Functional contributions of bootlegging and entrepreneurship in research organizations

Bootlegging and entrepreneurship by scientists in research organization

Pathogenesis, prevention, and management of bleeding and thrombosis in patients with liver diseases

Patients with liver diseases may develop alterations in all components of the hemostatic system. Thrombocytopenia, low levels of coagulation factors and inhibitors, low levels of fibrinolytic proteins, and increased levels of endothelial-derived proteins such as von Willebrand factor are all part of the coagulopathy of liver disease. Due to concomitant changes in pro- and antihemostatic drivers, the net effects of these complex hemostatic changes have long been unclear. According to current concepts, the hemostatic system of patients with liver disease is in an unstable balance, which explains the occurrence of both bleeding and thrombotic complications. This review will discuss etiology and management of bleeding and thrombosis in liver disease and will outline unsolved clinical questions. In addition, we will discuss the role of intrahepatic activation of coagulation for progression of liver disease, a novel paradigm with potential consequences for the general management of patients with liver disease.</p

Laparoscopic Versus Open Cholecystectomy: A Prospective Matched-Cohort Study

To compare the results of laparoscopic cholecystectomy (LC) and open cholecystectomy (OC) for symptomatic cholelithiasis in elective surgery we performed a prospective matched-cohort study. Hundred consecutive patients who underwent LC in the period Sept. 1990-June 1992, and 100 patients who were age and sex matched and underwent an elective OC in the foregoing two years (1989-1990) were studied. The median operation time for LC (75, 40-180 min) was significantly longer than for OC (55, 20-155 min; p < 0.001). Postoperative hospitalization was significantly shorter after LC (3, 1-16 days), compared with OC (7, 4-22 days; p<0.001). Conversion of LC to OC occurred in 12 (12%) patients initially scheduled to undergo LC. Complications occurred in 5 patients (5%) after LC and in 5 patients (5%) after OC. The calculated expenses (operation and postoperative hospitalization, 3rd class) were approximately fl. 3740,- for LC (excl. investments for pieces of apparatus) and fl. 6725,- for OC. This study demonstrates that LC can be performed safely with the number of complications comparable to those for OC. Bile duct injury is a serious potential threat. The main advantages ofLC are the minimal trauma, with more rapid recovery. Insurers seem to benefit from reduced postoperative disability and earlier discharge

Blood Markers of Portal Hypertension Are Associated with Blood Loss and Transfusion Requirements during Orthotopic Liver Transplantation

There is increasing evidence that portal hypertension plays a major role in bleeding risk during orthotopic liver transplantation (OLT). We investigated the association between preoperative blood levels of von Willebrand factor (VWF) and soluble CD163 (sCD163), which are established markers of portal hypertension, and blood loss and transfusion requirements during OLT. We measured levels of VWF and sCD163 in preoperative serum samples of 168 adult patients undergoing a primary OLT between 1998 and 2012. Preoperative levels of VWF and sCD163 correlated with the model of end-stage liver disease (MELD) score (r = 0.414, p < 0.001 and r = 0.382, p < 0.001, respectively). Patients with high VWF or sCD163 levels (VWF and sCD163 levels above the median) had a substantially increased risk of needing red blood cell transfusion compared with patients with low VWF or sCD163 levels (VWF and sCD163 levels below the median) (odds ratio 3.5 [95% confidence interval, CI 1.7-7.0] and 2.3 [95% CI 1.1-4.5], respectively). Blood loss was highest in patients with both high VWF or sCD163 levels and a high preoperative international normalized ratio. Elevated blood levels of markers of portal hypertension are associated with increased blood loss and transfusion requirements during OLT and support the notion that portal hypertension is an important contributor to perioperative blood loss

Anticoagulant Management and Synthesis of Hemostatic Proteins during Machine Preservation of Livers for Transplantation

Liver transplantation remains the only curative treatment for patients with end-stage liver disease. Despite a steadily increasing demand for suitable donor livers, the current pool of donor organs fails to meet this demand. To resolve this discrepancy, livers traditionally considered to be of suboptimal quality and function are increasingly utilized. These marginal livers, however, are less tolerant to the current standard cold preservation of donor organs. Therefore, alternative preservation methods have been sought and are progressively applied into clinical practice. Ex situ machine perfusion is a promising alternative preservation modality particularly for suboptimal donor livers as it provides the ability to resuscitate, recondition, and test the viability of an organ prior to transplantation. This review addresses the modalities of machine perfusion currently being applied, and particularly focuses on the hemostatic management employed during machine perfusion. We discuss the anticoagulant agents used, the variation in dosage, and administration, as well as the implications of perfusion for extended periods of time in terms of coagulation activation associated with production of coagulation factors during perfusion. Furthermore, in regard to viability testing of an organ prior to transplantation, we discuss the possibilities and limitations of utilizing the synthesis of liver-derived coagulation factors as potential viability markers

A transient network of telechelic polymers and microspheres : structure and rheology

We study the structure and dynamics of a transient network composed of droplets of microemulsion connected by telechelic polymers. The polymer induces a bridging attraction between droplets without changing their shape. A viscoelastic behaviour is induced in the initially liquid solution, characterised in the linear regime by a stretched exponential stress relaxation. We analyse this relaxation in the light of classical theories of transient networks. The role of the elastic reorganisations in the deformed network is emphasized. In the non linear regime, a fast relaxation dynamics is followed by a second one having the same rate as in the linear regime. This behaviour, under step strain experiments, should induce a non monotonic behaviour in the elastic component of the stress under constant shear rate. However, we obtain in this case a singularity in the flow curve very different from the one observed in other systems, that we interpret in terms of fracture behaviour.Comment: 9 pages, 4 figure

Normothermic liver machine perfusion as a dynamic platform for regenerative purposes. What does the future have in store for us?

Liver transplantation has become an immense success; nevertheless, far more recipients are registered on waiting lists than there are available donor livers for transplantation. High-risk, extended criteria donor livers are increasingly used to reduce the discrepancy between organ demand and supply. Especially for high-risk livers, dynamic preservation using machine perfusion can decrease post-transplantation complications and may increase donor liver utilization by resuscitation and viability testing before transplantation. To further increase the availability of donor livers suitable for transplantation, new strategies are required that make it possible to use organs that are initially too damaged to be transplanted. With the current progress in experimental liver transplantation research, (long-term) normothermic machine perfusion may be used in the future as a dynamic platform for regenerative medicine approaches, enabling repair and regeneration of injured donor livers. Currently explored therapeutics such as defatting cocktails, ribonucleic acid interference, senolytics, and stem cell therapy may assist in the repair and/or regeneration of injured livers before transplantation. This review will provide a forecast of the future utility of normothermic machine perfusion for repair and regeneration of damaged donor livers to ultimately decrease the imbalance between donor liver demand and supply

Time scales in shear banding of wormlike micelles

Transient stress and birefringence measurements are performed on wormlike micellar solutions that "shear band", i.e. undergo flow-induced coexistence of states of different viscosities along a constant stress "plateau". Three well-defined relaxation times are found after a strain rate step between two banded flow states on the stress plateau. Using the Johnson-Segalman model, we relate these time scales to three qualitatively different stages in the evolution of the bands and the interface between them: band destabilization, reconstruction of the interface, and travel of the fully formed interface. The longest timescale is then used to estimate the magnitude of the (unknown) "gradient" terms that must be added to constitutive relations to explain the history independence of the steady flow and the plateau stress selection

Entropic phase separation of linked beads

We study theoretically a model system of a transient network of microemulsion droplets connected by telechelic polymers and explain recent experimental findings. Despite the absence of any specific interactions between either the droplets or polymer chains, we predict that as the number of polymers per drop is increased, the system undergoes a first order phase separation into a dense, highly connected phase, in equilibrium with dilute droplets, decorated by polymer loops. The phase transition is purely entropic and is driven by the interplay between the translational entropy of the drops and the configurational entropy of the polymer connections between them. Because it is dominated by entropic effects, the phase separation mechanism of the system is extremely robust and does not depend on the particlular physical realization of the network. The discussed model applies as well to other polymer linked particle aggregates, such as nano-particles connected with short DNA linkers