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 purpose of this study was to examine how intra-abdominal sepsis and extracellular matrix proteins (fibronectin, laminin) affect adherent polymorphonuclear leukocyte (PMN) function. Two groups of swine were studied: Group I (n = 5) underwent sham laparotomy; Group II (n = 8) underwent cecal ligation and incision. PMN adherent to either fibronectin (F) or laminin (L) had increased candicidal activity over buffer (B) by Group I but not by post-operative day 8 Group II PMN. (Percent specific release 51Cr-Group I--35.00, 68.25, 64.75% for B, F, and L; P less than 0.001 comparing B vs. F or L; Group II--14.25, 12.50, 12.75% for B, F, and L; P = NS comparing B vs. F or L.) To determine the mechanism for this finding, PMN priming was then assessed by evaluating both PMN adherence to extracellular matrix proteins and the cell surface expression of CR1/CR3 by using sheep RBC opsonized with C3b or C3bi. PMN activation was assayed by using MTT-Formazan, myeloperoxidase, and hypochlorous acid (HOCl) production. Fibronectin and laminin increased PMN adherence and CR1/CR3 expression over buffer by Group I and Group II animals. Fibronectin and laminin increased MTT-Formazan, myeloperoxidase, and HOCl production over buffer by Group I PMN but not POD 8 Group II PMN. These results suggest that untreated intra-abdominal sepsis partially abrogates the effect of extracellular matrix proteins on PMN function; in particular, the activation but not priming of adherent PMN by extracellular matrix proteins is reduced in this clinical situation.
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PMID:Polymicrobial sepsis disrupts normal neutrophil extracellular matrix protein interactions. 132 74

Widespread intravascular coagulation is common in patients with sepsis. Coagulation abnormalities may result from exposure to endotoxin, from tumor necrosis factor alpha or interleukin 1 release, or from the actions of a more specific mediator, such as vascular permeability factor. The result is marked activation of the contact and coagulation systems; simultaneously, there is decreased fibrinolysis and depressed levels of the inhibitors of the contact and coagulation systems. Multiple agents are being studied to correct these abnormalities. Antithrombin III holds promise because it inhibits a number of factors important in contact and coagulation activation, not just thrombin. Plasminogen activators may prove helpful in increasing fibrinolysis during sepsis; because they have been associated with rebound thrombin generation, however, plasminogen activators may be most effective if used in conjunction with hirudin or a synthetic hirudin analogue. Bradykinin may offset hypotension in sepsis. Protein C may inhibit thrombin formation and also complex with plasminogen activator inhibitor 1, thereby promoting fibrinolysis. Other agents that may prove effective include alpha 1-antitrypsin Pittsburgh, C1-esterase inhibitor, monoclonal antibodies to contact factors, soybean trypsin inhibitors, thrombomodulin, prostaglandin I2, and aprotinin. There are no data to support the use of heparin or fibronectin, except in limited circumstances.
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PMID:Modulators of coagulation. A critical appraisal of their role in sepsis. 162 18

Plasma fibronectin levels, assayed by rocket immunoelectrophoresis, were measured in adult burn patients with 25-75 per cent total body surface area burns. Significant differences in the level of plasma fibronectin were detected in the one fatally injured patient prior to death (at 48 and 24 h) as a precipitous and persistent drop to 0.07 and 0.09 g/l, respectively. This deficiency coincided with early clinical signs of sepsis, the severity of which was not clinically apparent prior to overwhelming sepsis and incipient shock. This report supports previous suggestions that secondary deficiencies in plasma fibronectin may be predictive of mortality occurring after day 6 postburn. The need for routine assay of plasma fibronectin using rocket immunoelectrophoresis is demonstrated.
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PMID:Plasma fibronectin levels as predictive of survival in major thermal injury. 189 47

It has long been hypothesized that fibronectin (Fn) is essential to the function of the reticuloendothelial system (RES) and that the reversal of Fn deficiency in critically ill patients would result in a clinical benefit to these patients. Fn administration to deficient patients was postulated to improve the function of the RES, decrease the incidence of organ failure, sepsis and ultimately mortality. Over the past 15 years, several clinical studies have been performed to test these hypotheses. The initial anecdotal studies using cryoprecipitate (a plasma fraction enriched in Fn) revealed promising results but were neither controlled nor blinded. Further controlled studies were published utilizing both cryoprecipitate and purified Fn. Unfortunately, the great majority of authors found no beneficial effects of Fn administration in critically ill patients, in relation to incidence of organ failure, sepsis, or mortality. These results do not support the use of Fn in this setting. Fn utilization in wound healing has shown promising results in case reports. Although its role in wound healing is not yet fully delineated, initial reports with corneal wounds show a beneficial influence of Fn administration. Further studies are needed to determine the exact function(s) of Fn in a healing wound. Efficacy must still be shown in controlled clinical trials; dosing and administration regimens need to be elucidated.
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PMID:Current status of fibronectin in transfusion medicine: focus on clinical studies. 192 27

To better understand the role of granulocyte elastase (GE) in mediating tissue injury during sepsis, GE levels were measured in plasma and bronchoalveolar lavage fluid (BALF) in patients with septic shock (n = 16) and hemorrhagic shock (n = 30). Granulocyte elastase levels were compared to levels of alpha 1-protease inhibitor (alpha 1-PI). Results show that although plasma GE-alpha 1-PI complex was initially elevated in patients with hemorrhagic and septic shock, elevations in plasma GE-alpha 1-PI complex (831 +/- 241 micrograms/L) persisted in septic shock patients. alpha 1-Protease inhibitor levels in serum were increased, resulting in an inhibition of serum GE activity. Granulocyte elastase activity in BALF, however, was significantly higher in those patients with septic, as compared to hemorrhagic shock (31.4 +/- 25.8 versus 3.7 +/- 4.0 U/L, respectively). In addition GE levels were compared to other parameters, including respiratory index, blood neutrophil count, and plasma levels of endotoxin, fibronectin, and coagulation factor XIII. Significant correlations were observed between GE-alpha 1-PI and increased endotoxin concentration and decreased fibronectin and coagulation factor XIII levels. Significant correlation was found also between GE activity in BALF and respiratory index. These findings suggest that severe tissue damage occurred in patients with septic shock complicated by multiple-organ failure. Although GE activity appeared to be adequately inhibited by alpha 1-PI in blood, increased GE activity in local tissues, such as lung alveoli, may be responsible for significant local tissue injury during septic shock.
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PMID:Role of granulocyte elastase in tissue injury in patients with septic shock complicated by multiple-organ failure. 198 43

Acute gestational pyelonephritis infrequently leads to nonhydrostatic permeability pulmonary edema known clinically as acute respiratory distress syndrome (ARDS). In this form of ARDS, sepsis is considered the primary cause of pulmonary dysfunction. Decreases in colloid osmotic pressure, plasma fibronectin, and arterial oxygen saturation are associated with a worsening prognosis in septic conditions. We sought to investigate the changes in these parameters with acute gestational pyelonephritis to gain insight into the factors that may place the patient at risk for sepsis-related morbidity. Colloid osmotic pressure, plasma fibronectin, and arterial oxygen saturation via pulse oximetry were prospectively measured during the inpatient treatment of 17 pregnant patients with acute gestational pyelonephritis. All three parameters achieved their nadir within 24 hours of hospitalization and the initiation of therapy. Although no patient developed significant pulmonary dysfunction, we believe that patient susceptibility for pulmonary edema and general morbidity could be maximal in the first 24 hours after therapy. Future studies using a larger number of patients may identify one or more of these laboratory parameters as helpful in identifying gravid patients who are at risk of developing gestational ARDS.
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PMID:Acute gestational pyelonephritis: the impact on colloid osmotic pressure, plasma fibronectin, and arterial oxygen saturation. 202 86

Basic therapeutic methods based on early diagnosis of septic ARDS were described. Concerning early diagnosis exertional hypoxemia and increased broncho-vascular markings on chest X-ray were observed in the pre-ARDS stage of septic patients. These findings were also observed in the initial stage of endotoxin-induced pulmonary edema in rabbits and the basic mechanisms were thought to be as follows, based or our experimental studies. The former is related on impairment of alveolar diffusion and the latter reflect increased peri-vascular cuffing due to increase in pulmonary edema. The diffuse infiltrative shadows on the both back area in CT scanning was also a helpful sign indicating the early stage of pulmonary edema. This finding was seen at the stage at which the edematous shadow had not yet appeared on conventional chest X-ray. Increase in serum laminin and decrease in plasma fibronectin were also important biochemical findings predicting ARDS in gram negative sepsis. Using these findings, it is considered that early prediction of septic ARDS is possible. Concerning therapeutic methods based on early prediction, the usefulness of cortico-steroids and the protease inhibitor "Urinastatin" were observed in experimental in vitro and in vivo studies. Some findings induced by endotoxin administration in rats or rabbits, such as the increase in endotoxin in peripheral blood, the distraction of PMN-elastase, the increase in pulmonary lymph flow and mortality within 48 hours were significantly suppressed by simultaneous treatment by corticosteroid. In an in vitro study, PMN superoxide production and elastase release following incubation of endotoxin and PMNs were significantly inhibited by adding a concomitant level of corticosteroid and/or urinastatin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Sepsis and ARDS]. 203 89

The levels of fibronectin, alpha-1 antitrypsin, and fibrinogen have been studied in 34 patients after orthotopic liver transplantation (OLT). Patients were grouped according to A: postoperative course without complications (n = 18), B: development of sepsis accompanied by organ insufficiency (n = 8), and C: acute rejection (n = 6). The plasma levels of alpha-1 antitrypsin and fibrinogen did not show a typical pattern with respect to the postoperative course. The levels of fibronectin, however, did respond to the postoperative events. Starting from a subnormal level a significant increase was observed in group A (p less than 0.005) and C (p less than 0.05) whereas in group B plasma levels remained low. Significant differences (p less than 0.05) were found on day 3 and 5 between group A and C and group B and C. At the end of the observation period survivors (group A and C) had significantly higher levels of fibronectin than nonsurvivors (group B). Therefore fibronectin might aid to diagnose immunologic disturbances after OLT.
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PMID:[Plasma proteins in the early postoperative course after liver transplantation]. 209 69

Time-dependent serum concentrations of extracellular matrix proteins were studied in 32 patients with pancreatitis in order to find potential markers of the reparative response during the disease. Patients were subdivided by clinical and biochemical criteria: severe acute pancreatitis (n = 10), moderate acute pancreatitis (n = 17), and acute attack of chronic pancreatitis (n = 5). Serum and plasma samples were collected on days 1-7, 10, 14, and 21 for measurements of the aminoterminal propeptide of type III procollagen (PIIINP), hyaluronic acid, laminin, fibronectin, and routine clinical-chemical parameters. During an acute attack of chronic pancreatitis all parameters were within the reference range. In moderate acute pancreatitis concentrations of PIIINP, laminin, and hyaluronic acid fluctuated around the upper reference limit, but declined to mid-normal levels at day 21. In severe acute pancreatitis all three parameters increased. In patients who died as a consequence of sepsis and multi-organ failure the increase in PIIINP, laminin and hyaluronic acid was much more pronounced and paralleled by a decrease in plasma concentrations of fibronectin. In conclusion, this study revealed a relation between the severity of acute pancreatitis and the increase in serum concentrations of extracellular matrix components, especially PIIINP.
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PMID:Follow-up of the serum levels of extracellular matrix components in acute and chronic pancreatitis. 212 79

The level of plasma fibronectin was measured to 20 patients suffering from erysipelas and 10 normal controls. Significantly low levels of plasma fibronectin were detected in the group of patients (134 +/- 7.4 g./ml) in comparison to the normal control group (352.6 +/- 42.9 g./ml) p less than 0.001. This could be of prognostic value and also of therapeutic one. Some centres have tried fibronectin replacement therapy in the treatment of critically ill patients with severe bacterial sepsis.
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PMID:Plasma fibronectin level in erysipelas. 213 94


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