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

Recent studies indicated that prefeeding of a glycine supplemented diet reduces the hepatic inflammatory response and liver damage in sepsis. We investigated the effect of a glycine-enriched infusion on hepatic microcirculatory disturbances and mortality in a rat model of sepsis after the onset of the disease. Male Wistar rats (240 +/- 13 g) underwent cecal ligation and puncture (CLP) or laparotomy (LAP). A glycine (CLP + Gly, n = 24), valine (CLP + Val, n = 24), or sodium chlorid (CLP + Sc, n = 24) infusion was started 2 h after CLP. The LAP group received sodium chloride intravenously (LAP + Sc, n = 18 ). Five hours, 10 h, and 20 h after CLP or LAP intravital microscopy (IVM) was performed to investigate leukocyte-endothelial interaction (LEI) and mean erythrocyte velocity in liver sinusoids (sMEV) and postsinosoidal venules (vMEV). The portal blood flow (PBF), hepatic enzyme liberation, and glycine values in blood were measured. Immunohistochemical staining for ICAM-1 in liver tissue was performed and survival was observed. Glycine values were significantly elevated in the CLP + Gly vs. the CLP + Val and the CLP + Sc group at every timepoint of investigation. Glycine infusion had no beneficial effects on sMEV, vMEV, LEI, hepatic enzyme liberation, and survival. Heart rate and mean arterial pressure remained stable but PBF decreased significantly in all groups 20 h after CLP. Although glycine reduces the hepatic inflammatory response and liver damage in pretreatment of septic rats, there was no effect of intravenous glycine after the onset of sepsis in our experiments. Our animal model does not support the use of glycine in patients.
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PMID:Intravenous glycine after cecal ligation and puncture has no effect on impaired hepatic microperfusion, leukocyte adhesion, and mortality in septic rats. 1579 63

We investigated the efficacy of LL-37, the C-terminal part of the only cathelicidin in humans identified to date (termed human cationic antimicrobial protein), in three experimental rat models of gram-negative sepsis. Adult male Wistar rats (i) were given an intraperitoneal injection of 1 mg Escherichia coli 0111:B4 LPS, (ii) were given 2 x 10(10) CFU of Escherichia coli ATCC 25922, or (iii) had intra-abdominal sepsis induced via cecal ligation and puncture. For each model, all animals were randomized to receive intravenously isotonic sodium chloride solution, 1-mg/kg LL-37, 1-mg/kg polymyxin B, 20-mg/kg imipenem, or 60-mg/kg piperacillin. Lethality; growth of bacteria in blood, peritoneum, spleen, liver, and mesenteric lymph nodes; and endotoxin and tumor necrosis factor alpha (TNF-alpha) concentrations in plasma were evaluated. All compounds reduced lethality compared to levels in controls. Endotoxin and TNF-alpha plasma levels were significantly higher in conventional antibiotic-treated rats than in LL-37- and polymyxin B-treated animals. All drugs tested significantly reduced bacterial growth compared to saline treatment. No statistically significant differences between LL-37 and polymyxin B were noted for antimicrobial and antiendotoxin activities. LL-37 and imipenem proved to be the most effective treatments in reducing all variables measured. Due to its multifunctional properties, LL-37 may become an important future consideration for the treatment of sepsis.
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PMID:LL-37 protects rats against lethal sepsis caused by gram-negative bacteria. 1664 34

Percutaneous suprapubic cystostomy is generally considered to be a safe procedure provided the bladder is distended adequately, as palpable bladder is the landmark for insertion of a trocar. This report describes fatality due to septicemia and hemorrhage following suprapubic catheter insertion in a tetraplegic male patient with long-term indwelling urethral catheter drainage and urine infection with Escherichia coli, Pseudomonas species, and Enterococcus faecalis. Before the surgical procedure was begun, the urinary bladder was distended by repeated injection of 50 mL of sterile, 0.9% sodium chloride through the urethral catheter with a catheter-tip syringe until the bladder became palpable in the suprapubic region; by this time, the bladder had been filled forcibly with 500 mL of saline. Percutaneous cystostomy was performed with the use of an Add-a-Cath trocar and cannula (Femcare Limited, Nottingham, Nottinghamshire, UK). Immediately after a 16 French Foley catheter had been inserted, the drainage fluid appeared heavily stained with blood. The patient developed septicemia, and a blood culture report, received posthumously, showed growth of E. coli. Despite resuscitative measures, the patient expired 13 hours after suprapubic catheter insertion. Postmortem examination revealed bilateral hydronephrosis with fluid and clotted blood in the renal pelves and ureters; the urinary bladder showed a thick wall and hemorrhagic mucosa. This fatal incident raises the question of whether forcible distention of the urinary bladder for percutaneous cystostomy is safe in patients with spinal cord injury who have a small-capacity bladder, infected urine, and ischemic heart disease. In such patients, it may be prudent to avoid forcible distention of the urinary bladder and instead perform ultrasound-guided or fluoroscopically guided suprapubic cystostomy.
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PMID:Fatality due to septicemia and hemorrhage in a patient with spinal cord injury and ischemic heart disease with the need for long-term catheter drainage. 1675 Nov 67

Sepsis remains a serious clinical problem despite intense efforts to improve survival. In this study, the efficacy of ertapenem combined with the cathelicidin tritrpticin was investigated in two rat models of septic shock. Main outcome measures were bacterial growth in blood, peritoneum, spleen, liver, and mesenteric lymph nodes; endotoxin, interleukin 6, and tumor necrosis factor alpha concentrations in plasma; and lethality. Adult male Wistar rats were given (1) an intraperitoneal injection of 1 mg Escherichia coli serotype 0111:B4 LPS or (2) intra-abdominal sepsis induced via cecal ligation and puncture. For each model, all animals were randomized to receive intraperitoneally isotonic sodium chloride solution, 1 mg/kg tritrpticin, 15 mg/kg ertapenem, and 1 mg/kg tritrpticin combined with 15 mg/kg ertapenem. Each group included 20 animals. All compounds significantly reduced bacterial growth and lethality as compared with saline treatment. Treatment with tritrpticin resulted in significant decrease in plasma endotoxin and cytokine levels, whereas ertapenem exerted opposite effect. The combination between tritrpticin and ertapenem proved to be the most effective treatment in reducing all variables measured. In conclusion, tritrpticin enhances ertapenem efficacy in gram-negative septic shock rat models.
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PMID:The cathelicidin-derived tritrpticin enhances the efficacy of ertapenem in experimental rat models of septic shock. 1687 29

A mouse model of staphylococcal sepsis was used to evaluate the efficacy of RNAIII-inhibiting peptide (RIP) combined with the cathelicidin BMAP-28. Preliminary in vitro studies showed that both peptides, alone or combined, were able to inhibit the lipoteichoic acid-induced production of tumor necrosis factor alpha and nitric oxide by RAW 264.7 cells. For in vivo experiments, the main outcome measures were lethality, quantitative blood cultures, and detection of tumor necrosis factor alpha and interleukin 6 plasma levels. BALB/c mice were injected i.v. with 2.0 x 10(6) colony-forming units of live Staphylococcus aureus ATCC 25923 or with 5.0 x 10(8) heat-killed cells of the same strain. All animals were randomized to receive i.v. isotonic sodium chloride solution, 10-mg/kg RIP, alone or in combination with 2-mg/kg BMAP-28, 7-mg/kg imipenem, or 7-mg/kg vancomycin, immediately and at 6 hours after bacterial challenge. In in vivo experiments performed with live bacteria, all compounds reduced lethality rates and bacteremia when compared with controls. In general, combined-treated groups had significantly lower bacteremia when compared with single-treated groups. Lowest lethality rates and bacteremia were obtained when RIP was administered in combination with BMAP-28 or vancomycin. In the experiments performed using heat-killed organisms, only BMAP-28 demonstrated significant efficacy on lethality rates and cytokines plasma levels when compared with controls. RIP combined with BMAP-28 exhibited the highest efficacy on all main outcome measurements. These data were observed on both immediate and delayed treatments. These results highlight the capacity of RIP and BMAP-28 to reduce the septic effects of bacterial cell components and exotoxins, and suggest their potential use in the treatment of severe staphylococcus-associated sepsis.
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PMID:RNAIII-inhibiting peptide in combination with the cathelicidin BMAP-28 reduces lethality in mouse models of staphylococcal sepsis. 1691 56

Besides providing effective analgesia, thoracic epidural anesthesia (TEA) has been shown to decrease perioperative morbidity and mortality. Because of its vasodilatory properties in association with the sympathetic blockade, however, TEA may potentially aggravate cardiovascular dysfunctions resulting from sepsis and systemic inflammatory response syndrome. The objective of the present study was to assess the effects of TEA on hemodynamics, global oxygen transport, and renal function in ovine endotoxemia. After a baseline measurement in healthy sheep (n = 18), Salmonella typhosa endotoxin was centrally infused at incremental doses to induce and maintain a hypotensive-hypodynamic circulation using an established protocol. The animals were then randomly assigned to one of two groups. In the treatment group, continuous TEA was initiated with 0.1 mL.kg of 0.125% bupivacaine at the onset of endotoxemia and maintained with 0.1 mL.kg.h. In the control group, the same amount of isotonic sodium chloride solution was injected through the epidural catheter. In the animals surviving the entire experiment (n = 7 per group), cardiac index and mean arterial pressure decreased in a dose-dependent manner during endotoxin infusion. In the TEA group, neither systemic hemodynamics nor global oxygen transport were impaired beyond the changes caused by endotoxemia itself. Urinary output was increased in the TEA group as compared with the control group (P < 0.05). In this model of endotoxic shock, TEA improved renal perfusion without affecting cardiopulmonary hemodynamics and global oxygen transport.
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PMID:Effects of thoracic epidural anesthesia on hemodynamics and global oxygen transport in ovine endotoxemia. 1711 38

Drug-related outbreaks are frequently reported from various medical departments. A systematic review was performed to describe characteristics of these outbreaks and to determine the most frequent occasions in which contamination of substances for patient care take place. Articles were assessed by a search of the outbreak database, a search of PubMed, and hand search of reference lists from relevant articles. Articles published before 1990 were excluded. Data on affected patients, hospital-acquired infections, substances, pathogens and graded information about the location of the contamination incidence were extracted. A total of 2250 patients in 128 articles were included, mostly from intensive care units or haematological departments. Septicaemia was the most frequent hospital-acquired infection. Most often articles report contamination of blood products and heparin-sodium chloride solutions. The most frequent pathogens were hepatitis A virus, Yersinia enterocolitica, and Serratia spp. for blood products and Burkholderia cepacia and Enterobacter spp. for substances other than blood products. Mortality was highest if red blood cells or total parenteral nutrition formulas were contaminated. In 64 of the outbreaks multi-dose vials had been used against the manufacturers' recommendations. Thus, drug-related outbreaks are likely to occur particularly when basic hygiene measures are disobeyed. A large proportion of drug-related nosocomial infections could have been prevented, for example, by avoiding the use of multi-dose vials.
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PMID:Hospital-acquired infections related to contaminated substances. 2566 39

Microcirculatory dysfunction contributes significantly to tissue hypoxia and multiple organ failure in sepsis. Ischemia of the gut and intestinal hypoxia are especially relevant for the evolution of sepsis because the mucosal barrier function may be impaired, leading to translocation of bacteria and toxins. Because sympathetic blockade enhances intestinal perfusion under physiologic conditions, we hypothesized that thoracic epidural anesthesia (TEA) may attenuate microcirculatory perturbations during sepsis. The present study was designed as a prospective and controlled laboratory experiment to assess the effects of continuous TEA on the mucosal microcirculation in a cecal ligation and perforation model of sepsis in rats. Anesthetized Sprague-Dawley rats underwent laparotomy and cecal ligation and perforation to induce sepsis. Subsequently, either bupivacaine 0.125% (n = 10) or isotonic sodium chloride solution (n = 9) was continuously infused via the thoracic epidural catheter for 24 h. In addition, a sham laparotomy was carried out in eight animals. Intravital videomicroscopy was then performed on six to ten villi of ileum mucosa. The capillary density was measured as areas encircled by perfused capillaries, that is, intercapillary areas. The TEA accomplished recruitment of microcirculatory units in the intestinal mucosa by decreasing total intercapillary areas (1,317 +/- 403 vs. 1,001 +/- 236 microm2) and continuously perfused intercapillary areas (1,937 +/- 512 vs. 1,311 +/- 678 microm2, each P < 0.05). Notably, TEA did not impair systemic hemodynamic variables beyond the changes caused by sepsis itself. Therefore, sympathetic blockade may represent a therapeutic option to treat impaired microcirculation in the gut mucosa resulting from sepsis. Additional studies are warranted to assess the microcirculatory effects of sympathetic blockade on other splanchnic organs in systemic inflammation.
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PMID:Continuous thoracic epidural anesthesia improves gut mucosal microcirculation in rats with sepsis. 1758 85

We investigated the efficacy of tazobactam/piperacillin (TZP), tachyplesin III and granulocyte-colony stimulating factor (G-CSF) in an experimental murine neutropenic intraabdominal infection. BALB/c male mice were rendered neutropenic by intraperitoneal administration of cyclophosphamide on days -4 and -2 pre-infection. Septic shock was induced by cecal ligation and puncture. Animals received intravenously isotonic sodium chloride solution (control group C1), 1mg/kg of tachyplesin III, 120 mg/kg of TZP, 0.1mg/kg of G-CSF, tachyplesin III plus TZP, G-CSF plus TZP and finally tachyplesin III plus G-CSF plus TZP, respectively. Lethality, bacterial growth in blood, peritoneum, spleen, liver, and mesenteric lymph nodes, endotoxin, IL-6 and TNF-alpha concentrations in plasma were evaluated. All compounds reduced the lethality when compared to controls. Endotoxin and cytokine plasma levels were significantly higher in TZP-treated animals compared to tachyplesin III-treated animals. Finally, all drug combinations showed to be the most effective treatment in reducing all variables measured. Interestingly, the strongest results concerning the bacterial growth inhibition, lethality and endotoxemia were obtained when the three compounds were contemporaneously administered. The presence of their positive interaction makes tachyplesin III and G-CSF potentially valuable as an adjuvant for antimicrobial chemotherapy of sepsis.
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PMID:Tachyplesin III and granulocyte-colony stimulating factor enhance the efficacy of tazobactam/piperacillin in a neutropenic mouse model of polymicrobial peritonitis. 1806 69

A promising therapeutic strategy for the management of severe Pseudomonas infection in neutropenic patients may result from the coadministration of colony-stimulating factors (CSFs) that help maintain immune competence and antimicrobial peptides, a novel generation of adjunctive therapeutic agents with antimicrobial and anti-inflammatory properties. A promising peptide with these properties is LL-37, the only member of the cathelicidin family of antimicrobial peptides found in humans. BALB/c male mice were rendered neutropenic by intraperitoneal administration of cyclophosphamide on days -4 and -2 preinfection. Septic shock was induced at time 0 by intraperitoneal injection of 2x10 colony-forming units of P. aeruginosa American Type Culture Collection (ATCC) 27853. All animals were randomized to receive intravenously isotonic sodium chloride solution, 1 mg/kg of LL-37, 20 mg/kg of imipenem, 0.1 mg/kg of granulocyte CSF (G-CSF), 1 mg/kg of LL-37+0.1 mg/kg of G-CSF, or 20 mg/kg of imipenem+0.1 mg/kg of G-CSF. Lethality and bacterial growth in blood, peritoneum, spleen, liver, and kidney were evaluated. All regimens were significantly superior to controls at reducing the mouse lethality rate and bacterial burden in organs. Particularly, the combination between LL-37 and G-CSF was the most effective in protecting neutropenic mice from the onset of sepsis and in vitro significantly reduced the apoptosis of neutrophils. Combination therapy between LL-37 and G-CSF is a promising therapeutic strategy for the management of severe Pseudomonas infection complicated by neutropenia.
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PMID:Efficacy of LL-37 and granulocyte colony-stimulating factor in a neutropenic murine sepsis due to Pseudomonas aeruginosa. 1839 59


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