A microscale in vitro physiological model of the liver: predictive screens for drug metabolism and enzyme induction.

In vitro models of the liver using isolated primary hepatocytes have been used as screens for measuring the metabolism, toxicity and efficacy of xenobiotics, for studying hepatocyte proliferation, and as bioartificial liver support systems. Yet, primary isolated hepatocytes rapidly lose liver specific functions when maintained under standard in vitro cell culture conditions. Many modifications to conventional culture methods have been developed to foster retention of hepatocyte function. Still, not all of the important functions -- especially the biotransformation functions of the liver -- can as yet be replicated at desired levels, prompting continued development of new culture systems. In the first part of this article, we review primary hepatocyte in vitro systems used in metabolism and enzyme induction studies. We then describe a scalable microreactor system that fosters development of 3D-perfused micro-tissue units and show that primary rat cells cultured in this system are substantially closer to native liver compared to cells cultured by other in vitro methods, as assessed by a broad spectrum of gene expression, protein expression and biochemical activity metrics. These results provide a foundation for extension of this culture model to other applications in drug discovery -- as a model to study drug-drug interactions, as a model for the assessment of acute and chronic liver toxicity arising from exposure to drugs or environmental agents; and as a disease model for the study of viral hepatitis infection and cancer metastasis.

Comparative study of risk factors for skin breakdown with cervical orthotic devices: Philadelphia and Aspen.

PURPOSE: To compare risk factors for skin breakdown between Philadelphia and Aspen cervical collars. METHODS: Crossover design. Twenty healthy volunteers wore Philadelphia and Aspen cervical collars in random order. Occipital pressure, relative skin humidity, and skin temperature measured at 0 and 30 minutes. Paired t-tests compared changes between collars from 0 to 30 minutes. FINDINGS: Occipital pressure and skin temperature were not statistically different between collars. Relative skin humidity increased more in Philadelphia (29% +/- 17%) than Aspen (8% +/- 9%), p < 0.001. CONCLUSIONS: Aspen resulted in lower relative skin humidity.

Designing an incentive compensation program that works.

To encourage innovation and improve departmental and organizational bottom lines, Winchester Hospital, Winchester, Massachusetts, developed and implemented a middle management and staff incentive compensation plan. Middle managers and staff who participate in projects that provide savings to the hospital are paid a share of the savings. The plan allows staff the option of designing "horizontal" projects, in which a project leader carries out a project individually or with peers, or "vertical" projects, in which a project leader directs a team of key individuals. Increasing numbers of vertical projects have been proposed since the plan's inception in 1994. In addition to increasing the hospital's operating income, the program provides cost-effective, variable compensation, which especially appeals to motivated, high-performing employees; motivates employees to overcome roadblocks; facilitates a team approach that bridges traditional departmental boundaries; and encourages a beneficial and collegial competitiveness among managers.

Trauma multidisciplinary QI project: evaluation of cervical spine clearance, collar selection, and skin care.

PURPOSE: To evaluate data regarding cervical collars and develop guidelines related to product selection, cervical spine clearance, and skin care. METHODS: Production selection and skin care were evaluated by multidisciplinary teams review of QI data. RESULTS: The multidisciplinary teams identified a c-spine clearance algorithm, a methodology for continuous skin evaluation, and a new policy for skin care under the c-collar. CONCLUSIONS: Focused attention to problems surrounding cervical spine immobilization can decrease patient complications.

Ascaris suum: localization by immunochemical and fluorescent probes of host proteases and parasite proteinase inhibitors in cross-sections.

Cross-sections of muscle, intestine, and genital tract fluoresced in defined locations when live Ascaris suum adults were incubated in medium containing chymotrypsin liganded with fluorescein-5-isothiocyanate. This suggests that the protease, or portions of it, are assimilated by A. suum. A. suum chymotrypsin/elastase isoinhibitors were found in muscle sarcolemma, eggs, sperm, and intestine, and host chymotrypsin was localized in the same regions of these tissues by immunofluorescence and immunoperoxidase techniques. These experiments demonstrate that host chymotrypsin enters the parasite, that it is present in specific regions of Ascaris, and that it probably exists as an enzyme-inhibitor complex.