The criterion of proportionality in the activation of Left Ventricular Assist Device implants: the method of "four boxes" to analyze the pre-implant phase.

BACKGROUND: Life-saving technologies have completely changed the normal conception of medical treatments. Left Ventricular Assist Devices (LVAD) can prolong survival for patients who are not candidates for heart transplantation. In order to analyze the pre-implantation phase, which involves a shared-decision making process before activation of the device, attention should be paid to the criterion of "proportionality" in order to properly assess the risks and benefits of implantation. AIM: The aim of our analysis is to provide an useful tool for the assessment of LVAD proportionality during the physicians' decision making. METHODS: The method of the "four boxes", developed by Jonsen et al, was chosen to analyze the notion of proportionality and the other main ethical issues regarding LVAD activation in adult patients. RESULTS: Medical issues are not the sole factors, which influence the choice of implantation by patients. Indeed, patient preferences, his/her quality of life, and contextual features should be taken into consideration when proposing LVADs: these factors are as important as clinical issues where outcomes are concerned. CONCLUSIONS: In order to assess the proportionality of such a device, we present, discuss and examine, in the framework of the pre-implant phase, the content of each topic treated by the "four boxes method", that is, an essential tool for the assessment of the proportionality of the treatment for LVAD candidates.

Donation After Circulatory Death: When Withdrawing Life-Sustaining Treatments Is Ethically Acceptable.

The possibility to determine death based on cardiocirculatory criteria in controlled cases, namely when there is a request to withhold treatment-or, more frequently, withdraw it-specifically recalls the recent Italian law on advance treatment directives and leaves the following question unanswered: Under what conditions is the patient's request legally and ethically acceptable? We present three ethical proportionality criteria for supporting physicians' decision-making facing patients' requests of treatment withdrawal, namely: 1. irreversible pathology with an ominous and worsening prognosis; 2. within an evaluation considering both clinical data and the patient's history; and 3. facing burdens that are no longer bearable. We finally argue that reflection over controlled donor may be a model for giving medicine the chance to responsibly deal with broader end-of-life issues.

Primary and immortalised human pancreatic islet endothelial cells: phenotypic and immunological characterisation.

AIMS/HYPOTHESIS: Studies on the biology of the microvascular endothelial cells (MECs) that surround and penetrate the pancreatic islets are hampered by difficulties in isolating and culturing large numbers of pure cells. We aimed to morphologically and functionally characterise primary MECs purified and cultured from human islets, and to establish a simian virus 40 (SV40)-immortalised cell line from these primary cultures. MATERIALS AND METHODS: Human islet MECs were extracted and purified using anti-CD105 coated immunomagnetic beads, and endothelial markers and surface molecules analysed by flow cytometric analysis. An immortalised cell line was then established by using a chimeric adeno5/SV40 virus. RESULTS: Islet MECs expressed classic and specific endothelial markers, a high basal level of intercellular adhesion molecule-1, and low levels of E-selectin and TNF (previously known as TNF-alpha) inducible vascular cell adhesion molecule-1. IFNG (previously known as IFN-gamma) induced expression of HLA class II molecules. The immortalised islet MECs expanded rapidly, exhibited increased DNA synthesis, and were passaged approximately 30 times, without signs of senescence. They retained the endothelial characteristics of the parental cells, and behaved as the primary cells in terms of TNF stimulation of expression of adhesion molecules and support of leucocyte adhesion and transmigration. CONCLUSIONS/INTERPRETATION: The immortalised islet MECs that we have established could effectively represent a substitute for primary counterparts for in vitro studies on the role of the microvasculature in pathophysiological processes involved in type 1 and type 2 diabetes.

Platelet activation supports the development of venous thrombosis in hyperlipidemic rats.

This investigation sought to determine how different components of the hemostatic system affect the development of venous thrombosis in rats displaying hyperlipidemia, either on a genetic basis or secondary to metabolic disorders. On employing an experimental model of collagen-triggered venous thrombosis, both spontaneously hyperlipidemic (Yoshida strain) and streptozotocin-induced diabetic rats generated about 2.3-fold greater thrombi than normolipidemic controls. This was associated with significant platelet activation, as revealed by increased levels of serum thromboxane B2 in diabetics (1.5-fold) as well as in Yoshida (8-fold) rats, in comparison with controls. In contrast, ex vivo total fibrinolytic activity, as measured by euglobulin lysis time, did not differ between normo- and hyperlipidemic or diabetic animals. Plasminogen activator inhibitor activity was lower in both Yoshida and diabetic rats than in controls. However, tissue-type plasminogen activator activity was differently affected by the genetic or the diabetes-related hyperlipidemia, showing significantly lower values in Yoshida (-26%), but significantly higher values in diabetic rats (+29%) than in normolipidemic controls. We conclude that platelet activation, rather than consistent modifications of the fibrinolytic system, is likely to influence the enhanced thrombus development associated with primary or secondary forms of hyperlipidemia.

Occupational exposure to polychlorinated biphenyls in electrical workers. I. Environmental and blood polychlorinated biphenyls concentrations.

Industrial exposure to polychlorinated biphenyls (PCBs) and internal dose were investigated in 80 worker exposed for many years to PCB mixtures with a 42% chlorine content (Pyralene 3010 and Apirolio). PCBs were determined by liquid gas chromatography on samples taken from workroom air, workroom surfaces and tools, the palms of the hand, and the blood of the workers. In the workroom air samples, PCB concentrations ranged from 48 to 275 micrograms/m3. All tested surfaces and tools were heavily contaminated, with a range from 0.2 to 159 micrograms PCBs per cm2 of surface. Considerable amounts of PCBs were detected on the palms of the hands of the workers (2-28 microgram/cm2 of skin surface). In blood, total PCB concentrations from 88 to 1319 micrograms/kg were observed: comparing the blood concentrations of low and high chlorine content biphenyls, a significant difference was found for the low-chlorinated biphenyl concentrations between workers currently exposed and workers exposed only in the past. In groups of workers who were homogeneous as regards work area and job, the PCB concentrations in the blood were closely correlated with the length of actual occupational exposure to these compounds. These findings led to the conclusion that absorption of PCBs in these workers had occurred mainly through the skin, therefore industrial preventive surveillance must take this route of exposure into account. Since blood PCB concentrations appear to be correlated with the length of exposure, PCB determination on whole blood may be used to monitor industrial and environmental exposure to PCBs.