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

The high incidence of fatal septicemia associated with severe thermal injury is believed to result from a loss of immunocompetence. To detect burn-mediated immune defects, lymphocyte function in peripheral blood leukocytes from 18 individuals sustaining 20-80% full thickness thermal burns was investigated. We examined the kinetics of the mitogen responses, the development of suppressive activity, and the correlation of mononuclear cell functional abnormalities with the incidence of sepsis. Patients were divided into three groups corresponding to their clinical course. The phytohemagglutinin responses of Ficoll-Hypaque purified leukocytes from eight of these patients (group III) were normal at day 1-2 after injury, but were significantly depressed (mean 16% of normal) at days 5-10 after injury. All of these group III patients experienced multiple, severe, septic episodes, and septic mortality was 75%. The other 10 burned individuals showed either augmented (group II) or unaltered (group I) mitogen responsiveness. Concomitant with evaluation of their mitogen responses, the cells of burn patients were assessed for development of suppressive activity by addition to on-going normal mixed leukocyte reactions (MLR). Only the addition of mononuclear cells with depressed phytohemagglutinin responsiveness (group III) significantly decreased MLR proliferation (mean 80% reduction) by the previously highly responsive, normal MLR combinations. Addition of cells from group III burn patients collected immediately after injury had no suppressive effect. Addition of cells from patients in group I or II or of normal individual's cells had no suppressive effect. These experimental results strongly suggest that a suppressive mononuclear cell is at least partially responsible for the decreased immunocompetence of burn patients.
 ...
PMID:Changes in lymphocyte activity after thermal injury. The role of suppressor cells. 15 76

Serum complement (C) and C components were examined during a systemic graft versus host (GVH) reaction in the rat. In our series of experiments (Lewis times Brown Norway) F-1 hybrid rats (60-80g) were given 200 times 10-6 or 400 times 10-6 Lewis spleen cells intravenously. Clinical GVH disease appeared 5-7 days after cell injection. Five of six rats in the experimental groups had a fall in levels of serum C2 (20-76%) and C4 (75-98%). Only one of six rats in the control group had a significant fall in C components. In a subsequent experiment (Fisher 344 times Brown Norway) F-1hybrid rats (60g) were given 400 times 10-6 Fischer 344 spleen cells or 200 times 10-6 Fischer 344 Ficoll-Hypaque separated spleen lymphocytes. Clincal GVH disease in this instance appeared on day 10. As in the previous experiments C2 and C4 fell markedly, 20-60% and 60-8-%, respectively, from baseline titers. The control groups did not have a significant fall in C2 or C4. Further examination showed reduction in C3, C5, C6,AND C8 suggesting a sequential activation of the C system via the classical pathway. We have postulated that the cells undergoing blast transformation may be activating the C system through membrane changes during the GVH reaction. Furthermore, the deficiency of C AND C components during GVH disease may contribute to the increased susceptibility of the host to infection and sepsis.
 ...
PMID:Complement in graft versus host disease: IL Depletion of complement components during a systemic graft versus host reaction in the rat (38499). 23 66

For much of the last decade, an increasing number of surgeons have been interested in objective assessment of cellular contributors to host defense function. In order to study many of these processes, it is apparently desirable that the cells be isolated to the extent feasible for the purpose of analyzing a more or less pure population of cellular elements. The purpose of this paper is to describe the physiologic activation of mononuclear cells that occurs as a result of the isolation process. Therefore, it follows logically that such cells are therein intrinsically less responsive to further physiologic manipulation in vitro. Analyses of such data without an awareness of this intrinsic aberration will undoubtedly lead to misinterpretation of the capacity of such cells for further modulation by immunostimulants or by the intrinsic processes related to injury, anesthesia, and operation. Furthermore, it may indicate that certain agents, e.g., cytokines, are unable to stimulate cellular function when, in fact, the defense function of the cell has been initially stimulated by the isolation procedure. Fractionation of human peripheral blood over Hypaque-Ficoll and subsequent purification of monocytes by adherence to plastic lead to an increase in the relative density of HLA-DR on monocytes. This increase occurred when carried out in endotoxin lipopolysaccharide (LPS)-contaminated or LPS-depleted reagents. LPS, added experimentally to whole blood, enhanced HLA-DR expression on monocytes without further manipulation. Monocyte HLA-DR expression measured in whole blood was reduced in patients with major sepsis (n = 19) compared to normal subjects (n = 10).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Experimental and clinical significance of endotoxin-dependent HLA-DR expression on monocytes. 273 99

Previously, we reported that Ficoll-Hypaque-purified leukocytes from burned patients were activated in vivo, even when the mitogen response of these cells was depressed. In these patients, the SBT (endogenous blastogenesis), but not the mitogen response predicted sepsis. The current experiments were performed to clarify why the SBT is increased even when mitogen-stimulated blastogenesis is impaired. We found that neither selective lymphocyte subpopulation (OKT3, T4, T8), nor macrophage depletion returned the increased SBT to normal and that by phenotype and flow cytometric morphology, the Ficoll-Hypaque-purified leukocyte preparations of the burned patients contained fewer lymphocytes than controls (p less than 0.001). Discontinuous Percoll gradients and sheep-RBC rosetting were used to determine the relative contribution of T cells and non-T cells to the increased SBT. These studies indicated that both T cells and non-T cells were activated; however, the non-T cells were primarily responsible for the increased SBT. Thus the peripheral blood of burned patients contains a large fraction of metabolically active non-mononuclear cells that cosediment with mature lymphocytes and could result in artifactual alterations in the assessment of lymphocyte function by in vitro tests.
 ...
PMID:Ficoll-Hypaque leukocyte preparations from burned patients contain activated nonlymphoid cell populations that take up thymidine. 278 6

Nephro-intestinal fistulas involve the GI tract and the kidney or pyelocalyceal system. The main causes may be urologic or digestive, the site diverse. Reno-colic fistulas, although rare, are more frequently observed. We describe a case of left reno-colic fistula secondary to lithiasic pyonephrosis that presented as sepsis. Diagnosis was confirmed by retrograde pyelography. Treatment was by surgery (left nephrectomy, closure of the fistula, and colonorhaphy).
 ...
PMID:[Reno-colic fistula]. 281 88

Twenty-six patients with major thermal injury were studied with sequential tests of immunocompetence. Five to 8 days after burn, 12 of 26 patients developed a marked depression in the phytohemagglutinin response (17 +/- 8 percent of baseline) and an increase in suppression of the normal mixed leukocyte response (70 +/- 13 percent suppression), which was followed by severe life-threatening sepsis 4 to 5 days later. Concomitant with this marked immunosuppression, the 12 patients developed red debris in the normally white mononuclear layer of the Ficoll-Hypaque density centrifugation gradients used to separate mononuclear cells. None of the 14 patients with minimal or no sepsis developed red debris in Ficoll-Hypaque gradients, nor did they show signs of immune depression by phytohemagglutinin or mixed leukocyte response assays. The only patients in the severe sepsis group who survived were those given aminoglycosides at the time red debris was observed on the Ficoll-Hypaque gradients. The presence of red debris on Ficoll-Hypaque separation appears to be a simple and reliable predictor of impending sepsis, which allows the use of antibiotics before the clinical onset of sepsis.
 ...
PMID:A simple method of predicting severe sepsis in burn patients. 644 67