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 gastromucosal barrier (GMB) can be disrupted by a number of aggressive factors or by a decrease in mucosal defense factors. If there is back diffusion of hydrogen ions into the mucosa, mucosal damage ranging from an erythematous gastro-duodenitis to erosive and ulcerative gastritis or life-threatening hemorrhage may ensue. The pathogenesis of stress-related mucosal damage seen in critically ill patients suffering from burns, sepsis, head trauma, respiratory insufficiency, or multisystem disease is also related to a decrease in mucosal resistance. Early studies of cimetidine in animals and in humans demonstrated its ability to increase gastric transmucosal potential difference, indicating an enhancement of the integrity of the GMB. Several studies show that cimetidine protects the stomach from aspirin-induced mucosal damage; increases gastric mucus production and mucus glycoprotein content, which contributes to the protective action of mucus; increases mucosal secretion of bicarbonate; increases gastric mucosal blood flow, which prevents mucosal hypoxia seen in patients in shock or otherwise critically ill patients; increases endogenous mucosal prostaglandin synthesis; and increases the rate of epithelial cell renewal, a factor important to mucosal healing. Since cimetidine suppresses acid secretion and enhances mucosal defense, it is an important therapeutic tool in the management of acid-related disorders, particularly stress-related mucosal damage.
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PMID:Gastric acid secretion and mucosal defense mechanisms with special reference to the role of cimetidine in critically ill patients. 353 48

1. Plasma fibronectin, a glycoprotein, is an opsonin of the reticuloendothelial system. 2. In ten healthy volunteers starved for 4.5 d, daily measurements showed a rapid reduction in plasma fibronectin, no alteration in either C3 or plasma transferrin and, at the end of the starvation period, an elevated serum albumin. 3. On refeeding, plasma fibronectin rapidly returned to its prestarvation level but plasma transferrin was significantly reduced and did not recover by the end of the study. 4. Changes in plasma fibronectin may be a sensitive index of nutritional status. The reduction of plasma fibronectin in short-term starvation may compromise host defence tolerance of injury and sepsis.
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PMID:Changes in plasma fibronectin during acute nutritional deprivation in healthy human subjects. 366 79

Clindamycin pharmacokinetics was compared in critically ill patients with sepsis and healthy volunteers, and the relationship between pharmacokinetic values and physiological measurements obtained from the critically ill patients was characterized. Pharmacokinetic evaluations were performed on 10 patients with sepsis who were receiving clindamycin phosphate 900 mg i.v. every eight hours and on 6 previously studied healthy men receiving the same dosage regimen. Physiological variables measured included age, weight, cardiac index, systemic vascular resistance, central venous pressure, liver-function tests, alpha 1-acid glycoprotein concentration, and APACHE II score. Clindamycin was administered to the critically ill patients via a central venous catheter over 30 minutes; the healthy volunteers received their infusions via a peripheral venous catheter over 30 minutes. Blood samples were obtained at five minutes before and at various intervals after drug administration. Serum clindamycin concentrations were determined by a gas-liquid chromatographic method. Serum concentration data were analyzed using noncompartmental methods based on statistical moment theory, and the a priori level of significance was 0.05. The critically ill patients had significantly increased values for area under the curve (AUC), area under the moment curve (AUMC), mean residence time (MRT), and average concentration at steady state (Css), while total body clearance (TBC) was less than half that in the healthy volunteers. TBC in three of the critically ill patients was not different from that in the healthy volunteers. The apparent volume of distribution at steady state (Vss) was not significantly different between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Decreased hepatic clearance of clindamycin in critically ill patients with sepsis. 366 68

Low plasma levels of the opsonic glycoprotein fibronectin (Fn) have been suggested to imply an impaired host defense against sepsis. However, the mechanism(s) behind Fn depletion in sepsis are obscure. We measured the Fn plasma concentration in 32 patients 12 to 24 h after the diagnosis of septic shock. Although the average plasma level was low (214 +/- 80 [SD] mg/L) compared to that of a reference material (p less than .001), the range was great (60 to 403 mg/L). A multivariate analysis of some possible influencing factors showed significant (p less than .01) positive correlations to the prothrombin level (r = .62) and the amount of insulin infused per 24 h (r = .63). The relationships to disseminated intravascular coagulation-related variables, hemodilution, and outcome were weak. Cryoprecipitate was infused into 16 patients; Fn levels increased by 52 +/- 18% of the expected increase. The most severely ill patients displayed the lowest rates of increase. The postinfusion decrease in Fn plasma concentration indicated that the plasma half-life of cryoprecipitate Fn was about 25 h. The results support the concept that decreased Fn synthesis, probably in the liver, is the major reason for Fn depletion in sepsis, rather than an increased rate of consumption.
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PMID:Plasma fibronectin levels in sepsis: influencing factors. 367 61

Fibronectin is a glycoprotein found in a soluble form in plasma and in an insoluble form in many tissues. We evaluated the influence of postoperative intraperitoneal sepsis on the clearance, tissue distribution, and synthesis of plasma fibronectin in rats (300-400 g). Experimental sepsis was induced by cecal ligation following laparotomy, whereas control animals underwent laparotomy (5 cm) alone. At 24 and 48 h after laparotomy, plasma fibronectin levels were normal. After laparotomy plus cecal ligation, plasma fibronectin increased by 47% at 24 h and remained elevated (52% above 0 time) at 48 h. At 24 h postsurgery the disappearance and tissue distribution of 75Se-plasma fibronectin and 75Se-plasma albumin was evaluated. Tissue distribution was quantified at 2 and 24 h after intravenous injection of both tracer proteins in separate groups. Both fibronectin and albumin demonstrated an initial distribution between vascular and extravascular sites and then a progressive decrease in plasma. In control (laparotomy) rats the half-life (t1/2) for plasma clearance of 75Se-plasma fibronectin was 25.33 +/- 2.53 h compared with 13.21 +/- 0.78 h in the septic rats. Septic rats manifested decreased sequestration of 75Se-fibronectin at the area of surgical incision (laparotomy), increased sequestration at the focus of intraperitoneal infection, and increased uptake in the nonviable portion of the cecum. The synthetic rate for plasma fibronectin in laparotomized control rats was 3.03 +/- 0.29 mg X 100 g-1 X 24 h-1, whereas after laparotomy plus cecal ligation the synthetic rate increased to 4.58 +/- 0.35 mg X 100 g-1 X 24 h-1. In contrast the synthetic rate for albumin decreased from 84.70 +/- 1.66 mg X 100 g-1 X 24 h-1 in controls to 52.38 +/- 1.77 mg X 100 g-1 X 24 h-1 in the septic animals. Thus intraperitoneal sepsis in the rat will enhance the vascular clearance, alter the distribution, and increase the synthetic rate for plasma fibronectin.
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PMID:Clearance and tissue distribution of fibronectin in septic rats: relationship to synthetic rate. 376 72

Plasma fibronectin (FN) is one of the major blood opsonins. The content of the glycoprotein reduces in sepsis which in turn may aggravate the course of the infection. FN is detectable in the content of cryoglobulins and cryofibrinogen. The formation of the heparin precipitate following plasma incubation in the cold in the presence of heparin is determined by FN involvement. Fibrinogen (FG) is another main component of the heparin precipitate. To determine the functional activity of plasma FN in sepsis and other pathological conditions, a study was made of the ability of FN and FG to go into the precipitate formed in blood plasma in the cold after its incubation with heparin. Unlike normal subjects in whom over 80% of FN on the average and about 20% of FG went into the heparin precipitate, in patients with hemoblastoses and aplastic anemia complicated by sepsis, less than 40% of FN on the average and about 7% of FG went into the precipitate. In some patients with sepsis, the heparin precipitate did not form. The reduction of FN ability to go into the heparin precipitate correlated with the gravity of the patients' condition. In uncomplicated hemoblastoses, cryoglobulinemia and cryofibrinogenemia and in immunocomplex pathology, the consumption of FN and FG during heparin precipitate formation did not significantly differ from the control. The data indicate that sepsis patients with blood system pathology may develop not only quantitative FN deficiency in the blood but also disorder of the functional activity of the opsonin.
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PMID:[Decreased effectiveness of cold-induced heparin precipitation of plasma fibronectin in infection]. 379 36

Low levels of plasma fibronectin (PFN), an adhesive glycoprotein postulated to augment reticuloendothelial function, can predispose animals to a poor clinical outcome following sepsis. In the present study, the PFN levels of adult male rats were measured prior to injection of intraperitoneal Escherichia coli and/or stroma-free hemoglobin (SFH) and subsequently at 4, 24, and 48 hours. Intraperitoneal E coli alone elicited insignificant PFN level depression at four hours, with significantly elevated levels only in the high-dose group at 24 (P less than .05) and 48 hours (P less than .01). Intraperitoneal SFH alone did not alter PFN levels from baseline values; when combined with E coli significant four-hour level depression is noted (P less than .05). Elevation of PFN levels by 24 hours occurs in a dose-dependent fashion, returning to baseline values 48 hours postinoculation. Significant mortality was observed only with high doses of E coli combined with SFH. The PFN levels are elevated 24 to 48 hours following high-dose E coli injection. Stroma-free hemoglobin alone has no effect, but when combined with E coli results in PFN level depression four hours postinoculation, contributing to impairment of systemic host defenses and possibly predisposing to greater mortality.
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PMID:Plasma fibronectin response to Escherichia coli and hemoglobin. 388 48

Plasma fibronectin is regarded to play an important part in a decrease of the resistance to infections. To specify the role of fibronectin in the pathogenesis of infectious complications in patients with depressions of hemopoiesis, the content of this opsonin was measured by ELISA in 113 patients with different patterns of hemoblastoses, lymphoproliferative diseases and with an aplastic syndrome. In 42 patients, the concentration of opsonin was measured in the presence of the superimposed infection of varying gravity. The fibronectin content was examined in 39 patients before, during and after completion of the cytostatic polychemotherapy. It turned out that in patients with paraproteinemic hemoblastoses, lymphogranulomatosis, aplastic anemia, chronic lympholeukemia, acute lympho- and myelo(mono)blastic leukemias, cyclic neutropenia, chronic myelosis and hematosarcomas, the concentration of fibronectin remained normal in the absence of infections. The computation of the linear correlation ratio did not reveal any association between the opsonin level and the concentration of neoplastic elements in the peripheral blood. Repeated measurements of the fibronectin level in patients whose underlying disease ran its course in association with marked neoplastic fever failed to detect any deficiency of the glycoprotein. The lowering of the fibronectin level was recorded in patients with a grave concomitant infection of the type of sepsis, necrotic enteropathy and lobar pneumonia. The degree of opsonin deficiency correlated with the patients' disease gravity. Prolonged reduction in the blood fibronectin level was of unfavourable prognostic importance. Cytostatic polychemotherapy, myelotoxic agranulocytosis as well as infectious complications of low gravity did not influence the concentration of fibronectin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Plasma fibronectin level in patients with depression of hematopoiesis]. 404 64

No single diagnostic test for neonatal sepsis is both rapid and reliable. Combining leukocyte (wbc) counts with acute phase reactants (APR) enhances diagnostic accuracy. The most helpful wbc counts are leukopenia (less than 5.0 x 10(9)/l), increased immature/total neutrophils (greater than or equal to 0.2) and profound neutropenia (less than 1.0 x 10(9)). Of the APR, C-reactive protein responds most rapidly, but alpha 1-acid glycoprotein (orosomucoid), haptoglobin and mini-ESR (greater than or equal to 15 mm/h) are also useful. Rapid, quantitative determinations of APR are now available with nephelometric techniques. Abnormal wbc counts frequently appear before APR changes in group B streptococcal infection. Sequential determinations of wbc counts and APR may provide valuable diagnostic and prognostic information.
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PMID:White blood cells and acute phase reactants in neonatal sepsis. 608 34

Fibronectin (FN) is a glycoprotein (disulfite-bonded dimer of 200 to 220 Kd submits) found in a soluble form in blood (concentration 250--500 microg/ml), it can be removed from it by cryoprecipitation and affinity chromatography on gelatin or heparin-agarose. It is also found in an insoluble fibrillar form as a component of connective tissue matrix like collagen, proteoglycans... FN fundamentally forms molecular complexes with collagen, fibrinogen or fibrin, heparin, activated factor XIII, bacteria, cellular membranes..., these various proteins binding with now well known functional "domains" on subunits. Thus FN mediates adhesion of cells to cells as well to biomaterials or tissue, cell migration and chemotactic activity, tissue stromal organization... The transformed cultured cells in presence of oncogen virus loose ability to secrete FN which contribute to their invasive tendency. FN also interacts with hemostatic and fibrinolytic systems, as component of the subendothelium (secreted, like Willbrand factor, by endothelial cells) and of platelet alpha-granules released by stimulated platelets. FN could then provoke platelet spreading on the subendothelium surface after collagen-platelet adhesion, triggered by Willebrand factor, has happened. FN is a part of the fibrinous clot. It participates in anchorage of the clot to subendothelium and mediates its colonisation by fibroblasts, first step to wound reparation. Lastly FN probably has an important role in organism defence. It acts as a non-immunological opsonin, promoting phagocytosis by RES macrophages of bacteria, cellular or fibrin fragments, immune complexes... present in blood. Plasmatic FN concentration is strongly decreased in several ill patients following major trauma, extensive burns, shock, sepsis, with or not evidence of DIVC, of respiratory distress... SABA and various other authors have obtained good results after injections of FN (as cryoprecipitates or concentrated fractions). It is yet necessary to confirm therapeutic role of FN.
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PMID:[Plasma fibronectin]. 641


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