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Biomedical subjects

B Osterud

Publications and source records attributed to B Osterud.

At least 91 records · Page 5Linked to original sources

Mononuclear phagocyte thromboplastin and endotoxin in patients with secondary bacterial peritonitis.

Endotoxin levels and mononuclear phagocyte thromboplastin activities in samples from peripheral blood and peritoneal fluid were determined in nine patients with secondary bacterial peritonitis (appendicitis with perforation, or diverticulitis) and in five control patients (uncomplicated duodenal ulcer or gallbladder stones). None or only negligible amounts of endotoxin, always less than 0.01 ng/dl (contamination), and no growth of bacteria were detected in controls. In the patients with peritonitis, peritoneal fluid samples always contained gram-negative bacteria, and large amounts (mean, 31.6 ng/dl) of endotoxin were seen. Plasma from these patients also contained endotoxin (mean, 0.56 ng/dl) despite negative blood cultures. Mononuclear phagocytes from controls had low thromboplastin values, whereas both circulating monocytes and peritoneal macrophages from peritonitis patients showed a substantial increase (multifold) of thromboplastin.

Adolescent↗

Rare factor VII variant inherited through genetic variant in proband's mother and another genetic variant in proband's father.

An 11-year-old girl with hereditary factor-VII deficiency and her family have been studied for factor VII coagulation activity (VII:C) and factor VII antigen level (VII:Ag). The proband had 11% VII:C, whereas her VII:Ag was at a level that corresponds to about 50% coagulation activity. Forty-two members of the proband's family were tested. This study disclosed that the proband's factor VII deficiency had been inherited through both her mother and her father. Although her father was dead, testing of her father's family showed a factor VII defect of the type VII+ variant, that is, normal production of VII:Ag but reduced VII:C. The maternal side of her family was found to have reduced but identical levels of VII:C and VII:Ag (variant VIIR). The proband's factor VII deficiency is therefore apparently inherited through two different variants, and that could explain this rare genetic type of factor VII deficiency. To our knowledge no such variant has ever been described.

Antigens↗

Effect of antibiotics on gram-negative sepsis in the rat. Lack of endotoxin burst.

Endotoxin and monocyte thromboplastin activity were evaluated in rats with gram-negative septicaemia induced by caecal perforation or intravenous Escherichia coli challenge and treated with antibiotics or placebo. Endotoxin burst was not detected in either form of septicaemia during antibiotic treatment. Thromboplastin synthesis in monocytes is known to be stimulated by endotoxin, but the rats showed no increase of monocyte thromboplastin activity after antibiotic treatment, which constituted further evidence against the concept of massive endotoxin liberation during antibiotic therapy for gram-negative septicaemia.

Animals↗

Splenectomy in the rat. Immediate and late effects on clearance of gram-negative bacteria and on monocyte activation as expressed by thromboplastin synthesis.

Young rats (weight 190-200 g) were subjected to splenectomy or sham laparotomy and gram-negative bacteraemia was induced by caecal perforation or by injection of viable Escherichia coli intraperitoneally (10(9) bacteria) or intravenously (2 X 10(8]. Clearance of bacteria was significantly less in the splenectomized than in the sham-laparotomized rats, irrespective of the mode of microbial inoculation. Monocyte thromboplastin activity, shown to be a sensitive indicator of gram-negative bacterial presence, was heightened in the asplenic rats. When the infectious challenge was made 15 weeks postoperatively, however, no significant difference in bacterial clearance or in monocyte thromboplastin values was found between splenectomized rats and controls. Nor was increased susceptibility to gram-negative bacteria found in asplenic rats when both operation (splenectomy vs. sham laparotomy) and bacterial challenge were performed at a late age (weight 530-580 g). The postsplenectomy clearance of gram-negative bacteria thus seemed to be age-dependent.

Animals↗

Effects of ethanol on human blood fibrinolysis and coagulation.

The effect of ethanol (serum concentrations 10 and 22 mM) on whole blood clotting time, thromboplastin activity and whole blood clot lysis time were studied in eight healthy humans. Each subject serving as its own control. Ethanol (22 mM) increased the whole blood clotting time by 26 +/- 29% (p less than 0.05), whereas the thromboplastin activity (in both unstimulated and endotoxin stimulated monocytes) was significantly decreased in presence of ethanol (both 10 and 22 mM). The whole blood clot lysis time was increased by 83 +/- 9 and 260 +/- 178 percent in presence of 10 and 22 mM ethanol respectively. After the high ethanol doses, ten hours after the end of the voluntary ethanol intake, the whole blood clot lysis time was increased with 133 +/- 105 percent. According to the present findings, acute ethanol intake affect blood fibrinolysis activity, as measured by whole blood clot lysis time, in a way which might precipitate a state of increased risk of thrombotic diseases.

Adult↗

Thromboplastin content in the vessel walls of different arteries and organs of rabbits.

Homogenized arterial walls of rabbits were shown to possess significant amounts of thromboplastin activity. The specific activity, percent activity per mg tissue, varied in different arteries. Thus the thromboplastin activity of the carotid was found to be about ten-fold higher compared to the femoral. Thromboplastin activity measurements of different organs revealed a very high level of thromboplastin in lung, whereas kidney and spleen had respectively 6 and 25 times less activity than the lung. Induction of generalized Shwartzman reaction by giving two doses of endotoxin 24 hours apart, caused no significant rise in thromboplastin activity of either arteries or organs, but induced a 35-fold increase of thromboplastin activity of circulating monocytes. The very high thromboplastin activity in the lung probably reflects the widespread and dense population of vessel in this particular organ. It is concluded that the amount of thromboplastin present in the vessel wall gives the possibility for a potent activation of the clotting system in normal haemostasis.

Animals↗

Experimental gram-negative peritonitis: decreased thromboplastin activity in organs with a simultaneous rise of thromboplastin in blood monocytes and peritoneal macrophages.

Thromboplastin values in blood monocytes, peritoneal macrophages, and in tissue samples from lung, aortic wall, liver, spleen, pancreas, kidney, jejunum, and colon were determined at 4, 10, and 16 h after induction of acute peritonitis (cecal perforation) or sham operation in rats. A maximum 35-fold and 100-fold rise of values was respectively demonstrated in monocytes and peritoneal macrophages in septic animals as compared to controls. This monocyte-macrophage-derived thromboplastin is probably central to the activation of blood coagulation and fibrin depositions/adhesion formation in septic peritonitis. A simultaneous and significant fall in thromboplastin content of standardized specimens from lung, aortic wall, liver, spleen, pancreas, and jejunum was observed in rats with peritonitis. This could reflect mobilization of thromboplastin in favor of the infectious focus. No significant changes were detected in tissue from kidney, whereas samples from the colon of septic animals showed a consistent increase as compared to controls.

Animals↗

Thromboplastin activity in blood monocytes from oral contraceptive users.

The thromboplastin activity in blood monocytes from 13 women on oral contraceptives and from a reference group of 20 women not on oral contraceptives has been compared. The thromboplastin activity in endotoxin-stimulated monocytes from the oral contraceptive (OC) users was on average 54% of the activity in the reference group (p less than 0.05). The thromboplastin activity in unstimulated monocytes was also lower in the OC group than in the reference group although not statistically significant. Factor VII was significantly higher (p less than 0.05) in the OC group, whereas no difference was observed in fibrinogen and factor V levels.

Adult↗

Endotoxin-induced human and porcine leucocyte reactions in vitro.

Tube migration of a fixed number of PMN cells in plasma (5 X 10(9) cells/l) was approximately reduced by 50% when 1 ml of cell suspension was exposed to 20 micrograms E. coli endotoxin in 100 microliter NaCl for 2 hours. Procoagulant activity in monocytes increased approximately eight-fold when 1 ml of whole blood was exposed to 2 ng endotoxin in 10 microliters NaCl for 2 hours. Chemiluminescence in both PMN cells (5 X 10(9) cells/l) and mononuclear cells (2 X 10(9) cells/l) in plasma was markedly increased when 100 microliters cell suspension was added to 100 microliters Luminol, exposed to 20 micrograms endotoxin in 100 microliters NaCl and tested immediately. Decreased lysosomal enzyme levels in PMN and mononuclear cells were demonstrated when 1 ml cells in plasma (the same cell numbers as aforementioned) were incubated for 4 hours at 37 degrees C with 200 micrograms endotoxin in 100 microliters NaCl. Similar results were obtained in human and porcine leucocytes, making the pig a suitable animal for studies of humoral and cellular reactions to infections complications following trauma and major surgery.

Animals↗

Mononuclear phagocyte thromboplastin, bacterial counts and endotoxin levels in experimental endogenous gram-negative sepsis.

The relationship between mononuclear phagocyte thromboplastin activity, microorganisms and levels of endotoxin in peritoneal fluid and splanchnic and systemic circulation was evaluated during experimental endogenous gram-negative peritonitis in the rat. Significant rise in thromboplastin activity of mononuclear phagocytes was demonstrated in all three compartments. This newly synthesized thromboplastin is a trigger for important biologic systems such as the coagulation cascade, and thus may play a major role in the development of disseminated intravascular coagulation so often occurring in gram-negative sepsis. It probably also participates in the formation of fibrous intraabdominal adhesions. Aerobic and anaerobic microorganisms together with endotoxin were detected already 1 1/2 hours after induction of peritonitis, and subsequently were found to increase in parallel fashion. Determination of endotoxin is a rapid and seemingly reliable method for early detection of gram-negative infection and thus may be of clinical value.

Animals↗

Reduced thromboplastin activity in blood monocytes and reduced sensitivity to stimuli in vitro of blood monocytes from pregnant women.

The thromboplastin activity in blood monocytes from 18 normal third trimester pregnant women has been compared with a group of 20 healthy non-pregnant women. The thromboplastin activity in unstimulated monocytes from the normal pregnant group was on average 40% of the activity in the non-pregnant group (P less than 0.01). In endotoxin stimulated monocytes, the thromboplastin activity was also significantly lower in the pregnant group as compared to the non-pregnant group (P less than 0.001). Fibrinogen and factors V, VII and VIII were significantly higher in the pregnant than in the non-pregnant group, whereas no difference was observed in AT-III, prekallikrein and alpha 2-antiplasmin levels.

Adolescent↗

Increased sensitivity to thromboplastin synthesis in blood monocytes from pre-eclamptic patients.

The thromboplastin activity in blood monocytes was investigated in third-trimester pregnancies comprising 11 patients with severe pre-eclampsia, 10 with essential hypertension and 18 normal pregnancies. Thromboplastin activity in unstimulated monocytes from the severe pre-eclamptic group was on average three times that found in the normal pregnant group, but variation was wide and the differences were not statistically significant. Thromboplastin activity in endotoxin-stimulated monocytes was significantly higher in the severe pre-eclamptic group than in the other two groups (normal and chronic hypertensive). In the severe pre-eclamptic group, there was a significant negative linear correlation between thromboplastin activity of the endotoxin-stimulated monocytes and factor VII. Fibrinogen, factor VII and alpha 2-antiplasmin were significantly lower in the severe pre-eclamptic group than in the normal pregnant group, whereas no differences were observed in factors V, VIII, AT-III and prekallikrein.

Adult↗

Thromboplastin activity in amniotic fluid.

Thromboplastin activity in amniotic fluid from 39 patients pregnant in weeks 14-40 has been studied. Amniotic fluid was obtained by amniocentesis. All fluids were fractionated and the activity studied in both supernatant and sediment in a highly specific and sensitive test system. All samples tested showed a very high thromboplastin activity. No correlation to gestational age was found. Amniotic samples from 19 of the patients were incubated with endotoxin. Endotoxin did not further increase the procoagulant activity.

Amniotic Fluid↗

Interaction of endotoxins, blood elements and the vessel wall.

Endotoxins are potent activators of the complement system. Formed activated complement factors, in turn, are capable of inducing metabolite production that may be essential in the killing of parasites. However, the products formed may also induce severe damage and cause great pathological changes that can be fatal for the individual infected. In the present review article the interaction of endotoxin with monocytes, granulocytes and endothelial cells, as well as the central role of complement activation will be discussed. Also a method is provided for the detection of cell activation in Neisseria meningitidis infection.

Animals↗

Tissue thromboplastin generation in circulating mononuclear phagocytes and development of coagulation disorders during E. coli endotoxinaemia in pigs.

Tissue thromboplastin generation in monocytes was studied during various stages of Escherichia coli endotoxinaemia in pigs. The pigs were monitored in halothane anaesthesia and mechanically ventilated. Blood was sampled from the superior caval vein before and during endotoxin infusion and up to 6 hours after its start. Monnuclear leukocytes were harvested with Lymphoprep separation and monocyte counts were made, using TRITC-labelled sheep erythrocytes, acridine orange and a fluorescence microscope. Thromboplastin was quantified in a two-stage assay by incubating the test sample together with purified factor X, factor VII and Ca++. The generated factor Xa was thereafter assayed. There was statistically significant increase of tissue thromboplastin activity in monocytes after endotoxin infusion. Maximum level was reached at the end of the infusion and was maintained throughout the observation period. Decrease occurred in platelets, leukocytes, antithrombin III, fibrinogen and clotting factors V, VII and VIII, and clotting time was prolonged. These findings indicated significant disseminated intravascular coagulation. The endotoxin-stimulated monocytes with their elevated tissue thrombo-plastin activity thus may play an important part in development of the DIC which so often follows septicemia.

Animals↗

Faecal peritonitis in the rat. An experimental model for evaluation of surgical and adjuvant therapies.

Wistar rats were equipped with two central venous catheters used for parenteral nutrition/antibiotics and blood sampling. The rats were conditioned in special cages and given a meat pellet diet to achieve a bowel flora more similar to man. When the animals after two weeks were adjusted to life in cages, meat pellets and indwelling non-functioning venous catheters, peritonitis was induced with a standardized 3 mm caecal perforation without any ligation or devascularization. Within few hours the animals were severe septic and blood cultures were positive in all with a mixed flora of gram-negative coliforms and anaerobic bacteroides. Important occurrence of circulating endotoxin was detected and found to increase gradually till death. Without any treatment this form of septic peritonitis gave a 100% mortality. Total parenteral nutrition (TPN) reduced mortality to 50%. Substitution of TPN with a simple saline/glucose solution gave the same survival rate demonstrating the importance of fluid supply and crystalloids during the early phase of septicaemia. Intravenously given antimicrobial agents active against anaerobes (tinidazole) and aerobes (cefotaxim) will in combination reduce mortality to less than 15%. The lethal effect of a 3 mm caecal perforation was almost abolished when TPN was added to this combination of antimicrobial agents. Continuous peritoneal irrigation did not increase survival rate.

Animals↗