Citations

AbstractBackground: Positive control materials for clinical diagnostic molecular genetic testing are in critically short supply. High-quality DNA that closely resembles DNA isolated from patient specimens can be obtained from Epstein–Barr virus (EBV)–transformed peripheral blood lymphocyte cell lines. Here we report the development of a process to (a) recover residual blood samples with clinically important mutations detected during routine medical care, (b) select samples likely to provide viable lymphocytes for EBV transformation, (c) establish stable cell lines and confirm the reported mutation(s), and (d) validate the cell lines for use as positive controls in clinical molecular genetic testing applications.Methods: A network of 32 genetic testing laboratories was established to obtain anonymous, residual clinical samples for transformation and to validate resulting cell lines for use as positive controls. Three panel meetings with experts in molecular genetic testing were held to evaluate results and formulate a process that could function in the context of current common practices in molecular diagnostic testing.Results: Thirteen laboratories submitted a total of 113 residual clinical blood samples with mutations for 14 genetic disorders. Forty-one EBV-transformed cell lines were established. Thirty-five individual point and deletion mutations were shown to be stable after 20 population doublings in culture. Thirty-three cell lines were characterized for specific mutations and validated for use as positive controls in clinical diagnostic applications.Conclusions: A process for producing and validating positive control cell lines from residual clinical blood samples has been developed. Sustainable implementation of the process could help alleviate the current shortage of positive control materials.

AbstractAmong 454 operations done for peptic ulcer between 1956 and 1985 on residents of Rochester, Minnesota, U.S.A. in whom ulcer size could be determined accurately, 50 operations (11% of the total) were performed for giant ulcers and 404 (89%) for nongiant ulcers. The annual operation rate per 100,000 residents for giant ulcer did not clearly decline during the 30‐year period in contrast to the dramatic fall in operation rates for nongiant ulcers. Nonetheless, the ratio of operation rates for giant ulcer compared to nongiant ulcer changed relatively little. Giant ulcers required emergency operation for massive bleeding more often than nongiant ulcers. Also, giant ulcers presented with unusual and severe complications such as gastrocolic fistula. Survival after surgery for giant ulcer was poorer than survival after an operation for nongiant ulcer. We conclude that giant ulcers are operated on somewhat less often today than in the past, while operations for nongiant ulcers are much less frequent. The giant ulcers that are operated on, however, are more prone to massive bleeding and are associated with poorer postoperative survival than their nongiant counterparts.