Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0243026 (sepsis)
 52,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The objective of this paper is to report 5 cases of rhabdomyolysis (RML) in patients with acute leukemia (AL). This occurred consecutively after the administration of chemotherapy, during the ensuing period of myelosuppression. Thirty-six patients with AL received, in a three-month period, 51 cycles of combined chemotherapy which included, in all of them, cytosine arabinoside (ARA-C); among them, along with myelosuppression, five experienced fever, infectious complications, gastrointestinal tract symptoms and severe myalgias. Serum creatine kinase (CK), liver function tests and a light microscopy muscle biopsy were performed on all of them. Ten-17 days after receiving chemotherapy, five patients (4 males and 1 female) with acute lymphoblastic leukemia developed incapacitating myalgias in neck, thighs and arms. CK and/or alanine aminotransferase and aspartate aminotransferase were increased 5-24 times above the normal range in four of these patients, and the muscle biopsy showed focal RML in all five. Myalgias were self-limited and lasted 4-10 days. In addition to the chemotherapy, other factors known to be capable of producing RML, such as sepsis, other medications, and dehydration were found. In conclusion, myalgias were due to focal RML produced probably by a combination of factors, particularly the chemotherapy along with dehydration due to gastrointestinal complications, infection, and the use of diverse antibiotics. The endemic nature of the finding in such a short period of time is outstanding.
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PMID:Rhabdomyolysis in patients with acute lymphoblastic leukemia. 929 34

Up-regulation of the leukocyte beta 2 integrin, CD18, is a key event in neutrophil-endothelial adhesion and neutrophil-mediated organ injury. Inhibition of CD18 with monoclonal antibodies reduces lung and liver neutrophil sequestration in animal models of Gram-negative bacteremia or endotoxemia. However, with a persistent septic challenge, interference with host leukocyte phagocytic defense could adversely affect outcome. To assess the effects of inhibiting CD18 on organ neutrophil responses, bacteremia, and organ injury after fecal peritonitis, mice underwent cecal ligation and puncture (CLP). At the time of CLP and 12 h later, mice received intravenous anti-CD18 antibody or control IgG. At 3, 6, and 18 h after CLP, lung and liver tissue neutrophil content were measured by myeloperoxidase (MPO) assay, peritoneal cells and blood leukocytes were differentially counted, blood was cultured, and serum aspartate aminotransferase was measured. There was a significant reduction in peritoneal neutrophil migration and an increase in blood neutrophils after anti-CD18 treatment compared with results from treatment with the control antibody. In the anti-CD18-treated group, liver MPO was increased fivefold at 6 and 18 h, while lung MPO was increased two-fold at 18 h when compared with the control antibody-treated group. The anti-CD18-treated group also had an increase in bacteria cultured from the blood at 6 and 18 h and an increase in serum aminotransferase at 18 h. Our data demonstrate that peritoneal neutrophil migration in response to an endogenous fecal challenge is CD18-dependent, and that this mechanism forms a vital part of host defense. Inhibition of CD18 increased neutrophil sequestration in the liver and lung and increased liver injury. This study demonstrates a paradoxical increase in organ neutrophil sequestration using a leukocyte anti-adhesion therapy during sepsis and suggests that anti-adhesion therapies targeted towards neutrophil may worsen outcome if given during an ongoing, localized infection.
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PMID:Inhibition of neutrophil migration at the site of infection increases remote organ neutrophil sequestration and injury. 937 66

Cytomegalovirus (CMV) infection is an important cause of disease in immunocompromised patients. In a prospective longitudinal study of 34 septic patients, the incidence of active CMV infection was examined. Eleven of 34 patients (32.4%) had active CMV infection, diagnosed by immunocytochemical staining of CMV pp65 antigen in blood leukocytes and/or detection of CMV DNA by PCR. Positive results for CMV infection were obtained in a median of 4 days (by PCR) or 11 days (by staining of pp65 antigen) after onset of sepsis. Twenty patients for whom more than one sample was examined were selected for further analysis. Among the patients with active CMV infection (nine of 20) there was a trend toward higher median values of tumor necrosis factor alpha, interleukin-1 beta, alanine aminotransferase, and aspartate aminotransferase in plasma, in comparison with the values for patients without CMV infection. Sepsis in patients with CMV infection may affect outcome of the disease.
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PMID:High incidence of active cytomegalovirus infection among septic patients. 959 30

Graft size-matching is one of the critical concerns in adult-to-adult living donor liver transplantation (ATALDLT). In this study, we evaluated regeneration of a small-for-size graft less than 50% of the standard liver volume (SLV). We reviewed nine patients of united network of organ sharing (UNOS) status 2 or 3 who had undergone ATALDLT with a left lobe graft. For the comparison of liver regeneration, 20 hepatectomized patients for biliary malignancy were selected as non-transplant control group. In the ATALDLT group, graft size ranged from 30 to 49% of the SLV of recipients and their regeneration rates were 158%, 182%, 200% and 185% after 1,2, 3 and 4 weeks following transplantation, respectively. In the control group, preoperative volume of left lobe to whole liver volume ranged between 40 and 54% and their regeneration rates were 145%, 156%, 163% and 177% after 1,2, 3 and 4 weeks following extended right lobectomy, respectively. There was no statistical difference in regeneration rates between two groups. In the ATALDLT group, serum aspartate aminotransferase showed the median peak level of 198 IU/L on the first postoperative day and it was normalized within one week. Recovery of bilirubin clearance lagged behind rapid volume regeneration by about one week. Two patients died of sepsis. We postulate that the regenerative power of small-for-size grafts from living donors is preserved, although time-lag between volume regeneration and metabolic capability occurs in small-for-size grafts, when the initial graft volume meets metabolic demands during the early postoperative days.
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PMID:Regeneration of graft liver in adult-to-adult living donor liver transplantation using a left lobe graft. 974 37

The aim of this study was to monitor hepatic function in patients with pneumonia meeting the sepsis criteria of the American College of Chest Physicians/Society of Critical Care Medicine (ACCP/SCCM) and to determine if hepatic dysfunction is related to the systemic inflammatory response. Twenty patients were recruited. The monoethylglycinexylidide (MEGX) test was carried out on days 1-10 after admittance to the intensive care unit. Blood samples for determination of serum concentrations of hyaluronic acid, C-reactive protein (CRP), interleukin (IL)-6, IL-8, IL-10 and conventional liver function tests (aspartate aminotransferase, alanine aminotransferase, bilirubin, albumin) were also drawn. Patients were classified into two groups according to illness severity estimated by the simplified acute physiology score (SAPS II) on the day of admission. Patients in group I (n=10) had a SAPS II probability of mortality >3% while those in group II (n=10) had a SAPS II < 3%. The MEGX level over the first five days was significantly lower in group I than in group II (p<0.0001). Significant inverse correlations during the first 5 days were observed between the MEGX 30 min test results and IL-6, CRP and SAPS II and more modest correlations with hyaluronic acid (p=0.0025) and IL-10 (p=0.021). The conventional liver function tests did not differ between the two groups and were mostly within the respective reference ranges. We conclude that the MEGX test is a sensitive marker of liver dysfunction early in sepsis and that low MEGX values are associated with an enhanced inflammatory response.
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PMID:The monoethylglycinexylidide (MEGX) test as a marker of hepatic dysfunction in septic patients with pneumonia. 1115 41

Sustained upregulation of inducible nitric oxide (NO) synthase in the liver after endotoxin [lipopolysaccharide (LPS)] challenge may result in hepatocellular injury. We hypothesized that administration of a NO scavenger, NOX, may attenuate LPS-induced hepatocellular injury. Sprague-Dawley rats received NOX or saline via subcutaneous osmotic pumps, followed 18 h later by LPS challenge. Hepatocellular injury was assessed using biochemical assays, light, and transmission electron microscopy (TEM). Interleukin (IL)-6 mRNA was measured by RT-PCR. Tumor necrosis factor (TNF)-alpha protein expression was determined by immunohistochemistry. NOX significantly reduced serum levels of ornithine carbamoyltransferase and aspartate aminotransferase. TNF-alpha and IL-6 expression were increased in the livers of saline-treated but not NOX-treated rats. Although there was no difference between groups by light microscopy, TEM revealed obliteration of the space of Disse in saline-treated but not in NOX-treated animals. Electron paramagnetic resonance showed the characteristic mononitrosyl complex in NOX-treated rats. We conclude that NOX reduces hepatocellular injury after endotoxemia. NOX may be useful in the management of hepatic dysfunction secondary to sepsis or other diseases associated with excessive NO production.
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PMID:Scavenging nitric oxide reduces hepatocellular injury after endotoxin challenge. 1140 70

Over the past decade we have reported excellent outcomes in pediatric living-donor liver transplantation (LDLT) with recipient survival exceeding 90%. Principles established in these patients were extended to LDLT in adults. To compare outcomes in donors and recipients between adult and pediatric LDLT in a single center, we reviewed patient records of 45 LDLT performed between 1/98 and 2/01: 23 adult LDLT (54 +/- 6.5 yr) and 22 pediatric LDLT (33.7 +/- 53.5 months). Preoperative liver function was worse in adults (International Normalized Ratio [INR] 1.5 +/- 0.4 vs. INR 1.2 +/- 0.5; p = 0.032). 4 adults (17%) met criteria for status 1 or 2A. Only 1 child was transplanted urgently. Analysis included descriptive statistics and Kaplan-Meier estimation. Donor mortality was 0% with 1 re-exploration, 2.4%. Median hospital stay (LOS) was 6.0 days (range, 4-12 days). Donor morbidity and LOS did not differ by sex, extent of hepatectomy, or adult and pediatric LDLT ( p = 0.49). In contrast, recipient outcomes were worse for adults. Adult 1 year graft survival was 65% (3 retransplants [ReTx], 5 deaths) vs. 91% for children (1 ReTx, 1 death) p = 0.02. Graft losses in adults were due to sepsis (n = 3), small for size (n = 2), suicide, and hepatic artery thrombosis (HAT), whereas in children graft losses were due to portal thrombosis and total parenteral nutrition (TPN) liver failure. Biliary leaks occurred in 22% of adults and 9% of children. Hepatic vein obstruction occurred in 17% of adults and in none of the children. Median LOS was comparable (adult, 16.5 days (range, 7-149 days); child, 17 days (range, 10-56 days), p = 0.2). Graft function (total bilirubin (TBili) < 5mg/dl, INR < 1.2, aspartate aminotransferase (AST) < 100 U/l) normalizing by day 4 in children and by day 14 in adults. Adults fared worse, with an array of problems not seen in children, in particular, hepatic vein obstruction and small-for-size syndrome. Biliary leaks were diagnosed later in adults and were lethal in 3 cases; this was later avoided with biliary drainage in adult recipients. Finally, use of LDLT in decompensated adults led to death in 3 of 4 patients, and should be restricted to elective use.
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PMID:Analysis of failure in living donor liver transplantation: differential outcomes in children and adults. 1260 66

The role of endothelin ETA receptors in sepsis-induced mortality and edema formation was evaluated with a selective antagonist ABT-627 [2-(4-methoxyphenyl)-4-(1,3-benzodioxol-5-yl)-1-(N,N-di(n-butyl)amino carbonylmethyl)-pyrrolidine-3-carboxylic acid]. Sprague-Dawley rats received saline (control group), Escherichia coli endotoxin (10 mg/kg, sepsis group) or infusion of ABT-627 prior and immediately after saline and endotoxin injection. Mortality, edema formation (wet/dry ratios), and multiple tissue injury (indicated by serum concentrations of creatinine, urea, bilirubin, creatine kinase, lactate dehydrogenase, and aspartate aminotransferase) were monitored within 5 h. Endotoxin injection elicited 64% mortality, significantly augmented edema formation in liver, heart, lung, and kidney, and raised serum levels of tissue injury markers. Pretreatment with ABT-627 completely reversed endotoxin-induced mortality, significantly attenuated wet/dry ratios of the heart, liver, and kidney, but not lungs, and reduced serum levels of creatine kinase, creatinine, aspartate aminotransferase, and lactate dehydrogenase, but not that of urea and bilirubin. These results suggest that endothelin ETA receptors play a significant role in promoting mortality, edema formation (except in the lungs), and tissue injury in animals with severe sepsis.
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PMID:Role of endothelin ETA receptors in sepsis-induced mortality, vascular leakage, and tissue injury in rats. 1290 4

The liver is one of the major target organs affected in sepsis, and its failure always results in critical consequences. It has been reported that recombinant human interleukin 11 (rhIL-11), a pleiotropic cytokine, may be useful in the treatment of sepsis. However, the effect of IL-11 specifically on the hepatic failure in sepsis has not been evaluated. In the present study, we examined the effect of rhIL-11 on the hepatic injury in a rat endotoxemia model. Acute endotoxemia was induced in male Sprague-Dawley rats by intraperitoneal injection (i.p.) of bacterial lipopolysaccharide (LPS, 20 mg/kg). Immediately after injection of LPS, rats were treated with rhIL-11 (150 microg/kg, i.p.) or the vehicle. LPS treatment induced severe hepatic injury as revealed by marked increases in serum alanine transaminase (ALT) and aspartate transaminase (AST) activities, extensive hepatocyte necrosis, tumor necrosis factor-alpha (TNF-alpha) mRNA, inducible nitric oxide synthase (iNOS) mRNA, and DNA-binding activity of nuclear factor-kappaB (NF-kappaB). In contrast, rhIL-11 treatment significantly ameliorated the LPS-induced hepatic injury, as judged by marked improvement in all these indices. In addition, rhIL-11 treatment markedly decreased LPS-induced mortality. These results indicate that rhIL-11 plays a significant protective role in LPS-induced hepatic injury in acute endotoxemia.
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PMID:A protective role of interleukin 11 on hepatic injury in acute endotoxemia. 1475 86

Several studies have implicated a role of peptidoglycan (PepG) as a pathogenicity factor in sepsis and organ injury, in part by initiating the release of inflammatory mediators. We wanted to elucidate the structural requirements of PepG to trigger inflammatory responses and organ injury. Injection of native PepG into anesthetized rats caused moderate but significant increases in the levels of alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, and bilirubin (markers of hepatic injury and/or dysfunction) and creatinine and urea (markers of renal dysfunction) in serum, whereas PepG pretreated with muramidase to digest the glycan backbone failed to do this. In an ex vivo model of human blood, PepG containing different amino acids induced similar levels of the cytokines tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), IL-8, and IL-10, as determined by plasma analyses (enzyme-linked immunosorbent assay). Hydrolysis of the Staphylococcus aureus cross-bridge with lysostaphin resulted in moderately reduced release of TNF-alpha, IL-6, IL-8, and IL-10, whereas muramidase digestion nearly abolished the ability to induce cytokine release and IL-6 mRNA accumulation in CD14(+) monocytes compared to intact PepG. However, additional experiments showed that muramidase-treated PepG synergized with lipopolysaccharide to induce TNF-alpha and IL-10 release in whole blood, despite its lack of inflammatory activity when administered alone. Based on these studies, we hypothesize that the structural integrity of the glycan chain of the PepG molecule is very important for the pathogenic effects of PepG. The amino acid composition of PepG, however, does not seem to be essential for the inflammatory properties of the molecule.
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PMID:Organ injury and cytokine release caused by peptidoglycan are dependent on the structural integrity of the glycan chain. 1497 33


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