Characteristics of bloodstream infections in burn patients: An 11-year retrospective study.

AIMS: The principal aim of this study was to describe infection related characteristics of blood stream infections (BSI) in patients with burns. We sought to determine the organisms that caused BSI and factors that could predict the outcome of BSI. METHODS: Data was collected on admitted patients with burns from January 1998 to December 2008. Selected information from databases was analysed using SPSS version 17 (SPSS Inc., Chicago). Descriptive, univariate and multivariate analysis was undertaken to determine factors predictive of clinical outcome. The factors analysed by univariate analysis were selected on clinical plausibility. Multivariate analysis used a crosstabs procedure initially to estimate maximum likelihood. Factors that were associated with a p value <0.15 were entered into a binary logistic regression to detect which factors were independent predictors of mortality in BSI and outcome according to specific organisms. RESULTS: Ninety-nine out of 2364 (4%) patients developed 212-documented BSI. The median time from burn to BSI was 7 (interquartile range 3-16) days. Gram-positive organisms, in particular Methicillin resistant Staphylococcus aureus and Coagulase negative Staphylococci, were the most common bacteria associated with BSI in the first week of hospital admission. The mortality rate for all admissions over the data collection period was 3%. Of the 99 patients with BSI, 13 died giving a mortality rate, in the presence of BSI, of 13%. Univariate analysis found that the factors predictive of P. aeruginosa mortality were inhalational injury, higher total body surface area burns, total days of antibiotic treatment and elevated Acute Physiological and Chronic Health Evaluation (APACHE) II scores. Multivariate analysis identified inhalational injury to be the only factor associated with BSI-related mortality. CONCLUSION: Whilst the overall mortality in our cohort was low, the presence of BSI increased this four-fold. Whilst infections caused by Gram-positive pathogens occurred earlier in the patient stay than Gram-negative organisms, the highest mortality was associated with P. aeruginosa infections. This study highlights the negative effects of BSI on clinical outcomes in burn patients.

Identification of sakurasosaponin as a cytotoxic principle from Jacquinia flammea.

The crude ethanolic extract of leaves, stem-bark and roots of J. flammea were tested for their cytotoxic effect against two mammalian cell lines (HeLa and RAW 264.7) and four bacterial species (Staphylococcus aureus, Bacillus subtilis, Escherichia coli and Pseudomonas aeruginosa). When tested at the concentration of 100 microg/mL, the root extract showed the highest cytotoxic activity against mammalian cells followed by the stem-bark extract while the leaves extract did not show significant activity. No antibacterial activity was detected for all extracts when tested up to 500 microg/disc in the disc diffusion assay. The cytotoxic root extract was subjected to fractionation using solvents of ascending polarity: petroleum ether, chloroform, ethylacetate, butanol and water. The water fraction which showed cytotoxic activity was further subjected to routine bioassay-guided fraction to lead to the isolation of sakurasosaponin as the active principle. The recorded IC50 value for sakurasosaponin was 11.3 +/- 1.52 and 3.8 +/- 0.25 microM (n=3) against HeLa and RAW 264.7 respectively. The identification of sakurasosaponin was based on analysis of spectroscopic data.

Longitudinal profiles of 15 serum bile acids in patients with intrahepatic cholestasis of pregnancy.

OBJECTIVES: Increased maternal serum bile acids are implicated in intrahepatic cholestasis of pregnancy. Individual bile acid profiles and their relationship with disease progression, however, remain unknown. The purpose of this prospective study was to determine the temporal changes in bile acids in normal pregnancy and in pregnancies complicated with intrahepatic cholestasis of pregnancy and pruritus gravidarum. METHODS: A validated method for the evaluation of 15 bile acids (conjugated and unconjugated) in a single serum sample was developed using high-performance liquid chromatography/mass spectrometry (HPLC-MS) with an electrospray interface. Bile acid concentrations were assessed in samples (16 weeks of gestation to 4 weeks postpartum) from women with, or who later developed, intrahepatic cholestasis of pregnancy (n=63) and were compared with those from normal pregnant women (n=26) and from women with pruritus gravidarum (n=43). RESULTS: Intrahepatic cholestasis of pregnancy was associated with a predominant increase in cholic acid conjugated with taurine and glycine, from 24 weeks of pregnancy. Ursodeoxycholic acid (UDCA) treatment (> or =21 days, n=15) significantly reduced serum taurocholic and taurodeoxycholic acid concentrations (P<0.01). Bile acid profiles were similar in normal pregnancy and pregnancy associated with pruritus gravidarum. CONCLUSIONS: The bile acid profiles and effects of treatment by UDCA implicate a role for taurine-conjugated bile acids in the syndrome of intrahepatic cholestasis of pregnancy. [corrected] With regard to individual bile acid profiles, pruritus gravidarum is a disorder quite distinct from intrahepatic cholestasis of pregnancy.

Mycocerosic acid biomarkers for the diagnosis of tuberculosis in the Coimbra Skeletal Collection.

Tuberculosis has been a scourge of humans over many millennia, but questions remain regarding its evolution and epidemiology. Fossil biomarkers, such as DNA and long-chain mycolic acids, can be detected in ancient skeletal and other materials. The phthiocerol dimycocerosate waxes are also robust biomarkers for tuberculosis and sensitive methods are available for the detection of their mycocerosic acid components. The presence of mycocerosic acids was investigated in 49 individuals from the 1837-1936 Coimbra Identified Skeletal Collection (Portugal), half with documentary data indicating tuberculosis as a cause of death. Samples were hydrolysed, acidic components converted to pentafluorobenzyl esters, the non-hydroxylated long-chain esters isolated, and this fraction separated into multimethyl-branched and other esters by normal phase high performance liquid chromatography. Negative ion chemical ionisation gas chromatography mass spectrometry was used to detect diagnostic C29, C30 and C32 mycocerosic acids. Mycocerosic acids were detected in archaeological material for the first time, illustrating that they are valuable biomarkers for the diagnosis of ancient tuberculosis. A 72% correlation with the Coimbra burial record supported TB as the major cause of death. In addition, 30% of the skeletons, positive for mycocerosates, showed the presence of related long-chain mycolipenic acids.

Triterpenoid saponins from a cytotoxic root extract of Sideroxylon foetidissimum subsp. gaumeri.

Evaluation of the cytotoxicity of an ethanolic root extract of Sideroxylonfoetidissimum subsp. gaumeri (Sapotaceae) revealed activity against the murine macrophage-like cell line RAW 264.7. Systematic bioassay-guided fractionation of this extract gave an active saponin-containing fraction from which four saponins were isolated. Use of 1D ((1)H, (13)C, DEPT135) and 2D (COSY, TOCSY, HSQC, and HMBC) NMR, mass spectrometry and sugar analysis gave their structures as 3-O-(beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranosyl)-28-O-(alpha-L-rhamnopyranosyl-(1-->3)[beta-D-xylopyranosyl-(1-->4)]-beta-D-xylopyranosyl-(1-->4)-alpha-L-rhamnopyranosyl-(1-->2)-alpha-L-arabinopyranosyl)-16alpha-hydroxyprotobassic acid, 3-O-beta-D-glucopyranosyl-28-O-(alpha-L-rhamnopyranosyl-(1-->3)[beta-D-xylopyranosyl-(1-->4)]-beta-D-xylopyranosyl-(1-->4)-alpha-L-rhamnopyranosyl-(1-->2)-alpha-L-arabinopyranosyl)-16alpha-hydroxyprotobassic acid, 3-O-(beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranosyl)-28-O-(alpha-L-rhamnopyranosyl-(1-->3)-beta-D-xylopyranosyl-(1-->4)[beta-D-apiofuranosyl-(1-->3)]-alpha-L-rhamnopyranosyl-(1-->2)-alpha-L-arabinopyranosyl)-16alpha-hydroxyprotobassic acid, and the known compound, 3-O-beta-D-glucopyranosyl-28-O-(alpha-L-rhamnopyranosyl-(1-->3)[beta-D-xylopyranosyl-(1-->4)]-beta-D-xylopyranosyl-(1-->4)-alpha-L-rhamnopyranosyl-(1-->2)-alpha-L-arabinopyranosyl)-protobassic acid. Two further saponins were obtained from the same fraction, but as a 5:4 mixture comprising 3-O-(beta-D-glucopyranosyl)-28-O-(alpha-L-rhamnopyranosyl-(1-->3)-beta-D-xylopyranosyl-(1-->4)[beta-D-apiofuranosyl-(1-->3)]-alpha-L-rhamnopyranosyl-(1-->2)-alpha-L-arabinopyranosyl)-16alpha-hydroxyprotobassic acid and 3-O-(beta-D-apiofuranosyl-(1-->3)-beta-D-glucopyranosyl)-28-O-(alpha-L-rhamnopyranosyl-(1-->3)[beta-D-xylopyranosyl-(1-->4)]-beta-D-xylopyranosyl-(1-->4)-alpha-L-rhamnopyranosyl-(1-->2)-alpha-L-arabinopyranosyl)-16alpha-hydroxyprotobassic acid, respectively. This showed greater cytotoxicity (IC(50)=11.9+/-1.5 microg/ml) towards RAW 264.7 cells than the original extract (IC(50)=39.5+/-4.1 microg/ml), and the saponin-containing fraction derived from it (IC(50)=33.7+/-6.2 microg/ml).

Influence of isoprostane F2alpha-III on reflow after myocardial infarction.

AIMS: To investigate whether the vasoconstrictor isoprostane F2alpha-III (iPF2alpha-III), released during myocardial reperfusion, contributes to the low/no reflow phenomenon observed following acute myocardial infarction (AMI). METHODS AND RESULTS: Thirteen patients undergoing primary percutaneous coronary intervention (PCI) for AMI had iPF2alpha-III measured by high-performance liquid and gas chromatography-mass spectrometry. Isoprostane F2alpha-III concentrations were significantly higher following PCI than in controls (1.5+/-1.3 vs.16+/-0.06 nM, p < 0.001). Mean iPF2alpha-III concentration correlated positively with ST-segment resolution at 90 min (R = 0.62, p < 0.05). In the isolated murine heart: (a) coronary vasoconstriction occurred at, or above, iPF2alpha-III concentrations of 1 microM. From 1 to 10 microM, iPF2alpha-III induced dose-dependent vasoconstriction (p = 0.005) with reduction in coronary flows (f) of 57+/-5% and 31+/-4% (percentage baseline), respectively; (b) SQ29548 1 microM completely reversed the vasoconstrictive effects of iPF2alpha-III 10 microM; (c) SQ29548 1 microM infused during reperfusion following 30 min ischaemia had no effect on CF or infarct volume. CONCLUSION: Concentrations of iPF2alpha-III released into the venous circulation during reperfusion following AMI in humans are significantly lower than those required to diminish coronary flow in the murine heart; increased levels indicate successful reperfusion. Inhibition of iPF2alpha-III has no effect on coronary flow or infarct size in the murine heart, suggesting that iPF2alpha-III alone does not account for the low/no reflow phenomenon observed following AMI.

Vitamin C and E supplementation in women at risk of preeclampsia is associated with changes in indices of oxidative stress and placental function.

OBJECTIVE: We have previously reported a reduced incidence of preeclampsia in women who were at risk and were taking vitamin C (1000 mg/d) and vitamin E (400 IU/d) supplements. In this study, we determined whether supplementation in the same cohort was associated with an improvement in indices of placental dysfunction and oxidative stress toward values determined in women who were at low risk of preeclampsia. STUDY DESIGN: Seventy-nine women who were at high risk and who were taking vitamin supplements and 81 who were taking placebos were compared with 32 women who were at low risk and who were not taking supplements who were studied simultaneously. RESULTS: Indices of oxidative stress and placental function were abnormal in the placebo group. When the placebo group was compared with the women who were at low risk, ascorbic acid, plasminogen activator inhibitor-2, and placenta growth factor concentrations were decreased; and 8-epi-prostaglandin F(2alpha),leptin, and the plasminogen activator inhibitor-1/-2 ratio were increased. In the group that received vitamin supplements, ascorbic acid, 8-epi-prostaglandin F(2alpha), leptin, and plasminogen activator inhibitor-1/-2 values were similar to women who were at low risk. CONCLUSION: Antioxidant supplementation in women who were at risk of preeclampsia was associated with improvement in biochemical indices of the disease.

A longitudinal study of biochemical variables in women at risk of preeclampsia.

OBJECTIVE: The purpose of this study was to characterize gestational profiles of biochemical markers that are associated with preeclampsia in the blood of pregnant women in whom preeclampsia developed later and to compare these markers with the markers of women who were delivered of small-for-gestational-age infants without preeclampsia and with women who were at low risk for the development of preeclampsia. STUDY DESIGN: This was a prospective case control study. The subjects were women at risk of preeclampsia who were enrolled in the placebo arm of a clinical trial. Indices of antioxidant status, oxidative stress, placental and endothelial function, and serum lipid concentrations were evaluated from 20 weeks of gestation until delivery in 21 women in whom preeclampsia developed later, in 17 women without preeclampsia who were delivered of small-for-gestational-age infants, and in 27 women who were at low risk for the development of preeclampsia. RESULTS: Ascorbic acid was reduced early in preeclampsia and small-for-gestational-age pregnancies. Leptin, placenta growth factor, the plasminogen activator inhibitor (PAI-1)/PAI-2 ratio, and uric acid were predictive of the development of preeclampsia. CONCLUSION: Gestational profiles of several markers were abnormal in the group with preeclampsia, and some of the markers that may prove useful in the selective prediction of preeclampsia were identified.

Identification of diacylated ureas as a novel family of fungus-specific leukocyte-activating pathogen-associated molecules.

Polymorphonuclear leukocytes represent primary components of the host's innate immune defenses against fungal infection, suggesting involvement of fungal leukocyte attractants. We have found in various fungi, but not in bacteria or host cells, unstable lipid-like leukocyte chemoattractants, which also induced adherence and degranulation in human neutrophils. Purification from bakers' yeast and structural analyses by electrospray mass spectrometry, (1)H NMR spectroscopy, and chemical synthesis revealed these inflammatory mediators as diacylated ureas, a novel class of unstable lipoids. The N,N'-dipalmitoleyl urea appeared to be the most potent innate immune responses inducing compound eliciting half-maximum neutrophil chemotactic activity at 140 nm. The all-trans isomer, N,N'-dipalmitelaidyl urea, was found to be inactive with respect to stimulation of degranulation in neutrophils, which indicates a Delta(9) cis-double bond to be essential for bioactivity of these diacyl ureas. N,N'-Dipalmitoleyl urea elicited Ca(2+) mobilization in neutrophils, which was found to be pertussis toxin-sensitive and sensitive toward a carboxylmethyltransferase inhibitor, indicating that these diacyl ureas activate leukocytes via a putative Galpha(i)-protein-coupled receptor. Their isolation exclusively from fungi suggests that these lipoids are fungus-specific pathogen-associated molecules that may alert the human innate immunity system to the presence of a fungal infection.