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Query: UMLS:C0243026 (sepsis)
 52,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Advances in liver transplantation have made the procedure an accepted therapeutic measure for patients with end-stage liver disease. This report is based on the authors experience on the first adult liver transplant in Singapore. The anaesthetic management is a challenge as patients are in long-standing hepatic failure with derangements of cardiovascular, renal, pulmonary, central nervous, and haematological systems. Therefore, individual preoperative assessment must incorporate a thorough understanding of these pathophysiologic phenomena and their interactions with anaesthetic drugs. Similarly, the postoperative care of the recipient will require intensive critical monitoring of all vital organ, systems and aggressive intervention to support failing organ systems. The important early concerns in the immediate postoperative period (less than 72 hours) include bleeding and graft function. After the first 72 hours, if the liver is functioning and the patient is not bleeding, it is a period of repair for the organ systems which were damaged prior to or during the transplant procedure. Intravenous nutrition is begun, and the immunosuppression maintenance dose is established. During the first three weeks, most of the technical causes of graft dysfunction, sepsis, and acute rejection become apparent. The distinction between rejection and infection continues to be an enigma, and requires rapid differentiation as the modes of therapy are totally different. The role of anaesthesiologists in the extraoperative care of the liver transplant recipient involves awareness and interdisplinary communication.
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PMID:Extraoperative management of the liver transplant patient. 179 72

Despite the fact that the clinical experience with TPN has been gathered from patients of all age groups suffering from a variety of underlying diseases running very different clinical courses and often complicated by a number of septic metabolic and therapeutic problems, certain points can be made with regard to predisposing factors. 1) Prematures and neonates are particularly at risk. 2) Cholestasis occurs earlier and has a greater chance of leading to chronic liver disease in surgical patients. 3) Hepatobiliary abnormalities are more likely to develop after a prolonged period of TPN and are less frequent in patients who are also receiving oral feedings. Definition of the mechanism of hepatobiliary complications remains a problem. Although calcium bilirubinate appears to be responsible for sludge and stones, there is as yet no explanation for the presence of large amounts of indirect-reacting bilirubin in gallbladder and hepatic bile in patients on TPN. The pathogenesis of cholestatic liver disease remains an enigma; the lack of normal gastrointestinal stimuli for bile formation, abnormalities of bile acid metabolism, and sepsis might play roles, but attention has recently been attracted to amino acid toxicity and this possibility deserves further study.
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PMID:Hepatobiliary complications associated with TPN: an enigma. 393 7

Congenital stenosis of the pulmonary veins is a rare but frequently lethal congenital cardiac abnormality. Eight patients with this malformation were diagnosed, evaluated and treated. All eight patients had associated congenital cardiac defects. Two of the eight died, one of sepsis and one after operative pulmonary venoplasty. In three patients who underwent transvenous balloon catheter dilation of the stenosis the procedure provided immediate but transient relief of the stenosis. The prognosis for symptomatic infants with pulmonary vein stenosis is poor and its treatment an enigma.
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PMID:Congenital stenosis of individual pulmonary veins: clinical spectrum and unsuccessful treatment by transvenous balloon dilation. 621 Oct 76

Cellular mechanisms of sepsis-induced ileus remain an enigma. The study aim was to determine the role of nitric oxide (NO) in mediating the suppression of rat jejunal circular smooth muscle activity during endotoxemia. Isolated muscularis inducible NO synthase (iNOS) mRNA was measured by RT-PCR, immunohistochemistry was employed to localize iNOS protein, and contractile activity was measured in an organ bath. The low basal expression of muscularis iNOS mRNA expression was increased in a time-dependent fashion after lipopolysaccharide (LPS), resulting in a 20-fold increase over controls 3 h after injection. Immunohistochemistry of muscularis whole mounts and dissociated muscularis cells for iNOS revealed staining only in the muscularis macrophages 12 h after LPS. LPS caused a 68% reduction in spontaneous muscle activity 12 h after injection, which improved by 53% after the in vitro application of the selective iNOS inhibitor L-N(6)-(1-iminoethyl)lysine. Similar results were obtained in C57BL/6 mice but not in iNOS knockout mice. These data demonstrate that macrophage iNOS plays an important role in mediating LPS-induced intestinal circular muscle suppression.
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PMID:LPS-induced muscularis macrophage nitric oxide suppresses rat jejunal circular muscle activity. 1044 63

Calcitonin precursors (CTpr), including procalcitonin, are important markers and also potentially harmful mediators in response to microbial infections. The source and function of CTpr production in sepsis, however, remains an enigma. In the classical view, the transcription of the CT-I gene is restricted to neuroendocrine cells, in particular the C cells of the thyroid. To better understand the pathophysiology of CTpr induction in sepsis, we used an animal model analog to human sepsis, in which bacterial infection is induced in hamsters by implanting Escherichia coli pellets ip. Compared with control hamsters, levels of CTpr were elevated several fold in septic plasma and in nearly all septic hamster tissues analyzed. Unexpectedly, CT-messenger RNA was ubiquitously and uniformly expressed in multiple tissues throughout the body in response to sepsis. Notably, the transcriptional expression of CT-messenger RNA seemed more widely up-regulated in sepsis than were classical cytokines (e.g. tumor necrosis factor-alpha and interleukin-6). Our findings, which describe a potentially new mechanism of host response to a microbial infection mediated by CTpr, introduce a new pathophysiological role for the CT-I gene.
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PMID:Ubiquitous expression of the calcitonin-i gene in multiple tissues in response to sepsis. 1123 31

In this study, we demonstrate that mice deficient in TNFR1 (TNFR1(-/-)) were resistant to LPS-induced encephalopathy. Systemic administration of lipopolysaccharide (LPS) induces a widespread inflammatory response similar to that observed in sepsis. Following LPS administration TNFR1(-/-) mice had less caspase-dependent apoptosis in brain cells and fewer neutrophils infiltrating the brain (p<0.039), compared to control C57Bl6 (TNFR1(+/+)) mice. TNFR1-dependent increase in aquaporin (AQP)-4 mRNA and protein expression was observed with a concomitant increase in water content, in brain (18% increase in C57Bl6 mice treated with LPS versus those treated with saline), similar to cerebral edema observed in sepsis. Furthermore, absence of TNFR1 partially but significantly reduced the activation of astrocytes, as shown by immunofluorescence and markedly inhibited iNOS mRNA expression (p<0.01). Septic encephalopathy is a devastating complication of sepsis. Although, considerable work has been done to identify the mechanism causing the pathological alterations in this setting, the culprit still remains an enigma. Our results demonstrate for the first time that endotoxemia leads to inflammation in brain, with alteration in blood-brain barrier, up-regulation of AQP4 and associated edema, neutrophil infiltration, astrocytosis, as well as apoptotic cellular death, all of which appear to be mediated by TNF-alpha signaling through TNFR1.
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PMID:TNF is a key mediator of septic encephalopathy acting through its receptor, TNF receptor-1. 1788 56

Despite several decades of research and phenomenal advances in technology and therapeutics, sepsis remains a catastrophic enigma. As a frequent cause of death, sepsis now rivals acute myocardial infarction. The longstanding therapeutic principles of early antibiotics use and supportive care have been difficult to improve upon. The authors conducted a concise review of pertinent literature on the pathophysiologic mechanisms of sepsis and the pharmacologic effects of statins. They conclude that, though statins possess anti-inflammatory and lipid-lowering properties, these effects may not be advantageous throughout the changing immunoresponse that can occur in sepsis syndrome. Based on the available information, statin therapy seems advantageous before the onset of sepsis and during sepsis resolution--but not during the compensatory anti-inflammatory response that may occur. Thus, the authors recommend that, until the status of a patient's changing immune response can be clearly determined, the uninterrupted use of statin therapy throughout the full spectrum of sepsis should be avoided.
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PMID:Statins and sepsis: good bullet, disappearing target. 1880 77

Septic encephalopathy is a frequent complication of the sepsis syndrome, with no therapies available that can prevent the associated neurological dysfunction in humans. It is caused by a number of processes and networks going awry, the exact cellular and molecular mechanisms of which remain an enigma. Several mediators of inflammation have been assigned a key role in sepsis, including cytokines, chemokines and complement cascade. With the observations that brain dysfunction in a sepsis setting can be alleviated by regulation of the cytokines and complement proteins in various species of animals, optimism is building for a possible therapy of sepsis-damaged brain. This article reviewed the advances in the understanding of the underlying mechanisms causing pathology in SE, with an emphasis on the inflammatory and excitatory mediators such as the cytokines, complement proteins and neurotransmitters, investigating their potential as possible therapeutic targets.
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PMID:Septic encephalopathy: inflammation in man and mouse. 2121 56

Sepsis is among the leading causes of death worldwide and its incidence is increasing. Defined as the host response to infection, sepsis is a clinical syndrome considered to be the expression of a dysregulated immune reaction induced by danger signals that may lead to organ failure and death. Remarkable progresses have been made in our understanding of the molecular basis of host defenses in recent years. The host defense response is initiated by innate immune sensors of danger signals designated under the collective name of pattern-recognition receptors. Members of the family of microbial sensors include the complement system, the Toll-like receptors, the nucleotide-binding oligomerization domainlike receptors, the RIG-I-like helicases and the C-type lectin receptors. Ligand-activated pattern-recognition receptors kick off a cascade of intracellular events resulting in the expression of co-stimulatory molecules and release of effector molecules playing a fundamental role in the initiation of the innate and adaptive immune responses. Fine tuning of proinflammatory and anti-inflammatory reactions is critical for keeping the innate immune response in check. Overwhelming or dysregulated responses induced by infectious stimuli may have dramatic consequences for the host as shown by the profound derangements observed in sepsis. Unfortunately, translational research approaches aimed at the development of therapies targeting newly identified innate immune pathways have not held their promises. Indeed, all recent clinical investigations of adjunctive anti-sepsis treatments had little, if any, impact on morbidity and all-cause mortality of sepsis. Dissecting the mechanisms underlying the transition from infection to sepsis is essential for solving the sepsis enigma. Important components of the puzzle have already been identified, but the hunt must go on in the laboratory and at the bedside.
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PMID:Host innate immune responses to microbial pathogens. 2350 91

Mitogen-activated protein kinase phosphatase (Mkp)-1 exerts its anti-inflammatory activities during Gram-negative sepsis by deactivating p38 and c-Jun N-terminal kinase (JNK). We have previously shown that Mkp-1+/+ mice, but not Mkp-1-/- mice, exhibit hypertriglyceridemia during severe sepsis. However, the regulation of hepatic lipid stores and the underlying mechanism of lipid dysregulation during sepsis remains an enigma. To understand the molecular mechanism underlying the sepsis-associated metabolic changes and the role of Mkp-1 in the process, we infected Mkp-1+/+ and Mkp-1-/- mice with Escherichia coli i.v., and assessed the effects of Mkp-1 deficiency on tissue lipid contents. We also examined the global gene expression profile in the livers via RNA-seq. We found that in the absence of E. coli infection, Mkp-1 deficiency decreased liver triglyceride levels. Upon E. coli infection, Mkp-1+/+ mice, but not Mkp-1-/- mice, developed hepatocyte ballooning and increased lipid deposition in the livers. E. coli infection caused profound changes in the gene expression profile of a large number of proteins that regulate lipid metabolism in wildtype mice, while these changes were substantially disrupted in Mkp-1-/- mice. Interestingly, in Mkp-1+/+ mice E. coli infection resulted in downregulation of genes that facilitate fatty acid synthesis but upregulation of Cd36 and Dgat2, whose protein products mediate fatty acid uptake and triglyceride synthesis, respectively. Taken together, our studies indicate that sepsis leads to a substantial change in triglyceride metabolic gene expression programs and Mkp-1 plays an important role in this process.
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PMID:Dysregulation of Lipid Metabolism in Mkp-1 Deficient Mice during Gram-Negative Sepsis. 3056 3


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