Inflammatory markers and in-hospital mortality in acute ischaemic stroke

BACKGROUND: There is substantial evidence that cerebral ischaemia triggers an inflammatory response. We examined the short-term prognostic value on mortality of C-reactive protein (CRP), interleukin-6 (IL-6) and serum amyloid A (SAA) in patients with ischaemic stroke. METHODS: We recruited 203 consecutive patients, under the age of 66 years (mean age=54.2+/-8.1 years, men=132) who admitted to the Neurology Department with the diagnosis of non-haemorrhagic stroke. Patients in atrial fibrillation or with evidence of inflammatory or malignant disease were excluded. The diagnosis was confirmed with a computed tomography or magnetic resonance imaging of the brain within 24h of admission. CRP, IL-6 and SAA levels were determined within 12h from admission. RESULTS: Fourteen (6.9%) patients died during hospitalization. Serum concentrations of CRP, IL-6 and SAA were significantly higher in patients who died compared with those who survived and were independently associated with early death, after adjusting for various confounding factors. For one unit increase in IL-6, CRP and SAA there was an 18%, 14% and 9% higher risk of dying during hospitalization, respectively. Comparisons of the areas under the ROC curve showed that IL-6 had the best predictive ability. Age-adjusted cut-off point analysis showed that IL-6 levels >13 pg/ml were the optimal point that discriminated those who died from the rest of the patients (sensitivity=85% and specificity=93%). CONCLUSIONS: We demonstrated that in-hospital mortality in ischaemic stroke is associated with an exacerbation of inflammatory response as it is reflected by the higher serum levels of IL-6, CRP and SAA. From the inflammatory markers high IL-6 levels had the strongest independent predictive value for in-hospital mortality.     

Screening of patients after colectomy: virtual colonography

Background Virtual colonography is a powerful new method of imaging the entire colon and is useful to assess polyps and diagnose colon cancer. We evaluated virtual colonography in the postoperative screening of patients who had colon cancer. Methods Fifty-three patients were examined with virtual colonography 12 to 48 months postoperatively. Forty-four patients had received segmental colectomy with restoration of the gastrointestinal tract, and nine patients underwent abdominoperineal resection and permanent colostomy. After proper cleaning of the colon and distention with air, spiral computed tomographic examination of the abdomen with a slice thickness of 5 mm (table speed [TS] 10 mm, reconstruction interval [RI] 2.5 mm) was performed in the supine and prone positions (including intravenous contrast medium infusion). Images were transferred to a separate workstation (Philips Easy Vision) for postprocessing, three-dimensional rendering, and endoluminal viewing. Results Eleven recurrences (16.41%) were identified in 10 patients by virtual colonography, but one recurrence was missed. Conventional colonoscopy was incomplete in six cases, and two patients with colostomy refused colonoscopy. In these eight cases (15%), virtual colonoscopy was completed without problems. A second tumor in one patient who had received abdominoperineal resection was demonstrated by virtual colonography, but conventional colonoscopy failed to demonstrate the lesion. Liver metastases were identified in only one patient. Conclusions Virtual colonography seems to provide a good alternative in the follow-up of patients after colectomy. The technique is effective in the diagnosis of locoregional recurrences and distant metastases and is well accepted by patients, and results are equal to those of the conventional colonoscopy.     

Attributable mortality of Acinetobacter baumannii infections in critically ill patients: a systematic review of matched cohort and case-control studies

Introduction  

There has been a continuing controversy about whether infection with Acinetobacter baumannii increases morbidity and mortality independently of the effect of other confounding factors.     

Activation of membrane androgen receptors potentiates the antiproliferative effects of paclitaxel on human prostate cancer cells

Genomic signaling mechanisms require a relatively long time to get into action and represent the main way through which steroid hormones affect target cells. In addition, steroids may rapidly activate cellular functions by non-genomic signaling mechanisms involving membrane sites. Understanding in depth the molecular mechanisms of the non-genomic action represents an important frontier for developing new and more selective pharmacologic tools for endocrine therapies. In the present study, we report that membrane-impermeable testosterone-bovine serum albumin (BSA) acts synergistically with paclitaxel in modifying actin and tubulin cytoskeleton dynamics in LNCaP (androgen sensitive) and DU-145 (androgen insensitive) human prostate cancer cell lines. In addition, coincubation of either cell line with testosterone-BSA and paclitaxel induced inhibition of cell proliferation and apoptosis. Finally, in vivo experiments in LNCaP and DU-145 tumor xenografts in nude mice showed that both agents decrease tumor mass, whereas testosterone-BSA enhances the effect of paclitaxel. Our findings suggest that chronic activation of membrane androgen receptors in vitro and in vivo facilitates and sustains for a longer time the antitumoral action of cytoskeletal acting agents.     

Magnetic resonance spectroscopic investigation of mitochondrial fuel metabolism and energetics in cultured human fibroblasts: effects of pyruvate dehydrogenase complex deficiency and dichloroacetate

The pyruvate dehydrogenase complex (PDC) is integral to metabolism and energetics. Congenital PDC deficiency leads to lactic acidosis, neurological degeneration and early death. An investigational compound for such defects is dichloroacetate (DCA), which activates the PDC (inhibiting reversible phosphorylation of the E1alpha subunit) and decreases its turnover. Here, primary human fibroblast cultures from five healthy subjects and six patients with mutations in the PDC-E1 component were grown in media+/-DCA, exposed to media containing (13)C-labeled glucose, and studied (as cell extracts) by nuclear magnetic resonance (NMR) spectroscopy. Computer modeling of NMR-derived (13)C-glutamate isotopomeric patterns estimated relative carbon flow through TCA cycle-associated pathways and characterized effects of PDC deficiency on metabolism and energetics. Rates of glucose consumption (GCR) and lactate production (LPR) were measured. With the exception of one patient cell line expressing an unusual splicing mutation, PDC-deficient cells had significantly higher GCR, LPR and label-derived acetyl-CoA, indicative of increased glycolysis vs. controls. In all cells, DCA caused a major shift (40% decrease) from anaplerotic-related pathways (e.g., pyruvate carboxylase) toward flux through PDC. Ignoring the patient with the splicing mutation, DCA decreased average glycolysis (29%) in patient cells, but had no significant effect on control cells, and did not change LPR or the nucleoside triphosphate to diphosphate ratio (NTP/NDP) in either cell type. Maintenance of NTP despite reduced glycolysis indicates that DCA improves metabolic efficiency by increasing glucose oxidation. This study demonstrates that NMR spectroscopy provides insight into biochemical consequences of PDC deficiency and the mechanism of putative therapeutic agents.     

The gamma subunit of the eighth complement component (C8) in rainbow trout

Of the 35 proteins, enzymes, receptors and regulatory components of the complement system, C8gamma is unique in that it is the only lipocalin. C8gamma is a subunit of the C8 molecule, which is one of the five components (C5b, C6, C7, C8 and C9) that interact as a consequence of complement activation to form the membrane attack complex. Until now, C8gamma has been characterized only in mammalian species. In order to elucidate the phylogeny of this molecule, we have cloned the C8gamma subunit in rainbow trout (Oncorhynchus mykiss), a teleost fish representing a critical point in the evolutionary divergence of the complement system. The deduced amino acid sequence of trout C8gamma shows significant identity (37%) to the human C8gamma homolog and much lower to the other known lipocalins. The lipocalin domain is present and all the cysteine residues are conserved. The trout C8gamma gene is probably present as a single copy in the trout genome showing a differential expression pattern among tissues investigated.     

RNAi suppression of recognition protein mediated immune responses in the tobacco hornworm Manduca sexta causes increased susceptibility to the insect pathogen Photorhabdus

Bacterial pathogens either hide from or overcome the immune response of their hosts. Here we show that two different species of insect pathogenic bacteria, Photorhabdus luminescens TT01 and Photorhabdus asymbiotica ATCC43949, were both recognized by the immune system of their host Manduca sexta, as indicated by a rapid increase in the levels of mRNAs encoding three different inducible microbial recognition proteins, Hemolin, Immulectin-2 and peptidoglycan recognition protein. RNA interference (RNAi)-mediated inhibition of expression (“knock-down”) of each of these genes at the level of both mRNA and protein was achieved through injection of double-stranded RNA (dsRNA). Knock-down of any one of these genes markedly decreased the ability of the insects to withstand infection when exposed to either species of Photorhabdus, as measured by the rate at which infected insects died. RNAi against Immulectin-2 caused the greatest reduction in host resistance to infection. The decreased resistance to infection was associated with reduced hemolymph phenoloxidase activity. These results show not only that Photorhabdus is recognized by the Manduca sexta immune system but also that the insect's immune system plays an active, but ultimately ineffective, role in countering infection.     

Prospective study of the value of quantitative culture of organisms from blood collected through central venous catheters in differentiating between contamination and bloodstream infection

Collection of blood through a central venous catheter for the diagnosis of bacteremia is a debated topic. Quantitative cultures of organisms from blood collected through central venous catheters were found to be highly sensitive, specific, and predictive of bacteremia, especially when a cutoff point of 15 colonies of skin organisms was used.