IntroductionLiver failure patients might be at risk for citrate accumulation during continuous venovenous hemodialysis (CVVHD) with regional citrate anticoagulation. The aim of this study was to investigate the predictive capability of baseline liver function parameters regarding citrate accumulation, expressed as an increase in the calcium total/calcium ionized (Catot/Caion) ratio ≥2.5, and to describe the feasibility of citrate CVVHD in liver failure patients.MethodsWe conducted a prospective observational study in medical ICU patients treated in a German university hospital. We performed 43 CVVHD runs using citrate for regional anticoagulation in 28 critically ill patients with decompensated liver cirrhosis or acute liver failure (maximum of two CVVHD runs per patient). Liver function was characterized before CVVHD using laboratory parameters, calculation of Child-Pugh and Model of End-stage Liver Disease scores, and determination of the plasma disappearance rate of indocyanine green. In addition to blood gas analysis, we measured total calcium and citrate in serum at baseline and after definitive time points for each CVVHD run.ResultsAccumulation of citrate in serum correlated with an increase in the Catot/Caion ratio. Although the critical upper threshold of Catot/Caion ratio ≥2.5 was exceeded 10 times in seven different CVVHD runs, equalization of initial metabolic acidosis was possible without major disturbances of acid-base and electrolyte status. Standard laboratory liver function parameters showed poor predictive capabilities regarding citrate accumulation in terms of an elevated Catot/Caion ratio ≥2.5. In contrast, serum lactate ≥3.4 mmol/l and prothrombin time ≤26% predicted an increase in the Catot/Caion ratio ≥2.5 with high sensitivity (86% for both lactate and prothrombin time) and specificity (86% for lactate, 92% for prothrombin time).ConclusionsDespite substantial accumulation of citrate in serum, CVVHD with regional citrate anticoagulation seems feasible in patients with severely impaired liver function. Citrate accumulation in serum is reflected by an increase in the Catot/Caion ratio. To identify patients at risk for citrate accumulation in terms of a Catot/Caion ratio ≥2.5, baseline serum lactate (threshold ≥3.4 mmol/l) and prothrombin time (threshold ≤26%) may be useful for risk prediction in daily clinical practice. Careful monitoring of electrolytes and acid-base status is mandatory to ensure patient safety.

pancreatic cancer ͉ RCAS ͉ tumor virus A ͉ RNA interference ͉ molecular in vivo imaging I n the postgenome area, there is an increasing need for tools allowing the spatiotemporal evaluation of gene function in vivo. Genetically engineered mouse models that permit conditional expression or inactivation of genes have dramatically improved our basic understanding of gene function in vivo. However, gene knockout and knockin technologies such as the Cre-loxP system are difficult, time-consuming, and expensive (1). This problem can be overcome with an alternative strategy by using avian retroviral vectors to deliver genes to specific proliferating somatic mammalian cells (2-4). The retroviral RCASBP(A) (replication competent avian sarcoma-leukosis virus long terminal repeat with splice acceptor, Bryan RSV polymerase and subgroup A envelope)-expression vector derived from subgroup A avian sarcoma-leukosis virus can be used to produce high-titer viral stocks in chicken DF-1 fibroblasts and deliver transgenes stable to proliferating cells that express the specific receptor for avian sarcoma-leukosis virus subgroup A envelope (envA), tumor virus A (TVA) (2,5,6). In addition, other retroviral or lentiviral vectors can be pseudotyped with envA and used to transduce TVA-positive cells (7). Mammalian cells do not express TVA and therefore are resistant to infection by RCASBP(A) viruses. However, ectopic expression of TVA confers susceptibility to infection in vitro and in vivo. Because RCASBP(A) viruses are replication incompetent in mammalian cells, the virus does not spread (2-4). The RCASBP(A) vector itself does not cause a significant immune response in the host (8). However, an immune response against foreign genes expressed by RCAS-mediated gene transfer has been observed. Interestingly, the extent of the immune response seems to be tissue specific, which may limit the use of the RCAS-TVA system in certain tissue types (8). Mammalian cells remain susceptible to reinfection, which allows simultaneous or sequential introduction of genes into the same cells. This makes the system particularly useful to study the cooperation of specific genes (3, 9).The RCAS-TVA somatic gene transfer system has been used in a variety of murine models in vivo (9-19), and the advantages and disadvantages are well documented (2-4). In particular, the system has been widely used to model sporadic human cancer in mice. For example, glioblastoma, ovary cancer, pancreatic cancer, liver cancer, and mammary cancer have been induced by the introduction of oncogenes in a tissue-specific fashion (9,12,15,17,18). Interestingly, all existing TVA-expressing mouse lines have been generated by random transgenesis by using pronuclear injection that often results in variable and mosaic transgene expression. Cell-specific TVA expression has been achieved in these models by using tissue-specific promoters. Therefore, individual transgenic lines must be generated for different tissue types that limit the broad use of the system.To generate a universal, tissue-sp...

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The contents of 15 different phenolic compounds in apple leaves and fruit skin from various orchards were determined by HPLC. High concentrations of flavan‐3‐ols were found in those orchards which were not infected by Venturia inaequalis. This observation corroborates earlier findings on different cultivars. The hypothesis that these compounds could be involved in the resistance of apple to scab was tested by inhibiting the key enzyme of the phenol biosynthesis, the phenylalanine‐ammonia‐lyase, in young shoots of the resistant genotype ‘Sir Prize'. After inoculation of the inhibitor‐treated leaves, severe symptoms of the disease occurred. The fungal infection was confirmed by histological studies. No flavonal‐accumulation could be observed at the infection site which was the case in the non‐inhibited but inoculated controls.

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Fungal "colonisation" is independently associated to mortality in cirrhotic ICU-patients. Early antimycotic therapy should be considered in critically ill cirrhotic patients with FC.

Sooty blotch and flyspeck (SBFS) fungi colonize the surface wax layer of the fruit of apple, pear, persimmon, banana, orange, papaya, and several other cultivated tree and vine crops. In addition to colonizing cultivated fruit crops, SBFS fungi also grow on the surfaces of stems, twigs, leaves, and fruit of a wide range of wild plants. The disease occurs worldwide in regions with moist growing seasons. SBFS is regarded as a serious disease by fruit growers and plant pathologists because it can cause substantial economic damage. The smudges and stipples of SBFS often result in downgrading of fruit from premium fresh-market grade to processing use. This review describes the major shifts that have occurred during the past decade in understanding the genetic diversity of the SBFS complex, clarifying its biogeography and environmental biology, and developing improved management strategies.

Background Early recognition of high-risk-patients with acute respiratory distress syndrome (ARDS) might improve their outcome by less protracted allocation to intensified therapy including extracorporeal membrane oxygenation (ECMO). Among numerous predictors and classifications, the American European Consensus Conferenece (AECC)-and Berlin-definitions as well as the oxygenation index (OI) and the Murray-/Lung Injury Score are the most common. Most studies compared the prediction of mortality by these parameters on the day of intubation and/or diagnosis of ARDS. However, only few studies investigated prediction over time, in particular for more than three days. Objective Therefore, our study aimed at characterization of the best predictor and the best day(s) to predict 28-days-mortality within four days after intubation of patients with ARDS. Methods In 100 consecutive patients with ARDS severity according to OI (mean airway pressure*-F i O 2 /p a O 2), modified Murray-score without radiological points (Murray_mod), AECC-and Berlin-definition, were daily documented for four days after intubation. In the subgroup of 49 patients with transpulmonary thermodilution (TPTD) monitoring (PiCCO), extravascular lung water index (EVLWI) was measured daily.