2% with type III. In comparison, older patients had a more even distribution of achalasia sub-types (type I: 36.1%; type II:

33.3% and type III: 30.6%; Figure). Furthermore, older subjects had a decrease in the incidence of type II (p < 0.05), and a trend towards a higher prevalence of type III (p = 0.1) when compared to younger patients. Conclusion: The lower incidence of type II, and the trend towards an increased incidence in type III achalasia in older patients was unexpected given the concept of a progression towards aperistalsis over time. The reasons for this are unclear, but if confirmed, may have implications for treatment approaches in older patients. 1. Pandolfino JE, et al. Gastroenterology 2008; 135(5): 1526–1533 2. Bredenoord AJ, et al. Neurogastroenterol Motil 2012; 24: 57–65. 3. Nicodeme F, et al. PD98059 mouse Clinical Gastroenterol Hepatol 2013; 11(2):131–137 CM BURGSTAD,1 LK BESANKO,1 R HEDDLE,1 E CLIFTON,1 S LAU,1 D KPT330 HOFFMAN,1 J MARTIN,1 RJL FRASER,2 C COCK1 1Investigation & Procedures Unit, 2Repatriation General Hospital, Daw Park and Department of Gastroenterology & Hepatology, Flinders University, Bedford Park; South Australia Background: The differentiation of achalasia according

to subtype (type I, II and III) has clinical relevance for type of treatment and subsequent outcome. The Chicago classification involves detailed analysis of oesophageal body and lower oesophageal sphincter using high resolution manometry. Data on the reproducibility of this analysis and diagnostic findings between expert and non-experienced reporters are limited1. Aim: To assess the “reliability” HAS1 of achalasia sub-typing using the Chicago classification, and evaluate the diagnostic consistency between reporters with varying experience.

Methods: Motility studies from 117 patients with a manometric diagnosis of “achalasia” were reviewed by eight raters, divided into 2 groups: ‘experienced’ (n = 4) and ‘inexperienced’ (n = 4). Studies were re-classified according to sub-type (I, II or III) based on Chicago criteria2. Post hoc analysis of all data for experienced raters was used to determine “gold standard” ratings. Cases where agreement could not be reached were excluded from analysis. Absolute agreement between raters was determined using intraclass correlation co-efficient (SPSS v16.0) and a P value < 0.05 was considered significant. Results: Intra-class correlation coefficient (ICC) was high for both experienced [0.905 (0.870–0.932)] and inexperienced [0.875 (0.831–0.910)] raters with an overall ICC for all raters of 0.879 (0.781–0.928; p < 0.001). When comparing the intra-rater reliability, the experienced raters had good to very good agreement for type I (91%) and type II (88%) sub-types, but were more variable with type III achalasia (75%). In contrast, the inexperienced raters were in highest agreement for sub-types II (72%) and III (92%), but consistency was lower with type 1 (58%); Figure.

Multiple oesophageal

biopsies did not show evidence of dysplasia or malignancy. He presented with dysphagia in 2013. A diagnostic upper GI endoscopy showed stricture at 40 cm from incisor. The stricture was unsuccessfully treated with CRE wireguided TTO ballon dilatations (inflated up to 12 mm). Multiple biopsies confirmed high grade adenocarcinoma. CT staging, PET scan and EUS showed T3, N0, M0. He received pre-operative adjuvant chemotherapy followed by total oesophagectomy. Conclusion: Up to 90% of patients with EIPD have associated stenosis of the esophagus of various levels due to chronic oesophagitis from reflux disease. Metaplastic squamous epithelium had been found within the excretory ducts of esophageal submucosal glands in EIPD may be the link between EIPD LEE011 in vivo and esophageal carcinoma. The increased prevalence of EPID in patients with oesophageal carcinoma may warrant periodic surveillance in this small population

of patients. Key Word(s): 1. EPID; 2. Malignant stricture; Presenting Author: XUAN JIANG Additional Authors: HANLONG YAN, XINHUA PENG, YULAN LIU Corresponding Author: YULAN LIU Affiliations: Department of Gastroenterology, Peking University People’s Hospital Objective: To analyze the common symptoms and investigate the overlap rate of GERD CAL 101 and FBD in visited GI clinic in a general hospital. Methods: During April to June, 2011, Data collected were demographic information\chief complaints. A validated Chinese version Reflux Disease Questionnaire (RDQ) was used to assess the typical GER symptoms and diagnosed GERD. Reflux esopheagitis (RE) and non-erosive gastroesopheal reflux disease (NERD) were differentiate according to RDQ

scores\endoscopic diagnosis\PPI response. Lumacaftor manufacturer Functional bowl disease (FBD) was diagnosed using Rome III criteria. SPSS 17.0 programs were performed for statistical analyses. Results: 1074 (98.3%) finished questionnaire. The chief complaints in GI clinic patients included abdominal pain (32.5%, 12 missing cases), discomfort of abdomen (20.7%), abdominal bloating (13,7%), acid regurgitation and/or heartburn (17.3%), change in bowel habits (8.2%) and others. GER symptoms presented in 32.7% (351) of the subjects, and 10.0% (107) was diagnosed as GERD. 37.6% (404) of the subjecsts had chronic symptoms of abdominal pain/bloating, diarrhea/constipation; and 19.2% (207) was diagnosed as FBD. Higher RDQ scores of typical GER symptoms accompanied with higher rate of atypical GER symptoms in esophageal and extraesophageal (all P < 0.05), as well as the trend of increased possibility of comorbid symptoms of chronic bloating/constipation, and irritable bowl syndrome (IBS), functional constipation (FC) (trend chi-square test, all P < 0.05). Further, GERD patients presented with chronic bloating (27, 25.2%), chronic constipatin (15, 14.0%), and overlapping with IBS (11, 10.

Multiple oesophageal

biopsies did not show evidence of dysplasia or malignancy. He presented with dysphagia in 2013. A diagnostic upper GI endoscopy showed stricture at 40 cm from incisor. The stricture was unsuccessfully treated with CRE wireguided TTO ballon dilatations (inflated up to 12 mm). Multiple biopsies confirmed high grade adenocarcinoma. CT staging, PET scan and EUS showed T3, N0, M0. He received pre-operative adjuvant chemotherapy followed by total oesophagectomy. Conclusion: Up to 90% of patients with EIPD have associated stenosis of the esophagus of various levels due to chronic oesophagitis from reflux disease. Metaplastic squamous epithelium had been found within the excretory ducts of esophageal submucosal glands in EIPD may be the link between EIPD see more and esophageal carcinoma. The increased prevalence of EPID in patients with oesophageal carcinoma may warrant periodic surveillance in this small population

of patients. Key Word(s): 1. EPID; 2. Malignant stricture; Presenting Author: XUAN JIANG Additional Authors: HANLONG YAN, XINHUA PENG, YULAN LIU Corresponding Author: YULAN LIU Affiliations: Department of Gastroenterology, Peking University People’s Hospital Objective: To analyze the common symptoms and investigate the overlap rate of GERD Crenolanib and FBD in visited GI clinic in a general hospital. Methods: During April to June, 2011, Data collected were demographic information\chief complaints. A validated Chinese version Reflux Disease Questionnaire (RDQ) was used to assess the typical GER symptoms and diagnosed GERD. Reflux esopheagitis (RE) and non-erosive gastroesopheal reflux disease (NERD) were differentiate according to RDQ

scores\endoscopic diagnosis\PPI response. Anacetrapib Functional bowl disease (FBD) was diagnosed using Rome III criteria. SPSS 17.0 programs were performed for statistical analyses. Results: 1074 (98.3%) finished questionnaire. The chief complaints in GI clinic patients included abdominal pain (32.5%, 12 missing cases), discomfort of abdomen (20.7%), abdominal bloating (13,7%), acid regurgitation and/or heartburn (17.3%), change in bowel habits (8.2%) and others. GER symptoms presented in 32.7% (351) of the subjects, and 10.0% (107) was diagnosed as GERD. 37.6% (404) of the subjecsts had chronic symptoms of abdominal pain/bloating, diarrhea/constipation; and 19.2% (207) was diagnosed as FBD. Higher RDQ scores of typical GER symptoms accompanied with higher rate of atypical GER symptoms in esophageal and extraesophageal (all P < 0.05), as well as the trend of increased possibility of comorbid symptoms of chronic bloating/constipation, and irritable bowl syndrome (IBS), functional constipation (FC) (trend chi-square test, all P < 0.05). Further, GERD patients presented with chronic bloating (27, 25.2%), chronic constipatin (15, 14.0%), and overlapping with IBS (11, 10.

Multiple oesophageal

biopsies did not show evidence of dysplasia or malignancy. He presented with dysphagia in 2013. A diagnostic upper GI endoscopy showed stricture at 40 cm from incisor. The stricture was unsuccessfully treated with CRE wireguided TTO ballon dilatations (inflated up to 12 mm). Multiple biopsies confirmed high grade adenocarcinoma. CT staging, PET scan and EUS showed T3, N0, M0. He received pre-operative adjuvant chemotherapy followed by total oesophagectomy. Conclusion: Up to 90% of patients with EIPD have associated stenosis of the esophagus of various levels due to chronic oesophagitis from reflux disease. Metaplastic squamous epithelium had been found within the excretory ducts of esophageal submucosal glands in EIPD may be the link between EIPD NVP-BGJ398 mw and esophageal carcinoma. The increased prevalence of EPID in patients with oesophageal carcinoma may warrant periodic surveillance in this small population

of patients. Key Word(s): 1. EPID; 2. Malignant stricture; Presenting Author: XUAN JIANG Additional Authors: HANLONG YAN, XINHUA PENG, YULAN LIU Corresponding Author: YULAN LIU Affiliations: Department of Gastroenterology, Peking University People’s Hospital Objective: To analyze the common symptoms and investigate the overlap rate of GERD Imatinib research buy and FBD in visited GI clinic in a general hospital. Methods: During April to June, 2011, Data collected were demographic information\chief complaints. A validated Chinese version Reflux Disease Questionnaire (RDQ) was used to assess the typical GER symptoms and diagnosed GERD. Reflux esopheagitis (RE) and non-erosive gastroesopheal reflux disease (NERD) were differentiate according to RDQ

scores\endoscopic diagnosis\PPI response. Exoribonuclease Functional bowl disease (FBD) was diagnosed using Rome III criteria. SPSS 17.0 programs were performed for statistical analyses. Results: 1074 (98.3%) finished questionnaire. The chief complaints in GI clinic patients included abdominal pain (32.5%, 12 missing cases), discomfort of abdomen (20.7%), abdominal bloating (13,7%), acid regurgitation and/or heartburn (17.3%), change in bowel habits (8.2%) and others. GER symptoms presented in 32.7% (351) of the subjects, and 10.0% (107) was diagnosed as GERD. 37.6% (404) of the subjecsts had chronic symptoms of abdominal pain/bloating, diarrhea/constipation; and 19.2% (207) was diagnosed as FBD. Higher RDQ scores of typical GER symptoms accompanied with higher rate of atypical GER symptoms in esophageal and extraesophageal (all P < 0.05), as well as the trend of increased possibility of comorbid symptoms of chronic bloating/constipation, and irritable bowl syndrome (IBS), functional constipation (FC) (trend chi-square test, all P < 0.05). Further, GERD patients presented with chronic bloating (27, 25.2%), chronic constipatin (15, 14.0%), and overlapping with IBS (11, 10.

LC/MS-TOF analysis

shows that Azadinium dex-teroporum produces azaspiracids in low amounts. Some of them have the same molecular weight as known compounds such as azaspiracid-3 and -7 and Compound 3 from Amphidoma languida, as well as similar fragmentation patterns in some cases. This is the first finding of a species producing azapiracids in the Mediterranean Sea. “
“The widespread coccolithophorid Emiliania huxleyi (Lohmann) W. W. Hay et H. Mohler plays a pivotal role in the carbon pump and is known to exhibit Doxorubicin chemical structure significant morphological, genetic, and physiological diversity. In this study, we compared photosynthetic pigments and morphology of triplicate strains of Southern Ocean types A and B/C. The two morphotypes differed in width of coccolith distal shield elements (0.11–0.24 μm, type A; 0.06–0.12 μm, type B/C) and morphology of distal shield central area (grill of curved rods in type A; thin plain plate in type B/C) and showed differences in carotenoid composition. The mean 19′-hexanoyloxyfucoxanthin (Hex):chl a ratio in type B/C was >1, whereas the type A ratio was <1. The Hex:fucoxanthin (fuc) ratio for type B/C was 11 times greater than that for type A, and the proportion of fuc in type A was 6 times higher than that in type B/C. The fuc derivative 4-keto-19′-hexanoyloxyfucoxanthin (4-keto-hex)

was present in type A but undetected in B/C. DNA sequencing of tufA distinguished morphotypes A, B/C (indistinguishable RG 7204 from B), and R, while little variation was observed within morphotypes. Thirty single nucleotide polymorphisms were identified in the 710 bp tufA sequence, of which 10 alleles were unique to B/C and B morphotypes,

seven alleles were unique to type A, and six alleles were unique to type R. We propose that the morphologically, physiologically, and genetically distinct Southern Ocean type B/C sensu PJ34 HCl Young et al. (2003) be classified as E. huxleyi var. aurorae var. nov. S. S. Cook et Hallegr. “
“The genus Esoptrodinium Javornický consists of freshwater, athecate dinoflagellates with an incomplete cingulum. Strains isolated thus far feed on microalgae and most possess obvious pigmented chloroplasts, suggesting mixotrophy. However, some geographic isolates lack obvious pigmented chloroplasts. The purpose of this study was to comparatively examine this difference and the associated potential for mixotrophy among different isolates of Esoptrodinium. All isolates phagocytized prey cells through an unusual hatch-like peduncle located on the ventral episome, and were capable of ingesting various protist taxa. All Esoptrodinium isolates required both food and light to grow. However, only the tested strain with visible pigmented chloroplasts benefited from light in terms of increased biomass (phototrophy). Isolates lacking obvious chloroplasts received no biomass benefit from light, but nevertheless required light for sustained growth (i.e., photoobligate, but not phototrophic).

, in 2013. The planned 240 subjects are being enrolled over the course of a year, with investigators in Chile and Australia. The study results can therefore be expected in late 2014 or early 2015. The multiple ongoing trials of CGRP antibodies should provide a definitive answer as to whether this therapeutic approach will lead to a new class of antimigraine agents. Phase 2 efficacy data for anti-CGRP antibodies can be expected in 2014 from Arteaus, Alder, and Amgen. Perhaps more importantly, these data should provide a significant assessment of whether chronic modulation of CGRP will lead to a viable treatment

for migraine after 25 years of research supporting its role in the disorder. At this point in time, it is sobering to note that clinical research in the field of migraine has been BGJ398 decreasing steadily over the past few years, with the exception check details of a recent increase in the clinical evaluation of CGRP antagonists in migraine. Particularly striking is the fact that all but one of the ongoing clinical trials (Table 1) involve migraine prevention or the treatment of chronic migraine. This may be the first time in many decades

that so few new agents are being evaluated in the acute treatment of migraine. The reasons for this significant decrease in clinical development are numerous. First and foremost, a number of new pharmaceutical agents that modulate novel therapeutic targets (eg, glutamate and orexin receptors) have failed

to demonstrate efficacy in clinical trials. Second, a few agents have demonstrated efficacy, yet have safety profiles that appear to limit their further development. However, there also appears to be a third reason for the slower development of novel therapies in migraine. This reason for decreased clinical development might be termed “pharmaceutical limbo,” defined as the discontinuation of development for agents that do demonstrate clinical efficacy with an acceptable safety profile, but whose degree of efficacy is not deemed sufficient by the sponsor to warrant further clinical development. Within the past few years, a number of potentially novel migraine therapies appear to have fallen into 6-phosphogluconolactonase this category, most prominently of which are the small molecule CGRP antagonists. There have now been at least 5 different small molecule CGRP antagonists that have demonstrated statistical proof of efficacy in the acute treatment of migraine. At least 2 of these agents are orally available with no known major safety concerns. However, future development of these agents (eg, BMS-927711 and BI 44370) appears to have been discontinued or suspended. Lasmiditan, an 5-HT1F receptor agonist, is another example of this situation. Although 6 clinical studies with lasmiditan have been completed successfully, including a Phase 2B double-blind, placebo-controlled oral dose ranging study treating a single migraine attack, the drug has been unable to progress to Phase 3.

, in 2013. The planned 240 subjects are being enrolled over the course of a year, with investigators in Chile and Australia. The study results can therefore be expected in late 2014 or early 2015. The multiple ongoing trials of CGRP antibodies should provide a definitive answer as to whether this therapeutic approach will lead to a new class of antimigraine agents. Phase 2 efficacy data for anti-CGRP antibodies can be expected in 2014 from Arteaus, Alder, and Amgen. Perhaps more importantly, these data should provide a significant assessment of whether chronic modulation of CGRP will lead to a viable treatment

for migraine after 25 years of research supporting its role in the disorder. At this point in time, it is sobering to note that clinical research in the field of migraine has been Tanespimycin purchase decreasing steadily over the past few years, with the exception Lorlatinib concentration of a recent increase in the clinical evaluation of CGRP antagonists in migraine. Particularly striking is the fact that all but one of the ongoing clinical trials (Table 1) involve migraine prevention or the treatment of chronic migraine. This may be the first time in many decades

that so few new agents are being evaluated in the acute treatment of migraine. The reasons for this significant decrease in clinical development are numerous. First and foremost, a number of new pharmaceutical agents that modulate novel therapeutic targets (eg, glutamate and orexin receptors) have failed

to demonstrate efficacy in clinical trials. Second, a few agents have demonstrated efficacy, yet have safety profiles that appear to limit their further development. However, there also appears to be a third reason for the slower development of novel therapies in migraine. This reason for decreased clinical development might be termed “pharmaceutical limbo,” defined as the discontinuation of development for agents that do demonstrate clinical efficacy with an acceptable safety profile, but whose degree of efficacy is not deemed sufficient by the sponsor to warrant further clinical development. Within the past few years, a number of potentially novel migraine therapies appear to have fallen into cAMP this category, most prominently of which are the small molecule CGRP antagonists. There have now been at least 5 different small molecule CGRP antagonists that have demonstrated statistical proof of efficacy in the acute treatment of migraine. At least 2 of these agents are orally available with no known major safety concerns. However, future development of these agents (eg, BMS-927711 and BI 44370) appears to have been discontinued or suspended. Lasmiditan, an 5-HT1F receptor agonist, is another example of this situation. Although 6 clinical studies with lasmiditan have been completed successfully, including a Phase 2B double-blind, placebo-controlled oral dose ranging study treating a single migraine attack, the drug has been unable to progress to Phase 3.

Deficiency of inflammasome components NLRP3, ASC or Caspase-1, or lack of IL-1 signaling prevented alcohol-induced liver inflammation suggesting that IL-1 determines Trichostatin A the onset of inflammation in AH. Next we evaluated whether IL-1 also drives the persistence of liver inflammation in AH. We observed that liver

inflammation and increased IL-1 were sustained for at least three days after cessation of alcohol, followed by delayed apoptosis of inflammatory cells in the liver and limited degree of hepatocyte regeneration. We discovered that inhibition of IL-1 signaling using a single dose of IL-1Ra at cessation of alcohol increased apoptosis of liver immune cells, facilitated regeneration of hepatocytes, and resulted in increased rate of recovery from liver injury in AH. These findings were consistent with in vitro studies showing that IL-1 administration Temsirolimus price promotes cytotoxicity of primary hepatocytes while it provides pro-survival benefit for BM-derived immune cells Conclusions: Our novel findings demonstrate that IL-1 drives sustained liver inflammation

and impaired hepatocyte regeneration even after cessation of ethanol exposure in AH. Therapeutic inhibition of IL-1 improves hepatocyte survival and promotes death of activated harmful immune cells in a preclin-ical model of AH. Disclosures: Gyongyi Szabo – Consulting: Idenix; Grant/Research Support: BMS, GSK, Cona-tus, Idera, Johnson&Johnson, Novartis, Ocera, Roche, Shering – Plough, Wyeth, Integrated not Therapeutics, Idera The following people have nothing to disclose: Jan Petrasek, Arvin Irache-ta-Vellve, Shashi Bala, Timea Csak, Karen Kodys, Evelyn A. Kurt-Jones Background: Epidemiological studies revealed that nearly 80% of heavy drinkers with alcoholic liver disease (ALD) also smoke tobacco. This finding suggests that tobacco and possibly its toxins have cofactor roles in ALD pathogenesis. Our research focused on the potential role of NNK as a mediator

of hepa-tocellular injury in ALD because previous efforts showed that other nitrosamines can cause hepatic steatosis or steatohep-atitis with insulin resistance, inflammation, oxidative and ER stress, and lipotoxicity. Moreover, toxic lipids, particularly ceramides, can promote the same effects. Due to the inability to detect significant molecular profiles by routine histological studies, we explored the potential use of matrix assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry as a diagnostic aid for characterizing the nature and possibly etiology of steatohepatitis. Hypothesis: IMS can be used to generate biochemical signatures of steatohepatitis caused by different agents.

Deficiency of inflammasome components NLRP3, ASC or Caspase-1, or lack of IL-1 signaling prevented alcohol-induced liver inflammation suggesting that IL-1 determines see more the onset of inflammation in AH. Next we evaluated whether IL-1 also drives the persistence of liver inflammation in AH. We observed that liver

inflammation and increased IL-1 were sustained for at least three days after cessation of alcohol, followed by delayed apoptosis of inflammatory cells in the liver and limited degree of hepatocyte regeneration. We discovered that inhibition of IL-1 signaling using a single dose of IL-1Ra at cessation of alcohol increased apoptosis of liver immune cells, facilitated regeneration of hepatocytes, and resulted in increased rate of recovery from liver injury in AH. These findings were consistent with in vitro studies showing that IL-1 administration Wee1 inhibitor promotes cytotoxicity of primary hepatocytes while it provides pro-survival benefit for BM-derived immune cells Conclusions: Our novel findings demonstrate that IL-1 drives sustained liver inflammation

and impaired hepatocyte regeneration even after cessation of ethanol exposure in AH. Therapeutic inhibition of IL-1 improves hepatocyte survival and promotes death of activated harmful immune cells in a preclin-ical model of AH. Disclosures: Gyongyi Szabo – Consulting: Idenix; Grant/Research Support: BMS, GSK, Cona-tus, Idera, Johnson&Johnson, Novartis, Ocera, Roche, Shering – Plough, Wyeth, Integrated 4��8C Therapeutics, Idera The following people have nothing to disclose: Jan Petrasek, Arvin Irache-ta-Vellve, Shashi Bala, Timea Csak, Karen Kodys, Evelyn A. Kurt-Jones Background: Epidemiological studies revealed that nearly 80% of heavy drinkers with alcoholic liver disease (ALD) also smoke tobacco. This finding suggests that tobacco and possibly its toxins have cofactor roles in ALD pathogenesis. Our research focused on the potential role of NNK as a mediator

of hepa-tocellular injury in ALD because previous efforts showed that other nitrosamines can cause hepatic steatosis or steatohep-atitis with insulin resistance, inflammation, oxidative and ER stress, and lipotoxicity. Moreover, toxic lipids, particularly ceramides, can promote the same effects. Due to the inability to detect significant molecular profiles by routine histological studies, we explored the potential use of matrix assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry as a diagnostic aid for characterizing the nature and possibly etiology of steatohepatitis. Hypothesis: IMS can be used to generate biochemical signatures of steatohepatitis caused by different agents.

0001). There was no significant difference in age between subjects with stainable iron and those without stainable iron. Subjects with positive iron staining had a lower mean BMI than subjects without iron (33.2 versus 34.9 kg/m2, P = 0.0002). Iron staining was more common in non-Hispanics (36%) versus Hispanics (25%, P = 0.04); otherwise, no racial differences were identified between subjects

with stainable iron and those without stainable iron. The results of laboratory tests for subjects with or without stainable hepatic iron are shown in Table 2. Subjects with a liver biopsy sample showing a positive iron stain tended to have evidence of more active http://www.selleckchem.com/products/torin-1.html and advanced disease, as shown by higher serum alanine aminotransferase (ALT) levels (P = 0.004), total bilirubin levels (P < 0.0001), and prothrombin times (P = 0.09) and lower platelet counts (P < 0.0001). In contrast, metabolic abnormalities, including fasting insulin and glucose levels, homeostasis model assessment of insulin resistance (HOMA-IR), and lipid levels, were slightly worse among subjects without stainable iron, but with the exception of total cholesterol (P = 0.02), these were not statistically significant. The high-density LDE225 molecular weight lipoprotein (HDL) level was

higher in subjects without iron (P = 0.004). As might be expected, patients with stainable hepatic iron had higher serum iron studies [iron, total iron-binding capacity (TIBC), ferritin, and transferrin saturation (TS) percentage; for all, P < 0.0001]. We examined the effects of factors potentially influencing body iron stores, such as diet (i.e., iron consumption, vitamin C,

coffee, and tea), alcohol, and other factors (e.g., a history of gastrointestinal bleeding, iron overload, and menstruation in the past 5 years). In a multivariate stepwise logistic regression analysis using these a priori selected variables and adjusting for age, gender, BMI, ethnicity, and diabetes, male sex [odds ratio (OR) = 5.08, 95% confidence interval (CI) = 3.67-7.02, P < 0.0001], older age (OR = 1.02, 95% CI = 1.01-1.04, P = 0.001), and lower BMI (OR = 0.967, 95% CI = 0.941-0.991, P Histamine H2 receptor = 0.009) were independently associated with the presence of hepatic iron. Among women, rare or no periods (in the past 5 years) were also strongly associated with iron deposition (OR = 1.57, 95% CI = 1.28-1.94, P < 0.0001). Three distinct patterns of hepatic iron staining were observed as follows: iron was localized solely in hepatocytes in 63 of 849 subject biopsy samples (7.4%), iron was localized solely in RES cells (mainly Kupffer cells) in 91 of 849 biopsy samples (10.7%), and a mixed pattern of HC/RES staining was present in 139 of 849 biopsy samples (16.4%). Clinical and laboratory values that were significantly different among the various iron-staining groups and subjects without stainable hepatic iron are shown in Table 3.