Evolution of antimicrobial prophylaxis in cardiovascular surgery

Objective: To examine the optimal duration of antibiotic prophylaxis in major cardiovascular surgery. Methods: In the past 15 years, four prospective randomized, controlled studies, conducted by the same group of authors, compared seven prophylactic antimicrobial regimens in 2970 patients undergoing major cardiovascular surgery. In 1980/81, a 4-day cefazolin (CFZ) prophylaxis was compared with a 2-day cefuroxime (CFX) administration (n=566). In 1982/83, a 2-day CFX prophylaxis was compared with a two shot ceftriaxone (CRO) prophylaxis (n=512). In 1984/87, a 1-day CFZ prophylaxis was compared with a single shot prophylaxis of CRO (n=883). In 1994/1995, a 4 day combination of amoxicillin (AM) and netilmicin (NET) prophylaxis was compared with a single shot prophylaxis of CFX (n=1009). Results: Total infection rate varied between 4.5 and 5.7%, despite different antimicrobial regimen used and their varying duration. Wound infection rate was 1.1% (range 0.4-2.5%), sepsis rate was 0.8% (range 0.4-1.6%), pneumonia rate 2% (0.7-2.9%), urinary tract infection rate 0.4% (range 0-1.4%), and central venous catheter-related infection rate was 0.4% (0-1%). The 30-day mortality rate was 1.3% (range 0.4-2%). All these differences were not statistically significant. Conclusions: A low infection rate (range 4.5-5.7%) occurred despite changes in duration of various prophylactic antibiotic regimen with cephalosporins of first, second or third generation. As a single shot prophylaxis could nowadays successfully be used in cardiovascular surgery, no postoperative antibiotics should be used, unless an intraoperative or a postoperative infection is documented or in presence of major perioperative complication

Role of PINCH and Its Partner Tumor Suppressor Rsu-1 in Regulating Liver Size and Tumorigenesis

Particularly interesting new cysteine-histidine-rich protein (PINCH) protein is part of the ternary complex known as the IPP (integrin linked kinase (ILK)-PINCH-Parvin-α) complex. PINCH itself binds to ILK and to another protein known as Rsu-1 (Ras suppressor 1). We generated PINCH 1 and PINCH 2 Double knockout mice (referred as PINCH DKO mice). PINCH2 elimination was systemic whereas PINCH1 elimination was targeted to hepatocytes. The genetically modified mice were born normal. The mice were sacrificed at different ages after birth. Soon after birth, they developed abnormal hepatic histology characterized by disorderly hepatic plates, increased proliferation of hepatocytes and biliary cells and increased deposition of extracellular matrix. After a sustained and prolonged proliferation of all epithelial components, proliferation subsided and final liver weight by the end of 30 weeks in livers with PINCH DKO deficient hepatocytes was 40% larger than the control mice. The livers of the PINCH DKO mice were also very stiff due to increased ECM deposition throughout the liver, with no observed nodularity. Mice developed liver cancer by one year. These mice regenerated normally when subjected to 70% partial hepatectomy and did not show any termination defect. Ras suppressor 1 (Rsu-1) protein, the binding partner of PINCH is frequently deleted in human liver cancers. Rsu-1 expression is dramatically decreased in PINCH DKO mouse livers. Increased expression of Rsu-1 suppressed cell proliferation and migration in HCC cell lines. These changes were brought about not by affecting activation of Ras (as its name suggests) but by suppression of Ras downstream signaling via RhoGTPase proteins. In conclusion, our studies suggest that removal of PINCH results in enlargement of liver and tumorigenesis. Decreased levels of Rsu-1, a partner for PINCH and a protein often deleted in human liver cancer, may play an important role in the development of the observed phenotype. © 2013 Donthamsetty et al

Development of a chemically defined medium and discovery of new mitogenic growth factors for mouse hepatocytes: Mitogenic effects of FGF1/2 and PDGF

Chemically defined serum-free media for rat hepatocytes have been useful in identifying EGFR ligands and HGF/MET signaling as direct mitogenic factors for rat hepatocytes. The absence of such media for mouse hepatocytes has prevented screening for discovery of such mitogens for mouse hepatocytes. We present results obtained by designing such a chemically defined medium for mouse hepatocytes and demonstrate that in addition to EGFR ligands and HGF, the growth factors FGF1 and FGF2 are also important mitogenic factors for mouse hepatocytes. Smaller mitogenic response was also noticed for PDGF AB. Mouse hepatocytes are more likely to enter into spontaneous proliferation in primary culture due to activation of cell cycle pathways resulting from collagenase perfusion. These results demonstrate unanticipated fundamental differences in growth biology of hepatocytes between the two rodent species. Copyright: © 2014 Reekie et al

Macroscopic Dynamics of Multi-Lane Traffic

We present a macroscopic model of mixed multi-lane freeway traffic that can be easily calibrated to empirical traffic data, as is shown for Dutch highway data. The model is derived from a gas-kinetic level of description, including effects of vehicular space requirements and velocity correlations between successive vehicles. We also give a derivation of the lane-changing rates. The resulting dynamic velocity equations contain non-local and anisotropic interaction terms which allow a robust and efficient numerical simulation of multi-lane traffic. As demonstrated by various examples, this facilitates the investigation of synchronization patterns among lanes and effects of on-ramps, off-ramps, lane closures, or accidents.Comment: For related work see http://www.theo2.physik.uni-stuttgart.de/helbing.htm

Spectroscopic parameters for silacyclopropynylidene, SiC2_2, from extensive astronomical observations toward CW Leo (IRC +10216) with the Herschel satellite

A molecular line survey has been carried out toward the carbon-rich asymptotic giant branch star CW Leo employing the HIFI instrument on board of the Herschel satellite. Numerous features from 480 GHz to beyond 1100 GHz could be assigned unambiguously to the fairly floppy SiC$_2$ molecule. However, predictions from laboratory data exhibited large deviations from the observed frequencies even after some lower frequency data from this survey were incorporated into a fit. Therefore, we present a combined fit of all available laboratory data together with data from radio-astronomical observations.Comment: 7 pages, 1 figure, J. Mol. Spectrosc., appeared; CDMS links corrected (version 2; current version: 3; may be updated later this year

Modeling and Simulation of Multi-Lane Traffic Flow

A most important aspect in the field of traffic modeling is the simulation of bottleneck situations. For their realistic description a macroscopic multi-lane model for uni-directional freeways including acceleration, deceleration, velocity fluctuations, overtaking and lane-changing maneuvers is systematically deduced from a gas-kinetic (Boltzmann-like) approach. The resulting equations contain corrections with respect to previous models. For efficient computer simulations, a reduced model delineating the coarse-grained temporal behavior is derived and applied to bottleneck situations.Comment: For related work see http://www.theo2.physik.uni-stuttgart.de/helbing.htm

Screening for candidate hepatic growth factors by selective portal infusion after canine Eck's fistula

Completely diverting portacaval shunt (Eck's fistula) in dogs causes hepatocyte atrophy, disruption of hepatocyte organelles, fatty infiltration and lowgrade hyperplasia. The effect of hepatic growth regulatory substances on these changes was assessed by constantly infusing test substances for four postoperative days after Eck's fistula into the detached left portal vein above the shunt. The directly infused left lobes were compared histopathologically with the untreated right lobes. In what has been called an hepatotrophic effect, stimulatory substances prevented the atrophy and increased hepatocyte mitoses. Of the hormones tested, only insulin was strongly hepatotrophic; T3 had a minor effect, and glucagon, prolactin, angiotensin II, vasopressin, norepinephrine and estradiol were inert. Insulin‐like growth factor, hepatic stimulatory substance, transforming growth factor–α and hepatocyte growth factor (also known as hematopoietin A) were powerfully hepatotrophic, but epidermal growth factor had a barely discernible effect. Transforming growth factor–β was inhibitory, but tamoxifen, interleukin‐1 and interleukin‐2 had no effect. The hepatotrophic action of insulin was not altered when the insulin infusate was mixed with transforming growth factor–β or tamoxifen. These experiments show the importance of in vivo in addition to in vitro testing of putative growth control factors. They illustrate how Eck's fistula model can be used to screen for such substances and possibly to help delineate their mechanisms of action. (HEPATOLOGY 1991;14:665–670.) Copyright © 1991 American Association for the Study of Liver Disease

Studies on mechanisms of augmentation of liver regeneration by cyclosporine and FK 506

Evidence could not be found of immune modulation of liver regeneration. The powerful immunosuppressive drug FK 506, which augments the response after partial hepatectomy in normal rats, had the same effect in T cell—deficient nude rats. The cytotoxicity of natural killer cells in treated nude rats was not significantly changed by FK 506 therapy. However, the serum of FK 506—treated nude rats increased hepatocyte proliferation when added to third‐party hepatocyte cultures, suggesting that FK 506 had induced a serum growth factor in the nude rats or had suppressed an inhibitory factor. A hypothesis was advanced that FK 506 (and cyclosporine) affects hepatic growth by nonimmunological pathways. (HEPATOLOGY 1991;14:140–143.) Copyright © 1991 American Association for the Study of Liver Disease

Conditional Genetic Elimination of Hepatocyte Growth Factor in Mice Compromises Liver Regeneration after Partial Hepatectomy

Hepatocyte growth factor (HGF) has been shown to be indispensable for liver regeneration because it serves as a main mitogenic stimulus driving hepatocytes toward proliferation. We hypothesized that ablating HGF in adult mice would have a negative effect on the ability of hepatocytes to regenerate. Deletion of the HGF gene was achieved by inducing systemic recombination in mice lacking exon 5 of HGF and carrying the Mx1-cre or Cre-ERT transgene. Analysis of liver genomic DNA from animals 10 days after treatment showed that a majority (70-80%) of alleles underwent cre-induced genetic recombination. Intriguingly, however, analysis by RT-PCR showed the continued presence of both unrecombined and recombined forms of HGF mRNA after treatment. Separation of liver cell populations into hepatocytes and non-parenchymal cells showed equal recombination of genomic HGF in both cell types. The presence of the unrecombined form of HGF mRNA persisted in the liver in significant amounts even after partial hepatectomy (PH), which correlated with insignificant changes in HGF protein and hepatocyte proliferation. The amount of HGF produced by stellate cells in culture was indirectly proportional to the concentration of HGF, suggesting that a decrease in HGF may induce de novo synthesis of HGF from cells with residual unrecombined alleles. Carbon tetrachloride (CCl4)-induced regeneration resulted in a substantial decrease in preexisting HGF mRNA and protein, and subsequent PH led to a delayed regenerative response. Thus, HGF mRNA persists in the liver even after genetic recombination affecting most cells; however, PH subsequent to CCl4 treatment is associated with a decrease in both HGF mRNA and protein and results in compromised liver regeneration, validating an important role of this mitogen in hepatic growth. © 2013 Nejak-Bowen et al

Effect of cimetidine, ranitidine, famotidine and omeprazole on hepatocyte proliferation in vitro

Recently reports have indicated that both cimetidine and ranitidine delay cell proliferation in rats following 70% partial hepatectomy and result in an increased mortality following this procedure. The present study was designed to determine whether three H2 blocking agents (cimetidine, ranitidine, famotidine) and a new, powerful antisecretory drug (omeprazole) specifically influence hepatocyte proliferation in primary culture. Hepatocytes were isolated from livers of normal male rats by the standard collagenase perfusion technique. Hepatic DNA synthesis and percent of labelled nuclei were determined after 48 h incubation. Hepatocytes in culture were incubated with the H2 blocking agents and omeprazole or with different concentrations of serum obtained from shamoperated or 70% hepatectomized rats treated or not with the same agents. Rats were injected intraperitoneally at 8:00 a.m. on two consecutive days. In hepatectomized rats, the first dose was injected at 8:00 a.m. immediately after surgery, the second, 24 h later. The serum of sham-operated or 70% hepatectomized rats that did not receive drugs served as control. No changes in DNA synthesis, percentage of labelled nuclei and transaminase were detected when the agents were added to the hepatocytes in culture at concentrations within the effective pharmacological dosage and 30 times higher. Similarly, no changes in these parameters were obtained when different concentrations of serum obtained from sham-operated rats treated with H2 blocking agents or omeprazole were added to the basal culture medium. However, a significant inhibition of DNA synthesis and of percentage of labelled nuclei was observed when hepatocytes were incubated in the presence of serum from 70% hepatectomized rats that had been treated with cimetidine or with ranitidine. The serum of 70% hepatectomized rats treated with famotidine and omeprazole had no effect on hepatocyte proliferation in vitro. No effect on transaminase was found in these conditions. © 1989