Relationship between outcome and baseline blood pressure and other haemodynamic measures in acute ischaemic stroke: data from the TAIST trial

BACKGROUND: A poor outcome after stroke is associated independently with high blood pressure during the acute phase; however, relationships with other haemodynamic measures [heart rate (HR), pulse pressure (PP), rate-pressure product (RPP)] remain less clear. METHODS: The Tinzaparin in Acute Ischaemic Stroke Trial is a randomised, controlled trial assessing the safety and efficacy of tinzaparin versus aspirin in 1484 patients with acute ischaemic stroke. Systolic blood pressure (SBP), diastolic blood pressure (DBP) and HR measurements taken immediately prior to randomization were averaged, and the mid-blood pressure (MBP), PP, mean arterial pressure (MAP), pulse pressure index, and RPP were calculated. The relationship between these haemodynamic measures and functional outcome (death or dependency, modified Rankin Scale > 2) and early recurrent stroke, were studied with adjustment for baseline prognostic factors and treatment group. Odds ratios (OR) and 95% confidence intervals (CI) refer to a change in haemodynamic measure by 10 points. RESULTS: A poor functional outcome was associated with SBP (adjusted OR; 1.11; 95% CI, 1.03-1.21), HR (adjusted OR; 1.15; 95% CI, 1.00-1.31), MBP (adjusted OR; 1.15, 95% CI, 1.03-1.29), PP (adjusted OR; 1.14; 95% CI, 1.02-1.26), MAP (adjusted OR; 1.15; 95% CI, 1.02-1.31) and RPP (adjusted OR; 1.01; 95% CI, 1.00-1.02). Early recurrent stroke was associated with SBP, DBP, MBP and MAP. CONCLUSIONS: A poor outcome is independently associated with elevations in blood pressure, HR and their derived haemodynamic variables, including PP and the RPP. Agents that modify these measures may improve functional outcome after stroke.     

Longitudinal Analysis of Gene Expression in Porcine Skeletal Muscle After Post-Injection Local Injury

Purpose The purpose of this study is to describe the time course of gene expression in a skeletal muscle local injury induced by an intramuscular (IM) injection, and to compare the dynamics of gene expression with pathological events. Materials and Methods Ten piglets received 4 IM injections of propylene glycol in the longissimus dorsi muscles 6 h, 2, 7, and 21 days before euthanasia, where control and injected muscle sites were sampled for RNA isolation and microscopic examination. The hybridization of nylon cDNA microarrays was carried out with radioactive probes obtained from the muscle RNA. Results 153 genes were found under- or over-expressed at least once among the investigated time-conditions. The eight most discriminant genes were also identified: Two genes (GTP-binding protein RAD and Ankyrin repeat domain protein) were over-expressed at 6 h and six genes between 2 and 21 days (Osteonectin, Fibronectin, Matrix metalloproteinase-2, Collagen alpha 1(I) chain, Collagen alpha 2(I) chain, and Thymosin beta-4). Necrosis, inflammation and regeneration were observed through both the dynamics of gene expression profiles and through the microscopic examinations. Conclusion Our data demonstrate that several pathways are involved in post-injection muscle injury, and that necrosis, inflammation and regeneration are not sequential but occur in parallel. PJF and LL contributed equally to this work and both should be considered as first authors.     

Molecular diagnosis of bloodstream infections caused by non-cultivable bacteria

Bloodstream infections are an important cause of morbidity and mortality in patients. Blood culture is clearly the most important diagnostic procedure for identifying micro-organisms involved in bloodstream infections except when the patient has previously received antibiotics or in the presence of slow-growing or intracellular micro-organisms. Detection of micro-organisms, mainly in blood, using pathogen-specific or broad-range PCR assays is promising. However, it is very important to emphasise that the interpretation of this molecular tool is critical because of the risk of interfering contamination, underlining the necessity to interpret the results obtained with caution. Presently, due to more widely available data and to rapid advances in biotechnology, two significant improvements allow new perspectives for molecular diagnosis. Indeed, the complete sequences of genomes have provided an important source of gene sequences for PCR-based assays. In addition, the development of real-time PCR offers several advantages in comparison to conventional PCR, including speed, simplicity, quantitative capability and low risk of contamination. Herein, we review the usefulness of molecular diagnosis of highly fastidious micro-organisms in the context of three different bloodstream infections: systemic diseases (rickettsiosis, Q fever, bartonellosis, Whipple's disease), blood-culture-negative endocarditis and bioterrorism attack.     

Stromal growth and epithelial cell proliferation in ventral prostates of liver X receptor knockout mice

With specific liver X receptor α and β (LXRα and LXRβ) antibodies, we found that LXRα is strongly expressed in the luminal and basal cells of prostatic epithelium. The ventral prostates (VP) of LXRα^−/− mice are characterized by the presence of smooth-muscle actin-positive stromal overgrowth around the prostatic ducts and by numerous fibrous nodules pushing into the ducts and causing obstruction, so that most of the ducts were extremely dilated. BrdU labeling and Ki67 staining revealed epithelial and stromal proliferation in the fibrous nodules. However, the dense stroma surrounding the ducts was not positive for proliferation markers. There was no detectable difference between WT and LXRα^−/− mice VP in the expression of the androgen receptor, but there was an increase in nuclear expression of Snail and Smad 2/3, indicating enhanced TGF-β signaling. Upon treatment of WT mice for 3 months with the LXR agonist T2320 or for 3 weeks with β-sitosterol, LXRα was downregulated, and a VP phenotype similar to that of LXRα^−/− mice resulted. We conclude that in rodents, LXRα seems to control VP stromal growth and that LXRα^−/− mice may be a useful model to study prostatic stromal hyperplasia. Because LXRα is expressed in the epithelium, the excessive stromal growth in LXRα^−/− mice indicates that LXRα is essential for epithelial stromal communication.     

Peripatetic health-care workers as potential superspreaders

Many nosocomial outbreaks exhibit “superspreading events” in which cross-transmission occurs via a single individual to a large number of patients. We investigated how heterogeneity in Health-Care Worker (HCW) behaviors, especially compliance to hand hygiene, may cause superspreading events. In particular, we compared the superspreading potential of peripatetic (noncohorted) HCWs with that of other HCWs. We developed an agent-based model for hand transmission of a pathogen in a hospital ward. Three HCW profiles were allowed: 2 assigned profiles, one with frequent contacts with a limited number of patients, another with fewer contacts but with more patients; and one peripatetic profile, with a single daily contact with all patients. We used data from the literature on common nosocomial pathogens (Staphylococcus aureus, Enterococci). The average number of patients colonized over 1 month increases with noncompliance to hand hygiene. Importantly, we show that this increase depends on the profile of noncompliant HCWs; for instance, it remains low for a single noncompliant assigned HCW but can be quite large for a single noncompliant peripatetic HCW. Outbreaks with this single fully noncompliant peripatetic HCW (representing only 4.5% of the staff) are similar to those predicted when all HCWs are noncompliant following 23% of patient contacts. Noncompliant peripatetic HCWs may play a disproportionate role in disseminating pathogens in a hospital ward. Their unique profile makes them potential superspreaders. This suggests that average compliance to hygiene may not be a good indicator of nosocomial risk in real life health care settings with several HCW profiles.     

Protein array technology to investigate cytokine production by monocytes from patients with advanced alcoholic cirrhosis: An ex vivo pilot study

Aim:  In patients with advanced cirrhosis, little is known about the ability of peripheral blood monocytes to spontaneously produce signaling proteins such as cytokines. The aim of this ex vivo study was to evaluate cytokine production under baseline conditions and after stimulation by lipopolysaccharide (LPS), a toll-like receptor (TLR) agonist.
Methods:  Peripheral blood monocytes were isolated from patients with advanced alcoholic cirrhosis (without ongoing bacterial infections) and normal subjects. Cells were left unstimulated or were stimulated with LPS. The abundance of 24 cytokines was measured using a filter-based, arrayed sandwich enzyme-linked immunosorbent assay (ELISA) in the supernatant of cultured monocytes.
Results:  Cirrhotic monocytes spontaneously produced six proteins (TNF-α, IL-6, IL-8, MCP-1, RANTES and Gro), whereas normal monocytes produced only small amounts of IL-8 and RANTES. Analyses with the online gene set analysis toolkit WebGestalt ( http://bioinfo.vanderbilt.edu/webgestalt ) found enrichment for the six proteins in the human gene ontology subcategory ( http://www.geneontology.org ), Kyoto Encyclopedia of Genes and Genome pathways ( http://www.genome.ad.jp/kegg/ ) and BioCarta pathways ( http://www.biocarta.com/genes/index.asp ) consistent with a proinflammatory phenotype of cirrhotic monocytes resulting from activated TLR signaling. Interestingly, LPS-elicited TLR engagement further increased the production of the six proteins and did not induce the secretion of any others, in particular the anti-inflammatory cytokine IL-10. LPS-stimulated normal monocytes produced TNF-α, IL-6, IL-8, MCP-1, RANTES, Gro and IL-10.
Conclusion:  In patients with advanced cirrhosis, peripheral blood monocytes spontaneously produce proinflammatory cytokines, presumably in response to unrestricted TLR signaling.