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Diagnosis of Lynch syndrome (LS) may be complex. Knowledge of mutation spectrum and founder mutations in specific populations facilitates the diagnostic process. Aim of the study is to describe genetic features of LS in the Israeli population and report novel and founder mutations. Patients were studied at high-risk clinics. Diagnostics followed a multi-step process, including tumor testing, gene analysis and testing for founder mutations. LS was defined by positive mutation testing. We diagnosed LS in 242 subjects from 113 families coming from different ethnicities. We identified 54 different mutations; 13 of them are novel. Sixty-seven (59%) families had mutations in MSH2, 20 (18%) in MSH6, 19 (17%) in MLH1 and 7 (6%) in PMS2; 27% of the MSH2 mutations were large deletions. Seven founder mutations were detected in 61/113 (54%) families. Constitutional mismatch repair deficiency ( CMMR-D) was identified in five families. Gene distribution in the Israeli population is unique, with relatively high incidence of mutations in MSH2 and MSH6. The mutation spectrum is wide; however, 54% of cases are caused by one of seven founder mutations. CMMR-D occurs in the context of founder mutations and consanguinity. These features should guide the diagnostic process, risk estimation, and genetic counseling. [ABSTRACT FROM AUTHOR]

This report describes injury to the hepatic artery with pseudoaneurysm formation and hemobilia following the use of laser-assisted dissection to perform laparoscopic cholecystectomy. A 57-year-old woman was referred emergently 2 weeks after laser laparoscopic cholecystectomy with upper abdominal pain, upper gastrointestinal bleeding, and jaundice. A selective hepatic arteriogram showed a right hepatic artery pseudoaneurysm which was embolized. Two weeks later the patient had recurrent hemobilia as the result of blood flow restoration in the pseudoaneurysm and a fistula to the cystic duct remnant. She was treated with two additional embolizations and direct injection of the aneurysm with thrombogenic material. Follow-up at 2 years showed no further recurrence. Since the laser has never been shown to have advantages over electrocautery, its use during laparoscopic cholecystectomy is difficult to justify. [ABSTRACT FROM AUTHOR]

Summary:We conducted an open-label, multicenter, single-arm clinical trial to investigate the safety and efficacy of drotrecogin alfa (activated) (Drot AA) in hematopoietic stem cell transplant (HSCT) patients with severe sepsis. Drot AA was administered as a continuous i.v. infusion of 24 μg/kg/h for 96 h. The target enrollment was 250 patients in 15–20 transplant centers over a 2-year period (March 2003–March 2005). However, after only 10 months, in December 2003, the trial was stopped due to a low enrollment of seven patients at three of the 15 sites that were open for accrual. Six of the seven patients completed the drug infusion. Two patients experienced serious bleeding events. The first patient developed a nonfatal diffuse alveolar hemorrhage 2 days after study-drug completion. The second patient had severe coagulopathy and developed a fatal intracranial hemorrhage on the third day of drug infusion. Three of the seven patients were alive 100 days after the HSCT. The slow enrollment rate was attributed to changes in transplant preparatory regimens, enhancements in antimicrobial prophylactic protocols and the use of antimicrobial-coated catheters. The small number of patients in this report precludes a definitive assessment of the safety and efficacy of Drot AA in HSCT patients.Bone Marrow Transplantation (2005) 36, 721–724. doi:10.1038/sj.bmt.1705124; published online 8 August 2005 [ABSTRACT FROM AUTHOR]

Presents a study that examined the safety and efficacy of drotrecogin alfa in patients with severe sepsis after hematopoietic stem cell transplantation (HSCT). Causes of morbidity after HSCT; Factors that contibute to sepsis syndrome; Role of protein C in coagulation during sepsis.