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The etiology of inflammatory bowel disease (IBD) is unknown but may relate to an unidentified bacterial pathogen or an immunological reaction to gut microbiota. Antibiotics have therefore been proposed as a therapy for Crohn's disease (CD) and ulcerative colitis (UC) to induce remission in active disease to prevent relapse. Current data are conflicting and we therefore conducted a systematic review of randomized controlled trials (RCTs) evaluating antibiotics in IBD. Only parallel group RCTs were considered eligible. Studies with adult patients receiving any dose of therapy for at least 7 days and up to 16 weeks for active disease, or at least 6 months of follow-up for preventing relapse in quiescent disease were analyzed. We included any antibiotics alone or in combination using predefined definitions of remission and relapse. Two reviewers independently assessed eligibility and extracted data. The primary outcome was remission or relapse using an intention-to-treat methodology. The data were summarized using relative risk (RR) and pooled using a random effects model. For active CD, there were 10 RCTs involving 1,160 patients. There was a statistically significant effect of antibiotics being superior to placebo (RR of active CD not in remission=0.85; 95% confidence interval (CI)=0.73-0.99, P=0.03). There was moderate heterogeneity between results (I(2)=48%) and a diverse number of antibiotics were tested (anti-tuberculosis therapy, macrolides, fluroquinolones, 5-nitroimidazoles, and rifaximin) either alone or in combination. Rifamycin derivatives either alone or in combination with other antibiotics appeared to have a significant effect at inducing remission in active CD. In perianal CD fistula there were three trials evaluating 123 patients using either ciprofloxacin or metronidazole. There was a statistically significant effect in reducing fistula drainage (RR=0.8; 95% CI=0.66-0.98) with no heterogeneity (I(2)=0%) and an number needed to treat 5 (95% CI=3-20). For quiescent CD, there were 3 RCTs involving 186 patients treated with different antibiotics combinations (all including antimycobacterials) vs. placebo. There was a statistically significant effect in favor of antibiotics vs. placebo (RR of relapse=0.62; 95% CI=0.46-0.84), with no heterogeneity (I(2)=0%). In active UC, there were 9 RCTs with 662 patients and there was a statistically significant benefit for antibiotics inducing remission (RR of UC not in remission=0.64; 95% CI=0.43-0.96). There was moderate heterogeneity (I(2)=69%) and antibiotics used were all different single or combination drugs. Antibiotic therapy may induce remission in active CD and UC, although the diverse number of antibiotics tested means the data are difficult to interpret. This systematic review is a mandate for further trials of antibiotic therapy in IBD.

Background & Aims: Both cholecystokinin (CCK)-A and CCK-B receptors are expressed in the pancreas, and exogenous gastrin administration stimulates glucagon secretion from human islets. Although gastrin action has been linked to islet neogenesis, transdifferentiation, and beta-cell regeneration, an essential physiologic role(s) for gastrin in the pancreas has not been established. Methods: We examined glucose homeostasis, glucagon gene expression, glucagon secretion, and islet mass in mice with a targeted gastrin gene disruption. Results: Gastrin −/− mice exhibit fasting hypoglycemia and significantly reduced glycemic excursion following glucose challenge. Insulin sensitivity was normal and levels of circulating insulin and insulin messenger RNA transcripts were appropriately reduced in gastrin −/− mice. In contrast, levels of circulating glucagon and pancreatic glucagon messenger RNA transcripts were not up-regulated in hypoglycemic gastrin −/− mice. Furthermore, the glucagon response to epinephrine in isolated perifused islets was moderately impaired in gastrin −/− versus gastrin +/+ islets (40% reduction; P P Conclusions: These findings show an essential physiologic role for gastrin in glucose homeostasis; however, the gastrin gene is not essential for murine islet development or the adaptive islet proliferative response to beta-cell injury.

Cutaneous leishmaniasis is a disease endemic to Central and South America, Mexico and the Caribbean, and affects millions of people. As travel to these regions becomes more common, cutaneous leishmaniasis is becoming a disease of increasing importance in the developed world. However, disease recognition and access to appropriate therapy for cutaneous leishmaniasis remains a challenge in North America. The present article reports a case of cutaneous leishmaniasis in a Canadian man following a trip to Costa Rica. Species-specific diagnosis was confirmed by polymerase chain reaction analysis of a skin biopsy, which was positive forLeishmania panamensis. After failing a course of itraconazole, the patient was successfully treated with sodium stibogluconate, despite significant barriers to administering this therapy, and the paucity of data regarding its efficacy and tolerability. The pathophysiology, diagnosis and systemic treatment of cutaneous leishmaniasis, as well as its emerging presence in the developed world, are reviewed.

Background Exogenous arginine vasopressin (VP) has been increasingly used in the hemodynamic management of critically ill patients with septic shock, but its use in septic burn patients has not been systematically examined. Purpose To review our experience with the use of VP in septic burn patients. Methods Retrospective review of all patients who received VP at a tertiary care adult regional burn centre. Only patients who strictly met the American College of Chest Physicians/Society of Critical Care Medicine Consensus Criteria for sepsis at the time of VP initiation were analysed. Results There were 30 septic burn patients treated on 43 distinct occasions with VP. This group had a mean (±S.D.) age of 49 ± 19 years, a mean % TBSA burn of 41 ± 15% and a 37% incidence of inhalation injury. A significant increase in mean arterial pressure (MAP), a significant decrease in heart rate (HR), and a trend towards increased urine output (UO) occurred following initiation of VP. When VP was added to an existing infusion of norepinephrine (NE), there was a significant NE sparing effect. VP was implicated in the death of one patient who developed diffuse upper gastrointestinal necrosis while on VP. Other complications in patients treated with VP included peripheral ischemia (2), skin graft failure (1) and donor site conversion (1). In all complications, VP had been administered in combination with prolonged NE infusions (mean of 10 μg/min over a mean of 177 h). Conclusion VP is a useful adjunctive pressor that spares NE requirements in septic burn patients, but its use is not without risks, particularly when VP is combined with sustained moderate to high infusions of NE.

Both cholecystokinin (CCK)-A and CCK-B receptors are expressed in the pancreas, and exogenous gastrin administration stimulates glucagon secretion from human islets. Although gastrin action has been linked to islet neogenesis, transdifferentiation, and beta-cell regeneration, an essential physiologic role(s) for gastrin in the pancreas has not been established.We examined glucose homeostasis, glucagon gene expression, glucagon secretion, and islet mass in mice with a targeted gastrin gene disruption.Gastrin -/- mice exhibit fasting hypoglycemia and significantly reduced glycemic excursion following glucose challenge. Insulin sensitivity was normal and levels of circulating insulin and insulin messenger RNA transcripts were appropriately reduced in gastrin -/- mice. In contrast, levels of circulating glucagon and pancreatic glucagon messenger RNA transcripts were not up-regulated in hypoglycemic gastrin -/- mice. Furthermore, the glucagon response to epinephrine in isolated perifused islets was moderately impaired in gastrin -/- versus gastrin +/+ islets (40% reduction; P0.01, gastrin +/+ vs. gastrin -/- mice). Moreover, the glucagon response but not the epinephrine response to hypoglycemia was significantly attenuated in gastrin -/- compared with gastrin +/+ mice (P0.05). Despite gastrin expression in the developing fetal pancreas, beta-cell area, islet topography, and the islet proliferative response to experimental injury were normal in gastrin -/- mice.These findings show an essential physiologic role for gastrin in glucose homeostasis; however, the gastrin gene is not essential for murine islet development or the adaptive islet proliferative response to beta-cell injury.

The development of intestinal metaplasia (IM) has been purported to be a critical step in the pathogenesis of gastric cancer. However, the natural history of IM in migrant human populations has not been well elucidated. The purpose of this study was to determine the risk of gastric cancer posed by IM in Asian immigrants undergoing gastric cancer screening. A retrospective review of Asian immigrants found to have IM during screening was conducted over an 18-month period. In total, 222 patients were found to have IM. Altogether, 24% had a history of smoking, 48% had a family history of gastric cancer, and 52% had a history of Helicobacter pylori (H. pylori) infection with a 96% eradication rate. Patients with stable IM (SIM) were then compared with those who developed high risk pathology (HRP), specifically dysplasia and/or adenocarcinoma. Thirty-five patients (16%) were included in the HRP group. 31 with dysplasia (14%) and 4 with adenocarcinoma (2%). Of those with dysplasia, 55% demonstrated regression to IM over the course of follow-up. Patients in the SIM group were more likely to be female (60% vs. 31%, P = 0.002) and more likely to have had a normal biopsy during follow-up (32% vs. 9%, P = 0.005). Odds ratios for IM stability were 3.3 (95% CI 1.5-7.0) and 5.0 (95% CI 1.5-17.1) for female gender and presence of a normal biopsy, respectively. Intestinal metaplasia in immigrant Asian populations is predominantly a stable histologic finding associated with a low rate of persistent dysplasia and adenocarcinoma.