Internal Audit of Compliance with a Perioperative Checklist in a Tertiary Care Neurosurgical Unit.

Background: In 1999, the Institute of Medicine reported that, in the United States, 44,000 to 98,000 people die annually as a result of avoidable medical errors. Among the many initiatives undertaken to stem avoidable surgical errors, the World Health Organization (WHO) Surgical Safety Checklist has certainly been one of the most successful. Many surgical units have implemented adapted versions of the WHO Surgical Safety Checklist, audited their performance and discussed issues relating to the implementation process.

Joint effects between UDP-glucuronosyltransferase 1A7 genotype and dietary carcinogen exposure on risk of colon cancer.

The UDP-glucuronosyltransferase 1A7 (UGT1A7) gene is polymorphic and encodes an enzyme involved in the detoxification of heterocyclic amines (HCA) and polycyclic aromatic hydrocarbons (PAH). Consumption of pan-fried and well-done meat are surrogates for HCA and PAH exposure and are possibly associated with colon cancer. We have evaluated whether UGT1A7 allelic variations are associated with colon cancer and whether UGT1A7 genotype modified associations among meat intake, exposure to HCAs and PAHs, and colon cancer in a population-based case-control study of African Americans (197 cases and 202 controls) and whites (203 cases and 210 controls).

The functional UGT1A1 promoter polymorphism decreases endometrial cancer risk.

UDP-glucuronosyltransferase (UGT) 1A1 is involved in the inactivation of estradiol (E(2)) and its oxidized metabolites. These metabolites have been shown to contribute to the development of endometrial cancer in animal studies. Thus UGT1A1 represents a candidate gene in endometrial carcinogenesis.

Novel functional polymorphisms in the UGT1A7 and UGT1A9 glucuronidating enzymes in Caucasian and African-American subjects and their impact on the metabolism of 7-ethyl-10-hydroxycamptothecin and flavopiridol anticancer drugs.

In vitro metabolic studies revealed that along with UDP-glucuronosyltransferase (UGT) 1A1, the hepatic UGT1A9 and the extrahepatic UGT1A7 are involved in the biotransformation of the active and toxic metabolite of irinotecan, 7-ethyl-10-hydroxycamptothecin (SN-38). Variant UGT1A1 and UGT1A7 alleles have been reported but the polymorphic nature of the UGT1A9 gene has not been revealed yet. To further clarify the molecular determinants of irinotecan-induced toxicity, we have identified and characterized the functionality of novel UGT1A9 polymorphisms and determined whether additional missense polymorphisms exist in UGT1A7.

Common human UGT1A polymorphisms and the altered metabolism of irinotecan active metabolite 7-ethyl-10-hydroxycamptothecin (SN-38).

7-Ethyl-10-hydroxycamptothecin (SN-38) is the pharmacologically active metabolite of irinotecan, in addition to being responsible for severe toxicity. Glucuronidation is the main metabolic pathway of SN-38 and has been shown to protect against irinotecan-induced gastrointestinal toxicity. The purpose of this study was to determine whether common polymorphic UDP-glucuronosyltransferase (UGT) affects SN-38 glucuronidation.

Targeted delivery of indinavir to HIV-1 primary reservoirs with immunoliposomes.

The tissue distribution of indinavir, free or incorporated into sterically stabilized anti-HLA-DR immunoliposomes, has been evaluated after a single subcutaneous injection to C3H mice. Administration of free indinavir resulted in low drug levels in lymphoid organs. In contrast, sterically stabilized anti-HLA-DR immunoliposomes were very efficient in delivering high concentrations of indinavir to lymphoid tissues for at least 15 days post-injection increasing by up to 126 times the drug accumulation in lymph nodes.