Erector spinae plane block did not improve postoperative pain-related outcomes and recovery after video-assisted thoracoscopic surgery : a randomised controlled double-blinded multi-center trial.

INTRODUCTION: There is a sizable niche for a minimally invasive analgesic technique that could facilitate ambulatory video-assisted thoracoscopic surgery (VATS). Our study aimed to determine the analgesic potential of a single-shot erector spinae plane (ESP) block for VATS. The primary objective was the total hydromorphone consumption with patient-controlled analgesia (PCA) 24 h after surgery. METHODS: We conducted a randomized, controlled, double-blind study with patients scheduled for VATS in two major university-affiliated hospital centres. We randomized 52 patients into two groups: a single-shot ESP block using bupivacaine or an ESP block with normal saline (control). We administered a preoperative and postoperative (24 h) quality of recovery (QoR-15) questionnaire and assessed postoperative pain using a verbal numerical rating scale (VNRS) score. We evaluated the total standardized intraoperative fentanyl administration, total postoperative hydromorphone consumption (PCA; primary endpoint), and the incidence of adverse effects. RESULTS: There was no difference in the primary objective, hydromorphone consumption at 24 h (7.6 (4.4) mg for the Bupivacaine group versus 8.1 (4.2) mg for the Control group). Secondary objectives and incidence of adverse events were not different between the two groups at any time during the first 24 h following surgery. CONCLUSION: Our multi-centre randomized, controlled, double-blinded study found no advantage of an ESP block over placebo for VATS for opioid consumption, pain, or QoR-15 scores. Further studies are ongoing to establish the benefits of using a denser block (single-shot paravertebral with a continuous ESP block), which may provide a better quality of analgesia.

Flaw strength distributions and statistical parameters for ceramic fibers: the normal distribution.

The present paper investigates large sets of ceramic fibre failure strengths (500 to 1000 data) produced using tensile tests on tows that contained either 500 or 1000 filaments. The probability density function was determined through acoustic emission monitoring which allowed detection and counting of filament fractures. The statistical distribution of filament strengths was described using the normal distribution. The Weibull equation was then fitted to this normal distribution for estimation of statistical parameters. A perfect agreement between both distributions was obtained, and a quite negligible scatter in statistical parameters was observed, as opposed to the wide variability that is reported in the literature. Thus it was concluded that flaw strengths are distributed normally and that the statistical parameters that were derived are the true ones. In a second step, the conventional method of estimation of Weibull parameters was applied to these sets of data and, then, to subsets selected randomly. The influence of other factors involved in the conventional method of determination of statistical parameters is discussed. It is demonstrated that selection of specimens, sample size, and method of construction of so-called Weibull plots are responsible for statistical parameters variability.

Murine candidate bleomycin induced pulmonary fibrosis susceptibility genes identified by gene expression and sequence analysis of linkage regions.

BACKGROUND: Pulmonary fibrosis is a complex disease for which the predisposing genetic variants remain unknown. In a prior study, susceptibility to bleomycin induced pulmonary fibrosis was mapped to loci Blmpf1 and Blmpf2 on chromosomes 17 and 11, respectively, in a C57BL/6J (B6, susceptible) and C3Hf/KAM (C3H, resistant) mouse cross. METHODS: Herein, the genetic basis of bleomycin induced pulmonary fibrosis was investigated in an approach combining gene expression and sequencing data with previously mapped linkage intervals. RESULTS: In this study, gene expression analysis with microarrays revealed 1892 genes or ESTs (expressed sequence tags) to be differentially expressed between bleomycin treated B6 and C3H mice and 67 of these genetic elements map to Blmpf1 or Blmpf2. This group included genes involved in an oxidative stress response, in apoptosis, and in immune regulation. A comparison of the B6 and C3H sequence, for Blmpf1 and Blmpf2, made using the NCBI database and available C3H sequence, revealed approximately 35% of the genes in these regions contain non-synonymous coding sequence changes. An assessment of genotype/phenotype correlation among other inbred strains revealed 36% of these B6/C3H sequence variations predict for the known bleomycin induced fibrosis susceptibility of the DBA (susceptible) and A/J (resistant) mouse strains. CONCLUSIONS: Combining genomics approaches of differential gene expression and sequence variation potentially identifies approximately 5% the linked genes as fibrosis susceptibility candidate genes in this mouse cross.

BIAS: Bioinformatics Integrated Application Software.

MOTIVATION: We introduce a development platform especially tailored to Bioinformatics research and software development. BIAS (Bioinformatics Integrated Application Software) provides the tools necessary for carrying out integrative Bioinformatics research requiring multiple datasets and analysis tools. It follows an object-relational strategy for providing persistent objects, allows third-party tools to be easily incorporated within the system and supports standards and data-exchange protocols common to Bioinformatics. AVAILABILITY: BIAS is an OpenSource project and is freely available to all interested users at http://www.mcb.mcgill.ca/~bias/. This website also contains a paper containing a more detailed description of BIAS and a sample implementation of a Bayesian network approach for the simultaneous prediction of gene regulation events and of mRNA expression from combinations of gene regulation events. CONTACT: hallett@mcb.mcgill.ca.

Dnmt3a binds deacetylases and is recruited by a sequence-specific repressor to silence transcription.

The Dnmt3a DNA methyltransferase is essential for mammalian development and is responsible for the generation of genomic methylation patterns, which lead to transcriptional silencing. Here, we show that Dnmt3a associates with RP58, a DNA-binding transcriptional repressor protein found at transcriptionally silent heterochromatin. Dnmt3a acts as a co-repressor for RP58 in a manner that does not require its de novo methyltransferase activity. Like other characterized co-repressors, Dnmt3a associates with the histone deacetylase HDAC1 using its ATRX-homology domain. This domain of Dnmt3a represents an independent transcriptional repressor domain whose silencing functions require HDAC activity. These results identify Dnmt3a as a co-repressor protein carrying deacetylase activity and show that Dnmt3a can be targeted to specific regulatory foci via its association with DNA-binding transcription factors.

A novel N-acyl phosphatidylethanolamine-containing delivery vehicle for spermine-condensed plasmid DNA.

A unique method for formulation of plasmid DNA with phospholipids has been devised for the purpose of producing vehicles that can mediate gene delivery and transfection of living cells. The polycation, spermine, was used to condense plasmid DNA within a water-in-chloroform emulsion stabilized by phospholipids. After organic solvent removal, the particles formed could be extruded to a number average size of about 200 nm and retained DNA that was protected from nuclease digestion. This resulted in a relatively high protected DNA-to-lipid ratio of approximately 1 microg DNA/micromol lipid. The size distribution of the preparation was relatively homogeneous as judged by light microscopy and quasi-elastic light scattering. Electron microscopic studies showed structural heterogeneity, but suggested that at least some of the plasmid DNA in this preparation was in the form of the previously observed spermine-condensed bent rods and toroids and was encapsulated within liposomal membranes. Preparations with the fusogenic phospholipid composition, 1, 2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-dodecanoyl/ 1, 2-dioleoyl-sn-glycero-3-phosphocholine, showed transfection activity for several cells lines, particularly OVCAR-3 cells. The transfection activity sedimented with the lipid during centrifugation, confirming the association of active plasmid DNA with phospholipids. Transfection efficiency in culture was found to be of the same order of magnitude as cationic lipoplexes but much less toxic to the cells. Significant transfection of OVCAR-3 cells in tissue culture could also be observed, even in the presence of the intraperitoneal fluid from a mouse with an OVCAR-3 ascites tumor. These data indicate a new type of liposomal gene delivery system devoid of cationic lipids, phosphatidylethanolamine, cationic polymers and viral components.

AIDS: is a safe vaccine readily available?

Intense efforts are presently being made world-wide to produce an efficient AIDS vaccine. Based on a review of current medical research and scientific papers, a strategy to obtain quickly an effective, safe and marketable AIDS Vaccine with available monoclonal antibodies is described.

[The role of ultrasonography in the diagnosis of diffuse liver disease]. / L'apport de l'ultrasonographie dans le diagnostic des hépatopathies diffuses.

131 patients thought to have diffuse liver disease underwent ultrasonography and percutaneous liver biopsy. The ultrasonographic criteria examined were hepatic echogenicity compared to that of the renal cortex, homogeneity of hepatic parenchyma, and regularity of hepatic outline. On the basis of histologic examination of liver biopsies, several groups of pathologic lesions (not diagnostic entities) were established. Evaluation of ultrasound and histology was double blind. When the lobular architecture of the liver was respected histologically (normal liver, granulomatosis, siderosis, hepatitis), the ultrasound was normal in 86% of cases. The sensitivity of ultrasound was 0.9 for detection of fatty liver and 0.6 for cirrhosis. An abnormal ultrasound predicted structural modifications or a fatty liver in 93% of cases. Ultrasound proved incapable of differentiating between fatty liver and cirrhosis.

Loss of suppressor T-cells in active inflammatory bowel disease.

The proportions and absolute numbers of helper and suppressor T-cells in 40 patients with inflammatory bowel disease and 22 control subjects were determined, using the monoclonal antibodies OKT 4 and OKT 8. There were no significant differences in helper or suppressor cell proportions among 15 steroid treated patients with active inflammatory bowel disease, 10 patients with inactive inflammatory bowel disease, 10 patients with other gastrointestinal diseases, or 12 normal control subjects. In contrast, 15 patients with active inflammatory bowel disease not treated with corticosteroids manifested increased proportions of helper cells and decreased proportions of suppressor cells (p less than 0.001), compared with all other patient groups and to normal controls. When absolute numbers of helper and suppressor subsets were measured, these alterations in proportions of helper and suppressor cells were primarily attributable to decreased counts of suppressor T-cells both in patients with active Crohn's disease and in those with ulcerative colitis (p less than 0.01). In four patients undergoing serial study, the helper/suppressor ratios appeared to rise and fall respectively with clinical exacerbations and remissions of disease. These data provide additional evidence for the involvement of cellular immune systems in these disease processes.

[Mycotic aneurysms of the intrapulmonary arteries: unusual manifestation of right-sided endocarditis]. / Anévrysmes mycotiques des artères intrapulmonaires: une manifestation exceptionnelle de l'endocardite droite.

We report the case of a 27 year old man admitted to hospital for investigation of radiological opacities of recent origin. A diagnosis of mycotic aneurysms was made on a surgical biopsy. Although a right sided endocarditis could not be detected clinically, a trial of antibiotic therapy was instituted. However, no improvement occurred. The patient died, following a massive pulmonary haemorrhage. The necropsy revealed an active right sided endocarditis with multiple aneurysms of the intra-pulmonary arteries.