Percutaneous transhepatic cholangiography and biliary drainage after liver transplantation: A five-year experience

Evaluation of the biliary tract by percutaneous transhepatic cholangiography (PTC) is often required in liver transplant patients with an abnormal postoperative course. Indications for PTC include failure of liver enzyme levels to return to normal postoperatively, an elevation of serum bilirubin or liver enzyme levels, suspected bile leak, biliary obstructive symptoms, cholangitis, and sepsis. Over a 5-year period 625 liver transplants in 477 patients were performed at the University Health Center of Pittsburgh. Fifty-three patients (56 transplants) underwent 70 PTCs. Complications diagnosed by PTC included biliary strictures, bile leaks, bilomas, liver abscesses, stones, and problems associated with internal biliary stents. Thirty-two percutaneous transhepatic biliary drainage procedures were performed. Ten transplantation patients underwent balloon dilatation of postoperative biliary strictures. Interventional radiologic techniques were important in treating other complications and avoiding additional surgery in many of these patients. © 1987 Springer-Verlag New York Inc

Orexinergic Input to Dopaminergic Neurons of the Human Ventral Tegmental Area

The mesolimbic reward pathway arising from dopaminergic (DA) neurons of the ventral tegmental area (VTA) has been strongly implicated in reward processing and drug abuse. In rodents, behaviors associated with this projection are profoundly influenced by an orexinergic input from the lateral hypothalamus to the VTA. Because the existence and significance of an analogous orexigenic regulatory mechanism acting in the human VTA have been elusive, here we addressed the possibility that orexinergic neurons provide direct input to DA neurons of the human VTA. Dual-label immunohistochemistry was used and orexinergic projections to the VTA and to DA neurons of the neighboring substantia nigra (SN) were analyzed comparatively in adult male humans and rats. Orexin B-immunoreactive (IR) axons apposed to tyrosine hydroxylase (TH)-IR DA and to non-DA neurons were scarce in the VTA and SN of both species. In the VTA, 15.062.8% of TH-IR perikarya in humans and 3.260.3% in rats received orexin B-IR afferent contacts. On average, 0.2460.05 and 0.0560.005 orexinergic appositions per TH-IR perikaryon were detected in humans and rats, respectively. The majority(86–88%) of randomly encountered orexinergic contacts targeted the dendritic compartment of DA neurons. Finally, DA neurons of the SN also received orexinergic innervation in both species. Based on the observation of five times heavierorexinergic input to TH-IR neurons of the human, compared with the rat, VTA, we propose that orexinergic mechanism acting in the VTA may play just as important roles in reward processing and drug abuse in humans, as already established well in rodents

Impact of Sauropod Dinosaurs on Lagoonal Substrates in the Broome Sandstone (Lower Cretaceous), Western Australia

Existing knowledge of the tracks left by sauropod dinosaurs (loosely ‘brontosaurs’) is essentially two-dimensional, derived mainly from footprints exposed on bedding planes, but examples in the Broome Sandstone (Early Cretaceous) of Western Australia provide a complementary three-dimensional picture showing the extent to which walking sauropods could deform the ground beneath their feet. The patterns of deformation created by sauropods traversing thinly-stratified lagoonal deposits of the Broome Sandstone are unprecedented in their extent and structural complexity. The stacks of transmitted reliefs (underprints or ghost prints) beneath individual footfalls are nested into a hierarchy of deeper and more inclusive basins and troughs which eventually attain the size of minor tectonic features. Ultimately the sauropod track-makers deformed the substrate to such an extent that they remodelled the topography of the landscape they inhabited. Such patterns of substrate deformation are revealed by investigating fragmentary and eroded footprints, not by the conventional search for pristine footprints on intact bedding planes. For that reason it is not known whether similar patterns of substrate deformation might occur at sauropod track-sites elsewhere in the world

Invasion of the Red Seaweed \u3cem\u3eHeterosiphonia japonica\u3c/em\u3e Spans Biogeographic Provinces in the Western North Atlantic Ocean

The recent invasion of the red alga Heterosiphonia japonica in the western North Atlantic Ocean has provided a unique opportunity to study invasion dynamics across a biogeographical barrier. Native to the western North Pacific Ocean, initial collections in 2007 and 2009 restricted the western North Atlantic range of this invader to Rhode Island, USA. However, through subtidal community surveys, we document the presence of Heterosiphonia in coastal waters from Maine to New York, USA, a distance of more than 700 km. This geographical distribution spans a well-known biogeographical barrier at Cape Cod, Massachusetts. Despite significant differences in subtidal community structure north and south of Cape Cod, Heterosiphonia was found at all but two sites surveyed in both biogeographic provinces, suggesting that this invader is capable of rapid expansion over broad geographic ranges. Across all sites surveyed, Heterosiphonia comprised 14% of the subtidal benthic community. However, average abundances of nearly 80% were found at some locations. As a drifting macrophyte, Heterosiphonia was found as intertidal wrack in abundances of up to 65% of the biomass washed up along beaches surveyed. Our surveys suggest that the high abundance of Heterosiphonia has already led to marked changes in subtidal community structure; we found significantly lower species richness in recipient communities with higher Heterosiphona abundances. Based on temperature and salinity tolerances of the European populations, we believe Heterosiphonia has the potential to invade and alter subtidal communities from Florida to Newfoundland in the western North Atlantic

Generalisability of Randomised Controlled Trials in Heart Failure with Reduced Ejection Fraction

BACKGROUND: Heart failure (HF) trials have stringent in- and ex- clusion criteria, but limited data exists regarding generalisability of trials. We compared patient characteristics and outcomes between patients with HF and reduced ejection fraction (HFrEF) in trials and observational registries. METHODS AND RESULTS: Individual patient data for 16922 patients from five randomised clinical trials and 46914 patients from two HF registries were included. The registry patients were categorised into trial-eligible and non-eligible groups using the most commonly used in- and ex-clusion criteria. A total of 26104 (56%) registry patients fulfilled the eligibility criteria. Unadjusted all-cause mortality rates at one year were lowest in the trial population (7%), followed by trial-eligible patients (12%) and trial-non-eligible registry patients (26%). After adjustment for age and sex, all-cause mortality rates were similar between trial participants and trial-eligible registry patients (standardised mortality ratio (SMR) 0.97; 95% confidence interval (CI) 0.92 -1.03) but cardiovascular mortality was higher in trial participants (SMR 1.19; 1.12 -1.27). After full case-mix adjustment, the SMR for cardiovascular mortality remained higher in the trials at 1.28 (1.20- 1.37) compared to RCT-eligible registry patients. CONCLUSION: In contemporary HF registries, over half of HFrEF patients would have been eligible for trial enrolment. Crude clinical event rates were lower in the trials, but, after adjustment for case-mix, trial participants had similar rates of survival as registries. Despite this, they had about 30% higher cardiovascular mortality rates. Age and sex were the main drivers of differences in clinical outcomes between HF trials and observational HF registries

Role of the Drosophila Non-Visual ß-Arrestin Kurtz in Hedgehog Signalling

The non-visual ß-arrestins are cytosolic proteins highly conserved across species that participate in a variety of signalling events, including plasma membrane receptor degradation, recycling, and signalling, and that can also act as scaffolding for kinases such as MAPK and Akt/PI3K. In Drosophila melanogaster, there is only a single non-visual ß-arrestin, encoded by kurtz, whose function is essential for neuronal activity. We have addressed the participation of Kurtz in signalling during the development of the imaginal discs, epithelial tissues requiring the activity of the Hedgehog, Wingless, EGFR, Notch, Insulin, and TGFβ pathways. Surprisingly, we found that the complete elimination of kurtz by genetic techniques has no major consequences in imaginal cells. In contrast, the over-expression of Kurtz in the wing disc causes a phenotype identical to the loss of Hedgehog signalling and prevents the expression of Hedgehog targets in the corresponding wing discs. The mechanism by which Kurtz antagonises Hedgehog signalling is to promote Smoothened internalization and degradation in a clathrin- and proteosomal-dependent manner. Intriguingly, the effects of Kurtz on Smoothened are independent of Gprk2 activity and of the activation state of the receptor. Our results suggest fundamental differences in the molecular mechanisms regulating receptor turnover and signalling in vertebrates and invertebrates, and they could provide important insights into divergent evolution of Hedgehog signalling in these organisms

Lung abscess predicts the surgical outcome in patients with pleural empyema

<p>Abstract</p> <p>Objectives</p> <p>Most cases of pleural empyema are caused by pulmonary infections, which are usually combined with pneumonia or lung abscess. The mortality of patients with pleural empyema remains high (up to 20%). It also contributes to higher hospital costs and longer hospital stays. We studied pleural empyema with combined lung abscess to determine if abscess was associated with mortality.</p> <p>Methods</p> <p>From January 2004 to December 2006, we retrospectively reviewed 259 patients diagnosed with pleural empyema who received thoracscopic decortications of the pleura in a single medical center. We evaluated their clinical data and analyzed their chest computed tomography scans. Outcomes of pleural empyema were compared between groups with and without lung abscess.</p> <p>Results</p> <p>Twenty-two pleural empyema patients had lung abscesses. Clinical data showed significantly higher incidences in the lung abscess group of pre-operative leukocytosis, need for an intensive care unit stay and mortality.</p> <p>Conclusion</p> <p>Patients with pleural empyema and lung abscess have higher intensive care unit admission rate, higher mortality during 30 days and overall mortality than patients with pleural empyema. The odds ratio of lung abscess is 4.685. Physician shall pay more attention on high risk patient of lung abscess for early detection and management.</p

Chemical combination effects predict connectivity in biological systems

Efforts to construct therapeutically useful models of biological systems require large and diverse sets of data on functional connections between their components. Here we show that cellular responses to combinations of chemicals reveal how their biological targets are connected. Simulations of pathways with pairs of inhibitors at varying doses predict distinct response surface shapes that are reproduced in a yeast experiment, with further support from a larger screen using human tumour cells. The response morphology yields detailed connectivity constraints between nearby targets, and synergy profiles across many combinations show relatedness between targets in the whole network. Constraints from chemical combinations complement genetic studies, because they probe different cellular components and can be applied to disease models that are not amenable to mutagenesis. Chemical probes also offer increased flexibility, as they can be continuously dosed, temporally controlled, and readily combined. After extending this initial study to cover a wider range of combination effects and pathway topologies, chemical combinations may be used to refine network models or to identify novel targets. This response surface methodology may even apply to non-biological systems where responses to targeted perturbations can be measured

Early biomarkers and potential mediators of ventilation-induced lung injury in very preterm lambs

BACKGROUND: Bronchopulmonary dysplasia (BPD) is closely associated with ventilator-induced lung injury (VILI) in very preterm infants. The greatest risk of VILI may be in the immediate period after birth, when the lungs are surfactant deficient, still partially filled with liquid and not uniformly aerated. However, there have been very few studies that have examined this immediate post-birth period and identified the initial injury-related pathways that are activated. We aimed to determine if the early response genes; connective tissue growth factor (CTGF), cysteine rich-61 (CYR61) and early growth response 1 (EGR1), were rapidly induced by VILI in preterm lambs and whether ventilation with different tidal volumes caused different inflammatory cytokine and early response gene expression. METHODS: To identify early markers of VILI, preterm lambs (132 d gestational age; GA, term approximately 147 d) were resuscitated with an injurious ventilation strategy (V(T) 20 mL/kg for 15 min) then gently ventilated (5 mL/kg) for 15, 30, 60 or 120 min (n = 4 in each). To determine if early response genes and inflammatory cytokines were differentially regulated by different ventilation strategies, separate groups of preterm lambs (125 d GA; n = 5 in each) were ventilated from birth with a V(T) of 5 (VG5) or 10 mL/kg (VG10) for 135 minutes. Lung gene expression levels were compared to levels prior to ventilation in age-matched control fetuses. RESULTS: CTGF, CYR61 and EGR1 lung mRNA levels were increased approximately 25, 50 and 120-fold respectively (p < 0.05), within 30 minutes of injurious ventilation. VG5 and VG10 caused significant increases in CTGF, CYR61, EGR1, IL1- , IL-6 and IL-8 mRNA levels compared to control levels. CTGF, CYR61, IL-6 and IL-8 expression levels were higher in VG10 than VG5 lambs; although only the IL-6 and CYR61 mRNA levels reached significance. CONCLUSION: CTGF, CYR61 and EGR1 may be novel early markers of lung injury and mechanical ventilation from birth using relatively low tidal volumes may be less injurious than using higher tidal volumes

Farmer-Scientist Knowledge Exchange

The last 25 years has seen a paradigm shift in the understanding of the nature of knowledge and how it is exchanged in the agricultural context. A changing backdrop, with the move towards multi-functional land management, persistent environmental problems and the search for sustainable agricultural approaches, has brought new challenges. At the same time the research agenda on knowledge has changed as an era of positivism, during which science and scientific experts were given unrivalled authority, was challenged by social studies of science that began to question the superiority of scientific knowledge, and value alternative forms of knowledge such as those held by farmers. Theory and practice of knowledge exchange in agriculture has evolved in line with this, shifting from a linear model of knowledge transfer to a perspective that integrates knowledge from multiple actors through facilitation and participation and emphasises learning in a social context