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)

Circulating phospholipase A2 (PLA2) has been recognized as a mediator of circulatory collapse in experimental endotoxic shock. To assess the role of serum PLA2 in septic shock in man, we determined serum PLA2 profiles in a prospective study in 12 patients with septic shock. During the hypotensive phase of sepsis, serum PLA2 levels were consistently elevated as high as 33,428 U/ml (normal range 115 +/- 12 [SE]; n = 101). In all 12 patients, PLA2 levels correlated directly with the magnitude and duration of circulatory collapse (p less than .001), with a progressive fall of serum PLA2 levels during convalescence. In contrast, serum PLA2 levels in patients with cardiogenic shock secondary to myocardial infarction remained low. In pancreatitis, PLA2 levels paralleled fluctuations of serum amylase and lipase, whereas in septic shock without pancreatic involvement, PLA2 changes were discordant with changes in pancreatic enzymes. As well, septic shock serum PLA2 failed to crossreact by radioimmunoassay with antiserum against human pancreatic PLA2. These data are consistent with an extrapancreatic source of intravascular PLA2 release during sepsis. Since endogenous serum PLA2 levels correlate directly with the magnitude of hypotension in both experimental endotoxic shock and clinical septic shock, and since parenteral administration of purified exogenous PLA2 reproduces hypotension in experimental models, we conclude that high levels of intravascular PLA2 may contribute similarly to the circulatory collapse in septic shock in man.
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PMID:Pathogenesis of hypotension in septic shock: correlation of circulating phospholipase A2 levels with circulatory collapse. 333 73

Macrophages are induced by LPS to release a number of products that determine the host response during gram negative sepsis. To examine the role of one such substance, tumor necrosis factor (TNF), in mediating LPS-induced injury, we employed a rabbit model of endotoxic shock to (a) determine the kinetics and extent of release of TNF into plasma after injection of LPS, and (b) to evaluate the protective effect of in vivo neutralization of LPS-induced TNF by prior infusion of anti-TNF antibody. TNF was maximally induced 45-100 min after injection of 10 micrograms i.v. parent Salmonella minnesota Re595 LPS or 250 micrograms Re595 LPS-HDL complexes. Maximal induction of TNF by LPS was associated with development of hypotension, focal hepatic necrosis, intravascular fibrin deposition and lethality. Based on (a) the peak levels of TNF observed in serum, 2.5 X 10(3) U/ml, (b) the specific activity of purified rabbit macrophage-derived TNF, 1 X 10(8) U/mg, and (c) the biphasic disappearance of intravenously injected purified TNF (t1/2 = 0.5 min, 11 min) we constructed a kinetic model showing that at least 130 micrograms of TNF (1.3 X 10(7) U) was released into plasma 30-200 min postinjection of LPS. Prior infusion of anti-TNF antibody (30-45 min before LPS injection) resulted in neutralization of the LPS-induced serum TNF activity and provided significant protection from the development of hypotension, fibrin deposition, and lethality. Thus, these results provide further evidence that TNF plays a central role mediating the pathophysiologic changes that occur during gram negative endotoxic shock.
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PMID:Participation of tumor necrosis factor in the mediation of gram negative bacterial lipopolysaccharide-induced injury in rabbits. 338 55

Gram-negative septic shock remains a major clinical problem. One frequently encountered complication of sepsis is disseminated intravascular coagulation (DIC). The present study was to determine in an Escherichia coli endotoxemia awake rat model the efficacy of antithrombin-III (AT-III) prophylaxis and to explore the role of DIC in the pathogenesis of endotoxemia. We demonstrated that DIC occurs very early, before the appearance of detectable serious abnormalities in cardiovascular, metabolic, and biochemical variables indicative of organ damage or dysfunction; AT-III prophylaxis significantly ameliorates DIC, as evidenced by completely preventing the fall in plasma fibrinogen concentration and significantly limiting the increases in prothrombin time and activated partial thromboplastin time after 4 hours of endotoxemia; and AT-III prophylaxis dramatically increases permanent survival. Results of this study suggest that AT-III prophylaxis is very protective above a threshold dosage in an endotoxemic rat model and that protection is in part due to ameliorating DIC. Our data also suggest that DIC occurs very early during endotoxemia and may in part be responsible for the pathogenesis of endotoxemia in the rat. We conclude that AT-III prophylaxis may be efficacious in conditions of impending DIC, such as gram-negative septicemia/endotoxemia.
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PMID:Protection against disseminated intravascular coagulation and death by antithrombin-III in the Escherichia coli endotoxemic rat. 354 29

An evaluation was made of 106 surgical patients with Gram-negative septic shock, both for clinical criteria as well as the biochemical mediators endotoxin, prostaglandin F2 alpha, prostaglandin I2 (prostacyclin), and thromboxane. These data were correlated to various defined shock phases, functional data of vital organs, and clinical outcome. Patients underwent invasive organ function monitoring and the usual laboratory tests of intensive care. Prostaglandins and thromboxane were measured radioimmunologically, endotoxin by the limulus amebocyte lysate test. Endotoxin proved to be a more accurate predictor of severe sepsis than did positive blood cultures. Endotoxin as well as prostaglandins and thromboxane are predominantly released in early shock phases, appearing in plasma concentrations, which correlate with the severity of organ failure. Sepsis-induced respiratory failure coincides with a deterioration of pulmonary prostaglandin inactivation, which contributes to the release mechanism. High systemic prostacyclin activity benefits the patients' organ functions and clinical outcomes, while a predominance of thromboxane seems to effect the opposite. Transpulmonary-thromboxane gradients correlate significantly with pulmonary hypertension in the early phases of septic shock.
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PMID:The clinical significance of prostaglandins and thromboxane as mediators of septic shock. 355 Feb 66

Endotoxemia and gram negative sepsis remain a clinically important problem since mortality rate is still high in these diseases. Recently, the participation of some new potential mediators in this pathology is beginning to be demonstrated but the results obtained on animal models with specific inhibitors are contradictory. In order to clarify the pathological importance of icosanoids and PAF-acether in the septicemic process, we investigated the effects of indomethacin (IND) a cyclooxygenase inhibitor, NDGA and EP 10045 two lipoxygenase inhibitors, dexamethasone (DXM) a phospholipase A2 inhibitor and BN 52021 a PAF-acether receptor antagonist, on the Salmonella enteritidis-induced endotoxic shock (E.S.) in the rat. Injected subcutaneously 15 min before the test, NDGA, EP 10045 and IND were moderately effective when DXM completely prevented the endotoxin lethality. BN 52021 decreased the death rate in a dose-related manner and exerted at a non-active dose a synergistic effect on IND treatment. Furthermore, given orally 1 hour before endotoxin, it provided a potent protective effect. Our results seem to confirm that PAF-acether exerted alone, or in conjunction with products of the cyclooxygenase pathway, a key role in E.S. when LTs seem to play a role of minor importance.
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PMID:The relative role of PAF-acether and icosanoids in septic shock. 377 51

Records of adolescent girls in Nigeria admitted to the gynecologic ward of the University of Benin Teaching Hospital from 1974-79 show that abortion accounted for 28% of gynecologic admissions in Nigeria. In a review of 244 cases, 60.8% of the patients were adolescent girls and 53.7% of them had septic abortions. 37.5% of the authors' patients already had 1-3 induced abortions or live births at the time of admission and yet had no knowledge of contraception. Only 16.8% were attended by physicians, 9.8% were self induced. The most common complications were hemorrhage, sepsis, cervical laceration, and hypovolemic shock. The main causes of severe morbidity and mortality were uterine and bowel perforation, peritonitis, and endotoxic shock. Several studies indicate that unsuccessful illegal induced abortion is one of the main causes of death among unmarried Nigerian girls of school age, who are ignorant of and lack access to contraception. 2.8% of illegal abortions in this series resulted in death compared to 11% in 1963-67 in Lagos. 62.5% of abortion-related deaths occurred in adolescent girls and 20% of all female adolescent deaths in the entire hospital. Morbidity and mortality associated with adolescent induced abortion are extraordinarily high in Nigeria compared with the U.K., Denmark, and Sweden. The Federal Government of Nigeria is urged to liberalize the abortion law and to provide basic sex education and family planning for adolescent boys and girls in order to discourage criminal abortion and its attendant complications.
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PMID:Adolescent induced abortion in Benin City, Nigeria. 612 34

The potential role of thromboxane (TxA2), a platelet aggregator and vasoconstrictor, and prostacyclin (PGI2) a platelet anti-aggregator and vasodilator, in endotoxic and septic shock was investigated. Early endotoxic shock in the rat is associated with marked elevations of plasma TxB2 (the stable metabolite of TxA2) and lesser increases in plasma 6-keto-PGF1 alpha (the stable metabolite of PGI2). Selective inhibition of TxA2 synthesis by several different chemical classes of Tx synthetase inhibitors was beneficial in endotoxic shock. In contrast, shock induced by acute intra-abdominal sepsis in the rat was characterized by high levels of plasma 6-keto-PGF1 alpha, which exceeded plasma TxA2 six- to eight fold at most time intervals studied. Tx synthetase inhibitors were not protective in this model of acute sepsis, but treatment with fatty acid cyclo-oxygenase inhibitors, an antibiotic (gentamicin), or reduction in arachidonic acid metabolism by essential fatty acid (EFA) deficiency significantly prolonged survival time. An important aspect of the latter study is that decreased arachidonic acid metabolism was an effective adjunct to antibiotic therapy. Conjoint administration of gentamicin in EFA-deficient rats or with indomethacin synergistically improved long-term survival, a result that was not evident with single treatment interventions. In addition to experimental studies, plasma TxB2 levels were measured during clinical sepsis. These studies demonstrated that plasma TxB2 levels were elevated tenfold in patients dying of septic shock compared with septic survivors or nonseptic controls. These composite experimental and clinical observations suggest that arachidonic acid metabolites play a role in the pathogenesis of endotoxic and septic shock.
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PMID:The potential role of thromboxane and prostacyclin in endotoxic and septic shock. 644 May 69

Clinical records of 181 children, aged between one month and seven years, admitted in a four year period, from 1978 through 1982, with the diagnosis of bacterial meningitis are revised. Peak incidence occurred in the age group between six months and three years, and during the months of January to May. N. meningitidis (35%), pneumococcus (4.9%) and H. influenzae (2.7%) were the most frequently isolated bacteria. CSF culture was negative in 56% of the children. All of them had previously taken antibiotics. Complications were present in 6.4%, with highest incidence in the known-agent group, on the following order: septic shock, 11%, seizures, 6.6%, and subdural effusion, 2.2%. Permanent sequelae were present in 3.8%, being deafness predominant. Twelve (6.3%) out of the 181 died, and death was result of fulminant meningococcal sepsis with endotoxic shock in ten of these patients. Clinical and psychological followed-up of twenty-nine children with isolated causal agent, were compared with a control group, finding no statistically-significant difference.
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PMID:[Bacterial meningitis in children. Analysis of 181 cases]. 650 29

283 records of all Wellington, New Zealand, Hospital patients categorized as having had a septic abortion from 1960 to 1979 were retrieved and reviewed; 7 records could not be found. Morbidity was assessed by duration of hospital stay and the incidence of complications. Septicemia was defined by a positive blood culture rigors. Hypotension was assumed to be due to hemorrhage unless endotoxic shock was positively identified. Significant hemorrhage was also diagnosed if a blood transfusion was required. The annual number of admissions for septic abortion over the 20-year period decreased substantially: 203 cases from 1960 to 1969 and 80 cases from 1970 to 1979. The total number of abortion admissions of all types also decreased over the same period. During this period the total number of births in Wellington public hospitals initially increased and then declined, suggesting some degree of independence between total abortions and birthrate. The peak of total abortions in 1978-79 represents the initial increase in hospital therapeutic abortions under the Contraception, Sterilization and Abortion Act 1977. The gestational age at the time of septic abortion ranged from 7 to 26 weeks. The mean gestation by year ranged from 8.6 to 15 weeks. No trend was obvious. The mean duration of hospital stay declined, e.g., 7.3, 7.6, 6.0, and 5.3 days in successive 5-year periods. Morbidity was greater during the 1st decade but there were 2 patients who in 1974 and 1975 stayed 23 and 28 days, respectively. Septicemia patients numbered 39 (35%) in the first 5 years, and fell successively to 31 (33%), 17 (36%), and 6 (17%) in each succeeding 5-year period. A similar trend was noted for significant hemorrhage: 38 (34.5%), 39 (42%), 13 (28%), and 3 (8.5%) between 1975 and 1979. Only maternal death due to septic abortion occurred in 1960. The patient was noted to be fairly "feebl minded" and the diagnosis was delayed because she hid her symptoms. She went into acute renal failure, fitted, then collapsed and died quite suddenly. The Wellington admissions for septic abortion represented 1 in 16 of the New Zealand total in 1965 and 1 in 28 in 1979. It would seem that the trend of decreased septic abortion admissions in Wellington is a mirror of the national trend.
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PMID:Septic abortion in Wellington 1960-1979. 658 28

Naloxone clorhidrate was administered intravenously to 15 patients with endotoxic shock and refractary hypotension, following meningococcal sepsis. Doses used were between 0.01-0.2 mg/kg. Three patients (two of them with moderate shock) showed an increase in sistolic arterial pressure, which was maintained and above 20 mm/Hg. Among the rest of them (except one with severe shock) naloxone action was non-existent in nine cases, or with short action and without answer to next doses in other three. Eleven patients died. A blood pressure increase was maintained only in two of the four survivors. Usefulness of naloxone in this kind of patients is not clear. Presence in endotoxin shock of a variety of refractory factors besides beta endorphins, greatly limits therapeutic efficiency of this drug.
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PMID:[Naloxone and endotoxic shock: a wonder drug?]. 671 29


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