Natural anticoagulants in sepsis--Too much of a good thing?
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Anticoagulants↗
Biomedical subjects
Simon V Baudouin
Publications and source records attributed to Simon V Baudouin.
Mitochondrial DNA and survival after sepsis: a prospective study.
BACKGROUND: Human genome evolution has been shaped by infectious disease. Although most genetic studies have focused on the immune system, recovery after sepsis is directly related to physiological reserve that is critically dependent on mitochondrial function. We investigated whether haplogroup H, the most common type of mitochondrial DNA (mtDNA) in Europe, contributes to the subtle genetic variation in survival after sepsis. METHODS: In a prospective study, we included 150 individuals who were sequentially admitted to the intensive care unit in a hospital in Newcastle upon Tyne, UK. After clinical data were obtained, patients underwent mtDNA haplotyping by analysis with PCR and restriction fragment length polymorphism. As endpoints, we used death during the 6-month period or survival at 6 months. FINDINGS: Follow-up was complete for all study participants, although the haplotype of two patients could not be reliably determined. On admission to the intensive care unit, the frequency of mtDNA haplogroup H in study patients did not differ between study patients admitted with severe sepsis and 542 age-matched controls from the northeast of England. MtDNA haplogroup H was a strong independent predictor of outcome during severe sepsis, conferring a 2.12-fold (95% CI 1.02-4.43) increased chance of survival at 180 days compared with individuals without the haplogroup H. INTERPRETATION: Although haplogroup H is the most recent addition to the group of European mtDNA, paradoxically it is also the most common. Increased survival after sepsis provides one explanation for this observation. MtDNA haplotyping offers a new means of risk stratification of patients with severe infections, which suggests new avenues for therapeutic intervention.
APACHE↗
Exogenous surfactant replacement in ARDS--one day, someday, or never?
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1,2-Dipalmitoylphosphatidylcholine↗
Neutrophil chemotaxis and receptor expression in clinical septic shock.
OBJECTIVE: To examine the hypothesis that neutrophil chemotaxis to interleukin-8 (IL-8) is reduced in septic shock. Surface expression of neutrophil CXC chemokine receptors and the adhesion molecule CD11b were also examined and associations between disease severity, gas exchange and receptor expression were studied. DESIGN: Prospective cohort clinical study. SETTING. Intensive care unit in a tertiary referral teaching hospital. PATIENTS: Patients with septic shock ( n=15) and healthy controls ( n=8) were studied. MEASUREMENTS AND RESULTS: Daily (for 5 consecutive days) flow cytometric measurements of chemokine and beta integrin surface expression. "In vitro" neutrophil chemotaxis to IL-8 was also compared between patients with sepsis and healthy controls. CXCR2 expression significantly fell, CD11b expression increased and CXCR1 expression was unchanged throughout the study in the septic group compared with healthy controls. CD11b positively correlated with increasing APACHE II scores ( p<0.0001) and worsening PaO(2)/FIO(2) ratios ( p<0.0001). CXCR2 expression negatively correlated with both APACHE II scores ( p=0.016) and PaO(2)/FIO(2) ratios ( p=0.01). There was no correlation between CXCR1 expression and either APACHE II score or PaO(2)/FIO(2) ratios. Chemotaxis to IL-8 was reduced in patients with sepsis compared with healthy volunteers. CONCLUSIONS: Surface expression of the chemokine receptor CXCR2 and the beta-integrin CD11b, but not CXCR1, were reduced on neutrophils isolated from patients with septic shock compared with healthy controls. Chemotaxis to IL-8 was also reduced in neutrophils from septic patients compared with healthy controls. The changes in receptor expression correlated with measures of disease severity.
Adolescent↗
Smooth muscle alpha-actin expression in endothelial cells derived from CD34+ human cord blood cells.
Human fetal cord blood contains subsets of mononuclear cells with the potential to form both hematological and endothelial cells. Vascular progenitor cells, which can produce all three elements of mature blood vessels, including smooth muscle, have been identified in animals. We hypothesized that similar multipotential progenitor cells exist in humans and used the expression of alpha-smooth muscle actin (alpha-SMA) to identify such cells in fetal cord blood. Mononuclear cell preparations were isolated from human umbilical cord blood and CD34(+) and CD133(+) cells obtained by magnetic bead separation. Isolated cells were cultured on fibronectin-coated dishes with medium containing vascular endothelial growth factor, basic fibroblast growth factor, and insulin-like growth factor. mRNA was extracted, and the expression of alpha-SMA and a number of endothelial cell markers (VEGFR-2, vWF, eNOS, VE-Cadhein, PECAM-1 and Tie-2) was determined by reverse transcriptase-PCR techniques. Human umbilical vein endothelial cells (HUVECs) were used as positive controls. Freshly isolated CD34(+) and CD133(+) cells expressed all endothelial cell markers, but did not express alpha-SMA. HUVECs expressed alpha-SMA. Following 4 weeks of culture, CD34(+) isolates produced morphologically endothelial-like cells that expressed both endothelial cell markers and alpha-SMA. CD133(+) cells failed to produce morphological endothelial-like cells but expressed a range of endothelial markers. However, they did not express alpha-SMA. Following culture in an endothelial cell-promoting environment, CD34(+), but not CD133(+), isolates produced endothelial-like cells that expressed alpha-SMA. Human fetal cord blood contains a population of cells that may differentiate toward both an endothelial and a smooth muscle phenotype in culture.
AC133 Antigen↗
Nutritional support in critical care.
Despite the key role of nutrition in health and the almost universal use of supplemental feeding in the ICU, there is a lack of high-quality evidence to guide clinical practice. Enteral nutrition is superior to TPN in almost all circumstances and most patients in the ICU can be fed successfully by this route. There is little evidence to support the use of special feeds and the role of immunonutrients remains unproven. Nutritional support cannot completely prevent the adverse effects of catabolic illness and overfeeding should be avoided.
Basal Metabolism↗
Survival in Duchenne muscular dystrophy: improvements in life expectancy since 1967 and the impact of home nocturnal ventilation.
We reviewed the notes of 197 patients with Duchenne muscular dystrophy whose treatment was managed at the Newcastle muscle centre from 1967 to 2002, to determine whether survival has improved over the decades and whether the impact of nocturnal ventilation altered the pattern of survival. Patients were grouped according to the decade of death and whether or not they were ventilated. Kaplan Meier survival analyses showed significant decade on decade improvement in survival. Mean age of death in the 1960s was 14.4 years, whereas for those ventilated since 1990 it was 25.3 years. Cardiomyopathy significantly shortened life expectancy from 19 years to a mean age of 16.9 years. Better coordinated care probably improved the chances of survival to 25 years from 0% in the 1960s to 4% in the 1970s and 12% in the 1980s, but the impact of nocturnal ventilation has further improved this chance to 53% for those ventilated since 1990.
Female↗