Faithful segregation of replicated chromosomes is essential for maintenance of genetic stability and seems to be monitored by several mitotic checkpoints. Various components of these checkpoints have been identified in mammals, but their physiological relevance is largely unknown. Here we show that mutant mice with low levels of the spindle assembly checkpoint protein BubR1 develop progressive aneuploidy along with a variety of progeroid features, including short lifespan, cachectic dwarfism, lordokyphosis, cataracts, loss of subcutaneous fat and impaired wound healing. Graded reduction of BubR1 expression in mouse embryonic fibroblasts causes increased aneuploidy and senescence. Male and female mutant mice have defects in meiotic chromosome segregation and are infertile. Natural aging of wild-type mice is marked by decreased expression of BubR1 in multiple tissues, including testis and ovary. These results suggest a role for BubR1 in regulating aging and infertility.

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Alendronate can cause chemical esophagitis, including severe ulcerations, in some patients. Recommendations to reduce the risk of esophagitis include swallowing alendronate with 180 to 240 ml (6 to 8 oz) of water on arising in the morning, remaining upright for at least 30 minutes after swallowing the tablet and until the first food of the day has been ingested, and discontinuing the drug promptly if esophageal symptoms develop.

Budd-Chiari syndrome (BCS) is a rare disorder that is characterized by hepatic venous outflow obstruction. The aim of this study was to assess determinants of survival and to evaluate the effect of portosystemic shunting. In this international multicenter study, 237 patients with BCS, diagnosed between 1984 and 2001, were investigated. Univariate, multivariate, and time-dependent Cox regression analyses were performed. Overall survival at 1, 5, and 10 years was 82% (95% CI, 77%-87%), 69% (95% CI, 62%-76%), and 62% (95% CI, 54%-70%), respectively. Encephalopathy, ascites, prothrombin time, and bilirubin were independent determinants of survival. A prognostic classification combining these factors could identify three classes of patients (classes I-III). The 5-year survival rate was 89% (95% CI, 79%-99%) for class I, 74% (95% CI, 65%-83%) for class II, and 42% (95% CI, 28%-56%) for class III. Anticoagulants were administered to 72%; only for patients in class I was this associated with a trend toward improved survival (relative risk [

FISH is significantly more sensitive than and nearly as specific as conventional cytology for the detection of malignant biliary strictures in biliary brushing specimens. FISH may improve the clinical management of patients who are being evaluated for malignancy in bile duct strictures.