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)

Fibronectin was given in the form of cryoprecipitate of human plasma to patients with severe surgical sepsis in a double blind, prospective and randomized clinical study. Of the 19 patients assigned to the control group receiving no fibronectin, only eight (42 per cent) survived. Of the 12 patients given the cryoprecipitate, nine survived (75 per cent) (p less than 0.05). In the control group, initial serum fibronectin levels were depressed to 121 micrograms per milliliter (normal = 313). The mean values in the blank plasma controls did not increase after 24 hours, with a mean of 122. In contrast, the group treated with cryoprecipitate increased serum fibronectin values after 24 hours to 216 micrograms per milliliter, up from initial values of 161 micrograms per milliliters. Improvements in pulmonary function, serum bilirubin and serum creatinine values were also noted, but the changes fell short of statistical significance. Fibronectin appears to benefit patients in severe surgical sepsis in this study of a relatively small number of patients.
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PMID:Fibronectin in severe sepsis. 308 23

Sequestration of activated polymorphonuclear leukocytes (PMN) within the lung microcirculation may contribute to pulmonary vascular injury following trauma, sepsis, or disseminated intravascular coagulation. In this study cultured rat endothelial cells were utilized to evaluate the effect of PMN activation on endothelial cell attachment. The concept that disruption of the extracellular fibronectin matrix is associated with altered endothelial cell adhesion was also tested. Rat endothelial cells were grown in culture and identified by morphological techniques as well as immunofluorescent staining of Factor VIII R:Ag. Endothelial cells were labeled with 51Cr in order to establish a cell injury assay based on release of free 51Cr or cell-associated 51Cr. PMN activation was verified microscopically and by chemiluminescence activity following phorbol myristate acetate (PMA) or opsonized zymosan exposure. Following incubation with PMA, the leukocytes aggregated, chemiluminesced vigorously, and caused endothelial cell injury and detachment as determined by release of 51Cr-labeled endothelial cells. PMNs exposed to serum-treated zymosan exhibited a more modest chemiluminescence burst which was consistent with their decreased activity to injure the endothelial monolayer. With PMA activation the degree of endothelial detachment from the monolayer increased as a function of time with a plateau observed by 3 hr. Microscopic immunofluorescent analysis of extracellular fibronectin in endothelial cell cultures revealed disruption of the fibrillar matrix fibronectin after incubation with PMA-activated neutrophils in association with endothelial cell disadhesion. Thus, exposure of activated rat PMN to rat endothelial cells in culture induces endothelial damage and an associated disruption of the fibronectin matrix which may contribute to endothelial cell detachment.
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PMID:Matrix fibronectin disruption in association with altered endothelial cell adhesion induced by activated polymorphonuclear leukocytes. 309 67

Septic surgical patients often require fluid administration to maintain cardiovascular stability due, in part, to the sepsis-induced increase in vascular permeability and associated plasma volume depletion. Plasma fibronectin deficiency exists in such septic patients. We determined if maintenance of fibronectin levels by administration of fibronectin-rich human plasma cryoprecipitate would lower the resuscitative fluid volume needed for support of arterial pressure in septic postoperative sheep which were experimentally depleted of plasma fibronectin. Following a 2-hr postoperative baseline period, denatured collagen (gelatin, 8.7 mg/kg), which has a high affinity for fibronectin, was infused into both control and experimental sheep in order to acutely deplete plasma fibronectin. Sheep were then challenged both intraperitoneally and intravenously with live Pseudomonas (5 x 10(10) bacteria IP; 5 x 10(9) bacteria IV). Experimentals were given fresh plasma cryoprecipitate intravenously at a dose of 4 units bolus, followed by 3 units/hr for 5 hr. Controls received plasma cryoprecipitate selectively depleted of fibronectin by affinity chromatography. Bacterial challenge rapidly resulted in severe systemic hypotension. Ringer's lactate was infused intravenously into both groups at a rate sufficient to maintain a systemic arterial pressure of approximately 50 mm Hg with a maximum pulmonary artery wedge pressure of 15-18 mm Hg. Its rate of infusion was periodically adjusted to maintain this hemodynamic status. Comparison was made of the volume of Ringer's lactate required to maintain an arterial pressure of 50 mm Hg in both groups. Net fluid requirement was significantly (p less than 0.05) less in postoperative septic sheep (47.4 +/- 6.2 mg/kg/hr) treated with fibronectin-rich cryoprecipitate compared to the fluid requirement (71.7 +/- 4.7 mg/kg/hr) for postoperative septic sheep receiving fibronectin-deficient cryoprecipitate. Thus elevation of plasma fibronectin concentration lowers the fluid requirements needed for hemodynamic support in postoperative Gram-negative sepsis.
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PMID:Effect of fibronectin-rich human cryoprecipitate on fluid volume requirements in sheep during postoperative sepsis. 313 Apr 90

A purified freeze-dried fibronectin concentrate prepared by the Centre National de Transfusion Sanguine from blood donors' plasma pools was tested for safety and effects on recipients' plasma fibronectin levels. The product was administered on 17 occasions to 10 patients with severe sepsis, either as bolus intravenous injection (group B) or as bolus injection of one-half of the dose followed by continuous infusion of the remaining half-dose over a 6-hour period (group B + P). The drug was well tolerated both clinically and biochemically. Following a 1 mg/kg dose of fibronectin, the maximum increase in mean plasma fibronectin levels was 17 +/- 5 mg/l in group B patients and 20 +/- 5 mg/l in group B + P patients. Mean times to peak were 188 +/- 53 min and 282 +/- 106 min respectively in the two groups. A cooperative randomized double-blind trial is currently in progress to evaluate the clinical effectiveness of the product.
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PMID:[Human fibronectin in the treatment of septic states. Tolerance and course of plasma levels]. 315 29

Severe sepsis leads to depression of the reticulo-endothelial system (RES) with delayed bloodstream clearance of particulate matter and bacteria. Splenectomy results in increased susceptibility to infection with encapsulated organisms but its effect on the resistance to postoperative Gram-negative infection has been little studied. We have investigated the effect of splenectomy on RES function by measurement of plasma fibronectin concentrations and bacterial clearance in the presence and absence of sepsis. In experiment 1, rabbits underwent splenectomy (n = 8) or laparotomy only (n = 8) 4 weeks before a second laparotomy. In experiment 2, animals had either splenectomy (n = 8) or laparotomy only (n = 8) followed 4 weeks later by devascularization of the appendix (sepsis). Plasma fibronectin concentrations and the blood clearance and organ distribution of an intravenous injection of 75Se-labelled viable Escherichia coli (2-3 X 10(8) colony forming units (c.f.u.] were measured 24 h after the second operation. Splenectomy resulted in: (1) a persistent reduction in plasma fibronectin concentration in the presence and absence of sepsis, and (2) a delay in the bloodstream clearance with reduced hepatic (Kupffer cell) uptake of E. coli which was exaggerated in the septic splenectomized animal. It is concluded that the spleen may be important for Gram-negative bacterial clearance, possibly related to its influence on plasma fibronectin concentration and Kupffer cell function.
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PMID:Effect of splenectomy on gram-negative bacterial clearance in the presence and absence of sepsis. 328 88

Immunoreactive plasma fibronectin depletion has been associated with the presence of collagen-fibronectin complexes in patients after trauma and in animal models of traumatic and burn injuries. However, the role of plasma fibronectin in the development of sepsis after traumatic and burn injuries in patients is unknown. Treatment of patients and animals with purified human plasma fibronectin ameliorates some of the clinical and metabolic effects of systemic endotoxemia. We report that the induction of immunoreactive plasma fibronectin deficiency by gelatin infusion is associated with enhanced effects of intraperitoneal Escherichia coli endotoxin injection. We have observed a significant increase in the concentrations of ammonia in plasma of treated rats compared with those in control rats administered the same dose of endotoxin.
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PMID:Enhanced endotoxin effects in plasma fibronectin-deficient rats. 329 66

Plasma fibronectin may be an important component of host defense in critically ill patients, particularly after trauma and during sepsis. This paper reviews recent studies that have sought to characterize the natural history of plasma fibronectin during sepsis, as well as those studies that tested the effect of therapy with concentrated fibronectin in sepsis. The decrease in plasma fibronectin that generally is seen in humans during sepsis probably is due to many factors, and it has been difficult to produce a similar pattern in animal models. Depletion of plasma fibronectin is not a sensitive or specific predictor of imminent sepsis, and once sepsis is established, the concentration of plasma fibronectin is no more sensitive a predictor of mortality than are many other clinical markers. Early, uncontrolled trials of therapy with a fibronectin concentrate in patients with sepsis appeared to indicate a propitious effect on organ function. However, more recent controlled trials have failed to show a significant effect of therapy with fibronectin concentrate on either organ function or patient survival.
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PMID:Plasma fibronectin and fibronectin therapy in sepsis and critical illness. 332 38

In this brief review a description of changes in specific immune response with regard to surgical trauma is presented. The effect of anesthesia on these responses appears to be minimal. The mechanisms underlying functional abnormalities include serum inhibitory factors, suppressor monocytes, deficiency of lymphocyte-monocyte-associated fibronectin, and deficiency of IL-2 production. The factor of stress should be taken into consideration when interpreting the effect of surgery, because stress is known to influence various immune responses. The reason for various discrepancies among investigators appear to be due to technical differences, type of surgery, duration of surgery, temperature at which surgery was done (both hypothermia and hyperthermia modify the immune response), blood or plasma infusion (they appear to activate T-cells in vivo), underlying disease, and baseline immunologic status (for example, patients with malignancy with depressed preoperative immunologic status might be more or less susceptible to the effects of surgical trauma), nutritional status, drugs used, etc. Quantitative analysis should be done using monoclonal antibodies and FACS. In none of the studies published was FACS used. More detailed studies are required to understand non-T- and non-B-cell and macrophage functions in patients undergoing surgical trauma. Specific antibody responses should be studied to explain the high frequency of sepsis in the postoperative period.
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PMID:Immune response following surgical trauma. 333 6

Decreases in plasma fibronectin levels following surgery and subsequent to trauma and sepsis have been previously reported. There have been no reports, however, regarding plasma fibronectin levels following cesarean section. Plasma fibronectin levels were followed for 3 days postpartum in 49 patients including cesarean section control patients, patients with cephalopelvic disproportion, pregnancy-induced hypertension, and endometritis. Cesarean section and cephalopelvic disproportion were not associated with a change in postpartum fibronectin levels. Pregnancy-induced hypertension and endometritis did show a significant increase (p less than 0.05) in plasma fibronectin levels. These levels are probably not decreased because of the large fibronectin pool in these otherwise healthy women.
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PMID:Postcesarean section plasma fibronectin levels. 334 22

The levels of fibronectin were determined by immunoturbidimetric assay in two populations: (a) plasma of healthy nonpregnant and pregnant women, and in amniotic fluid of healthy pregnant females; (b) plasma of umbilical cord blood of healthy newborns and of newborns with sepsis. Fibronectin concentrations of amniotic fluid showed a significant decrease during pregnancy, but the changes of plasma fibronectin levels were not significant in this period. In newborn sepsis, the levels of plasma fibronectin were significantly decreased. We did not find a significant difference between the fibronectin concentration of umbilical cord blood of premature infants compared to mature infants.
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PMID:Fibronectin determination in pregnancy. 339 Aug 97


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