New class of highly selective 5-HT4 receptor agonists provides the next generation of GI treatments New class of 5-HT4 receptor agonists expected to offer improved efficacy and safety for patients with gastrointestinal motility disorders [Turnhout, Belgium, 30/01/08] - A scientific review of the different pharmacological profiles of 5-HT4 receptor agonists published today in Neurogastroenterology and Motility concludes that, due to a more selective mode of action, next-generation 5-HT4 compounds are expected to be safer and more effective treatment options for common, debilitating gastrointestinal (GI) motility disorders such as chronic constipation (CC) and gastroparesis1. “Millions of people – adults and children – suffer from common, debilitating GI conditions that are caused by impaired motility,” commented Jan Schuurkes, Chief Scientific Officer, Movetis NV, Belgium. “This research supports that the next generation of 5-HT4 receptor agonists has the potential to offer superior selectivity in the treatment of a variety of motility disorders and we are confident that these compounds have the potential to meet the needs of many doctors and patients seeking a more effective and safer prokinetic treatment.” Research in the last decade has focused on the development of high-affinity 5-HT4 receptor agonists designed to be free of the side effects associated with older-generation, nonselective compounds, such as cisapride and tegaserod. It is now known that 5-HT4 receptor agonists differ substantially, not only in their selectivity for other receptors or channels, but also in their interaction with the 5-HT4 receptor itself. Combined, these two properties support why next-generation, selective, 5-HT4 receptor agonists are expected to better target the GI system alone, resulting in greater safety for patients. According to the authors of this review, Prof. Romain A Lefebvre (Heymans Institute of Pharmacology, Ghent University, Ghent, Belgium) and Joris H De Maeyer, PhD (Movetis NV, Belgium), ‘We have known for a long time that 5-HT4 receptor agonists have considerable therapeutic potential for patients with motility disorders. Unfortunately, older generation drugs in this class have a high affinity for other tissue receptors or channels which, in some cases, can lead to adverse side effects, and thereby result in a negative perception of these drugs and confusion about their risk–benefit profile.’ RESOLOR® (prucalopride) is currently the most advanced selective, high-affinity 5-HT4 receptor agonist in research1. It belongs to a new chemical class of 5-HT4 agonists that elicits responses in many GI tissues. Through this more selective approach, RESOLOR® appears to offer patients a novel enterokinetic treatment that increases colon motility and restores the slow movement of the bowels. This scientific review and the latest results from Phase III clinical trials evaluating the safety and effectiveness of RESOLOR® in patients with CC for whom laxatives do not provide adequate relief2 suggest that the compound has an attractive safety profile, making it a promising candidate for the treatment of this condition. For further information please contact: Ludivine Delattre Sarah Griffin Tel: +44 (0) 20 8439 9477 Tel: +44 (0) 20 8439 9582 ldelattre@axon-com.com sgriffin@axon-com.com About Movetis Through a clear focus on GI, Movetis seeks to improve the lives of millions of patients – both adults and children – by discovering, developing and commercialising innovative treatments targeting GI conditions that have recently benefited less from innovation. Movetis NV – founded in Belgium in December 2006 – aims to become the leading European specialty pharmaceutical organisation focused on GI diseases. Movetis has a broad GI portfolio with four products in clinical development and four in preclinical, all aiming to address important areas of unmet medical need, including chronic constipation (CC), ascites, paediatric reflux, diabetic gastroparesis, specific subgroups of patients with severe forms of IBS or dyspepsia and secretory diarrhoea. In addition, Movetis has rights to a large library of qualified lead compounds with potential for development. The current portfolio has been licensed from Janssen Pharmaceutica NV, Belgium and Ortho-McNeil Pharmaceutical Inc., two Johnson & Johnson (J&J) companies. The current clinical portfolio includes: · RESOLOR® (prucalopride), a compound for the treatment of CC currently in preregistration · M0002, a compound for the treatment of ascites, which has completed recruitment of a Phase IIa trial; results are expected before the end of Q2 2008 · M0003, a gastrokinetic compound for the treatment of paediatric reflux and gastroparesis, which has recently entered Phase IIa clinical trials in gastroparesis · M0004, another gastrokinetic compound for nocturnal he Join discussion...

A previously healthy 12-year-old boy presented with abdominal pain, vomiting, and abdominal distention of 3 days' duration. On physical examination, hyperpigmented macules were seen on his lips (Panel A). A computed tomographic scan showed proximal jejunojejunal (Panel B, arrow) and ileocolic intussusceptions. Surgical exploration revealed dilatation of the small bowel and necrosis of the jejunal intussusceptum. Resection of this segment and a short ileal intussusceptum containing a large polyp was performed, followed by primary anastomosis. Pathological evaluation showed multiple hamartomatous polyps in the necrotic jejunum and an ileal polyp 3.5 cm in diameter. The diagnosis was Peutz–Jeghers syndrome, an autosomal Join discussion...

Helicobacter pylori (H. pylori) remains a prevalent, worldwide, chronic infection. Though the prevalence of this infection appears to be decreasing in many parts of the world, H. pylori remains an important factor linked to the development of peptic ulcer disease, gastric malignanc and dyspeptic symptoms. Whether to test for H. pylori in patients with functional dyspepsia, gastroesophageal reflux disease (GERD), patients taking nonsteroidal antiinflammatory drugs, with iron deficiency anemia, or who are at greater risk of developing gastric cancer remains controversial. H. pylori can be diagnosed by endoscopic or nonendoscopic methods. A variety of factors including the need for endoscopy, pretest probability of infection, local availability, and an understanding of the performance characteristics and cost of the individual tests influences choice of evaluation in a given patient. Testing to prove eradication should be performed in patients who receive treatment of H. pylori for peptic ulcer disease, individuals with persistent dyspeptic symptoms despite the test-and-treat strategy, those with H. pylori-associated MALT lymphoma, and individuals who have undergone resection of early gastric cancer. Recent studies suggest that eradication rates achieved by first-line treatment with a proton pump inhibitor (PPI), clarithromycin, and amoxicillin have decreased to 70–85%, in part due to increasing clarithromycin resistance. Eradication rates may also be lower with 7 versus 14-day regimens. Bismuth-containing quadruple regimens for 7–14 days are another first-line treatment option. Sequential therapy for 10 days has shown promise in Europe but requires validation in North America. The most commonly used salvage regimen in patients with persistent H. pylori is bismuth quadruple therapy. Recent data suggest that a PPI, levofloxacin, and amoxicillin for 10 days is more effective and better tolerated than bismuth quadruple Join discussion...

Since licensure in 1995 of a hepatitis A vaccine, the Centers for Disease Control and Prevention and the American Academy of Pediatrics have been implementing an incremental hepatitis A immunization strategy for children. In 1996, children living in populations with the highest rates of disease were targeted for immunization, and in 1999 the program was expanded to immunization of children 2 years and older living in states and counties with rates of hepatitis A that historically have been highe Join discussion...

The widespread availability and use of serum blood chemistries for screening both symptomatic and asymptomatic patients has resulted in a dramatic increase in the number of normal and abnormal liver chemistry tests that must be interpreted by physicians. Therefore, a rational approach for the appropriate evaluation of serum liver chemistries is essential for providing high-quality, cost-effective health care. Although there are no controlled clinical trials examining the optimal approach for eva Join discussion...

In the United States, metastatic disease is the most common cause of malignancy in the liver and is 20 to 50 times more common than primary liver cancer. The colon, stomach, pancreas, and breast are the most common primary sites. The appearance of a new lesion in the liver in a patient with a history of cancer strongly suggests hepatic metastasis. On the other hand, most small (1-1.5 cm) liver lesions, even in patients with known malignancy, are not malignant, especially if there are fewer than Join discussion...

Due to the high prevalence of benign focal hepatic lesions in adults, liver lesion characterization is an important objective of diagnostic imaging. For example, “incidental” liver masses discovered in healthy adults as well as liver lesions detected during staging of a known malignancy often need to be characterized. Common benign liver masses include cysts and hemangiomas, and common malignant tumors are metastases and hepatocellular carcinoma (HCC). Less common liver tumors include focal n Join discussion...

One of the difficulties in determining a rational imaging strategy to evaluate jaundiced patients stems from the fact that jaundice is a clinical finding, not a single disease entity. The causes of nonhemolytic jaundice can be divided into two distinct categories: intrahepatic biliary stasis (hepatocellular jaundice) and mechanical biliary obstruction. Because imaging Join discussion...

Background: A 21-year-old white male with a 3-year history of back pain presented with a 6-month history of weight loss (without significant gastrointestinal symptoms), lethargy and left hip pain, and diarrhea that had lasted 4 days. Investigations: Barium follow-through, upper and lower gastrointestinal endoscopy and biopsies, capsule enteroscopy, CT of the chest and abdomen, measurement of the concentration of fecal calprotectin, intestinal absorption permeability test and wireless capsule end Join discussion...

Scientists at the University of Bonn, together with colleagues from Romania, have discovered a gene variant that significantly increases the risk of developing gallstones (Hepatology No. 46, 11 July 2007, DOI 10.1002/hep.21847). It is estimated that one in ten Europeans has this variant in their hereditary disposition. For those affected, the likelihood of developing a gallstone in the course of their life is two to three times higher. The relevant gene contains the instructions for building a m Join discussion...