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

Sepsis causes lymphopenia which is inversely correlated with patient survival. The role of apoptosis-specific immune-activation and activation-induced cell-death in sepsis is incompletely understood. Fifteen septic patients and 20 healthy controls were included. T-cell proliferation was measured by [3H]thymidine uptake. Apoptosis and cell phenotype were determined by FACS. sTNFR1, sCD95, interleukin-1beta converting enzyme (sICE), and interleukin (IL)-10 were measured by ELISA. PHA and CD3-driven T-cell proliferation were significantly decreased in septic patients. The percentages of CD3(+) and CD4(+) T cells and CD19(+) B cells were significantly reduced. Percent memory T-cells (CD45RO(+)) and cells undergoing apoptosis (CD95(+)/annexin-V(+)) were significantly increased in sepsis. Moreover, sCD95, sTNFRI, and ICE were significantly increased. Anti-CD3 antibody triggering induced a 56% increase of CD4 T-cell death in septic patients vs. 7.5% in controls relative to IgG. Serum level of IL-10, a Th2 cytokine, was enhanced. These findings strongly suggest that in septic patients Th1 T-cells are selectively susceptible to undergo apoptosis. This observation provides an additional pathophysiological concept in the genesis of Th2 dominance.
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PMID:Susceptibility to programmed cell death in T-lymphocytes from septic patients: a mechanism for lymphopenia and Th2 predominance. 1292 95

This retrospective study evaluated complications associated with caesarean section in HIV-infected women. For each HIV-positive patient ( n=45) a control group of ten seronegative women ( n=450) was matched for age, number of foetuses, gestational age, indication for caesarean section, status of the membranes and kind of anaesthesia. All women delivered in the same hospital using a uniform protocol. We evaluated the duration of stay in hospital after operation, the need for antibiotics after caesarean section, the incidence of minor postoperative complications (mild anaemia, mild temperature or fever 24 h after surgery, wound haematoma or infection, urinary tract infection, endometritis) and major postoperative complications (severe anaemia, pneumonia, pleural effusion, peritonitis, sepsis, disseminated intravascular coagulation, thromboembolism). Most HIV-positive women (64.5%) had a complicated recovery after surgery. A higher incidence of major and minor postoperative complications were observed in the HIV-positive group than in the control group. There was a statistically significant greater incidence of mild anaemia, mild temperature or fever, urinary tract infection and pneumonia in the HIV-positive group. HIV-positive women with less than 500x10(6) CD4(+) lymphocytest/l had higher post-caesarean section morbidity than HIV-positive women with more than 500x10(6) CD4(+) lymphocytest/l. The median duration of hospital stay was significantly higher in the HIV-positive group (median 7 days) than in the HIV-negative group (median 4 days). The rate of HIV vertical transmission was 8.8%. Higher post-caesarean section morbidity was found in HIV-positive women than in controls. Unfortunately, the HIV-positive women (with low CD4 lymphocytes counts), whose infants theoretically will benefit most from caesarean delivery, are also the women who are most likely to experience post-operative complications.
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PMID:Post-operative complications after caesarean section in HIV-infected women. 1450 67

We have previously demonstrated that the detergent Tyloxapol is effective in preventing reactions to endotoxin. We studied the effects of Tyloxapol on the morbidity and mortality from endotoxemia in rabbits and on the mortality in rats with sepsis. The effects of Tyloxapol on endotoxin binding and macrophage activation were studied in the macrophage cell line RAW264.7 and CHO cells expressing CD14. Isolated human leukocytes were used to study the effects of Tyloxapol on immune reactions, leukocyte motility, and phagocytosis. Intravenous Tyloxapol (200 mg/kg), given prior to or at the time of endotoxin infusion protected rabbits from developing shock. In rats with peritoneal sepsis, a lipid-rich diet and Tyloxapol given at the time of induction of peritonitis protected them from septic death. In vitro, Tyloxapol blocked the binding of endotoxin to murine macrophages and CHO cells expressing CD14, activation of macrophages, and also some antigen-antibody immune reactions (mediated by CD2, CD4, CD22, HLA-DR). Tyloxapol may prevent the reaction to endotoxin by desensitizing endotoxin-recognizing receptors.
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PMID:Tyloxapol attenuates the pathologic effects of endotoxin in rabbits and mortality following cecal ligation and puncture in rats by blockade of endotoxin receptor-ligand interactions. 1452 71

Citrobacter rodentium uses virulence factors similar to the enteropathogenic Escherichia coli to produce attaching and effacing lesions in the distal colon of mice. We used this infection model to determine components of adaptive immunity needed to survive infection. During acute infection, wild-type mice develop breaks across infected epithelial surfaces but resolve infection. Surprisingly, mice markedly deficient in mucosal lymphocyte populations from beta(7) integrin deficiency resolve infection, as do CD8alpha-/- or TCR-delta-/- mice. In contrast, CD4-/- or TCR-beta-/- mice develop polymicrobial sepsis and end-organ damage, and succumb during acute infection, despite epithelial damage similar to wild-type mice. B cell-deficient (MuMT-/-) or B and T cell-deficient (recombinase-activating gene 2-/-) mice develop severe pathology in colon and internal organs, and deteriorate rapidly during acute infection. Surviving mice develop robust Citrobacter-specific serum IgM responses during acute infection, whereas mice that succumb do not. However, CD4-/- mice receiving serum Igs from infected wild-type mice survive and clear the infection. Our data show that survival of apparently self-limited and luminal mucosal infections requires a systemic T cell-dependent Ab response against bacteria that enter through damaged mucosa. These findings have implications for understanding host defense against mucosal infections, including the pathogenesis of these diseases in immunocompromised populations.
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PMID:Critical role of T cell-dependent serum antibody, but not the gut-associated lymphoid tissue, for surviving acute mucosal infection with Citrobacter rodentium, an attaching and effacing pathogen. 1468 52

We have generated transgenic mice expressing the leech anticoagulant hirudin and human tissue factor pathway inhibitor tethered to the cell surface by fusion with fragments of human CD4 and P-selectin. Expression of the transgenes is under the control of the CD31 (platelet endothelial cell adhesion molecule [PECAM]) promoter, limiting expression to endothelial cells, monocytes, and platelets. In addition, the P-selectin sequence directs expression to secretory granules. Functional cell surface expression only occurs when the cells are activated. In a mouse model of systemic lipopolysaccharide (LPS)-induced endotoxemia, we show that expression of either anticoagulant on activated endothelium inhibits the widespread intravascular thrombosis, thrombocytopenia, and consumptive coagulopathy associated with endotoxemia. Importantly, non- LPS-treated transgenic mice had normal baseline bleeding times. We speculate that targeted delivery of anticoagulants to the endothelium may be a strategy worth pursuing in clinical sepsis to improve efficacy of systemic anticoagulation while minimizing potential hemorrhagic side effects.
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PMID:Inhibition of intravascular thrombosis in murine endotoxemia by targeted expression of hirudin and tissue factor pathway inhibitor analogs to activated endothelium. 1512 22

The physiological alterations induced by acute inflammation present significant management challenges for anaesthesiologists. Major surgery, trauma, burns and sepsis all have large inflammatory components. Acute inflammation is characterized by vasodilatation, fluid exudation and neutrophil infiltration. These processes are activated and amplified by a series of intracellular and extracellular factors that tightly co-ordinate the inflammatory process. The innate immune system responds rapidly to infection or injury. Macrophages, natural killer cells, CD8 + T-lymphocytes and neutrophils provide an early response to injurious factors in an effort to contain and eliminate harmful stimuli. The adaptive immune response requires prior exposure to microbial antigens, is mediated primarily by CD4 + T-lymphocytes and serves to further amplify acute inflammation. Although acute inflammation is fundamentally beneficial, severe inflammation can precipitate the systemic inflammatory response syndrome. This syndrome is characterized by hyperinflammation and can cause organ injury, shock and death in its most severe forms. Overall, our understanding of inflammation has increased tremendously during the past 20 years. However, these basic science advances have not yet translated into widespread benefit for patients suffering from trauma, sepsis and systemic inflammation.
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PMID:Mechanisms of the inflammatory response. 1521 35

Dendritic cells (DCs) play a key role in critical illness and are depleted in spleens from septic patients and mice. To date, few studies have characterized the systemic effect of sepsis on DC populations in lymphoid tissues. We analyzed the phenotype of DCs and Th cells present in the local (mesenteric) and distant (inguinal and popliteal) lymph nodes of mice with induced polymicrobial sepsis (cecal ligation and puncture). Flow cytometry and immunohistochemical staining demonstrated that there was a significant local (mesenteric nodes) and partial systemic (inguinal, but not popliteal nodes) loss of DCs from lymph nodes in septic mice, and that this process was associated with increased apoptosis. This sepsis-induced loss of DCs occurred after CD3(+)CD4(+) T cell activation and loss in the lymph nodes, and the loss of DCs was not preceded by any sustained increase in their maturation status. In addition, there was no preferential loss of either mature/activated (MHCII(high)/CD86(high)) or immature (MHCII(low)/CD86(low)) DCs during sepsis. However, there was a preferential loss of CD8(+) DCs in the local and distant lymph nodes. The loss of DCs in lymphoid tissue, particularly CD8(+) lymphoid-derived DCs, may contribute to the alterations in acquired immune status that frequently accompany sepsis.
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PMID:Characterization of the systemic loss of dendritic cells in murine lymph nodes during polymicrobial sepsis. 1532 63

Liver transplantation (LT) in human immunodeficiency virus (HIV)-positive individuals is considered to be an experimental therapy with limited reported worldwide experience, and little long-term survival data. Published data suggest that the short-term outcome is encouraging in selected patients. Here, we report our experience in 14 HIV-infected liver allograft recipients, and compare outcomes between those coinfected with hepatitis C virus (HCV) and the non-HCV group. A total of 14 HIV-infected patients (12 male, 2 female, age range 26-59 years) underwent LT between January 1995 and April 2003. Indications for LT were HCV (n = 7), hepatitis B virus (HBV; n = 4), alcohol-induced liver disease (n = 2), and seronegative hepatitis (n = 1); 3 patients presented with acute liver failure. At LT, CD4 cell counts (T-helper cells that are targets for HIV) ranged from 124 to 500 cells/microL (mean 264), and HIV viral loads from <50 to 197,000 copies/mL. Nine of 12 patients were exposed to highly active antiretroviral therapy (HAART) before LT. In the non-HCV group (n = 7), all patients are alive, all surviving more than 365 days (range 668-2,661 days). No patient has experienced HBV recurrence, and graft function is normal in all 7 patients. However, 5 of 7 HCV-infected patients died after LT at 95-784 days (median 161 days). A total of 4 patients died of complications due to recurrent HCV infection and sepsis, despite antiviral therapy in 3 of them. A total of 3 patients experienced complications relating to HAART therapy. In conclusion, outcome of LT in HIV-infected patients with HBV or other causes of chronic liver disease indicates that LT is an acceptable therapeutic option in selected patients. However, longer follow-up in larger series is required before a conclusive directive can be provided for HCV / HIV coinfected patients requiring LT.
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PMID:Outcomes of liver transplantation in HIV-infected individuals: the impact of HCV and HBV infection. 1537 7

Over a three-year period, the authors prospectively implemented a protocol for management of musculoskeletal sepsis (MSS) in HIV carriers in Yaounde, Cameroon. The diagnosis of MSS was based on conventional criteria. HIV carriage was screened by an ELISA test and confirmed with the Western Blot technique. The immune status was based on CD4 lymphocyte count by flow cytometry; patients were classified as non-immunodepressed (NID), mildly immunodepressed (MID), or severely immunodepressed (SID) based on their CD4 lymphocyte count, as the latter was respectively over 500, between 200 and 500 or less than 200 per ml. Infection was treated by surgical debridement followed by a long-course targeted antibiotic therapy. All SID patients and some MID patients with AIDS-related symptoms also had standard antiretroviral (ARV) therapy. Thirty-one of 294 patients seen with musculoskeletal sepsis during the study period and tested for HIV were found to be HIV carriers. Their mean age was 33 years; the male/female ratio was 1.58. The following clinical pictures were observed: chronic osteomyelitis (COM) in 32.3% of the cases, septic arthritis (SA) in 38.7%, soft tissue infection (STI) in 25.8%; the last case was a severe leg complication of Buruli Ulcer (BU). Among these 31 patients, 38.7% were classified as SID (5 COM, 4 SA, 2 STI and the BU patient), 25.8% as MID (2 COM, 4 SA, 2 STI) and 35.5% as NID (3 COM, 6 SA, 2 STI). The organisms involved were not specific. Fifteen patients were managed conventionally, while the other 16 had the usual treatment associated with ARV therapy. The immediate outcome of MSS was good in 29 patients, after a mean hospital stay of five weeks; in two cases of septic arthritis of the knee, a second debridement was needed, due to persistent drainage, and the sinuses all closed. Three months after discharge, one patient with COM of the humerus developed a low-flow fistula which was closed after a revision sequestrectomy. After one year, none of the patients complained of any symptom suggesting reactivation of their MSS. There is no evidence that HIV carriage is in itself a high risk factor for musculoskeletal sepsis; the incidence of HIV carriage was indeed virtually similar in the 294 patients with MSS and in the general population, i.e. around 10%. However, in order to improve the outcome following musculoskeletal infections in patients with HIV, their management should take into account their immune status, based on a CD4 lymphocyte count. NID patients should be treated as any other patients with MSS, while SID should have additional standard ARV treatment. For those who are MID, the indication for antiretroviral therapy should depend on the presence of one or more AIDS-related signs.
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PMID:The management of musculoskeletal infection in HIV carriers. 1548 21

Sepsis is associated with depression of T cell-dependent immune reactivity with proinflammatory cytokines, such as tumour necrosis factor (TNF)-alpha, playing an important role. Recent investigations describe an association between these immunological alterations and disturbances of the endocrine system, related most frequently to sex steroid hormones. Dehydroepiandrosterone (DHEA), one of the most abundant adrenal sex steroid precursors, seems to have a protective immunological effect towards septic insults. In this study, both the role of TNF-receptor I (RI) and possible interactions in the protective role of DHEA were investigated in a murine model of polymicrobial sepsis. Polymicrobial sepsis was induced by caecal ligation and puncture (CLP) in a murine model. The effects of DHEA on survival, clinical parameters and cellular immunity (T lymphocytes and natural killer (NK) cells) were investigated. CLP was performed in genetically modified TNF-RI knock-out (TNF-RI(-/-)) and genetically unmodified (wild-type, WT) mice. DHEA application was associated with a decrease in the mortality rate in WT animals. A mortality rate of 91.7% was observed in TNF-RI(-/-) mice after CLP. This mortality rate was reduced to 37.5% by the application of DHEA. In sham-operated TNF-RI(-/-) animals, a significantly higher proportion of NK cells within the lymphocyte population was measured compared with the corresponding WT group. After CLP, a significant increase in the percentage cell count of NK cells was recorded in WT mice. Overall, following DHEA application in WT mice, an alteration in the cellular immune response was characterized by a reduction in the percentage counts of CD4(+), CD8(+) and NK cells. In the group of TNF-RI(-/-) mice treated with DHEA, no increase in the percentage cell count of NK cells was observed after CLP. No data for cell analysis were available from the CLP-TNF-RI(-/-) mice treated with saline, due to the high mortality rate in these animals. DHEA reduces the complications of sepsis in a TNF-RI-independent manner. Our study suggests that NK cells are involved in the protective mechanism of DHEA in WT mice. It would therefore seem that DHEA represents a feasible alternative therapy for the dysregulated immune system in sepsis.
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PMID:Are alterations of lymphocyte subpopulations in polymicrobial sepsis and DHEA treatment mediated by the tumour necrosis factor (TNF)-alpha receptor (TNF-RI)? A study in TNF-RI (TNF-RI(-/-)) knock-out rodents. 1549 30


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