Generation of conditional Hoxc8 loss-of-function and Hoxc8-->Hoxc9 replacement alleles in mice.

The Hox family of transcription factors are expressed at different domains along the rostrocaudal (R-C) body axis during development. To examine the function of Hoxc8 and Hoxc9 in specific cell types and at different developmental times, we have generated and characterized loxP flanked (floxed) Hoxc8 and Hoxc8-->Hoxc9 replacement alleles of mice, with either GFP or LacZ reporters. Although all four alleles of mice behave like wild-type controls in motor behavioral testing, slight differences in endogenous Hox gene expression were observed among these alleles depending on the type of reporters used and the presence of Hoxc9 cDNA in the targeting constructs. The efficiency of Cre-mediated recombination was evaluated by crossing these mice with the Nestin-cre and Isl1-cre mice, and the loss of Hoxc8 expression with or without Hoxc9 misexpression was confirmed in embryonic spinal cord. In addition, an upregulation of reporter gene expression was observed after Cre-mediated recombination. These mice will be useful tools to analyze Hox gene function in a cell type-specific manner.

Screening for colorectal cancer in adults at average risk: a summary of the evidence for the U.S. Preventive Services Task Force.

PURPOSE: To assess the effectiveness of different colorectal cancer screening tests for adults at average risk. DATA SOURCES: Recent systematic reviews; Guide to Clinical Preventive Services, 2nd edition; and focused searches of MEDLINE from 1966 through September 2001. The authors also conducted hand searches, reviewed bibliographies, and consulted context experts to ensure completeness. STUDY SELECTION: When available, the most recent high-quality systematic review was used to identify relevant articles. This review was then supplemented with a MEDLINE search for more recent articles. DATA EXTRACTION: One reviewer abstracted information from the final set of studies into evidence tables, and a second reviewer checked the tables for accuracy. Discrepancies were resolved by consensus. DATA SYNTHESIS: For average-risk adults older than 50 years of age, evidence from multiple well-conducted randomized trials supported the effectiveness of fecal occult blood testing in reducing colorectal cancer incidence and mortality rates compared with no screening. Data from well-conducted case-control studies supported the effectiveness of sigmoidoscopy and possibly colonoscopy in reducing colon cancer incidence and mortality rates. A nonrandomized, controlled trial examining colorectal cancer mortality rates and randomized trials examining diagnostic yield supported the use of fecal occult blood testing plus sigmoidoscopy. The effectiveness of barium enema is unclear. Data are insufficient to support a definitive determination of the most effective screening strategy. CONCLUSIONS: Colorectal cancer screening reduces death from colorectal cancer and can decrease the incidence of disease through removal of adenomatous polyps. Several available screening options seem to be effective, but the single best screening approach cannot be determined because data are insufficient.

Bile duct crystals do not contribute to sphincter of Oddi dysfunction.

BACKGROUND: Microlithiasis has been proposed as a cause of both occult gallbladder disease and of idiopathic pancreatitis. Theoretically, microlithiasis could also cause postcholecystectomy pain by causing temporary biliary obstruction and may be more common in patients with sphincter of Oddi dysfunction. The frequency of crystals in bile duct aspirates was assessed from patients with symptoms after cholecystectomy with and without elevated baseline sphincter of Oddi pressures. METHODS: A prospective analysis was performed on all patients with recurrent biliary pain after cholecystectomy who presented for ERCP and manometry between January 1998 and June 2000. All patients had aspirates obtained from the common bile duct for crystal analysis by using the aspirating port of the manometry catheter before the injection of contrast. Four to 20 mL of bile was examined by microscopy for both cholesterol and bilirubinate crystals. RESULTS: Sixty patients (83% women, mean age 44 years) were studied. Thirty-five had normal baseline biliary sphincter pressures and 25 elevated biliary baseline sphincter pressures (>40 mm Hg). Two patients in the normal pressure group and 1 in the elevated pressure group had cholesterol crystals present in their aspirate. No patient had bilirubinate crystals present. A 5% frequency of microlithiasis was identified overall. CONCLUSIONS: Bile duct crystals occur infrequently in patients with symptoms after cholecystectomy and are found in patients with normal and abnormal biliary sphincter manometry. This study suggests that the presence of bile duct crystals, or microlithiasis, does not play a role in sphincter of Oddi dysfunction.