AstraZeneca Canada Research Articles

Birth of the Canadian Digestive Health Foundation.

The Canadian Digestive Disease Foundation, renamed the Canadian Digestive Health Foundation--Fondation canadienne pour la promotion de la santé digestive--in December 2001, is the culmination of ongoing efforts by the Canadian Association of Gastroenterology to establish an independent charitable organization. In February 2001, it was officially endorsed as the Foundation for the Canadian Association of Gastroenterology. The initial efforts to establish this Foundation, led by Dr Richard McKenna in 1963, were unsuccessful. In 1991, Glaxo Canada (now GlaxoSmithKline) became a founding donor, and with the four founding physicians--Drs Ivan T Beck, Richard H Hunt, Suzanne E Lemire and Alan BR Thomson--the expenses to establish the Foundation were met. A charitable number was obtained in 1995 (0997427-11). The second founding donor was Janssen Canada (now Janssen-Ortho), and public education support came from Astra Canada (now AstraZeneca Canada). The Foundation initially relied on corporate donors, but now approaches physicians, patients and the general public. The objectives of the Foundation are to advance the science of gastroenterology and to provide knowledge of digestive diseases and nutrition to the general public, to enhance the quality of life of persons who are afflicted with these disorders. The major achievements of the Foundation are the provision of one-year operating grants to new investigators, which have allowed them to accumulate early data and subsequently obtain support from other major granting organizations. It also provides Fellowships and studentship support grants, in conjunction with the Canadian Institutes of Health Research and the pharmaceutical industry. The education committee found that there was little research support in this field, considering the large economic burden of digestive disease and the amount of outstanding work done by Canadian researchers. A bilingual Web site, a web-based specialist's discussion program and bilingual pamphlets facilitate public awareness and allow patients to voice concerns.

Patient Handling of a Dry-Powder Inhaler in Clinical Practice

Multi-dose dry-powder inhalers are perceived as being easier for patients to use than conventional pressurized aerosol inhalers; however, no study has determined whether patients handle such devices adequately and whether there is a need for patient education in this area. We used trained observers to assess the handling of a specific multi-dose dry powder inhaler (Turbuhaler; AstraZeneca Canada; Mississauga, ON) by patients currently using the device for the management of their asthma. Fourteen discrete steps were scored independently by two observers simultaneously. Patients were divided into two groups for analysis: those who had received formal instruction in the use of the inhaler at The Asthma Centre and those who had received no formal instruction in the community. There was no significant difference between the formally trained groups and control groups in the percentage of handling steps performed correctly (79% vs 78%, respectively; p > 0.05). Fewer than 50% of patients in both groups demonstrated optimal breath-holding when using the device. Patient handling of Turbuhaler was generally good, with no evidence that a structured education intervention offered an advantage over the usual education incidental to the prescribing or dispensing process. The most common handling flaw, suboptimal breath-holding, is not specific to this device and is of uncertain clinical significance.

Immune requirements and inflammatory mediators in a murine model of post-infectious irritable bowel syndrome

Post-Infectious Irritable Bowel Syndrome (PI-IBS) occurs in up to 30% of patients following an episode of bacterial gastroenteritis. A long duration of the acute diarrheal illness is a risk factor for the development of PI-IBS. This raises the possibility that the nature of the host response during the acute infection influences the development of the persistent changes in enteric neuro-muscular function in the post-infectious state. Recently we showed that primary infection of NIH/Swiss mice results in enteric neuromuscular dysfunction that persists for at least 6 weeks after infection, reminiscent of PI-IBS. In this study we have explored mechanisms underlying the persistent neuromuscular changes in this model, focussing on the host response to infection. We used RT-PCR to evaluate the expression of mediators in the neuromuscular layers of the jejunum before, during and after the infection. Infection induced the expression of the Th2 cytokines interleukins -4 and 13 during the enteric phase of infection (day 10 PI), but these cytokines did not persist beyond the duration of the infection. Studies in mice with Severe Combined Immune Deficiency (SCID) showed that acute infection and inflammation did not result in peristent neuromuscular dysfunction, indicating that at least the initiation of these events is immunologically driven. We next examined mediators responsible for the maintenance of the neuromuscular dysfunction, focussing on prostaglandins. As expected, there was no constitutive expression of inducible cycle-oxygenase COX-2 in the neuromuscular layers but the gene encoding this enzyme was expressed during the acute infection (day 10 PI). Moreover, COX-2 mRNA expression remained elevated for at least 28 days PI, together with an increased production of prostaglandin E2 in the neuromuscular layer. Since the persistently increased contractility of muscle in this model could be abrogated by indomethacin, local PGE2 production is critical for the ongoing expression of muscle hypercontractility in this model. These results demonstrate that the Th2 cytokines IL-4 and IL-13 are neccessary for the induction but not thr maintenance of post-infectious muscle hypercontractility in this model. Our results suggest that the maintainance of the hypercontractility is mediated by the local production of PGE2, possibly via COX-2. Supported by AstraZeneca and MRC Canada.

CAG news page

NEW CAG EXECUTIVE DIRECTOR It is with great pleasure that we announce the appointment of Paul Sinclair MSc as the new executive director of the Canadian Association of Gastroenterology (CAG). Paul started in this position on July 1, 2000. Many members of CAG will be familiar with Paul from his previous position as the principal gastrointestinal scientist at AstraZeneca Canada. Paul has been a member of CAG for several years and played an instrumental role in the establishment of the CAG-Astra Research Initiative Awards that have been so valuable in providing funding for research fellows over the past five years. We welcome Paul to this new position with great enthusiasm and look forward to working with him in the strategic planning process for CAG in the years to come. Paul can be reached at the CAG National Office in Oakville, Ontario (e-mail: cag@cable.com).