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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gram negative sepsis causes changes in oxygen supply-demand relationships. We have used a primate model of hyperdynamic gram negative sepsis produced by intravenous infusion of Escherichia coli (E. coli) to evaluate sepsis-induced alterations in mitochondrial oxidation-reduction (redox) state in muscle in vivo. The redox state of cytochrome a,a3, the terminal member of the intramitochondrial respiratory chain, was assessed in the intact forearm by near-infrared (NIR) spectroscopy. The muscle NIR data were compared to routine measures of oxygen delivery (DO2) and oxygen consumption (VO2). After E. coli infusion and fluid resuscitation, DO2 and VO2 showed minimal changes through 24 hr of sepsis. In contrast, changes in cytochrome a,a3 redox state evaluated by NIR occurred within a few hours and were progressive. Mitochondrial functional responses were correlated with structural changes observed on serial muscle biopsies. Gross morphological changes in muscle mitochondria were present in some animals as early as 12 hr, and, in most animals, by 24 hr. The morphologic changes were consistent with decreases in oxidative capacity as suggested by NIR spectroscopy. The NIR data also suggest that two mechanisms are operating to explain abnormalities in oxygen metabolism and mitochondrial function in lethal sepsis. These mechanisms include an early defect in oxygen provision to mitochondria that is followed by a progressive loss in functional cytochrome a,a3 in the muscle.
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PMID:Altered mitochondrial redox responses in gram negative septic shock in primates. 798 71

Gram-negative bacterial sepsis is associated with endotoxemia and a high mortality rate. In previous studies, we demonstrated the therapeutic benefit of an anti-lipopolysaccharide factor isolated from amebocytes of Limulus polyphemus, and of a recombinant version of this protein, termed endotoxin neutralizing protein (ENP), in rabbits challenged with purified lipopolysaccharides. To assess the benefit of ENP in treating a live bacterial infection, we established a rabbit model of Escherichia coli (E. coli) peritonitis and bacteremia with high mortality despite gentamicin treatment. Twenty-four pairs of New Zealand white rabbits were challenged intraperitoneally (IP) with E. coli O18ac K1 in 5% porcine mucin (mean bacteria per dose = 2.5 x 10(8)). The animals were treated with intravenous (i.v.) gentamicin (2.5 mg/kg), and with either ENP (5 mg/kg) or saline i.v. at 1 hr after E. coli challenge. All rabbits were bacteremic 1 hr after challenge (geometric mean 4.1 +/- 1.2 x 10(4) cfu/mL). Peak geometric mean serum endotoxin (2.62 v 10.54 EU/mL, P = .013) and tumor necrosis factor (TNF) (2540 v 6438 TNF units/mL, P = .046) concentrations were lower in ENP-treated animals as compared to control animals. Seven of 24 animals treated with ENP survived 24 hr compared with 4 of 24 controls (Kaplan-Meier analysis, P = .19). However, in the subgroup of 13 paired animals in whom bacteremia was eliminated by gentamicin treatment, 5 of 13 ENP-treated animals survived 24 hr, compared with 1 of 13 controls (Kaplan-Meier analysis, P = .032).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Efficacy of a recombinant endotoxin neutralizing protein in rabbits with Escherichia coli sepsis. 801 61

We studied retrospectively the clinical records of 291 hospital patients with liver cirrhosis, 95% of which was alcohol related. Within this group, 114 patients presented 155 episodes of infection in 144 separate hospital admissions. In a previous communication, we pointed out that although infection was the fourth cause of admission, it was the main cause of death in this group. The main incidence of infection was among the female group. The most common infections episodes were respiratory and bacterial spontaneous peritonitis (BSP). On admission, 57% of the patients were diagnosed as belonging to the C Child group; 38% presented sepsis and 22% were hospitalary infections. The most frequent infections were respiratory and BSP. We obtained bacteriologic documentation in 55% of the episodes with prevalence of Gram negative bacilli (E. coli), with high relative frequency of neumoccocus. The most frequent complications were related to hepatic insufficiency. Global death rate was 27.1%, while nosocomial death rates were 42.1% and 40.9% for patients with Child C. We observed the highest incidence of mortality in patients with SBP and non localized bacteriemia. Survival rates were 42% for 2 years and 18% for 5 years. In summary, we stress the relevancy of checking the presence of infection systematically in every cirrhotic patient with encephalopathy and/or renal insufficiency without justifiable cause.
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PMID:[Infections during the hospitalization of patients with liver cirrhosis]. 829 12

The case of a patient with abdominal crisis and shock without any discernible origin who died 36 hours after hospital admission despite maximal therapy is described. Gram-negative sepsis, peritonitis and haemochromatosis with hepatic siderosis was the post-mortem diagnosis. We consider spontaneous peritonitis arising from translocation of normal intestinal flora (E. coli) through the intact wall of the gut combined with the impaired ability of the reticulo-endothelial system to remove endotoxin to be the causative factors. It is unknown whether the adrenal insufficiency due to siderophilic adrenal hypophysis and adrenal glands contributed to the fulminant course of the disease. Undiagnosed liver cirrhosis and especially haemochromatosis should therefore be included in the differential diagnostic considerations in patients presenting with these symptoms, and in whom no obvious cause for a septic focus can be found.
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PMID:[Septic shock with acute abdomen in idiopathic hemochromatosis]. 835 6

The role of free radicals in septic-shock-associated tissue injury and the mechanisms underlying the generation of free radicals in sepsis was investigated in a primate model using electron spin resonance (ESR) spectroscopy and spin-trapping techniques paired with physiological measurements. Baboons were administered the spin trap, 5,5-dimethyl-1-pyrroline N-oxide (DMPO) during infusions of live Escherichia coli (E. coli) with or without challenge with tumor necrosis factor (TNF). ESR spectra suggesting the trapping of carbon-centered and oxygen-centered radicals were detected in liver lipid extracts of E. coli infused animals which exhibited pathophysiological changes indicative of sepsis. In animals demonstrating a toxic response to E. coli. TNF challenge appeared to intensify the ESR signal observed. These data provide evidence of free radical production during sepsis and suggest a role for TNF in the production of these radicals.
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PMID:Free radicals and septic shock in primates: the role of tumor necrosis factor. 838 84

Alcohol, consumed as 36% of the caloric intake for 8-10 wk, causes a potentiation of cardiac dysfunction induced by a second insult, sepsis. Because chronic alcoholism may attenuate the responsiveness of the myocardium to catecholamine stimulation, and because catecholamine support seems to be essential for the myocardium to generate an adequate cardiac output in sepsis, we hypothesized that the heart from the alcoholic septic rat would show a compromised inotropic responsiveness to catecholamines compared with the heart from the nonalcoholic septic rat. To test this hypothesis, rats were fed an ethanol-containing or control liquid diet for 8-10 wk and were then made septic with live Escherichia coli (10(10) E. coli) through a dorsal subcutaneous catheter. The next day, hearts were removed and perfused at a constant hydrostatic pressure, and a compliant balloon was placed in the left ventricule for measurement of pressure (LVP). Hearts were paced at 350-360 beats/min. Hearts were allowed to stabilize for 15 min, and then the response to a submaximal dose of isoproterenol (Iso) was measured. Hearts recovered for 30 min, at which time the response to a maximum dose of Iso was recorded. Basal (pre-Iso) LVP was lower in the control septic and alcoholic septic groups than in the control and alcohol groups. However, the maximum increase in LVP in response to Iso was greater in the two septic groups than in the two nonseptic groups. The peak LVP in response to Iso was similar in the control, septic, and alcoholic septic groups, and was significantly greater than in the alcohol group.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Myocardial responses to isoproterenol are altered by chronic alcoholism and infection. 844 52

To investigate whether the inhibition of protein kinases including protein kinase C can antagonize endotoxicosis, the in vivo effects of K252a, a potent inhibitor of protein kinases, on endotoxin-induced lethality and glucose dyshomeostasis were determined in conscious rats. Sprague-Dawley rats (260-340 g) were divided into the following four groups: Group DS, 2.5% dimethyl sulfoxide (DMSO), 6 ml/kg iv + 0.9% saline, 2 ml/kg iv; group KS, K252a in 2.5% DMSO, 4 mg/kg iv + 0.9% saline; group DE, 2.5% DMSO + endotoxin (E. coli), 15 mg/kg iv; and group KE, K252a in 2.5% DMSO + endotoxin. A quarter of DMSO or K252a solution was continuously infused over a 15 min period before a bolus injection of either saline or endotoxin. The remaining dose was administered over a 180 min period after saline or endotoxin. All animals in the DS and KS groups survived for 24 hrs. K252a significantly improved endotoxic lethality. It attenuated the initial hyperglycemia, and late hypoglycemia, hyperlactacidemia, and base deficit after endotoxin. However, K252a had no influence on the endotoxic alterations of blood pressure, PaCO2 or PaO2. These results suggest that the activations of protein kinases, particularly protein kinase C, are involved in the pathogenesis of lethal endotoxicosis and sepsis.
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PMID:K252a, a potent protein kinase inhibitor, improves endotoxic lethality and glucose dyshomeostasis. 846 75

Microbial translocation has been suspected to be a major contributing factor in the development of sepsis of unknown origin and multiple organ failure syndrome, but there are currently no tests capable of detecting and quantitating translocation sequentially in humans. The purpose of this study was to develop a sensitive polymerase chain reaction (PCR) test to detect Escherichia coli (E. coli) DNA in the blood of animals after inducing bacterial translocation from the gut. DNA was extracted from blood and primers were used to amplify an 800-bp gene fragment of E. coli by 30-cycle PCR. Detection by southern blotting achieved a sensitivity of 10-100 organisms per 0.3 cc blood. Experimental groups included mice gavaged with 10(10) E. coli followed by 20% body surface area thermal injury, or no injury. Controls included burn only and no treatment groups. Blood was obtained by cardiac puncture 1 hr after burn. Cultures were done on blood samples from all groups. More animals in the burn/gavage group had positive bacterial cultures. All controls were culture negative. E. coli detection by PCR was 100% sensitive in culture positive animals with detection in the gavage/burn group higher than that in all other groups. PCR was negative for all mice without treatment. Several culture negative animals had detectable bacterial DNA by PCR. This highly sensitive and specific method can be used repeatedly to test the blood of patients for the presence of microbial DNA, which could be originating from the gut.
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PMID:Detection of intestinal bacterial translocation using PCR. 866 Nov 73

Neonatal sepsis is a life-threatening emergency and any delay in treatment may cause death. Initial signs of neonatal sepsis are slight and nonspecific. Therefore, in suspected sepsis, two or three days empirical antibiotic therapy should begin immediately after cultures have been obtained without awaiting the results. Antibiotics should be reevaluated when the results of the cultures and susceptibility tests are available. If the cultures are negative and the clinical findings are well, antibiotics should be stopped. Because of the nonspecific nature of neonatal sepsis, especially in small preterm infants, physicians continue antibiotics once started. If a baby has pneumonia or what appears to be sepsis, antibiotics should not be stopped, although cultures are negative. The duration of therapy depends on the initial response to the appropriate antibiotics but should be 10 to 14 days in most infants with sepsis and minimal or absent focal infection. In infants who developed sepsis during the first week of life, empirical therapy must cover group B streptococci, Enterobacteriaceae (especially E. coli) and Listeria monocytogenes. Penicillin or ampicillin plus an aminoglycoside is usually effective against all these organisms. Initial empirical antibiotic therapy for infants who developed sepsis beyond the first days of life must cover the organisms associated with early-onset sepsis as well as hospital-acquired pathogens such as staphylococci, enterococci and Pseudomonas aeruginosa. Penicillin or ampicillin and an aminoglycoside combination may also be used in the initial therapy of late-onset sepsis as in cases with early-onset sepsis. In nosocomial infections, netilmicin or amikacin should be preferred. In cases showing increased risk of staphylococcal infection (e.g. presence of vascular catheter) or Pseudomonas infection (e.g. presence of typical skin lesions), antistaphylococcal or anti-Pseudomonas agents may be preferred in the initial empirical therapy. In some centers, third-generation cephalosporins in combinations with penicillin or ampicillin have been used in the initial therapy of early-onset and late-onset neonatal sepsis. Third-generation cephalosporin may also be combined with an aminoglycoside in places where aminoglycoside-resistance to this antibiotic is high. However, third-generation cephalosporins should not be used in the initial therapy of suspected sepsis, because 1) extensive use of cephalosporins for initial therapy of neonatal sepsis may lead to the emergence of drug-resistant microorganisms (this has occurred more rapidly as compared with the aminoglycosides), 2) Antagonistic interactions have been demonstrated when the other beta-lactam antibiotics (e.g. penicillins) were combined with cephalosporins. Infections due to gram-negative bacilli can be treated with the combination of a penicillin-derivative (ampicillin or extended-spectrum penicillins) and an aminoglycoside. Third-generation cephalosporins in combination with an aminoglycoside or an extended-spectrum penicillin have been used in the treatment of sepsis due to these organisms. Piperacillin and azlocillin are the most active of extended-spectrum penicillins against Pseudomonas aeruginosa. Among the third-generation cephalosporins, cefoperazone and ceftazidime possess anti-Pseudomonas activity. Ceftazidime was found to be more active in vitro against Pseudomonas than cefoperazone or piperacillin. New antibiotics for gram-negative bacteria resistant to other agents are carbapenems, aztreonam, quinolones and isepamicin. Enterococci can be treated with a cell wall-active agent (e.g. penicillin, ampicillin, or vancomycin) and an aminoglycoside. Staphylococci are susceptible to penicillinase-resistant penicillins (e.g. oxacillin, nafcillin and methicillin). Resistant strains are uniformly sensitive to vancomycin. A penicillin or vancomycin and an aminoglycoside combination result in a more rapid bacteriocidal effect than is produced by either dr
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PMID:Antibiotic use in neonatal sepsis. 972 68

We studied clinical effect of a combination therapy with cefozopran (CZOP) and tobramycin (TOB) for infections in 80 patients with hematologic diseases in 15 institutes. Combined doses with CZOP 2 g and TOB 60-90 mg twice a day had been given intravenously. Of the 80 patients, 61 patients (42 with acute leukemia, 10 with malignant lymphoma, 3 with aplastic anemia, 2 with chronic myeloid leukemia, 2 with multiple myeloma, and 2 with myelodysplastic syndrome) were evaluable. Those consisted of 6 patients with septicemia, 49 with suspected septicemia, 3 with pneumonia, and 3 with other infections. Clinical efficacy by the treatment was excellent in 24, good in 17, fair in 9, and poor in 11 patients, and the overall efficacy rate including excellent and good was 67.2%. Microbiologically, 5 of the 6 patients with septicemia (1 coagulase negative Staphylococcus, 2 S. pneumoniae, 1 S. oralis, and 1 E. coli) were responded. The efficacy rate in patients with severe granulocytopenia showing 100/microliter or lesser neutrophil counts during the drug administration was 57.1% (12/21). Side effects and abnormal changes of clinical laboratory findings were observed in 5 patients, and 16 patients, respectively, but most of them were mild. The findings above suggested that the combination therapy with CZOP and TOB is useful as an empiric therapy for severe infections in patients with hematologic diseases.
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PMID:[Clinical effects of combination therapy with cefozopran and tobramycin for severe infections in patients with hematologic diseases]. 1022 Nov 80


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