Citations

ABSTRACT Staphylococcus lugdunensis is an atypically virulent coagulase-negative staphylococcal species associated with acute and destructive infections that often resemble Staphylococcus aureus infections. Several types of infection caused by S. lugdunensis (e.g., native valve endocarditis, prosthetic joint infection, and intravascular catheter infection) are associated with biofilm formation, which may lead to an inability to eradicate the infection due to the intrinsic nature of biofilms to resist high levels of antibiotics. In this study, planktonic MICs and MBCs and biofilm bactericidal concentrations of 10 antistaphylococcal antimicrobial agents were measured for 15 S. lugdunensis isolates collected from patients with endocarditis, medical device infections, or skin and soft tissue infections. Planktonic isolates were susceptible to all agents studied, but biofilms were resistant to high concentrations of most of the drugs. However, moxifloxacin was able to kill 73% of isolates growing in biofilms at ≤0.5 μg/ml. Relative to the effect on cell density, subinhibitory concentrations of nafcillin substantially stimulated biofilm formation of most isolates, whereas tetracycline and linezolid significantly decreased biofilm formation in 93 and 80% of isolates, respectively. An unexpected outcome of MBC testing was the observation that vancomycin was not bactericidal against 93% of S. lugdunensis isolates, suggesting widespread vancomycin tolerance in this species. These data provide insights into the response of S. lugdunensis isolates when challenged with various levels of antimicrobial agents in clinical use.

AbstractTwo simplified methods for quantitative lipoprotein analysis have been calibrated and compared with each other using analytic ultracentrifugation as a standard reference procedure. The first method was the Friedewald procedure and the second was an automated agarose gel electrophoresis system. Both procedures offer comparable quantitative lipoprotein analysis with potential for large scale screening purposes at low cost ($4.00–$5.00 per analysis). There were advantages and limitations to both procedures. The Friedwald procedure can be used on frozen sera but requires 3 ml sera. In contrast, the electrophoresis system must be used with fresh serum but requires only 50 μl serum and the electrophoretic slides may be quantitatively analyzed several years retrospectively.

Data from the records of patients who underwent 2223 carotid endarterectomies at the Mayo Clinic between January 1, 1972, and December 31, 1985, were abstracted to compare the effects of isoflurane, enflurane, and halothane on the critical cerebral blood flow (CBF) (i.e., the CBF below which the majority of patients develop EEG ischemic changes within 3 min of carotid occlusion), the incidence of EEG ischemic changes, and the neurologic outcome. In a total of 2196 of these procedures, the patient received one of the three volatile anesthetics and, in 2010 of these, both the EEG and the CBF were monitored. Chronologically, halothane was the primary agent from 1972–1974; enflurane progressively replaced halothane during 1975–1981; and isoflurane was used almost exclusively since 1982. This analysis confirmed a previous study that the critical CBF during isoflurane anesthesia (703 procedures) was approximately 10 ml ± 100 g−1 • min−1, as contrasted to that of approximately 20 ml ± 100 g−1 • min−1 during halothane anesthesia (467 procedures). This analysis also established that the critical CBF during enflurane anesthesia (840 procedures) was approximately 15 ml ± 100 g−1 • min−1. The incidence of EEG ischemic changes was significantly less (P < 0.001) during isoflurane anesthesia (18%) than during either enflurane (26%) or halothane (25%) anesthesia. This difference occurred despite the fact that the preoperative risk status was greater in the patients given isoflurane. There was no difference in neurologic outcome between the three anesthetics, and none was expected, since all patients with EEG changes were immediately shunted, if possible. The authors conclude that relative to halothane and enflurane, isoflurane does offer a degree of cerebral protection for transient incomplete regional cerebral ischemia during carotid endarterectomy.

Abstract The proper treatment of synovial proliferative disorders depends on an accurate diagnosis and a knowledge of the natural history of these afflictions. A simple classification of the major synovial disorders with a brief general description of each, highlighting the prominent clinical features, is helpful. A thorough history and physical examination should enable the clinician to categorize the nature of the synovial disorder. Further evaluation and consultation can then be directed within the appropriate category. Radiologic, laboratory, and microscopic studies aid in arriving at a definitive diagnosis. Once a diagnosis has been established, therapy or further evaluation can be instituted.

AbstractThis article reviews progress in chemopreventive drug development, especially data and concepts that are new since the 2002 AACR report on treatment and prevention of intraepithelial neoplasia. Molecular biomarker expressions involved in mechanisms of carcinogenesis and genetic progression models of intraepithelial neoplasia are discussed and analyzed for how they can inform mechanism-based, molecularly targeted drug development as well as risk stratification, cohort selection, and end-point selection for clinical trials. We outline the concept of augmenting the risk, mechanistic, and disease data from histopathologic intraepithelial neoplasia assessments with molecular biomarker data. Updates of work in 10 clinical target organ sites include new data on molecular progression, significant completed trials, new agents of interest, and promising directions for future clinical studies. This overview concludes with strategies for accelerating chemopreventive drug development, such as integrating the best science into chemopreventive strategies and regulatory policy, providing incentives for industry to accelerate preventive drugs, fostering multisector cooperation in sharing clinical samples and data, and creating public-private partnerships to foster new regulatory policies and public education.