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.

AbstractWe have reviewed 108 cases of bacterial endocarditis treated surgically since 1968. The mean age of the patients was 47.7±15.6 years (± SD) (range, 14–79 yr). Seventy‐seven percent were male. The most common causative organisms were staphylococci (46%), streptococci viridans group (25%), and other streptococci (20%). Forty‐five percent, 25%, and 13% of patients had native aortic valve, native mitral valve, or native double valve (AV/MV) involvement, respectively. Eighteen patients had prosthetic valve endocarditis. No patient underwent surgery for tricuspid valve endocarditis. Seventy‐three patients were considered to have active endocarditis (AE) (positive blood or tissue cultures and/or annular abscesses). The 35 remaining patients had healed endocarditis (HE). Preoperative complications in patients with either AE or HE were stroke (11%, 11%), renal failure (33%, 3%;p<0.001), pulmonary edema (83%, 34%;p<0.001), anemia (36%, 8%;p<0.01), and inotrope dependence (22%, 6%;p<0.05). Hospital mortality for native valve AE was 19.6% (11/56), and for healed endocarditis, 5.7% (2/35). Independent predictors of hospital mortality were inotrope dependence (p<0.001), annular abscess (p<0.01), pulmonary edema (p<0.01), and staphylococcal infection (p<0.05). The 5‐year actuarial survival for operative survivors was 68.4±7.5% (AE) and 78.3±9.2% (HE). We conclude that the operative mortality for patients with continuing sepsis is high and that surgery should be undertaken early in staphylococcal endocarditis. If surgery is successful, then the long‐term prognosis is good.

Among 2, 195 reference citations, published during 1975 in ten major US medical journals, 634 (29%) were found to be erroneous on direct checking of the original source. The percentage of error within individual journals ranged from 14 to 50 per cent. Such a high error rate would seem to seriously diminish the usefulness of published reference lists and, possibly, raise questions about the accuracy of other portions of the literature also.

Both science and the public can be harmed by premature or inaccurate publicity. Physicians' concern centers on the damaging effects of inaccuracy and sensationalism and on the hazards of invasion of privacy. Balancing these concerns is a legitimate desire by the public to know about scientific progress. Medicine has fairly specific ethical guidelines for physicians' conduct in this area; an analogous code for science writers might help to control the occasional abuses of trust by these writers. At the same time physicians must become more skillful in communicating information.

Purpose Epothilones are a new class of nontaxane tubulin polymerization agents that have activity in taxane-resistant tumors. Epothilone B (BMS-247550) is a semisynthetic analog of the natural product epothilone B. This study was performed to determine the activity of BMS-247550 in patients with soft tissue sarcomas (STSs) who had not received prior chemotherapy for metastatic disease. Patients and Methods Patients with measurable, advanced, or metastatic STS with no prior chemotherapy for metastatic disease were treated with BMS-2457550 50 mg/m 2 intravenously during 1 hour every 21 days. All responses were confirmed 4 weeks later. Results Thirty-one patients (median age, 54 years; range, 19 to 78 years; 48% female) were entered onto the trial and were assessable for response. All but one patient had an Eastern Cooperative Oncology Group performance score of 0% or 1%, and 39% had received prior adjuvant chemotherapy. Mean follow-up was 22 months, with a confirmed response rate of 6% (95% CI, 0% to 17%). Median time to progression was 4.5 months (95% CI, 1.9 to 8.3 months), and 1 year progression-free survival was 17% (95% CI, 8% to 38%). Median survival was 16.4 months, with a 1-year survival of 61% (95% CI, 46% to 81%). Toxicity was mainly hematologic, with eight of 31 (26%) patients experiencing grade 3 to 4 leukopenia; 15 of 31 patients (48%) experienced grade 3 to 4 neutropenia. The grade 3 to 4 nonhematologic toxicities included neuropathies (26%), myalgia (13%), and fatigue (10%). Conclusion BMS-247550 has limited activity against STSs when given in this dose and schedule. The clinical toxicity is similar to that of taxanes.