Screening for MRSA and GISA in the intensive care unit.
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Cross Infection↗
Biomedical subjects
G Bellingan
Publications and source records attributed to G Bellingan.
Computer keyboards and the spread of MRSA.
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Computers↗
Door-opening motion can potentially lead to a transient breakdown in negative-pressure isolation conditions: the importance of vorticity and buoyancy airflows.
A patient with severe chickenpox was admitted to a negative-pressure isolation room. He remained sedated, intubated and mechanically ventilated throughout his admission. He was managed only by nurses immune to chickenpox. A non-immune male nurse occasionally handed equipment through the doorway, without entering the room. Ten days later, he also developed chickenpox. Sequencing of viruses from the patient and nurse showed the same rare genotype, indicating nosocomial transmission. An experimental model demonstrated that, despite negative pressure, opening the door could have resulted in transport of infectious air out of the isolation room, leading to a breakdown in isolation conditions.
Air Pressure↗
Leukocytes: friend or foe.
Leukocytes have a fundamental role in innate and adaptive immunity, wound healing, tumour surveillance and in tissue remodelling. It is their function in the inflammatory response however that is of most interest to us in the intensive care setting. Over the last three decades we have gained significant insights into leukocyte activation, recruitment and mediator secretion and the contribution of these agents to both the onset and resolution of sepsis and inflammation. The body relies on the inflammatory response for protection. Leukocytes occupy a pivotal position in this but to maintain these cells in a state of permanent activation would be unsustainable, with widespread microvascular plugging, uncontrolled free radical release and an excessive metabolic demand. Leukocytes thus circulate in a quiescent state and are rapidly activated by invading pathogens and other stimuli. A direct consequence of this protective strategy is that the inflammatory response may be inadequate, with the risk of overwhelming sepsis, or excessive, leading to rampant systemic inflammation and consequent multiple organ damage. It is now becoming apparent however that in addition to leukocytes other cells have important roles both in defence against invading pathogens and in driving malignant inflammation. This review will focus on two new facets of the innate immune system, the Toll family of proteins as the signal transduction element for endotoxin, and the antimicrobial peptides. These exemplify potential damaging and protective response elements but importantly neither are restricted to leukocytes. The capacity of cells and tissues other than the leukocytes to participate and even lead in the inflammatory responses will also be explored.
Humans↗
Comparison of a specialist retrieval team with current United Kingdom practice for the transport of critically ill patients.
OBJECTIVE: The inter-hospital transfer of critically ill patients in the United Kingdom is commonly undertaken using standard ambulance under junior doctor escort, despite recommendations for the use of specialist retrieval teams. Patients are transferred into University College London Hospitals (UCLH) intensive care unit (ICU) by both methods. We undertook to evaluate the effect of transfer method on acute physiology (within 2 h of ICU admission) and early mortality ( < 12 h after ICU admission). DESIGN: Retrospective review of all transfers over 1 year. SETTING: UCLH ICU. SUBJECTS: 259 transfers; 168 by specialist retrieval team (group A) and 91 by standard ambulance with doctor provided by referring hospital (group B). INTERVENTIONS: None. MAIN OUTCOME MEASURES: Acute physiology (pH, PaO2, PaCO2, heart rate (HR), mean arterial blood pressure (MAP), 24 h severity of illness scores (APACHE II, SAPS II), length of stay and mortality. RESULTS: There were no differences in demographic characteristics or severity of illness between the two groups; nevertheless significantly more patients in group B than in group A were severely acidotic (pH < 7.1: 11% vs. 3%, p < 0.008) and hypotensive (MAP < 60: 18 % vs. 9%, p < 0.03) upon arrival. In addition, there were more deaths within the first 12 h after admission with 7.7 % deaths (7/91) in group B transfers vs. 3% (5/168) in group A. CONCLUSIONS: The use of a specialist transfer team may significantly improve the acute physiology of critically ill patients and may reduce early mortality in ICU.
Ambulances↗
Disseminated fungal infection following falciparum malaria.
Falciparum malaria can cause immune suppression sufficient to allow opportunistic infection during the recovery phase. A patient is described who died from a disseminated infection with Aspergillus flavus and Absidia corymbifera, unresponsive to treatment with amphotericin and voriconazole.
Absidia↗
Fibroproliferation occurs early in the acute respiratory distress syndrome and impacts on outcome.
The fibroproliferative phase of acute respiratory distress syndrome (ARDS) has traditionally been regarded as a late event but recent studies that suggest increased lung collagen turnover within 24 h of diagnosis challenge this view. We hypothesized that fibroproliferation is initiated early in ARDS, characterized by the presence of fibroblast growth factor activity in the lung and would relate to clinical outcome. Patients fulfilling American/European Consensus Committee criteria for ARDS and control patients ventilated for non-ARDS respiratory failure underwent bronchoalveolar lavage (BAL) and serum sampling within 24 h of diagnosis and again at 7 d. The ability of BAL fluid (BALF) to stimulate human lung fibroblast proliferation in vitro was examined in relation to concentrations of N-terminal peptide for type III procollagen (N-PCP-III) in BALF/serum and clinical indices. At 24 h, ARDS lavage fluid demonstrated potent mitogenic activity with a median value equivalent to 70% (range 31-164) of the response to serum, and was significantly higher than control lavage (32% of serum response, range 11-42; p < 0.05). At 24 h, serum N-PCP-III concentrations were elevated in the ARDS group compared with control patients (2.8 U/ml; range 0.6-14.8 versus 1.1 U/ml; range 0.4-3.7, p < 0.0001) as were BALF N-PCP-III concentrations (2.9 U/ml; range 0. 6-11.4 versus 0.46 U/ ml; range 0.00-1.63, p < 0.01). In addition, BALF N-PCP-III concentrations at 24 h were significantly elevated in nonsurvivors of ARDS compared with survivors (p < 0.05). At 7 d, the mitogenic activity remained elevated in the ARDS group compared with control (p < 0.05) and was also significantly higher in ARDS nonsurvivors compared with survivors (67%; range 45-120 versus 31%; range 16-64, p < 0.05). These data are consistent with the hypothesis that fibroproliferation is an early response to lung injury and an important therapeutic target.
Adolescent↗
Inflammatory cell activation in sepsis.
The body relies for protection on an effective inflammatory response. To sustain an armoury of inflammatory cells in a state of permanent activation would be impossible and a system whereby such cells can be rapidly activated is, therefore, employed. Upon transition from the resting to activated state inflammatory cells perform multiple defensive functions and are then removed, limiting the duration of inflammation. Neutrophils are the major circulating inflammatory cells but macrophages exert a more powerful regulatory effect. If the inflammatory response is inadequate there is a risk of overwhelming sepsis. By contrast, an unregulated response can lead to systemic inflammation and consequent multiple organ damage. This review focuses on the mechanisms whereby inflammatory cells are activated, how the regulatory system may misfunction and how it may in the future be manipulated to therapeutic advantage.
Cell Adhesion Molecules↗
Endotoxin reduces maximal oxygen consumption in hepatocytes independent of any hypoxic insult.
OBJECTIVE: The cause of the metabolic disturbances in sepsis remains uncertain, but there is increasing evidence suggesting that haemodynamic changes are not solely responsible. We addressed the question of whether endotoxin has a significant effect on cellular oxygen metabolism, independent of confounding haemodynamic defects. DESIGN: Prospective, controlled experimental study. SETTING: University Laboratory. MODEL: Human hepatocyte cell line. METHODS: The oxygen consumption rate (OCR) was calculated from the fall in oxygen tension in a sealed cuvette containing Hep G2 cells in suspension. The oxygen tension was measured by porphyrin phosphorescence half-life analysis. Resting OCR was measured in control cells and after 1, 6 and 24 h of endotoxin exposure. In a second series of experiments, resting and maximal OCR was measured after 6 and 24 h of endotoxin exposure and in control cells using the addition of a mitochondrial uncoupler (FCCP); this uncouples the respiratory chain from ATP synthesis, thereby removing negative feedback and allowing the respiratory chain to work at maximal rate. RESULTS: Endotoxin caused a rise in resting OCR at 1 h which was significant by 6 h but had returned to control values by 24 h. Maximal OCR also increased at 6 h, however exposure to endotoxin for 24 h significantly reduced maximal OCR compared to the control cells. CONCLUSIONS: Endotoxin has complex effects on cellular energy metabolism causing an initial rise in the oxygen consumption rate and a significant limitation in oxygen consumption capacity at 24 h. These complex effects would be in keeping with the varied responses seen in patients.
Cell Line↗
The acute respiratory distress syndrome: fibrosis in the fast lane.
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Cytokines↗
Immunotherapy of sepsis syndrome: a comparison of the available treatments.
OBJECTIVE: To evaluate the current range of immunotherapy for sepsis syndrome. DATA: Three major, recent anti-endotoxin and two human polyclonal, immunoglobulin clinical trials are reviewed. COMPARISONS: Comparisons are made in their trial design, definitions, patient selection and exclusion criteria and patient demographics. The results in specific subsets are compared and reasons for the differences in efficacy, discussed. RESULTS: J5 anti-sera, E-5, and HA-1A are all effective in reducing the mortality in patients with gram-negative infections. They also result in enhanced resolution of organ failure. Similarities in the efficacies of J5 anti-sera and HA-1A for bacteremic patients with and without shock are noted. High-dose polyclonal human immunoglobulins have been shown to be of benefit in both gram-positive and gram-negative infections in two small clinical trials and deserve further evaluation. CONCLUSION: Anti-endotoxin monoclonal antibodies benefit patients with gram-negative sepsis. They are proof of a concept, but are costly and do not show an overall intention-to-treat effect. There is an urgent need to accurately identify, clinically or by a cytokine profile, those patients who will specifically benefit.
Antibodies, Monoclonal↗