Prevalence of Wernicke-Korsakoff syndrome in Australia: has thiamine fortification made a difference?

OBJECTIVE: To determine the prevalence of the Wernicke-Korsakoff syndrome (WKS) in Australia and compare this with previous studies. DESIGN AND SETTING: Prospective autopsy study at the New South Wales Institute of Forensic Medicine, 1996-1997. METHODS: Brains of deceased people (aged over 15 years) derived from 2212 sequential autopsies performed between 1 January 1996 and 31 December 1997 were studied macroscopically and microscopically to identify cases of WKS. MAIN OUTCOME MEASURES: Standard histological criteria for WKS and any available clinical data. RESULTS: Twenty-five cases of WKS were identified (prevalence, 1.1%), mostly among the 5.9% of the 2212 people who had a history suggestive of alcohol abuse. Only four cases (16%) had been diagnosed during life. CONCLUSIONS: There has been a significant reduction in the prevalence of WKS in Australia since the introduction of thiamine enrichment of bread flour. While the prevalence is still higher than in most other Western countries, further research is needed before adding thiamine to alcoholic beverages can be recommended.

Detection of HER-2/neu oncogene amplification in flow cytometry-sorted breast ductal cells by competitive polymerase chain reaction.

BACKGROUND: The amplification and/or overexpression of the HER-2/neu oncogene has been proposed as an important prognostic marker in breast cancer. However, contradictory results from various groups regarding whether there is statistical significance in HER-2 amplification or overexpression in predicting overall and disease free survival in node positive versus node negative patients exist in the literature. Current assays on quantifying the HER-2 oncogene rely on DNA extracted from homogenized breast tissue. Not only is a large amount of tissue required, but also, the DNA extract is contaminated with DNA from stromal cells and leukocytes, leading to decreased specificity and sensitivity of the HER-2 assay. Improving the specificity (DNA from breast ductal cells) and the sensitivity (competitive polymerase chain reaction [PCR]) of the HER-2 amplification detection assay will help resolve some of these controversies. METHODS: Using multiparameter flow cytometry (FCM), ductal cells from breast biopsies and fine needle aspirations (FNAs) are identified and selectively sorted using anti-cytokeratin, anti-HER-2 antibody labeling and DNA staining. HER-2 amplification in these sorted cells is then quantified by competitive DNA PCR using a competitive reference standard mutant template that is susceptible to the restriction enzyme Sma-1. RESULTS: Applying this strategy, SK-BR-3, an HER-2 amplified breast cancer cell line, was found to have approximately 9x baseline HER-2 oncogene copies. In addition, MCF-7, a known HER-2 nonamplified breast cancer cell line, was found to have baseline HER-2 oncogene copies. In the 10 clinical breast samples tested, 4 of the 10 breast cancers were HER-2 amplified using as few as 1000 cells. The cytokeratin positive cells of these cancers, in contrast to the cytokeratin negative cells, have detectably higher HER-2 amplification (7.2 +/- 2.8x versus 3.2 +/- 1.1x, respectively). Hence, HER-2 gene amplification would have been underestimated if unsorted cells were used because of stromal dilution. In the cytokeratin positive cells that were HER-2 oncogene amplified, corresponding HER-2 oncoprotein overexpression was detected by FCM. CONCLUSIONS: Using FCM, the ductal cell subpopulation of a breast specimen can be successfully sorted from breast biopsy and FNA specimens. Moreover, by applying the technique of competitive PCR, improved specificity and sensitivity in HER-2 oncogene amplification detection is achieved. The entire procedure can be accomplished in 1 day, allowing for a cost-effective assay and rapid turnaround time.