Canadian Helicobacter Study Group Consensus Conference: Update on the management of Helicobacter pylori--an evidence-based evaluation of six topics relevant to clinical outcomes in patients evaluated for H pylori infection.

As an update to previously published recommendations for the management of Helicobacter pylori infection, an evidence-based appraisal of six topics was undertaken in a consensus conference sponsored by the Canadian Helicobacter Study Group. The issues addressed and recommendations made were: bismuth-containing quadruple therapy is appropriate as an alternative first-line eradication strategy for H pylori infection; searching for and treating H pylori infection is warranted in patients considered to be at high risk for gastric cancer; H pylori infection should be eradicated before initiating long-term treatment with nonsteroidal anti-inflammatory drugs or acetylsalicylic acid; the stool antigen test has a limited role in the diagnosis of H pylori infection; the benefits of H pylori eradication in patients on long-term proton pump inhibitor therapy are not sufficient to warrant recommending a strategy of searching for and eradicating the infection among these patients; and a strategy of "test and eradicate" for H pylori infection in patients with uninvestigated dyspepsia is cost-effective in Canada relative to a trial of proton pump inhibitor therapy. The goal was to establish guidelines on the best evidence using the same structure to address and formulate recommendations for each issue. The degree of consensus for each issue is presented.

Etiology of dyspepsia: implications for empirical therapy.

Dyspepsia describes a symptom complex thought to arise in the upper gastrointestinal tract and includes, in addition to epigastric pain or discomfort, symptoms such as heartburn, acid regurgitation, excessive burping or belching, a feeling of slow digestion, early satiety, nausea and bloating. Based on the evidence that heartburn cannot be reliably distinguished from other dyspeptic symptoms, the Rome definition appears to be too narrow and restrictive. It is particularly ill suited to the management of uninvestigated dyspepsia at the level of primary care. In patients presenting with uninvestigated dyspepsia, a symptom benefit is associated with a 'test and treat' approach for Helicobacter pylori infection. A substantial proportion of those who do not benefit prove to have esophagitis on endoscopy. In those with functional dyspepsia, the benefits of H pylori eradication, if any, appear to be modest. Hence, a 'symptom and treat' acid-suppression trial with proton pump inhibitors, and a 'test and treat' strategy for H pylori are two acceptable empirical therapies for patients with univestigated dyspepsia.

(R)-N-[11C]methyl-3-pyrrolidyl benzilate, a high-affinity reversible radioligand for PET studies of the muscarinic acetylcholine receptor.

We recently reported the synthesis and binding affinity of ligands for the muscarinic acetylcholine receptor (mAChR) based on both the pyrrolidyl and piperidyl benzilate scaffold. One of these, (R)-3-pyrrolidyl benzilate, was successfully radiolabeled with [(11)C]methyl triflate and the resulting compound, (R)-N-[(11)C]methyl-3-pyrrolidyl benzilate (3-[(11)C]NMPYB), was evaluated as a reversible, acetylcholine-sensitive tracer for the mAChR (K(i) of unlabeled 3-NMPYB is 0.72 nM). This compound displayed high, receptor-mediated retention in regions of the mouse and rat brain known to have high concentrations of mAChRs. Moreover, bolus studies in a pigtail monkey showed that this compound had superior clearance from the brain when compared to muscarinic radiotracers previously employed in human PET studies. Infusion studies in the same monkey revealed that it was possible to achieve equilibrium of radiotracer distribution for 3-[(11)C]NMPYB in both the striatum and cortex. Sensitivity to endogenous acetylcholine levels was evaluated by injecting phenserine (5 mg/kg) into rats prior to administration of 3-[(11)C]NMPYB in an equilibrium infusion protocol. This pretreatment produced a modest, statistically significant decrease (9-11%) in the distribution volume ratios for muscarinic receptor rich regions of the rat brain as compared to controls.

Risks and benefits of Helicobacter pylori eradication: current status.

In patients with diseases known to be associated with Helicobacter pylori infection, such as peptic ulcer, treatment of the underlying infection is the standard of care. However, in most major consensus management guidelines, including those published in Canada, widespread testing for H pylori infection is not recommended. This practice is not encouraged because of insufficient evidence of cost-benefit in gastric cancer prevention, the potential for increases in antibiotic resistance and the controversial hypothesis of potential negative effects of eradication in certain clinical entities. For example, there is insufficient evidence to recommend against eradicating H pylori discovered in a patient with symptoms of gastroesophageal reflux disease. The management guidelines designed specifically in Canada should, therefore, continue to be applied, with H pylori diagnosed and treated in appropriately selected patients.