Worsening of cerebral hyperemia by the administration of terlipressin in acute liver failure with severe hepatic encephalopathy

There is increasing evidence that terlipressin is useful in patients with cirrhosis and hepatorenal syndrome, but there are no data of its use in patients with acute liver failure (ALF) in whom hepatorenal syndrome is common. Although terlipressin produces systemic vasoconstriction, it produces cerebral vasodilatation and may increase cerebral blood flow (CBF). Increased CBF contributes to intracranial hypertension in patients with ALF. The aim of this study was to evaluate the safety of terlipressin in patients with ALF with respect to cerebral haemodynamics. Six successive patients with ALF were electively ventilated for grade IV hepatic encephalopathy. Patients were monitored invasively and CBF was measured (Kety- Schmidt technique). Measurements were made before, at 1, 3 hour and 5 hours after intravenous (single bolus) administration of terlipressin (0.005 mg/kg) )intravenously (single bolus), median 0.25mg (range 0.2-0.3). There was no significant change in heart rate, mean arterial pressure or cardiac output. CBF and jugular venous oxygen saturation both increased significantly at 1 hour (p<0.0=0.016) respectively. Intracranial pressure increased significantly at 21 hours (p<0=.0.031), returning back to baseline values at 42 hours. This study shows that administration of terlipressin, at a dose that did not alter systemic haemodynamicshemodynamics, resulted in worsening of cerebral hyperemia and intracranial hypertension in patients with ALF and severe hepatic encephalopathy. These data suggest the need to exercise extreme caution in the use of terlipressin in these patients in view of its potentially deleterious consequences on cerebral haemodynamics

The reaction of ovine neutrophils to Histophilus ovis in relation to genital infection of rams

Histophilus ovis was shown to be phagocytized by neutrophils when the organisms enter the lumen of the reproductive tract of the ram. The phagocytosis and destruction of H. ovis by neutrophils was demonstrated in vitro by the viable count method and by electron microscopy. It was shown that immunoglobulins and complement had no influence on the phagocytosis and destruction of H. ovis. Phagocytosis and killing of H. ovis was accomplished equally well by neutrophils from immunized and non-immunized rams. Immunized rams showed a massive infiltration of neutrophils into the walls, epithelium and lumen of their ampullae when dead H. ovis were introduced into their lumen.The articles have been scanned in colour with a HP Scanjet 5590; 600dpi. Adobe Acrobat XI Pro was used to OCR the text and also for the merging and conversion to the final presentation PDF-format

SMOG 2: A versatile software package for generating structure-based models

Molecular dynamics simulations with coarse-grained or simplified Hamiltonians have proven to be an effective means of capturing the functionally important long-time and large-length scale motions of proteins and RNAs. Originally developed in the context of protein folding, structure-based models (SBMs) have since been extended to probe a diverse range of biomolecular processes, spanning from protein and RNA folding to functional transitions in molecular machines. The hallmark feature of a structure-based model is that part, or all, of the potential energy function is defined by a known structure. Within this general class of models, there exist many possible variations in resolution and energetic composition. SMOG 2 is a downloadable software package that reads user-designated structural information and user-defined energy definitions, in order to produce the files necessary to use SBMs with high performance molecular dynamics packages: GROMACS and NAMD. SMOG 2 is bundled with XML-formatted template files that define commonly used SBMs, and it can process template files that are altered according to the needs of each user. This computational infrastructure also allows for experimental or bioinformatics-derived restraints or novel structural features to be included, e.g. novel ligands, prosthetic groups and post-translational/transcriptional modifications. The code and user guide can be downloaded at http://smog-server.org/smog2

Meta-analysis of type 2 Diabetes in African Americans Consortium

Type 2 diabetes (T2D) is more prevalent in African Americans than in Europeans. However, little is known about the genetic risk in African Americans despite the recent identification of more than 70 T2D loci primarily by genome-wide association studies (GWAS) in individuals of European ancestry. In order to investigate the genetic architecture of T2D in African Americans, the MEta-analysis of type 2 DIabetes in African Americans (MEDIA) Consortium examined 17 GWAS on T2D comprising 8,284 cases and 15,543 controls in African Americans in stage 1 analysis. Single nucleotide polymorphisms (SNPs) association analysis was conducted in each study under the additive model after adjustment for age, sex, study site, and principal components. Meta-analysis of approximately 2.6 million genotyped and imputed SNPs in all studies was conducted using an inverse variance-weighted fixed effect model. Replications were performed to follow up 21 loci in up to 6,061 cases and 5,483 controls in African Americans, and 8,130 cases and 38,987 controls of European ancestry. We identified three known loci (TCF7L2, HMGA2 and KCNQ1) and two novel loci (HLA-B and INS-IGF2) at genome-wide significance (4.15 × 10(-94)<P<5 × 10(-8), odds ratio (OR)  = 1.09 to 1.36). Fine-mapping revealed that 88 of 158 previously identified T2D or glucose homeostasis loci demonstrated nominal to highly significant association (2.2 × 10(-23) < locus-wide P<0.05). These novel and previously identified loci yielded a sibling relative risk of 1.19, explaining 17.5% of the phenotypic variance of T2D on the liability scale in African Americans. Overall, this study identified two novel susceptibility loci for T2D in African Americans. A substantial number of previously reported loci are transferable to African Americans after accounting for linkage disequilibrium, enabling fine mapping of causal variants in trans-ethnic meta-analysis studies.Peer reviewe

Age-related differences of oncological outcomes in primary extremity soft tissue sarcoma: a multistate model including 6260 patients

Abstract Purpose: No studies extensively compared the young adults (YA, 18e39 years), middle-aged (40e69 year