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Objectives: Breath tests (BTs) are important for the diagnosis of carbohydrate maldigestion syndromes and small intestinal bacterial overgrowth (SIBO). However, standardization is lacking regarding indications for testing, test methodology and interpretation of results. A consensus meeting of experts was convened to develop guidelines for clinicians and research., Methods: Pre-meeting survey questions encompassing five domains; indications, preparation, performance, interpretation of results, and knowledge gaps, were sent to 17 clinician-scientists, and 10 attended a live meeting. Using an evidence-based approach, 28 statements were finalized and voted on anonymously by a working group of specialists., Results: Consensus was reached on 26 statements encompassing all five domains. Consensus doses for lactulose, glucose, fructose and lactose BT were 10, 75, 25 and 25 g, respectively. Glucose and lactulose BTs remain the least invasive alternatives to diagnose SIBO. BT is useful in the diagnosis of carbohydrate maldigestion, methane-associated constipation, and evaluation of bloating/gas but not in the assessment of oro-cecal transit. A rise in hydrogen of ≥20 p.p.m. by 90 min during glucose or lactulose BT for SIBO was considered positive. Methane levels ≥10 p.p.m. was considered methane-positive. SIBO should be excluded prior to BT for carbohydrate malabsorption to avoid false positives. A rise in hydrogen of ≥20 p.p.m. from baseline during BT was considered positive for maldigestion., Conclusions: BT is a useful, inexpensive, simple and safe diagnostic test in the evaluation of common gastroenterology problems. These consensus statements should help to standardize the indications, preparation, performance and interpretation of BT in clinical practice and research.

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: Antibiotics for presumed small intestinal bacterial overgrowth have been shown to improve irritable bowel syndrome symptoms in at least 40% of subjects. A lactulose breath test for small intestinal bacterial overgrowth has been used to select patients who will respond. However, its predictive value, using the classic definition of a positive lactulose breath test, has been disappointing., Aims: We conducted a retrospective evaluation to study characteristics of the lactulose breath test that may be predictive of a response to antibiotics in patients with the irritable bowel syndrome., Methods: A clinical practice database was interrogated for consecutive patients who had a lactulose breath test for irritable bowel syndrome symptoms and a subsequent antibiotic course. Hydrogen + methane levels with carbon dioxide correction were plotted against time. Various profiles of the breath test curves were catalogued and compared with respect to their predictive value for symptom response to antibiotics., Results: Lactulose breath test graphs of 561 patients of all irritable bowel syndrome subtypes were grouped into categories based on their hydrogen + methane levels with respect to time. Of subjects whose hydrogen + methane rise was <20 ppm throughout the test (group 1; N = 95), 94.7% improved after antibiotics (95% CI 90.1-99.3). Of those with a rise <20 ppm within the first 90 min but a rise >50 ppm thereafter (group 3; N = 53), 47.2% improved (95% CI 33.7-60.6). The difference between groups 1 and 3 was statistically significant P < 0.001., Conclusion: A lactulose breath test appears to be useful in predicting response to antibiotics in patients with the irritable bowel syndrome. A hydrogen + methane rise <20 ppm throughout the duration of the test is most predictive. This observation contradicts the classic definition of a positive lactulose breath test.

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.

Background: Budesonide foam, a rectally administered, second-generation corticosteroid with extensive hepatic first-pass metabolism, is efficacious for the treatment of mild-to-moderate ulcerative proctitis and ulcerative proctosigmoiditis., Aim: The aim of this study was to comprehensively assess the safety and pharmacokinetic profile of budesonide foam., Methods: Data from five phase III studies were pooled to further evaluate safety, including an open-label study (once-daily treatment for 8 weeks), an active-comparator study (once-daily treatment for 4 weeks), and two placebo-controlled studies and an open-label extension study (twice-daily treatment for 2 weeks, then once daily for 4 weeks). Data from the placebo-controlled studies and two phase I studies (i.e., patients with mild-to-moderate ulcerative colitis and healthy volunteers) were pooled to evaluate the pharmacokinetics of budesonide foam., Results: A similar percentage of patients reported adverse events in the budesonide foam and placebo groups, with the majority of adverse events being mild or moderate in intensity (93.3 vs 96.0%, respectively). Adverse events occurred in 41.4 and 36.3% of patients receiving budesonide foam and placebo, respectively. Mean morning cortisol concentrations remained within the normal range for up to 8 weeks of treatment; there were no clinically relevant effects of budesonide foam on the hypothalamic-pituitary-adrenal axis. Population pharmacokinetic analysis demonstrated low systemic exposure after budesonide foam administration., Conclusions: This integrated analysis demonstrated that budesonide foam for the induction of remission of distal ulcerative colitis is safe overall, with no clinically relevant effects on the hypothalamic-pituitary-adrenal axis.

Background & Aims: Budesonide is a high-potency, second-generation corticosteroid designed to minimize systemic adverse consequences of conventional corticosteroids. We performed 2 randomized, phase 3 trials to evaluate the ability of budesonide rectal foam, formulated to optimize retention and provide uniform delivery of budesonide to the rectum and distal colon, to induce remission in patients with ulcerative proctitis or ulcerative proctosigmoiditis., Methods: Two identically designed, randomized, double-blind, placebo-controlled trials evaluated the efficacy of budesonide foam for induction of remission in 546 patients with mild to moderate ulcerative proctitis or ulcerative proctosigmoiditis who received budesonide foam 2 mg/25 mL twice daily for 2 weeks, then once daily for 4 weeks, or placebo., Results: Remission at week 6 occurred significantly more frequently among patients receiving budesonide foam than placebo (Study 1: 38.3% vs 25.8%; P = .0324; Study 2: 44.0% vs 22.4%; P < .0001). A significantly greater percentage of patients receiving budesonide foam vs placebo achieved rectal bleeding resolution (Study 1: 46.6% vs 28.0%; P = .0022; Study 2: 50.0% vs 28.6%; P = .0002) and endoscopic improvement (Study 1: 55.6% vs 43.2%; P = .0486; Study 2: 56.0% vs 36.7%; P = .0013) at week 6. Most adverse events occurred at similar frequencies between groups, although events related to changes in cortisol values were reported more frequently with budesonide foam. There were no cases of clinically symptomatic adrenal insufficiency., Conclusions: Budesonide rectal foam was well tolerated and more efficacious than placebo in inducing remission in patients with mild to moderate ulcerative proctitis and ulcerative proctosigmoiditis. ClinicalTrials.gov ID: NCT01008410 and NCT01008423., (Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.)

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 < 0.001). Rectal bleeding, stool frequency and the physician's rating of disease activity remained unchanged after 6 months in a higher percentage of patients using MG compared with those on placebo (P < 0.004 for each endpoint)., Conclusion: Mesalazine granules 1.5 g once-daily is effective for maintenance of remission in UC patients who switch from other 5-ASA formulations. ClinicalTrials.gov identifiers NCT00744016, NCT00767728., (© 2012 Blackwell Publishing Ltd.)

Background: Neurokinin receptors may play an important role in the visceral hypersensitivity and exaggerated motor/secretory activity associated with diarrhoea-predominant irritable bowel syndrome (IBS-D)., Aim: To evaluate the effects of DNK333, a novel neurokinin antagonist, in women with IBS-D., Methods: In two consecutive phase II studies, women with IBS-D were randomised to twice-daily (b.d.) DNK333 25 mg, DNK333 100 mg or placebo for 2 weeks (Trial 1), or DNK333 25 mg b.d. or placebo for 4 weeks (Trial 2). Primary efficacy variables studied were change from baseline of stool form at week 2, and satisfactory relief of IBS-related abdominal pain/discomfort and global IBS-D symptoms. Secondary efficacy variables, pharmacokinetics and safety were also evaluated., Results: In total, 315 subjects were randomised. There were no statistically significant differences between treatment groups for the primary efficacy variables. However, analysis of combined data from both trials revealed significant differences favouring DNK333 25 mg over placebo for satisfactory relief of IBS-related abdominal pain/discomfort and global IBS-D symptoms. Trends favouring improvement with DNK333 25 mg vs. placebo were seen for all secondary efficacy variables. DNK333 had a safety profile similar to placebo., Conclusions: DNK333 25 mg b.d. appears to be effective and well tolerated in women with IBS-D. Further studies with neurokinin antagonists are warranted., (© 2011 Blackwell Publishing Ltd.)

Background: Evidence suggests that gut flora may play an important role in the pathophysiology of the irritable bowel syndrome (IBS). We evaluated rifaximin, a minimally absorbed antibiotic, as treatment for IBS., Methods: In two identically designed, phase 3, double-blind, placebo-controlled trials (TARGET 1 and TARGET 2), patients who had IBS without constipation were randomly assigned to either rifaximin at a dose of 550 mg or placebo, three times daily for 2 weeks, and were followed for an additional 10 weeks. The primary end point, the proportion of patients who had adequate relief of global IBS symptoms, and the key secondary end point, the proportion of patients who had adequate relief of IBS-related bloating, were assessed weekly. Adequate relief was defined as self-reported relief of symptoms for at least 2 of the first 4 weeks after treatment. Other secondary end points included the percentage of patients who had a response to treatment as assessed by daily self-ratings of global IBS symptoms and individual symptoms of bloating, abdominal pain, and stool consistency during the 4 weeks after treatment and during the entire 3 months of the study., Results: Significantly more patients in the rifaximin group than in the placebo group had adequate relief of global IBS symptoms during the first 4 weeks after treatment (40.8% vs. 31.2%, P=0.01, in TARGET 1; 40.6% vs. 32.2%, P=0.03, in TARGET 2; 40.7% vs. 31.7%, P<0.001, in the two studies combined). Similarly, more patients in the rifaximin group than in the placebo group had adequate relief of bloating (39.5% vs. 28.7%, P=0.005, in TARGET 1; 41.0% vs. 31.9%, P=0.02, in TARGET 2; 40.2% vs. 30.3%, P<0.001, in the two studies combined). In addition, significantly more patients in the rifaximin group had a response to treatment as assessed by daily ratings of IBS symptoms, bloating, abdominal pain, and stool consistency. The incidence of adverse events was similar in the two groups., Conclusions: Among patients who had IBS without constipation, treatment with rifaximin for 2 weeks provided significant relief of IBS symptoms, bloating, abdominal pain, and loose or watery stools. (Funded by Salix Pharmaceuticals; ClinicalTrials.gov numbers, NCT00731679 and NCT00724126.).

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 <2] who took MG 1.5 g or placebo once-daily for up to 6 months. Primary efficacy endpoint: the percentage of patients who remained relapse-free at month 6/end of treatment. Relapse was defined as SDAI rectal bleeding score ≥1 and a mucosal appearance score ≥2, a UC flare, or initiation of medication to treat a UC flare., Results: The percentage of relapse-free patients at month 6/end of treatment was higher with MG than placebo (78.9% vs. 58.3%, P < 0.001) in the intent-to-treat analysis. Significant differences (P ≤ 0.025) favouring MG were observed for most secondary endpoints including improvement in rectal bleeding, physician's disease activity rating, stool frequency, the SDAI at month 6/end of treatment, patients classified as a treatment success and relapse-free duration. The incidence of adverse events was similar between groups., Conclusions: Once-daily mesalamine (mesalazine) was effective in maintaining remission of UC for 6 months., (© 2010 Salix Pharmaceuticals.)

The role of biliary excretion in Tc-99m ethylenedicysteine (EC) renal imaging was studied. Of 2,215 dynamic renal studies performed with Tc-99m EC, only nine cases of gallbladder visualizations and/or biliary excretion were identified. In no case did biliary excretion affect the interpretation of the renal study.

The aim of this study was to facilitate the diagnosis of brain death based on semi-quantitative parameters as well as the other scintigraphic signs and symptoms of brain death. Altogether, 72 studies were performed in 54 patients (35 males, 19 females) to evaluate the diagnoses of brain death which were confirmed in 49 cases. Perfusion dynamic acquisition and static imaging were performed after the intravenous injection of 700-900 MBq 99Tcm-hexamethylpropyleneamine oxime (HMPAO). We reviewed the following parameters retrospectively: (1) qualitative visual assessment of the presence or absence of delayed HMPAO deposition in the brain area; (2) qualitative visual assessment of a 'three-pronged fork' of the cerebral arteries during the first-pass study; (3) any evidence of 'hollow skull' during the first-pass study; (4) any evidence of 'hot nose'; (5) blood flow index (i.e. the ratio of the area under the brain time-activity curve vs that under the curve for the carotid arteries); and (6) delayed uptake index (i.e. the ratio of HMPAO deposition in the brain vs that in the facial regions of interest). We were able to demonstrate the validity of individual signs and symptoms and to confirm the highly reliable nature of semi-quantitative scintigraphic parameters.

During contact dissolution of gallstones, solvents may escape from the gallbladder and damage the intestinal mucosa. In order to compare the extent of this potential injury, we developed a method to objectively quantify the effects of two commonly used cholesterol solvents, methyl tert-butyl ether and mono-octanoin, on mucosal transport function in the rat intestine. Two intestinal segments in each of 184 anesthetized rats were cannulated. Three milliliters of either solvent were instilled in one segment and left for varying periods of time, while saline was instilled in the other as control. The segments were then washed and perfused for 45 min with an isotonic solution containing [3H]polyethylene glycol 4000 (a nonabsorbable reference marker) and either [14C]alpha-aminoisobutyric acid (a marker for active absorption) or [14C]mannitol (a marker for passive permeability). Methyl tert-butyl ether caused more inhibition of alpha-aminoisobutyric acid absorption (64%) than mono-octanoin (48%) and a greater reduction of dry weight per centimeter of the perfused segment (22%) compared with mono-octanoin (10%). Such effects appeared after only 1 min of solvent exposure and did not appreciably increase with longer exposures. Permeation of mannitol increased by 26% after 1 min of exposure to mono-octanoin and by 54% after a similar period of exposure to methyl tert-butyl ether. Longer exposures to both solvents did not seem to cause progressive increases in mannitol permeation. The results indicate that brief exposure of the rat jejunum to either of the two solvents causes a reduction in active transport ([14C]alpha-aminoisobutyric acid absorption), an increase in passive permeability (mannitol permeation), and a loss of mucosal constituents. We conclude that the intestinal mucosa is susceptible to solvent damage and may be used as a selectively sensitive model that can characterize the biological injury of gallstone solvents. The study also suggests that escape of the currently available solvents into the small intestine in patients undergoing contact dissolution of gallbladder stones may cause injury to the small intestine.

Renal parenchymal volume is important for clinical interpretation. The phantom study was carried out to validate the volume calculation. The volume of kidney phantom was determined using reoriented single photon emission computed tomography (RSPECT). The phantom volume range was 20-300 ml. There are two major factors in the determination of volume which are radioactivity concentration and organ/background ratio. Our results showed that the effect of radioactivity concentration on the volume in the kidney phantom is -3.3 to 7.5% whereas the effect of organ/background ration was only 2.2%. Our relative volume deviation, therefore, from the real volume was 1.43%. We concluded that it is feasible to use kidney volume in clinical work.

An extensive study to compare planar and single photon emission computed tomographic (SPECT) 99Tcm-dimercaptosuccinic acid (DMSA) determination of differential kidney function (DKF) has been carried out. The study has demonstrated that it is possible to use SPECT differential kidney function in place of that obtained using planar scintigraphy. The SPECT DKF value correlated with the planar DKF value. Gradient shaded three-dimensional surface images, reoriented transaxial, sagittal and coronal slices were produced during the same processing method.

The demonstration that methyl tert-butyl ether is a safe and effective gallstone solvent and the development of the microprocessor-assisted solvent transfer system have revived the procedure of chemical contact dissolution of gallbladder stones, which was first described 100 years ago. This procedure of automatic computerized solvent litholysis is further enhanced by the development of a CT-index for the selection of patients with amenable stones and percutaneous gallbladder endoscopy for evaluation after dissolution. Preliminary studies have shown that ACSL with MTBE is safe and highly effective for gallbladder stone dissolution, making this technique a viable non-surgical alternative for the treatment of gallbladder stones. The emergence of new safer and more effective solvent such as ethyl propionate along with the procedure of percutaneous gallbladder ablation for the definitive prevention of gallstone recurrence promise to render ACSL highly competitive even with laparoscopic cholecystectomy.

Ultrasonography is currently the most sensitive non-invasive imaging modality for the diagnosis of gallbladder stones. It has low sensitivity, however, for the detection of fine residue, stone debris, or mucosal ulcers after percutaneous chemical contact dissolution of gallstones. Percutaneous endoscopy is much more sensitive and specific for this purpose. Computed tomography of the gallbladder and gallstones, when properly used, can help in identifying patients suitable for percutaneous contact dissolution of gallstones using cholesterol solvent such as methyl tert-butyl ether. Attention to details and appropriate analysis of the data obtained will overcome many of the shortcomings in the majority of studies that failed to appropriately correlate CT findings with gallstone dissolvability.

The effects of methyl tert-butyl ether exposure on the human gallbladder in five patients who were treated for gallstones by contact dissolution is described. Two patients underwent cholecystectomy within 1 week of methyl tert-butyl ether treatment, one patient 2 weeks after, another 10 weeks after, and one 12 weeks after. Indications for cholecystectomy were bilirubinate stones (resistant to methyl tert-butyl ether), catheter dislodgement, bile leakage, and gallstone recurrence (2 patients). Gallstones were dissolved completely in three patients, there was approximately 50% stone reduction in one patient, and no dissolution occurred in the fifth patient. Each gallbladder was examined grossly and histologically. Electron microscopic evaluation was performed in one cases. Typical inflammatory findings of chronic cholecystitis were observed in each gallbladder and were most conspicuous in the submucosa; the mucosal and serosal surfaces were intact. Mild acute inflammatory changes were noted in the submucosa in the two patients with the shortest interval between methyl tert-butyl ether administration and cholecystectomy. There were no ulcerations in the mucosa and no unusual wall thickening or fibrosis in any patient. These observations support the safety of methyl tert-butyl ether perfusion in the human gallbladder; the mild acute changes may be a transient and reversible phenomenon.

The effect of vanadate (orthovanadate, VO4-) on water and ion transport was studied in rat jejunum. Water transport was tested by single-pass perfusion in vivo and ion fluxes by the Ussing-chamber technique in vitro. The results suggest that vanadate has two actions on ion and water transport: At low concentrations (10(-4) M) it causes Cl-, Na+ and water secretion by stimulation of adenylate cyclase; At higher concentrations (10(-3) and 10(-2) M) it decreases net absorption of Na+ and Cl- by inhibition of (Na+ + K+)-ATPase.

This article is a pictorial review of the current status of interventional radiology of the gallbladder. The indications and technical aspects of various procedures are presented. Specifically discussed are: (1) needle puncture for percutaneous biopsy, withdrawal of bile for culture, or imaging of the biliary tract; (2) catheter insertion for decompression or abscess drainage; and (3) gallstone management via contact dissolution, fragmentation and basketing, or contact lithotripsy. The management of vagal hypotension and bile leak, the major complication of these procedures is also discussed.