentration of mucin is the major determinant of biliary viscosity and may contribute by this mechanism to the role of mucin in the pathogenesis of gallstones. PMID:11819761

Dissecting the regulation of bile-induced biofilm formation in Staphylococcus aureus.

PubMed

Ulluwishewa, Dulantha; Wang, Liang; Pereira, Callen; Flynn, Stephanie; Cain, Elizabeth; Stick, Stephen; Reen, F Jerry; Ramsay, Joshua P; O'Gara, Fergal

2016-08-01

Aspiration of bile into the cystic fibrosis (CF) lung has emerged as a prognostic factor for reduced microbial lung biodiversity and the establishment of often fatal, chronic pathogen infections. Staphylococcus aureus is one of the earliest pathogens detected in the lungs of children with CF, and once established as a chronic infection, strategies for its eradication become limited. Several lung pathogens are stimulated to produce biofilms in vitro in the presence of bile. In this study, we further investigated the effects of bile on S. aureus biofilm formation. Most clinical S. aureus strains and the laboratory strain RN4220 were stimulated to form biofilms with sub-inhibitory concentrations of bovine bile. Additionally, we observed bile-induced sensitivity to aminoglycosides, which we exploited in a bursa aurealis transposon screen to isolate mutants reduced in aminoglycoside sensitivity and augmented in bile-induced biofilm formation. We identified five mutants that exhibited hypersensitivity to bile with respect to bile-induced biofilm formation, three of which carried transposon insertions within gene clusters involved in wall teichoic acid (WTA) biosynthesis or transport. Strain TM4 carried an insertion between the divergently oriented tagH and tagG genes, which encode the putative WTA membrane translocation apparatus. Ectopic expression of tagG in TM4 restored a wild-type bile-induced biofilm response, suggesting that reduced translocation of WTA in TM4 induced sensitivity to bile and enhanced the bile-induced biofilm formation response. We propose that WTA may be important for protecting S. aureus against exposure to bile and that bile-induced biofilm formation may be an evolved response to protect cells from bile-induced cell lysis.

Nuclear factor-E2-related factor 2 is a major determinant of bile acid homeostasis in the liver and intestine

PubMed Central

Weerachayaphorn, Jittima; Mennone, Albert; Soroka, Carol J.; Harry, Kathy; Hagey, Lee R.; Kensler, Thomas W.

2012-01-01

The transcription factor nuclear factor-E2-related factor 2 (Nrf2) is a key regulator for induction of hepatic detoxification and antioxidant mechanisms, as well as for certain hepatobiliary transporters. To examine the role of Nrf2 in bile acid homeostasis and cholestasis, we assessed the determinants of bile secretion and bile acid synthesis and transport before and after bile duct ligation (BDL) in Nrf2−/− mice. Our findings indicate reduced rates of biliary bile acid and GSH excretion, higher levels of intrahepatic bile acids, and decreased expression of regulators of bile acid synthesis, Cyp7a1 and Cyp8b1, in Nrf2−/− compared with wild-type control mice. The mRNA expression of the bile acid transporters bile salt export pump (Bsep) and organic solute transporter (Ostα) were increased in the face of impaired expression of the multidrug resistance-associated proteins Mrp3 and Mrp4. Deletion of Nrf2 also decreased ileal apical sodium-dependent bile acid transporter (Asbt) expression, leading to reduced bile acid reabsorption and increased loss of bile acid in feces. Finally, when cholestasis is induced by BDL, liver injury was not different from that in wild-type BDL mice. These Nrf2−/− mice also had increased pregnane X receptor (Pxr) and Cyp3a11 mRNA expression in association with enhanced hepatic bile acid hydroxylation. In conclusion, this study finds that Nrf2 plays a major role in the regulation of bile acid homeostasis in the liver and intestine. Deletion of Nrf2 results in a cholestatic phenotype but does not augment liver injury following BDL. PMID:22345550

CT differentiation of mucin-producing cystic neoplasms of the liver from solitary bile duct cysts.

PubMed

Kim, Hyoung Jung; Yu, Eun Sil; Byun, Jae Ho; Hong, Seung-Mo; Kim, Kyoung Won; Lee, Jong Seok; Kim, So Yeon

2014-01-01

The purpose of this study was to identify the CT features required for differentiating mucin-producing cystic neoplasms of the liver (mucinous cystic neoplasms and cyst-forming intraductal papillary neoplasms of the bile duct) from solitary bile duct cysts. CT images of pathologically confirmed mucinous cystic neoplasms (n = 15), cyst-forming intraductal papillary neoplasms of the bile duct (n = 16), and solitary bile duct cysts (n = 31) were reviewed. Analysis of the CT findings included shape, presence of septa, location of septa (peripheral vs central), thickness of septa (thin vs thick), mosaic pattern, mural nodules, intracystic debris, calcification, upstream bile duct dilatation, downstream bile duct dilatation, and communication between a cystic lesion and the bile duct. The maximum size of a cystic lesion and the maximum size of the largest mural nodule were measured. The presence of septa, central septa, mural nodules, upstream bile duct dilatation, and downstream bile duct dilatation were found to be significant CT findings for differentiating mucinous cystic neoplasms and cyst-forming intraductal papillary neoplasms of the bile duct from solitary bile duct cysts (p < 0.05 for each finding). When two of these five criteria were used in combination, the sensitivity and specificity for diagnosing mucin-producing cystic neoplasms and cyst-forming intraductal papillary neoplasms of the bile duct were 87% (27 of 31) and 87% (27 of 31), respectively. When two of these five criteria were used in combination, the sensitivity and specificity for diagnosing mucinous cystic neoplasms and cyst-forming intraductal papillary neoplasms of the bile duct were 87% (27 of 31) and 87% (27 of 31), respectively [corrected]. With the use of specific CT criteria, mucin-producing cystic neoplasms of the liver can be differentiated from solitary bile duct cysts with a high degree of accuracy.

Contribution of Three Bile-Associated Loci, bsh, pva, and btlB, to Gastrointestinal Persistence and Bile Tolerance of Listeria monocytogenes

PubMed Central

Begley, Máire; Sleator, Roy D.; Gahan, Cormac G. M.; Hill, Colin

2005-01-01

Listeria monocytogenes must resist the deleterious actions of bile in order to infect and subsequently colonize the human gastrointestinal tract. The molecular mechanisms used by the bacterium to resist bile and the influence of bile on pathogenesis are as yet largely unexplored. This study describes the analysis of three genes—bsh, pva, and btlB—previously annotated as bile-associated loci in the sequenced L. monocytogenes EGDe genome (lmo2067, lmo0446, and lmo0754, respectively). Analysis of deletion mutants revealed a role for all three genes in resisting the acute toxicity of bile and bile salts, particularly glycoconjugated bile salts at low pH. Mutants were unaffected in the other stress responses examined (acid, salt, and detergents). Bile hydrolysis assays demonstrate that L. monocytogenes possesses only one bile salt hydrolase gene, namely, bsh. Transcriptional analyses and activity assays revealed that, although it is regulated by both PrfA and σB, the latter appears to play the greater role in modulating bsh expression. In addition to being incapable of bile hydrolysis, a sigB mutant was shown to be exquisitely sensitive to bile salts. Furthermore, increased expression of sigB was detected under anaerobic conditions and during murine infection. A gene previously annotated as a possible penicillin V amidase (pva) or bile salt hydrolase was shown to be required for resistance to penicillin V but not penicillin G but did not demonstrate a role in bile hydrolysis. Finally, animal (murine) studies revealed an important role for both bsh and btlB in the intestinal persistence of L. monocytogenes. PMID:15664931

Persistent reflux symptoms cause anxiety, depression, and mental health and sleep disorders in gastroesophageal reflux disease patients

PubMed Central

Kimura, Yoshihide; Kamiya, Takeshi; Senoo, Kyouji; Tsuchida, Kenji; Hirano, Atsuyuki; Kojima, Hisayo; Yamashita, Hiroaki; Yamakawa, Yoshihiro; Nishigaki, Nobuhiro; Ozeki, Tomonori; Endo, Masatsugu; Nakanishi, Kazuhisa; Sando, Motoki; Inagaki, Yusuke; Shikano, Michiko; Mizoshita, Tsutomu; Kubota, Eiji; Tanida, Satoshi; Kataoka, Hiromi; Katsumi, Kohei; Joh, Takashi

2016-01-01

Some patients with gastroesophageal reflux disease experience persistent reflux symptoms despite proton pump inhibitor therapy. These symptoms reduce their health-related quality of life. Our aims were to evaluate the relationship between proton pump inhibitor efficacy and health-related quality of life and to evaluate predictive factors affecting treatment response in Japanese patients. Using the gastroesophageal reflux disease questionnaire, 145 gastroesophageal reflux disease patients undergoing proton pump inhibitor therapy were evaluated and classified as responders or partial-responders. Their health-related quality of life was then evaluated using the 8-item Short Form Health Survey, the Pittsburgh Sleep Quality Index, and the Hospital Anxiety and Depression Scale questionnaires. Sixty-nine patients (47.6%) were partial responders. These patients had significantly lower scores than responders in 5/8 subscales and in the mental health component summary of the 8-item Short Form Health Survey. Partial responders had significantly higher Pittsburgh Sleep Quality Index and Hospital Anxiety and Depression Scale scores, including anxiety and depression scores, than those of responders. Non-erosive reflux disease and double proton pump inhibitor doses were predictive factors of partial responders. Persistent reflux symptoms, despite proton pump inhibitor therapy, caused mental health disorders, sleep disorders, and psychological distress in Japanese gastroesophageal reflux disease patients. PMID:27499583

Recent effectiveness of proton pump inhibitors for severe reflux esophagitis: the first multicenter prospective study in Japan.

PubMed

Mizuno, Hideki; Matsuhashi, Nobuyuki; Sakaguchi, Masahiro; Inoue, Syuji; Nakada, Koji; Higuchi, Kazuhide; Haruma, Ken; Joh, Takashi

2015-11-01

Proton pump inhibitors are the first-line treatment for reflux esophagitis. Because severe reflux esophagitis has very low prevalence in Japan, little is known about the effectiveness of proton pump inhibitors in these patients. This prospective multicenter study assessed the effectiveness of proton pump inhibitors for severe reflux esophagitis in Japan. Patients with modified Los Angeles grade C or D reflux esophagitis were treated with daily omeprazole (10 or 20 mg), lansoprazole (15 or 30 mg), or rabeprazole (10, 20, or 40 mg) for 8 weeks. Healing was assessed endoscopically, with questionnaires administered before and after treatment to measure the extent of reflux and dyspepsia symptoms. Factors affecting healing rates, including patient characteristics and endoscopic findings, were analyzed. Of the 115 patients enrolled, 64 with grade C and 19 with grade D reflux esophagitis completed the study. The healing rate was 67.5% (56/83), with 15 of the other 27 patients (55.6%) improving to grade A or B. No patient characteristic or endoscopic comorbidity was significantly associated with healing rate. Reflux and dyspepsia symptoms improved significantly with treatment. The low healing rate suggests the need of endoscopic examination to assess healing of reflux esophagitis at the end of therapy. (UMIN000005271).

Persistent reflux symptoms cause anxiety, depression, and mental health and sleep disorders in gastroesophageal reflux disease patients.

PubMed

Kimura, Yoshihide; Kamiya, Takeshi; Senoo, Kyouji; Tsuchida, Kenji; Hirano, Atsuyuki; Kojima, Hisayo; Yamashita, Hiroaki; Yamakawa, Yoshihiro; Nishigaki, Nobuhiro; Ozeki, Tomonori; Endo, Masatsugu; Nakanishi, Kazuhisa; Sando, Motoki; Inagaki, Yusuke; Shikano, Michiko; Mizoshita, Tsutomu; Kubota, Eiji; Tanida, Satoshi; Kataoka, Hiromi; Katsumi, Kohei; Joh, Takashi

2016-07-01

Some patients with gastroesophageal reflux disease experience persistent reflux symptoms despite proton pump inhibitor therapy. These symptoms reduce their health-related quality of life. Our aims were to evaluate the relationship between proton pump inhibitor efficacy and health-related quality of life and to evaluate predictive factors affecting treatment response in Japanese patients. Using the gastroesophageal reflux disease questionnaire, 145 gastroesophageal reflux disease patients undergoing proton pump inhibitor therapy were evaluated and classified as responders or partial-responders. Their health-related quality of life was then evaluated using the 8-item Short Form Health Survey, the Pittsburgh Sleep Quality Index, and the Hospital Anxiety and Depression Scale questionnaires. Sixty-nine patients (47.6%) were partial responders. These patients had significantly lower scores than responders in 5/8 subscales and in the mental health component summary of the 8-item Short Form Health Survey. Partial responders had significantly higher Pittsburgh Sleep Quality Index and Hospital Anxiety and Depression Scale scores, including anxiety and depression scores, than those of responders. Non-erosive reflux disease and double proton pump inhibitor doses were predictive factors of partial responders. Persistent reflux symptoms, despite proton pump inhibitor therapy, caused mental health disorders, sleep disorders, and psychological distress in Japanese gastroesophageal reflux disease patients.

The overlap of gastroesophageal reflux disease and functional constipation in children: the efficacy of constipation treatment.

PubMed

Baran, Masallah; Cagan Appak, Yeliz; Karakoyun, Miray; Yalcinkaya, Sevda; Eliacik, Kayi; Dundar, Bumin N

2017-11-01

This study was designed to investigate the frequency of gastroesophageal reflux disease (GERD) in children with functional constipation (FC). It was structured to assess the improvement level in reflux symptoms by measuring the acid reflux in these patients after they had received FC treatment. Ninety-four children who suffered from constipation were evaluated prospectively. Data forms were completed to assess the GERD symptoms in all the cases. Twenty-four-hour pH meter monitoring was performed in 55 of the patients with GERD symptoms. The cases with abnormal acid reflux were treated by conventional therapy for FC. These cases were re-evaluated for GERD symptoms and weekly defecation frequency, and 24-h pH meter monitoring was performed at the end of a 3-month period. An abnormal level of acid reflux was determined in 23 of the 55 cases. After the constipation treatment, a significant improvement was achieved in the acid reflux index and GERD symptoms, whereas the weekly defecation frequency increased. GERD is a frequent problem in children with FC. Treatment of the constipation can improve the reflux symptoms and abnormal acid reflux in these cases. Physicians should bear in mind the co-occurrence of these two prevalent problems for better disease management.

Pathogenesis of Potassium-Competitive Acid Blocker-Resistant Non-Erosive Reflux Disease.

PubMed

Kawami, Noriyuki; Hoshino, Shintaro; Hoshikawa, Yoshimasa; Takenouchi, Nana; Umezawa, Mariko; Hanada, Yuriko; Kaise, Mitsuru; Iwakiri, Katsuhiko

2018-06-05

The present study examined the pathogenesis of potassium-competitive acid blocker (P-CAB)-resistant non-erosive reflux disease (NERD). Forty-three patients with NERD, who had persistent reflux symptoms despite the administration of P-CAB, were included in this study. After excluding eosinophilic esophagitis and primary esophageal motility disorders, esophageal impedance-pH monitoring was performed. In symptom index (SI)-positive patients, the mechanism of SI-positivity and percent time with intragastric pH > 4 and with esophageal pH < 4 were investigated according to the presence or absence of Helicobacter pylori infection. One (2.3%) of 43 patients had a primary esophageal motility disorder (Jackhammer esophagus). Eighteen (41.9%) and 3 (7%) patients were SI-positive for liquid and gas-only reflux, respectively, and the remaining 21 patients who were SI-negative (48.8%) had functional heartburn. All patients SI-positive for liquid reflux were SI-positive for weakly acidic reflux. Gastric acid was sufficiently suppressed by P-CAB, regardless of the presence or absence of H. pylori infection. The pathogenesis of -P-CAB-resistant NERD was elucidated in 51% of patients. Symptoms in all patients SI-positive for liquid reflux were related to weakly acidic reflux, and symptoms related to acid reflux may be ruled out by the administration of P-CAB. © 2018 S. Karger AG, Basel.

Reflux episodes and esophageal impedance levels in patients with typical and atypical symptoms of gastroesophageal reflux disease.

PubMed

Ye, Bi Xing; Jiang, Liu Qin; Lin, Lin; Wang, Ying; Wang, Meifeng

2017-09-01

To determine the relationship between baseline impedance levels and gastroesophageal reflux, we retrospectively enrolled 110 patients (54 men and 56 female; mean age, 51 ± 14 years) with suspected gastroesophageal reflux disease (GERD) who underwent 24-h multichannel intraluminal impedance and pH monitoring. Patients were stratified according to symptom (typical or atypical) and reflux types (acid reflux, nonacid reflux [NAR], or no abnormal reflux). Mean nocturnal baseline impedance (MNBI) were measured 3 cm (distal esophagus) and 17 cm (proximal esophagus) above the lower esophageal sphincter. Median distal esophageal MNBI was lower in the acid reflux group (1244 Ω; 647-1969 Ω) than in the NAR (2586 Ω; 1368-3666 Ω) or no abnormal reflux groups (3082 Ω; 2495-4472 Ω; all P < .05). Distal MNBI were negatively correlated with DeMeester score and acid exposure time. Atypical symptoms were more frequently associated with NAR than typical symptoms (P < .01). Among patients with positive symptom-association probability (SAP) for NAR, median proximal MNBI tended to be lower in patients with typical symptoms (median, 3013 Ω; IQR, 2535-3410 Ω) than in those with atypical symptoms (median, 3386 Ω; IQR, 3044-3730 Ω, P = .05). Thus, atypical GERD symptoms were more likely to be associated with NAR. The mucosal integrity of the proximal esophagus might be relatively impaired in GERD patients with typical symptoms for NAR.

Work productivity and activity impairment in gastroesophageal reflux disease in Korean full-time employees: a multicentre study.

PubMed

Shin, Woon Geon; Kim, Heung Up; Kim, Sang Gyun; Kim, Gwang Ha; Shim, Ki-Nam; Kim, Jeong Wook; Kim, Jin Il; Kim, Jae Gyu; Kim, Jae J; Yim, Da-Hae; Park, Sue K; Park, Soo-Heon

2012-04-01

The costs of gastroesophageal reflux disease have not been assessed in Asia, even though the prevalence of gastroesophageal reflux disease is gradually increasing. We evaluated work presenteeism and absenteeism as indirect costs of gastroesophageal reflux disease in Korea. This was a cross-sectional and multicentre study using patient-reported outcome instruments. A total of 1009 full-time employees who visited the gastrointestinal department for any reason (281 patients with gastroesophageal reflux disease and 728 controls) were included. Main outcomes were presenteeism and absenteeism measured as work productivity loss and monetary cost per week. Absenteeism and presenteeism were significantly higher in the gastroesophageal reflux disease than the control group (1.49% vs. 0.46%, P=0.0010; 34.13% vs. 9.23%, P<0.0001). Loss of work productivity was significantly greater in the gastroesophageal reflux disease than the control group (33.09% vs. 9.02%; P<0.0001). This loss of work productivity difference between the two groups represented an additional productivity loss of 11.7h/week in the gastroesophageal reflux disease group compared with the control group. Assuming average hourly wages of $14.12, the weekly burden of gastroesophageal reflux disease reached $165.07 per person. Gastroesophageal reflux disease was associated with substantial work productivity loss, mainly due to presenteeism rather than absenteeism, in Korean full-time employees. Copyright © 2011 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Esophageal motility abnormalities in gastroesophageal reflux disease

PubMed Central

Martinucci, Irene; de Bortoli, Nicola; Giacchino, Maria; Bodini, Giorgia; Marabotto, Elisa; Marchi, Santino; Savarino, Vincenzo; Savarino, Edoardo

2014-01-01

Esophageal motility abnormalities are among the main factors implicated in the pathogenesis of gastroesophageal reflux disease. The recent introduction in clinical and research practice of novel esophageal testing has markedly improved our understanding of the mechanisms contributing to the development of gastroesophageal reflux disease, allowing a better management of patients with this disorder. In this context, the present article intends to provide an overview of the current literature about esophageal motility dysfunctions in patients with gastroesophageal reflux disease. Esophageal manometry, by recording intraluminal pressure, represents the gold standard to diagnose esophageal motility abnormalities. In particular, using novel techniques, such as high resolution manometry with or without concurrent intraluminal impedance monitoring, transient lower esophageal sphincter (LES) relaxations, hypotensive LES, ineffective esophageal peristalsis and bolus transit abnormalities have been better defined and strongly implicated in gastroesophageal reflux disease development. Overall, recent findings suggest that esophageal motility abnormalities are increasingly prevalent with increasing severity of reflux disease, from non-erosive reflux disease to erosive reflux disease and Barrett’s esophagus. Characterizing esophageal dysmotility among different subgroups of patients with reflux disease may represent a fundamental approach to properly diagnose these patients and, thus, to set up the best therapeutic management. Currently, surgery represents the only reliable way to restore the esophagogastric junction integrity and to reduce transient LES relaxations that are considered to be the predominant mechanism by which gastric contents can enter the esophagus. On that ground, more in depth future studies assessing the pathogenetic role of dysmotility in patients with reflux disease are warranted. PMID:24868489

Esophageal motility abnormalities in gastroesophageal reflux disease.

PubMed

Martinucci, Irene; de Bortoli, Nicola; Giacchino, Maria; Bodini, Giorgia; Marabotto, Elisa; Marchi, Santino; Savarino, Vincenzo; Savarino, Edoardo

2014-05-06

Esophageal motility abnormalities are among the main factors implicated in the pathogenesis of gastroesophageal reflux disease. The recent introduction in clinical and research practice of novel esophageal testing has markedly improved our understanding of the mechanisms contributing to the development of gastroesophageal reflux disease, allowing a better management of patients with this disorder. In this context, the present article intends to provide an overview of the current literature about esophageal motility dysfunctions in patients with gastroesophageal reflux disease. Esophageal manometry, by recording intraluminal pressure, represents the gold standard to diagnose esophageal motility abnormalities. In particular, using novel techniques, such as high resolution manometry with or without concurrent intraluminal impedance monitoring, transient lower esophageal sphincter (LES) relaxations, hypotensive LES, ineffective esophageal peristalsis and bolus transit abnormalities have been better defined and strongly implicated in gastroesophageal reflux disease development. Overall, recent findings suggest that esophageal motility abnormalities are increasingly prevalent with increasing severity of reflux disease, from non-erosive reflux disease to erosive reflux disease and Barrett's esophagus. Characterizing esophageal dysmotility among different subgroups of patients with reflux disease may represent a fundamental approach to properly diagnose these patients and, thus, to set up the best therapeutic management. Currently, surgery represents the only reliable way to restore the esophagogastric junction integrity and to reduce transient LES relaxations that are considered to be the predominant mechanism by which gastric contents can enter the esophagus. On that ground, more in depth future studies assessing the pathogenetic role of dysmotility in patients with reflux disease are warranted.

Plasma lathosterol as a screening test for bile acid malabsorption due to ileal resection: correlation with 75SeHCAT test and faecal bile acid excretion.

PubMed

Färkkilä, M A; Kairemo, K J; Taavitsainen, M J; Strandberg, T A; Miettinen, T A

1996-04-01

1. Plasma lathosterol concentration, known to reflect cholesterol and bile acid synthesis, was evaluated as a screening test for bile acid malabsorption, comparing it with faecal bile acid measurements, SeHCAT test and Schilling test in 22 subjects of whom six were healthy controls and 16 had Crohn's disease with ileal resections of varying length. 2. Plasma lathosterols and other non-cholesterol sterols were determined by GLC. Faecal bile acids were measured by GLC, and SeHCAT retention times by gamma camera. The study subjects were divided into two groups according to the degree of bile acid malabsorption: controls (faecal bile acids < 10 mg day-1 kg-1, n = 9) and bile acid malabsorption (faecal bile acids > 10 mg day-1 kg-1, n = 13). 3. Faecal bile acid excretion was 5.9 +/- 1.0 mg day-1 kg-1 in control subjects and 45.7 +/- 6.1 mg day-1 kg-1 in the bile acid malabsorption group. The biological half-life of 75SeHCAT (T1/2) was 95.6 +/- 16.3 h and 14.1 +/- 4.1 h, respectively. Plasma lathosterol levels were significantly elevated in patients with bile acid malabsorption (742 +/- 84 micrograms/ml compared with 400 +/- 59 micrograms/ml in control subjects) and correlated closely with faecal bile acid levels (r = 0.779, P < 0.001), with 75SeHCAT T1/2 (r = -0.524, P < 0.05) and with Schilling test (r = -0.591, P < 0.05). Significant correlations were also obtained for delta 8-cholestenol with faecal bile acids (r = 0.784, P < 0.001) and 75SeHCAT (r = -0.505, P < 0.05). The biological half-life of SeHCAT correlated with faecal bile acid excretion (r = -0.702, P < 0.001). Using mean+2 SD of lathosterol (In micrograms/ml cholesterol) as a cut-off value and 10 mg day-1 kg-1 as the upper limit for faecal bile acid excretion, the test gives 100% sensitivity and 82% specificity for plasma lathosterol determination to detect bile acid malabsorption. 4. The results indicate that both the 75SeHCAT test and plasma lathosterol detect bile acid malabsorption in patients with ileal resections for Crohn's disease. However, plasma lathosterol is a simpler and less expensive method.

Probabilities of Dilating Vesicoureteral Reflux in Children with First Time Simple Febrile Urinary Tract Infection, and Normal Renal and Bladder Ultrasound.

PubMed

Rianthavorn, Pornpimol; Tangngamsakul, Onjira

2016-11-01

We evaluated risk factors and assessed predicted probabilities for grade III or higher vesicoureteral reflux (dilating reflux) in children with a first simple febrile urinary tract infection and normal renal and bladder ultrasound. Data for 167 children 2 to 72 months old with a first febrile urinary tract infection and normal ultrasound were compared between those who had dilating vesicoureteral reflux (12 patients, 7.2%) and those who did not. Exclusion criteria consisted of history of prenatal hydronephrosis or familial reflux and complicated urinary tract infection. The logistic regression model was used to identify independent variables associated with dilating reflux. Predicted probabilities for dilating reflux were assessed. Patient age and prevalence of nonEscherichia coli bacteria were greater in children who had dilating reflux compared to those who did not (p = 0.02 and p = 0.004, respectively). Gender distribution was similar between the 2 groups (p = 0.08). In multivariate analysis older age and nonE. coli bacteria independently predicted dilating reflux, with odds ratios of 1.04 (95% CI 1.01-1.07, p = 0.02) and 3.76 (95% CI 1.05-13.39, p = 0.04), respectively. The impact of nonE. coli bacteria on predicted probabilities of dilating reflux increased with patient age. We support the concept of selective voiding cystourethrogram in children with a first simple febrile urinary tract infection and normal ultrasound. Voiding cystourethrogram should be considered in children with late onset urinary tract infection due to nonE. coli bacteria since they are at risk for dilating reflux even if the ultrasound is normal. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Is the etiology of eosinophilic esophagitis in adults a response to allergy or reflux injury? Study of cellular proliferation markers.

PubMed

Lewis, C J; Lamb, C A; Kanakala, V; Pritchard, S; Armstrong, G R; Attwood, S E A

2009-01-01

Recent research suggests that allergy may be the key factor in the etiology of eosinophilic esophagitis (EE); however, historically, the condition was hypothesized as related to reflux injury to the esophageal mucosa. We studied this hypothesis by comparing markers of inflammation and cellular proliferation in EE and reflux esophagitis. Lower esophageal biopsies of adult patients with EE (n = 10), reflux esophagitis (n = 8), and normal controls (n = 13) were assessed quantitatively for the expression of the cyclooxygenase-2 (COX-2) enzyme, cellular proliferation, and oncogenic resistance to apoptosis using monoclonal antibodies for COX-2, Ki-67, and Bcl-2, respectively. Normal esophageal epithelium demonstrated weak diffuse uptake of COX-2 stain in the basal layer. No COX-2 expression was demonstrated in the EE group, significantly less than the control and reflux groups (P < 0.01 and P < 0.001, respectively). Cellular proliferation measured by Ki-67 expression was higher in EE and reflux compared with control (P < 0.001 and P < 0.01). Ki-67 expression, and thus degree of hyperplasia, appeared greater in EE than reflux, but was not statistically significant (P = 0.228). The degree of apoptosis was similar in all study groups. EE and reflux esophagitis are proliferative conditions expressing Ki-67 in higher concentrations than control. Mucosal proliferation in reflux esophagitis is COX-2 dependent. This novel research in EE has demonstrated downregulation of COX-2 expression compared with reflux esophagitis and control. We hypothesize that the allergy-related cytokine IL-13 known to inhibit COX-2 expression and found in high concentrations in EE as responsible for this. The pathogenesis of EE is likely dependent on allergy rather than reflux injury to the esophagus.

Sleeve gastrectomy and anti-reflux procedures.

PubMed

Crawford, Christopher; Gibbens, Kyle; Lomelin, Daniel; Krause, Crystal; Simorov, Anton; Oleynikov, Dmitry

2017-03-01

Obesity is an epidemic in the USA that continues to grow, becoming a leading cause of premature avoidable death. Bariatric surgery has become an effective solution for obesity and its comorbidities, and one of the most commonly utilized procedures, the sleeve gastrectomy, can lead to an increase in gastroesophageal reflux following the operation. While these data are controversial, sometimes operative intervention can be necessary to provide durable relief for this problem. We performed an extensive literature review examining the different methods of anti-reflux procedures that are available both before and after a sleeve gastrectomy. We reviewed several different types of anti-reflux procedures, including those that supplement the lower esophageal sphincter anatomy, such as magnetic sphincter augmentation and radiofrequency ablation procedures. Re-operation was also discussed as a possible treatment of reflux in sleeve gastrectomy, especially if the original sleeve becomes dilated or if a conversion to a Roux-en-Y gastric bypass or biliopancreatic diversion is deemed necessary. Sleeve gastrectomy with concomitant anti-reflux procedure was also reviewed, including the anti-reflux gastroplasty, hiatal hernia repair, and limited fundoplication. A number of techniques can be used to mitigate the severity of reflux, either by maintaining the normal anatomic structures that limit reflux or by supplementing these structures with a plication or gastroplasty. Individuals with existing severe reflux should not be considered for a sleeve gastrectomy. New techniques that incorporate plication at the time of the index sleeve gastrectomy show some improvement, but these are in small series that will need to be further evaluated. The only proven method of treating intractable reflux after sleeve gastrectomy is conversion to a Roux-en-Y gastric bypass.

Control of transient lower oesophageal sphincter relaxations and reflux by the GABAB agonist baclofen in patients with gastro-oesophageal reflux disease

PubMed Central

Zhang, Q; Lehmann, A; Rigda, R; Dent, J; Holloway, R H

2002-01-01

Background and aims: Transient lower oesophageal sphincter relaxations (TLOSRs) are the major cause of gastro-oesophageal reflux in normal subjects and in most patients with reflux disease. The gamma aminobutyric acid (GABA) receptor type B agonist, baclofen, is a potent inhibitor of TLOSRs in normal subjects. The aim of this study was to investigate the effect of baclofen on TLOSRs and postprandial gastro-oesophageal reflux in patients with reflux disease. Methods: In 20 patients with reflux disease, oesophageal motility and pH were measured, with patients in the sitting position, for three hours after a 3000 kJ mixed nutrient meal. On separate days at least one week apart, 40 mg oral baclofen or placebo was given 90 minutes before the meal. Results: Baclofen reduced the rate of TLOSRs by 40% from 15 (13.8–18.3) to 9 (5.8–13.3) per three hours (p<0.0002) and increased basal lower oesophageal sphincter pressure. Baclofen also significantly reduced the rate of reflux episodes by 43% from 7.0 (4.0–12.0) to 4.0 (1.5–9) per three hours (median (interquartile range); p<0.02). However, baclofen had no effect on oesophageal acid exposure (baclofen 4.9% (1.7–12.4) v placebo 5.0% (2.7–15.5)). Conclusions: In patients with reflux disease, the GABAB agonist baclofen significantly inhibits gastro-oesophageal reflux episodes by inhibition of TLOSRs. These findings suggest that GABAB agonists may be useful as therapeutic agents for the management of reflux disease. PMID:11772961

Therapeutic targeting of bile acids

PubMed Central

Gores, Gregory J.

2015-01-01

The first objectives of this article are to review the structure, chemistry, and physiology of bile acids and the types of bile acid malabsorption observed in clinical practice. The second major theme addresses the classical or known properties of bile acids, such as the role of bile acid sequestration in the treatment of hyperlipidemia; the use of ursodeoxycholic acid in therapeutics, from traditional oriental medicine to being, until recently, the drug of choice in cholestatic liver diseases; and the potential for normalizing diverse bowel dysfunctions in irritable bowel syndrome, either by sequestering intraluminal bile acids for diarrhea or by delivering more bile acids to the colon to relieve constipation. The final objective addresses novel concepts and therapeutic opportunities such as the interaction of bile acids and the microbiome to control colonic infections, as in Clostridium difficile-associated colitis, and bile acid targeting of the farnesoid X receptor and G protein-coupled bile acid receptor 1 with consequent effects on energy expenditure, fat metabolism, and glycemic control. PMID:26138466

GERD

MedlinePlus

Gastroesophageal reflux disease (GERD) Overview Gastroesophageal reflux disease (GERD) occurs when stomach acid frequently flows back into the tube connecting your mouth and stomach (esophagus). This backwash (acid reflux) ...

Bladder volume at onset of vesicoureteral reflux is an independent risk factor for breakthrough febrile urinary tract infection.

PubMed

Alexander, Siobhan E; Arlen, Angela M; Storm, Douglas W; Kieran, Kathleen; Cooper, Christopher S

2015-04-01

Improved identification of children with vesicoureteral reflux at risk for recurrent febrile urinary tract infection may impact management decisions. We hypothesized that reflux occurring earlier during bladder filling increases the duration of exposure of the kidneys to bacteria, and, therefore, increases the risk of pyelonephritis. Children with vesicoureteral reflux and detailed voiding cystourethrogram data were identified. Bladder volume at onset of reflux was normalized for age. Demographics, reflux grade, laterality, presence/absence of bladder-bowel dysfunction and breakthrough febrile urinary tract infections were assessed. Median followup was 24 months (IQR 12 to 52). A total of 208 girls and 47 boys were analyzed with a mean ± SD age at diagnosis of 3.1 ± 2.6 years. On univariate analysis history of febrile urinary tract infection (HR 2.17, 95% CI 1.33-2.85, p = 0.01), dilating vesicoureteral reflux (HR 1.6, 95% CI 1.05-2.42, p = 0.03) and bladder-bowel dysfunction (HR 1.66, 95% CI 0.99-2.75, p = 0.05) were associated with an increased risk of breakthrough febrile urinary tract infection. Median bladder volume at onset of reflux in children with breakthrough febrile urinary tract infection was significantly less (33.1%) than in those without infection (49.5%, p = 0.003). Reflux onset at 35% predicted bladder capacity or less was associated with a significantly increased risk of breakthrough febrile urinary tract infection on multivariate analysis (HR 1.58, 95% CI 1.05-2.38, p = 0.03). Children with early filling vesicoureteral reflux are at increased risk for breakthrough febrile urinary tract infection independent of reflux grade. Bladder volume at onset of reflux should be recorded during cystograms since it provides additional prognostic information about the risk of pyelonephritis and resolution, and may assist with counseling and clinical decision making. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

The influence of the speed of food intake on multichannel impedance in patients with gastro-oesophageal reflux disease

PubMed Central

Bor, Serhat; Bayrakci, Berna; Yildirim, Esra; Vardar, Rukiye

2013-01-01

Background There is a general belief that gastro-oesophageal reflux increases after meals and especially following a rapid intake. Objective To evaluate the impact of rapid vs. slow food intake on gastro-oesophageal reflux disease (GORD) patients. Materials and methods Forty-six GORD patients with heartburn and / or acid regurgitation once a week or more often common were included in this study. Participants were asked to eat the same standard meal within either 5 or 30 minutes under observation in a random order on 2 consecutive days. A total of 28 hours of recording were obtained by intraoesophageal impedance pH and number of liquid and mixed reflux episodes within 3 hours of the slow- and fast-eating postprandial periods were calculated. Results While all patients defined GORD symptoms, 10 (21.7%) had pathological 24-h intraoesophageal impedance measurement, 15 (32.6%) had pathological DeMeester and 21.7% had erosive oesophagitis. No difference has been shown according to the eating speed when all reflux episodes were taken together (754 vs. 733). Speed of food intake also did not have an impact on patients with normal vs. pathological 24-h intraoesophageal impedance or erosive vs. non-erosive. During the first postprandial hour, approximately half of the reflux events were non-acid, compared to 34.2% during the second hour and 26.8% during the third hour (p < 0.001). The number of acid reflux episodes was significantly higher than non-acid reflux especially during the second and third hours and in total for 3 hours. Conclusions This first study addressing the effect of eating speed on reflux episodes in GORD patients did not support the general belief that reflux increases following fast eating. Acid and non-acid reflux were similar at the first postprandial hour, then acid reflux episodes were predominantly higher, which implicate the importance of acid pockets. PMID:24917982

Idiopathic pulmonary fibrosis is associated with increased impedance measures of reflux compared to non-fibrotic disease among pre-lung transplant patients.

PubMed

Gavini, S; Finn, R T; Lo, W-K; Goldberg, H J; Burakoff, R; Feldman, N; Chan, W W

2015-09-01

Gastroesophageal reflux (GER) has been associated with idiopathic pulmonary fibrosis (IPF), although the mechanism remains unclear. Gastroesophageal reflux/microaspiration may lead to lung fibrosis, while increased pulmonary workload may also worsen GER. Comparing the GER profile of IPF patients to chronic obstructive pulmonary disease (COPD) patients with similar lung function may help delineate the role of GER in IPF pathogenesis. This was a retrospective cohort study of IPF and COPD patients undergoing pre-lung transplant multichannel intraluminal impedance and pH study (MII-pH) off acid suppression at a tertiary center in 2008-2014. Patients with prior fundoplication were excluded. Baseline demographics, pulmonary function test, and MII-pH results were recorded. Univariate analyses were performed using Fisher's exact (binary variables) and Student's t (continuous variables) tests. Logistic regression was performed to adjust for potential confounders. A total of 90 subjects (54 IPF, 36 COPD) met inclusion criteria. Compared to COPD, IPF patients had increased total reflux episodes (65.9 vs 46.1, p = 0.02), proximal reflux episodes (30.3 vs 20.3, p = 0.04), and prevalence of abnormal total reflux episodes (38.9% vs 16.7%, p = 0.02). On multivariate analyses, abnormal total reflux episodes (OR: 4.9, p = 0.05) and bolus reflux exposure time (OR: 4, p = 0.04) remained significantly associated with IPF. Abnormal reflux was significantly more prevalent among IPF patients after controlling for lung disease severity. Gastroesophageal reflux/microaspiration likely plays a role in fibrosis in IPF. A significant portion of IPF patients had increased non-acid reflux. Therapies aiming to prevent reflux of gastric contents may be more beneficial than antisecretory medications alone in these patients. © 2015 John Wiley & Sons Ltd.

The influence of the speed of food intake on multichannel impedance in patients with gastro-oesophageal reflux disease.

PubMed

Bor, Serhat; Bayrakci, Berna; Erdogan, Askin; Yildirim, Esra; Vardar, Rukiye

2013-10-01

There is a general belief that gastro-oesophageal reflux increases after meals and especially following a rapid intake. To evaluate the impact of rapid vs. slow food intake on gastro-oesophageal reflux disease (GORD) patients. Forty-six GORD patients with heartburn and / or acid regurgitation once a week or more often common were included in this study. Participants were asked to eat the same standard meal within either 5 or 30 minutes under observation in a random order on 2 consecutive days. A total of 28 hours of recording were obtained by intraoesophageal impedance pH and number of liquid and mixed reflux episodes within 3 hours of the slow- and fast-eating postprandial periods were calculated. While all patients defined GORD symptoms, 10 (21.7%) had pathological 24-h intraoesophageal impedance measurement, 15 (32.6%) had pathological DeMeester and 21.7% had erosive oesophagitis. No difference has been shown according to the eating speed when all reflux episodes were taken together (754 vs. 733). Speed of food intake also did not have an impact on patients with normal vs. pathological 24-h intraoesophageal impedance or erosive vs. non-erosive. During the first postprandial hour, approximately half of the reflux events were non-acid, compared to 34.2% during the second hour and 26.8% during the third hour (p < 0.001). The number of acid reflux episodes was significantly higher than non-acid reflux especially during the second and third hours and in total for 3 hours. This first study addressing the effect of eating speed on reflux episodes in GORD patients did not support the general belief that reflux increases following fast eating. Acid and non-acid reflux were similar at the first postprandial hour, then acid reflux episodes were predominantly higher, which implicate the importance of acid pockets.

Gastro-oesophageal reflux is common in oligosymptomatic patients with dental erosion: A pH-impedance and endoscopic study

PubMed Central

Materna, Andrea; Martig, Lukas; Lussi, Adrian

2015-01-01

Background Dental erosion is a complication of gastro-oesophageal reflux disease (GORD) according to the Montreal consensus statement. However, GORD has not been comprehensively characterized in patients with dental erosions and pH-impedance measures have not been reported. Objectives Characterize GORD in patients with dental erosions using 24-h multichannel intraluminal pH-impedance measurements (pH-MII) and endoscopy. Methods This single-centre study investigated reflux in successive patients presenting to dentists with dental erosion using pH-MII and endoscopy. Results Of the 374 patients, 298 (80%) reported GORD symptoms <2 per week, 72 (19%) had oesophagitis and 59 (16%) had a hiatal hernia. In the 349 with pH-MII the mean percentage time with a pH <4 (95% CI) was 11.0 (9.3–12.7), and 34.4% (31.9–36.9) for a pH <5.5, a critical threshold for dental tissue. The mean numbers of total, acidic and weakly acidic reflux episodes were 71 (63–79), 43 (38–49) and 31 (26–35), respectively. Of the reflux episodes, 19% (17–21) reached the proximal oesophagus. In 241 (69%) patients reflux was abnormal using published normal values for acid exposure time and reflux episodes. No significant associations between the severity of dental erosions and any reflux variables were found. The presence of GORD symptoms and of oesophagitis or a hiatal hernia was associated with greater reflux, but not with increased dental erosion scores. Conclusions Significant oligosymptomatic gastro-oesophageal reflux occurs in the majority of patients with dental erosion. The degree of dental erosion did not correlate with any of the accepted quantitative reflux indicators. Definition of clinically relevant reflux parameters by pH-MII for dental erosion and of treatment guidelines are outstanding. Gastroenterologists and dentists need to be aware of the widely prevalent association between dental erosion and atypical GORD. PMID:25922678

Gastro-oesophageal reflux is common in oligosymptomatic patients with dental erosion: A pH-impedance and endoscopic study.

PubMed

Wilder-Smith, Clive H; Materna, Andrea; Martig, Lukas; Lussi, Adrian

2015-04-01

Dental erosion is a complication of gastro-oesophageal reflux disease (GORD) according to the Montreal consensus statement. However, GORD has not been comprehensively characterized in patients with dental erosions and pH-impedance measures have not been reported. Characterize GORD in patients with dental erosions using 24-h multichannel intraluminal pH-impedance measurements (pH-MII) and endoscopy. This single-centre study investigated reflux in successive patients presenting to dentists with dental erosion using pH-MII and endoscopy. Of the 374 patients, 298 (80%) reported GORD symptoms <2 per week, 72 (19%) had oesophagitis and 59 (16%) had a hiatal hernia. In the 349 with pH-MII the mean percentage time with a pH <4 (95% CI) was 11.0 (9.3-12.7), and 34.4% (31.9-36.9) for a pH <5.5, a critical threshold for dental tissue. The mean numbers of total, acidic and weakly acidic reflux episodes were 71 (63-79), 43 (38-49) and 31 (26-35), respectively. Of the reflux episodes, 19% (17-21) reached the proximal oesophagus. In 241 (69%) patients reflux was abnormal using published normal values for acid exposure time and reflux episodes. No significant associations between the severity of dental erosions and any reflux variables were found. The presence of GORD symptoms and of oesophagitis or a hiatal hernia was associated with greater reflux, but not with increased dental erosion scores. Significant oligosymptomatic gastro-oesophageal reflux occurs in the majority of patients with dental erosion. The degree of dental erosion did not correlate with any of the accepted quantitative reflux indicators. Definition of clinically relevant reflux parameters by pH-MII for dental erosion and of treatment guidelines are outstanding. Gastroenterologists and dentists need to be aware of the widely prevalent association between dental erosion and atypical GORD.

Endoscopic Injection of Dextranomer/Hyaluronic Acid as First-Line Treatment in 851 Consecutive Children with High Grade Vesicoureteral Reflux: Efficacy and Long-Term Results.

PubMed

Friedmacher, Florian; Colhoun, Eric; Puri, Prem

2018-03-15

Endoscopic injection of dextranomer/hyaluronic is widely acknowledged as first-line treatment of lower grade vesicoureteral reflux. We demonstrate its long-term efficacy and safety in eradicating high grade reflux. A total of 518 girls and 333 boys with a median age of 2.3 years (range 2 months to 13.7 years) underwent endoscopic correction of high grade vesicoureteral reflux using dextranomer/hyaluronic acid. Reflux was unilateral in 415 cases and bilateral in 436, comprising 1,287 refluxing units. Reflux was grade IV in 1,153 ureters (89.6%) and grade V in 134 (10.4%). 99m Technetium dimercaptosuccinic acid scintigraphy identified renal scarring in 317 patients (37.3%). Followup ultrasound and voiding cystourethrogram were performed 3 months after intervention and renal ultrasound yearly thereafter. Median followup was 8.5 years (range 6 months to 16 years). Overall resolution rate after the first endoscopic injection was 69.5% (895 of 1,287 cases), with resolution in 70.4% of grade IV and 61.9% of grade V cases. Reflux resolved after a second injection in 259 cases (20.1%) and after a third injection in 133 (10.4%). Persistent reflux after initial treatment was significantly more common in patients younger than age 1 year and in individuals with renal scarring. No significant postoperative complications were observed and no patient required ureteral reimplantation. Following reflux resolution febrile urinary tract infection developed in 43 children (5.1%), including 24 (55.8%) during the first year, 15 (34.9%) during the second year and 4 (9.3%) during year 3 or later. Of these patients 6 had reflux recurrence and 8 had neocontralateral grade III reflux, which was successfully treated with a single endoscopic injection of dextranomer/hyaluronic acid. Endoscopic injection of dextranomer/hyaluronic acid is an efficient and safe long-term treatment for grade IV and V vesicoureteral reflux, and can easily be repeated in patients with treatment failure, with a high subsequent resolution rate. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

[Association between acid reflux and esophageal dysmotility in patients with gastroesophageal reflux disease].

PubMed

Yi, Zhi-hui; Feng, Li; Wen, Mao-yao; Liu, Jian-rong; Yang, Li

2014-05-01

To investigate the association between esophageal motility and acid reflux in patients with gastroesophageal reflux disease (GERD). A total of 94 patients with typical reflux symptoms such as heartburn, regurgitation and chest pain, whose score (Sc) of reflux diagnostic questionnaire (RDQ) was greater than or equal to 12 were enrolled in the study. Each participant was evaluated by upper gastrointestinal endoscopy, high resolution manometry (HRM) of esophagus and 24 h esophageal pH monitoring. The participants were divided into groups of reflux esophagitis (RE) and non-erosive reflux disease (NERD) on the basis of endoscopy findings. The 24 h esophageal pH monitoring categorized participants into physiologic reflux (pH) and pathologic reflux (pH+). The characteristics of esophageal motility and acid reflux were compared between the two groups of participants. Lower but non-significant differences (P > 0.05) were found in pressure of lower esophageal sphincter (LESP), length of lower esophageal sphincter (LESL), esophageal contraction amplitude (CA), distal contractile integral (DCI) and effective peristalsis proportion (EPP) in the participants in the RE group compared with those in the NERD group. Participants in the RE group had significantly higher prevalence of reduced LESP (63.0% vs. 31.7%, P < 0.01) and hiatus hernia (HH) (37.0% vs. 14.3%, P < 0.05) than those in the NERD group, pH+ was more prevalent in the RE group than in the NERD group (63.0% vs. 17.5%, P < 0.01). Indicators of 24 h esophageal pH monitoring were significantly higher in participants in the RE group compared with those in the NERD group (P < 0.05). Participants with pH+ had significantly lower LESP, CA and higher HH and prevalence of reduced LESP compared with those with pH (P < 0.05). LESL, DCI and EPP were lower in those with pH+ compared with those with pH-, but without statistical significance (P > 0.05). RE is closely associated with acid reflux and hiatus hernia. Esophageal dysmotility is more likely to appear in patients with pH+. The interaction of acid reflux and esophageal dysmotility may play a role in GERD.

Bile leakage test in liver resection: A systematic review and meta-analysis

PubMed Central

Wang, Hai-Qing; Yang, Jian; Yang, Jia-Yin; Yan, Lu-Nan

2013-01-01

AIM: To assess systematically the safety and efficacy of bile leakage test in liver resection. METHODS : Randomized controlled trials and controlled clinical trials involving the bile leakage test were included in a systematic literature search. Two authors independently assessed the studies for inclusion and extracted the data. A meta-analysis was conducted to estimate postoperative bile leakage, intraoperative positive bile leakage, and complications. We used either the fixed-effects or random-effects model. RESULTS: Eight studies involving a total of 1253 patients were included and they all involved the bile leakage test in liver resection. The bile leakage test group was associated with a significant reduction in bile leakage compared with the non-bile leakage test group (RR = 0.39, 95%CI: 0.23-0.67; I2 = 3%). The white test had superiority for detection of intraoperative bile leakage compared with the saline solution test (RR = 2.38, 95%CI: 1.24-4.56, P = 0.009). No significant intergroup differences were observed in total number of complications, ileus, liver failure, intraperitoneal hemorrhage, pulmonary disorder, abdominal infection, and wound infection. CONCLUSION: The bile leakage test reduced postoperative bile leakage and did not increase incidence of complications. Fat emulsion is the best choice of solution for the test. PMID:24363535

Bile leakage test in liver resection: a systematic review and meta-analysis.

PubMed

Wang, Hai-Qing; Yang, Jian; Yang, Jia-Yin; Yan, Lu-Nan

2013-12-07

To assess systematically the safety and efficacy of bile leakage test in liver resection. Randomized controlled trials and controlled clinical trials involving the bile leakage test were included in a systematic literature search. Two authors independently assessed the studies for inclusion and extracted the data. A meta-analysis was conducted to estimate postoperative bile leakage, intraoperative positive bile leakage, and complications. We used either the fixed-effects or random-effects model. Eight studies involving a total of 1253 patients were included and they all involved the bile leakage test in liver resection. The bile leakage test group was associated with a significant reduction in bile leakage compared with the non-bile leakage test group (RR = 0.39, 95%CI: 0.23-0.67; I (2) = 3%). The white test had superiority for detection of intraoperative bile leakage compared with the saline solution test (RR = 2.38, 95%CI: 1.24-4.56, P = 0.009). No significant intergroup differences were observed in total number of complications, ileus, liver failure, intraperitoneal hemorrhage, pulmonary disorder, abdominal infection, and wound infection. The bile leakage test reduced postoperative bile leakage and did not increase incidence of complications. Fat emulsion is the best choice of solution for the test. © 2013 Baishideng Publishing Group Co., Limited. All rights reserved.

Protection of dried probiotic bacteria from bile using bile adsorbent resins.

PubMed

Mahbubani, Krishnaa T; Slater, Nigel K H; Edwards, Alexander D

2014-01-25

Enteric coated oral tablets or capsules can deliver dried live cells directly into the intestine. Previously, we found that a live attenuated bacterial vaccine acquired sensitivity to intestinal bile when dried, raising the possibility that although gastric acid can be bypassed, significant loss of viability might occur on release from an enteric coated oral formulations. Here we demonstrate that some food-grade lyophilised preparations of Lactobacillus casei and Lactobacillus salivarius also show temporary bile sensitivity that can be rapidly reversed by rehydration. To protect dried bacterial cells from temporary bile sensitivity, we propose using bile acid adsorbing resins, such as cholestyramine, which are bile acid binding agents, historically used to lower cholesterol levels. Vcaps™ HPMC capsules alone provided up to 830-fold protection from bile. The inclusion of 50% w/w cholestyramine in Vcaps™ HPMC capsules resulted in release of up to 1700-fold more live Lactobacillus casei into simulated intestinal fluid containing 1% bile, when compared to dried cells added directly to bile. We conclude that delivery of dried live probiotic organisms to the intestine may be improved by providing protection from bile by addition of bile adsorbing resins and the use of HPMC capsules. Copyright © 2013 Elsevier B.V. All rights reserved.

Bile Acid Signaling in Metabolic Disease and Drug Therapy

PubMed Central

Li, Tiangang

2014-01-01

Bile acids are the end products of cholesterol catabolism. Hepatic bile acid synthesis accounts for a major fraction of daily cholesterol turnover in humans. Biliary secretion of bile acids generates bile flow and facilitates hepatobiliary secretion of lipids, lipophilic metabolites, and xenobiotics. In the intestine, bile acids are essential for the absorption, transport, and metabolism of dietary fats and lipid-soluble vitamins. Extensive research in the last 2 decades has unveiled new functions of bile acids as signaling molecules and metabolic integrators. The bile acid–activated nuclear receptors farnesoid X receptor, pregnane X receptor, constitutive androstane receptor, vitamin D receptor, and G protein–coupled bile acid receptor play critical roles in the regulation of lipid, glucose, and energy metabolism, inflammation, and drug metabolism and detoxification. Bile acid synthesis exhibits a strong diurnal rhythm, which is entrained by fasting and refeeding as well as nutrient status and plays an important role for maintaining metabolic homeostasis. Recent research revealed an interaction of liver bile acids and gut microbiota in the regulation of liver metabolism. Circadian disturbance and altered gut microbiota contribute to the pathogenesis of liver diseases, inflammatory bowel diseases, nonalcoholic fatty liver disease, diabetes, and obesity. Bile acids and their derivatives are potential therapeutic agents for treating metabolic diseases of the liver. PMID:25073467

Endoscopic Management of Bile Leakage after Liver Transplantation

PubMed Central

Oh, Dongwook; Lee, Sung Koo; Song, Tae Jun; Park, Do Hyun; Lee, Sang Soo; Seo, Dong-Wan; Kim, Myung-Hwan

2015-01-01

Background/Aims Endoscopic retrograde cholangiopancreatography (ERCP) can be an effective treatment for bile leakage after liver transplantation. We evaluated the efficacy of endoscopic treatment in liver transplantation in patients who developed bile leaks. Methods Forty-two patients who developed bile leaks after liver transplantation were included in the study. If a bile leak was observed on ERCP, a sphincterotomy was performed, and a nasobiliary catheter was then inserted. If a bile leak was accompanied by a bile duct stricture, either the stricture was dilated with balloons, followed by nasobiliary catheter insertion across the bile duct stricture, or endoscopic retrograde biliary drainage was performed. Results In the bile leakage alone group (22 patients), endoscopic treatment was technically successful in 19 (86.4%) and clinically successful in 17 (77.3%) cases. Among the 20 patients with bile leaks with bile duct strictures, endoscopic treatment was technically successful in 13 (65.0%) and clinically successful in 10 (50.0%) cases. Among the 42 patients who underwent ERCP, technical success was achieved in 32 (76.2%) cases and clinical success was achieved in 27 (64.3%) cases. Conclusions ERCP is an effective and safe therapeutic modality for bile leaks after liver transplantation. ERCP should be considered as an initial therapeutic modality in post-liver transplantation patients. PMID:25717048

Key discoveries in bile acid chemistry and biology and their clinical applications: history of the last eight decades

PubMed Central

Hofmann, Alan F.; Hagey, Lee R.

2014-01-01

During the last 80 years there have been extraordinary advances in our knowledge of the chemistry and biology of bile acids. We present here a brief history of the major achievements as we perceive them. Bernal, a physicist, determined the X-ray structure of cholesterol crystals, and his data together with the vast chemical studies of Wieland and Windaus enabled the correct structure of the steroid nucleus to be deduced. Today, C24 and C27 bile acids together with C27 bile alcohols constitute most of the bile acid “family”. Patterns of bile acid hydroxylation and conjugation are summarized. Bile acid measurement encompasses the techniques of GC, HPLC, and MS, as well as enzymatic, bioluminescent, and competitive binding methods. The enterohepatic circulation of bile acids results from vectorial transport of bile acids by the ileal enterocyte and hepatocyte; the key transporters have been cloned. Bile acids are amphipathic, self-associate in solution, and form mixed micelles with polar lipids, phosphatidylcholine in bile, and fatty acids in intestinal content during triglyceride digestion. The rise and decline of dissolution of cholesterol gallstones by the ingestion of 3,7-dihydroxy bile acids is chronicled. Scientists from throughout the world have contributed to these achievements. PMID:24838141

Superficial venous reflux duration and cessation with two concurrent duplex probes.

PubMed

Lattimer, Christopher R; Mendoza, Erika

2015-04-01

Venous reflux is the principal hemodynamic disorder and therapeutic target in patients with superficial venous insufficiency. To date, no studies have identified where or when it stops, anatomically or regionally, along the course of the refluxive conduit. Duplex measurements of reflux are performed invariably with a single probe. Because many anatomic locations are studied, repeated provocation maneuvers are required. However, this fails to appreciate reflux as a circulation. The use of two probes placed concurrently in different regions may address this limitation. The study compared venous reflux duration and cessation, above the knee and below the knee simultaneously, with two duplex probes. Seventeen legs from 17 consecutive patients (12 female, nine left) with great saphenous vein reflux were studied. Their median (range) age was 51 (28-71) years; weight, 76.8 (63.5-189) kg; height, 169 (153-180) cm; and Venous Clinical Severity Score, 5 (1-12). The clinical class of the Clinical, Etiologic, Anatomic, and Pathophysiologic (CEAP) classification was as follows: C2, 6; C3, 4; C4a, 5; and C4b, 2. After 2 minutes of elevation, the leg was assessed for reflux duration with duplex ultrasound. This occurred when the patient stood up during venous filling. One probe was positioned 10 cm below the saphenofemoral junction over the great saphenous vein (point A) and the other over a refluxive saphenous vein or tributary below the knee (point B). Concurrent images were displayed on adjacent monitors and recorded by a single video camera. Reflux duration was from the onset of dependency, indicated by the start of the video, to the termination of the red color (reflux) on video playback. The probes were swapped to negate for differences in machine sensitivity. Each leg was tested three times. Simultaneous was defined when there was <0.1 second difference between the two sites. The median (range) vein diameters at points A and B were 6.1 (2.8-9.3) mm and 5.5 (2.5-8.1) mm, respectively, with an intertransducer distance of 41 (23-59) cm. There was no significant difference in reflux duration between point A with 27 (9-150) seconds and point B with 27 (10-149) seconds (P = .943 [Wilcoxon]). The correlation was excellent (r = .986; P < .0005 [Spearman]). This is the first study to investigate reflux cessation by introducing a novel two-probe technique. It has demonstrated that reflux may stop simultaneously above and below the knee with use of the elevation to dependency maneuver to provoke reflux. It has shown that either site may be used to measure reflux duration. Furthermore, the two-probe technique confirms the belief that the mechanism of refluxive venous filling is through the descending path of a recirculation circuit. Copyright © 2015 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Microbiota transplantation restores normal fecal bile acid composition in recurrent Clostridium difficile infection.

PubMed

Weingarden, Alexa R; Chen, Chi; Bobr, Aleh; Yao, Dan; Lu, Yuwei; Nelson, Valerie M; Sadowsky, Michael J; Khoruts, Alexander

2014-02-15

Fecal microbiota transplantation (FMT) has emerged as a highly effective therapy for refractory, recurrent Clostridium difficile infection (CDI), which develops following antibiotic treatments. Intestinal microbiota play a critical role in the metabolism of bile acids in the colon, which in turn have major effects on the lifecycle of C. difficile bacteria. We hypothesized that fecal bile acid composition is altered in patients with recurrent CDI and that FMT results in its normalization. General metabolomics and targeted bile acid analyses were performed on fecal extracts from patients with recurrent CDI treated with FMT and their donors. In addition, 16S rRNA gene sequencing was used to determine the bacterial composition of pre- and post-FMT fecal samples. Taxonomic bacterial composition of fecal samples from FMT recipients showed rapid change and became similar to the donor after the procedure. Pre-FMT fecal samples contained high concentrations of primary bile acids and bile salts, while secondary bile acids were nearly undetectable. In contrast, post-FMT fecal samples contained mostly secondary bile acids, as did non-CDI donor samples. Therefore, our analysis showed that FMT resulted in normalization of fecal bacterial community structure and metabolic composition. Importantly, metabolism of bile salts and primary bile acids to secondary bile acids is disrupted in patients with recurrent CDI, and FMT corrects this abnormality. Since individual bile salts and bile acids have pro-germinant and inhibitory activities, the changes suggest that correction of bile acid metabolism is likely a major mechanism by which FMT results in a cure and prevents recurrence of CDI.

History of hepatic bile formation: old problems, new approaches.

PubMed

Javitt, Norman B

2014-12-01

Studies of hepatic bile formation reported in 1958 established that it was an osmotically generated water flow. Intravenous infusion of sodium taurocholate established a high correlation between hepatic bile flow and bile acid excretion. Secretin, a hormone that stimulates bicarbonate secretion, was also found to increase hepatic bile flow. The sources of the water entering the biliary system with these two stimuli were differentiated by the use of mannitol. An increase in its excretion parallels the increase in bile flow in response to bile acids but not secretin, which led to a quantitative distinction between canalicular and ductular water flow. The finding of aquaglyceroporin-9 in the basolateral surface of the hepatocyte accounted for the rapid entry of mannitol into hepatocytes and its exclusion from water movement in the ductules where aquaporin-1 is present. Electron microscopy demonstrated that bile acids generate the formation of vesicles that contain lecithin and cholesterol after their receptor-mediated canalicular transport. Biophysical studies established that the osmotic effect of bile acids varies with their concentration and also with the proportion of mono-, di-, and trihydroxy bile acids and provides a basis for understanding their physiological effects. Because of the varying osmotic effect of bile acids, it is difficult to quantify bile acid independent flow generated by other solutes, such as glutathione, which enters the biliary system. Monohydroxy bile acids, by markedly increasing aggregation number, severely reduce water flow. Developing biomarkers for the noninvasive assessment of normal hepatic bile flow remains an elusive goal that merits further study. Copyright © 2014 The American Physiological Society.

H. pylori in the pathogenesis of duodenal ulcer: interaction between duodenal acid load, bile, and H. pylori.

PubMed

Graham, D Y; Osato, M S

2000-01-01

Helicobacter pylori (H. pylori) growth is inhibited by bile yet it can grow in the duodenal bulb and cause ulcer disease. The aim of this study was to test the effect of bile on H. pylori viability and growth and to determine whether acidification of bile reduces its inhibitory activity. Fresh human bile was collected at laparotomy and tested for inhibitory activity of H. pylori using broth dilution assays. Six clinical isolates of H. pylori obtained from patients with duodenal ulcer were used for each experiment. The bile was diluted from 1:3 to 1:192; its inhibitory effect on H. pylori was tested before and after acidification, treatment with cholestyramine, or chloroform. Bile was acidified to a pH of 2-6, centrifuged at 8000 rpm for 20 min to remove precipitated bile acids, and the supernatant pH readjusted. Controls included BHI broth without bile (positive control) and bile that was acidified to pH 2 and neutralized without centrifugation. Human bile inhibited H. pylori growth in a dose dependent manner. Growth of all strains was supported for all strains only at a dilution of 1:192. In contrast, after acidification to pH < or =5 and centrifugation to remove precipitated bile acids, all strains grew at a bile dilution of 1:12. Neither chloroform extraction of lipids, nor acidification without centrifugation removed the inhibitory action of bile. In contrast, cholestyramine sequestration of bile acids completely removed all inhibitory activity. The duodenal acid load may be the critical factor to explain the ability of H. pylori to colonize the duodenal bulb by precipitating glycine-conjugated bile salts. The combination of a high duodenal acid load and H. pylori infection is likely the critical event in the pathogenesis of H. pylori-related duodenal ulcer disease.

The Mystery and Misery of Acid Reflux in Children

ERIC Educational Resources Information Center

Davenport, Mike; Davenport, Tracy

2006-01-01

When a child is sick, parents want answers. They want to know what is wrong, what they can do, and how to get their child healthy--pronto. Regrettably, there are some puzzling illnesses affecting children that are surrounded by mystery. One of them is gastroesophageal reflux (GER), otherwise known as acid reflux--or "reflux" for short. Reflux…

The oesophagus and cough: laryngo-pharyngeal reflux, microaspiration and vagal reflexes

PubMed Central

2013-01-01

Gastro-oesophageal reflux disease is generally considered to be one of the commonest causes of chronic cough, however randomised controlled trials of proton pump inhibitors have often failed to support this notion. This article reviews the most recent studies investigating the mechanisms thought to link reflux and cough, namely laryngo-pharyngeal reflux, micro-aspiration and neuronal cross-organ sensitisation. How recent evidence might shed light on the failure of acid suppressing therapies and suggest new approaches to treating reflux related cough are also discussed. PMID:23590893

Treatment of Post-Stent Gastroesophageal Reflux by Anti-Reflux Z-Stent

DOE Office of Scientific and Technical Information (OSTI.GOV)

Davies, Roger Philip; Kew, Jacqueline; Byrne, Peter D.

2000-11-15

Severe symptoms of heartburn and retrosternal pain consistent with gastro-esophageal reflux (GER) developed in a patient following placement of a conventional self-expanding 16-24-mm-diameter x 12-cm-long esophageal stent across the gastroesophageal junction to treat an obstructing esophageal carcinoma. A second 18-mm-diameter x 10-cm-long esophageal stent with anti-reflux valve was deployed coaxially and reduced symptomatic GER immediately. Improvement was sustained at 4-month follow-up. An anti-reflux stent can be successfully used to treat significant symptomatic GER after conventional stenting.

[Proton pump inhibitors in gastro-oesophageal reflux disease: what is the further step?].

PubMed

Simon, Mireille; Zerbib, Frank

2013-01-01

Optimisation of proton pump inhibitors use may improve reflux symptoms in 20-25% of the patients. Pathological gastro-oesophageal reflux should be documented in a patient with refractory reflux symptoms using upper endoscopy and/or pH testing. While on proton pump inhibitors twice daily, persistent symptoms are not related to gastro-oesophageal refluxdisease(GERD) in 50% of the patients. The new anti-reflux compounds have yet a limited efficacy and side effects that currently limit their development. Copyright © 2012. Published by Elsevier Masson SAS.

History of Hepatic Bile Formation: Old Problems, New Approaches

ERIC Educational Resources Information Center

Javitt, Norman B.

2014-01-01

Studies of hepatic bile formation reported in 1958 established that it was an osmotically generated water flow. Intravenous infusion of sodium taurocholate established a high correlation between hepatic bile flow and bile acid excretion. Secretin, a hormone that stimulates bicarbonate secretion, was also found to increase hepatic bile flow. The…

Bile Duct Cancer (Cholangiocarcinoma) Treatment (PDQ®)—Health Professional Version

Cancer.gov

Bile duct cancer (also called cholangiocarcinoma) can occur in the bile ducts in the liver (intrahepatic) or outside the liver (perihilar or distal extrahepatic). Learn about the types of bile duct cancer, risk factors, clinical features, staging, and treatment for bile duct cancer in this expert-reviewed summary.

Consequences of bile salt biotransformations by intestinal bacteria

PubMed Central

Ridlon, Jason M.; Harris, Spencer C.; Bhowmik, Shiva; Kang, Dae-Joong; Hylemon, Phillip B.

2016-01-01

ABSTRACT Emerging evidence strongly suggest that the human “microbiome” plays an important role in both health and disease. Bile acids function both as detergents molecules promoting nutrient absorption in the intestines and as hormones regulating nutrient metabolism. Bile acids regulate metabolism via activation of specific nuclear receptors (NR) and G-protein coupled receptors (GPCRs). The circulating bile acid pool composition consists of primary bile acids produced from cholesterol in the liver, and secondary bile acids formed by specific gut bacteria. The various biotransformation of bile acids carried out by gut bacteria appear to regulate the structure of the gut microbiome and host physiology. Increased levels of secondary bile acids are associated with specific diseases of the GI system. Elucidating methods to control the gut microbiome and bile acid pool composition in humans may lead to a reduction in some of the major diseases of the liver, gall bladder and colon. PMID:26939849

Bile duct hamartomas (von Mayenburg complexes) mimicking liver metastases from bile duct cancer: MRC findings

PubMed Central

Nagano, Yasuhiko; Matsuo, Kenichi; Gorai, Katsuya; Sugimori, Kazuya; Kunisaki, Chikara; Ike, Hideyuki; Tanaka, Katsuaki; Imada, Toshio; Shimada, Hiroshi

2006-01-01

We present a case of a 72-year-old man with a common bile duct cancer, who was initially believed to have multiple liver metastases based on computed tomography findings, and in whom magnetic resonance cholangiography (MRC) revealed a diagnosis of bile duct hamartomas. At exploration for pancreaticoduodenectomy, liver palpation revealed disseminated nodules at the surface of the liver. These nodules showed gray-white nodular lesions of about 0.5 cm in diameter scattered on the surface of both liver lobes, which were looked like multiple liver metastases from bile duct cancer. Frozen section of the liver biopsy disclosed multiple bile ducts with slightly dilated lumens embedded in the collagenous stroma characteristics of multiple bile duct hamartomas (BDHs). Only two reports have described the MRC features of bile duct hamartomas. Of all imaging procedures, MRC provides the most relevant features for the imaging diagnosis of bile duct hamartomas. PMID:16534895

Bile Acid Metabolism and Signaling

PubMed Central

Chiang, John Y. L.

2015-01-01

Bile acids are important physiological agents for intestinal nutrient absorption and biliary secretion of lipids, toxic metabolites, and xenobiotics. Bile acids also are signaling molecules and metabolic regulators that activate nuclear receptors and G protein-coupled receptor (GPCR) signaling to regulate hepatic lipid, glucose, and energy homeostasis and maintain metabolic homeostasis. Conversion of cholesterol to bile acids is critical for maintaining cholesterol homeostasis and preventing accumulation of cholesterol, triglycerides, and toxic metabolites, and injury in the liver and other organs. Enterohepatic circulation of bile acids from the liver to intestine and back to the liver plays a central role in nutrient absorption and distribution, and metabolic regulation and homeostasis. This physiological process is regulated by a complex membrane transport system in the liver and intestine regulated by nuclear receptors. Toxic bile acids may cause inflammation, apoptosis, and cell death. On the other hand, bile acid-activated nuclear and GPCR signaling protects against inflammation in liver, intestine, and macrophages. Disorders in bile acid metabolism cause cholestatic liver diseases, dyslipidemia, fatty liver diseases, cardiovascular diseases, and diabetes. Bile acids, bile acid derivatives, and bile acid sequestrants are therapeutic agents for treating chronic liver diseases, obesity, and diabetes in humans. PMID:23897684

Fatty acid bile acid conjugates (FABACs)—New molecules for the prevention of cholesterol crystallisation in bile

PubMed Central

Gilat, T; Somjen, G; Mazur, Y; Leikin-Frenkel, A; Rosenberg, R; Halpern, Z; Konikoff, F.

2001-01-01

BACKGROUND—Cholesterol gall stones are a frequent disease for which at present surgery is the usual therapy. Despite the importance of bile acids it has become evident that phospholipids are the main cholesterol solubilisers in bile. Even phospholipid components, such as fatty acids, have anticrystallising activity.
AIM—To synthesise fatty acid bile acid conjugates (FABACs) and study their effects on cholesterol crystallisation in bile in vitro and in vivo.
METHODS—FABACs were prepared by conjugation of cholic acid at position 3 with saturated fatty acids of variable chain length using an amide bond. Cholesterol crystallisation and its kinetics (crystal observation time, crystal mass) were studied in model bile, pooled enriched human bile, and fresh human bile using FABACs with saturated fatty acids of varying chain length (C-6 to C-22). Absorption of FABACs into blood and bile was tested in hamsters. Prevention of biliary cholesterol crystallisation in vivo was tested in hamsters and inbred mice.
RESULTS—FABACs strongly inhibited cholesterol crystallisation in model as well as native bile. The FABACs with longer acyl chains (C-16 to C-22) were more effective. At a concentration of 5 mM, FABACs almost completely inhibited cholesterol crystallisation in fresh human bile for 21 days. FABACs were absorbed and found in both portal and heart blood of hamsters. Levels in bile were 2-3 times higher than in blood, indicating active secretion. Appreciable levels were found in the systemic circulation 24-48 hours after a single administration. Ingested FABACs completely prevented the formation of cholesterol crystals in the gall bladders of hamsters and mice fed a lithogenic diet.
CONCLUSIONS—FABACs are potent inhibitors of cholesterol crystallisation in bile. They are absorbed and secreted into bile and prevent the earliest step of cholesterol gall stone formation in animals. These compounds may be of potential use in cholesterol gall stone disease in humans.


Keywords: gall stones; bile; phospholipids; cholesterol crystallisation; fatty acid bile acid conjugates PMID:11115826

Influence of anti-adhesive agent on incidence of bile leakage after liver resection: A prospective cohort study.

PubMed

Yu, Young-Dong; Kim, Dong-Sik; Jung, Sung-Won; Han, Jae-Hyun; Suh, Sung-Ock

2016-07-01

Anti-adhesive agents are increasingly used to reduce the incidence of postoperative adhesions following abdominal surgery. Bile leakage after liver resection remains a major cause of postoperative morbidity. The aim of this study was to examine the effect of anti-adhesive agent on bile leakage after liver resection. 77 patients were enrolled to receive an anti-adhesive agent (study group) during liver resection between May 2012 and August 2013. The study group was compared to a match-paired control group. Clinical data were collected including bilirubin concentration in serum and drain fluid and bile leakage rate. In addition, a separate analysis was performed between patients with and without postoperative bile leakage. There was no difference in bile leakage rate or hospital stay between the study group (n = 77) and control group (n = 77). Of the total number of patients (n = 154), there were 29 patients with postoperative bile leak and 125 patients without bile leak. On univariate analysis, patients without history of hepatitis were significantly associated with bile leakage. In addition, liver resection with broader cut surface area was associated with bile leakage. Application of anti-adhesive agent was not associated with bile leakage. On multivariate analysis, resection with broader cut surface area (OR = 2.788, p = 0.026) and patients without history of hepatitis (OR = 5.153, p = 0.039) were significantly associated with bile leakage. Larger area of cut-surface and patients without history of hepatitis were significant risk factors for bile leakage. The use of anti-adhesive agent was not associated with increased risk of bile leakage. Copyright © 2016 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

Clinical Factors and Postoperative Impact of Bile Leak After Liver Resection.

PubMed

Martin, Allison N; Narayanan, Sowmya; Turrentine, Florence E; Bauer, Todd W; Adams, Reid B; Stukenborg, George J; Zaydfudim, Victor M

2018-04-01

Despite technical advances, bile leak remains a significant complication after hepatectomy. The current study uses a targeted multi-institutional dataset to characterize perioperative factors that are associated with bile leakage after hepatectomy to better understand the impact of bile leak on morbidity and mortality. Adult patients in the 2014-2015 ACS NSQIP targeted hepatectomy dataset were linked to the ACS NSQIP PUF dataset. Bivariable and multivariable regression analyses were used to assess the associations between clinical factors and post-hepatectomy bile leak. Of 6859 patients, 530 (7.7%) had a postoperative bile leak. Proportion of bile leaks was significantly greater in patients after major compared to minor hepatectomy (12.6 vs. 5.1%, p < 0.001). The proportion of patients with bile leak was significantly greater in patients after major hepatectomy who had concomitant enterohepatic reconstruction (31.8 vs. 10.1%, p < 0.001). Postoperative mortality was significantly greater in patients with bile leaks (6.0 vs. 1.7%, p < 0.001). After adjusting for significant covariates, bile leak was independently associated with increased risk of postoperative morbidity (OR = 4.55; 95% CI 3.72-5.56; p < 0.001). After adjusting for significant effects of postoperative complications, liver failure, and reoperation (all p<0.001), bile leak was not independently associated with increased risk of postoperative mortality (p = 0.262). Major hepatectomy and enterohepatic biliary reconstruction are associated with significantly greater rates of bile leak after liver resection. Bile leak is independently associated with significant postoperative morbidity. Mitigation of bile leak is critical in reducing morbidity and mortality after liver resection.

Reflux episodes and esophageal impedance levels in patients with typical and atypical symptoms of gastroesophageal reflux disease

PubMed Central

Ye, Bi Xing; Jiang, Liu Qin; Lin, Lin; Wang, Ying; Wang, Meifeng

2017-01-01

Abstract To determine the relationship between baseline impedance levels and gastroesophageal reflux, we retrospectively enrolled 110 patients (54 men and 56 female; mean age, 51 ± 14 years) with suspected gastroesophageal reflux disease (GERD) who underwent 24-h multichannel intraluminal impedance and pH monitoring. Patients were stratified according to symptom (typical or atypical) and reflux types (acid reflux, nonacid reflux [NAR], or no abnormal reflux). Mean nocturnal baseline impedance (MNBI) were measured 3 cm (distal esophagus) and 17 cm (proximal esophagus) above the lower esophageal sphincter. Median distal esophageal MNBI was lower in the acid reflux group (1244 Ω; 647–1969 Ω) than in the NAR (2586 Ω; 1368–3666 Ω) or no abnormal reflux groups (3082 Ω; 2495–4472 Ω; all P < .05). Distal MNBI were negatively correlated with DeMeester score and acid exposure time. Atypical symptoms were more frequently associated with NAR than typical symptoms (P < .01). Among patients with positive symptom-association probability (SAP) for NAR, median proximal MNBI tended to be lower in patients with typical symptoms (median, 3013 Ω; IQR, 2535–3410 Ω) than in those with atypical symptoms (median, 3386 Ω; IQR, 3044–3730 Ω, P = .05). Thus, atypical GERD symptoms were more likely to be associated with NAR. The mucosal integrity of the proximal esophagus might be relatively impaired in GERD patients with typical symptoms for NAR. PMID:28906377

Sexual activity does not predispose to reflux episodes in patients with gastroesophageal reflux disease

PubMed Central

Bor, Serhat; Valytova, Elen; Yildirim, Esra; Vardar, Rukiye

2014-01-01

Background The role of sexual activity on gastroesophageal reflux disease (GERD) is an under-recognized concern of patients, and one rarely assessed by physicians. Objective The objective of this article is to determine the influence of sexual activity on the intraesophageal acid exposure and acid reflux events in GERD patients. Methods Twenty-one patients with the diagnosis of GERD were prospectively enrolled. Intraesophageal pH monitoring was recorded for 48 hours with a Bravo capsule. All patients were instructed to have sexual intercourse or abstain in a random order two hours after the same refluxogenic dinner within two consecutive nights. Patients were requested to have sex in the standard “missionary position” and women were warned to avoid abdominal compression. The patients completed a diary reporting the time of the sexual intercourse and GERD symptoms. The percentage of reflux time and acid reflux events were compared in two ways: within 30 and 60 minutes prior to and after sexual intercourse on the day of sexual intercourse and in the same time frame of the day without sexual intercourse. Results Fifteen of 21 GERD patients were analyzed. The percentage of reflux time and number of acid reflux events did not show a significant difference within the 30- and 60-minute periods prior to and after sexual intercourse on the day of sexual intercourse and on the day without sexual intercourse, as well. Conclusion Sexual activity does not predispose to increased intraesophageal acid exposure and acid reflux events. Larger studies are needed to confirm our findings in patients who define reflux symptoms during sexual intercourse. PMID:25452843

Acid reflux directly causes sleep disturbances in rat with chronic esophagitis.

PubMed

Nakahara, Kenichi; Fujiwara, Yasuhiro; Tsukahara, Takuya; Yamagami, Hirokazu; Tanigawa, Tetsuya; Shiba, Masatsugu; Tominaga, Kazunari; Watanabe, Toshio; Urade, Yoshihiro; Arakawa, Tetsuo

2014-01-01

Gastroesophageal reflux disease (GERD) is strongly associated with sleep disturbances. Proton pump inhibitor (PPI) therapy improves subjective but not objective sleep parameters in patients with GERD. This study aimed to investigate the association between GERD and sleep, and the effect of PPI on sleep by using a rat model of chronic acid reflux esophagitis. Acid reflux esophagitis was induced by ligating the transitional region between the forestomach and the glandular portion and then wrapping the duodenum near the pylorus. Rats underwent surgery for implantation of electrodes for electroencephalogram and electromyogram recordings, and they were transferred to a soundproof recording chamber. Polygraphic recordings were scored by using 10-s epochs for wake, rapid eye movement sleep, and non-rapid eye movement (NREM) sleep. To examine the role of acid reflux, rats were subcutaneously administered a PPI, omeprazole, at a dose of 20 mg/kg once daily. Rats with reflux esophagitis presented with several erosions, ulcers, and mucosal thickening with basal hyperplasia and marked inflammatory infiltration. The reflux esophagitis group showed a 34.0% increase in wake (232.2±11.4 min and 173.3±7.4 min in the reflux esophagitis and control groups, respectively; p<0.01) accompanied by a reduction in NREM sleep during light period, an increase in sleep fragmentation, and more frequent stage transitions. The use of omeprazole significantly improved sleep disturbances caused by reflux esophagitis, and this effect was not observed when the PPI was withdrawn. Acid reflux directly causes sleep disturbances in rats with chronic esophagitis.

Acid Reflux Directly Causes Sleep Disturbances in Rat with Chronic Esophagitis

PubMed Central

Nakahara, Kenichi; Fujiwara, Yasuhiro; Tsukahara, Takuya; Yamagami, Hirokazu; Tanigawa, Tetsuya; Shiba, Masatsugu; Tominaga, Kazunari; Watanabe, Toshio; Urade, Yoshihiro; Arakawa, Tetsuo

2014-01-01

Background & Aims Gastroesophageal reflux disease (GERD) is strongly associated with sleep disturbances. Proton pump inhibitor (PPI) therapy improves subjective but not objective sleep parameters in patients with GERD. This study aimed to investigate the association between GERD and sleep, and the effect of PPI on sleep by using a rat model of chronic acid reflux esophagitis. Methods Acid reflux esophagitis was induced by ligating the transitional region between the forestomach and the glandular portion and then wrapping the duodenum near the pylorus. Rats underwent surgery for implantation of electrodes for electroencephalogram and electromyogram recordings, and they were transferred to a soundproof recording chamber. Polygraphic recordings were scored by using 10-s epochs for wake, rapid eye movement sleep, and non-rapid eye movement (NREM) sleep. To examine the role of acid reflux, rats were subcutaneously administered a PPI, omeprazole, at a dose of 20 mg/kg once daily. Results Rats with reflux esophagitis presented with several erosions, ulcers, and mucosal thickening with basal hyperplasia and marked inflammatory infiltration. The reflux esophagitis group showed a 34.0% increase in wake (232.2±11.4 min and 173.3±7.4 min in the reflux esophagitis and control groups, respectively; p<0.01) accompanied by a reduction in NREM sleep during light period, an increase in sleep fragmentation, and more frequent stage transitions. The use of omeprazole significantly improved sleep disturbances caused by reflux esophagitis, and this effect was not observed when the PPI was withdrawn. Conclusions Acid reflux directly causes sleep disturbances in rats with chronic esophagitis. PMID:25215524

Association Between Infant Feeding Modes and Gastroesophageal Reflux: A Repeated Measurement Analysis of the Infant Feeding Practices Study II.

PubMed

Chen, Pei-Lin; Soto-Ramírez, Nelís; Zhang, Hongmei; Karmaus, Wilfried

2017-05-01

Gastroesophageal reflux in neonates is frequently reported by parents, potentially motivating changes in infant feeding mode and/or addition of solid food. The authors prospectively analyzed associations between repeated measurement of feeding modes and reflux in infancy. The Infant Feeding Practices Study II, conducted between 2005 and 2007 (2,841 infants), provides data on reflux and feeding modes at nine time points from months 1 to 12. Feeding modes were defined based on direct breastfeeding, feeding of bottled human milk, formula feeding, their combinations, and use of solid food. Repeated measurements were investigated using 1-month delayed models to estimate risk ratios (RRs) and their 95% confidence intervals (CIs). Risk ratios of different feeding modes were estimated for reflux; addressing a reverse association, RRs for feeding mode were estimated as responses to prior reflux. Compared to direct breastfeeding, combinations with formula feeding showed a statistically significant risk for reflux (bottled human milk plus formula feeding: RR = 2.19, 95% CI [1.11, 4.33]; formula feeding: RR = 1.95, 95% CI [1.39, 2.74]; and mixed breastfeeding plus formula feeding: RR = 1.59, 95% CI [1.40, 2.42]). Addition of solid food was not protective (RR = 1.21, 95% CI [0.86, 1.70]). Analyses of reverse association (reflux → feeding) showed fewer breastfed infants among those with reflux in the prior month. Any combination of infant feeding with formula seems to be a risk for reflux. Although breastfeeding was protective, mothers with a child with reflux were more likely to wean their child.

Bile acid malabsorption after intestinal bypass surgery for obesity. A comparison between jejunoileal shunt and biliointestinal bypass.

PubMed

Nyhlin, H; Brydon, G; Danielsson, A; Eriksson, F

1990-01-01

Seventeen patients were operated on with intestinal shunts for morbid obesity, in eight a biliointestinal bypass (BI) was constructed and in the rest a conventional jejunoileal (JI)-shunt. The reduction in weight was similar in both groups, and so was malabsorption of fat, but the BI-group had significantly less bowel motions with less watery diarrhoea. Bile acid malabsorption was measured both chemically by estimating the total amount of faecal bile acids excreted, as well as indirectly by using a 75Se-labelled synthetic bile acid (SeHCAT). Both techniques revealed a substantial loss of bile acid after both types of operation, but patients with BI bypass surgery had significantly lower elimination time of the bile acid than those with JI-shunts. There was a significant negative correlation between SeHCAT retention and total faecal bile acids. However, some patients with low SeHCAT retention had normal or even reduced output of faecal bile acids. Estimation of faecal bile acids may display false negative results when the bile acid pool is decreased. The SeHCAT-test seems to be a better technique for measuring bile acid losses. The study suggests that BI bypass surgery for obesity seems to be advantageous over the JI shunt in reducing the postoperative loss of bile acids and choleretic diarrhoea, without influencing the weight loss.

Key discoveries in bile acid chemistry and biology and their clinical applications: history of the last eight decades.

PubMed

Hofmann, Alan F; Hagey, Lee R

2014-08-01

During the last 80 years there have been extraordinary advances in our knowledge of the chemistry and biology of bile acids. We present here a brief history of the major achievements as we perceive them. Bernal, a physicist, determined the X-ray structure of cholesterol crystals, and his data together with the vast chemical studies of Wieland and Windaus enabled the correct structure of the steroid nucleus to be deduced. Today, C24 and C27 bile acids together with C27 bile alcohols constitute most of the bile acid "family". Patterns of bile acid hydroxylation and conjugation are summarized. Bile acid measurement encompasses the techniques of GC, HPLC, and MS, as well as enzymatic, bioluminescent, and competitive binding methods. The enterohepatic circulation of bile acids results from vectorial transport of bile acids by the ileal enterocyte and hepatocyte; the key transporters have been cloned. Bile acids are amphipathic, self-associate in solution, and form mixed micelles with polar lipids, phosphatidylcholine in bile, and fatty acids in intestinal content during triglyceride digestion. The rise and decline of dissolution of cholesterol gallstones by the ingestion of 3,7-dihydroxy bile acids is chronicled. Scientists from throughout the world have contributed to these achievements. Copyright © 2014 by the American Society for Biochemistry and Molecular Biology, Inc.

Determining the origin of superficial venous reflux in the groin with duplex ultrasound and implications for varicose vein surgery.

PubMed

Zollmann, Paul; Zollmann, Christine; Zollmann, Philipp; Veltman, Juergen; Kerzig, Dennis; Doerler, Martin; Stücker, Markus

2017-01-01

The purpose of this paper was to describe patterns of superficial reflux in the groin with respect to the terminal valve (TV), which is located at the saphenous opening to the common femoral vein, the great saphenous vein, and its tributary veins. This study included 2019 legs with chronic venous insufficiency that received endoluminal varicose vein treatment because of varicosities with insufficiency of the saphenofemoral junction (SFJ). In a preoperative duplex ultrasound investigation of the superficial vein system, reflux after provocation in the SFJ, great saphenous vein, cranial veins (superficial external pudendal vein, superficial epigastric vein, superficial circumflex iliac vein), and anterior and posterior accessory saphenous veins was recorded and classified on the basis of the origin of reflux. In 1348 legs (66.8%), the reflux had its origin exclusively in the common femoral vein. In 170 legs (8.4%), the reflux had its origin in the common femoral and cranial veins. In 430 legs (21.3%), the insufficiency was due to saphenocranial reflux only. In 71 legs (3.5%), the origin of reflux could not be determined. Reflux in the SFJ does not involve the TV in 24.8% of the legs, implying that routine high ligation and ablation close to the TV might be overtreatment in these patients. Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Impaired Upper Esophageal Sphincter Reflexes in Patients with Supra-Esophageal Reflux Disease

PubMed Central

Babaei, Arash; Venu, Mukund; Naini, Sohrab Rahimi; Gonzaga, Jason; Lang, Ivan; Massey, Benson; Jadcherla, Sudarshan; Shaker, Reza

2015-01-01

Background & Aims Normal responses of the upper esophageal sphincter (UES) and esophageal body to liquid reflux events prevent esophagopharyngeal reflux and its complications, but abnormal responses have not been characterized. We investigated whether patients with supra-esophageal reflux disease (SERD) have impaired UES and esophageal body responses to simulated reflux events. Methods We performed a prospective study of 25 patients with SERD (19–82 y old, 13 female) and complaints of regurgitation and supra-esophageal manifestations of reflux. We also included 10 patients with gastroesophageal reflux disease (GERD; 32–60 y old, 7 female) without troublesome regurgitation and supra-esophageal symptoms and 24 healthy asymptomatic individuals (controls; 19–49 y old, 13 female). UES and esophageal body pressure responses, along with luminal distribution of infusate during esophageal rapid and slow infusion of air or liquid, were monitored by concurrent high-resolution manometry and intraluminal impedance. Results A significantly smaller proportion of patients with SERD had UES contractile reflexes in response to slow esophageal infusion of acid than controls or patients with GERD. Only patients with SERD had abnormal UES relaxation responses to rapid distension with saline. Diminished esophageal peristaltic contractions resulted in esophageal stasis in patients with GERD or SERD. Conclusions Patients with SERD and complaints of regurgitation have impaired UES and esophageal responses to simulated liquid reflux events. These patterns could predispose them to esophagopharyngeal reflux. PMID:26188682

Detection of gastro-oesophageal reflux in the neonatal unit.

PubMed

Rossor, Thomas; Lingam, Ingran; Douiri, Abdel; Bhat, Ravindra; Greenough, Anne

2018-03-13

To determine whether a pH probe or multichannel intraluminal impedance (MII) more frequently detected gastro-oesophageal reflux and test the hypothesis that acid reflux was associated with lower baseline impedance. A prospective study of infants in whom reflux was suspected and evaluated using combined pH and multichannel impedance. Studies were considered abnormal if the acid index was >10% or there were >79MII reflux events in 24 hours. The acid index was the percentage of total study time with a pH

CPI-613 in Treating Patients With Advanced or Metastatic Bile Duct Cancer That Cannot Be Removed By Surgery

ClinicalTrials.gov

2018-05-22

Adult Primary Cholangiocellular Carcinoma; Advanced Adult Primary Liver Cancer; Cholangiocarcinoma of the Extrahepatic Bile Duct; Cholangiocarcinoma of the Gallbladder; Localized Unresectable Adult Primary Liver Cancer; Metastatic Extrahepatic Bile Duct Cancer; Recurrent Adult Primary Liver Cancer; Recurrent Extrahepatic Bile Duct Cancer; Unresectable Extrahepatic Bile Duct Cancer

Evaluation of the White Test for the Intraoperative Detection of Bile Leakage

PubMed Central

Leelawat, Kawin; Chaiyabutr, Kittipong; Subwongcharoen, Somboon; Treepongkaruna, Sa-ad

2012-01-01

We assess whether the White test is better than the conventional bile leakage test for the intraoperative detection of bile leakage in hepatectomized patients. This study included 30 patients who received elective liver resection. Both the conventional bile leakage test (injecting an isotonic sodium chloride solution through the cystic duct) and the White test (injecting a fat emulsion solution through the cystic duct) were carried out in the same patients. The detection of bile leakage was compared between the conventional method and the White test. A bile leak was demonstrated in 8 patients (26.7%) by the conventional method and in 19 patients (63.3%) by the White test. In addition, the White test detected a significantly higher number of bile leakage sites compared with the conventional method (Wilcoxon signed-rank test; P < 0.001). The White test is better than the conventional test for the intraoperative detection of bile leakage. Based on our study, we recommend that surgeons investigating bile leakage sites during liver resections should use the White test instead of the conventional bile leakage test. PMID:22547901

Evaluation of the white test for the intraoperative detection of bile leakage.

PubMed

Leelawat, Kawin; Chaiyabutr, Kittipong; Subwongcharoen, Somboon; Treepongkaruna, Sa-Ad

2012-01-01

We assess whether the White test is better than the conventional bile leakage test for the intraoperative detection of bile leakage in hepatectomized patients. This study included 30 patients who received elective liver resection. Both the conventional bile leakage test (injecting an isotonic sodium chloride solution through the cystic duct) and the White test (injecting a fat emulsion solution through the cystic duct) were carried out in the same patients. The detection of bile leakage was compared between the conventional method and the White test. A bile leak was demonstrated in 8 patients (26.7%) by the conventional method and in 19 patients (63.3%) by the White test. In addition, the White test detected a significantly higher number of bile leakage sites compared with the conventional method (Wilcoxon signed-rank test; P < 0.001). The White test is better than the conventional test for the intraoperative detection of bile leakage. Based on our study, we recommend that surgeons investigating bile leakage sites during liver resections should use the White test instead of the conventional bile leakage test.

Rat Liver Canalicular Membrane Vesicles Contain an ATP-Dependent Bile Acid Transport System

NASA Astrophysics Data System (ADS)

Nishida, Toshirou; Gatmaitan, Zenaida; Che, Mingxin; Arias, Irwin M.

1991-08-01

The secretion of bile by the liver is primarily determined by the ability of the hepatocyte to transport bile acids into the bile canaliculus. A carrier-mediated process for the transport of taurocholate, the major bile acid in humans and rats, was previously demonstrated in canalicular membrane vesicles from rat liver. This process is driven by an outside-positive membrane potential that is, however, insufficient to explain the large bile acid concentration gradient between the hepatocyte and bile. In this study, we describe an ATP-dependent transport system for taurocholate in inside-out canalicular membrane vesicles from rat liver. The transport system is saturable, temperature-dependent, osmotically sensitive, specifically requires ATP, and does not function in sinusoidal membrane vesicles and right side-out canalicular membrane vesicles. Transport was inhibited by other bile acids but not by substrates for the previously demonstrated ATP-dependent canalicular transport systems for organic cations or nonbile acid organic anions. Defects in ATP-dependent canalicular transport of bile acids may contribute to reduced bile secretion (cholestasis) in various developmental, inheritable, and acquired disorders.

Pharyngeal manifestations of gastroesophageal reflux disease.

PubMed

Rubesin, Stephen E; Levine, Marc S

2018-06-01

This article discusses the extraesophageal manifestations of gastroesophageal reflux disease, focusing primarily on the gamut of pharyngeal abnormalities that can be detected on barium swallows. Abnormalities of pharyngeal swallowing caused by gastroesophageal reflux are illustrated. We particularly emphasize how pharyngoesophageal relationships can guide the radiologist for performing tailored barium swallows to optimally evaluate pharyngeal abnormalities in patients with underlying gastroesophageal reflux disease.

Gastroesophageal reflux disease and its association with bronchiolitis obliterans syndrome in allogeneic hematopoietic stem cell transplant recipients.

PubMed

Khalid, Mohammed; Aljurf, Mahmoud; Saleemi, Sarfraz; Khan, Mohammed Qaseem; Khan, Basha; Ahmed, Shad; Ibrahim, Khalid El Tayeb; Mobeireek, Abdullah; Al Mohareb, Fahad; Chaudhri, Naeem

2013-06-01

Bronchiolitis obliterans syndrome is a significant postallogeneic hematopoietic stem cell transplant problem. Recent data in lung transplant patients suggest an association with gastroesophageal reflux disease and bronchiolitis obliterans syndrome. We studied posthematopoietic stem cell transplant patients with bronchiolitis obliterans syndrome for gastroesophageal reflux disease and its response to a proton pump inhibitor. Seven postallogeneic hematopoietic stem cell transplant patients with bronchiolitis obliterans syndrome were studied. Gastroesophageal reflux disease was assessed by 24-hour pH monitoring with a Bravo catheter-free radio pH capsule. Patients with positive gastroesophageal reflux disease were started on omeprazole. Pretreatment and posttreatment pulmonary function tests were done at 3-month intervals. Of 7 patients, 5 had positive results for gastroesophageal reflux disease (71%). Omeprazole had a disease-stabilizing effect on the patients' pulmonary function tests. Our study shows a significant association between bronchiolitis obliterans syndrome and gastroesophageal reflux disease in postallogeneic hematopoietic stem cell transplant patients. Use of omeprazole may have a disease-stabilizing effect in short-term follow-up.

Nonerosive reflux disease: clinical concepts.

PubMed

Gyawali, C Prakash; Azagury, Dan E; Chan, Walter W; Chandramohan, Servarayan M; Clarke, John O; de Bortoli, Nicola; Figueredo, Edgar; Fox, Mark; Jodorkovsky, Daniela; Lazarescu, Adriana; Malfertheiner, Peter; Martinek, Jan; Murayama, Kenric M; Penagini, Roberto; Savarino, Edoardo; Shetler, Katerina P; Stein, Ellen; Tatum, Roger P; Wu, Justin

2018-05-15

Esophageal symptoms can arise from gastroesophageal reflux disease (GERD) as well as other mucosal and motor processes, structural disease, and functional esophageal syndromes. GERD is the most common esophageal disorder, but diagnosis may not be straightforward when symptoms persist despite empiric acid suppressive therapy and when mucosal erosions are not seen on endoscopy (as for nonerosive reflux disease, NERD). Esophageal physiological tests (ambulatory pH or pH-impedance monitoring and manometry) can be of value in defining abnormal reflux burden and reflux-symptom association. NERD diagnosed on the basis of abnormal reflux burden on ambulatory reflux monitoring is associated with similar symptom response from antireflux therapy for erosive esophagitis. Acid suppression is the mainstay of therapy, and antireflux surgery has a definitive role in the management of persisting symptoms attributed to NERD, especially when the esophagogastric junction is compromised. Adjunctive approaches and complementary therapy may be of additional value in management. In this review, we describe the evaluation, diagnosis, differential diagnosis, and management of NERD. © 2018 New York Academy of Sciences.

Experimental model of smoking and simulation of reflux with acid and pepsin in rats.

PubMed

Zen Junior, José Hélio; Del Negro, André; Colli Neto, José Alexandre; Araujo, Marina Rachel; Altemani, Albina Maria; Andreollo, Nelson Adami

2012-01-01

To develop experimental models to evaluate the effects of hydrochloric acid associated with the pepsin instilled in the mucosa of the upper esophagus and the esophagogastric junction of young male rats Wistar, simulating injury caused by gastroesophageal reflux on the mucosa of aero-digestive tract in humans as well as the action of the risk exposure of mucosa to cigarette smoke. Fifty young male Wistar rats divided in 5 groups with 10 animals each one, respectively simulating pharyngo-laryngeal reflux and gastroesophageal reflux, pharyngo-laryngeal reflux and smoking, smoking only, gastroesophageal reflux and control group. The histopathologic studies no recorded neoplasias, only mild changes and no significant alterations. The hemo-oximetry (carboxyhemoglobin and methemoglobim) and CO2 concentration confirm that the animals were submitted to high intensity of exposure to carcinogens in tobacco and its derivatives. The experimental models were highly efficient, practical, easy to use and economical and can be employed in other similar studies to determine the harmful effects by smoking and reflux.

Gastro-oesophageal reflux in children--what's the worry?

PubMed

Allen, Katie; Ho, Shaun S C

2012-05-01

Gastro-oesophageal reflux is common and benign in children, especially during infancy. Distinguishing between gastrooesophageal reflux, gastro-oesophageal reflux disease and other illnesses presenting as chronic vomiting can be difficult. The general practitioner has a key role to play in identifying if a child requires referral for further investigation. This article outlines the main differential diagnoses to be considered in children presenting with chronic vomiting and/ or regurgitation. We also discuss key management decisions regarding gastro-oesophageal reflux disease in children and when to refer to a specialist for further investigation. Chronic vomiting and regurgitation frequently occurs in infancy and is most commonly due to simple, benign gastrooesophageal reflux, which is usually self limiting without requirement for further investigation. In contrast, gastrooesophageal reflux disease requires considered management and may be a presenting symptom of food allergy requiring more intensive therapy than simple acid suppression. Regular review by the general practitioner to ascertain warning signs will ensure that other serious illnesses are not overlooked and that appropriate investigation and specialist referral are made.

[Correlations of bile acids in the bile of rats in conditions of alloxan induced diabetes melitus].

PubMed

Danchenko, N M; Vesel'skyĭ, S P; Tsudzevych, B O

2014-01-01

The ratio of bile acids in the bile of rats with alloxan diabetes was investigated using the method of thin-layer chromatography. Changes of coefficients of conjugation and hydroxylation of bile acids were calculated and analyzed in half-hour samples of bile obtained during the 3-hour experiment. It has been found that the processes of conjugation of cholic acid with glycine and taurine are inhibited in alloxan diabetes. At the same time a significant increase of free threehydroxycholic and dixydroxycholic bile acids and conjugates of the latter ones with taurine has been registered. Coefficients of hydroxylation in alloxan diabetes show the domination of "acidic" pathway in bile acid biosynthesis that is tightly connected with the activity of mitochondrial enzymes.

Evolutionary diversity of bile salts in reptiles and mammals, including analysis of ancient human and extinct giant ground sloth coprolites

PubMed Central

2010-01-01

Background Bile salts are the major end-metabolites of cholesterol and are also important in lipid and protein digestion and in influencing the intestinal microflora. We greatly extend prior surveys of bile salt diversity in both reptiles and mammals, including analysis of 8,000 year old human coprolites and coprolites from the extinct Shasta ground sloth (Nothrotherium shastense). Results While there is significant variation of bile salts across species, bile salt profiles are generally stable within families and often within orders of reptiles and mammals, and do not directly correlate with differences in diet. The variation of bile salts generally accords with current molecular phylogenies of reptiles and mammals, including more recent groupings of squamate reptiles. For mammals, the most unusual finding was that the Paenungulates (elephants, manatees, and the rock hyrax) have a very different bile salt profile from the Rufous sengi and South American aardvark, two other mammals classified with Paenungulates in the cohort Afrotheria in molecular phylogenies. Analyses of the approximately 8,000 year old human coprolites yielded a bile salt profile very similar to that found in modern human feces. Analysis of the Shasta ground sloth coprolites (approximately 12,000 years old) showed the predominant presence of glycine-conjugated bile acids, similar to analyses of bile and feces of living sloths, in addition to a complex mixture of plant sterols and stanols expected from an herbivorous diet. Conclusions The bile salt synthetic pathway has become longer and more complex throughout vertebrate evolution, with some bile salt modifications only found within single groups such as marsupials. Analysis of the evolution of bile salt structures in different species provides a potentially rich model system for the evolution of a complex biochemical pathway in vertebrates. Our results also demonstrate the stability of bile salts in coprolites preserved in arid climates, suggesting that bile salt analysis may have utility in selected paleontological research. PMID:20444292

Boldine enhances bile production in rats via osmotic and Farnesoid X receptor dependent mechanisms

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cermanova, Jolana; Kadova, Zuzana; Deparment of Pharmacology and Toxicology, Charles University in Prague, Faculty of Pharmacy in Hradec Kralove

Boldine, the major alkaloid from the Chilean Boldo tree, is used in traditional medicine to support bile production, but evidence to support this function is controversial. We analyzed the choleretic potential of boldine, including its molecular background. The acute- and long-term effects of boldine were evaluated in rats either during intravenous infusion or after 28-day oral treatment. Infusion of boldine instantly increased the bile flow 1.4-fold in healthy rats as well as in animals with Mrp2 deficiency or ethinylestradiol induced cholestasis. This effect was not associated with a corresponding increase in bile acid or glutathione biliary excretion, indicating that themore » effect is not related to stimulation of either bile acid dependent or independent mechanisms of bile formation and points to the osmotic activity of boldine itself. We subsequently analyzed bile production under conditions of changing biliary excretion of boldine after bolus intravenous administration and found strong correlations between both parameters. HPLC analysis showed that bile concentrations of boldine above 10 μM were required for induction of choleresis. Importantly, long-term pretreatment, when the bile collection study was performed 24-h after the last administration of boldine, also accelerated bile formation despite undetectable levels of the compound in bile. The effect paralleled upregulation of the Bsep transporter and increased biliary clearance of its substrates, bile acids. We consequently confirmed the ability of boldine to stimulate the Bsep transcriptional regulator, FXR receptor. In conclusion, our study clarified the mechanisms and circumstances surrounding the choleretic activity of boldine. - Highlights: • Boldine may increase bile production by direct as well as indirect mechanisms. • Biliary concentrations of boldine above 10 μM directly stimulate bile production. • Long-term oral boldine administration increases bile acid (BA) biliary secretion. • Boldine induces Bsep-mediated transport of BA by FXR receptor stimulation.« less

Carcinoids of the common bile duct: a case report and literature review

PubMed Central

Ross, Alison C.; Hurley, James B.; Hay, W. Bruce; Rusnak, Conrad H.; Petrunia, Denis M.

1999-01-01

Carcinoids of the extrahepatic bile ducts and particularly the common bile duct are extremely rare. A 65-year-old woman presented with obstructive jaundice. Laboratory and imaging studies gave results that were consistent with an obstructing lesion in the common bile duct. In this case, a stent was inserted initially to decompress the bile ducts. Subsequently a laparotomy and pancreaticoduodenectomy were performed and a tissue diagnosis of carcinoid of the common bile duct was made. The patient was well with no evidence of recurrence 17 months postoperatively. The authors believe this is the 19th reported case of an extrahepatic bile duct carcinoid. PMID:10071590

Achalasia following gastro-oesophageal reflux.

PubMed Central

Smart, H L; Mayberry, J F; Atkinson, M

1986-01-01

Five patients initially presenting with symptomatic gastro-oesophageal reflux, proven by radiology or pH monitoring, subsequently developed achalasia, confirmed by radiology and manometry, after an interval of 2-10 years. During this period dysphagia, present as a mild and intermittent symptom accompanying the initial reflux in 3 of the 5, became severe and resulted in oesophageal stasis of food in all. Three of the 5 had a demonstrable hiatal hernia. In none was reflux a troublesome symptom after Rider-Moeller dilatation or cardiomyotomy undertaken for the achalasia. Gastro-oesophageal reflux does not protect against the subsequent development of achalasia. It is suggested that the autonomic damage eventually leading to achalasia may in its initial phases cause gastro-oesophageal reflux. Images Figure 1. A Figure 1. B Figure 2. PMID:3950898

Bile

MedlinePlus

... the digestive tract. Bile contains: Mostly cholesterol Bile acids (also called bile salts) Bilirubin (a breakdown product or red blood cells) It also contains: Water Body salts (such as potassium and sodium) Copper and other metals

Postoperative Biliary Leak Treated with Chemical Bile Duct Ablation Using Absolute Ethanol: A Report of Two Cases.

PubMed

Sasaki, Maho; Hori, Tomohide; Furuyama, Hiroaki; Machimoto, Takafumi; Hata, Toshiyuki; Kadokawa, Yoshio; Ito, Tatsuo; Kato, Shigeru; Yasukawa, Daiki; Aisu, Yuki; Kimura, Yusuke; Takamatsu, Yuichi; Kitano, Taku; Yoshimura, Tsunehiro

2017-08-08

BACKGROUND Postoperative bile duct leak following hepatobiliary and pancreatic surgery can be intractable, and the postoperative course can be prolonged. However, if the site of the leak is in the distal bile duct in the main biliary tract, the therapeutic options may be limited. Injection of absolute ethanol into the bile duct requires correct identification of the bile duct, and balloon occlusion is useful to avoid damage to the surrounding tissues, even in cases with non-communicating biliary fistula and bile leak. CASE REPORT Two cases of non-communicating biliary fistula and bile leak are presented; one case following pancreaticoduodenectomy (Whipple's procedure), and one case following laparoscopic cholecystectomy. Both cases were successfully managed by chemical bile duct ablation with absolute ethanol. In the first case, the biliary leak occurred from a fistula of the right posterior biliary tract following pancreaticoduodenectomy. Cannulation of the leaking bile duct and balloon occlusion were achieved via a percutaneous route, and seven ablation sessions using absolute ethanol were required. In the second case, perforation of the bile duct branch draining hepatic segment V occurred following laparoscopic cholecystectomy. Cannulation of the bile duct and balloon occlusion were achieved via a transhepatic route, and seven ablation sessions using absolute ethanol were required. CONCLUSIONS Chemical ablation of the bile duct using absolute ethanol is an effective treatment for biliary leak following hepatobiliary and pancreatic surgery, even in cases with non-communicating biliary fistula. Identification of the bile duct leak is required before ethanol injection to avoid damage to the surrounding tissues.

Role of cholangiocyte bile Acid transporters in large bile duct injury after rat liver transplantation.

PubMed

Cheng, Long; Zhao, Lijin; Li, Dajiang; Liu, Zipei; Chen, Geng; Tian, Feng; Li, Xiaowu; Wang, Shuguang

2010-07-27

The pathogenesis of nonanastomotic strictures with a patent hepatic artery remains to be investigated. This study focuses on the role of cholangiocyte bile acid transporters in bile duct injury after liver transplantation. Sprague-Dawley rats were divided into three groups (n=20 for each): the sham-operated group (Sham), the transplant group with 1-hr donor liver cold preservation (CP-1h), and the transplant group with 12-hr donor liver cold preservation (CP-12h). Bile was collected for biochemical analysis. The histopathologic evaluation of bile duct injury was performed and the cholangiocyte bile acid transporters apical sodium-dependent bile acid transporter (ASBT), ileal lipid binding protein (ILBP), and Ostalpha/Ostbeta were investigated. RESULTS.: The immunohistochemical assay suggested that ASBT and ILBP were expressed exclusively on large bile duct epithelial cells, whereas Ostalpha and Ostbeta were expressed on both small and large bile ducts. Western blot and quantitative polymerase chain reaction analysis showed that the expression levels of these transporters dramatically decreased after transplantation. It took seven to 14 days for ILBP, Ostalpha, and Ostbeta to recover, whereas ASBT recovered within 3 days and even reached a peak above the normal level seven days after operation. In the CP-12h group, the ratios of the ASBT/ILBP, ASBT/Ostalpha and ASBT/Ostbeta expression levels were correlated with the injury severity scores of large but not small bile ducts. The results suggest that the unparallel alteration of cholangiocyte bile acid transporters may play a potential role in large bile duct injury after liver transplantation with prolonged donor liver preservation.

Comparison of endogenous and radiolabeled bile acid excretion in patients with idiopathic chronic diarrhea

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schiller, L.R.; Bilhartz, L.E.; Santa Ana, C.A.

Fecal recovery of radioactivity after ingestion of a bolus of radiolabeled bile acid is abnormally high in most patients with idiopathic chronic diarrhea. To evaluate the significance of this malabsorption, concurrent fecal excretion of both exogenous radiolabeled bile acid and endogenous (unlabeled) bile acid were measured in patients with idiopathic chronic diarrhea. Subjects received a 2.5-microCi oral dose of taurocholic acid labeled with 14C in the 24th position of the steroid moiety. Endogenous bile acid excretion was measured by a hydroxysteroid dehydrogenase assay on a concurrent 72-h stool collection. Both radiolabeled and endogenous bile acid excretion were abnormally high inmore » most patients with chronic diarrhea compared with normal subjects, even when equivoluminous diarrhea was induced in normal subjects by ingestion of osmotically active solutions. The correlation between radiolabeled and endogenous bile acid excretion was good. However, neither radiolabeled nor endogenous bile acid excretion was as abnormal as is typically seen in patients with ileal resection, and none of these diarrhea patients responded to treatment with cholestyramine with stool weights less than 200 g. These results suggest (a) that this radiolabeled bile acid excretion test accurately reflects excess endogenous bile acid excretion; (b) that excess endogenous bile acid excretion is not caused by diarrhea per se; (c) that spontaneously occurring idiopathic chronic diarrhea is often associated with increased endogenous bile acid excretion; and (d) that bile acid malabsorption is not likely to be the primary cause of diarrhea in most of these patients.« less

[Advances in studies on bear bile powder].

PubMed

Zhou, Chao-fan; Gao, Guo-jian; Liu, Ying

2015-04-01

In this paper, a detailed analysis was made on relevant literatures about bear bile powder in terms of chemical component, pharmacological effect and clinical efficacy, indicating bear bile powder's significant pharmacological effects and clinical application in treating various diseases. Due to the complex composition, bear bile powder is relatively toxic. Therefore, efforts shall be made to study bear bile powder's pharmacological effects, clinical application, chemical composition and toxic side-effects, with the aim to provide a scientific basis for widespread reasonable clinical application of bear bile powder.

Surgery for Gastroesophageal Reflux Disease in the Morbidly Obese Patient.

PubMed

Duke, Meredith C; Farrell, Timothy M

2017-01-01

The prevalence of gastroesophageal reflux disease (GERD) has mirrored the increase in obesity, and GERD is now recognized as an obesity-related comorbidity. There is growing evidence that obesity, specifically central obesity, is associated with the complications of chronic reflux, including erosive esophagitis, Barrett's esophagus, and esophageal adenocarcinoma. While fundoplication is effective in creating a competent gastroesophageal junction and controlling reflux in most patients, it is less effective in morbidly obese patients. In these patients a bariatric operation has the ability to correct both the obesity and the abnormal reflux. The Roux-en-Y gastric bypass is the preferred procedure.

Alkylating Derivatives of Vitamin D Hormone for Prostate Cancer

DTIC Science & Technology

2006-10-01

Acetic Anhydride / Pyridine/ 40C 1. UV / Toluene 2. EtOH - Reflux TBDMSCl / Imidazole /DMF BrCH2COOH / DCC / DMAP / CH2Cl2 1,25(OH)2D3-3-BE Figure 1...BE OH SO2 OTBDMS OH OTBDMS 1. Liq. SO2 / Reflux 2. TBDMSCl / Imidazole /DMF NaHCO3 / EtOH / Reflux NMO / SeO2 / CH2Cl2 / Reflux OH OTBDMSHO OTHP...containing 200 mg of 25-hydroxyvitamin D3 in a flask fitted with a trap that was cooled with dry ice-acetone (-780C). The yellow solution was refluxed

Serum bile acid concentrations in dairy cattle with hepatic lipidosis.

PubMed

Garry, F B; Fettman, M J; Curtis, C R; Smith, J A

1994-01-01

This study was designed to evaluate serum bile acid measurements as indicatory, of liver function and/or hepatic fat infiltration in dairy cattle. Serum bile acid concentrations were measured in healthy dairy cattle at different stages of lactation after fasting or feeding. Bile acid concentrations were compared with liver fat content and sulfobromophthalein (BSP) half-life (T 1/2). Serum bile acid concentrations were higher in cows in early lactation and with higher daily milk production. Compared with prefasting values, bile acid concentrations were decreased at 8, 14, and 24 hours of fasting. Blood samples from fed cows at 1- to 2-hour intervals had wide and inconsistent variations in bile acid concentration. Because serum bile acids correlated well with BSP T 1/2, it is suggested that both measurements evaluate a similar aspect of liver function. Neither bile acids nor BSP T 1/2 correlated with differences in liver fat content among cows. Because of large variability in serum bile acid concentrations in fed cows and the lack of correlation of measured values with liver fat content, bile acid determinations do not appear useful for showing changes in hepatic function in fed cows with subclinical hepatic lipidosis nor serve as a screening test for this condition.

A simple and accurate HPLC method for fecal bile acid profile in healthy and cirrhotic subjects: validation by GC-MS and LC-MS[S

PubMed Central

Kakiyama, Genta; Muto, Akina; Takei, Hajime; Nittono, Hiroshi; Murai, Tsuyoshi; Kurosawa, Takao; Hofmann, Alan F.; Pandak, William M.; Bajaj, Jasmohan S.

2014-01-01

We have developed a simple and accurate HPLC method for measurement of fecal bile acids using phenacyl derivatives of unconjugated bile acids, and applied it to the measurement of fecal bile acids in cirrhotic patients. The HPLC method has the following steps: 1) lyophilization of the stool sample; 2) reconstitution in buffer and enzymatic deconjugation using cholylglycine hydrolase/sulfatase; 3) incubation with 0.1 N NaOH in 50% isopropanol at 60°C to hydrolyze esterified bile acids; 4) extraction of bile acids from particulate material using 0.1 N NaOH; 5) isolation of deconjugated bile acids by solid phase extraction; 6) formation of phenacyl esters by derivatization using phenacyl bromide; and 7) HPLC separation measuring eluted peaks at 254 nm. The method was validated by showing that results obtained by HPLC agreed with those obtained by LC-MS/MS and GC-MS. We then applied the method to measuring total fecal bile acid (concentration) and bile acid profile in samples from 38 patients with cirrhosis (17 early, 21 advanced) and 10 healthy subjects. Bile acid concentrations were significantly lower in patients with advanced cirrhosis, suggesting impaired bile acid synthesis. PMID:24627129

Interactions between Bacteria and Bile Salts in the Gastrointestinal and Hepatobiliary Tracts

PubMed Central

Urdaneta, Verónica; Casadesús, Josep

2017-01-01

Bile salts and bacteria have intricate relationships. The composition of the intestinal pool of bile salts is shaped by bacterial metabolism. In turn, bile salts play a role in intestinal homeostasis by controlling the size and the composition of the intestinal microbiota. As a consequence, alteration of the microbiome–bile salt homeostasis can play a role in hepatic and gastrointestinal pathological conditions. Intestinal bacteria use bile salts as environmental signals and in certain cases as nutrients and electron acceptors. However, bile salts are antibacterial compounds that disrupt bacterial membranes, denature proteins, chelate iron and calcium, cause oxidative damage to DNA, and control the expression of eukaryotic genes involved in host defense and immunity. Bacterial species adapted to the mammalian gut are able to endure the antibacterial activities of bile salts by multiple physiological adjustments that include remodeling of the cell envelope and activation of efflux systems and stress responses. Resistance to bile salts permits that certain bile-resistant pathogens can colonize the hepatobiliary tract, and an outstanding example is the chronic infection of the gall bladder by Salmonella enterica. A better understanding of the interactions between bacteria and bile salts may inspire novel therapeutic strategies for gastrointestinal and hepatobiliary diseases that involve microbiome alteration, as well as novel schemes against bacterial infections. PMID:29043249

A new, major C27 biliary bile acid in the Red-winged tinamou (Rhynchotus rufescens):(25R)-1β,3α,7α-trihydroxy-5β-cholestan-27-oic acid*

PubMed Central

Hagey, Lee R.; Kakiyama, Genta; Muto, Akina; Iida, Takashi; Mushiake, Kumiko; Goto, Takaaki; Mano, Nariyasu; Goto, Junichi; Oliveira, Cleida A.; Hofmann, Alan F.

2009-01-01

The chemical structures of the three major bile acids present in the gallbladder bile of the Red-winged tinamou (Rhynchotus rufescens), an early evolving, ground-living bird related to ratites, were determined. Bile acids were isolated by preparative reversed-phase HPLC. Two of the compounds were identified as the taurine N-acylamidates of (25R)-3α,7α-dihydroxy-5β-cholestan-27-oic acid (constituting 22% of biliary bile acids) and (25R)-3α,7α,12α-trihydroxy-5β-cholestan-27-oic acid (constituting 51%). The remaining compound, constituting 21% of biliary bile acids, was an unknown C27 bile acid. Its structure was elucidated by LC/ESI-MS/MS and NMR and shown to be the taurine conjugate of (25R)-1β,3α,7α-trihydroxy-5β-cholestan-27-oic acid, a C27 trihydroxy bile acid not previously reported. Although C27 bile acids with a 1β-hydroxyl group have been identified as trace bile acids in the alligator, this is the first report of a major biliary C27 bile acid possessing a 1β-hydroxyl group. PMID:19011113

Bear bile: dilemma of traditional medicinal use and animal protection

PubMed Central

Feng, Yibin; Siu, Kayu; Wang, Ning; Ng, Kwan-Ming; Tsao, Sai-Wah; Nagamatsu, Tadashi; Tong, Yao

2009-01-01

Bear bile has been used in Traditional Chinese Medicine (TCM) for thousands of years. Modern investigations showed that it has a wide range of pharmacological actions with little toxicological side effect and the pure compounds have been used for curing hepatic and biliary disorders for decades. However, extensive consumption of bear bile made bears endangered species. In the 1980's, bear farming was established in China to extract bear bile from living bears with "Free-dripping Fistula Technique". Bear farming is extremely inhumane and many bears died of illness such as chronic infections and liver cancer. Efforts are now given by non-governmental organizations, mass media and Chinese government to end bear farming ultimately. At the same time, systematic research has to be done to find an alternative for bear bile. In this review, we focused on the literature, laboratory and clinical results related to bear bile and its substitutes or alternative in English and Chinese databases. We examined the substitutes or alternative of bear bile from three aspects: pure compounds derived from bear bile, biles from other animals and herbs from TCM. We then discussed the strategy for stopping the trading of bear bile and issues of bear bile related to potential alternative candidates, existing problems in alternative research and work to be done in the future. PMID:19138420

Bile acid-induced necrosis in primary human hepatocytes and in patients with obstructive cholestasis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Woolbright, Benjamin L.; Dorko, Kenneth; Antoine, Daniel J.

Accumulation of bile acids is a major mediator of cholestatic liver injury. Recent studies indicate bile acid composition between humans and rodents is dramatically different, as humans have a higher percent of glycine conjugated bile acids and increased chenodeoxycholate content, which increases the hydrophobicity index of bile acids. This increase may lead to direct toxicity that kills hepatocytes, and promotes inflammation. To address this issue, this study assessed how pathophysiological concentrations of bile acids measured in cholestatic patients affected primary human hepatocytes. Individual bile acid levels were determined in serum and bile by UPLC/QTOFMS in patients with extrahepatic cholestasis with,more » or without, concurrent increases in serum transaminases. Bile acid levels increased in serum of patients with liver injury, while biliary levels decreased, implicating infarction of the biliary tracts. To assess bile acid-induced toxicity in man, primary human hepatocytes were treated with relevant concentrations, derived from patient data, of the model bile acid glycochenodeoxycholic acid (GCDC). Treatment with GCDC resulted in necrosis with no increase in apoptotic parameters. This was recapitulated by treatment with biliary bile acid concentrations, but not serum concentrations. Marked elevations in serum full-length cytokeratin-18, high mobility group box 1 protein (HMGB1), and acetylated HMGB1 confirmed inflammatory necrosis in injured patients; only modest elevations in caspase-cleaved cytokeratin-18 were observed. These data suggest human hepatocytes are more resistant to human-relevant bile acids than rodent hepatocytes, and die through necrosis when exposed to bile acids. These mechanisms of cholestasis in humans are fundamentally different to mechanisms observed in rodent models. - Highlights: • Cholestatic liver injury is due to cytoplasmic bile acid accumulation in hepatocytes. • Primary human hepatocytes are resistant to BA-induced injury compared to rodents. • Primary human hepatocytes largely undergo necrosis in response to BA toxicity. • Cholestatic liver injury in vivo is predominantly necrotic with minor apoptosis. • Rodent models of bile acid toxicity may not recapitulate the injury in man.« less

The diagnostic value of 24-hour ambulatory intraesophageal pH-impedance in patients with laryngopharyngeal reflux symptoms comparable with typical symptoms.

PubMed

Sakin, Yusuf S; Vardar, Rukiye; Sezgin, Baha; Cetin, Zeynep Erdogan; Alev, Yasemin; Yildirim, Esra; Kirazli, Tayfun; Bor, Serhat

2017-08-01

The diagnosis of laryngopharyngeal reflux is currently based on a combination of the patient history of multichannel intraluminal impedance and ambulatory pH (MII-pH); however, none of these findings alone is specific for the diagnosis of laryngopharyngeal reflux. We aimed to compare the baseline characteristics and esophageal baseline impedance values between patients with and without laryngopharyngeal reflux symptoms. We retrospectively analyzed data from two groups of patients with laryngopharyngeal reflux according to their reflux finding score (RFS) as scored by ENTs. Control patients were nonerosive reflux disease patients without laryngopharyngeal reflux. All MII-pH parameters and baseline impedance were analyzed from six levels and the proximal and distal baseline impedance and the ratio of the proximal to distal baseline impedance levels was calculated. Altogether 123 patients with laryngopharyngeal reflux and 49 control patients were included. A total of 81 of 123 patients had RFS ≥ 7, and 42 of 123 patients had RFS < 7. Baseline impedance analysis showed that patients with laryngopharyngeal reflux symptoms had significantly lower proximal baseline impedance values (1997 ± 51 vs 2245 ± 109, p  < 0.05) than the control group. Additionally, patients with laryngopharyngeal reflux symptoms had a significantly lower proximal-to-distal ratio (1.28 ± 0.05 vs 1.53 ± 0.09, p  < 0.05). In the subgroup analysis, patients with RFS < 7 were found to have a significantly lower acid exposure time than either the patients with RFS ≥ 7 (3.85 ± 0.65 vs 8.2 ± 1.52, p  < 0.05) or the control group (3.85 ± 0.65 vs 6.1 ± 0.81, p  < 0.05). Additionally, patients with RFS ≥ 7 had significantly lower proximal baseline impedance levels than the control group (1970 ± 63 vs 2245 ± 109, p  < 0.05). Patients with pathologic laryngopharyngeal reflux symptom scores had lower proximal baseline impedance levels and lower proximal-to-distal ratios, which may reflect the proximal mucosal noxious effect of the refluxate. These results may indicate that laryngopharyngeal reflux symptoms may be due to chronic acid exposure in the proximal segments of the esophagus, and the proximal-to-distal ratio may be used as a new metric for diagnosis.

Vesicoureteral reflux and urinary tract infection in children with a history of prenatal hydronephrosis--should voiding cystourethrography be performed in cases of postnatally persistent grade II hydronephrosis?

PubMed

Estrada, Carlos R; Peters, Craig A; Retik, Alan B; Nguyen, Hiep T

2009-02-01

The clinical relevance of prenatal hydronephrosis is not well-defined. We determined the risk of febrile urinary tract infection in the absence of screening for vesicoureteral reflux, and whether postnatal voiding cystourethrography should be performed in patients with a history of prenatal hydronephrosis and postnatally persistent Society for Fetal Urology grade II hydronephrosis. From a longitudinal database of patients with prenatal hydronephrosis maintained since 1998 we identified those with postnatally persistent grade II hydronephrosis. This cohort was divided into patients who were and were not screened with an initial voiding cystourethrogram. The rates of vesicoureteral reflux and development of febrile urinary tract infection were determined. Of 2,076 patients with prenatal hydronephrosis 1,514 had grade II hydronephrosis. Of the patients 76% underwent an initial voiding cystourethrogram and vesicoureteral reflux was found in 28%. There was no relation between laterality of hydronephrosis and incidence of vesicoureteral reflux. There was no difference between nonscreened and screened patients with respect to gender and laterality of hydronephrosis. Urinary tract infection developed in 1.3% of the patients who were screened and did not have vesicoureteral reflux and, therefore, were not receiving antibiotics. Of the screened patients with vesicoureteral reflux who were receiving prophylactic antibiotics urinary tract infection developed in 1.6% at a mean age of 9.4 months. In 363 patients who did not undergo an initial voiding cystourethrogram we estimated (based on the screened population) that 101 would have vesicoureteral reflux and 5 would have a urinary tract infection. However, a febrile urinary tract infection developed in 16 patients (4.4% overall, p <0.0001) at a mean age of 9.3 months. Voiding cystourethrogram performed in these 16 patients revealed vesicoureteral reflux in 12. Of all the patients with a urinary tract infection who were ultimately observed to have vesicoureteral reflux (including those initially screened and those discovered to have reflux after a urinary tract infection) the laterality of hydronephrosis, grade of reflux and laterality of reflux were comparable. In patients with a history of prenatal hydronephrosis who are observed to have postnatally persistent grade II hydronephrosis identification of vesicoureteral reflux and use of prophylactic antibiotics significantly reduce the risk of febrile urinary tract infection. Therefore, we recommend that patients with a history of prenatal hydronephrosis and postnatally persistent hydronephrosis be screened with voiding cystourethrography early in life, and be placed on prophylactic antibiotics until the screening results are known.

Mechanisms of bile acid mediated inflammation in the liver.

PubMed

Li, Man; Cai, Shi-Ying; Boyer, James L

2017-08-01

Bile acids are synthesized in the liver and are the major component in bile. Impaired bile flow leads to cholestasis that is characterized by elevated levels of bile acid in the liver and serum, followed by hepatocyte and biliary injury. Although the causes of cholestasis have been extensively studied, the molecular mechanisms as to how bile acids initiate liver injury remain controversial. In this chapter, we summarize recent advances in the pathogenesis of bile acid induced liver injury. These include bile acid signaling pathways in hepatocytes as well as the response of cholangiocytes and innate immune cells in the liver in both patients with cholestasis and cholestatic animal models. We focus on how bile acids trigger the production of molecular mediators of neutrophil recruitment and the role of the inflammatory response in this pathological process. These advances point to a number of novel targets where drugs might be judged to be effective therapies for cholestatic liver injury. Copyright © 2017 Elsevier Ltd. All rights reserved.

Gastroesophageal reflux in infants

MedlinePlus

... this page: //medlineplus.gov/ency/article/001134.htm Gastroesophageal reflux in infants To use the sharing features on this page, please enable JavaScript. Gastroesophageal reflux occurs when stomach contents leak backward from the ...

Pressure and Flow Rate Changes During Contrast Injections in Cerebral Angiography: Correlation to Reflux Length.

PubMed

Kovarovic, Brandon; Woo, Henry H; Fiorella, David; Lieber, Baruch B; Sadasivan, Chander

2018-03-01

Cerebral angiography involves the antegrade injection of contrast media through a catheter into the vasculature to visualize the region of interest under X-ray imaging. Depending on the injection and blood flow parameters, the bolus of contrast can propagate in the upstream direction and proximal to the catheter tip, at which point contrast is said to have refluxed. In this in vitro study, we investigate the relationship of fundamental hemodynamic variables to this phenomenon. Contrast injections were carried out under steady and pulsatile flow using various vessel diameters, catheter sizes, working fluid flow rates, and injection rates. The distance from the catheter tip to the proximal edge of the contrast bolus, called reflux length, was measured on the angiograms; the relation of this reflux length to different hemodynamic parameters was evaluated. Results show that contrast reflux occurs when the pressure distal to the catheter tip increases to be greater than the pressure proximal to the catheter tip. The ratio of this pressure difference to the baseline flow rate, called reflux resistance here, was linearly correlated to the normalized reflux length (reflux length/vessel diameter). Further, the ratio of blood flow to contrast fluid momentums, called the Craya-Curtet number, was correlated to the normalized reflux length via a sigmoid function. A sigmoid function was also found to be representative of the relationship between the ratio of the Reynolds numbers of blood flow to contrast and the normalized reflux length. As described by previous reports, catheter based contrast injections cause substantial increases in local flow and pressure. Contrast reflux should generally be avoided during standard antegrade angiography. Our study shows two specific correlations between contrast reflux length and baseline and intra-injection parameters that have not been published previously. Further studies need to be conducted to fully characterize the phenomena and to extract reliable indicators of clinical utility. Parameters relevant to cerebral angiography are studied here, but the essential principles are applicable to all angiographic procedures involving antegrade catheter injections.

[Esophageal motility characteristics of refractory heartburn: a study based on high resolution manometry and 24 hour pH-impedance monitoring].

PubMed

Wang, Kun; Duan, Liping; Xia, Zhiwei; Xu, Zhijie; Ge, Ying

2014-09-16

To analyze the esophageal motility characteristics of refractory heartburn with different reflux patterns and preliminarily clarify the roles of esophageal disorder in refractory heartburn. A total of 176 refractory heartburn patients were enrolled from 2009 to 2013. After gastroscopy and 24 hour pH-impedance monitoring, they were divided into 4 groups of reflux esophagitis (RE, n = 29), non-erosive reflux disease with acid reflux (NERD-acid, n = 51), NERD with weakly acidic reflux (NERD-weakly acid, n = 51) and non-reflux associated heartburn (n = 45). All subjects undertake high resolution manometry test and their esophageal motility functions were analyzed by the Chicago classification criteria 2012. Among them, 60.23% (106/176) patients presented esophageal motility disorders. And 42.61% (75/176) fulfilled the criteria of weak peristalsis, 7.39% (13/176) distal esophageal spasm, 4.55% (8/176) rapid contraction, 3.98% (7/176) EGJ outflow obstruction, 1.14% (2/176) hiatus hernia and 1 Jackhammer esophagus. The detection rates of esophageal motility disorder were similar among 4 groups and weak peristalsis was the most common disorder in all groups (41.38% in RE, 37.25% in NERD-acid patients, 54.90% in NERD-weakly acid and 35.56% in non-reflux associated heartburn patients). However, hypertensive motility disorders in non-reflux associated heartburn group (31.11%, 14/45) were more than GERD subgroups (11.45%, 15/131) (P < 0.05) . The relax ratio of low esophagus sphincter (LES) in GERD subgroups were higher than that in non-reflux associated heartburn patients. And the relax ratio of NERD-weakly acid was significantly higher than that in non-reflux associated heartburn patients (65% (50%-80%) vs 58% (42%-67%) , P < 0.05). The integrated relaxation pressure in GERD subgroups were lower than that of non-reflux associated heartburn patients without significant differences (P > 0.05). Esophageal weak peristalsis is one of the most common motility disorders in refractory heartburn patients, and esophageal hypertensive motility disorders are common in non-reflux associated heartburn patients. Esophageal manometry is necessary for the diagnosis and treatment of refractory heartburn.

Prevalence of Helicobacter pylori in patients with gastro-oesophageal reflux disease: systematic review

PubMed Central

Raghunath, Anan; Hungin, A Pali S; Wooff, David; Childs, Susan

2003-01-01

Objectives To ascertain the prevalence of Helicobacter pylori in patients with gastro-oesophageal reflux disease and its association with the disease. Design Systematic review of studies reporting the prevalence of H pylori in patients with and without gastro-oesophageal reflux disease. Data sources Four electronic databases, searched to November 2001, experts, pharmaceutical companies, and journals. Main outcome measure Odds ratio for prevalence of H pylori in patients with gastro-oesophageal reflux disease. Results 20 studies were included. The pooled estimate of the odds ratio for prevalence of H pylori was 0.60 (95% confidence interval 0.47 to 0.78), indicating a lower prevalence in patients with gastro-oesophageal reflux disease. Substantial heterogeneity was observed between studies. Location seemed to be an important factor, with a much lower prevalence of H pylori in patients with gastro-oesophageal reflux disease in studies from the Far East, despite a higher overall prevalence of infection than western Europe and North America. Year of study was not a source of heterogeneity. Conclusion The prevalence of H pylori infection was significantly lower in patients with than without gastro-oesophageal reflux, with geographical location being a strong contributor to the heterogeneity between studies. Patients from the Far East with reflux disease had a lower prevalence of H pylori infection than patients from western Europe and North America, despite a higher prevalence in the general population. What is already known on this topicThe relation between H pylori infection and gastro-oesophageal reflux disease is controversialStudies on the prevalence of H pylori in patients with gastro-oesophageal reflux disease have given conflicting resultsRecent guidelines recommend eradication of H pylori in patients requiring long term proton pump inhibitors, essentially for reflux diseaseWhat this study addsDespite heterogeneity between studies, the prevalence of H pylori was significantly lower in patients with than without gastro-oesophageal reflux diseaseFurther well designed studies are required to establish the clinical relevance of the findings, particularly in eradication therapy PMID:12676842

Use of D(acid)-, D(bile)-, z(acid)-, and z(bile)-values in evaluating Bifidobacteria with regard to stomach pH and bile salt sensitivity.

PubMed

Jia, Li; Shigwedha, Nditange; Mwandemele, Osmund D

2010-01-01

The survival of bifidobacteria in simulated conditions of the gastrointestinal (GI) tract was studied based on the D- and z-value concept. Some Bifidobacterium spp. are probiotics that improve microbial balance in the human GI tract. Because they are sensitive to low pH and bile salt concentrations, their viability in the GI tract is limited. The D- and z-value approach was therefore adopted as a result of observing constant log-cell reduction (90%) when Bifidobacterium spp. were exposed to these 2 different stressing factors. Survivals of one strain each or 4 species of Bifidobacterium was studied at pH between 3.0 and 4.5 and in ox-bile between 0.15% and 0.60% for times up to 41 h. From the D(acid)- and D(bile)-values, the order of resistance to acid and bile was B. bifidum > B. infantis > B. longum > B. adolescentis. While the former 3 strains retained high cell viability at pH 3.5 (>5.5 log CFU/mL after 5 h) and at elevated bile salt concentration of 0.6% (>4.5 log CFU/mL after 3 h), B. adolescentis was less resistant (<3.4 log CFU/mL). The z(acid)- and z(bile)-values calculated from the D(acid)- and D(bile)-values ranged from 1.11 to 1.55 pH units and 0.40% to 0.49%, respectively. The results suggest that the D(acid)-, D(bile)-, z(acid)-, and z(bile)-value approach could be more appropriate than the screening and selection method in evaluating survival of probiotic bacteria, and in measuring their tolerance or resistance to gastric acidity and the associated bile salt concentration in the small intestine. The evaluation of the tolerance of bifidobacteria to bile salts and low pH has been made possible by use of D- and z-value concept. The calculated z(acid)- and z(bile)-values were all fairly similar for the strains used and suggest the effect of increasing the bile salt concentration or decreasing the pH on the D(acid)- and D(bile)-values. This approach would be useful for predicting the suitability of bifidobacteria and other lactic acid bacteria (LAB) as probiotics for use in real-life situations.

The comparative analyses of different diagnostic approaches in detection of gastroesophageal reflux disease in children.

PubMed

Ristic, Nina; Milovanovic, Ivan; Radusinovic, Milica; Stevic, Marija; Ristic, Milos; Ristic, Maja; Kisic Tepavcevic, Darija; Alempijevic, Tamara

2017-01-01

The aim of this study was to compare the different diagnostic approaches in detection of gastroesophageal reflux disease in children presented with symptoms suggesting gastroesophageal reflux disease. The study design was cross sectional. The study retrospectively included all children who underwent combined multiple intraluminal impedance and pH (pH-MII) monitoring due to gastrointestinal and/or extraesophageal symptoms suggesting gastroesophageal reflux disease at University Children's Hospital in Belgrade, from July 2012 to July 2016. A total of 218 (117 boys/101 girls), mean age 6.7 years (range 0.06-18.0 years), met the inclusion criteria. Gastroesophageal reflux disease was found in 128 of 218 children (57.4%) by pH-MII and in 76 (34.1%) children by pH metry alone. Using pH-MII monitoring as gold standard, sensitivity of pH-metry was lowest in infants (22.9%), with tendency to increase in older age groups (reaching 76.4% in children ≥ 9 years). The sensitivity of pH-metry alone in children with extraesophageal symptoms was 38.1%, while the sensitivity of pH-metry in children with gastrointestinal symptoms was 63.8%. Reflux esophagitis was identified in 31 (26.1%) of 119 children who underwent endoscopy. Logistic regression analysis showed that best predictors of endoscopic reflux esophagitis are the longest acid episode (OR = 1.52, p<0.05) and DeMeester reflux composite score (OR = 3.31, p<0.05). The significant cutoff values included DeMeester reflux composite score ≥ 29 (AUC 0.786, CI 0.695-0.877, p<0.01) and duration of longest acid reflux ≥ 18 minutes (AUC 0.784, CI 0.692-0.875, p<0.01). The results of our study suggested that compared with pH-metry alone, pH-MII had significantly higher detection rate of gastroesophageal reflux disease, especially in infants. Our findings also showed that pH-MII parameters correlated significantly with the endoscopically confirmed erosive esophagitis.

Small volume acid reflux in gastroesophageal reflux disease patients with hiatal hernia is only detectable by pH-metry but not by multichannel intraluminal impedance.

PubMed

Weigt, J; Malfertheiner, P

2013-07-01

Until now, it is uncertain if the so-called pH-only reflux episodes that consist of a pH drop without evidence of retrograde bolus movement in multichannel intraluminal impedance (MII) represent reflux episodes or artifacts. Hiatal hernia (HH) may allow reflux of small volumes to occur that can be detected by pH-metry but not by MII. The aim was to search for a mechanism that can explain pH-only reflux, 20 patients (12 females and 8 males, median age 52 years, interquartile range [IQR]: 40.5-60.75 years) were investigated with MII-pH off PPI. Impedance and pH-metry data were analyzed separately. The differences in detection rate of acid reflux between pH-metry and MII were correlated with the presence of HH. In an in vitro experiment, MII-pH probes were flushed with citric acid in plastic tubes of different size with capillary diameter and diameters of 2.5 mm and 4.5 mm, while recording pH values and impedance. HH was present in six patients and absent in 14 patients. In patients with HH in comparison with patients with absent HH, the difference of acid reflux detection between pH-metry and MII is significantly higher (70%, IQR: 15-88% and 3.6%, IQR: 0-31%, respectively). In vitro all simulated reflux lead to a fall in pH whereas a corresponding decrease in impedance was only recognizable in the 4.5-mm plastic tubes. Acid reflux episodes in patients with HH are more frequently detected by pH-metry than by MII. Small volume reflux that does not lead to a decrease in impedance is the likely explanation for this phenomenon. © 2012 Copyright the Authors. Journal compilation © 2012, Wiley Periodicals, Inc. and the International Society for Diseases of the Esophagus.

An alginate-antacid formulation localizes to the acid pocket to reduce acid reflux in patients with gastroesophageal reflux disease.

PubMed

Rohof, Wout O; Bennink, Roel J; Smout, Andre J P M; Thomas, Edward; Boeckxstaens, Guy E

2013-12-01

Alginate rafts (polysaccharide polymers that precipitate into a low-density viscous gel when they contact gastric acid) have been reported to form at the acid pocket, an unbuffered pool of acid that floats on top of ingested food and causes postprandial acid reflux. We studied the location of an alginate formulation in relation to the acid pocket and the corresponding effects on reflux parameters and acid pocket positioning in patients with gastroesophageal reflux disease (GERD). We randomly assigned patients with symptomatic GERD and large hiatal hernias to groups who were given either (111)In-labeled alginate-antacid (n = 8, Gaviscon Double Action Liquid) or antacid (n = 8, Antagel) after a standard meal. The relative positions of labeled alginate and acid pocket were analyzed for 2 hours by using scintigraphy; reflux episodes were detected by using high-resolution manometry and pH-impedance monitoring. The alginate-antacid label localized to the acid pocket. The number of acid reflux episodes was significantly reduced in patients receiving alginate-antacid (3.5; range, 0-6.5; P = .03) compared with those receiving antacid (15; range, 5-20), whereas time to acid reflux was significantly increased in patients receiving alginate-antacid (63 minutes; range, 23-92) vs those receiving antacid (14 minutes; range, 9-23; P = .01). The acid pocket was located below the diaphragm in 71% of patients given alginate-antacid vs 21% of those given antacid (P = .08). There was an inverse correlation between a subdiaphragm position of the acid pocket and acid reflux (r = -0.76, P < .001). In a study of 16 patients with GERD, we observed that the alginate-antacid raft localizes to the postprandial acid pocket and displaces it below the diaphragm to reduce postprandial acid reflux. These findings indicate the importance of the acid pocket in GERD pathogenesis and establish alginate-antacid as an appropriate therapy for postprandial acid reflux. Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.

Asia-Pacific consensus on the management of gastro-oesophageal reflux disease: an update focusing on refractory reflux disease and Barrett's oesophagus.

PubMed

Fock, Kwong Ming; Talley, Nicholas; Goh, Khean Lee; Sugano, Kentaro; Katelaris, Peter; Holtmann, Gerald; Pandolfino, John E; Sharma, Prateek; Ang, Tiing Leong; Hongo, Michio; Wu, Justin; Chen, Minhu; Choi, Myung-Gyu; Law, Ngai Moh; Sheu, Bor-Shyang; Zhang, Jun; Ho, Khek Yu; Sollano, Jose; Rani, Abdul Aziz; Kositchaiwat, Chomsri; Bhatia, Shobna

2016-09-01

Since the publication of the Asia-Pacific consensus on gastro-oesophageal reflux disease in 2008, there has been further scientific advancement in this field. This updated consensus focuses on proton pump inhibitor-refractory reflux disease and Barrett's oesophagus. A steering committee identified three areas to address: (1) burden of disease and diagnosis of reflux disease; (2) proton pump inhibitor-refractory reflux disease; (3) Barrett's oesophagus. Three working groups formulated draft statements with supporting evidence. Discussions were done via email before a final face-to-face discussion. We used a Delphi consensus process, with a 70% agreement threshold, using Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria to categorise the quality of evidence and strength of recommendations. A total of 32 statements were proposed and 31 were accepted by consensus. A rise in the prevalence rates of gastro-oesophageal reflux disease in Asia was noted, with the majority being non-erosive reflux disease. Overweight and obesity contributed to the rise. Proton pump inhibitor-refractory reflux disease was recognised to be common. A distinction was made between refractory symptoms and refractory reflux disease, with clarification of the roles of endoscopy and functional testing summarised in two algorithms. The definition of Barrett's oesophagus was revised such that a minimum length of 1 cm was required and the presence of intestinal metaplasia no longer necessary. We recommended the use of standardised endoscopic reporting and advocated endoscopic therapy for confirmed dysplasia and early cancer. These guidelines standardise the management of patients with refractory gastro-oesophageal reflux disease and Barrett's oesophagus in the Asia-Pacific region. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Numerical analysis of seawater circulation in carbonate platforms: II. The dynamic interaction between geothermal and brine reflux circulation

USGS Publications Warehouse

Jones, G.D.; Whitaker, F.F.; Smart, P.L.; Sanford, W.E.

2004-01-01

Density-driven seawater circulation may occur in carbonate platforms due to geothermal heating and / or reflux of water of elevated salinity. In geothermal circulation lateral contrasts in temperature between seawater and platform groundwaters warmed by the geothermal heat flux result in upward convective flow, with colder seawater drawn into the platform at depth. With reflux circulation, platform-top waters concentrated by evaporation flow downward, displacing less dense underlying groundwaters. We have used a variable density groundwater flow model to examine the pattern, magnitude and interaction of these two different circulation mechanisms, for mesosaline platform-top waters (50???) and brines concentrated up to saturation with respect to gypsum (150???) and halite (246???). Geothermal circulation, most active around the platform margin, becomes restricted and eventually shut-off by reflux of brines from the platform interior towards the margin. The persistence of geothermal circulation is dependent on the rate of brine reflux, which is proportional to the concentration of platform-top brines and also critically dependent on the magnitude and distribution of permeability. Low permeability evaporites can severely restrict reflux whereas high permeability units in hydraulic continuity enhance brine transport. Reduction in permeability with depth and anisotropy of permeability (kv < < kh) focuses flow laterally in the shallow subsurface (<1 km), resulting in a horizontally elongated brine plume. Aquifer porosity and dispersivity are relatively minor controls on reflux. Platform brines can entrain surficial seawater when brine generating conditions cease but the platform-top remains submerged, a variant of reflux we term "latent reflux". Brines concentrated up to gypsum saturation have relatively long residence times of at least 100 times the duration of the reflux event. They thus represent a long-term control on post-reflux groundwater circulation, and consequently on the rates and spatial patterns of shallow burial diagenesis, such as dolomitization.

Bile salts as semiochemicals in fish

USGS Publications Warehouse

Buchinger, Tyler J.; Li, Weiming; Johnson, Nicholas S.

2014-01-01

Bile salts are potent olfactory stimuli in fishes; however the biological functions driving such sensitivity remain poorly understood. We provide an integrative review of bile salts as semiochemicals in fish. First, we present characteristics of bile salt structure, metabolism, and function that are particularly relevant to chemical communication. Bile salts display a systematic pattern of structural variation across taxa, are efficiently synthesized, and are stable in the environment. Bile salts are released into the water via the intestine, urinary tract, or gills, and are highly water soluble. Second, we consider the potential role of bile salts as semiochemicals in the contexts of detecting nearby fish, foraging, assessing risk, migrating, and spawning. Lastly, we suggest future studies on bile salts as semiochemicals further characterize release into the environment, behavioral responses by receivers, and directly test the biological contexts underlying olfactory sensitivity.

Conjugated bile acids in gallbladder bile and serum as potential biomarkers for cholesterol polyps and adenomatous polyps.

PubMed

Zhao, Mei-Fen; Huang, Peng; Ge, Chun-Lin; Sun, Tao; Ma, Zhi-Gang; Ye, Fei-Fei

2016-02-28

To identify conjugated bile acids in gallbladder bile and serum as possible biomarkers for cholesterol polyps (CPs) and adenomatous polyps (APs). Gallbladder bile samples and serum samples were collected from 18 patients with CPs (CP group), 9 patients with APs (AP group), and 20 patients with gallstones (control group) from March to November, 2013. High performance liquid chromatography (HPLC) assay with ultraviolent detection was used to detect the concentration of 8 conjugated bile acids (glycocholic acid, GCA; taurocholic acid, TCA; glycochenodeoxycholic acid, GCDCA; taurochenodeoxycholic acid, TCDCA; glycodeoxycholic acid, GDCA; taurodeoxycholic acid, TDCA; taurolithocholic acid, TLCA; tauroursodeoxycholic acid, TUDCA) in bile samples and serum samples. The diagnostic efficacy of serum GCA, GCDCA and TCDCA was evaluated. These 8 conjugated bile acids in gallbladder bile and serum were completely identified within 10 minutes with good linearity (correlation coefficient: R>0.9900; linearity range: 3.91-500 µg/mL). Among these conjugated bile acids, the levels of gallbladder bile GCDCA and TCDCA in the CP group were significantly higher than those in the AP group (p<0.05). Furthermore, serum GCDCA and TCDCA as well as GCA were significantly higher in the AP group than the CP group (p<0.05). Serum GCDCA alone (≤12 µg/mL) had relatively better diagnostic efficacy than the other conjugated bile acids. The levels of serum GCA, GCDCA and TCDCA may be valuable for differentiation of APs and CPs.

A new insight into the physiological role of bile salt hydrolase among intestinal bacteria from the genus Bifidobacterium.

PubMed

Jarocki, Piotr; Podleśny, Marcin; Glibowski, Paweł; Targoński, Zdzisław

2014-01-01

This study analyzes the occurrence of bile salt hydrolase in fourteen strains belonging to the genus Bifidobacterium. Deconjugation activity was detected using a plate test, two-step enzymatic reaction and activity staining on a native polyacrylamide gel. Subsequently, bile salt hydrolases from B. pseudocatenulatum and B. longum subsp. suis were purified using a two-step chromatographic procedure. Biochemical characterization of the bile salt hydrolases showed that the purified enzymes hydrolyzed all of the six major human bile salts under the pH and temperature conditions commonly found in the human gastrointestinal tract. Next, the dynamic rheometry was applied to monitor the gelation process of deoxycholic acid under different conditions. The results showed that bile acids displayed aqueous media gelating properties. Finally, gel-forming abilities of bifidobacteria exhibiting bile salt hydrolase activity were analyzed. Our investigations have demonstrated that the release of deconjugated bile acids led to the gelation phenomenon of the enzymatic reaction solution containing purified BSH. The presented results suggest that bile salt hydrolase activity commonly found among intestinal microbiota increases hydrogel-forming abilities of certain bile salts. To our knowledge, this is the first report showing that bile salt hydrolase activity among Bifidobacterium is directly connected with the gelation process of bile salts. In our opinion, if such a phenomenon occurs in physiological conditions of human gut, it may improve bacterial ability to colonize the gastrointestinal tract and their survival in this specific ecological niche.

Liver ischemia and ischemia-reperfusion induces and trafficks the multi-specific metal transporter Atp7b to bile duct canaliculi: possible preferential transport of iron into bile.

PubMed

Goss, John A; Barshes, Neal R; Karpen, Saul J; Gao, Feng-Qin; Wyllie, Samuel

2008-04-01

Both Atp7b (Wilson disease gene) and Atp7a (Menkes disease gene) have been reported to be trafficked by copper. Atp7b is trafficked to the bile duct canaliculi and Atp7a to the plasma membrane. Whether or not liver ischemia or ischemia-reperfusion modulates Atp7b expression and trafficking has not been reported. In this study, we report for the first time that the multi-specific metal transporter Atp7b is significantly induced and trafficked by both liver ischemia alone and liver ischemia-reperfusion, as judged by immunohistochemistry and Western blot analyses. Although hepatocytes also stained for Atp7b, localized intense staining of Atp7b was found on bile duct canaliculi. Inductive coupled plasma-mass spectrometry analysis of bile copper, iron, zinc, and manganese found a corresponding significant increase in biliary iron. In our attempt to determine if the increased biliary iron transport observed may be a result of altered bile flow, lysosomal trafficking, or glutathione biliary transport, we measured bile flow, bile acid phosphatase activity, and glutathione content. No significant difference was found in bile flow, bile acid phosphatase activity, and glutathione, between control livers and livers subjected to ischemia-reperfusion. Thus, we conclude that liver ischemia and ischemia-reperfusion induction and trafficking Atp7b to the bile duct canaliculi may contribute to preferential iron transport into bile.

Proton pump inhibitors

MedlinePlus

... used to: Relieve symptoms of acid reflux, or gastroesophageal reflux disease (GERD). This is a condition in which ... MF. Guidelines for the diagnosis and management of gastroesophageal reflux disease. Am J Gastroenterol . 2013;108(3):308- ...

Comparative study of two modes of gastroesophageal reflux measuring: conventional esophageal pH monitoring and wireless pH monitoring.

PubMed

Azzam, Rimon Sobhi; Sallum, Rubens A A; Brandão, Jeovana Ferreira; Navarro-Rodriguez, Tomás; Nasi, Ary

2012-01-01

Esophageal pH monitoring is considered to be the gold standard for the diagnosis of gastroesophageal acid reflux. However, this method is very troublesome and considerably limits the patient's routine activities. Wireless pH monitoring was developed to avoid these restrictions. To compare the first 24 hours of the conventional and wireless pH monitoring, positioned 3 cm above the lower esophageal sphincter, in relation to: the occurrence of relevant technical failures, the ability to detect reflux and the ability to correlate the clinical symptoms to reflux. Twenty-five patients referred for esophageal pH monitoring and with typical symptoms of gastroesophageal reflux disease were studied prospectively, underwent clinical interview, endoscopy, esophageal manometry and were submitted, with a simultaneous initial period, to 24-hour catheter pH monitoring and 48-hour wireless pH monitoring. Early capsule detachment occurred in one (4%) case and there were no technical failures with the catheter pH monitoring (P = 0.463). Percentages of reflux time (total, upright and supine) were higher with the wireless pH monitoring (P < 0.05). Pathological gastroesophageal reflux occurred in 16 (64%) patients submitted to catheter and in 19 (76%) to the capsule (P = 0.355). The symptom index was positive in 12 (48%) patients with catheter pH monitoring and in 13 (52%) with wireless pH monitoring (P = 0.777). 1) No significant differences were reported between the two methods of pH monitoring (capsule vs catheter), in regard to relevant technical failures; 2) Wireless pH monitoring detected higher percentages of reflux time than the conventional pH-metry; 3) The two methods of pH monitoring were comparable in diagnosis of pathological gastroesophageal reflux and comparable in correlating the clinical symptoms with the gastroesophageal reflux.

Interim results on abolishing reflux alongside a randomized clinical trial on laser ablation with phlebectomies versus foam sclerotherapy.

PubMed

Lattimer, C R; Kalodiki, E; Azzam, M; Makris, G C; Somiayajulu, S; Geroulakos, G

2013-08-01

The early results of a randomised clinical trial comparing local anaesthesia endovenous laser ablation (EVLA) with concurrent phlebectomies versus ultrasound-guided foam sclerotherapy (UGFS) into the great saphenous vein (GSV) revealed that laser was more expensive but the results on abolition of reflux were similar. The interim results at 15 month follow-up are reported. Evaluations included ultrasound, the venous clinical severity score (VCSS), the Aberdeen varicose vein questionnaire (AVVQ) and the saphenous treatment score (STS). The global absence of reflux defined technical success. Adjuvant sclerotherapy to areas of reflux was administered on patient choice. Occlusion of the GSV was more effective with EVLA at 42/44 (95.5%) versus 31/46 (67.4%) for UGFS. However both techniques were equally effective at abolishing global venous reflux. The number of legs (N.=100) with total reflux abolition, above-knee, below-knee or combined reflux and loss to follow-up was 18, 6, 12, 8, 6 with EVLA and 20, 8, 11, 7, 4 with UGFS, respectively. The VCSS, AVVQ and STS reduced compared to baseline (P<0.0005), but there was no statistical difference between the groups. The AVVQ remained unchanged between 3-15 months (P=0.601). Also during this time, 19/46(41%) UGFS versus 9/44(20%) EVLA legs received adjuvant treatment (2.1 times increase). However, overall, adjuvant foam was given 4.7 times more frequently in the UGFS patients. EVLA and UGFS are equally effective at abolishing global venous reflux with overall success of 41% and 43%, respectively. The high reflux rate was not related to deterioration in quality of life indicating that this reflux was largely asymptomatic.

The Role of Microaspiration in the Pathogenesis of Gastroesophageal Reflux-related Chronic Cough

PubMed Central

Özdemir, Pelin; Erdinç, Münevver; Vardar, Rukiye; Veral, Ali; Akyıldız, Serdar; Özdemir, Özer; Bor, Serhat

2017-01-01

Background/Aims Gastroesophageal reflux disease (GERD) is one of the main causes of chronic cough. We evaluated the role of microaspiration in the pathogenesis of reflux-related cough by determining the amount of lipid-laden macrophages (LLMs) in bronchoalveolar lavage (BAL) specimens. Methods A total of 161 cases of chronic cough were evaluated, and 36 patients (average age 48.2 years) were recruited for this single center prospective study. Patients with a history of smoking, angiotensin converting enzyme inhibitor usage, any abnormality on pulmonary function tests, abnormal chest X-rays, occupational or environmental exposures, or upper airway cough syndrome were excluded. GERD was evaluated by 24-hour esophageal impedance-pH monitoring. BAL specimens for LLM determination were obtained from 34 patients by flexible bronchoscopy. Results Patients with pathological intra-esophageal reflux according to multichannel intraluminal impedance and pH monitoring had higher LLM positivity in BAL specimens than patients without pathological reflux (8/14 in reflux positive group vs 1/22 in reflux negative group; P = 0.004). The BAL cell distribution was not different between the 2 groups (P = 0.574 for macrophages, P = 0.348 for lymphocytes, P = 0.873 for neutrophils and P = 0.450 for eosinophils). Conclusions Our results confirm the role of the microaspiration of refluxate in the pathogenetic mechanism of chronic cough. While bronchoscopy is indicated in patients with chronic cough, in addition to the routine airway evaluation, BAL and LLM detection should be performed. LLM can be used to diagnose aspiration in reflux-related chronic cough. Future studies are needed to evaluate the response to anti-reflux medications or surgery in patients with LLM positivity. PMID:27605525

Patterns of reflux in gastroesophageal reflux disease in pediatric population of New South Wales.

PubMed

Narayanan, Sarath Kumar; Cohen, Ralph Clinton; Karpelowsky, Jonathan Saul

2017-02-01

This study is to determine the association of ambulatory pH monitoring (24hr pH) with symptoms of gastroesophageal reflux and its other investigations. The clinical and epidemiological profiles of subjects referred for reflux disorders are also studied. Symptoms or group of symptoms, profiles and prior investigations of 1259 consecutive pediatric subjects (with 1332 24hr pH studies performed) referred for evaluation of reflux disorders between 1988 and 2012 were retrospectively studied. Chi-square or fisher exact test was used for hypothesis testing, student t-test for the comparison of means and the Wilcoxon rank-sum test for comparing medians of continuous variables. Gastroesophageal reflux disease (GERD), defined as reflux causing major symptoms and complications, was diagnosed in 57.5% subjects of the total sample. Forty-three percent were girls and 56.7% were boys. The most common age group was between 4 months and 2 years (51.2%). Vomiting (64.4%) and irritability (74%) were the most common symptoms with the neurological conditions (23.2%) being the most frequent underlying condition. The parameters used in 24hr pH were significantly higher in those diagnosed with GERD (P < 0.0001). The prevalence of GERD was found to be significantly higher when both gastrointestinal and respiratory symptoms were present (P = 0.008) at 66.4% than when compared with gastrointestinal (56.5%) and respiratory (52.2%) symptoms in isolation. Symptoms alone were not reliable in diagnosing GERD. Only 57.5% had GERD among patients referred for reflux disorders. 24hr pH is reliable and should be considered routine in reflux disorders, as it identifies patients with pathologic reflux and avoids a needless surgery. © 2016 International Society for Diseases of the Esophagus.

Comparison of clinical characteristics of chronic cough due to non-acid and acid gastroesophageal reflux.

PubMed

Xu, Xianghuai; Yang, Zhongmin; Chen, Qiang; Yu, Li; Liang, Siwei; Lü, Hanjing; Qiu, Zhongmin

2015-04-01

Little is known about non-acid gastroesophageal reflux-induced chronic cough (GERC). The purpose of the study is to explore the clinical characteristics of non-acid GERC. Clinical symptoms, cough symptom score, capsaicin cough sensitivity, gastroesophageal reflux diagnostic questionnaire (GerdQ) score, findings of multichannel intraluminal impedance-pH monitoring (MII-pH) and response to pharmacological anti-reflux therapy were retrospectively reviewed in 38 patients with non-acid GERC and compared with those of 49 patients with acid GERC. Non-acid GERC had the similar cough character, cough symptom score, and capsaicin cough sensitivity to acid GERC. However, non-acid GERC had less frequent regurgitation (15.8% vs 57.1%, χ(2)  = 13.346, P = 0.000) and heartburn (7.9% vs 32.7%, χ(2)  = 7.686, P  = 0.006), and lower GerdQ score (7.4 ± 1.4 vs 10.6 ± 2.1, t = -6.700, P = 0.003) than acid GERC. Moreover, MII-pH revealed more weakly acidic reflux episodes, gas reflux episodes and a higher symptom association probability (SAP) for non-acid reflux but lower DeMeester score, acidic reflux episodes and SAP for acid reflux in non-acid GERC than in acid GERC. Non-acid GERC usually responded to the standard anti-reflux therapy but with delayed cough resolution or attenuation when compared with acid GERC. Fewer patients with non-acid GERC needed an augmented acid suppressive therapy or treatment with baclofen. There are some differences in the clinical manifestations between non-acid and acid GERC, but MII-pH is essential to diagnose non-acid GERC. © 2014 John Wiley & Sons Ltd.

Acid suppressants for managing gastro-oesophageal reflux and gastro-oesophageal reflux disease in infants: a national survey.

PubMed

Bell, Jane C; Schneuer, Francisco J; Harrison, Christopher; Trevena, Lyndal; Hiscock, Harriet; Elshaug, Adam G; Nassar, Natasha

2018-02-22

To evaluate the diagnosis and management of reflux and gastro-oesophageal reflux disease (GORD) in infants aged <1 year presenting to general practitioners (GPs). A nationally representative, prospective, cross-sectional survey of GP activity in Australia, 2006-2016 (Bettering the Evaluation And Care of Health Study). Annually, a random sample of around 1000 GPs recorded details for 100 consecutive visits with consenting, unidentified patients. Diagnoses of reflux and GORD and their management including prescribing of acid-suppressant medicines (proton pump inhibitors (PPIs) and histamine receptor antagonists (H2RAs)) and counselling, advice or education. Of all infants' visits, 512 (2.7%) included a diagnosis of reflux (n=413, 2.2%) or GORD (n=99, 0.5%). From 2006 to 2016, diagnostic rates decreased for reflux and increased for GORD. Prescribing of acid suppressants occurred in 43.6% visits for reflux and 48.5% visits for GORD, similar to rates of counselling, advice or education (reflux: 38.5%, GORD: 43.4% of visits). Prescribing of PPIs increased (statistically significant only for visits for reflux), while prescribing of H2RAs decreased. Overprescribing of acid suppressants to infants may be occurring. In infants, acid-suppressant medicines are no better than placebo and may have significant negative side effects; however, guidelines are inconsistent. Clear, concise and consistent guidance is needed. GPs and parents need to understand what is normal and limitations of medical therapy. We need a greater understanding of the influences on GP prescribing practices, of parents' knowledge and attitudes and of the pressures on parents of infants with these conditions. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Airway Hypersensitivity, Reflux, and Phonation Contribute to Chronic Cough

PubMed Central

Francis, David O.; Slaughter, James C.; Ates, Fehmi; Higginbotham, Tina; Stevens, Kristin L.; Garrett, C. Gaelyn; Vaezi, Michael F.

2015-01-01

Background & Aims Although chronic cough is a common, its etiology is often elusive, making patient management a challenge. Gastroesophageal reflux and airway hypersensitivity can cause chronic cough. We explored the relationship between reflux, phonation, and cough in patients with idiopathic chronic cough. Methods We performed a blinded, cross-sectional study of non-smoking patients with chronic cough (duration > 8 weeks) refractory to reflux treatment referred to the Digestive Disease Center at Vanderbilt University. All underwent 24-hour acoustic recording concurrently and temporally synchronized with ambulatory pH-impedance monitoring. Cough, phonation, and pH-impedance events were recorded. We evaluated the temporal relationship between cough and phonation or reflux events using Poisson and logistic regression. Results Seventeen patients met the inclusion criteria (88% female; 100% Caucasian; median age, 63 years and interquartile age range, 52–66 years; mean body mass index, 30.6 and interquartile range 27.9–34.0); there were 2048 analyzable coughing events. The probability of subsequent coughing increased with higher burdens of preceding cough, reflux, or phonation. Within the first 15 min after a cough event, the cough event itself was the main trigger of subsequent cough events. After this period, de novo coughing occurred with increases of 1.46-fold in association with reflux alone (95% confidence interval, 1.17–1.82; P<.001) and 1.71-fold in association with the combination of phonation and reflux events. Conclusion Antecedent phonation and reflux increased the rate of cough events in patients with idiopathic chronic cough. Reflux events were more strongly associated with increased rate of coughing. Our findings support the concept that airway hypersensitivity is a cause of chronic cough, and that the vocal folds may be an effector in chronic cough. ClinicalTrials.gov number, NCT01263626. PMID:26492842

The Clinical Value of Deflation Cough in Chronic Coughers With Reflux Symptoms.

PubMed

Lavorini, Federico; Chellini, Elisa; Bigazzi, Francesca; Surrenti, Elisabetta; Fontana, Giovanni A

2016-06-01

Patients with deflation cough (DC), the cough-like expulsive effort(s) evoked by maximal lung emptying during a slow vital capacity maneuver, also present symptoms of gastroesophageal reflux. DC can be inhibited by prior intake of antacids. We wished to assess DC prevalence and association between DC and chemical characteristics of refluxate in patients with gastroesophageal reflux symptoms. A total of 157 consecutive outpatients underwent DC assessment and 24-h multichannel intraluminal impedance pH (MII-pH) monitoring; 93/157 also had chronic cough. Patients performed two to four slow vital capacity maneuvers and DC was detected aurally. Subsequently, they underwent 24-h MII-pH monitoring, the outcomes of which were defined as abnormal when acid or non-acid reflux events were > 73. DC occurred in 46/157 patients, 18 of whom had abnormal MII-pH outcomes; 28 of the remaining 111 patients without DC also had abnormal MII-pH findings. Thus, in the patients as a group, there was no association between DC and MII-pH outcomes. DC occurred in 40/93 of the chronic coughers; 15 of whom had acid reflux. All but 2 of the 53 patients without DC had normal MII-pH outcomes (P < .001), and the negative predictive value of DC for excluding acid reflux was 96.2%. At follow-up, 65% of coughers showed significant improvement after treatment. The overall prevalence of DC was 29%, increasing to 43% in chronic coughers in whom the absence of DC virtually excludes acid reflux. Therefore, DC assessment may represent a useful screening test for excluding acid reflux in chronic coughers with reflux symptoms. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

The Role of Microaspiration in the Pathogenesis of Gastroesophageal Reflux-related Chronic Cough.

PubMed

Özdemir, Pelin; Erdinç, Münevver; Vardar, Rukiye; Veral, Ali; Akyıldız, Serdar; Özdemir, Özer; Bor, Serhat

2017-01-30

Gastroesophageal reflux disease (GERD) is one of the main causes of chronic cough. We evaluated the role of microaspiration in the pathogenesis of reflux-related cough by determining the amount of lipid-laden macrophages (LLMs) in bronchoalveolar lavage (BAL) specimens. A total of 161 cases of chronic cough were evaluated, and 36 patients (average age 48.2 years) were recruited for this single center prospective study. Patients with a history of smoking, angiotensin converting enzyme inhibitor usage, any abnormality on pulmonary function tests, abnormal chest X-rays, occupational or environmental exposures, or upper airway cough syndrome were excluded. GERD was evaluated by 24-hour esophageal impedance-pH monitoring. BAL specimens for LLM determination were obtained from 34 patients by flexible bronchoscopy. Patients with pathological intra-esophageal reflux according to multichannel intraluminal impedance and pH monitoring had higher LLM positivity in BAL specimens than patients without pathological reflux (8/14 in reflux positive group vs 1/22 in reflux negative group; P = 0.004). The BAL cell distribution was not different between the 2 groups ( P = 0.574 for macrophages, P = 0.348 for lymphocytes, P = 0.873 for neutrophils and P = 0.450 for eosinophils). Our results confirm the role of the microaspiration of refluxate in the pathogenetic mechanism of chronic cough. While bronchoscopy is indicated in patients with chronic cough, in addition to the routine airway evaluation, BAL and LLM detection should be performed. LLM can be used to diagnose aspiration in reflux-related chronic cough. Future studies are needed to evaluate the response to anti-reflux medications or surgery in patients with LLM positivity.

Non-alcoholic fatty liver disease and the development of reflux esophagitis: A cohort study.

PubMed

Min, Yang Won; Kim, Youngha; Gwak, Geum-Youn; Gu, Seonhye; Kang, Danbee; Cho, Soo Jin; Guallar, Eliseo; Cho, Juhee; Sinn, Dong Hyun

2018-05-01

Non-alcoholic fatty liver disease (NAFLD), a hepatic manifestation of the metabolic syndrome, is associated with gastroesophageal reflux disease in cross-sectional studies, but a prospective association has not been evaluated. The current study aimed to determine whether NAFLD increases the risk of incident reflux esophagitis in a large cohort study. We conducted a cohort study of 34 063 men and women without reflux esophagitis or other upper gastrointestinal disease at baseline who underwent health checkup examinations between January 2003 and December 2013. Fatty liver was diagnosed by ultrasound based on standard criteria. Reflux esophagitis was defined by the presence of at least grade A mucosal break on esophagogastroduodenoscopy. The prevalence of NAFLD at baseline was 33.2%. During 153 520.2 person-years of follow-up, the cumulative incidences of reflux esophagitis for participants without and with NAFLD were 9.6% and 13.8%, respectively (P < 0.001). The age-adjusted and sex-adjusted hazard ratio for the risk of reflux esophagitis development in participants with NAFLD compared with those without NAFLD was 1.15 (95% confidence interval 1.07-1.23; P < 0.001). However, this association disappeared after adjusting for body mass index and other metabolic factors (hazard ratio 1.01, 95% confidence interval 0.94-1.09; P = 0.79). Similarly, in multivariable-adjusted models, there was no significant association between NAFLD severity and the risk of developing reflux esophagitis. Non-alcoholic fatty liver disease is not independently associated with the risk of the development of reflux esophagitis, but rather, reflux esophagitis is primarily the consequence of increased body mass index commonly associated with NAFLD. © 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Bile duct epithelial tight junctions and barrier function

PubMed Central

Rao, R.K.; Samak, G.

2013-01-01

Bile ducts play a crucial role in the formation and secretion of bile as well as excretion of circulating xenobiotic substances. In addition to its secretory and excretory functions, bile duct epithelium plays an important role in the formation of a barrier to the diffusion of toxic substances from bile into the hepatic interstitial tissue. Disruption of barrier function and toxic injury to liver cells appear to be involved in the pathogenesis of a variety of liver diseases such as primary sclerosing cholangitis, primary biliary cirrhosis and cholangiocarcinoma. Although the investigations into understanding the structure and regulation of tight junctions in gut, renal and endothelial tissues have expanded rapidly, very little is known about the structure and regulation of tight junctions in the bile duct epithelium. In this article we summarize the current understanding of physiology and pathophysiology of bile duct epithelium, the structure and regulation of tight junctions in canaliculi and bile duct epithelia and different mechanisms involved in the regulation of disruption and protection of bile duct epithelial tight junctions. This article will make a case for the need of future investigations toward our understanding of molecular organization and regulation of canalicular and bile duct epithelial tight junctions. PMID:24665411

Esophageal pH monitoring

MedlinePlus

... into the stomach. It is a test for gastroesophageal reflux disease ( GERD ). In infants, this test is also ... to: Barrett esophagus Difficulty swallowing (dysphagia) Esophageal scarring Gastroesophageal reflux disease (GERD) Heartburn Reflux esophagitis You may need ...

Effects of Obstructive Sleep Apnea and Gastroesophageal Reflux Disease on Asthma Control in Obesity

PubMed Central

Dixon, Anne E.; Clerisme-Beaty, Emmanuelle M.; Sugar, Elizabeth A.; Cohen, Rubin I.; Lang, Jason E.; Brown, Ellen D.; Richter, Joel E.; Irvin, Charles G.; Mastronarde, John G.

2011-01-01

Background Obesity is a risk factor for asthma. Obese asthmatics often have poor asthma control and respond poorly to therapy. It has been suggested that co-morbidities associated with obesity, such as reflux and obstructive sleep apnea, could be important factors contributing to poor asthma control in obese patients. Objectives The purpose of this study was to determine if (i) reflux and/or (ii) symptoms of sleep apnea contribute to poor asthma control in obesity. Methods We studied asthmatic subjects participating in a trial of reflux treatment. Participants underwent baseline evaluation of asthma symptoms and lung function. 304 participants underwent esophageal pH probe testing. 246 participants were evaluated for obstructive sleep apnea symptoms. Results Of 402 participants in this trial, 51% were obese. Role of reflux in asthma control Those with higher body mass index reported a higher prevalence of reflux symptoms, but the prevalence of pH probe acid reflux was similar in all groups. Reflux was not associated with measures of asthma control in obese patients. Role of obstructive sleep apnea in asthma control Symptoms and self-report of obstructive sleep apnea were more common with increasing body mass index and associated with worse asthma control as measured by the Juniper Asthma Control Questionnaire and Asthma Symptom Utility Index. Conclusions Our data suggest that obstructive sleep apnea, but not gastroesophageal reflux disease may contribute significantly to poor asthma control in obese patients. PMID:21819338

Classification of esophageal motor findings in gastro-esophageal reflux disease: Conclusions from an international consensus group.

PubMed

Gyawali, C P; Roman, S; Bredenoord, A J; Fox, M; Keller, J; Pandolfino, J E; Sifrim, D; Tatum, R; Yadlapati, R; Savarino, E

2017-12-01

High-resolution manometry (HRM) has resulted in new revelations regarding the pathophysiology of gastro-esophageal reflux disease (GERD). The impact of new HRM motor paradigms on reflux burden needs further definition, leading to a modern approach to motor testing in GERD. Focused literature searches were conducted, evaluating pathophysiology of GERD with emphasis on HRM. The results were discussed with an international group of experts to develop a consensus on the role of HRM in GERD. A proposed classification system for esophageal motor abnormalities associated with GERD was generated. Physiologic gastro-esophageal reflux is inherent in all humans, resulting from transient lower esophageal sphincter (LES) relaxations that allow venting of gastric air in the form of a belch. In pathological gastro-esophageal reflux, transient LES relaxations are accompanied by reflux of gastric contents. Structural disruption of the esophagogastric junction (EGJ) barrier, and incomplete clearance of the refluxate can contribute to abnormally high esophageal reflux burden that defines GERD. Esophageal HRM localizes the LES for pH and pH-impedance probe placement, and assesses esophageal body peristaltic performance prior to invasive antireflux therapies and antireflux surgery. Furthermore, HRM can assess EGJ and esophageal body mechanisms contributing to reflux, and exclude conditions that mimic GERD. Structural and motor EGJ and esophageal processes contribute to the pathophysiology of GERD. A classification scheme is proposed incorporating EGJ and esophageal motor findings, and contraction reserve on provocative tests during HRM. © 2017 John Wiley & Sons Ltd.

Gastroesophageal Reflux Disease in Children with Interstitial Lung Disease.

PubMed

Dziekiewicz, M A; Karolewska-Bochenek, K; Dembiński, Ł; Gawronska, A; Krenke, K; Lange, J; Banasiuk, M; Kuchar, E; Kulus, M; Albrecht, P; Banaszkiewicz, A

2016-01-01

Gastroesophageal reflux disease is common in adult patients with interstitial lung disease. However, no data currently exist regarding the prevalence and characteristics of the disease in pediatric patients with interstitial lung disease. The aim of the present study was to prospectively assess the incidence of gastroesophageal reflux disease and characterize its features in children with interstitial lung disease. Gastroesophageal reflux disease was established based on 24 h pH-impedance monitoring (MII-pH). Gastroesophageal reflux episodes (GERs) were classified according to widely recognized criteria as acid, weakly acid, weakly alkaline, or proximal. Eighteen consecutive patients (15 boys, aged 0.2-11.6 years) were enrolled in the study. Gastroesophageal reflux disease was diagnosed in a half (9/18) of children. A thousand GERs were detected by MII-pH (median 53.5; IQR 39.0-75.5). Of these, 585 (58.5 %) episodes were acidic, 407 (40.7 %) were weakly acidic, and eight (0.8 %) were weakly alkaline. There were 637 (63.7 %) proximal GERs. The patients in whom gastroesophageal reflux disease was diagnosed had a significantly higher number of proximal and total GERs. We conclude that the prevalence of gastroesophageal reflux disease in children with interstitial lung disease is high; thus, the disease should be considered regardless of presenting clinical symptoms. A high frequency of non-acid and proximal GERs makes the MII-pH method a preferable choice for the detection of reflux episodes in this patient population.

Mosapride for gastroesophageal reflux disease in neurologically impaired patients.

PubMed

Komura, Makoto; Kanamori, Yutaka; Tanaka, Yujiro; Kodaka, Tetsuro; Sugiyama, Masahiko; Terawaki, Kan; Suzuki, Kan; Iwanaka, Tadashi

2017-03-01

The prokinetic agent cisapride is effective for the treatment of gastroesophageal reflux disease (GERD) in infants and children, but is no longer used for this purpose because of safety concerns. Therefore, other pharmacological agents need to be investigated for efficacy in GERD treatment. In this study, we examined the effectiveness and safety of mosapride for the treatment of neurologically impaired children and adolescents with GERD. Mosapride (0.3 mg/kg/day) was administered to 11 neurologically impaired patients with GERD (five male; median age, 12.3 years). Esophageal acid exposure was measured using esophageal pH monitoring before and at >5 days after the start of mosapride treatment. The pressure and length of the lower esophageal sphincter were compared before and after mosapride treatment. In the 11 patients, median reflux index (percentage of the total monitoring period during which recorded pH was <4.0) was 17.5% (range, 4.4-59%) before and 8.2% (range, 2.8-20.7%) after mosapride treatment (P = 0.02). Median esophageal clearance was 1.0 min/reflux (range, 0.5-2.1 min/reflux) before and 0.7 min/reflux (range, 0.4-1.2 min/reflux) after treatment with mosapride (P = 0.02). The median number of reflux episodes before (219) and after (122) drug treatment did not differ significantly. The decreased reflux index in neurologically impaired patients with GERD is due to mosapride, therefore mosapride may be a candidate for GERD treatment. © 2016 Japan Pediatric Society.

Sleep disorders and the prevalence of asymptomatic nocturnal acid and non-acid reflux.

PubMed

Herdman, Christine; Marzio, Dina Halegoua-De; Shah, Paurush; Denuna-Rivera, Susie; Doghramji, Karl; Cohen, Sidney; Dimarino, Anthony J

2013-01-01

Nocturnal acid reflux is associated with symptomatic and asymptomatic sleep arousals, leading to fragmented sleep. The frequency and influence of acid reflux in patients with various forms of insomnia has not been reported. The aim of this study was to quantify nocturnal acid and nonacid reflux in patients with primary sleep disorders as previously diagnosed by polysomnography. THIRTY ONE SUBJECTS WERE STUDIED: (A) 9 subjects with a polysomnographically diagnosed sleep disorder (1 with restless legs syndrome, 4 with narcolepsy, 4 with periodic limb movement disorder); (B) 12 subjects with primary insomnia (PI) and unrevealing polysomnography; and (C) 10 controls without disturbed sleep. All subjects underwent a physical examination and 24 h transnasal pH and impedance monitoring to detect acid and non-acid reflux. The 21 subjects with fragmented sleep due to a primary sleep disorder had significantly more recumbent acid exposure (>1.2% of time) as compared with control subjects (33% versus 0%). When fragmented sleep subjects were divided into two groups, 17% of PI subjects and 55% of subjects with a diagnosed sleep disorder had significant recumbent acid exposure (P=0.009). Likewise, the median recumbent nonacid events were increased in the sleep disordered group (P=0.011). This study indicates that patients with primary sleep disorders have prominent nocturnal acid reflux without symptoms of daytime acid reflux. Acid reflux is most prominent in patients with polysomnographic findings of disturbed sleep as compared to patients with PI; while non acid reflux is increased minimally in these patients.

Combined multichannel intraluminal impedance and pH monitoring is helpful in managing children with suspected gastro-oesophageal reflux disease.

PubMed

Rossi, Paolo; Isoldi, Sara; Mallardo, Saverio; Papoff, Paola; Rossetti, Danilo; Dilillo, Anna; Oliva, Salvatore

2018-04-05

Gastro-oesophageal reflux is very common in the paediatric age group. There is no single and reliable test to distinguish between physiologic and pathological gastro-oesophageal reflux, and this lack of clear distinction between disease and normal can have a negative impact on the management of children. To evaluate the usefulness of 24-h oesophageal pH-impedance study in infants and children with suspected gastro-oesophageal reflux disease. Patients were classified by age groups (A-C) and reflux-related symptoms (typical and atypical). All underwent pH-impedance study. If the latter suggested an abnormal reflux, patients received therapy in accordance with NASPGHAN/ESPGHAN recommendations, while those with normal study had an additional diagnostic work-up. The efficacy of therapy was evaluated with a specific standardized questionnaire for different ages. The study was abnormal in 203/428 patients (47%) while normal in 225/428 (53%). Of those with abnormal study, 109 exhibited typical symptoms (54%), and 94 atypical (46%). The great majority of the patients with abnormal study were responsive to medical anti-reflux therapy. We confirm the utility of prolonged oesophageal pH-impedance study in detecting gastro-oesophageal reflux disease in children and in guiding therapy. Performing oesophageal pH-impedance monitoring in children with suspected gastro-oesophageal reflux disease is helpful to establish the diagnosis and avoid unnecessary therapy. Copyright © 2018 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

In vitro digestion with bile acids enhances the bioaccessibility of kale polyphenols.

PubMed

Yang, Isabelle; Jayaprakasha, Guddarangavvanahally K; Patil, Bhimanagouda

2018-02-21

Kale (Brassica oleracea) is a leafy green vegetable belonging to the Brassicaceae family, and kale leaves have large amounts of dietary fiber and polyphenolics. Dietary fiber can bind bile acids, thus potentially decreasing cholesterol levels; however, whether the polyphenols from kale contribute to in vitro bile acid binding capacity remains unclear. In the present study, kale was extracted with hexane, acetone, and MeOH : water and the dried extracts, as well as the fiber-rich residue, were tested for their bile acid binding capacity. The fiber-rich residue bound total bile acids in amounts equivalent to that bound by raw kale. The lyophilized acetone extract bound significantly more glycochenodeoxycholate and glycodeoxycholate and less of other bile acids. To test whether bile acid binding enhanced the bioaccessibility of polyphenolic compounds from kale, we used ultra-performance liquid chromatography coupled with electrospray ionization/quadrupole-time-of-flight mass spectrometry to identify chemical constituents and measure their bioaccessibility in an in vitro digestion reaction. This identified 36 phenolic compounds in kale, including 18 kaempferol derivatives, 13 quercetin derivatives, 4 sinapoyl derivatives, and one caffeoylquinic acid. The bioaccessibility of these phenolics was significantly higher (69.4%) in digestions with bile acids. Moreover, bile acids enhanced the bioaccessibility of quercetin by 25 times: only 2.7% of quercetin derivatives were bioaccessible in the digestion without bile acids, but with bile acids, their accessibility increased to 69.5%. Bile acids increased the bioaccessibility of kaempferol from 37.7% to 69.2%. The extractability and biostability of total phenolics in the digested residue increased 1.8 fold in the digestions with bile acids. These results demonstrated the potential use of kale to improve human health.

A Surgical Model in Male Obese Rats Uncovers Protective Effects of Bile Acids Post-Bariatric Surgery

PubMed Central

Setchell, Kenneth DR; Kirby, Michelle; Myronovych, Andriy; Ryan, Karen K.; Ibrahim, Samar H.; Berger, Jose; Smith, Kathi; Toure, Mouhamadoul; Woods, Stephen C.; Seeley, Randy J.

2013-01-01

Bariatric surgery elevates serum bile acids. Conjugated bile acid administration, such as tauroursodeoxycholic acid (TUDCA), improves insulin sensitivity, whereas short-circuiting bile acid circulation through ileal interposition surgery in rats raises TUDCA levels. We hypothesized that bariatric surgery outcomes could be recapitulated by short circuiting the normal enterohepatic bile circulation. We established a model wherein male obese rats underwent either bile diversion (BD) or Sham (SH) surgery. The BD group had a catheter inserted into the common bile duct and its distal end anchored into the middistal jejunum for 4–5 weeks. Glucose tolerance, insulin and glucagon-like peptide-1 (GLP-1) response, hepatic steatosis, and endoplasmic reticulum (ER) stress were measured. Rats post-BD lost significantly more weight than the SH rats. BD rats gained less fat mass after surgery. BD rats had improved glucose tolerance, increased higher postprandial glucagon-like peptide-1 response and serum bile acids but less liver steatosis. Serum bile acid levels including TUDCA concentrations were higher in BD compared to SH pair-fed rats. Fecal bile acid levels were not different. Liver ER stress (C/EBP homologous protein mRNA and pJNK protein) was decreased in BD rats. Bile acid gavage (TUDCA/ursodeoxycholic acid [UDCA]) in diet-induced obese rats, elevated serum TUDCA and concomitantly reduced hepatic steatosis and ER stress (C/EBP homologous protein mRNA). These data demonstrate the ability of alterations in bile acids to recapitulate important metabolic improvements seen after bariatric surgery. Further, our work establishes a model for focused study of bile acids in the context of bariatric surgery that may lead to the identification of therapeutics for metabolic disease. PMID:23592746

Role of bile acids and bile acid binding agents in patients with collagenous colitis

PubMed Central

Ung, K; Gillberg, R; Kilander, A; Abrahamsson, H

2000-01-01

BACKGROUND—In a retrospective study bile acid malabsorption was observed in patients with collagenous colitis.
AIMS—To study the occurrence of bile acid malabsorption and the effect of bile acid binders prospectively in patients with chronic diarrhoea and collagenous colitis.
METHODS—Over 36 months all patients referred because of chronic diarrhoea completed a diagnostic programme, including gastroscopy with duodenal biopsy, colonoscopy with biopsies, and the 75Se-homocholic acid taurine (75SeHCAT) test for bile acid malabsorption. Treatment with a bile acid binder (cholestyramine in 24, colestipol in three) was given, irrespective of the results of the 75SeHCAT test.
RESULTS—Collagenous colitis was found in 28 patients (six men, 22 women), 27 of whom had persistent symptoms and completed the programme. Four patients had had a previous cholecystectomy or a distal gastric resection. The 75SeHCAT test was abnormal in 12/27 (44%) of the collagenous colitis patients with 75SeHCAT values 0.5-9.7%, and normal in 15 patients (56%). Bile acid binding treatment was followed by a rapid, marked, or complete improvement in 21/27 (78%) of the collagenous colitis patients. Rapid improvement occurred in 11/12 (92%) of the patients with bile acid malabsorption compared with 10/15 (67%) of the patients with normal 75SeHCAT tests.
CONCLUSION—Bile acid malabsorption is common in patients with collagenous colitis and is probably an important pathophysiological factor. Because of a high response rate without serious side effects, bile acid binding treatment should be considered for collagenous colitis, particularly patients with bile acid malabsorption.


Keywords: bile acid malabsorption; collagenous colitis; diarrhoea; cholestyramine; colestipol PMID:10644309

A Stated Preference Investigation into the Chinese Demand for Farmed vs. Wild Bear Bile

PubMed Central

Dutton, Adam J.; Hepburn, Cameron; Macdonald, David W.

2011-01-01

Farming of animals and plants has recently been considered not merely as a more efficient and plentiful supply of their products but also as a means of protecting wild populations from that trade. Amongst these nascent farming products might be listed bear bile. Bear bile has been exploited by traditional Chinese medicinalists for millennia. Since the 1980s consumers have had the options of: illegal wild gall bladders, bile extracted from caged live bears or the acid synthesised chemically. Despite these alternatives bears continue to be harvested from the wild. In this paper we use stated preference techniques using a random sample of the Chinese population to estimate demand functions for wild bear bile with and without competition from farmed bear bile. We find a willingness to pay considerably more for wild bear bile than farmed. Wild bear bile has low own price elasticity and cross price elasticity with farmed bear bile. The ability of farmed bear bile to reduce demand for wild bear bile is at best limited and, at prevailing prices, may be close to zero or have the opposite effect. The demand functions estimated suggest that the own price elasticity of wild bear bile is lower when competing with farmed bear bile than when it is the only option available. This means that the incumbent product may actually sell more items at a higher price when competing than when alone in the market. This finding may be of broader interest to behavioural economists as we argue that one explanation may be that as product choice increases price has less impact on decision making. For the wildlife farming debate this indicates that at some prices the introduction of farmed competition might increase the demand for the wild product. PMID:21799733

Growth characteristics of Lactobacillus brevis KB290 in the presence of bile.

PubMed

Kimoto-Nira, Hiromi; Suzuki, Shigenori; Suganuma, Hiroyuki; Moriya, Naoko; Suzuki, Chise

2015-10-01

Live Lactobacillus brevis KB290 have several probiotic activities, including immune stimulation and modulation of intestinal microbial balance. We investigated the adaptation of L. brevis KB290 to bile as a mechanism of intestinal survival. Strain KB290 was grown for 5 days at 37 °C in tryptone-yeast extract-glucose (TYG) broth supplemented with 0.5% sodium acetate (TYGA) containing 0.15%, 0.3%, or 0.5% bile. Growth was determined by absorbance at 620 nm or by dry weight. Growth was enhanced as the broth's bile concentration increased. Bile-enhanced growth was not observed in TYG broth or with xylose or fructose as the carbon source, although strain KB290 could assimilate these sugars. Compared with cells grown without bile, cells grown with bile had twice the cell yield (dry weight) and higher hydrophobicity, which may improve epithelial adhesion. Metabolite analysis revealed that bile induced more lactate production by glycolysis, thus enhancing growth efficiency. Scanning electron microscopy revealed that cells cultured without bile for 5 days in TYGA broth had a shortened rod shape and showed lysis and aggregation, unlike cells cultured for 1 day; cells grown with bile for 5 days had an intact rod shape and rarely appeared damaged. Cellular material leakage through autolysis was lower in the presence of bile than in its absence. Thus lysis of strain KB290 cells cultured for extended periods was suppressed in the presence of bile. This study provides new role of bile and sodium acetate for retaining an intact cell shape and enhancing cell yield, which are beneficial for intestinal survival. Copyright © 2015 Elsevier Ltd. All rights reserved.

Percutaneous management of postoperative bile leaks with an ethylene vinyl alcohol copolymer (Onyx).

PubMed

Uller, W; Müller-Wille, R; Loss, M; Hammer, S; Schleder, S; Goessmann, H; Wiggermann, P; Stroszczynski, C; Wohlgemuth, W A

2013-12-01

The management of postoperative bile leakage is challenging especially if the leak rises from the cut surface of the liver and endoscopic treatment fails. Percutaneous transhepatic treatment of bile leaks with biliary drainage is accepted but often requires long-term placement of the drains and is associated with treatment failures. This series evaluates selective embolization of bile ducts with an ethylene vinyl alcohol copolymer (Onyx) in patients with postoperative bile leaks as an alternative treatment option. Between January and September 2012, five consecutive patients with persistent postoperative bile leaks underwent percutaneous transhepatic Onyx application and were analyzed regarding procedural management, complications and success rates. The persistent bile leaks were situated at the cystic stump (after cholecystectomy, n = 2), at the cut surface of the liver (after extended liver resection, n = 2) and at the surface of the liver after surgical exploration and perihepatic abscess (n = 1). Bile drainage alone (endoscopic or percutaneous) failed in all patients and open redo-surgery was deemed potentially harmful. Bilomas were externally drained in all patients before Onyx application. For the closure of bile leaks, Onyx was injected through a microcatheter in a previously built coil nest to keep Onyx in place. All bile leaks were initially closed immediately. In the 2nd week after Onyx embolization, 2 patients showed recurrent small bile leaks without clinical symptoms. In the 4th week after Onyx application, all leaks were closed. No complications occurred. All leaking bile ducts were initially closed immediately after Onyx application. In the 2nd week after Onyx application, 2 patients showed small bile leaks without clinical symptoms. All leaks were closed in the 4th week after Onyx application. © Georg Thieme Verlag KG Stuttgart · New York.

Risk Factors for Bile Duct Injury After Percutaneous Thermal Ablation of Malignant Liver Tumors: A Retrospective Case-Control Study.

PubMed

Lin, Man-Xia; Ye, Jie-Yi; Tian, Wen-Shuo; Xu, Ming; Zhuang, Bo-Wen; Lu, Ming-De; Xie, Xiao-Yan; Kuang, Ming

2017-04-01

Bile duct injury after ablation of malignant liver tumors (MLTs) was not unusual and should be avoided. However, few studies have focused on evaluating the risk factors for intrahepatic bile duct injury. To evaluate the risk factors for intrahepatic bile duct injury after ablation of MLTs and to evaluate the minimum safe distance for ablating tumors abutting bile ducts. Sixty-five patients with intrahepatic bile duct injury after ablation of MLTs, and 65 controls were recruited. Risk factors for intrahepatic bile duct injury were analyzed. Tumor location was recorded as ≤5 mm (group A), 5-10 mm (group B), and >10 mm (group C) from the right/left main duct or segmental bile duct. Ascites history (P < 0.001), TACE treatment history (P = 0.025), intrahepatic bile duct dilatation before ablation (P < 0.001), and tumor location (P = 0.000) were identified as significant risk factors for intrahepatic bile duct injury. Significant differences in the risk of intrahepatic bile duct injury were found between groups B and C (P = 0.000), but not between groups A and B (P = 0.751). Ascites history (P = 0.002) and tumor location (P < 0.001) were independent predictors with the OR (95 % confidence interval) of 39.31(3.95-391.69) and 16.56 (5.87-46.71), respectively. Bile duct injury after ablation of MLTs was the result of local treatment-related factors combined with the patients' general condition. The minimum safe distance for ablation of tumor abutting a bile duct was 10 mm.

A stated preference investigation into the Chinese demand for farmed vs. wild bear bile.

PubMed

Dutton, Adam J; Hepburn, Cameron; Macdonald, David W

2011-01-01

Farming of animals and plants has recently been considered not merely as a more efficient and plentiful supply of their products but also as a means of protecting wild populations from that trade. Amongst these nascent farming products might be listed bear bile. Bear bile has been exploited by traditional Chinese medicinalists for millennia. Since the 1980s consumers have had the options of: illegal wild gall bladders, bile extracted from caged live bears or the acid synthesised chemically. Despite these alternatives bears continue to be harvested from the wild. In this paper we use stated preference techniques using a random sample of the Chinese population to estimate demand functions for wild bear bile with and without competition from farmed bear bile. We find a willingness to pay considerably more for wild bear bile than farmed. Wild bear bile has low own price elasticity and cross price elasticity with farmed bear bile. The ability of farmed bear bile to reduce demand for wild bear bile is at best limited and, at prevailing prices, may be close to zero or have the opposite effect. The demand functions estimated suggest that the own price elasticity of wild bear bile is lower when competing with farmed bear bile than when it is the only option available. This means that the incumbent product may actually sell more items at a higher price when competing than when alone in the market. This finding may be of broader interest to behavioural economists as we argue that one explanation may be that as product choice increases price has less impact on decision making. For the wildlife farming debate this indicates that at some prices the introduction of farmed competition might increase the demand for the wild product.

Bile duct stricture

MedlinePlus

... duct, the tube that moves bile from the liver to the small intestine. Bile is a substance that helps with digestion. ... causes of this condition include: Cancer of the bile duct, liver or pancreas Damage and scarring due to a ...

A causal relationship between cough and gastroesophageal reflux disease (GERD) has been established: a pro/con debate.

PubMed

Kahrilas, Peter J; Smith, Jaclyn A; Dicpinigaitis, Peter V

2014-02-01

Along with upper airway cough syndrome (formerly, postnasal drip syndrome) and eosinophilic airway inflammation (asthma, nonasthmatic eosinophilic bronchitis), gastroesophageal reflux disease (GERD) is generally considered among the most common etiologies of chronic cough. Indeed, cough management guidelines published by numerous respiratory societies worldwide recommend evaluation and treatment of GERD as an integral component of the diagnostic/therapeutic algorithm for the management of chronic cough. However, a significant number of patients with chronic cough presumed due to GERD do not report improvement despite aggressive acid-suppressive therapy. Some of these refractory cases may be due to the recently appreciated entity of nonacid or weakly acidic reflux. Further contributing to the controversy are recent studies that demonstrate that patients with chronic cough do not have excessive reflux events relative to healthy volunteers. Although a temporal relationship between cough and reflux events has been suggested by studies utilizing impedance-pH monitoring of reflux events and objective cough recording, consensus is lacking in terms of whether this temporal relationship proves a causal link between reflux and cough. The fourth American Cough Conference (New York, June 2013) provided an ideal forum for the debate of this issue between two internationally recognized experts in the field of reflux and chronic cough.

A Causal Relationship Between Cough and Gastroesophageal Reflux Disease (GERD) Has Been Established: a Pro/Con Debate

PubMed Central

Kahrilas, Peter J.; Smith, Jaclyn A.; Dicpinigaitis, Peter V.

2014-01-01

Along with upper airway cough syndrome (formerly, postnasal drip syndrome) and eosinophilic airway inflammation (asthma, non-asthmatic eosinophilic bronchitis), gastroesophageal reflux disease (GERD) is generally considered among the most common etiologies of chronic cough. Indeed, cough management guidelines published by numerous respiratory societies worldwide recommend evaluation and treatment of GERD as an integral component of the diagnostic/therapeutic algorithm for the management of chronic cough. However, a significant number of patients with chronic cough presumed due to GERD do not report improvement despite aggressive acid-suppressive therapy. Some of these refractory cases may be due to the recently appreciated entity of non-acid or weakly acidic reflux. Further contributing to the controversy are recent studies demonstrating that patients with chronic cough do not have excessive reflux events relative to healthy volunteers. Although a temporal relationship between cough and reflux events has been suggested by studies utilizing impedance-pH monitoring of reflux events and objective cough recording, consensus is lacking in terms of whether this temporal relationship proves a causal link between reflux and cough. The 4th American Cough Conference, held in New York in June, 2013, provided an ideal forum for the debate of this issue between two internationally recognized experts in the field of reflux and chronic cough. PMID:24221340

Incidence of Biliary Reflux Esophagitis After Laparoscopic Omega Loop Gastric Bypass in Morbidly Obese Patients.

PubMed

Salama, Tamer M Said; Hassan, Mohamed Ibrahim

2017-06-01

Omega loop gastric bypass is a successful bariatric surgery with numerous favorable circumstances as being basic, effective on weight reduction and treatment of obesity associated metabolic disorder, the short expectation to learn and adapt, and the simplicity of correction and inversion. However, there are arguments about the possibility of biliary reflux and/or the potential danger of gastroesophageal malignancy after the procedure. Fifty patients experiencing morbid obesity with body mass index >40 or >35 kg/m 2 with two related comorbidities, for example, diabetes type II, hypertension, or dyslipidemia, underwent omega loop gastric bypass with a follow-up period up to 18 months, investigating for any symptom of reflux infection by upper gastrointestinal tract endoscopy and pH metry. Reflux esophagitis (a gastroesophageal reflux disease) was detected in 3 patients (6%); 2 cases (4%) showed (Grade A) acidic reflux esophagitis at 6 and 12 months postoperatively. Just 1 case (2%) had experienced gastroesophageal biliary reflux esophagitis (Grade A) at 12 months. No metaplasia or dysplasia was detected in the endoscopic biopsies. Omega loop gastric bypass is a safe and effective bariatric procedure with low incidence of postoperative biliary reflux, metaplasia, or dysplasia at the esophagogastric junction, confirmed 18 months after the operation.

Effect of decaffeination of coffee or tea on gastro-oesophageal reflux.

PubMed

Wendl, B; Pfeiffer, A; Pehl, C; Schmidt, T; Kaess, H

1994-06-01

Coffee and tea are believed to cause gastro-oesophageal reflux; however, the effects of these beverages and of their major component, caffeine, have not been quantified. The aim of this study was to evaluate gastro-oesophageal reflux induced by coffee and tea before and after a decaffeination process, and to compare it with water and water-containing caffeine. Three-hour ambulatory pH-metry was performed on 16 healthy volunteers, who received 300 ml of (i) regular coffee, decaffeinated coffee or tap water (n = 16), (ii) normal tea, decaffeinated tea, tap water, or coffee adapted to normal tea in caffeine concentration (n = 6), and (iii) caffeine-free and caffeine-containing water (n = 8) together with a standardized breakfast. Regular coffee induced a significant (P < 0.05) gastro-oesophageal reflux compared with tap water and normal tea, which were not different from each other. Decaffeination of coffee significantly (P < 0.05) diminished gastro-oesophageal reflux, whereas decaffeination of tea or addition of caffeine to water had no effect. Coffee adapted to normal tea in caffeine concentration significantly (P < 0.05) increased gastro-oesophageal reflux. Coffee, in contrast to tea, increases gastro-oesophageal reflux, an effect that is less pronounced after decaffeination. Caffeine does not seem to be responsible for gastro-oesophageal reflux which must be attributed to other components of coffee.

Randomised controlled trial of effects of Helicobacter pylori infection and its eradication on heartburn and gastro-oesophageal reflux: Bristol helicobacter project

PubMed Central

Harvey, Richard F; Lane, J Athene; Murray, Liam J; Harvey, Ian M; Donovan, Jenny L; Nair, Prakash

2004-01-01

Objectives To investigate the effects of Helicobacter pylori infection and its eradication on heartburn and gastro-oesophageal reflux. Design Cross sectional study, followed by a randomised placebo controlled trial. Setting Seven general practices in Bristol, England. Participants 10 537 people, aged 20-59 years, with and without H pylori infection (determined by the 13C-urea breath test). Main outcome measures Prevalence of heartburn and gastro-oesophageal acid reflux at baseline and two years after treatment to eradicate H pylori infection. Results At baseline, H pylori infection was associated with increased prevalence of heartburn (odds ratio 1.14, 95% confidence interval 1.05 to 1.23) but not reflux (1.05, 0.97 to 1.14). In participants with H pylori infection, active treatment had no effect on the overall prevalence of heartburn (0.99, 0.88 to 1.12) or reflux (1.04, 0.91 to 1.19) and did not improve pre-existing symptoms of heartburn or reflux. Conclusions H pylori infection is associated with a slightly increased prevalence of heartburn but not reflux. Treatment to eradicate H pylori has no net benefit in patients with heartburn or gastro-oesophageal reflux. PMID:15126313

A comparative proteomic analysis of bile for biomarkers of cholangiocarcinoma.

PubMed

Laohaviroj, Marut; Potriquet, Jeremy; Jia, Xinying; Suttiprapa, Sutas; Chamgramol, Yaovalux; Pairojkul, Chawalit; Sithithaworn, Paiboon; Mulvenna, Jason; Sripa, Banchob

2017-06-01

Cholangiocarcinoma is a primary malignant tumor of the bile duct epithelium. Cholangiocarcinoma is usually detected at an advanced stage when successful treatment is no longer possible. As the tumor originates from the bile duct epithelium, bile is an ideal source of tumor biomarkers for cholangiocarcinoma. In this study, we used a quantitative proteomics approach to identify potential tumor-associated proteins in the bile fluid of six cholangiocarcinoma patients. Three different gross-appearance tumor types were used in the analysis: mass-forming type ( n = 2), periductal infiltrating type ( n = 2), and intraductal growth type ( n = 2). Two bile samples from non-cancerous patients were used as controls. Isobaric labeling, coupled with Tandem mass spectrometry, was used to quantify protein levels in the bile of cholangiocarcinoma and control patients. In all, 63 proteins were significantly increased in cholangiocarcinoma bile compared to normal bile. Alpha-1-antitrypsin was one of the overexpressed proteins that increased in cholangiocarcinoma bile samples. Immunohistochemical analysis revealed that alpha-1-antitrypsin was detected in 177 (50%) of 354 cholangiocarcinoma tissues from our Tissue Bank. Immunoblotting of 54 cholangiocarcinoma bile samples showed that alpha-1-antitrypsin was positive in 38 (70%) samples. Fecal enzyme-linked immunosorbent assay showed that alpha-1-antitrypsin level was able to distinguish cholangiocarcinoma patients from normal individuals. In conclusion, alpha-1-antitrypsin is a potential marker for early diagnosis of cholangiocarcinoma.

Identification and differentiation of bear bile used in medicinal products in Taiwan.

PubMed

Lin, D L; Chang, H C; Chang, C P; Chen, C Y

1997-09-01

One hundred eighty-three suspect bear bile used in medicinal products, collected in Taiwan as gall bladders or dried powder forms, were analyzed using FTIR, HPTLC, and HPLC techniques to identify whether they are indeed bear bile. Those confirmed were further examined to determine whether the observed analytical parameters can be reliably used for source inference, i.e., differentiating products among North American black bear, farmed Asiatic black bear, polar bear, etc. Our data suggested that North American and polar bears contain a higher concentration of TC (relative to TUDC and TCDC), whereas the relative concentration of TC in Asiatic bears (wild or farmed) is much lower. Thus, the relative concentration of TC can potentially be used for differentiating Asiatic bear bile from North American and polar bear products, but it cannot be used for the differentiation of wild and farmed bear bile as suggested in an earlier report by Espinoza et al. The origin of the 183 samples analyzed were found to be as follows: 118 (64%), bile salts, or gall bladders were of domestic pig; 56 (31%), bile products of Asiatic bear; 4 (2.2%), Asiatic bear mixed with pig bile salts; 3 (1.6%) goat gall bladders; 1 (0.55%) water buffalo bile salts; and 1 (0.55%), pig bile salts mixed with water buffalo bile salts.

Allelic Variation of Bile Salt Hydrolase Genes in Lactobacillus salivarius Does Not Determine Bile Resistance Levels▿ †

PubMed Central

Fang, Fang; Li, Yin; Bumann, Mario; Raftis, Emma J.; Casey, Pat G.; Cooney, Jakki C.; Walsh, Martin A.; O'Toole, Paul W.

2009-01-01

Commensal lactobacilli frequently produce bile salt hydrolase (Bsh) enzymes whose roles in intestinal survival are unclear. Twenty-six Lactobacillus salivarius strains from different sources all harbored a bsh1 allele on their respective megaplasmids. This allele was related to the plasmid-borne bsh1 gene of the probiotic strain UCC118. A second locus (bsh2) was found in the chromosomes of two strains that had higher bile resistance levels. Four Bsh1-encoding allele groups were identified, defined by truncations or deletions involving a conserved residue. In vitro analyses showed that this allelic variation was correlated with widely varying bile deconjugation phenotypes. Despite very low activity of the UCC118 Bsh1 enzyme, a mutant lacking this protein had significantly lower bile resistance, both in vitro and during intestinal transit in mice. However, the overall bile resistance phenotype of this and other strains was independent of the bsh1 allele type. Analysis of the L. salivarius transcriptome upon exposure to bile and cholate identified a multiplicity of stress response proteins and putative efflux proteins that appear to broadly compensate for, or mask, the effects of allelic variation of bsh genes. Bsh enzymes with different bile-degrading kinetics, though apparently not the primary determinants of bile resistance in L. salivarius, may have additional biological importance because of varying effects upon bile as a signaling molecule in the host. PMID:19592587

How to differentiate non-erosive reflux disease from functional heartburn.

PubMed

Ke, Mei Yun

2012-12-01

Heartburn is a common symptom in gastroesophageal reflux disease. Endoscopic examination can differentiate between reflux esophagitis and non-erosive reflux disease (NERD), but not between NERD and functional heartburn. With the development of new techniques, more NERD patients could be identified among those previously diagnosed with functional heartburn. Most patients with NERD, however, could be identified based on their clinical characteristics and response to proton pump inhibitors and/or integrated anti-gastroesophageal reflux therapy. © 2012 The Author. Journal of Digestive Diseases © 2012 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

Endoscopic retrograde cholangio pancreatography (ERCP) - series (image)

MedlinePlus

... small intestine, also called the duodenum. The common bile duct carries bile from the liver to the duodenum, and enters ... sometimes pass from the gallbladder into the common bile duct, and block the flow of bile into ...

Discovering Novel Bile Protection Systems in Bifidobacterium breve UCC2003 through Functional Genomics

PubMed Central

Ruiz, Lorena; Zomer, Aldert; O'Connell-Motherway, Mary; van Sinderen, Douwe

2012-01-01

Tolerance of gut commensals to bile salt exposure is an important feature for their survival in and colonization of the intestinal environment. A transcriptomic approach was employed to study the response of Bifidobacterium breve UCC2003 to bile, allowing the identification of a number of bile-induced genes with a range of predicted functions. The potential roles of a selection of these bile-inducible genes in bile protection were analyzed following heterologous expression in Lactococcus lactis. Genes encoding three transport systems belonging to the major facilitator superfamily (MFS), Bbr_0838, Bbr_0832, and Bbr_1756, and three ABC-type transporters, Bbr_0406-0407, Bbr_1804-1805, and Bbr_1826-1827, were thus investigated and shown to provide enhanced resistance and survival to bile exposure. This work significantly improves our understanding as to how bifidobacteria respond to and survive bile exposure. PMID:22156415

The relationship between helicobacter pylori infection and gastro-esophageal reflux disease.

PubMed

Mahdi, Batool M

2011-03-01

Gastro-esophageal reflux disease is a common condition, affecting 25%-40% of the population. Increasing attention has been paid to the relationship between Helicobacter pylori infection and reflux esophagitis. The aim of this study was to investigate the association between CagA+ H. pylori and endoscopically proven gastro-esophageal reflux disease. The study group included 60 hospital patients with gastro-esophageal reflux disease between 2007 and 2009 as compared with 30 healthy patients from a control group that was age and sex matched. Helicobacter pylori CagA+ was identified by an immunological test (Immunochromatography test) (ACON, USA). Helicobacter pyloriCagA+ was present in 42/60 (70%) of the patients with gastro-esophageal reflux disease and in 11/30 (36.6%) patients in the control group (p=0.002). The Odds ratio = 0.8004 with 95% Confidence Interval = from 0.3188 to 2.0094. The relative risk=1.35 that indicates an association between Helicobacter pylori and disease. The presence of Helicobacter pylori is significantly increased in patients with gastro-esophageal reflux disease as compared with the control group.

Ivacaftor and symptoms of extra-oesophageal reflux in patients with cystic fibrosis and G551D mutation.

PubMed

Zeybel, Gemma L; Pearson, Jeffrey P; Krishnan, Amaran; Bourke, Stephen J; Doe, Simon; Anderson, Alan; Faruqi, Shoaib; Morice, Alyn H; Jones, Rhys; McDonnell, Melissa; Zeybel, Mujdat; Dettmar, Peter W; Brodlie, Malcolm; Ward, Chris

2017-01-01

Extra-oesophageal reflux (EOR) may lead to microaspiration in patients with cystic fibrosis (CF), a probable cause of deteriorating lung function. Successful clinical trials of ivacaftor highlight opportunities to understand EOR in a real world study. Data from 12 patients with CF and the G551D mutation prescribed ivacaftor (150mg bd) was collected at baseline, 6, 26 and 52weeks. The changes in symptoms of EOR were assessed by questionnaire (reflux symptom index (RSI) and Hull airway reflux questionnaire (HARQ)). Six patients presented EOR at baseline (RSI >13; median 13; range 2-29) and 5 presented airway reflux (HARQ >13; median 12; range 3 to 33). Treatment with ivacaftor was associated with a significant reduction of EOR symptoms (P<0∙04 versus baseline) denoted by the reflux symptom index and Hull airway reflux questionnaire. Ivacaftor treatment was beneficial for patients with symptoms of EOR, thought to be a precursor to microaspiration. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

[Influence of chest physiotherapy on gastro-œsophageal reflux in children].

PubMed

Reychler, G; Jacques, L; Arnold, D; Scheers, I; Smets, F; Sokal, E; Stephenne, X

2015-05-01

Chest physiotherapy is regularly prescribed for children, particularly in cystic fibrosis. Gastro-oesophageal reflux is common in this disease and is associated with certain chest physiotherapy manoeuvres. To evaluate the influence of two chest physiotherapy techniques on gastro-oesophageal reflux in children. Twenty-nine children were investigated by routine pHmetry. During the examination, they performed two chest physiotherapy manoeuvres in a seated position for 10 minutes each with a 5 minutes rest between them. The two manoeuvres used were a slow expiration technique (ELPr) and positive expiratory pressure (PEP). It was a prospective study and the order of manoeuvres was randomised. The pH traces were analysed blindly when all the studies had been completed. In the sample, 21% of children had gastro-oesophageal reflux during the physiotherapy session. No relationship was found between reflux during physiotherapy and pathological reflux (P=0.411) nor the physiotherapy technique used (P=0.219). The use of these two chest physiotherapy techniques in children in a seated position can produce gastro-oesophageal reflux. Copyright © 2015 SPLF. Published by Elsevier Masson SAS. All rights reserved.

In vitro bile acid binding of mustard greens, kale, broccoli, cabbage and green bell pepper improves with sautéing compared with raw or other methods of preparation.

USDA-ARS?s Scientific Manuscript database

Bile acid binding capacity has been related to cholesterol-lowering potential of foods and food fractions. Lowered recirculating bile acids results in utilization of cholesterol to synthesize bile acid and reduced fat absorption. Secondary bile acids have been associated with increased risk of can...

Metabolism of Oxo-Bile Acids and Characterization of Recombinant 12α-Hydroxysteroid Dehydrogenases from Bile Acid 7α-Dehydroxylating Human Gut Bacteria.

PubMed

Doden, Heidi; Sallam, Lina A; Devendran, Saravanan; Ly, Lindsey; Doden, Greta; Daniel, Steven L; Alves, João M P; Ridlon, Jason M

2018-05-15

Bile acids are important cholesterol-derived nutrient signaling hormones, synthesized in the liver, that act as detergents to solubilize dietary lipids. Bile acid 7α-dehydroxylating gut bacteria generate the toxic bile acids deoxycholic acid and lithocholic acid from host bile acids. The ability of these bacteria to remove the 7-hydroxyl group is partially dependent on 7α-hydroxysteroid dehydrogenase (HSDH) activity, which reduces 7-oxo-bile acids generated by other gut bacteria. 3α-HSDH has an important enzymatic activity in the bile acid 7α-dehydroxylation pathway. 12α-HSDH activity has been reported for the low-activity bile acid 7α-dehydroxylating bacterium Clostridium leptum ; however, this activity has not been reported for high-activity bile acid 7α-dehydroxylating bacteria, such as Clostridium scindens , Clostridium hylemonae , and Clostridium hiranonis Here, we demonstrate that these strains express bile acid 12α-HSDH. The recombinant enzymes were characterized from each species and shown to preferentially reduce 12-oxolithocholic acid to deoxycholic acid, with low activity against 12-oxochenodeoxycholic acid and reduced activity when bile acids were conjugated to taurine or glycine. Phylogenetic analysis suggests that 12α-HSDH is widespread among Firmicutes , Actinobacteria in the Coriobacteriaceae family, and human gut Archaea IMPORTANCE 12α-HSDH activity has been established in the medically important bile acid 7α-dehydroxylating bacteria C. scindens , C. hiranonis , and C. hylemonae Experiments with recombinant 12α-HSDHs from these strains are consistent with culture-based experiments that show a robust preference for 12-oxolithocholic acid over 12-oxochenodeoxycholic acid. Phylogenetic analysis identified novel members of the gut microbiome encoding 12α-HSDH. Future reengineering of 12α-HSDH enzymes to preferentially oxidize cholic acid may provide a means to industrially produce the therapeutic bile acid ursodeoxycholic acid. In addition, a cholic acid-specific 12α-HSDH expressed in the gut may be useful for the reduction in deoxycholic acid concentration, a bile acid implicated in cancers of the gastrointestinal (GI) tract. Copyright © 2018 American Society for Microbiology.

Obeticholic acid, a selective farnesoid X receptor agonist, regulates bile acid homeostasis in sandwich-cultured human hepatocytes.

PubMed

Zhang, Yuanyuan; Jackson, Jonathan P; St Claire, Robert L; Freeman, Kimberly; Brouwer, Kenneth R; Edwards, Jeffrey E

2017-08-01

Farnesoid X receptor (FXR) is a master regulator of bile acid homeostasis through transcriptional regulation of genes involved in bile acid synthesis and cellular membrane transport. Impairment of bile acid efflux due to cholangiopathies results in chronic cholestasis leading to abnormal elevation of intrahepatic and systemic bile acid levels. Obeticholic acid (OCA) is a potent and selective FXR agonist that is 100-fold more potent than the endogenous ligand chenodeoxycholic acid (CDCA). The effects of OCA on genes involved in bile acid homeostasis were investigated using sandwich-cultured human hepatocytes. Gene expression was determined by measuring mRNA levels. OCA dose-dependently increased fibroblast growth factor-19 (FGF-19) and small heterodimer partner (SHP) which, in turn, suppress mRNA levels of cholesterol 7-alpha-hydroxylase (CYP7A1), the rate-limiting enzyme for de novo synthesis of bile acids. Consistent with CYP7A1 suppression, total bile acid content was decreased by OCA (1 μmol/L) to 42.7 ± 20.5% relative to control. In addition to suppressing de novo bile acids synthesis, OCA significantly increased the mRNA levels of transporters involved in bile acid homeostasis. The bile salt excretory pump (BSEP), a canalicular efflux transporter, increased by 6.4 ± 0.8-fold, and the basolateral efflux heterodimer transporters, organic solute transporter α (OST α ) and OST β increased by 6.4 ± 0.2-fold and 42.9 ± 7.9-fold, respectively. The upregulation of BSEP and OST α and OST β, by OCA reduced the intracellular concentrations of d 8 -TCA, a model bile acid, to 39.6 ± 8.9% relative to control. These data demonstrate that OCA does suppress bile acid synthesis and reduce hepatocellular bile acid levels, supporting the use of OCA to treat bile acid-induced toxicity observed in cholestatic diseases. © 2017 Intercept Pharmaceuticals. Pharmacology Research & Perspectives published by John Wiley & Sons Ltd, British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics.

Optic properties of bile liquid crystals in human body

PubMed Central

Yang, Hai Ming; Wu, Jie; Li, Jin Yi; Zhou, Jian Li; He, Li Jun; Xu, Xian Fang

2000-01-01

AIM: To further study the properties of bile liquid crystals, and probe into the relationship between bile liquid crystals and gallbladder stone formation, and provide evidence for the prevention and treatment of cholecystolithiasis. METHODS: The optic properties of bile liquid crystals in human body were determined by the method of crystal optics under polarizing microscope with plane polarized light and perpendicular polarized light. RESULTS: Under a polarizing microscope with plane polarized light, bile liquid crystals scattered in bile appeared round, oval or irregularly round. The color of bile liquid crystals was a little lighter than that of the bile around. When the stage was turned round, the color of bile liquid crystals or the darkness and lightness of the color did not change obviously. On the border between bile liquid crystals and the bile around, brighter Becke-Line could be observed. When the microscope tube is lifted, Becke-Line moved inward, and when lowered, Becke-Line moved outward. Under a perpendicular polarized light, bile liquid crystals showd some special interference patterns, called Malta cross. When the stage was turning round at an angle of 360°, the Malta cross showed four times of extinction. In the vibrating direction of 45° angle of relative to upper and lower polarizing plate, gypsum test-board with optical path difference of 530 nm was inserted, the first and the third quadrants of Malt a cross appeared to be blue, and the second and the fourth quadrants appeared orange. When mica test-board with optical path difference of 147 nm was inserted, the first and the third quadrants of Malta cross appeared yellow, and the second and the fourth quadrants appeared dark grey. CONCLUSION: The bile liquid crystals were distributed in bile in the form of global grains. Their polychroism and absorption were slight, but the edge and Becke*Line were very clear. Its refractive index was larger than that of the bile. These liquid crystals were uniaxial positive crystals. The interference colors were the first order grey-white. The double refractive index of the liquid crystals was Δn = 0.011-0.015. PMID:11819567

Review article: bile acid diarrhoea - pathogenesis, diagnosis and management.

PubMed

Mottacki, N; Simrén, M; Bajor, A

2016-04-01

Bile acid diarrhoea results from imbalances in the homoeostasis of bile acids in the enterohepatic circulation. It can be a consequence of ileal disease/dysfunction, associated with other GI pathology or can be idiopathic. To summarise the different types of bile acid diarrhoea and discuss the currently available diagnostic methods and treatments. Bile acid diarrhoea is found in up to 40% of patients diagnosed as having functional diarrhoea/IBS-D, and in up to 80% of patients who have undergone ileal resection. It is likely under-diagnosed and under-treated. In idiopathic disease, errors in regulation feedback of fibroblast growth factor 19 contribute to the development of the condition. Clinical therapeutic trials for bile acid diarrhoea have been used to diagnose it, but the 75 SeHCAT test is the primary current method. It is sensitive, specific and widely available, though not in the USA. Other diagnostic methods (such as serum measurement of the bile acid intermediate 7α-hydroxy-4-cholesten-3-one, or C4) have less widespread availability and documentation, and some (such as faecal measurement of bile acids) are significantly more complex and costly. First-line treatment of bile acid diarrhoea is with the bile acid sequestrant cholestyramine, which can be difficult to administer and dose due to gastrointestinal side effects. These side effects are less prominent in newer agents such as colesevelam, which may provide higher efficacy, tolerability and compliance. Bile acid diarrhoea is common, and likely under-diagnosed. Bile acid diarrhoea should be considered relatively early in the differential diagnosis of chronic diarrhoea. © 2016 John Wiley & Sons Ltd.

Role of bile acids and bile acid binding agents in patients with collagenous colitis.

PubMed

Ung, K A; Gillberg, R; Kilander, A; Abrahamsson, H

2000-02-01

In a retrospective study bile acid malabsorption was observed in patients with collagenous colitis. To study the occurrence of bile acid malabsorption and the effect of bile acid binders prospectively in patients with chronic diarrhoea and collagenous colitis. Over 36 months all patients referred because of chronic diarrhoea completed a diagnostic programme, including gastroscopy with duodenal biopsy, colonoscopy with biopsies, and the (75)Se-homocholic acid taurine ((75)SeHCAT) test for bile acid malabsorption. Treatment with a bile acid binder (cholestyramine in 24, colestipol in three) was given, irrespective of the results of the (75)SeHCAT test. Collagenous colitis was found in 28 patients (six men, 22 women), 27 of whom had persistent symptoms and completed the programme. Four patients had had a previous cholecystectomy or a distal gastric resection. The (75)SeHCAT test was abnormal in 12/27 (44%) of the collagenous colitis patients with (75)SeHCAT values 0.5-9.7%, and normal in 15 patients (56%). Bile acid binding treatment was followed by a rapid, marked, or complete improvement in 21/27 (78%) of the collagenous colitis patients. Rapid improvement occurred in 11/12 (92%) of the patients with bile acid malabsorption compared with 10/15 (67%) of the patients with normal (75)SeHCAT tests. Bile acid malabsorption is common in patients with collagenous colitis and is probably an important pathophysiological factor. Because of a high response rate without serious side effects, bile acid binding treatment should be considered for collagenous colitis, particularly patients with bile acid malabsorption.

Boldine enhances bile production in rats via osmotic and farnesoid X receptor dependent mechanisms.

PubMed

Cermanova, Jolana; Kadova, Zuzana; Zagorova, Marie; Hroch, Milos; Tomsik, Pavel; Nachtigal, Petr; Kudlackova, Zdenka; Pavek, Petr; Dubecka, Michaela; Ceckova, Martina; Staud, Frantisek; Laho, Tomas; Micuda, Stanislav

2015-05-15

Boldine, the major alkaloid from the Chilean Boldo tree, is used in traditional medicine to support bile production, but evidence to support this function is controversial. We analyzed the choleretic potential of boldine, including its molecular background. The acute- and long-term effects of boldine were evaluated in rats either during intravenous infusion or after 28-day oral treatment. Infusion of boldine instantly increased the bile flow 1.4-fold in healthy rats as well as in animals with Mrp2 deficiency or ethinylestradiol induced cholestasis. This effect was not associated with a corresponding increase in bile acid or glutathione biliary excretion, indicating that the effect is not related to stimulation of either bile acid dependent or independent mechanisms of bile formation and points to the osmotic activity of boldine itself. We subsequently analyzed bile production under conditions of changing biliary excretion of boldine after bolus intravenous administration and found strong correlations between both parameters. HPLC analysis showed that bile concentrations of boldine above 10 μM were required for induction of choleresis. Importantly, long-term pretreatment, when the bile collection study was performed 24-h after the last administration of boldine, also accelerated bile formation despite undetectable levels of the compound in bile. The effect paralleled upregulation of the Bsep transporter and increased biliary clearance of its substrates, bile acids. We consequently confirmed the ability of boldine to stimulate the Bsep transcriptional regulator, FXR receptor. In conclusion, our study clarified the mechanisms and circumstances surrounding the choleretic activity of boldine. Copyright © 2015 Elsevier Inc. All rights reserved.

Organochloride pesticides modulated gut microbiota and influenced bile acid metabolism in mice.

PubMed

Liu, Qian; Shao, Wentao; Zhang, Chunlan; Xu, Cheng; Wang, Qihan; Liu, Hui; Sun, Haidong; Jiang, Zhaoyan; Gu, Aihua

2017-07-01

Organochlorine pesticides (OCPs) can persistently accumulate in body and threaten human health. Bile acids and intestinal microbial metabolism have emerged as important signaling molecules in the host. However, knowledge on which intestinal microbiota and bile acids are modified by OCPs remains unclear. In this study, adult male C57BL/6 mice were exposed to p, p'-dichlorodiphenyldichloroethylene (p, p'-DDE) and β-hexachlorocyclohexane (β-HCH) for 8 weeks. The relative abundance and composition of various bacterial species were analyzed by 16S rRNA gene sequencing. Bile acid composition was analyzed by metabolomic analysis using UPLC-MS. The expression of genes involved in hepatic and enteric bile acids metabolism was measured by real-time PCR. Expression of genes in bile acids synthesis and transportation were measured in HepG2 cells incubated with p, p'-DDE and β-HCH. Our findings showed OCPs changed relative abundance and composition of intestinal microbiota, especially in enhanced Lactobacillus with bile salt hydrolase (BSH) activity. OCPs affected bile acid composition, enhanced hydrophobicity, decreased expression of genes on bile acid reabsorption in the terminal ileum and compensatory increased expression of genes on synthesis of bile acids in the liver. We demonstrated that chronic exposure of OCPs could impair intestinal microbiota; as a result, hepatic and enteric bile acid profiles and metabolism were influenced. The findings in this study draw our attention to the hazards of chronic OCPs exposure in modulating bile acid metabolism that might cause metabolic disorders and their potential to cause related diseases in human. Copyright © 2017 Elsevier Ltd. All rights reserved.

Ablating L-FABP in SCP-2/SCP-x null mice impairs bile acid metabolism and biliary HDL-cholesterol secretion

PubMed Central

Martin, Gregory G.; Atshaves, Barbara P.; Landrock, Kerstin K.; Landrock, Danilo; Storey, Stephen M.; Howles, Philip N.; Kier, Ann B.

2014-01-01

On the basis of their abilities to bind bile acids and/or cholesterol, the physiological role(s) of liver fatty acid-binding protein (L-FABP) and sterol carrier protein (SCP) 2/SCP-x (SCP-2/SCP-x) gene products in biliary bile acid and cholesterol formation was examined in gene-ablated male mice. L-FABP (LKO) or L-FABP/SCP-2/SCP-x [triple-knockout (TKO)] ablation markedly decreased hepatic bile acid concentration, while SCP-2/SCP-x [double-knockout (DKO)] ablation alone had no effect. In contrast, LKO increased biliary bile acid, while DKO and TKO had no effect on biliary bile acid levels. LKO and DKO also altered biliary bile acid composition to increase bile acid hydrophobicity. Furthermore, LKO and TKO decreased hepatic uptake and biliary secretion of high-density lipoprotein (HDL)-derived 22-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-23,24-bisnor-5-cholen-3β-ol (NBD-cholesterol), while DKO alone had no effect. Finally, LKO and, to a lesser extent, DKO decreased most indexes contributing to cholesterol solubility in biliary bile. These results suggest different, but complementary, roles for L-FABP and SCP-2/SCP-x in biliary bile acid and cholesterol formation. L-FABP appears to function more in hepatic retention of bile acids as well as hepatic uptake and biliary secretion of HDL-cholesterol. Conversely, SCP-2/SCP-x may function more in formation and biliary secretion of bile acid, with less impact on hepatic uptake or biliary secretion of HDL-cholesterol. PMID:25277800

Determination of bile acid pool size, turnover time, and distribution of male broiler chicks during the first 6 weeks posthatch using SEHCAT, a gamma ray-emitting bile acid analogue.

PubMed

Green, J; Kellogg, T; Keirs, R; Cooper, R

1987-11-01

A bile acid analogue, SEHCAT (tauro-23-75SE-selena-homocholic acid), was used to determine bile acid pool size, turnover time, and distribution in the developing broiler chick. Bile acid pool size was significantly affected by age and followed a quintic trend (a fifth degree polynomial). It remained steady until 30 days of age when it decreased significantly and then rose significantly at 37 days of age. The bile acid pool half-life remained constant until 28 days of age when it increased significantly and then held steady until it increased again at 8 wk of age following a quartic trend. The distribution of bile acids was affected by age with the amount in the gizzard, duodenum, cloaca, liver, and gall bladder varying significantly with age. Jejunal, ileal, and cecal bile acids did not vary significantly with age. Liver bile acid levels followed a quintic trend, rising until 23 days of age and dropping sharply at 30 days of age and holding steady.

Human beta-glucuronidase. Measurement of its activity in gallbladder bile devoid of intrinsic interference.

PubMed

Ho, Y C; Ho, K J

1988-04-01

Our purpose is to develop a standard method for preparing the bile for beta-glucuronidase determination by removal of bile acids and conjugated bilirubin which interfere with its activity. The bile acids and conjugated bilirubin in their purified solutions and in the diluted gallbladder biles could be extracted completely with cholestyramine in powder form or tetrahexylammonium chloride (THAC) in chloroform or ethyl acetate. The enzyme was, however, partially precipitated with cholestyramine and denatured by chloroform but not by ethyl acetate. A standard procedure, therefore, includes extraction of the diluted gallbladder bile with THAC in ethyl acetate, followed by determination of the maximal velocity (Vmax) of the enzyme by a kinetic method employing phenolphthalein glucuronide as the substrate. The average Vmax of beta-glucuronidase in the 20 normal gallbladder biles was 165 +/- 86 nmol/min/ml (mean +/- SD), a 23.5-fold increase over the activity before extraction. The measured activity represented the true activity of the enzyme in the bile for recovery of activity of the enzyme added to the bile was practically complete.

Attitudes Toward Bile Extraction From Living Bears: Survey of Citizens and Students in Beijing.

PubMed

Liu, Zhao; Jiang, Zhigang; Yang, Aifang; Xu, Bingbing; Fang, Hongxia; Xie, Zongping; Li, Ning; Li, Chunwang; Meng, Zhibin; Zeng, Yan

2017-01-01

Bear bile is a traditional Chinese medicine that has been used for millennia. Several arguments support and oppose the use of bear farming in terms of conservation and nonhuman animal welfare. This study involved designing a questionnaire and surveying a random sample of general citizens and college students in Beijing to elicit their attitudes on bile extraction from living bears. Older people and people with lower education levels used more bear bile medicines. In total, 29.47% (n = 204) of citizens and 23.14% (n = 81) of students surveyed used bear bile medicine since 1990. Students were less willing to use bear bile medicines than citizens (p < .05). The level the respondents agreed with the blue side (against the extraction of bile from living bears; anti for short) was significantly higher than that for the red side (support the extraction of bile from living bears; pro for short; p < .05). Additionally, college students had a more distinct attitude toward the opposing views, which indicates they were more inclined to oppose bile extraction from living bears.

[Diagnosis and treatment of gastroesophageal reflux in children].

PubMed

Bairov, V G; Privorotskiĭ, V F; Azizov BDzh; Luppova, N E; Karavaeva, S A; Zhavoronkova, G V; Shavkin, L N

1999-01-01

The work is based on an analysis of results of treatment of 643 children with gastroesophageal reflux (operations were performed on 69 of them). Methods of anesthesia are described. Conservative treatment was used in correlation with the degree of reflux-esophagitis. Indications to operations were considered to be as follows: hiatal hernias, reflux-esophagitis in children with cerebral paralysis, failure of conservative treatment in the group of children having no anatomical causes of the reflux. A method of surgical treatment is proposed including a combination of fundoplication with the posterior gastropexy and fixation of the esophagus to the diaphragm at a distance of 3 cm from the gastric cuff (43 cases, no recurrences). In patients with a combination of gastroesophageal reflux with the esophagus stenosis resection of the altered portion was made followed by plasty with a colonic transplant or local tissues (10 patients with the diagnosed Barrett esophagus).

Proton Pump Inhibitors in Gastroesophageal Reflux Disease: Friend or Foe.

PubMed

Gyawali, C Prakash

2017-09-01

Proton pump inhibitor (PPI) use in gastroesophageal reflux disease (GERD) has been redefined, in light of recent advances highlighting GERD phenotypes that respond to PPIs, and fresh revelations of potential risks of long-term PPI therapy. Erosive esophagitis predicts excellent response to PPI therapy, but non-erosive reflux disease (NERD) with abnormal reflux parameters on ambulatory reflux monitoring also demonstrates a similar response. In contrast, response is suboptimal in the absence of abnormal reflux parameters. In this setting, if an alternate appropriate indication for PPI therapy does not coexist, risks may outweigh benefits of PPI therapy. Adverse events from long-term PPI therapy continue to be reported, most based on association rather than cause-and-effect. Appropriate indications need to be established before embarking on long-term PPI therapy. Future research will define true risks of long-term PPI therapy, and develop alternate management options for acid peptic diseases.

Motility abnormalities in esophageal body in GERD: are they truly related to reflux?

PubMed

Ciriza de los Ríos, C; García Menéndez, L; Díez Hernández, A; Fernández Eroles, A L; Vega Fernández, A; Enguix Armada, A

2005-03-01

Esophageal motility abnormalities have been observed in patients with gastroesophageal reflux disease. The aim of the present study was to determine if esophageal motor disorders in patients with a positive response to the omeprazole test are related to the existence of reflux or they are concomitant findings. A 24-hour pH monitoring and a stationary manometry were performed on 128 patients: 49 of them had normal manometry, 31 hypotensive lower esophageal sphincter, 29 motor disorder in esophageal body, and 19 hypotensive lower esophageal sphincter and motor disorder in esophageal body. We found an association between the presence of abnormal reflux and motor disorder in esophageal body (chi test; P < 0.05). However, ineffective esophageal motility was the disorder most strongly related to reflux, whereas the hypercontractile disorders were not clearly attributed to it. Esophageal manometric abnormalities should be considered cautiously before considering a motor disorder as a consequence of abnormal reflux.

Study on Tritium Removal Performance by Gas Separation Membrane with Reflux Flow for Tritium Removal System of Fusion Reactor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Iwai, Yasunori; Yamanishi, Toshihiko; Hayashi, Takumi

2005-07-15

Addition of gas separation membrane process into the usual tritium removal process from an indoor atmosphere is attractive for a fusion plant, where a large amount of atmosphere should be processed. As a manner to improve the partial pressure difference between feed and permeated side, intended reflux of vapor and the hydrogen concentrated at permeated side is conceived to enlarge the partial pressure difference. Membrane separation with reflux flow has been proposed as an attractive process to enhance the recovery ratio of tritium component. Effect of reflux on the recovery ratio of tritium component was evaluated by numerical analysis. Themore » effect of reflux on separation performance becomes striking as the target species have higher permeability coefficients. Hence, the gas separation by membrane with reflux flow is favorable for tritium recovery.« less

The gastric accommodation response to meal intake determines the occurrence of transient lower esophageal sphincter relaxations and reflux events in patients with gastro-esophageal reflux disease.

PubMed

Pauwels, A; Altan, E; Tack, J

2014-04-01

Gastro-esophageal reflux (GER), the retrograde flow of gastric contents into the esophagus is a physiologic phenomenon, which can evoke symptoms and/or lesions in the esophagus (=gastro-esophageal reflux disease or GERD). Proton pump inhibitors (PPIs) reduce gastric acidity; however, as they are unable to control transient lower esophageal sphincter relaxations (TLESRs), the main mechanism for reflux in GERD, they do not abolish reflux. TLESRs occur predominantly in the postprandial period, and they are believed to be triggered by gastric distention. Gastric accommodation (GA) is the physiologic response to gastric distention and serves to prevent a rise in gastric wall tension during food intake. We aimed to study the relationship between GA and TLESRs, as they both are triggered by gastric distention. We studied 12 GERD patients (average age 37 years [range 18-62], 7m/5f) and nine healthy volunteers (average age 27 years [range 22-36], 2m/7f) using high resolution manometry-impedance measurement before and after a mixed meal challenge. We determined the number of TLESRs (with or without reflux) and measured pre- and postprandial IGP. The change in IGP between the pre- and postprandial period (ΔIGP) is used as surrogate for GA. We also measured LES pressure before and after the meal and calculated the change (ΔLESp). There were no statistical differences between pre- and postprandial IGP in GERD and healthy volunteers and similarly, there was no significant difference between pre- and postprandial LES pressures in GERD patients and healthy volunteers. The number of TLESRs (with or without reflux) was similar in GERD and healthy volunteers. More importantly, we did observe a negative correlation between ΔIGP and the number of TLESRs, irrespective of whether they were associated with reflux or not, in the GERD patients (without reflux r = -0.67, p = 0.017; with reflux r = -0.81, p = 0.0014). The same observations were found in healthy volunteers, where ΔIGP and the number of TLESRs are significantly inversely correlated (without reflux r = -0.87, p = 0.0045; with reflux r = -0.75, p = 0.021). We could not establish a correlation between ΔLESp and the number of TLESRs, neither in GERD patients nor in healthy volunteers. This is the first study showing a clear negative correlation between ΔIGP and the number of TLESRs, irrespective of whether they were associated with reflux or not, both in GERD patients and in healthy subjects. These results suggest that TLESRs and GA are closely linked, probably through activation of mechanoreceptors involved in triggering of TLESRs. © 2014 John Wiley & Sons Ltd.

The ulcerogenic effect of bile and bile acid in rats during immobilization stress

NASA Technical Reports Server (NTRS)

Weisener, J.

1980-01-01

The effect of different concentrations of oxen bile and individual bile acids or their sodium salts on the gastric mucosa of rats was investigated in combination with immobilization stress. A statistically significant higher frequency of ulcers was only determined in the application of 10% oxen bile. Dosages on 10% sodium glycocholic acid demonstrated strong toxic damage with atonic dilation of the stomach and extensive mucosal bleeding.

Bile-Esculin Test for Presumptive Identification of Enterococci and Streptococci: Effects of Bile Concentration, Inoculation Technique, and Incubation Time

PubMed Central

Chuard, C.; Reller, L. B.

1998-01-01

The bile-esculin test is used to differentiate enterococci and group D streptococci from non-group D viridans group streptococci. The effects on test performance of the concentration of bile salts, inoculum, and duration of incubation were examined with 110 strains of enterococci, 30 strains of Streptococcus bovis, and 110 strains of non-group D viridans group streptococci. Optimal sensitivity (>99%) and specificity (97%) of the bile-esculin test can be obtained with a bile concentration of 40%, a standardized inoculum of 106 CFU, and incubation for 24 h. PMID:9542954

Bile-esculin test for presumptive identification of enterococci and streptococci: effects of bile concentration, inoculation technique, and incubation time.

PubMed

Chuard, C; Reller, L B

1998-04-01

The bile-esculin test is used to differentiate enterococci and group D streptococci from non-group D viridans group streptococci. The effects on test performance of the concentration of bile salts, inoculum, and duration of incubation were examined with 110 strains of enterococci, 30 strains of Streptococcus bovis, and 110 strains of non-group D viridans group streptococci. Optimal sensitivity (> 99%) and specificity (97%) of the bile-esculin test can be obtained with a bile concentration of 40%, a standardized inoculum of 10(6) CFU, and incubation for 24 h.

Choleperitoneum due to intrahepatic bile duct rupture - case report.

PubMed

Simion, L; Straja, Dn; Prunoiu, Vm; Alecu, M; Brătucu, E

2014-01-01

Non-traumatic perforations of the bile ducts are unfrequently encountered entities, all the more when they affect the intrahepatic bile ducts, exteriorizing their biliary content in the great peritoneal cavity. Reporting such a case has determined the authors to perform a careful overview of the cases present in the literature. An observation that can be made based on these is that the obstruction of the main bile duct due to lithiasis determines, by pressure increase, the dilation of the bile system branches, all on the background of an unknown malformation of the intrahepatic bile ducts. Celsius.

Impact of bile salt adaptation of Lactobacillus delbrueckii subsp. lactis 200 on its interaction capacity with the gut.

PubMed

Burns, Patricia; Reinheimer, Jorge; Vinderola, Gabriel

2011-10-01

In a previous work, bile-salt-resistant derivatives were obtained from non-intestinal lactobacilli. The aim of this work was to investigate the impact of bile adaptation of Lactobacillus delbrueckii subsp. lactis 200 on morphology, surface properties, in vivo interaction capacity with the gut and ability to activate the gut immune response. Electron microscopy studies, growth kinetics in the presence of bovine and porcine bile, the capacity to deconjugate bile acids, hydrophobicity, autoaggregation and co-aggregation capacities were studied for the parental strain and its bile-resistant derivative in vitro. Additionally, survival in intestinal fluid, the interaction with the gut and the immunomodulating capacities were studied in mice. Bile salt adaptation conferred upon the adapted strain a higher capacity to withstand physiological concentrations of bile salts and greater survival capacity in intestinal fluid. However, bile salt exposure reduced cell hydrophobicity, autoaggregation and adhesion capacities, resulting in reduced persistence in the intestinal lumen and delayed capacity to activate the gut immune response. Insight into the effects of bile salts upon the interaction and immunomodulating capacity of lactobacilli with the gut is provided, relating in vitro and in vivo results. Copyright © 2011 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

Rapid Determination of Bile Acids in Bile from Various Mammals by Reversed-Phase Ultra-Fast Liquid Chromatography.

PubMed

Si, Gu Leng Ri; Yao, Peng; Shi, Luwen

2015-08-01

A valid and efficient reversed-phase ultra-fast liquid chromatography method was developed for the simultaneous determination of 13 bile acids in the bile of three mammal species, including rat, pig and human gallstone patients. Chromatographic separation was performed with a Shim-pack XR-ODS column, and the mobile phase consisted of acetonitrile and potassium phosphate buffer (pH 2.6) at a flow rate of 0.5 mL min(-1). The linear detection range of most bile acids ranged from 2 to 600 ng µL(-1) with a good correlation coefficient (>0.9995). The precision of each bile acid was <1.8% for intraday and <4.8% for interday. All bile acids were separated in 15 min with satisfactory resolution, and the total analysis time was 18 min, including equilibration. The method was successfully applied in rapid screening of bile samples from the three mammals. Significant metabolic frameworks of bile acids among various species were observed, whereas considerable quantitative variations in both inter- and intraspecies were also observed, especially for gallstone patients. Our results suggest that detecting the change of bile acid profiles could be applied for the diagnosis of gallstone disease. © Crown copyright 2014.

Interaction of Gut Microbiota with Bile Acid Metabolism and its Influence on Disease States

PubMed Central

Staley, Christopher; Weingarden, Alexa R.

2016-01-01

Primary bile acids serve important roles in cholesterol metabolism, lipid digestion, host-microbe interactions, and regulatory pathways in the human host. While most bile acids are reabsorbed and recycled via enterohepatic cycling, ~5% serve as substrates for bacterial biotransformation in the colon. Enzymes involved in various transformations have been characterized from cultured gut bacteria and reveal taxa-specific distribution. More recently, bioinformatic approaches have revealed greater diversity in isoforms of these enzymes, and the microbial species in which they are found. Thus, the functional roles played by the bile acid-transforming gut microbiota and the distribution of resulting secondary bile acids, in the bile acid pool, may be profoundly affected by microbial community structure and function. Bile acids and the composition of the bile acid pool have historically been hypothesized to be associated with several disease states, including recurrent Clostridium difficile infection, inflammatory bowel diseases, metabolic syndrome, and several cancers. Recently, however, emphasis has been placed on how microbial communities in the dysbiotic gut may alter the bile acid pool to potentially cause or mitigate disease onset. This review highlights the current understanding of the interactions between the gut microbial community, bile acid biotransformation, and disease states, and addresses future directions to better understand these complex associations. PMID:27888332

Bile alcohols function as the ligands of membrane-type bile acid-activated G protein-coupled receptor

PubMed Central

Iguchi, Yusuke; Yamaguchi, Masafumi; Sato, Hiroyuki; Kihira, Kenji; Nishimaki-Mogami, Tomoko; Une, Mizuho

2010-01-01

TGR5 is a G protein-coupled receptor that is activated by bile acids, resulting in an increase in cAMP levels and the subsequent modulation of energy expenditure in brown adipose tissue and muscle. Therefore, the development of a TGR5-specific agonist could lead to the prevention and treatment of various metabolic disorders related to obesity. In the present study, we evaluated the ability of bile alcohols, which are structurally and physiologically similar to bile acids and are produced as the end products of cholesterol catabolism in evolutionarily primitive vertebrates, to act as TGR5 agonists. In a cell-based reporter assay and a cAMP production assay performed in vitro, most bile alcohols with a side chain containing hydroxyl group(s) were highly efficacious agonists for TGR5 comparable to its most potent ligand in the naturally occurring bile acid, lithocholic acid. However, the abilities of the bile alcohols to activate TGR5 varied with the position and number of the hydroxyl substituent in the side chain. Additionally, the conformation of the steroidal nucleus of bile alcohols is also important for its activity as a TGR5 agonist. Thus, we have provided new insights into the structure-activity relationships of bile alcohols as TGR5 agonists. PMID:20023205

The Role of Bile After Roux-en-Y Gastric Bypass in Promoting Weight Loss and Improving Glycaemic Control

PubMed Central

Pournaras, Dimitri J.; Glicksman, Clare; Vincent, Royce P.; Kuganolipava, Shophia; Alaghband-Zadeh, Jamie; Mahon, David; Bekker, Jan H.R.; Ghatei, Mohammad A.; Bloom, Stephen R.; Walters, Julian R.F.; le Roux, Carel W.

2012-01-01

Gastric bypass leads to the remission of type 2 diabetes independently of weight loss. Our hypothesis is that changes in bile flow due to the altered anatomy may partly explain the metabolic outcomes of the operation. We prospectively studied 12 patients undergoing gastric bypass and six patients undergoing gastric banding over a 6-wk period. Plasma fibroblast growth factor (FGF)19, stimulated by bile acid absorption in the terminal ileum, and plasma bile acids were measured. In canine and rodent models, we investigated changes in the gut hormone response after altered bile flow. FGF19 and total plasma bile acids levels increased after gastric bypass compared with no change after gastric banding. In the canine model, both food and bile, on their own, stimulated satiety gut hormone responses. However, when combined, the response was doubled. In rats, drainage of endogenous bile into the terminal ileum was associated with an enhanced satiety gut hormone response, reduced food intake, and lower body weight. In conclusion, after gastric bypass, bile flow is altered, leading to increased plasma bile acids, FGF19, incretin. and satiety gut hormone concentrations. Elucidating the mechanism of action of gastric bypass surgery may lead to novel treatments for type 2 diabetes. PMID:22673227

Bile acids: analysis in biological fluids and tissues

PubMed Central

Griffiths, William J.; Sjövall, Jan

2010-01-01

The formation of bile acids/bile alcohols is of major importance for the maintenance of cholesterol homeostasis. Besides their functions in lipid absorption, bile acids/bile alcohols are regulatory molecules for a number of metabolic processes. Their effects are structure-dependent, and numerous metabolic conversions result in a complex mixture of biologically active and inactive forms. Advanced methods are required to characterize and quantify individual bile acids in these mixtures. A combination of such analyses with analyses of the proteome will be required for a better understanding of mechanisms of action and nature of endogenous ligands. Mass spectrometry is the basic detection technique for effluents from chromatographic columns. Capillary liquid chromatography-mass spectrometry with electrospray ionization provides the highest sensitivity in metabolome analysis. Classical gas chromatography-mass spectrometry is less sensitive but offers extensive structure-dependent fragmentation increasing the specificity in analyses of isobaric isomers of unconjugated bile acids. Depending on the nature of the bile acid/bile alcohol mixture and the range of concentration of individuals, different sample preparation sequences, from simple extractions to group separations and derivatizations, are applicable. We review the methods currently available for the analysis of bile acids in biological fluids and tissues, with emphasis on the combination of liquid and gas phase chromatography with mass spectrometry. PMID:20008121

Simple resection of the lesion bile duct branch for treatment of regional hepatic bile duct stones

PubMed Central

Enliang, Li; Rongshou, Wu; Shidai, Shi; Jingling, Zhang; Qian, Feng; Wenjun, Liao; Linquan, Wu

2017-01-01

Abstract To evaluate the effectiveness and safety of simple resections of bile duct branch lesions for the treatment of regional hepatic bile duct stones. A retrospective analysis of the clinical data from patients in our hospital from November 2008 to November 2015, who only underwent a simple resection of the lesion bile duct branch. The patients’ clinical characteristics, surgical features, postoperative complications, stone clear rate, residual stone rate, and recurrence stone rate were analyzed. This study of 32 patients included 13 males and 19 females with intrahepatic bile duct stones confined to the right hepatic bile duct branch. The intraoperative blood loss, operation time, and postoperative hospital stay were 478.0 ± 86.5, 210.7 ± 6.6, and 10.8 ± 3.5, respectively. Postoperative complications occurred in 6 patients (18.8%), all of whom recovered with conservative management. There were no deaths during hospitalization. The intraoperative stone clearance rate was 95.8%. Three patients had a recurrence of stones at a mean of 22 months of follow-up (range, 4–36 months). Simple resection of bile duct branch lesions is safe and feasible for patients who have regional hepatic bile duct stones limited to the right hepatic bile duct branches. PMID:28682899

Role of AMACR (α-methylacyl-CoA racemase) and MFE-1 (peroxisomal multifunctional enzyme-1) in bile acid synthesis in mice.

PubMed

Autio, Kaija J; Schmitz, Werner; Nair, Remya R; Selkälä, Eija M; Sormunen, Raija T; Miinalainen, Ilkka J; Crick, Peter J; Wang, Yuqin; Griffiths, William J; Reddy, Janardan K; Baes, Myriam; Hiltunen, J Kalervo

2014-07-01

Cholesterol is catabolized to bile acids by peroxisomal β-oxidation in which the side chain of C27-bile acid intermediates is shortened by three carbon atoms to form mature C24-bile acids. Knockout mouse models deficient in AMACR (α-methylacyl-CoA racemase) or MFE-2 (peroxisomal multifunctional enzyme type 2), in which this β-oxidation pathway is prevented, display a residual C24-bile acid pool which, although greatly reduced, implies the existence of alternative pathways of bile acid synthesis. One alternative pathway could involve Mfe-1 (peroxisomal multifunctional enzyme type 1) either with or without Amacr. To test this hypothesis, we generated a double knockout mouse model lacking both Amacr and Mfe-1 activities and studied the bile acid profiles in wild-type, Mfe-1 and Amacr single knockout mouse line and Mfe-1 and Amacr double knockout mouse lines. The total bile acid pool was decreased in Mfe-1-/- mice compared with wild-type and the levels of mature C24-bile acids were reduced in the double knockout mice when compared with Amacr-deficient mice. These results indicate that Mfe-1 can contribute to the synthesis of mature bile acids in both Amacr-dependent and Amacr-independent pathways.

Metabolic changes in the lower esophageal sphincter influencing the result of anti-reflux surgical interventions in chronic gastroesophageal reflux disease.

PubMed

Altorjay, Aron; Juhasz, Arpad; Kellner, Viola; Sohar, Gellert; Fekete, Matyas; Sohar, Istvan

2005-03-21

With the availability of a minimally invasive approach, anti-reflux surgery has recently experienced a renaissance as a cost-effective alternative to life-long medical treatment in patients with gastroesophageal reflux disease (GERD). We are not aware of the fact whether reflux episodes causing complaints for a long time i.e., at least for one year are associated with metabolic changes in the lower esophageal sphincter, and if so, whether these may influence functional results achieved after anti-reflux surgery. Between 1 January 2001 and 31 December 2002 we performed anti-reflux surgery on 79 patients. Muscle samples were taken from the lower esophageal sphincter (LES) in 33 patients during anti-reflux surgery. Inclusion criteria were: LES resting pressure below 10 mmHg and a marked, pH proven acid exposure to the esophagus of at least one year's duration, causing subjective complaints and requiring continuous proton pump inhibitor treatment. Control samples were obtained from muscle tissue in the gastroesophageal junction that had been removed from 17 patients undergoing gastric or esophageal resection. Metabolic and lysosomal enzyme activities and special protein concentrations 16 parameters in total were evaluated in tissue taken from control specimens and tissue taken from patients with GERD. The biochemical parameters of these intra-operative biopsies were used to correlate the results of anti-reflux operations (Visick I and II-III). In the reflux-type muscle, we found a significant increase of the energy-enzyme activities e.g., creatine kinase, lactate dehydrogenase, beta-hydroxybutyrate dehydrogenase, and aspartate aminotransaminase-. The concentration of the structural protein S-100 and the myofibrillar protein troponin I were also significantly increased. Among lysosomal enzymes, we found that the activities of cathepsin B, tripeptidyl-peptidase I, dipeptidyl-peptidase II, beta-hexosaminidase B, beta-mannosidase and beta-galactosidase were significantly decreased as compared to the control LES muscles. By analyzing the activity values of the 9 patients in Visick groups II and III at two months post-surgery, we found a significant increase in the activity of the so-called energy-enzyme values and in the concentration of structural and myofibrillar proteins as compared to the rest of the reflux patients. Our results call attention to the metabolic changes that occurred in the LES muscles of reflux patients. The developing hypertrophy-like changes of LES muscles may be a reason for complaints after anti-reflux surgery, which consisted mainly of reports of persisting dysphagia.

Metabolic changes in the lower esophageal sphincter influencing the result of anti-reflux surgical interventions in chronic gastroesophageal reflux disease

PubMed Central

Altorjay, Aron; Juhasz, Arpad; Kellner, Viola; Sohar, Gellert; Fekete, Matyas; Sohar, Istvan

2005-01-01

AIM: With the availability of a minimally invasive approach, anti-reflux surgery has recently experienced a renaissance as a cost-effective alternative to life-long medical treatment in patients with gastroesophageal reflux disease (GERD). We are not aware of the fact whether reflux episodes causing complaints for a long time i.e., at least for one year are associated with metabolic changes in the lower esophageal sphincter, and if so, whether these may influence functional results achieved after anti-reflux surgery. METHODS: Between 1 January 2001 and 31 December 2002 we performed anti-reflux surgery on 79 patients. Muscle samples were taken from the lower esophageal sphincter (LES) in 33 patients during anti-reflux surgery. Inclusion criteria were: LES resting pressure below 10 mmHg and a marked, pH proven acid exposure to the esophagus of at least one year’ duration, causing subjective complaints and requiring continuous proton pump inhibitor treatment. Control samples were obtained from muscle tissue in the gastroesophageal junction that had been removed from 17 patients undergoing gastric or esophageal resection. Metabolic and lysosomal enzyme activities and special protein concentrations 16 parameters in total were evaluated in tissue taken from control specimens and tissue taken from patients with GERD. The biochemical parameters of these intra-operative biopsies were used to correlate the results of anti-reflux operations (Visick I and II-III). RESULTS: In the reflux-type muscle, we found a significant increase of the energy-enzyme activities e.g., creatine kinase, lactate dehydrogenase, β-hydroxybutyrate dehydrogenase, and aspartate aminotransaminase-. The concentration of the structural protein S-100 and the myofibrillar protein troponin I were also significantly increased. Among lysosomal enzymes, we found that the activities of cathepsin B, tripeptidyl-peptidase I, dipeptidyl-peptidase II, β-hexosaminidase B, β-mannosidase and β-galactosidase were significantly decreased as compared to the control LES muscles. By analyzing the activity values of the 9 patients in Visick groups II and III at two months post-surgery, we found a significant increase in the activity of the so-called energy-enzyme values and in the concentration of structural and myofibrillar proteins as compared to the rest of the reflux patients. CONCLUSION: Our results call attention to the metabolic changes that occurred in the LES muscles of reflux patients. The developing hypertrophy-like changes of LES muscles may be a reason for complaints after anti-reflux surgery, which consisted mainly of reports of persisting dysphagia. PMID:15786538

Are clinical, laboratory, and imaging markers suitable predictors of vesicoureteral reflux in children with their first febrile urinary tract infection?

PubMed

Mahyar, Abolfazl; Ayazi, Parviz; Mavadati, Shiva; Oveisi, Sonia; Habibi, Morteza; Esmaeily, Shiva

2014-08-01

This study was conducted to determine the predictive value of clinical, laboratory, and imaging variables for the diagnosis of vesicoureteral reflux in children with their first febrile urinary tract infection. One hundred fifty-three children with their first febrile urinary tract infection were divided into two groups according to the results of voiding cystourethrography: 60 children with vesicoureteral reflux and 93 children without. The sensitivity, specificity, positive and negative predictive value, likelihood ratio (positive and negative), and accuracy of the clinical, laboratory, and imaging variables for the diagnosis of vesicoureteral reflux were determined. Of the 153 children with febrile urinary tract infection, 60 patients (39.2%) had vesicoureteral reflux. There were significant differences between the two groups regarding fever>38℃, suprapubic pain, C-reactive protein quantitative level, number of red blood cells in the urine, and results of renal ultrasound and dimercaptosuccinic acid renal scanning (p<0.05). There were significant positive correlations between fever>38.2℃ and dimercaptosuccinic acid renal scanning and vesicoureteral reflux. Also, there were significant positive correlations between the erythrocyte sedimentation rate, positive urinary nitrite test, hyaline cast, and renal ultrasound and high-grade vesicoureteral reflux. This study revealed fever>38.2℃ and dimercaptosuccinic acid renal scanning as the best predictive markers for vesicoureteral reflux in children with their first febrile urinary tract infection. In addition, erythrocyte sedimentation rate, positive urinary nitrite test, hyaline cast, and renal ultrasound are the best predictive markers for high-grade vesicoureteral reflux.

Are Clinical, Laboratory, and Imaging Markers Suitable Predictors of Vesicoureteral Reflux in Children With Their First Febrile Urinary Tract Infection?

PubMed Central

Ayazi, Parviz; Mavadati, Shiva; Oveisi, Sonia; Habibi, Morteza; Esmaeily, Shiva

2014-01-01

Purpose This study was conducted to determine the predictive value of clinical, laboratory, and imaging variables for the diagnosis of vesicoureteral reflux in children with their first febrile urinary tract infection. Materials and Methods One hundred fifty-three children with their first febrile urinary tract infection were divided into two groups according to the results of voiding cystourethrography: 60 children with vesicoureteral reflux and 93 children without. The sensitivity, specificity, positive and negative predictive value, likelihood ratio (positive and negative), and accuracy of the clinical, laboratory, and imaging variables for the diagnosis of vesicoureteral reflux were determined. Results Of the 153 children with febrile urinary tract infection, 60 patients (39.2%) had vesicoureteral reflux. There were significant differences between the two groups regarding fever>38℃, suprapubic pain, C-reactive protein quantitative level, number of red blood cells in the urine, and results of renal ultrasound and dimercaptosuccinic acid renal scanning (p<0.05). There were significant positive correlations between fever>38.2℃ and dimercaptosuccinic acid renal scanning and vesicoureteral reflux. Also, there were significant positive correlations between the erythrocyte sedimentation rate, positive urinary nitrite test, hyaline cast, and renal ultrasound and high-grade vesicoureteral reflux. Conclusions This study revealed fever>38.2℃ and dimercaptosuccinic acid renal scanning as the best predictive markers for vesicoureteral reflux in children with their first febrile urinary tract infection. In addition, erythrocyte sedimentation rate, positive urinary nitrite test, hyaline cast, and renal ultrasound are the best predictive markers for high-grade vesicoureteral reflux. PMID:25132949

[Urinary tract infection caused by Enterobacteriaceae and its relationship with vesicoureteral reflux].

PubMed

Díaz Álvarez, Manuel; Acosta Batista, Bárbara; Pérez Córdova, Rodolfo; Hernández Robledo, Ernesto

The first urinary tract infection can be a marker of a urinary tract anomaly, mainly vesicoureteral reflux. The aim of this work was to determine the association between isolated enterobacteria with the presence and grade of vesicoureteral reflux in neonatal patients with their first urinary tract infection. A retrospective, observational and analytic study of newborns, who were admitted to the Neonatal Department, University Pediatric Hospital "Juan Manuel Márquez," in Havana, Cuba, from 1992 to 2013 was conducted. The causal microorganism of urinary tract infection was from the Enterobacteriaceae family. They were evaluated by radio imaging. The association between the presence and grade of vesicoureteral reflux with the causal microorganism of the urinary tract infection was analyzed. Newborn infants with urinary tract infection (450) were studied. Bacterial isolations in the urine cultures corresponded to E. coli in 316 cases (70.2%). The prevalence of vesicoureteral reflux was 18.2%. The presence of bacteria corresponding to the Enterobacteriaceae family (other than E. coli) had significant risk association with vesicoureteral reflux (OR: 2.02; p < 0.01) and vesicoureteral reflux classification (for higher grades, p < 0.01). E. coli is the most frequent causal microorganism in neonatal urinary tract infection. However, an association between the isolation of a microorganism of the Enterobacteriaceae family different to E. coli with the presence of vesicoureteral reflux and mainly with higher grades of vesicoureteral reflux exists. Copyright © 2017 Hospital Infantil de México Federico Gómez. Publicado por Masson Doyma México S.A. All rights reserved.

Gastroesophageal reflux activates the NF-κB pathway and impairs esophageal barrier function in mice

PubMed Central

Fang, Yu; Chen, Hao; Hu, Yuhui; Djukic, Zorka; Tevebaugh, Whitney; Shaheen, Nicholas J.; Orlando, Roy C.; Hu, Jianguo

2013-01-01

The barrier function of the esophageal epithelium is a major defense against gastroesophageal reflux disease. Previous studies have shown that reflux damage is reflected in a decrease in transepithelial electrical resistance associated with tight junction alterations in the esophageal epithelium. To develop novel therapies, it is critical to understand the molecular mechanisms whereby contact with a refluxate impairs esophageal barrier function. In this study, surgical models of duodenal and mixed reflux were developed in mice. Mouse esophageal epithelium was analyzed by gene microarray. Gene set enrichment analysis showed upregulation of inflammation-related gene sets and the NF-κB pathway due to reflux. Significance analysis of microarrays revealed upregulation of NF-κB target genes. Overexpression of NF-κB subunits (p50 and p65) and NF-κB target genes (matrix metalloproteinases-3 and -9, IL-1β, IL-6, and IL-8) confirmed activation of the NF-κB pathway in the esophageal epithelium. In addition, real-time PCR, Western blotting, and immunohistochemical staining also showed downregulation and mislocalization of claudins-1 and -4. In a second animal experiment, treatment with an NF-κB inhibitor, BAY 11-7085 (20 mg·kg−1·day−1 ip for 10 days), counteracted the effects of duodenal and mixed reflux on epithelial resistance and NF-κB-regulated cytokines. We conclude that gastroesophageal reflux activates the NF-κB pathway and impairs esophageal barrier function in mice and that targeting the NF-κB pathway may strengthen esophageal barrier function against reflux. PMID:23639809

Ambulatory reflux monitoring for diagnosis of gastro-esophageal reflux disease: Update of the Porto consensus and recommendations from an international consensus group.

PubMed

Roman, S; Gyawali, C P; Savarino, E; Yadlapati, R; Zerbib, F; Wu, J; Vela, M; Tutuian, R; Tatum, R; Sifrim, D; Keller, J; Fox, M; Pandolfino, J E; Bredenoord, A J

2017-10-01

An international group of experts evaluated and revised recommendations for ambulatory reflux monitoring for the diagnosis of gastro-esophageal reflux disease (GERD). Literature search was focused on indications and technical recommendations for GERD testing and phenotypes definitions. Statements were proposed and discussed during several structured meetings. Reflux testing should be performed after cessation of acid suppressive medication in patients with a low likelihood of GERD. In this setting, testing can be either catheter-based or wireless pH-monitoring or pH-impedance monitoring. In patients with a high probability of GERD (esophagitis grade C and D, histology proven Barrett's mucosa >1 cm, peptic stricture, previous positive pH monitoring) and persistent symptoms, pH-impedance monitoring should be performed on treatment. Recommendations are provided for data acquisition and analysis. Esophageal acid exposure is considered as pathological if acid exposure time (AET) is greater than 6% on pH testing. Number of reflux episodes and baseline impedance are exploratory metrics that may complement AET. Positive symptom reflux association is defined as symptom index (SI) >50% or symptom association probability (SAP) >95%. A positive symptom-reflux association in the absence of pathological AET defines hypersensitivity to reflux. The consensus group determined that grade C or D esophagitis, peptic stricture, histology proven Barrett's mucosa >1 cm, and esophageal acid exposure greater >6% are sufficient to define pathological GERD. Further testing should be considered when none of these criteria are fulfilled. © 2017 John Wiley & Sons Ltd.

Role of Laryngopharyngeal Reflux in Complications of Tonsillectomy in Pediatric Patients.

PubMed

Salturk, Ziya; Kumral, Tolgar Lutfi; Arslanoglu, Ahmet; Aydogdu, Imran; Yildirim, Guven; Berkiten, Guler; Uyar, Yavuz

2017-09-01

Tonsillectomy and tonsillectomy with adenoidectomy are among the most common surgical procedures in otolaryngology practice. Gastroesophageal reflux was identified as a risk factor for complications in tonsillectomy. This prospective study was designed to assess the role of reflux in the development of complications following tonsillectomy in pediatric patients. Children (n = 60) who underwent tonsillectomy with adenoidectomy were divided into two groups, i.e., the laryngopharyngeal reflux (LPR) group and control group. Patients with LPR were identified by reflux symptom index and reflux finding score. Pain, hemorrhage, fever, nausea, vomiting, fever, dehydration, infection, and pulmonary problems were evaluated post operatively. The mean lengths of hospital stay were 2.11 days in the reflux group and 1.05 days in the control group. The difference was statistically significant. Visual analogue scores of both groups were similar on day 1 but it was significantly higher on day 7 and 14 in LPR group. Nausea and vomiting rates were 11.1 and 9.5 % for the patients in the LPR group and the controls, respectively. The difference between the two groups was not significant. The mean fever was 37.6 °C in the reflux group and 37.3 °C in the controls, which were not significantly different. 19 % of the controls and 22 % of the LPR group patients were readmitted. This difference was not statistically significant. There were two cases of bleeding in the reflux group, while no bleeding occurred in the control group. This difference was significant statistically. LPR is a risk factor for complications following tonsillectomy.

Differences in clinical characteristics between patients with endoscopy-negative reflux disease and erosive esophagitis in Japan.

PubMed

Fujiwara, Yasuhiro; Higuchi, Kazuhide; Shiba, Masatsugu; Yamamori, Kazuki; Watanabe, Yoko; Sasaki, Eiji; Tominaga, Kazunari; Watanabe, Toshio; Oshitani, Nobuhide; Arakawa, Tetsuo

2005-04-01

Helicobacter pylori infection and atrophic gastritis are inversely related to erosive esophagitis. Whether these factors affect the pathogenesis of endoscopy-negative reflux disease is not clear. We aimed to elucidate the differences in clinical characteristics between endoscopy-negative erosive disease and erosive esophagitis. 253 subjects (89 with endoscopy-negative reflux disease and 164 with erosive esophagitis) were studied. Gastric atrophy was assessed by measurement of serum pepsinogen. Logistic regression was used to calculate the odds ratio (OR) and 95% confidence intervals (CI) of endoscopy-negative reflux disease compared with erosive esophagitis. Among GERD patients, female gender (OR = 2.27, 95% CI, 1.25-4.10), smoking (OR = 0.45, 95% CI, 0.22-0.91), and the presence of hiatal hernia (OR = 0.30, 95% CI, 0.17-0.56) were significantly associated with endoscopy-negative reflux disease compared with male gender, not smoking, and absence of hiatal hernia, respectively. Body mass index (BMI) was also significantly associated with a decreased OR for endoscopy-negative reflux disease. Although H. pylori infection and gastric atrophy were significantly more common in patients with endoscopy-negative reflux disease, these associations did not persist in a multiple-adjustment model. After adjustment for gender, BMI, smoking, and hiatal hernia, a decrease in serum pepsinogen I/II ratio was significantly associated with an increased OR for endoscopy-negative reflux disease (p for trend = 0.018). Female gender, low BMI, not smoking, absence of hiatal hernia, and severity of gastric atrophy were positively associated with endoscopy-negative reflux disease compared with erosive esophagitis among Japanese patients.

Rethinking the bile acid/gut microbiome axis in cancer

PubMed Central

Phelan, John P.; Reen, F. Jerry; Caparros-Martin, Jose A.; O'Connor, Rosemary; O'Gara, Fergal

2017-01-01

Dietary factors, probiotic agents, aging and antibiotics/medicines impact on gut microbiome composition leading to disturbances in localised microbial populations. The impact can be profound and underlies a plethora of human disorders, including the focus of this review; cancer. Compromised microbiome populations can alter bile acid signalling and produce distinct pathophysiological bile acid profiles. These in turn have been associated with cancer development and progression. Exposure to high levels of bile acids, combined with localised molecular/genome instability leads to the acquisition of bile mediated neoplastic alterations, generating apoptotic resistant proliferation phenotypes. However, in recent years, several studies have emerged advocating the therapeutic benefits of bile acid signalling in suppressing molecular and phenotypic hallmarks of cancer progression. These studies suggest that in some instances, bile acids may reduce cancer phenotypic effects, thereby limiting metastatic potential. In this review, we contextualise the current state of the art to propose that the bile acid/gut microbiome axis can influence cancer progression to the extent that classical in vitro cancer hallmarks of malignancy (cell invasion, cell migration, clonogenicity, and cell adhesion) are significantly reduced. We readily acknowledge the existence of a bile acid/gut microbiome axis in cancer initiation, however, in light of recent advances, we focus exclusively on the role of bile acids as potentially beneficial molecules in suppressing cancer progression. Finally, we theorise that suppressing aggressive malignant phenotypes through bile acid/gut microbiome axis modulation could uncover new and innovative disease management strategies for managing cancers in vulnerable cohorts. PMID:29383197

Comparison of the composition of bile acids in bile of patients with adenocarcinoma of the pancreas and benign disease.

PubMed

Rees, David O; Crick, Peter J; Jenkins, Gareth J; Wang, Yuqin; Griffiths, William J; Brown, Tim H; Al-Sarireh, Bilal

2017-11-01

Bile acids have been implicated in the development of gastrointestinal malignancies. Both the specific nature of individual bile acids and their concentration appear key factors in the carcinogenic potency of bile. Using liquid chromatography mass spectrometry (LC-MS) we performed quantitative profiling of bile extracted directly from the common bile duct in 30 patients (15 patients with pancreatic cancer and 15 patients with benign disease). Separation and detection of bile acids was performed using a 1.7μm particle size reversed-phase C 18 LC column at a flow rate of 200μL/min with negative electrospray ionization MS. A significant difference (p=0.018) was seen in the concentration of unconjugated cholic acid in the malignant group (0.643mmol/L) compared to the benign group (0.022mmol/L), with an overall significant difference (p=0.04) seen in the level of total unconjugated bile acids in the malignant group (1.816mmol/L) compared to the benign group (0.069mmol/L). This finding may offer the possibility of both understanding the biology of cancer development in the pancreas, as well as offering a potential diagnostic avenue to explore. However, a larger study is necessary to confirm the alterations in bile acid profiles reported here and explore factors such as diet and microbial populations on the bile acid profiles of these patient groups. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Pluronic®-bile salt mixed micelles.

PubMed

Patel, Vijay; Ray, Debes; Bahadur, Anita; Ma, Junhe; Aswal, V K; Bahadur, Pratap

2018-06-01

The present study was aimed to examine the interaction of two bile salts viz. sodium cholate (NaC) and sodium deoxycholate (NaDC) with three ethylene polyoxide-polypropylene polyoxide (PEO-PPO-PEO) triblock copolymers with similar PPO but varying PEO micelles with a focus on the effect of pH on mixed micelles. Mixed micelles of moderately hydrophobic Pluronic ® P123 were examined in the presence of two bile salts and compared with those from very hydrophobic L121 and very hydrophilic F127. Both the bile salts increase the cloud point (CP) of copolymer solution and decreased apparent micelle hydrodynamic diameter (D h ). SANS study revealed that P123 forms small spherical micelles showing a decrease in size on progressive addition of bile salts. The negatively charged mixed micelles contained fewer P123 molecules but progressively rich in bile salt. NaDC being more hydrophobic displays more pronounced effect than NaC. Interestingly, NaC shows micellar growth in acidic media which has been attributed to the formation of bile acids by protonation of carboxylate ion and subsequent solubilization. In contrast, NaDC showed phase separation at higher concentration. Nuclear Overhauser effect spectroscopy (NOESY) experiments provided information on interaction and location of bile salts in micelles. Results are discussed in terms of hydrophobicity of bile salts and Pluronics ® and the site of bile salt in polymer micelles. Proposed molecular interactions are useful to understand more about bile salts which play important role in physiological processes. Copyright © 2018 Elsevier B.V. All rights reserved.

Inhibition of buckwheat starch digestion by the formation of starch/bile salt complexes: possibility of its occurrence in the intestine.

PubMed

Takahama, Umeo; Hirota, Sachiko

2011-06-08

During the digestion of starch in foods, starch is mixed with bile in the duodenum. Because fatty acids and some kinds of polyphenols could bind to starch, it was postulated that bile salts might also bind to starch. The purpose of this paper is to study the effects of bile and bile salts on starch/iodine complex formation and pancreatin-induced starch digestion. Bile suppressed starch/iodine complex formation and inhibited pancreatin-induced starch digestion slightly in control buckwheat starch, but did so significantly in buckwheat starch from which fatty acids and polyphenols had been extracted. Such significant suppression and inhibition by bile were also observed in a reagent soluble starch. The effects of cholate and taurocholate on the starch/iodine complex formation and the pancreatin-induced starch digestion were essentially the same as those of bile. Bile, cholate, and taurocholate suppressed amylose/iodine complex formation more significantly than amylopectin/iodine complex formation and inhibited pancreatin-induced amylose digestion more effectively than the digestion of amylopectin. It is concluded from the results that bile salts could bind to starch, especially amylose, the helical structures of which were not occupied by other molecules such as fatty acids and polyphenols, and that the binding resulted in the inhibition of starch digestion by pancreatin. The conclusion suggests that the function of bile salts can be discussed from the point of not only lipid digestion but also starch digestion.

Reconstruction of Bile Duct Injury and Defect with the Round Ligament.

PubMed

Dokmak, Safi; Aussilhou, Béatrice; Ragot, Emilia; Tantardini, Camille; Cauchy, François; Ponsot, Philippe; Belghiti, Jacques; Sauvanet, Alain; Soubrane, Olivier

2017-09-01

Lateral injury of the bile duct can occur after cholecystectomy, bile duct dissection, or exploration. If direct repair is not possible, conversion to bilioenteric anastomosis can be needed with the risk of long-term bile duct infections and associated complications. We developed a new surgical technique which consist of reconstructing the bile duct with the round ligament. The vascularized round ligament is completely mobilized until its origin and used for lateral reconstruction of the bile duct to cover the defect. T tube was inserted and removed after few months. Patency of the bile duct was assessed by cholangiography, the liver function test and magnetic resonance imaging (MRI). Two patients aged 33 and 59 years old underwent lateral reconstruction of the bile duct for defects secondary to choledocotomy for stone extraction or during dissection for Mirizzi syndrome. The defects measured 2 and 3 cm and occupied half of the bile duct circumference. The postoperative course was marked by low output biliary fistula resolved spontaneously. In one patient, the T tube was removed at 3 months after surgery and MRI at 9 months showed strictly normal aspect of the bile duct with normal liver function test. The second patient is going very well 2 months after surgery and the T tube is closed. Lateral reconstruction of the bile duct can be safely achieved with the vascularized round ligament. We will extend our indications to tubular reconstruction.

Altered Bile Acid Metabolome in Patients with Nonalcoholic Steatohepatitis.

PubMed

Ferslew, Brian C; Xie, Guoxiang; Johnston, Curtis K; Su, Mingming; Stewart, Paul W; Jia, Wei; Brouwer, Kim L R; Barritt, A Sidney

2015-11-01

The prevalence of nonalcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) is increasing at an alarming rate. The role of bile acids in the development and progression of NAFLD to NASH and cirrhosis is poorly understood. This study aimed to quantify the bile acid metabolome in healthy subjects and patients with non-cirrhotic NASH under fasting conditions and after a standardized meal. Liquid chromatography tandem mass spectroscopy was used to quantify 30 serum and 16 urinary bile acids from 15 healthy volunteers and 7 patients with biopsy-confirmed NASH. Bile acid concentrations were measured at two fasting and four post-prandial time points following a high-fat meal to induce gallbladder contraction and bile acid reabsorption from the intestine. Patients with NASH had significantly higher total serum bile acid concentrations than healthy subjects under fasting conditions (2.2- to 2.4-fold increase in NASH; NASH 2595-3549 µM and healthy 1171-1458 µM) and at all post-prandial time points (1.7- to 2.2-fold increase in NASH; NASH 4444-5898 µM and healthy 2634-2829 µM). These changes were driven by increased taurine- and glycine-conjugated primary and secondary bile acids. Patients with NASH exhibited greater variability in their fasting and post-prandial bile acid profile. Results indicate that patients with NASH have higher fasting and post-prandial exposure to bile acids, including the more hydrophobic and cytotoxic secondary species. Increased bile acid exposure may be involved in liver injury and the pathogenesis of NAFLD and NASH.

The toxicological significance of post-mortem drug concentrations in bile.

PubMed

Ferner, Robin E; Aronson, Jeffrey K

2018-01-01

Some authors have proposed that post-mortem drug concentrations in bile are useful in estimating concentrations in blood. Both The International Association of Forensic Toxicologists (TIAFT) and the US Federal Aviation Administration recommend that samples of bile should be obtained in some circumstances. Furthermore, standard toxicological texts compare blood and bile concentrations, implying that concentrations in bile are of forensic value. To review the evidence on simultaneous measurements of blood and bile drug concentrations reported in the medical literature. We made a systematic search of EMBASE 1980-2016 using the search terms ("bile/" OR "exp drug bile level/concentration/") AND "drug blood level/concentration/", PubMed 1975-2017 for ("bile[tw]" OR "biliary[tw]") AND ("concentration[tw]" OR "concentrations[tw]" OR "level[tw]" OR "levels[tw]") AND "post-mortem[tw]" and also MEDLINE 1990-2016 for information on drugs whose biliary concentrations were mentioned in standard textbooks. The search was limited to human studies without language restrictions. We also examined recent reviews, indexes of relevant journals and citations in Web of Science and Google Scholar. We calculated the bile:blood concentration ratio. The searches together yielded 1031 titles with abstracts. We scanned titles and abstracts for relevance and retrieved 230, of which 161 were considered further. We excluded 49 papers because: the paper reported only one case (30 references); the data referred only to a metabolite (1); the work was published before 1980 (3); the information concerned only samples taken during life (10); or the paper referred to a toxin or unusual recreational drug (5). The remaining 112 papers provided data for analysis, with at least two observations for each of 58 drugs. Bile:blood concentration ratios: Median bile:blood concentration ratios varied from 0.18 (range 0.058-0.32) for dextromoramide to 520 (range 0.62-43,000) for buprenorphine. Median bile concentrations exceeded blood concentrations by one order of magnitude for several drugs, including dihydrocodeine, quetiapine and sildenafil; and by two orders of magnitude of for buprenorphine, colchicine and 3,4-methylenedioxy-methamphetamine (MDMA), among others. The minimum and maximum values for the ratio differed by a factor of three or more in three-quarters of the cases where data were available and by a factor of 10 or more for over half of the analytes. The data were difficult to find. Medline does not explicitly index the term "drug bile concentration". It may well be that other reports exist, although they would not alter our major conclusion. Many of the papers that contributed data failed to specify the source of the blood samples or the post-mortem interval, so that no judgment was possible regarding post-mortem redistribution in whole blood or bile. For most drugs, there are wide ranges of bile:blood concentration ratios, which means that bile and blood concentrations are generally poorly correlated. Bile concentration measurements cannot readily be used to establish post-mortem blood concentrations; nor can they be extrapolated to ante-mortem concentrations. However, because drug concentrations in bile often exceed those in blood, bile may allow qualitative identification of drugs present, even when the blood concentration is below the limit of detection.

Persistent gastro-oesophageal reflux symptoms despite proton pump inhibitor therapy

PubMed Central

Ang, Daphne; How, Choon How; Ang, Tiing Leong

2016-01-01

About one-third of patients with suspected gastro-oesophageal reflux disease (GERD) do not respond symptomatically to proton pump inhibitors (PPIs). Many of these patients do not suffer from GERD, but may have underlying functional heartburn or atypical chest pain. Other causes of failure to respond to PPIs include inadequate acid suppression, non-acid reflux, oesophageal hypersensitivity, oesophageal dysmotility and psychological comorbidities. Functional oesophageal tests can exclude cardiac and structural causes, as well as help to confi rm or exclude GERD. The use of PPIs should only be continued in the presence of acid reflux or oesophageal hypersensitivity for acid reflux-related events that is proven on functional oesophageal tests. PMID:27779277

Persistent gastro-oesophageal reflux symptoms despite proton pump inhibitor therapy.

PubMed

Ang, Daphne; How, Choon How; Ang, Tiing Leong

2016-10-01

About one-third of patients with suspected gastro-oesophageal reflux disease (GERD) do not respond symptomatically to proton pump inhibitors (PPIs). Many of these patients do not suffer from GERD, but may have underlying functional heartburn or atypical chest pain. Other causes of failure to respond to PPIs include inadequate acid suppression, non-acid reflux, oesophageal hypersensitivity, oesophageal dysmotility and psychological comorbidities. Functional oesophageal tests can exclude cardiac and structural causes, as well as help to confi rm or exclude GERD. The use of PPIs should only be continued in the presence of acid reflux or oesophageal hypersensitivity for acid reflux-related events that is proven on functional oesophageal tests. Copyright: © Singapore Medical Association.

In vivo multiphoton imaging of bile duct ligation

NASA Astrophysics Data System (ADS)

Liu, Yuan; Li, Feng-Chieh; Chen, Hsiao-Chin; Chang, Po-shou; Yang, Shu-Mei; Lee, Hsuan-Shu; Dong, Chen-Yuan

2008-02-01

Bile is the exocrine secretion of liver and synthesized by hepatocytes. It is drained into duodenum for the function of digestion or drained into gallbladder for of storage. Bile duct obstruction is a blockage in the tubes that carry bile to the gallbladder and small intestine. However, Bile duct ligation results in the changes of bile acids in serum, liver, urine, and feces1, 2. In this work, we demonstrate a novel technique to image this pathological condition by using a newly developed in vivo imaging system, which includes multiphoton microscopy and intravital hepatic imaging chamber. The images we acquired demonstrate the uptake, processing of 6-CFDA in hepatocytes and excretion of CF in the bile canaliculi. In addition to imaging, we can also measure kinetics of the green fluorescence intensity.

Bile acid malabsorption investigated by selenium-75-homocholic acid taurine ((75)SeHCAT) scans: causes and treatment responses to cholestyramine in 298 patients with chronic watery diarrhoea.

PubMed

Borghede, Märta K; Schlütter, Jacob M; Agnholt, Jørgen S; Christensen, Lisbet A; Gormsen, Lars C; Dahlerup, Jens F

2011-12-01

The liver produces and secretes bile acids into the small intestine. In the small intestine, most of the bile acids are absorbed in the distal ileum with portal vein transportation back to the liver and resecretion (enterohepatic recycling). Increased spillover of bile acids from the small intestine into the colon (bile acid malabsorption) may affect the secretion of colonic water and electrolytes and result in watery diarrhoea. The aim of this study was to investigate the frequency of bile acid malabsorption and treatment responses to cholestyramine with (75)SeHCAT scanning among patients suffering from chronic watery diarrhoea. This was a retrospective study that included all patients who received a (75)SeHCAT scan over a five-year period (2004-2009). In total, 298 patients (198 females, 100 men) with a median age of 42 years (range 16-82 years) were investigated. Bile acid malabsorption ((75)SeHCAT retention<15% after seven days) was identified in 201 patients (68%, 95% confidence interval (CI): 62%-73%). Bile acid malabsorption due to ileal dysfunction (Type I) was found in 77 patients, idiopathic bile acid malabsorption (Type II) was found in 68 patients and 56 patients with other conditions had bile acid malabsorption (Type III). Of the 150 patients who were able to take cholestyramine continuously, 108 patients (71%, CI: 63%-78%) reported a positive effect on their bowel habits. Bile acid malabsorption is a frequent problem in patients with chronic watery diarrhoea. Treatment with bile acid binders was effective regardless of type and severity. Copyright © 2011 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

Analysis of Shigella flexneri Resistance, Biofilm Formation, and Transcriptional Profile in Response to Bile Salts

PubMed Central

Nickerson, Kourtney P.; Chanin, Rachael B.; Sistrunk, Jeticia R.; Fink, Peter J.; Barry, Eileen M.; Nataro, James P.

2017-01-01

ABSTRACT The Shigella species cause millions of cases of watery or bloody diarrhea each year, mostly in children in developing countries. While many aspects of Shigella colonic cell invasion are known, crucial gaps in knowledge regarding how the bacteria survive, transit, and regulate gene expression prior to infection remain. In this study, we define mechanisms of resistance to bile salts and build on previous research highlighting induced virulence in Shigella flexneri strain 2457T following exposure to bile salts. Typical growth patterns were observed within the physiological range of bile salts; however, growth was inhibited at higher concentrations. Interestingly, extended periods of exposure to bile salts led to biofilm formation, a conserved phenotype that we observed among members of the Enterobacteriaceae. Characterization of S. flexneri 2457T biofilms determined that both bile salts and glucose were required for formation, dispersion was dependent upon bile salts depletion, and recovered bacteria displayed induced adherence to HT-29 cells. RNA-sequencing analysis verified an important bile salt transcriptional profile in S. flexneri 2457T, including induced drug resistance and virulence gene expression. Finally, functional mutagenesis identified the importance of the AcrAB efflux pump and lipopolysaccharide O-antigen synthesis for bile salt resistance. Our data demonstrate that S. flexneri 2457T employs multiple mechanisms to survive exposure to bile salts, which may have important implications for multidrug resistance. Furthermore, our work confirms that bile salts are important physiological signals to activate S. flexneri 2457T virulence. This work provides insights into how exposure to bile likely regulates Shigella survival and virulence during host transit and subsequent colonic infection. PMID:28348056

Ablating L-FABP in SCP-2/SCP-x null mice impairs bile acid metabolism and biliary HDL-cholesterol secretion.

PubMed

Martin, Gregory G; Atshaves, Barbara P; Landrock, Kerstin K; Landrock, Danilo; Storey, Stephen M; Howles, Philip N; Kier, Ann B; Schroeder, Friedhelm

2014-12-01

On the basis of their abilities to bind bile acids and/or cholesterol, the physiological role(s) of liver fatty acid-binding protein (L-FABP) and sterol carrier protein (SCP) 2/SCP-x (SCP-2/SCP-x) gene products in biliary bile acid and cholesterol formation was examined in gene-ablated male mice. L-FABP (LKO) or L-FABP/SCP-2/SCP-x [triple-knockout (TKO)] ablation markedly decreased hepatic bile acid concentration, while SCP-2/SCP-x [double-knockout (DKO)] ablation alone had no effect. In contrast, LKO increased biliary bile acid, while DKO and TKO had no effect on biliary bile acid levels. LKO and DKO also altered biliary bile acid composition to increase bile acid hydrophobicity. Furthermore, LKO and TKO decreased hepatic uptake and biliary secretion of high-density lipoprotein (HDL)-derived 22-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-23,24-bisnor-5-cholen-3β-ol (NBD-cholesterol), while DKO alone had no effect. Finally, LKO and, to a lesser extent, DKO decreased most indexes contributing to cholesterol solubility in biliary bile. These results suggest different, but complementary, roles for L-FABP and SCP-2/SCP-x in biliary bile acid and cholesterol formation. L-FABP appears to function more in hepatic retention of bile acids as well as hepatic uptake and biliary secretion of HDL-cholesterol. Conversely, SCP-2/SCP-x may function more in formation and biliary secretion of bile acid, with less impact on hepatic uptake or biliary secretion of HDL-cholesterol. Copyright © 2014 the American Physiological Society.

Bile Stress Response in Listeria monocytogenes LO28: Adaptation, Cross-Protection, and Identification of Genetic Loci Involved in Bile Resistance

PubMed Central

Begley, Máire; Gahan, Cormac G. M.; Hill, Colin

2002-01-01

Bile is one of many barriers that Listeria monocytogenes must overcome in the human gastrointestinal tract in order to infect and cause disease. We demonstrated that stationary-phase cultures of L. monocytogenes LO28 were able to tolerate concentrations of bovine, porcine, and human bile and bile acids well in excess of those encountered in vivo. Strain LO28 was relatively bile resistant compared with other clinical isolates of L. monocytogenes, as well as with Listeria innocua, Salmonella enterica serovar Typhimurium LT2, and Lactobacillus sakei. While exponential-phase L. monocytogenes LO28 cells were exquisitely sensitive to unconjugated bile acids, prior adaptation to sublethal levels of bile acids or heterologous stresses, such as acid, heat, salt, or sodium dodecyl sulfate (SDS), significantly enhanced bile resistance. This adaptive response was independent of protein synthesis, and in the cases of bile and SDS adaptation, occurred in seconds. In order to identify genetic loci involved in the bile tolerance phenotype of L. monocytogenes LO28, transposon (Tn917) and plasmid (pORI19) integration banks were screened for bile-sensitive mutants. The disrupted genes included a homologue of the capA locus required for capsule formation in Bacillus anthracis; a gene encoding the transcriptional regulator ZurR; a homologue of an Escherichia coli gene, lytB, involved in isoprenoid biosynthesis; a gene encoding a homologue of the Bacillus subtilis membrane protein YxiO; and a gene encoding an amino acid transporter with a putative role in pH homeostasis, gadE. Interestingly, all of the identified loci play putative roles in maintenance of the cell envelope or in stress responses. PMID:12450822

Predicting Infected Bile Among Patients Undergoing Percutaneous Cholecystostomy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Beardsley, Shannon L.; Shlansky-Goldberg, Richard D.; Patel, Aalpen

2005-04-15

Purpose. Patients may not achieve a clinical benefit after percutaneous cholecystostomy due to the inherent difficulty in identifying patients who truly have infected gallbladders. We attempted to identify imaging and biochemical parameters which would help to predict which patients have infected gallbladders. Methods. A retrospective review was performed of 52 patients undergoing percutaneous cholecystostomy for clinical suspicion of acute cholecystitis in whom bile culture results were available. Multiple imaging and biochemical variables were examined alone and in combination as predictors of infected bile, using logistic regression. Results. Of the 52 patients, 25 (48%) had infected bile. Organisms cultured included Enterococcus,more » Enterobacter, Klebsiella, Pseudomonas, E. coli, Citrobacter and Candida. No biochemical parameters were significantly predictive of infected bile; white blood cell count >15,000 was weakly associated with greater odds of infected bile (odds ratio 2.0, p = NS). The presence of gallstones, sludge, gallbladder wall thickening and pericholecystic fluid by ultrasound or CT were not predictive of infected bile, alone or in combination, although a trend was observed among patients with CT findings of acute cholecystitis toward a higher 30-day mortality. Radionuclide scans were performed in 31% of patients; all were positive and 66% of these patients had infected bile. Since no patient who underwent a radionuclide scan had a negative study, this variable could not be entered into the regression model due to collinearity. Conclusion. No single CT or ultrasound imaging variable was predictive of infected bile, and only a weak association of white blood cell count with infected bile was seen. No other biochemical parameters had any association with infected bile. The ability of radionuclide scanning to predict infected bile was higher than that of ultrasound or CT. This study illustrates the continued challenge to identify bacterial cholecystitis among patients referred for percutaneous cholecystostomy.« less

Endoscopic and laparoscopic treatment of gastroesophageal reflux.

PubMed

Watson, David I; Immanuel, Arul

2010-04-01

Gastroesophageal reflux is extremely common in Western countries. For selected patients, there is an established role for the surgical treatment of reflux, and possibly an emerging role for endoscopic antireflux procedures. Randomized trials have compared medical versus surgical management, laparoscopic versus open surgery and partial versus total fundoplications. However, the evidence base for endoscopic procedures is limited to some small sham-controlled studies, and cohort studies with short-term follow-up. Laparoscopic fundoplication has been shown to be an effective antireflux operation. It facilitates quicker convalescence and is associated with fewer complications, but has a similar longer term outcome compared with open antireflux surgery. In most randomized trials, antireflux surgery achieves at least as good control of reflux as medical therapy, and these studies support a wider application of surgery for the treatment of moderate-to-severe reflux. Laparoscopic partial fundoplication is an effective surgical procedure with fewer side effects, and it may achieve high rates of patient satisfaction at late follow-up. Many of the early endoscopic antireflux procedures have failed to achieve effective reflux control, and they have been withdrawn from the market. Newer procedures have the potential to fashion a surgical fundoplication. However, at present there is insufficient evidence to establish the safety and efficacy of endoscopic procedures for the treatment of gastroesophageal reflux, and no endoscopic procedure has achieved equivalent reflux control to that achieved by surgical fundoplication.

Pattern of food intolerance in patients with gastro-esophageal reflux symptoms.

PubMed

Caselli, Michele; Lo Cascio, Natalina; Rabitti, Stefano; Eusebi, Leonardo H; Zeni, Elena; Soavi, Cecilia; Cassol, Francesca; Zuliani, Giovanni; Zagari, Rocco M

2017-12-01

Many food items have been involved in gastro-esophageal reflux disease pathogenesis and dietary modification has been proposed as first-line treatment. Test-based exclusion diets have shown to significantly reduce reflux symptoms. We aimed to assess the patterns of food intolerance in a series of patients with typical gastro-esophageal reflux symptoms (GERS). We retrospectively evaluated all patients with typical reflux symptoms, attending the Centre Study Association on Food Intolerance and Nutrition of Ferrara from January 2010 to October 2015, who resulted positive to at least one food item at the Leucocytotoxic Test. The presence and severity of typical GERS (heartburn and/or acid regurgitation) were assessed using the Gastro-esophageal Reflux Disease Impact Scale (GIS) questionnaire. Only individuals with a GIS Score of at least 5 points were included. Almost all patients (91.1%) were intolerant to at least 5 food items. The most frequent food intolerance (more than 33% of patients) were found for milk (55.4%), lettuce (46.4%), coffee (43.7%), brewer's yeast (42.9%), pork (42.9%), tuna (37.5%), rice (35.7%), sole (34.8%), asparagus (34.8%) and eggs (33.9%). Nine different clusters of food intolerance were detected. Patients with typical gastro-esophageal reflux symptoms seem to have intolerance to multiple food items, some of which (lettuce, brewer's yeast, tuna, rice, sole and asparagus) have not yet been associated to gastro-esophageal reflux disease.

Gastroesophageal Reflux Management with the LINX® System for Gastroesophageal Reflux Disease Following Laparoscopic Sleeve Gastrectomy.

PubMed

Desart, Kenneth; Rossidis, Georgios; Michel, Michael; Lux, Tamara; Ben-David, Kfir

2015-10-01

Laparoscopic sleeve gastrectomy (LSG) has gained significant popularity in the USA, and consequently resulted in patients experiencing new-onset gastroesophageal reflux disease (GERD) following this bariatric procedure. Patients with GERD refractory to medical therapy present a more challenging situation limiting the surgical options to further treat the de novo GERD symptoms since the gastric fundus to perform a fundoplication is no longer an option. The aim of this study is to determine if the LINX® magnetic sphincter augmentation system is a safe and effective option for patients with new gastroesophageal reflux disease following laparoscopic sleeve gastrectomy. This study was conducted at the University Medical Center. This is a retrospective review of seven consecutive patients who had a laparoscopic LINX® magnetic sphincter device placement for patients with refractory gastroesophageal reflux disease after laparoscopic sleeve gastrectomy between July 2014 and April 2015. All patients were noted to have self-reported greatly improved gastroesophageal reflux symptoms 2-4 weeks after their procedure. They were all noted to have statistically significant improved severity and frequency of their reflux, regurgitation, epigastric pain, sensation of fullness, dysphagia, and cough symptoms in their postoperative GERD symptoms compared with their preoperative evaluation. This is the first reported pilot case series, illustrating that the LINX® device is a safe and effective option in patients with de novo refractory gastroesophageal reflux disease after a laparoscopic sleeve gastrectomy despite appropriate weight loss.

Risk Factors for Helicobacter pylori Infection and Endoscopic Reflux Esophagitis in Healthy Young Japanese Volunteers.

PubMed

Tanaka, Yuichiro; Sakata, Yasuhisa; Hara, Megumi; Kawakubo, Hiroharu; Tsuruoka, Nanae; Yamamoto, Koji; Itoh, Yoichiro; Hidaka, Hidenori; Shimoda, Ryo; Iwakiri, Ryuichi; Fujimoto, Kazuma

2017-11-15

Objective The aim of this study was to determine the prevalence and risk factors of reflux esophagitis and Helicobacter pylori (H.pylori) infection and their interrelationship in healthy young Japanese volunteers. Methods Between 2010 and 2016, 550 fifth-year medical students at Saga Medical School, aged 22 to 30 years, underwent upper gastrointestinal endoscopy and completed a questionnaire (frequency scale for symptoms of gastroesophageal reflux disease). H. pylori infection was determined by detecting urinary immunoglobulin G antibodies. Results H. pylori antibodies were detected in 45 of the 550 subjects (8.2%). Endoscopic reflux esophagitis was detected in 38 out of 550 (6.9%): grade A in 37 subjects (97.3%) and grade B in 1. Most subjects with reflux esophagitis were H. pylori-negative (35/37). Nodular gastritis was observed in 33.3% (15/45) of H. pylori-positive subjects. The risk factors for H. pylori infection were drinking well water in childhood, nodular gastritis, and duodenal ulcer scars. The risk factors for endoscopic reflux esophagitis were male gender and obesity (body mass index ≥25). Conclusion This study describes the risk factors for H. pylori infection and reflux esophagitis in healthy young Japanese subjects. The prevalence of reflux esophagitis was relatively high, and the infection rate of H. pylori was low compared with the aged Japanese population.

Preoperative endoscopy may reduce the need for revisional surgery for gastro-oesophageal reflux disease following laparoscopic sleeve gastrectomy.

PubMed

Madhok, B M; Carr, W R J; McCormack, C; Boyle, M; Jennings, N; Schroeder, N; Balupuri, S; Small, P K

2016-08-01

Laparoscopic sleeve gastrectomy is a safe and effective bariatric operation, but postoperative reflux symptoms can sometimes necessitate revisional surgery. Roux-en-Y gastric bypass is the preferred operation in morbidly obese patients with gastro-oesophageal reflux disease. In 2011, we introduced preoperative endoscopy to assess for hiatus hernia or evidence of oesophagitis in conjunction with an assessment of gastro-oesophageal reflux symptoms for all patients undergoing bariatric surgery with a view to avoid sleeve gastrectomy for these patients. A prospectively maintained database was used to identify patients who underwent sleeve gastrectomy before and after we changed the unit policy. The need for revisional surgery in patients with troublesome gastro-oesophageal reflux disease was examined. Prior to 2011, 130 patients underwent sleeve gastrectomy, and 11 (8.5%) of them required conversion to Roux-en-Y gastric bypass for symptomatic reflux disease. Following the policy change, 284 patients underwent sleeve gastrectomy, and to date, only five (1.8%) have required revisional surgery (p = 0.001). Baseline demographics were comparable between the groups, and average follow-up period was 47 and 33 months, respectively, for each group. Preoperative endoscopy and a detailed clinical history regarding gastro-oesophageal reflux symptoms may improve patient selection for sleeve gastrectomy. Avoiding sleeve gastrectomy in patients with reflux disease and/or hiatus hernia may reduce the incidence of revisional surgery. © 2016 World Obesity.

Clinical features and prevalence of gastroesophageal reflux disease in infants attending a pediatric gastroenterology reference service.

PubMed

Koda, Yu Kar Ling; Ozaki, Marcos J; Murasca, Kelly; Vidolin, Eliana

2010-01-01

In infants, it is not always easy to distinguish between pathological and physiological gastroesophageal reflux based only on clinical criteria. In Brazil, studies about gastroesophageal reflux disease in infants are few and are even rare those that used prolonged esophageal pH monitoring for its evaluation. To describe the clinical features of gastroesophageal reflux disease and to determine its prevalence in infants with gastroesophageal reflux attending a tertiary Pediatric Gastroenterology Service and submitted to esophageal pH monitoring for investigation. Descriptive study in 307 infants in whom esophageal pH monitoring (Mark III Digitrapper, Synectics Medical AB, Sweden) was performed during the period December, 1998-December, 2008. The clinical features studied were age group (1-12 months and 13-24 months), and clinical manifestations that motivated the indication of pH monitoring. One hundred twenty-four (40.4%) were female and 183 (59.6%) male with mean age 12.2 +/- 6.2 months (1-23 months). The prevalence of gastroesophageal reflux disease was 18.2% (56/307). One hundred forty-eight (48.2%) were 1-12 months old and 159 (51.8%), 13-24 months. No significant difference was found between the prevalence of these two age groups (P = 0.3006). Gastroesophageal reflux disease was more frequent in those with digestive manifestations (24.2%), crisis of cyanosis/apnea (23.8%) and mixed manifestations (21.5%). Respiratory manifestations were the most frequent indication (39.1%) of pH monitoring. However, the prevalence of gastroesophageal reflux disease was lower (12.5%) in this group compared with in those with digestive manifestations (P = 0.0574), crisis of cyanosis/apnea (P = 0.0882) and mixed manifestations (P = 0.1377). All infants that presented clinical manifestations as crisis of cyanosis/apnea and abnormal pH-metry were < 3 months of age. In our Service, the prevalence of gastroesophageal reflux disease associated with acid reflux in infants revealed elevated. Infants with crisis of cyanosis/apnea constitute risk population for gastroesophageal reflux disease in which diagnostic investigation needs to be considered.

Increased prandial air swallowing and postprandial gas-liquid reflux among patients refractory to proton pump inhibitor therapy.

PubMed

Bravi, Ivana; Woodland, Philip; Gill, Ravinder S; Al-Zinaty, Mohannad; Bredenoord, Albert J; Sifrim, Daniel

2013-07-01

Many patients with gastroesophageal reflux disease (GERD) have persistent reflux despite treatment with proton pump inhibitors (PPIs). Mixed gas-liquid reflux events are more likely to be perceived as symptomatic. We used esophageal impedance monitoring to investigate whether esophageal gas is processed differently among patients with GERD who do and do not respond to PPI therapy. We performed a prospective study of 44 patients with typical reflux symptoms with high levels of esophageal acid exposure during a 24-hour period; 18 patients were fully responsive, and 26 did not respond to PPI therapy. Twenty-four-hour pH impedance recordings were analyzed for fasting and prandial air swallows and reflux characteristics, including the presence of gas in the refluxate. PPI-refractory patients had a higher number (83.1 ± 12.7 vs 47.8 ± 7.3, P < .05) and rate (10.5 ± 1.4 vs 5.9 ± 0.8/10 minutes, P < .05) of prandial air swallows than patients who responded to PPI therapy; they also had a higher number (25.5 ± 4.0 vs 16.8 ± 3.3, P < .05) and proportion (70% ± 0.03% vs 54% ± 0.06%, P < .05) of postprandial, mixed gas-liquid reflux. Symptoms of PPI-refractory patients were more often preceded by mixed gas-liquid reflux events than those of PPI responders. Fasting air swallowing and other reflux characteristics did not differ between patients who did and did not respond to PPIs. Some patients with GERD who do not respond to PPI therapy swallow more air at mealtime than those who respond to PPIs and also have more reflux episodes that contain gas. These factors, combined with mucosal sensitization by previous exposure to acid, could affect perception of symptoms. These patients, who can be identified on standard 24-hour pH impedance monitoring, might be given behavioral therapy to reduce mealtime air swallowing. Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.

Incidence of gastroesophageal reflux disease and positive maxillary antral cultures in children with symptoms of chronic rhinosinusitis.

PubMed

Nation, Javan; Kaufman, Michael; Allen, Meredith; Sheyn, Anthony; Coticchia, James

2014-02-01

Studies have shown that gastroesophageal reflux disease occurs more frequently than expected in children with chronic rhinosinusitis. The objective of this study is to further understand the relationship of pediatric chronic rhinosinusitis and gastroesophageal reflux disease in children with symptoms of rhinorrhea, nasal congestion, and chronic cough. A retrospective chart review of 63 children, ages 6 months to 10 years old with rhinorrhea, nasal congestion, and chronic cough. The patients underwent maxillary cultures, adenoidectomy, and distal third esophageal biopsies. Children with esophageal biopsies showing esophagitis were classified as positive for gastroesophageal reflux disease, and maxillary antral swabs growing a high density of bacteria were classified as positive for chronic rhinosinusitis. Six months to 5 years old children (n=43), 6 (14%) had simultaneous positive maxillary antral cultures and positive esophageal biopsies, 11 (26%) had positive esophageal biopsies alone, 23 (53%) had positive maxillary antral cultures alone, and 3 (7%) had neither. Six to 10 years old children (n=20), 9 (45%) had simultaneous positive maxillary antral cultures and positive esophageal biopsies, 1 (5%) patient had positive esophageal biopsies alone, 3 (15%) patients had positive maxillary antral cultures alone, and 7 (35%) patients had neither. Twenty-seven (42%) of the patients from the whole study had gastroesophageal reflux positive biopsies. The younger children were statistically likely to have chronic rhinosinusitis and gastroesophageal reflux disease independently of each other (p=0.0002). A direct group comparison found the younger group to have independent chronic rhinosinusitis and gastroesophageal reflux disease and the older group to have simultaneous chronic rhinosinusitis and gastroesophageal reflux disease (p=0.0006). In children with the presenting symptoms of rhinorrhea, nasal congestion, and chronic cough, younger children tend to have either chronic rhinosinusitis or gastroesophageal reflux disease, whereas older children tend to have a more complicated etiology of chronic rhinosinusitis and gastroesophageal reflux disease or other. In all of these patients gastroesophageal reflux disease plays an important role, as over 40% of all patients had gastroesophageal positive biopsies. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

The comparative analyses of different diagnostic approaches in detection of gastroesophageal reflux disease in children

PubMed Central

Ristic, Nina; Milovanovic, Ivan; Radusinovic, Milica; Stevic, Marija; Ristic, Milos; Ristic, Maja; Kisic Tepavcevic, Darija; Alempijevic, Tamara

2017-01-01

Objectives The aim of this study was to compare the different diagnostic approaches in detection of gastroesophageal reflux disease in children presented with symptoms suggesting gastroesophageal reflux disease. Methods The study design was cross sectional. The study retrospectively included all children who underwent combined multiple intraluminal impedance and pH (pH-MII) monitoring due to gastrointestinal and/or extraesophageal symptoms suggesting gastroesophageal reflux disease at University Children's Hospital in Belgrade, from July 2012 to July 2016. Results A total of 218 (117 boys/101 girls), mean age 6.7 years (range 0.06–18.0 years), met the inclusion criteria. Gastroesophageal reflux disease was found in 128 of 218 children (57.4%) by pH-MII and in 76 (34.1%) children by pH metry alone. Using pH-MII monitoring as gold standard, sensitivity of pH-metry was lowest in infants (22.9%), with tendency to increase in older age groups (reaching 76.4% in children ≥ 9 years). The sensitivity of pH-metry alone in children with extraesophageal symptoms was 38.1%, while the sensitivity of pH-metry in children with gastrointestinal symptoms was 63.8%. Reflux esophagitis was identified in 31 (26.1%) of 119 children who underwent endoscopy. Logistic regression analysis showed that best predictors of endoscopic reflux esophagitis are the longest acid episode (OR = 1.52, p<0.05) and DeMeester reflux composite score (OR = 3.31, p<0.05). The significant cutoff values included DeMeester reflux composite score ≥ 29 (AUC 0.786, CI 0.695–0.877, p<0.01) and duration of longest acid reflux ≥ 18 minutes (AUC 0.784, CI 0.692–0.875, p<0.01). Conclusions The results of our study suggested that compared with pH-metry alone, pH-MII had significantly higher detection rate of gastroesophageal reflux disease, especially in infants. Our findings also showed that pH-MII parameters correlated significantly with the endoscopically confirmed erosive esophagitis. PMID:29095882

Effects of partial portal vein arterialization on the hilar bile duct in a rat model.

PubMed

Guo, Shao-Hua; Li, Chong-Hui; Chen, Yong-Liang; Song, Jian-Ning; Zhang, Ai-Qun; Zhou, Cheng

2011-10-01

Liver revascularization is frequently required during the enlarged radical operation for hilar cholangiocarcinoma involving the hepatic artery. Researchers have carried out a number of experiments applying partial portal vein arterialization (PVA) in clinical practice. In this study we aimed to establish a theoretical basis for clinical application of partial PVA and to investigate the effects of partial PVA on rat hilar bile duct and hepatic functions. Thirty rats were randomly and equally assigned into 3 groups: control (group A), hepatic artery ligation+bile duct recanalization (group B), and partial PVA+bile duct recanalization (group C). Proliferation and apoptosis of rat hilar bile duct epithelial cells, arteriolar counts of the peribiliary plexus (PBP) of the bile duct wall, changes in serum biochemistry, and pathologic changes in the bile duct were assessed 1 month after operation. The proliferation of hilar bile duct epithelial cells in group B was greater than in groups A and C (P<0.01). No apoptotic hilar bile duct epithelial cells were detected in any of the groups. The PBP arteriolar counts of the hilar bile duct wall were similar in groups A and C (P>0.05), but the count was lower in group B than in group A (P<0.01). No statistically significant differences in alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and albumin were found in the 3 groups. The gamma-glutamyltransferase value was higher in group B than in groups A and C (P<0.01). The hepatic tissues of groups A and C showed no significant abnormality. Chronic inflammatory changes in the hilar bile duct walls were observed only in group B. Partial PVA can restore the arterial blood supply of the hilar bile duct and significantly extenuate the injury to hilar bile duct epithelial cells resulting from hepatic artery ligation.

Integrated transcriptomic and proteomic analysis of the bile stress response in probiotic Lactobacillus salivarius LI01.

PubMed

Lv, Long-Xian; Yan, Ren; Shi, Hai-Yan; Shi, Ding; Fang, Dai-Qiong; Jiang, Hui-Yong; Wu, Wen-Rui; Guo, Fei-Fei; Jiang, Xia-Wei; Gu, Si-Lan; Chen, Yun-Bo; Yao, Jian; Li, Lan-Juan

2017-01-06

Lactobacillus salivarius LI01, isolated from healthy humans, has demonstrated probiotic properties in the prevention and treatment of liver failure. Tolerance to bile stress is crucial to allow lactobacilli to survive in the gastrointestinal tract and exert their benefits. In this work, we used a Digital Gene Expression transcriptomic and iTRAQ LC-MS/MS proteomic approach to examine the characteristics of LI01 in response to bile stress. Using culture medium with or without 0.15% ox bile, 591 differentially transcribed genes and 347 differentially expressed proteins were detected in LI01. Overall, we found the bile resistance of LI01 to be based on a highly remodeled cell envelope and a reinforced bile efflux system rather than on the activity of bile salt hydrolases. Additionally, some differentially expressed genes related to regulatory systems, the general stress response and central metabolism processes, also play roles in stress sensing, bile-induced damage prevention and energy efficiency. Moreover, bile salts appear to enhance proteolysis and amino acid uptake (especially aromatic amino acids) by LI01, which may support the liver protection properties of this strain. Altogether, this study establishes a model of global response mechanism to bile stress in L. salivarius LI01. L. salivarius strain LI01 exhibits not only antibacterial and antifungal properties but also exerts a good health-promoting effect in acute liver failure. As a potential probiotic strain, the bile-tolerance trait of strain LI01 is important, though this has not yet been explored. In this study, an analysis based on DGE and iTRAQ was performed to investigate the gene expression in strain LI01 under bile stress at the mRNA and protein levels, respectively. To our knowledge, this work also represents the first combined transcriptomic and proteomic analysis of the bile stress response mechanism in L. salivarius. Copyright © 2016. Published by Elsevier B.V.

The utility of 5-aminolevulinic acid-mediated photodynamic diagnosis in the detection of intraoperative bile leakage.

PubMed

Inoue, Yoshihiro; Imai, Yoshiro; Fujii, Kensuke; Hirokawa, Fumitoshi; Hayashi, Michihiro; Uchiyama, Kazuhisa

2017-06-01

The purpose of this retrospective study was to evaluate the utility of the new intraoperative bile leakage test as a preventive measure of postoperative bile leakage. 737 patients were retrospectively analyzed with respect to the management of intra- and post-operative bile leakage. Nine (8.3%) of 109 patients evaluated using conventional white light fluorescent imaging were recognized as having intra-operative bile leakage. However, performance of 5-aminolevulinic acid (5-ALA)-mediated PDD detected bile leakage intraoperatively not only in these 9 patients, but also in an additional 6 patients, such that 'red fluorescence' at the cut surface of the liver, was visualized in a total of 15 patients. The postoperative courses of most patients were uneventful, and postoperative bile leakages occurred in only one (0.9%) patient. 5-ALA fluorescence imaging may be needed to prevent postoperative bile leakage in patients at high risk for this surgical complication after hepatic resection. Copyright © 2016 Elsevier Inc. All rights reserved.

Taurocholic acid metabolism by gut microbes and colon cancer

PubMed Central

Ridlon, Jason M.; Wolf, Patricia G.; Gaskins, H. Rex

2016-01-01

ABSTRACT Colorectal cancer (CRC) is one of the most frequent causes of cancer death worldwide and is associated with adoption of a diet high in animal protein and saturated fat. Saturated fat induces increased bile secretion into the intestine. Increased bile secretion selects for populations of gut microbes capable of altering the bile acid pool, generating tumor-promoting secondary bile acids such as deoxycholic acid and lithocholic acid. Epidemiological evidence suggests CRC is associated with increased levels of DCA in serum, bile, and stool. Mechanisms by which secondary bile acids promote CRC are explored. Furthermore, in humans bile acid conjugation can vary by diet. Vegetarian diets favor glycine conjugation while diets high in animal protein favor taurine conjugation. Metabolism of taurine conjugated bile acids by gut microbes generates hydrogen sulfide, a genotoxic compound. Thus, taurocholic acid has the potential to stimulate intestinal bacteria capable of converting taurine and cholic acid to hydrogen sulfide and deoxycholic acid, a genotoxin and tumor-promoter, respectively. PMID:27003186

[Clinicopathologic features of drug-induced vanishing bile duct syndrome].

PubMed

Ye, L H; Wang, C K; Zhang, H C; Liu, Z Q; Zheng, H W

2017-04-20

Vanishing bile duct syndrome (VBDS) manifests as progressive destruction and disappearance of the intrahepatic bile duct caused by various factors and cholestasis. VBDS associated with drug-induced liver injury (D-VBDS) is an important etiology of VBDS, and immune disorder or immune imbalance may be the main pathogenesis. According to its clinical symptoms, serological markers, and course of the disease, D-VBDS is classified into major form and minor form, and its clinical features are based on various pathomorphological findings. Its prognosis is associated various factors including regeneration of bile duct cells, number of bile duct injuries, level and range of bile duct injury, bile duct proliferation, and compensatory shunt of bile duct branches. This disease has various clinical outcomes; most patients have good prognosis after drug withdrawal, and some patients may experience cholestatic cirrhosis, liver failure, and even death. Due to the clinical manifestation and biochemical changes are similar to the primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC), it need to identify by clinical physician.

Anomalous pancreatico-biliary ductal union with cystic dilatation of the bile duct.

PubMed

Richer, J P; Faure, J P; Morichau-Beauchant, M; Dugue, T; Maillot, N; Kamina, P; Carretier, M

1998-01-01

We report, in an adult, an asymptomatic association between cystic dilation of the bile duct (type IV A in Todani's classification) and anomalous pancreatico-biliary ductal union (APBD) with stones in a long common channel. In APBD, the connection between the common bile duct and the main pancreatic duct is located outside the duodenal wall andis therefore not under the influence of the sphincter of Boyden. An abnormally long common channel is in excess of 15 mm. Two types of convergence anomalies are defined according to whether the bile duct opens into the main pancreatic duct (BP) or the main pancreatic duct into the bile duct (PB). In APBD, there is probably a reverse pressure gradient between the bile and pancreatic ducts, with regurgitation of pancreatic juice into the bile duct, repeated attacks of cholangitis, stenosis and cystic dilatation. A long common channel is associated with a higher incidence of carcinoma of the gall bladder of the bile duct.

In Vitro Binding Capacity of Bile Acids by Defatted Corn Protein Hydrolysate

PubMed Central

Kongo-Dia-Moukala, Jauricque Ursulla; Zhang, Hui; Irakoze, Pierre Claver

2011-01-01

Defatted corn protein was digested using five different proteases, Alcalase, Trypsin, Neutrase, Protamex and Flavourzyme, in order to produce bile acid binding peptides. Bile acid binding capacity was analyzed in vitro using peptides from different proteases of defatted corn hydrolysate. Some crystalline bile acids like sodium glycocholate, sodium cholate and sodium deoxycholate were individually tested using HPLC to see which enzymes can release more peptides with high bile acid binding capacity. Peptides from Flavourzyme defatted corn hydrolysate exhibited significantly (p < 0.05) stronger bile acid binding capacity than all others hydrolysates tested and all crystalline bile acids tested were highly bound by cholestyramine, a positive control well known as a cholesterol-reducing agent. The bile acid binding capacity of Flavourzyme hydrolysate was almost preserved after gastrointestinal proteases digestion. The molecular weight of Flavourzyme hydrolysate was determined and most of the peptides were found between 500–180 Da. The results showed that Flavourzyme hydrolysate may be used as a potential cholesterol-reducing agent. PMID:21541043

Inhibition of bile salt transport by drugs associated with liver injury in primary hepatocytes from human, monkey, dog, rat, and mouse

PubMed Central

Zhang, Jie; He, Kan; Cai, Lining; Chen, Yu-Chuan; Yang, Yifan; Shi, Qin; Woolf, Thomas F.; Ge, Weigong; Guo, Lei; Borlak, Jürgen; Tong, Weida

2018-01-01

Interference of bile salt transport is one of the underlying mechanisms for drug-induced liver injury (DILI). We developed a novel bile salt transport activity assay involving in situ biosynthesis of bile salts from their precursors in primary human, monkey, dog, rat, and mouse hepatocytes in suspension as well as LC-MS/MS determination of extracellular bile salts transported out of hepatocytes. Glycine- and taurine-conjugated bile acids were rapidly formed in hepatocytes and effectively transported into the extracellular medium. The bile salt formation and transport activities were time– and bile-acid-concentration–dependent in primary human hepatocytes. The transport activity was inhibited by the bile salt export pump (BSEP) inhibitors ketoconazole, saquinavir, cyclosporine, and troglitazone. The assay was used to test 86 drugs for their potential to inhibit bile salt transport activity in human hepatocytes, which included 35 drugs associated with severe DILI (sDILI) and 51 with non-severe DILI (non-sDILI). Approximately 60% of the sDILI drugs showed potent inhibition (with IC50 values <50 μM), but only about 20% of the non-sDILI drugs showed this strength of inhibition in primary human hepatocytes and these drugs are associated only with cholestatic and mixed hepatocellular cholestatic (mixed) injuries. The sDILI drugs, which did not show substantial inhibition of bile salt transport activity, are likely to be associated with immune-mediated liver injury. Twenty-four drugs were also tested in monkey, dog, rat and mouse hepatocytes. Species differences in potency were observed with mouse being less sensitive than other species to inhibition of bile salt transport. In summary, a novel assay has been developed using hepatocytes in suspension from human and animal species that can be used to assess the potential for drugs and/or drug-derived metabolites to inhibit bile salt transport and/or formation activity. Drugs causing sDILI, except those by immune-mediated mechanism, are highly associated with potent inhibition of bile salt transport. PMID:27000539

Inhibition of bile salt transport by drugs associated with liver injury in primary hepatocytes from human, monkey, dog, rat, and mouse.

PubMed

Zhang, Jie; He, Kan; Cai, Lining; Chen, Yu-Chuan; Yang, Yifan; Shi, Qin; Woolf, Thomas F; Ge, Weigong; Guo, Lei; Borlak, Jürgen; Tong, Weida

2016-08-05

Interference of bile salt transport is one of the underlying mechanisms for drug-induced liver injury (DILI). We developed a novel bile salt transport activity assay involving in situ biosynthesis of bile salts from their precursors in primary human, monkey, dog, rat, and mouse hepatocytes in suspension as well as LC-MS/MS determination of extracellular bile salts transported out of hepatocytes. Glycine- and taurine-conjugated bile acids were rapidly formed in hepatocytes and effectively transported into the extracellular medium. The bile salt formation and transport activities were time‒ and bile-acid-concentration‒dependent in primary human hepatocytes. The transport activity was inhibited by the bile salt export pump (BSEP) inhibitors ketoconazole, saquinavir, cyclosporine, and troglitazone. The assay was used to test 86 drugs for their potential to inhibit bile salt transport activity in human hepatocytes, which included 35 drugs associated with severe DILI (sDILI) and 51 with non-severe DILI (non-sDILI). Approximately 60% of the sDILI drugs showed potent inhibition (with IC50 values <50 μM), but only about 20% of the non-sDILI drugs showed this strength of inhibition in primary human hepatocytes and these drugs are associated only with cholestatic and mixed hepatocellular cholestatic (mixed) injuries. The sDILI drugs, which did not show substantial inhibition of bile salt transport activity, are likely to be associated with immune-mediated liver injury. Twenty-four drugs were also tested in monkey, dog, rat and mouse hepatocytes. Species differences in potency were observed with mouse being less sensitive than other species to inhibition of bile salt transport. In summary, a novel assay has been developed using hepatocytes in suspension from human and animal species that can be used to assess the potential for drugs and/or drug-derived metabolites to inhibit bile salt transport and/or formation activity. Drugs causing sDILI, except those by immune-mediated mechanism, are highly associated with potent inhibition of bile salt transport. Published by Elsevier Ireland Ltd.

Single center experience with endoscopic subureteral dextranomer/hyaluronic acid injection as first line treatment in 1,551 children with intermediate and high grade vesicoureteral reflux.

PubMed

Puri, Prem; Kutasy, Balazs; Colhoun, Eric; Hunziker, Manuela

2012-10-01

In recent years the endoscopic injection of dextranomer/hyaluronic acid has become an established alternative to long-term antibiotic prophylaxis and the surgical management of vesicoureteral reflux. We determined the safety and effectiveness of the endoscopic injection of dextranomer/hyaluronic acid as first line treatment for high grade vesicoureteral reflux. Between 2001 and 2010, 1,551 children (496 male, 1,055 female, median age 1.6 years) underwent endoscopic correction of intermediate and high grade vesicoureteral reflux using dextranomer/hyaluronic acid soon after the diagnosis of vesicoureteral reflux on initial voiding cystourethrogram. Vesicoureteral reflux was unilateral in 761 children and bilateral in 790. Renal scarring was detected in 369 (26.7%) of the 1,384 patients who underwent dimercapto-succinic acid imaging. Reflux grade in the 2,341 ureters was II in 98 (4.2%), III in 1,340 (57.3%), IV in 818 (34.9%) and V in 85 (3.6%). Followup ultrasound and voiding cystourethrogram were performed 3 months after the outpatient procedure, and renal ultrasound was performed annually thereafter. Patients were followed for 3 months to 10 years (median 5.6 years). Vesicoureteral reflux resolved after the first, second and third endoscopic injection of dextranomer/hyaluronic acid in 2,039 (87.1%), 264 (11.3%) and 38 (1.6%) ureters, respectively. Febrile urinary tract infections developed during followup in 69 (4.6%) patients. None of the patients in the series needed reimplantation of ureters or experienced any significant complications. Our results confirm the safety and efficacy of the endoscopic injection of dextranomer/hyaluronic acid in the eradication of high grade vesicoureteral reflux. We recommend this 15-minute outpatient procedure as the first line of treatment for high grade vesicoureteral reflux. Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Dextranomer/hyaluronic acid endoscopic injection is effective in the treatment of intermediate and high grade vesicoureteral reflux in patients with complete duplex systems.

PubMed

Hunziker, Manuela; Mohanan, Nochiparambil; Puri, Prem

2013-05-01

Endoscopic subureteral injection of dextranomer/hyaluronic acid has become an established alternative to long-term antibiotic prophylaxis or surgical treatment for vesicoureteral reflux. We evaluated the effectiveness of endoscopic injection of dextranomer/hyaluronic acid in intermediate and high grade vesicoureteral reflux in patients with complete duplex collecting systems. A total of 123 children underwent endoscopic correction of intermediate or high grade vesicoureteral reflux using injection of dextranomer/hyaluronic acid into complete duplex systems between 2001 and 2010. Vesicoureteral reflux was diagnosed by voiding cystourethrogram, and dimercapto-succinic acid scan was performed to evaluate the presence of renal scarring. Followup ultrasound and voiding cystourethrogram were performed 3 months after the outpatient procedure and renal ultrasound thereafter every 2 years. Mean followup was 6.7 years. Complete duplex systems were unilateral in 110 patients and bilateral in 13. Reflux severity in the 136 refluxing units was grade II in 1 (0.7%), III in 52 (38.2%), IV in 61 (44.9%) and V in 22 (16.2%). Dimercapto-succinic acid scan revealed renal functional abnormalities in 63 children (51.2%). Vesicoureteral reflux resolved after the first endoscopic injection of dextranomer/hyaluronic acid in 93 ureters (68.4%), after a second injection in 35 (25.7%) and after a third injection in 8 (5.9%). Febrile urinary tract infection developed in 5 patients (4.1%) during followup. No patient required ureteral reimplantation or experienced significant complications. Our results confirm the safety and efficacy of endoscopic injection of dextranomer/hyaluronic acid in eradicating intermediate and high grade vesicoureteral reflux in patients with complete duplex systems. We recommend this minimally invasive, 15-minute outpatient procedure as a viable option for treating intermediate and high grade vesicoureteral reflux in patients with complete duplex collecting systems. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Discounting the duration of bolus exposure in impedance testing underestimates acid reflux.

PubMed

Vikneswaran, Namasivayam; Murray, Joseph A

2016-06-08

Combined impedance-pH testing (MII) allows for detection of reflux episodes regardless of pH. However impedance-based diagnosis of reflux may not routinely account for duration of the reflux episode. We hypothesize that impedance testing may be less sensitive than pH-testing in detecting acid reflux off therapy as a result of discounting duration of exposure. Baseline characteristics and reflux parameters of MII studies performed off-anti-secretory medications were analyzed. Studies on acid suppressive medication and those with recording times less than 20 h or low baseline impedance were excluded. A total of 73 consecutive MII studies were analyzed of which 31 MII studies had elevated acid exposure while 16 were abnormal by impedance criteria. MII testing off-therapy was more likely to be abnormal by pH criteria (percent time pH < 4) than impedance criteria (total reflux):[42 vs 22 % (p =0.02)]. Acid exposure (percent time pH < 4) identified more studies as abnormal than MII-detected acid reflux episodes [42 vs 34 % (p < 0.01)]. Mean acid clearance time (pH-detected) was significantly longer than median bolus clearance time (impedance-detected) in the total [98.7 s vs 12.6 s (p < 0.01)], upright [58.6 s vs 13.1 s (p < 0.01)], and recumbent positions [136.7 s vs 14.2 s (p < 0.01)] with the greatest difference seen in the recumbent position. The mean ratio of mean acid clearance time (pH-detected) and the median bolus clearance time (impedance-detected) was significantly higher in the recumbent position compared to the upright position [11. vs 5.3 (p = 0.01)]. Ambulatory impedance testing underestimates acid reflux compared to esophageal acid exposure by discounting the prolonged period of mucosal contact with each acid reflux episode, particularly in the recumbent position.

Primary venous insufficiency increases risk of deep vein thrombosis.

PubMed

Shaydakov, Maxim E; Comerota, Anthony J; Lurie, Fedor

2016-04-01

Varicose veins have been recognized as a risk factor for deep vein thrombosis (DVT). However, venous reflux has not carried the same correlation. This study evaluated the association between primary valvular reflux and DVT. We performed a nested case-control study with enrollment of outpatients presenting to the vascular laboratory with signs and symptoms of DVT. All patients had a complete bilateral venous duplex examination evaluating for DVT and superficial and deep venous valvular reflux. Eighty-seven patients with confirmed DVT on venous duplex were selected for the study group. The control group was randomly selected from the same cohort in a 4:1 ratio matched by age and gender (n = 348). Groups were compared for the prevalence of deep and superficial reflux. DVT outpatients were 4.7-times more likely to have primary valvular reflux than symptomatic controls (65.5% vs 29.0%; 95% confidence interval [CI], 2.8-7.7; P < .000001). Deep reflux was 2.1-times more prevalent (36.8% vs 21.6%; odds ratio, 2.12; 95% CI, 1.28-3.51; P = .005) and superficial reflux was 4.6-times more prevalent (43.7% vs 14.4%; odds ratio, 4.62; 95% CI, 2.75-7.77; P < .0000001) in DVT patients than in controls. DVT patients were also 2.1-times more likely to have combined deep and superficial reflux than non-DVT patients (13.8% vs 6.6%, 95% CI, 1.08-4.75; P = .044). The prevalence of primary valvular reflux in patients with DVT is significantly higher than expected. Reflux may be considered as a novel risk factor for DVT. Two-thirds of patients with DVT have pre-existent primary chronic venous disease, which is likely to contribute to post-thrombotic morbidity. Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Gastro-oesophageal reflux symptoms and coeliac disease: no role for routine duodenal biopsy.

PubMed

Mooney, Peter D; Evans, Kate E; Kurien, Matthew; Hopper, Andrew D; Sanders, David S

2015-06-01

Coeliac disease (CD) has been linked to gastro-oesophageal reflux disease (GORD). Previous studies have demonstrated an increased prevalence of reflux in patients with CD. However data on the risk for CD in patients presenting with reflux are conflicting. The aim of this study was to establish the prevalence of CD in patients with GORD and to elucidate the mechanisms for reflux symptoms in newly diagnosed CD patients. Group A: patients who had undergone routine duodenal biopsy were prospectively recruited between 2004 and 2014. Diagnostic yield was compared with that of a screening cohort. Group B: 32 patients with newly diagnosed CD who had undergone oesophageal manometry and 24-h pH studies were prospectively recruited. Group A: 3368 patients (58.7% female, mean age 53.4 years) underwent routine duodenal biopsy. Of these patients, 850 (25.2%) presented with GORD. The prevalence of CD among GORD patients was 1.3% (0.7-2.4%), which was not significantly higher than that in the general population (P=0.53). Within the context of routine duodenal biopsy at endoscopy (when corrected for concurrent symptoms, age and sex), reflux was found to be negatively associated with CD [adjusted odds ratio 0.12 (0.07-0.23), P<0.0001]. In group B, 34% of patients complained of reflux. On manometry, 9% had a hypotensive lower oesophageal sphincter and 40.6% had oesophageal motor abnormalities, with 25% significantly hypocontractile. On pH studies, 33% demonstrated reflux episodes. The prevalence of undiagnosed CD among GORD patients is similar to that in the general population, and routine duodenal biopsy cannot be recommended. A significant number of patients with newly diagnosed CD were found to have reflux and/or oesophageal dysmotility on pH/manometry studies; this may explain the high prevalence of reflux symptoms in CD.