Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of this study was to identify a novel immunological indicator useful for the early diagnosis (through a rapid and single determination) of neonatal sepsis (NS). Peripheral blood samples were taken from 63 neonates, who were classified into four groups: proven NS (n = 17); clinical NS (n = 14); disease without infection (n = 17); and healthy newborns (n = 15). Neutrophil expression of CD64, CD43, CD44, CD50, CD62L and Mac-1, and plasma levels of interleukin (IL)-1beta, IL-6, tumor necrosis factor-alpha (TNF-alpha) and soluble L-selectin (sCD62L), were determined. Expression of CD64 was significantly enhanced in the group with proven sepsis and clinical NS compared to newborns without infection (p < 0.05). Eight newborns with proven or clinical sepsis, but only one with disease without infection, showed an increased percentage of CD64+ cells (diagnostic specificity = 96.8%). No significant differences were found in the expression of the other leucocyte differentiation antigens studied. As previously described, TNF-alpha and IL-6 levels were significantly elevated in newborns with proven or clinical sepsis compared to neonates without infection (p < 0.05). Our results suggest that, through a single determination, the enhanced expression of CD64 is a highly specific indicator of NS, although its diagnostic sensitivity is low (25.8%). In contrast, we found that plasma levels of IL-1beta and sCD62L, as well as the expression of Mac-1, CD43, CD44, CD50, and CD62L, do not appear to be useful for the diagnosis of NS.
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PMID:Expression of CD64 as a potential marker of neonatal sepsis. 1243 Nov 90

Disorders in immune reactions represent one of the main pathogenetic mechanisms in patients of Intensive Care Units who suffer from sepsis or syndrome of systemic inflammatory response. The determination of early activation sign CD69 on T lymphocytes makes it possible to evaluate functional capacity of this cell population. The determination of other selected immunological parameters contributes to differential diagnosis of infectious and non-infectious etiology of systemic inflammatory response. The authors demonstrated lower expression of CD69 on CD3+ CD8+ lymphocytes after stimulation with phytohemagglutinin in patients with sepsis as well as patients with the syndrome of systemic inflammatory response of non-infections etiology. No statistically significant differences were proved in the concentrations of IgG, IgA and IgM, number of leukocytes, percentual representation of lymphocytes, TNF alpha production and the expression of surface sign of CD64 in both groups of patients. There were statistically significant differences in the concentrations of C3 and C4 components of complement, prealbumin and procalcitonin. The study did not show correlation between the expression of CD69 and selected immunological parameters (IgA, IgM, IgG, C3, C4, leukocytes, lymphocytes, prealbumin, procalcitonin, TNF alpha and CD64).
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PMID:[Evaluation of lymphocyte activation in patients in intensive care units by using flow cytometry for determining expression of early activation antigen CD69]. 1505 29

This prospective study aimed to evaluate the diagnostic utilities of neutrophil CD64 expression for the identification of early-onset clinical infection and pneumonia in term infants and to define the optimal cutoff value so that it may act as a reference with which future studies can be compared. Term newborns in whom infection was suspected when they were <72 h of age were recruited into the study. C-reactive protein (CRP) and expression of CD64 on neutrophils were measured at 0 h (at the time of sepsis evaluation) and 24 h. The sensitivity, specificity, positive predictive value, and negative predictive value (NPV) of CRP, CD64, and the combination of these two markers for predicting neonatal sepsis were determined. A total of 338 infants with suspected clinical sepsis were investigated, 115 of whom were found to be clinically infected. CRP and CD64 in infected infants were both significantly elevated at 0 and 24 h compared with noninfected infants (p < 0.001). The calculated optimal cutoff value for CD64 was 6136 antibody-phycoerythrin molecules bound/cell. CD64 has a very high sensitivity (96%) and NPV (97%) at 24 h. The addition of CRP only marginally enhanced the sensitivity and NPV (97 and 98%, respectively). In conclusion, neutrophil CD64 is a very sensitive diagnostic marker for the identification of early-onset clinical infection and pneumonia in term newborns. The results strongly suggest that measurement of neutrophil CD64 may allow neonatal clinicians to discontinue antibiotic treatment at 24 h in infants who are clinically stable and whose CD64 expressions are below the optimal cutoff level.
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PMID:Neutrophil CD64 is a sensitive diagnostic marker for early-onset neonatal infection. 1537 62

Pre-term neonates are at high risk to develop early-onset sepsis which possibly is caused by an immature immune system. Monocytes play a pivotal role as professional phagocytic and antigen-presenting cells in the innate immunity. In the present study, we investigated in monocytes from cord blood the expression of human leukocyte antigen (HLA)-DR as a marker for antigen-presenting capability, the expression of the high-affinity receptor for IgG (FcgammaRI/CD64), and the capacity to phagocytize non-opsonized Escherichia coli. We compared 70 infants in three groups according to their gestational age (group I: 20 very low birth weight infants (VLBWI), 24-31 weeks of gestation; group II: 25 pre-term infants, 32-36 weeks of gestation, and group III: 25 term neonates). The expression of CD64 as well as the phagocytic capacity of monocytes from cord blood were highest in VLBWI (p < 0.05 and p < 0.01, respectively). In contrast, HLA-DR expression was significantly (p < 0.05) diminished in VLBWI, which possibly leads to a reduced antigen-presenting capacity. We conclude that monocytes have different functional properties during gestational aging, which perhaps participate in the high incidence of infections in VLBWI.
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PMID:Monocyte switch in neonates: high phagocytic capacity and low HLA-DR expression in VLBWI are inverted during gestational aging. 1561 Mar 64

Sepsis is a major healthcare problem from the perspective of mortality and economics. Advances in diagnostic detection of infection and sepsis have been slow, but recent advances in both soluble biomarker detection and quantitative cellular measurements promise the availability of improved diagnostic techniques. Though the promise of cytokine measurements reaching clinical practice have not matured, procalcitonin levels are currently available in many countries and appear to offer enhanced diagnostic distinction between bacterial and viral etiologies. Cellular diagnostics is poised to enter clinical laboratory practice in the form of neutrophil CD64 measurements, which offer superior sensitivity and specificity to conventional laboratory assessment of sepsis. Neutrophil CD64 expression is negligible in the healthy state. However, it increases as part of the systemic response to severe infection or sepsis. The combination of cellular proteomics, as in the case of neutrophil CD64 quantification, and selected soluble biomarkers of the inflammatory response, such as procalcitonin or triggering receptor expressed on myeloid cells (TREM)-1, is predicted to remove the current subjectivity and uncertainty in the diagnosis and therapeutic monitoring of infection and sepsis.
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PMID:Improved diagnostic approaches to infection/sepsis detection. 1583 49

There is a clear need for improved indicators of infection or sepsis to increase the sensitivity and specificity of both diagnosis and therapeutic monitoring. One of the effects of inflammatory cytokines on the innate immune response is the rapid up-regulation of CD64 expression on the neutrophil membrane. We and others have hypothesized that the measurement of neutrophil CD64 expression might represent an improved diagnostic indicator of infection and sepsis. In this study we assessed the relative ability of flow cytometric neutrophil CD64 measurements, neutrophil counts, myeloid immaturity differential counts, and flagging on an automated hematology analyzer to correlate with the presence of infection, as determined by a retrospective clinical scoring system of infection or sepsis. A total of 160 blood samples were randomly selected to derive equal proportions of the 3 categories of flags on a Coulter STKS blood counter that indicate the presence of a myeloid left shift. The patients for these samples were scored by retrospective chart review and placed into 4 groups on the basis of likelihood of infection, sepsis, or severe tissue injury. Neutrophil CD64 expression demonstrated a superior sensitivity (94.1%), specificity (84.9%), and positive predictive likelihood ratio (6.24), compared with neutrophil counts (sensitivity, 79.4%; specificity, 46.8%; positive predictive likelihood ratio, 1.49), band counts (sensitivity, 87.5%; specificity, 43.5%; positive predictive likelihood ratio, 1.55), myeloid immaturity fraction (sensitivity, 94.6%; specificity, 84.5%; positive predictive likelihood ratio, 2.12), and flagging on an automated hematology analyzer (sensitivity, 94.1%; specificity, 40.5%; positive predictive likelihood ratio, 1.58). Relative to the other laboratory parameters, the neutrophil CD64 parameter also provided the best separation of the 4 clinical groups. The findings indicate that neutrophil CD64 expression as determined by quantitative flow cytometry is an improved diagnostic indicator of infection/sepsis relative to current laboratory indicators of relative or absolute myeloid cell counts or hematology analyzer flagging algorithms.
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PMID:Comparison of neutrophil CD64 expression, manual myeloid immaturity counts, and automated hematology analyzer flags as indicators of infection or sepsis. 1602 38

A patient with abdominal sepsis, had both intra and extracellular bacteria in a blood smear, and high levels of neutrophil membrane CD64 and HLA-Dr. Intracellular bacteria are only observed in the terminal phase of a sepsis. Our patient recovered, suggesting that a high expression of neutrophil CD64 is indicative for a good prognosis.
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PMID:Measurement of neutrophil membrane CD64 and HLA-Dr in a patient with abdominal sepsis. 1625 35

This study reports the design of an immunofluorescent method for the co-determination of neutrophil CD64 (PMN-CD64), monocyte CD64 (MON-CD64) and monocyte HLA-DR (MON-Ia) expression with the Cell-Dyn CD4,000 haematology analyser. Normal PMN-CD64, MON-CD64 and MON-Ia expression, defined as the mean+/-2SD of 25 healthy adults after correction for isotype control staining, corresponded to 17-67, 515-1045 and 170-670 AFU respectively. Analytical reproducibility determined by duplicate analysis of 12 random samples revealed good assay consistency for all three analysed antigens, with day to day variation in normal subjects being relatively minor in significance. CD4,000 PMN-CD64 and HLA-DR values showed good inter-method correlation with flow cytometry although short term (12 h) stability studies suggested an in vitro trend for increasing PMN-CD64 and variable HLA-DR antigen expression with progressive storage. Observed ranges of PMN-CD64, MON-CD64 and MON-Ia for 109 randomly-selected clinical samples were 31-1058, 307-2843 and 10-876 AFU. Abnormal PMN-CD64 and MON-CD64 shared the same trend (upregulation) while abnormal monocyte MON-Ia was characterised by declining expression. Normal PMN-CD64 was only seen with normal (45/52) or intermediate (7/52) MON-CD64, while high PMN-CD64 was mostly associated with intermediate (18/22) or high (3/22) MON-CD64. MON-Ia expression was largely independent (p=0.04) of PMN-CD64 although marked decreases in MON-Ia were invariably associated with intermediate or high PMN-CD64. MON-Ia expression was inversely related (p<0.0001) to absolute granulocyte counts, and patients with high PMN-CD64 were more likely (8/25) to have in excess of 10% Band Cells compared to samples with normal/intermediate PMN-CD64 (0/84). When compared to C-reactive protein (CRP), high PMN-CD64 and MON-CD64 were always associated with an increased CRP concentration, but minor proportions of samples with normal PMN-CD64 (11/52) or normal MON-CD64 (11/65) could also have an increased CRP. The procedures described in this communication overcome a number of limitations associated with flow cytometry, and co-determination of CD64 and HLA-DR antigen expression may provide complimentary insights into patient heterogeneity in the assessment of suspected sepsis compared to CD64 analysis alone.
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PMID:Simultaneous determination of membrane CD64 and HLA-DR expression by blood neutrophils and monocytes using the monoclonal antibody fluorescence capability of a routine haematology analyser. 1655 67

The aim of the present study was to investigate which biomarker/s reliably assess severity and mortality early in the sepsis process. In 47 critically-ill patients within the 24h of septic onset, Interleukins (IL)-8, -1beta, -6, -10, and -12p70, tumor necrosis factor-alpha (TNF-alpha), procalcitonin (PCT) and C-reactive protein (CRP) were measured in serum. Additionally, CD64 expression was measured in neutrophils. In early sepsis, neutrophil CD64 expression and IL-8 levels are the only biomarkers that increased with sepsis severity, differentiating disease stages: sepsis, severe sepsis and septic shock (p<0.001). The biomarkers that best evaluate the severity of sepsis (via APACHE II) were CD64, IL-8 and IL-6 (p<0.01), and the severity of organ failure (via SOFA) were CD64 and IL-8 (p<0.01). CD64 expression and IL-8 levels were associated with mortality within 28-days (OR=1.3, p=0.01 for CD64 and OR=1.26, p=0.024 for IL-8 by logistic regression analysis) and ROC curve analysis showed high sensitivity and specificity for predicting sepsis stages and the 28 day mortality. We conclude that there is an early increase of neutrophil CD64 expression and IL-8 levels during sepsis. Based on this single measurement it is possible to reliably assess the stage, detect the severity and predict the 28-day mortality of sepsis.
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PMID:Neutrophil CD64 expression and serum IL-8: sensitive early markers of severity and outcome in sepsis. 1736 39

Neonatal sepsis occurs from 1 to 21 newborns out of 1 000 live births with mortality rates as high as 30% up to 69%. The most important risk factors are prematurity, low birth weight, invasive medical procedure and prolonged hospitalization in neonatal intensive care units. An aimed and restrictive antibiotic therapy has an outstanding importance to reduce both morbidity-mortality rates and multiple drug-resistance. Generally, preterm newborns present nonspecific clinical signs of infection. The use of high sensitivity infection markers and a negative predictive value (near 100%) are important to distinguish infected and noninfected patients before the culture results and to verify adequacy and duration of antibiotic therapy. This article reviews the immunologic function and practical use of C reactive protein (CRP) and other markers in the diagnosis of neonatal sepsis. While CRP is a specific late infection marker, cytokines, cell surface markers and procalcitonin (PCT) are early infection markers. The use of multiple markers as CRP, PCT, IL-6, IL-8, CD64, CD11b is useful both to early (24-48 h) diagnose of neonatal sepsis, and to monitorate the antibiotic treatment while waiting for the results of cultural examinations.
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PMID:[Evaluation of C reactive protein and others immunologic markers in the diagnosis of neonatal sepsis]. 1751 72


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