Colorectal cancer screening practices in Saskatchewan: Survey of family physicians.

OBJECTIVE: To evaluate current colorectal cancer (CRC) screening practices in Saskatchewan and identify barriers to screening with the goal of improving current practice. DESIGN: Survey of family physicians. SETTING: Saskatchewan. PARTICIPANTS: A total of 773 family physicians were surveyed. MAIN OUTCOME MEASURES: Demographic characteristics, individual screening practices, and perceived barriers to screening. RESULTS: The response rate to the survey was 44.5%. When asked what method they used for fecal occult blood testing, almost 40% of respondents were either unsure or did not answer the question. Of those who did respond, 35.8% employed hemoccult testing following digital rectal examination, a practice not recommended for CRC screening. Screening guidelines for average-risk patients were generally well adhered to, with 79.9% of respondents recommending screening beginning at age 50. For screening patients at increased risk of CRC owing to family history, only 64.2% of respondents began screening 10 years before the age of the index patient at diagnosis. Physicians who were more likely to follow guidelines were female, in practice fewer than 10 years, trained in Canada, and practising in urban areas. More than 90% of family physicians agreed that a standard provincewide screening program would be beneficial. CONCLUSION: We have identified considerable knowledge gaps with regard to CRC screening. There is confusion about which fecal occult blood tests are recommended for screening. Also, screening guidelines for patients with a family history of CRC are poorly understood. These findings suggest that better physician education about CRC screening is required. Introduction of a provincewide screening program should improve overall screening success.

Site-directed mutagenesis of UDP-galactopyranose mutase reveals a critical role for the active-site, conserved arginine residues.

The flavoenzyme UDP-galactopyranose mutase (UGM) is a mediator of cell wall biosynthesis in many pathogenic microorganisms. UGM catalyzes a unique ring contraction reaction that results in the conversion of UDP-galactopyranose (UDP-Galp) to UDP-galactofuranose (UDP-Galf). UDP-Galf is an essential precursor to the galactofuranose residues found in many different cell wall glycoconjugates. Due to the important consequences of UGM catalysis, structural and biochemical studies are needed to elucidate the mechanism and identify the key residues involved. Here, we report the results of site-directed mutagenesis studies on the absolutely conserved residues in the putative active site cleft. By generating variants of the UGM from Klebsiella pneumoniae, we have identified two arginine residues that play critical catalytic roles (alanine substitution abolishes detectable activity). These residues also have a profound effect on the binding of a fluorescent UDP derivative that inhibits UGM, suggesting that the Arg variants are defective in their ability to bind substrate. One of the residues, Arg280, is located in the putative active site, but, surprisingly, the structural studies conducted to date suggest that Arg174 is not. Molecular dynamics simulations indicate that closed UGM conformations can be accessed in which this residue contacts the pyrophosphoryl group of the UDP-Gal substrates. These results provide strong evidence that the mobile loop, noted in all the reported crystal structures, must move in order for UGM to bind its UDP-galactose substrate.