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

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

During a study of the nutritional requirements of clinical isolates of Escherichia coli, we found that 21 (7.0%) of 301 strains required nicotinamide to grow in minimal medium. The nicotinamide-requiring strains were present in 16 (15.8%) of 101 cultures of urine from young women with acute cystitis, in 5 (5.0%) of 100 stool specimens from healthy adults, and in none of 100 blood samples from adult patients with bacteremia. Most of the strains belonged to serogroup O18:K1:H7, were hemolytic, possessed type 1 fimbriae, and exhibited similar patterns of antibiotic susceptibility. Two of the urinary isolates expressed S fimbriae, and all 16 urinary isolates contained the sfaS homologue gene on their chromosomes. One of the stool isolates contained the sfaS gene. The urinary isolates closely resembled a large clone of E. coli that is reportedly associated with neonatal meningitis and sepsis. It may be possible to detect this and related clones by their requirement for nicotinamide and to screen strains for S fimbriae by relatively inexpensive hemagglutination methods, including the use of avian P1 antigens to detect mannose-resistant, non-P-fimbriated E. coli; the agglutination of bovine erythrocytes; and the use of bovine mucin to detect sialyl galactosides in S fimbriae.
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PMID:Isolation of a nicotinamide-requiring clone of Escherichia coli O18:K1:H7 from women with acute cystitis: resemblance to strains found in neonatal meningitis. 809 16

The pathological spectrum of intrahepatic peribiliary glands is reviewed here. Several categories of histopathological changes such as necro-inflammation, cystic dilatation, hyperplasia and neoplasia have been identified in this glandular system. Necro-inflammation is associated with biliary tract diseases and chronic advanced liver diseases and may also appear in the livers of subjects with extrahepatic diseases such as sepsis. Cystic changes of microscopic sizes are not uncommon in autopsy livers of chronic advanced liver diseases, portal hypertensive diseases and also polycystic liver of adult type. Grossly recognizable cysts are, however, infrequent and occasionally cause compression of the adjoining bile ducts. Hyperplasia of these glands, which occurs consistently in hepatolithiasis and more variably in other conditions (e.g. biliary tract infection and submassive hepatic necrosis), may be associated with hypersecretion of seromucinous substances. Hyperplasia of peribiliary glands may then lead to mucin-related biliary diseases. In addition, these glands, particularly the hyperplastic ones, could be a precursor of cholangiocarcinoma. The pathological spectrum of the intrahepatic peribiliary glands is being expanded, although a clinical pathological correlation remains uncharted. Furthermore, age-related variations and non-specific reactive changes of these glands remain unexplored.
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PMID:Intrahepatic peribiliary glands of humans. II. Pathological spectrum. 815 73

Campylobacter upsaliensis is a recently recognized human enteric pathogen associated with enteritis, colitis, bacteremia, and sepsis. Very little is known about the mechanisms of pathogenesis of this organism. The goals of this study were to determine whether C. upsaliensis binds to epithelial cells and whether there are specific lipid molecules that might serve as cell membrane receptors. In addition, we also explored C. upsaliensis binding to purified human small-intestinal mucin, since the mucus gel overlying the epithelium provides an initial contact surface for the bacteria and must be penetrated for the organisms to reach their cell receptors. Binding of C. upsaliensis to model epithelial cells was shown by microscopy adhesion assays, and binding to lipids was detected by thin-layer chromatography-overlay assays. Bacteria bound to phosphatidylethanolamine (PE), gangliotetraosylceramide (Gg4), and, more weakly, to phosphatidylserine (PS). There was no binding to ceramide, cholesterol, phosphatidylcholine, and globosides. Using receptor-based microtiter well immunoassays, we observed binding to be equal, specific, and saturable for PE and Gg 4 but low and nonspecific for PS. At least five bacterial surface proteins (50 to 90 kDa) capable of PE binding were identified by a lipid-silica affinity column technique. In slot blot overlay assays, biotin-labeled C. upsaliensis also bound in a concentration-dependent fashion to purified human small-intestinal mucin, implying that these microorganisms also express an adhesin(s) recognizing a specific mucin epitope(s). We speculate that binding to mucins may influence access of the bacteria to cell membrane receptors and thereby influence host resistance to infection.
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PMID:Adherence to lipids and intestinal mucin by a recently recognized human pathogen, Campylobacter upsaliensis. 892 69

To determine whether treatment with recombinant human tissue factor pathway inhibitor (TFPI), an inhibitor of the extrinsic coagulation pathway, can improve survival in a clinically relevant model of gram-negative sepsis, rabbits were given an intraperitoneal inoculation of a suspension containing hemoglobin (40 microg/mL), porcine mucin (150 microg/mL), and viable Escherichia coli O18:K1 (1.0 +/- 0.5 x 10(5) cfu/kg). Treatment with gentamicin (5 mg/kg every 12 h for five doses) was instituted 4 h after induction of peritonitis. At the same time point, rabbits were randomized to receive a 24-h infusion of vehicle or one of three different doses of TFPI. Treatment groups, 7-day survival rates, and significance versus control were as follows: control, 1 of 20; TFPI(LOW DOSE) (0.1 mg/kg, then 1 microg/kg/min), 3 of 12 (P = .14); TFPI(MID DOSE), (0.5 mg/kg, then 5 microg/kg/min), 7 of 12 (P = .002); TFPI(HIGH DOSE) (10 mg/kg, then 10 microg/kg/min), 4 of 13 (P = .04). Thus, delayed treatment with TFPI improves survival in septic rabbits.
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PMID:Delayed treatment with recombinant human tissue factor pathway inhibitor improves survival in rabbits with gram-negative peritonitis. 949 46

Although the intestinal mucosa forms a crucial barrier between the host and the environment, bacterial translocation (BT) occurs frequently in neonates and may be a source of sepsis. The intestinal mucous gel layer is thought to be a vital component of the gut barrier and is composed, in part, of a family of glycoproteins known as mucins. Our aim was to study the effects of mucin on BT in an enterocyte cell-culture model using a fetal (I-407) and an adult (Caco-2) intestinal cell line. I-407 and Caco-2 cells were grown to confluence on porous filters in a two-chamber Transwell system. The integrity of the monolayers was confirmed by transepithelial electrical resistance (TEER) and permeability using the macromolecule dextran blue. Cells were treated with mucin (40 mg/ml) prior to inoculation of 1 x 10(6) Escherichia coli C25. The magnitude of BT was determined quantitatively by culturing the samples from the basal chamber of the wells and was expressed as log 10 [Colony Forming Units (CFU)/ml]. Statistical analysis was performed by the Mann-Whitney U test with statistical significance at P < 0.05. Mucin inhibited BT across both fetal and adult cultured enterocyte monolayers; however, the inhibitory effect was less on the fetal cells compared to the adult cells. Dextran-blue studies showed that monolayers were intact throughout the experiments. Despite 98% inhibition of BT, mucin had a statistically significant effect on post-bacterial inoculation TEER in Caco-2 cells and no effect in I-407 cells. The ability of mucin, a mucous-barrier glycoprotein, to inhibit BT across immature intestinal enterocytes, as in the neonate, may be diminished compared to mature adult enterocytes.
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PMID:The effect of mucin on bacterial translocation in I-407 fetal and Caco-2 adult enterocyte cultured cell lines. 1037 12

We hypothesized that the dietary threonine demand for the anabolic response may be increased more than that of other essential amino acids during sepsis. Using a flooding dose of either L-[1 -13C]valine or L-[U -13C]threonine, we measured valine and threonine utilization for syntheses of plasma proteins (minus albumin), and wall, mucosal, and mucin proteins of the small intestine in infected (INF; d 2 and d 6 of postinfection) and control pair-fed (PF) rats. At d 2, the protein absolute synthesis rate (ASR) of INF rats was 21% (mucins) to 41% (intestinal wall) greater than that of PF when measured using valine as tracer, and 45% (mucosa) to 113% (mucins) greater than that of PF when measured with threonine as tracer. Plasma protein ASR was higher in INF than in PF rats, reaching 5- to 6-fold the value of PF. The utilization of both amino acid tracers for the protein synthesis was significantly increased by the infection in all compartments studied. The daily increased absolute threonine utilization for protein synthesis in gut wall plus plasma proteins was 446 micromol/d compared with 365 micromol/d for valine, and it represented 2.6 times the dietary threonine intake of rats at d 2. Most changes in protein ASR and threonine utilization observed at d 6 of postinfection were limited. In conclusion, sepsis increased the utilization of threonine for the anabolic splanchnic response. Because this threonine requirement is likely covered by muscle protein mobilization, increasing the threonine dietary supply would be an effective early nutritional management for patients with sepsis.
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PMID:Threonine utilization for synthesis of acute phase proteins, intestinal proteins, and mucins is increased during sepsis in rats. 1758 34

We report an unusual case of mucinous adenocarcinoma of the anus associated with a chronic anal fistula, treated successfully by abdominoperineal resection (APR). Although multiple biopsies failed to reveal any histological evidence of malignancy, cancer was diagnosed from the mucin obtained for cytology. Subsequent histological examination of the resected specimen revealed clusters of cancer cells floating in a mucous lake, suggesting that it would have been difficult to acquire the cells in a biopsy sample. Conversely, the presence of mucin lakes and globules in specimens drained from the region of perianal sepsis may have been histologically informative for diagnosis. Thus, although biopsy of the lesion is undoubtedly essential for diagnosis, it often fails to provide enough information to make a definite diagnosis of mucinous carcinoma. This case illustrates that clinicians should base their decision on whether to perform surgery on clinical manifestations, imaging findings, and cytology of mucin obtained by drainage when it is difficult to obtain malignant cells by biopsy.
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PMID:Is histopathological evidence really essential for making a surgical decision about mucinous carcinoma arising in a perianal fistula? Report of a case. 1851 39

A minute, pleomorphic, motile, Gram-negative bacterium has been isolated from two specimens of nodular tissue from human verruga. In films and sections of the original tissues the organism in question is difficult to distinguish from Bartonella bacilliformis, with which it was associated, and even in pure culture it has a number of properties in common with that parasite. No sugars are fermented by it, it is an obligate aerobe, the optimum temperature for its growth is 25 degrees C., and it has two to four spiral flagella attached to one end of the body. It is, however, readily cultivated on any ordinary culture medium. Broth cultures contain much mucin, but no hydrogen sulfide is formed. Coagulated serum is liquefied by its growth, and the red corpuscles in a blood agar plate are hemolyzed. Rabbits, guinea pigs, rats, and mice develop acute, fatal septicemia as a result of intravenous or intratesticular inoculation of young cultures. The liver is characteristically affected and shows a general parenchymatous degeneration and necrosis; the entire gastrointestinal tract is intensely congested, and numerous hemorrhagic areas are present; the spleen, dark and soft, is rarely much enlarged; the kidneys are swollen and congested; the adrenals are much swollen and intensely red; the lungs are sometimes congested but otherwise normal. In the case of intratesticular inoculation the scrotum and testicle both undergo rapid gangrene. In monkeys no septicemia has been observed, but a violent local reaction-swelling, congestion, sometimes necrosis-follows intradermal inoculation. Since no microorganism corresponding in character with this one has previously been described, it is regarded as a new species, and because of its presence in material obtained from Peru it has been given the name Bacterium peruvianum. The significance of the association of B. peruvianum with Bartonella bacilliformis deserves further investigation; it is not impossible that the two organisms are introduced into the human body by the same blood-sucking insect.
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PMID:ETIOLOGY OF OROYA FEVER : IX. BACTERIUM PERUVIANUM, N. SP., A SECONDARY INVADER OF THE LESIONS OF VERRUGA PERUANA. 1986 95

C1 inhibitor (C1INH) is a serpin that regulates both complement and contact (kallikrein-kinin) system activation. It consists of a serpin domain that is highly homologous to other serpins and an amino terminal non-serpin mucin-like domain. Deficiency of C1INH results in hereditary angioedema, a disease characterised by episodes of angioedema of the skin or the mucosa of the gastrointestinal tract or the oropharynx. Although early data suggested that angioedema was mediated via complement system activation, the preponderance of the data indicate that bradykinin is the mediator. In the past few years, it has become apparent that C1INH has additional anti-inflammatory functions independent of protease inhibition. These include interactions with leukocytes that may result in enhanced phagocytosis, with endothelial cells via E- and P-selectins that interfere with leukocyte rolling and in turn results in suppression of transmigration of leukocytes across the endothelium, and interactions with extracellular matrix components that may serve to concentrate C1INH at sites of inflammation. In addition, C1INH suppresses gram negative sepsis and endotoxin shock, partly via direct interaction with endotoxin that interferes with its interaction with macrophages, thereby suppressing tumour necrosis factor-a and other inflammatory mediators. C1INH treatment improves outcome in a number of disease models, including sepsis and other bacterial infections, possibly malaria, ischaemia-reperfusion injury (intestinal, hepatic, muscle, cardiac, brain), hyper-acute transplant rejection, and other inflammatory disease models. Recent data suggest that this effectiveness is the result of mechanisms that do not require protease inhibition, in addition to both complement and contact system activation.
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PMID:C1 inhibitor, a multi-functional serine protease inhibitor. 2080 8


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