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Gastrointestinal (GI) lipomatosis has been reported in the GI medicine literature, but esophageal lipomatosis has never been reported at all. We report the case of an 86-year-old man with multiple medical comorbidities who was admitted to our hospital for community-acquired pneumonia. Computed tomography angiography of his pulmonary arteries ruled out the possibility of pulmonary embolism but showed a 9-mm circumferential wall thickening in the proximal esophagus measuring −172 HU, which is similar in opacity to the adipose tissue. The patient was asymptomatic and without any current or prior symptoms of dysphagia or odynophagia. The barium esophagogram was unremarkable; there were no strictures, masses, or mucosal abnormalities. There was no evidence of esophageal dilatation on either imaging modality. Esophageal lipomatosis is only described in a few case reports in the radiological literature and, to our knowledge, has not been reported in the GI literature at all. It is important to highlight in the GI literature this as a benign entity that does not cause symptoms and typically does not warrant invasive diagnostic or therapeutic interventions.

Background and aim Testing for Helicobacter pylori (Hp) infection is recommended for work-up of unexplained iron deficiency anemia (IDA), although the evidence supporting this recommendation is scant. The aim of this study was to investigate the association between Hp infection and unexplained iron deficiency (ID) or IDA in the older adult population without significant upper gastrointestinal source of blood loss. Methods Retrospective single-center cohort study; 523 out of 1253 consecutive patients who underwent esophagogastroduodenoscopy with no significant upper and/or lower gastrointestinal source for blood loss or risk factors for IDA. Comparisons were made between the Hp-positive and Hp-negative groups using Fisher exact test, chi-square test and Student’s t-test. Univariate and multiple logistic regression analyses were used to identify significant risk factors associated with ID and IDA. Results One hundred and three subjects (19.7%) had Hp infection and 420 (80.3%) were negative for Hp. Sixty-eight (22.1%) out of 307 subjects with available serum iron profile had unexplained ID and 28 (5.4%) out of 510 subjects with available hemoglobin profile had unexplained IDA. No association was found between ID/IDA and Hp infection in univariate and multiple logistic regression analyses. Conclusion We found no association between unexplained ID or IDA and Hp infection in older adult population without peptic ulcer disease or significant upper gastrointestinal source of blood loss.

Heartburn that persists despite proton-pump inhibitor (PPI) treatment is a frequent clinical problem with multiple potential causes. Treatments for PPI-refractory heartburn are of unproven efficacy and focus on controlling gastroesophageal reflux with reflux-reducing medication (e.g., baclofen) or antireflux surgery or on dampening visceral hypersensitivity with neuromodulators (e.g., desipramine).Patients who were referred to Veterans Affairs (VA) gastroenterology clinics for PPI-refractory heartburn received 20 mg of omeprazole twice daily for 2 weeks, and those with persistent heartburn underwent endoscopy, esophageal biopsy, esophageal manometry, and multichannel intraluminal impedance-pH monitoring. If patients were found to have reflux-related heartburn, we randomly assigned them to receive surgical treatment (laparoscopic Nissen fundoplication), active medical treatment (omeprazole plus baclofen, with desipramine added depending on symptoms), or control medical treatment (omeprazole plus placebo). The primary outcome was treatment success, defined as a decrease of 50% or more in the Gastroesophageal Reflux Disease (GERD)-Health Related Quality of Life score (range, 0 to 50, with higher scores indicating worse symptoms) at 1 year.A total of 366 patients (mean age, 48.5 years; 280 men) were enrolled. Prerandomization procedures excluded 288 patients: 42 had relief of their heartburn during the 2-week omeprazole trial, 70 did not complete trial procedures, 54 were excluded for other reasons, 23 had non-GERD esophageal disorders, and 99 had functional heartburn (not due to GERD or other histopathologic, motility, or structural abnormality). The remaining 78 patients underwent randomization. The incidence of treatment success with surgery (18 of 27 patients, 67%) was significantly superior to that with active medical treatment (7 of 25 patients, 28%; P = 0.007) or control medical treatment (3 of 26 patients, 12%; P0.001). The difference in the incidence of treatment success between the active medical group and the control medical group was 16 percentage points (95% confidence interval, -5 to 38; P = 0.17).Among patients referred to VA gastroenterology clinics for PPI-refractory heartburn, systematic workup revealed truly PPI-refractory and reflux-related heartburn in a minority of patients. For that highly selected subgroup, surgery was superior to medical treatment. (Funded by the Department of Veterans Affairs Cooperative Studies Program; ClinicalTrials.gov number, NCT01265550.).

Hydrothorax is a rare complication of peritoneal dialysis occurring in about 2% of continuous ambulatory peritoneal dialysis (CAPD) patients. These effusions occur soon after the onset of dialysis and are usually right-sided. We describe an unusual case of late-onset, left-sided, and recurrent effusions in the setting of CAPD. A 67-year-old patient with end-stage renal disease on CAPD for the last three years was admitted to our hospital with acute hypoxic respiratory failure secondary to a left-sided effusion. Although previously asymptomatic, he had three admissions for bilateral (left predominant) effusions in the last year, all of which were found to be transudative on analysis. Therapeutic thoracentesis once again revealed a transudative effusion with an elevated pleural fluid-serum glucose gradient. On this occasion, pleuro-peritoneal scintigraphy with technetium-99m was performed, uncovering a communication between the peritoneal cavity and the left pleural cavity. The peritoneal dialysis was substituted with hemodialysis, and the patient showed an eventual resolution of left-sided effusions within 18 months. Hydrothorax in peritoneal dialysis is due to the transudation of fluid across congenital or acquired pleuro-peritoneal communications. Pleural fluid with protein content less than 3 g/dl, high glucose, and low lactate dehydrogenase (LDH) relative to blood, and the presence of both D and L isomers of lactic acid suggest a transdiaphragmatic leak. Early diagnosis via peritoneal scintigraphy and appropriate management can prevent significant morbidity and mortality.

A capsule formulation of mesalamine granules (MG) was developed for once-daily dosing and better compliance. The study aim was to evaluate MG efficacy and tolerability in maintaining ulcerative colitis (UC) remission.Pooled analysis of 2 identical phase 3, randomized, double-blind trials of once-daily MG 1.5 g or placebo for up to 6 months. The primary endpoint was percentage of patients remaining relapse-free at month 6 versus placebo. Relapse was defined as revised Sutherland Disease Activity Index (SDAI) rectal bleeding score ≥1 and mucosal appearance score ≥2, UC flare, or UC-related adverse event (AE).Data were pooled for patients receiving MG (n = 373) and placebo (n = 189). Significantly more patients were relapse-free at 6 months with MG (79.4%) than placebo (62.4%; P0.001) and across subgroups based on select demographic and baseline characteristics (P0.05). Secondary outcome measures including rectal bleeding, physician rating of disease activity, stool frequency, total SDAI score, and relapse-free duration favored MG (P0.01). Common AEs with MG and placebo, respectively, were headache (10.9% and 7.6%), diarrhea (7.9% and 7.0%), and abdominal pain (6.3% and 6.5%).Once-daily MG was more efficacious than and as well tolerated as placebo in maintaining UC remission. ClinicalTrials.gov identifiers: NCT00744016 and NCT00767728.

Summary Background Mesalazine (mesalamine) granules (MG) were shown to be effective for the maintenance of remission of ulcerative colitis (UC) in two double-blind placebo-controlled trials. Aim To evaluate the efficacy of once-daily MG for maintenance of remission in patients with UC who switched from other 5-aminosalicylic acid (5-ASA) formulations. Methods Data from two independent multicenter, randomised, double-blind, placebo-controlled, 6-month trials evaluating patients with UC in remission were combined for analysis of a subpopulation of patients who switched from other 5-ASA formulations to MG 1.5 g or placebo upon randomisation. The primary endpoint was the percentage of patients who remained relapse-free at Month 6 or end of treatment. Relapse was defined as a Sutherland Disease Activity Index (SDAI) rectal bleeding score ≥1 and mucosal appearance score ≥2, a UC flare or medication used to treat a UC flare. Results Of the 487 patients who received 5-ASA maintenance therapy at enrolment, 322 were in the MG group and 165 were in the placebo group. The percentage of patients who remained relapse-free (based on Sutherland Disease Activity Index scores) after 6 months was significantly higher with MG than placebo (78.3% vs. 58.8%, P

Aliment Pharmacol Ther 2010; 32: 990–999 Summary Background Ulcerative colitis (UC) is a chronic relapsing and remitting idiopathic inflammatory bowel disorder. Aim To evaluate once-daily mesalamine (mesalazine) granules (MG) for maintenance of remission of UC. Methods Randomized, double-blind, placebo-controlled trial of patients (n = 209 MG, n = 96 placebo) with UC in remission [revised Sutherland Disease Activity Index (SDAI) rectal bleeding = 0, mucosal appearance

Background The risk of postpolypectomy bleeding (PPB) in patients undergoing colonoscopy on uninterrupted clopidogrel therapy has not been established. Objective To assess the PPB rate and outcome and identify risk factors associated with PPB in patients taking clopidogrel. Design Single-center, retrospective study. Demographics, clinical parameters, polyp characteristics, polypectomy techniques, and postpolypectomy events in the groups were compared by univariate analysis. Stepwise logistic regression analyses identified independent risk factors associated with PPB. Setting Veterans Affairs Medical Center. Patients A total of 142 patients (375 polypectomies) taking clopidogrel (cases) and 1243 patients (3226 polypectomies) not taking clopidogrel (controls). Interventions None. Main Outcome Measurements Postpolypectomy bleeding, hospitalization, and mortality. Results The immediate (intraprocedural) bleeding rate was similar in the 2 groups (2.1% vs 2.1%). Delayed (postprocedural) PPB rate was higher in the group taking clopidogrel (3.5% vs 1.0%, P = .02). Delayed bleeding of significance requiring hospitalization and transfusion/intervention was also higher in patients taking clopidogrel (2.1% vs 0.4%, P = .04). The length of hospital stay and interventions for PPB were comparable between the 2 groups. There was no mortality. Concomitant use of clopidogrel and aspirin/other nonsteroidal anti-inflammatory drugs (odds ratio 3.7; 95% CI, 1.6-8.5) and the number of polyps removed (OR 1.3; 95% CI, 1.2-1.4) were the only significant risk factors associated with PPB. Clopidogrel alone was not an independent risk factor for PPB. Limitations Retrospective study and small number of patients with PPB. Conclusions The PPB rate is significantly higher in patients undergoing polypectomy while taking clopidogrel and concomitant aspirin/nonsteroidal anti-inflammatory drugs; however, the risk is small and the outcome is favorable. Routine cessation of clopidogrel in patients before colonoscopy/polypectomy is not necessary.

Goals To evaluate the efficacy and safety of mesalamine granules 1.5 g once daily for maintenance of ulcerative colitis (UC) remission. Background Mesalamine is a first-line treatment for induction and maintenance of UC remission. Study A phase 3, randomized, double-blind, placebo-controlled trial of patients with a history of mild to moderate UC, currently in remission, who received mesalamine granules once daily for 6 months. The primary efficacy endpoint was percentage of patients maintaining UC remission at 6 months. Results A significantly greater percentage of patients receiving mesalamine granules versus placebo were in remission at 6 months (79.9% vs. 66.7%; P=0.03). A greater percentage of patients receiving mesalamine granules maintained a revised Sutherland Disease Activity Index (SDAI)≤2 with no individual component of revised SDAI>1 and rectal bleeding=0 at 6 months (72.0% vs. 58.1%; P=0.04). No significant differences between groups were observed for change from baseline to 6 months for total SDAI score or its components (ie, stool frequency, rectal bleeding, mucosal appearance, physician's rating of disease). Mesalamine granules treatment resulted in a significantly longer remission duration versus placebo (P=0.02) and decreased patients' risk of relapse by 43% (hazard ratio=0.57; 95% confidence interval, 0.35-0.93; P=0.02). Mesalamine granules were well tolerated, and adverse events related to hepatic, renal, and pancreatic function-potential concerns with long-term treatment-occurred at a rate similar to placebo. Conclusions Once-daily mesalamine granules are efficacious and safe for the maintenance of UC remission.

Background Patients with ulcerative colitis (UC) who achieve remission with corticosteroids often relapse after tapering or discontinuation; alternative treatments limiting steroid exposure and UC relapse would be beneficial. It remains uncertain whether patients with corticosteroid-induced remission experience benefit with mesalamine granules (MG), a locally acting aminosalicylate extended-release capsule formulation for maintenance of UC remission in adults. Aims Efficacy and safety of MG 1.5 g once daily was evaluated in patients with UC in corticosteroid-induced remission. Methods Data from patients with previous corticosteroid use to achieve baseline UC remission were analyzed from two 6-month randomized, double-blind, placebo-controlled trials and a 24-month open-label extension (OLE). Six-month relapse-free rates were assessed using the revised Sutherland Disease Activity Index. UC-related adverse events (AEs) were recorded during the 30 months. Results Included were 158 steroid-treated patients in UC remission (MG, n = 105; placebo, n = 53) and 74/105 MG-treated patients who continued MG in the OLE. A significantly larger percentage of patients remained relapse-free at 6 months with MG (77.1 %) versus placebo (54.7 %; P = 0.006), with a 55 % reduction in relapse risk (hazard ratio [HR] 0.45; 95 % CI 0.25–0.79). There was a similar (49.2 %) reduction in risk of UC-related AEs at 6 months (HR 0.51; 95 % CI 0.31–0.84; P = 0.009) that was sustained during the OLE. Conclusions MG 1.5 g once daily administered for maintenance of corticosteroid-induced remission was associated with low risk of relapse and UC-related AEs. ClinicalTrials.gov NCT00744016, NCT00767728, and NCT00326209.

SUMMARY Leaf spot disease caused by Alternaria helianthi (Hansf.) is an important fungal disease of sunflower in India and elsewhere. Non-availability of known sources for resistance to Alternaria is a major constraint in sunflower breeding. Hence, seeds of sunflower genotypes were subjected to gamma-irradiation to develop mutant populations. Mutants were selected from the M2 generation based on percent disease incidence and were passed on to the M3 generation. Genomic DNA from leaf samples was evaluated by PCR amplification using random decamer primers and the amplified DNA fragments from mutants were compared with their respective controls. Single marker and stepwise regression analysis carried out in relation to percent disease index indicate that the alleles OPC5-B, K, J, OPA12-D and OPA15-A are strongly associated with Alternaria helianthi resistance.

BACKGROUND: Aspirin, by virtue of inhibition of platelet hemostatic function, is withheld before many invasive procedures because of the bleeding risk. American Society of Gastrointestinal Endoscopy guidelines acknowledge the paucity of “high quality data” to make recommendations regarding the use of aspirin (ASA) and nonsteroidal anti-inflammatory drugs (NSAIDs) before endoscopic procedures. Yet the majority of endoscopists hold ASA/NSAIDs before polypectomy. METHODS: This single-center, retrospective, cohort study was conducted at Veterans Affairs Medical Center, Syracuse, NY. The objectives were to assess the postpolypectomy bleeding risk in ASA/NSAID users in a large cohort of veterans undergoing colonoscopic polypectomy and to identify risk factors associated with postpolypectomy bleeding. All patients undergoing polypectomy between January 2002 and October 2007 were eligible. Patients on anticoagulants/other antiplatelet agents were excluded. Patients were selected randomly by cluster sampling techniques. Electronic medical and pharmacy records were reviewed for patient demographics, polypectomy techniques, and postpolypectomy bleeding rates. Univariate analysis was performed between patients on ASA and NSAIDs (group A) versus those not on ASA or NSAIDs (group B). Multiple regression analysis was performed to identify independent risk factors associated with postpolypectomy bleeding. RESULTS: Five hundred two (43%) of 1174 patients (mean age 66 years, 92% white) were on ASA or NSAIDs, or both. There was no significant difference between postpolypectomy bleeding rates among the 2 groups (3.2% vs 3.0%). Age, sex, polyp characteristics, and polypectomy techniques were comparable between groups A and B. In multiple logistic regression analysis, ASA or NSAID use was not a significant risk factor for postpolypectomy bleeding. Number of polyps removed per patient was the only risk factor significantly associated with postpolypectomy bleeding (P .01, odds ratio 1.3, 95% confidence interval, 1.18-1.43). CONCLUSIONS: In this large study, use of ASA or NSAIDs did not increase the risk of postpolypectomy bleeding. Cessation of ASA/NSAIDs before colonoscopy/polypectomy is therefore unnecessary. Published by Elsevier Inc. • The American Journal of Medicine (2012) 125, 1222-1227

Introduction The causes of diffuse abdominal pain following pelvic surgery are numerous. We present a rare case of acute abdominal pain in a woman in the post-partum period. Case presentation A 25-year-old Caucasian woman with neurofibromatosis type 1 presented to our hospital with diffuse abdominal pain immediately after a cesarean section. The patient was acutely ill and toxic with a fever of 38.8°C, a pulse of 120 beats per minute and a distended abdomen with absent bowel sounds. A computed tomography scan showed air in the wall of the stomach and portal venous system. The patient was successfully treated with intravenous antibiotics, bowel rest and total parenteral nutrition. Conclusion It is rare for a case of emphysematous gastritis associated with portal venous air to be treated successfully without surgery. To the best of our knowledge, to date there has been no reported association of emphysematous gastritis with neurofibromatosis.

Total creatine kinase and its isoenzymes CK-MB and CK-BB were measured in the serum of patients admitted with acute abdominal pain or signs suggestive of an intraabdominal catastrophe. Total creatine kinase was measured by automated spectrophotometry, CK-MB by chemiluminescent assay, and CK-BB by radioimmunoassay. Patients were grouped according to their final diagnosis: intestinal infarction (N = 8); all other diagnoses (N = 22); controls (N = 20). CK-BB in the infarction group (22.3 +/- 5.3 ng/ml, mean +/- SE) was significantly greater (P less than 0.01) than in the noninfarction or the control groups (11.0 +/- 0.8 ng/ml and 5.8 +/- 0.7 ng/ml, respectively). There were no differences in total creatine kinase and CK-MB in the three groups. Stepwise deletion multiple regression analysis of 26 independent regressors showed that among a cluster of six significant variables (R2 = 0.92, P less than 0.005), CK-BB greater than 20 ng/ml was the best predictor of intestinal infarction. Results of this study indicate that CK-BB isoenzyme measurement may be useful in the diagnosis of intestinal infarction in man.

We studied the effect of gastric versus jejunal tube feedings on gastric pH and evaluated the acid-inhibiting effects of continuous gastric and jejunal infusions of cimetidine. pH was monitored by an intragastric pH probe in 19 gastrostomy and 13 jejunostomy patients during fasting, continuous infusions of Osmolyte, cimetidine, and simultaneously Osmolyte and cimetidine. Gastric Osmolyte increased fasting pH from a mean of 1.32 to 2.78 (P less than 0.01), while jejunal Osmolyte did not (pH 1.02). Continuous gastric infusion of cimetidine maintained a high gastric pH (5.06) in 17 of 19 patients. Jejunal cimetidine also achieved therapeutic serum levels and raised gastric pH to 4.81 in nine of 13 patients. We conclude that the persistently low gastric pH during jejunostomy tube feeding may play a major role in the upper gastrointestinal bleeding previously observed in such patients and that continuous gastric and jejunal cimetidine infusions effectively raise and sustain a high gastric pH.

Importance Clostridium difficile is the most common cause of health care–associated infection in US hospitals. Recurrence occurs in 25% to 30% of patients. Objective To determine the safety, fecal colonization, recurrence rate, and optimal dosing schedule of nontoxigenic C difficile strain M3 (VP20621; NTCD-M3) for prevention of recurrent C difficile infection (CDI). Design, Setting, and Participants Phase 2, randomized, double-blind, placebo-controlled, dose-ranging study conducted from June 2011 to June 2013 among 173 patients aged 18 years or older who were diagnosed as having CDI (first episode or first recurrence) and had successfully completed treatment with metronidazole, oral vancomycin, or both at 44 study centers in the United States, Canada, and Europe. Interventions Patients were randomly assigned to receive 1 of 4 treatments: oral liquid formulation of NTCD-M3, 10 4 spores/d for 7 days (n = 43), 10 7 spores/d for 7 days (n = 44), or 10 7 spores/d for 14 days (n = 42), or placebo for 14 days (n = 44). Main Outcomes and Measures The primary outcome was safety and tolerability of NTCD-M3 within 7 days of treatment. Exploratory secondary outcomes included fecal colonization with NTCD-M3 from end of study drug through week 6 and CDI recurrence from day 1 through week 6. Results Among 168 patients who started treatment, 157 completed treatment. One or more treatment-emergent adverse events were reported in 78% of patients receiving NTCD-M3 and 86% of patients receiving placebo. Diarrhea and abdominal pain were reported in 46% and 17% of patients receiving NTCD-M3 and 60% and 33% of placebo patients, respectively. Serious treatment-emergent adverse events were reported in 7% of patients receiving placebo and 3% of all patients who received NTCD-M3. Headache was reported in 10% of patients receiving NTCD-M3 and 2% of placebo patients. Fecal colonization occurred in 69% of NTCD-M3 patients: 71% with 10 7 spores/d and 63% with 10 4 spores/d. Recurrence of CDI occurred in 13 (30%) of 43 placebo patients and 14 (11%) of 125 NTCD-M3 patients (odds ratio [OR], 0.28; 95% CI, 0.11-0.69; P = .006); the lowest recurrence was in 2 (5%) of 43 patients receiving 10 7 spores/d for 7 days (OR, 0.1; 95% CI, 0.0-0.6; P = .01 vs placebo]). Recurrence occurred in 2 (2%) of 86 patients who were colonized vs 12 (31%) of 39 patients who received NTCD-M3 and were not colonized (OR, 0.01; 95% CI, 0.00-0.05; P Conclusions and Relevance Among patients with CDI who clinically recovered following treatment with metronidazole or vancomycin, oral administration of spores of NTCD-M3 was well tolerated and appeared to be safe. Nontoxigenic C difficile strain M3 colonized the gastrointestinal tract and significantly reduced CDI recurrence. Trial Registration clinicaltrials.gov Identifier:NCT01259726

The purpose of this study was to evaluate whole gut lavage with polyethylene glycol electrolyte solution (Colyte), as a potentially adjunctive measure in lowering serum acetaminophen levels. The effect of bowel lavage was evaluated on serial serum acetaminophen concentrations after 2-g and 4-g doses in 7 and 12 male patients, respectively. Mean peak level of serum acetaminophen after 2 g (60 min after intake) was not significantly lowered by bowel lavage. After 4 g, peak acetaminophen serum levels were significantly lower after bowel lavage (65.4% of controls, P < 0.001). Urinary concentrations of the mercapturic acid conjugate of the toxic metabolite were also significantly reduced by lavage (55% after 2 g and 45% after 4 g, P < 0.01). Activated charcoal given orally after administration of 4 g of acetaminophen had no significant effect on peak serum levels and had no additive effect on lavage. These studies suggest that rapid, complete bowel lavage with a polyethylene glycol electrolyte solution may be beneficial as an adjunct to the treatment of the acetaminophen intoxication.

Approximately 50% of Helicobacter pylori isolates produce a cytotoxin in vitro that induces vacuolation of eukaryotic cells. To determine the in vivo relevance of this phenomenon, we sought to detect cytotoxin-neutralizing antibodies in sera from H. pylori-infected persons. As a group, sera from 29 H. pylori-infected patients neutralized the activity of the purified cytotoxin to a significantly greater extent than sera from 24 uninfected persons (P = 0.007). The cytotoxin neutralizing activity in sera from H. pylori-infected persons was mediated predominantly by the purified IgG fraction. Sera from H. pylori-infected persons neutralized the cytotoxins produced by multiple H. pylori strains, but failed to neutralize trimethylamine-induced cell vacuolation. Neutralization of cytotoxin activity by human or immune rabbit sera was associated with immunoblot IgG recognition of an 87-kD H. pylori protein. Similarly, neutralization of the toxin by sera was associated with IgG recognition of the purified cytotoxin in an enzyme-linked immunosorbent assay (P less than 0.0001). The presence of cytotoxin-neutralizing antibodies in sera from H. pylori-infected persons indicates that the cytotoxin is synthesized in vivo.

Mesalamine granules (MG) are the first 5-aminosalicylate (5-ASA) formulation to use an innovative delivery system that combines delayedand extended-release mechanisms to release mesalamine directly in the ileum and colon. Agents with a low pill burden and favorable safety profile are more likely to enhance patient compliance in the long-term maintenance of UC remission. Two similarly designed multicenter, randomized, doubleblind, placebo-controlled, phase 3 trials (RCTs) have individually demonstrated significant efficacy of MG (1.5 g, q. d.) for the long-term maintenance of ulcerative colitis (UC). Additionally, an open-label extension trial (OLT) with new and rollover subjects from the two phase 3 trials was conducted to study the long term safety of MG for maintenance of UC remission. The integrated safety data in the expanded population of subjects who received MG from all three trials are presented here (All MG population). Methods: Data for the All MG analyses (n=557) included subjects who received MG in the two RCTs (n=367) and the OLT. The OLT included 197 MGtreated patients who rolled over from the RCTs; and 190 MG naive patients (83 placebo-treated patients from the RCTs, and 107 new patients) all in UC remission. Results: Of 557 patients included in the analysis, 250 patients were exposed for >1 year and 354 were exposed to MG (1.5 g, q.d.) for >6 months. Incidence of treatment-emergent adverse events (TEAEs) was 69.7% in the All MG group. Majority of TEAEs were mild or moderate in intensity, with a profile similar to that during the 6month RCTs. The notably lower incidence of UC flare observed in the RCTs for MG (10.9%) versus placebo (24.3%) was maintained (10.4%) in the OLT. Other common TEAEs in the All MG group were headache (13.8%), diarrhea (9.7%), nasopharyngitis (8.8%), abdominal pain (7.7%), sinusitis (5.4%), and nausea (5.2%). Incidences of serious adverse events and TEAEs leading to study discontinuation were comparable between the 6-month RCT group and the All MG population in the open label study. Occurrences of renal, hepatic, and pancreatic adverse events in patients in the open-label study were ≤1%. Long term compliance for the once-daily treatment regimen was high: mean compliance was ≥ 95% in each treatment group in the RCT population, and 88% for the All MG population. Conclusions: The favorable safety profile of MG when combined with a high compliance of once-daily dosing may support its dispensation as first-line therapy for long-term maintenance of UC remission.

Mesalamine granules (MG) are the first 5-aminosalicylate (5-ASA) formulation to use an innovative delivery system that combines delayedand extended-release mechanisms to release mesalamine directly in the ileum and colon. Agents with a low pill burden and favorable safety profile are more likely to enhance patient compliance in the long-term maintenance of UC remission. Two similarly designed multicenter, randomized, doubleblind, placebo-controlled, phase 3 trials (RCTs) have individually demonstrated significant efficacy of MG (1.5 g, q. d.) for the long-term maintenance of ulcerative colitis (UC). Additionally, an open-label extension trial (OLT) with new and rollover subjects from the two phase 3 trials was conducted to study the long term safety of MG for maintenance of UC remission. The integrated safety data in the expanded population of subjects who received MG from all three trials are presented here (All MG population). Methods: Data for the All MG analyses (n=557) included subjects who received MG in the two RCTs (n=367) and the OLT. The OLT included 197 MGtreated patients who rolled over from the RCTs; and 190 MG naive patients (83 placebo-treated patients from the RCTs, and 107 new patients) all in UC remission. Results: Of 557 patients included in the analysis, 250 patients were exposed for >1 year and 354 were exposed to MG (1.5 g, q.d.) for >6 months. Incidence of treatment-emergent adverse events (TEAEs) was 69.7% in the All MG group. Majority of TEAEs were mild or moderate in intensity, with a profile similar to that during the 6month RCTs. The notably lower incidence of UC flare observed in the RCTs for MG (10.9%) versus placebo (24.3%) was maintained (10.4%) in the OLT. Other common TEAEs in the All MG group were headache (13.8%), diarrhea (9.7%), nasopharyngitis (8.8%), abdominal pain (7.7%), sinusitis (5.4%), and nausea (5.2%). Incidences of serious adverse events and TEAEs leading to study discontinuation were comparable between the 6-month RCT group and the All MG population in the open label study. Occurrences of renal, hepatic, and pancreatic adverse events in patients in the open-label study were ≤1%. Long term compliance for the once-daily treatment regimen was high: mean compliance was ≥ 95% in each treatment group in the RCT population, and 88% for the All MG population. Conclusions: The favorable safety profile of MG when combined with a high compliance of once-daily dosing may support its dispensation as first-line therapy for long-term maintenance of UC remission.

Pleural effusion that develops in a patient with cirrhosis and portal hypertension, in the absence of cardiopulmonary disease, is termed hepatic hydrothorax. Hepatic hydrothorax very rarely presents in the absence of ascites. Although the exact mechanism is somewhat controversial, pleural effusion occurs when ascitic fluid moves through diaphragmatic defects which are opened up by increased intra-abdominal pressure. We report a case report of cirrhotic pleural effusion in a patient with no clinical or radiographic evidence of ascites and discuss the pathogenesis, diagnosis and management of this condition.

The morphological response of rabbit parietal cells to aspirin was evaluated by grading several ultra-structural features including the extent of the tubulovesicular system, intracellular secretory canaliculi, and microvilli. After exposure of isolated parietal cells and gastric glands to aspirin or histamine, there was an approximately twofold increase in the ratio of secretory to nonsecretory parietal cells, and depletion of extracellular Ca2+ abolished the aspirin-induced morphological changes. Morphometry in parietal cells showed that aspirin induced a sixfold increase in secretory canalicular membrane elaboration. Aspirin potentiated histamine-induced parietal cell respiration and aminopyrine uptake ratio but did not increase basal respiration or aminopyrine uptake, suggesting an apparent dissociation from aspirin-induced morphological changes.