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1

Group C streptococcal sepsis complicating Fournier gangrene.  

PubMed

Fournier gangrene is a life-threatening necrotizing fasciitis of the perineal-scrotal area that occurs in diabetic males. Patients typically present with systemic toxicity and significant inflammatory changes in the scrotum and perineum. Most cases of Fournier gangrene are polymicrobic and require urgent surgical debridement and broad-spectrum antibiotic therapy. We describe a case of Fournier gangrene in a young diabetic man that was associated with group C streptococcal bacteremia, an association previously unreported in the literature to our knowledge. PMID:16217985

Marinella, Mark A

2005-09-01

2

Multifocal streptococcal pyomyositis complicated by acute compartment syndrome: case report.  

PubMed

A 5-year-old girl sought treatment for pyrexia of unknown origin. Despite prompt surgical drainage of a streptococcal septic arthritis of the ankle joint, her condition deteriorated. Multifocal pyomyositis was subsequently diagnosed. This was complicated by acute compartment syndrome in three extremities. With aggressive surgical and medical management, the child made a complete recovery. Orthopaedic clinicians in nontropical areas must familiarize themselves with this rare, potentially life-threatening, but eminently curable disease. PMID:11360777

Harrington, P; Scott, B; Chetcuti, P

2001-04-01

3

[Sepsis in acute severe pancreatitis].  

PubMed

Retrospective analysis of 99 consecutive cases of acute severe pancreatitis established presence of systemic inflammation in all patients. Magnitude of acute phase response was characterised by C-reactive protein and Interleukin-6 values. Progression to multiple organ failure raised considerably lethality. Failure developed more frequently in respiratory system, liver and kidneys. General mortality was 38,4%. PMID:16927913

Hotineanu, V F; Balica, I M; Bogdan, V I

2006-01-01

4

Lymphocyte cell subpopulations during acute post-streptococcal glomerulonephritis: cell surface antigens and binding of streptococcal membrane antigens and C-reactive protein.  

PubMed Central

T lymphocyte surface markers were examined in 23 patients with acute post-streptococcal glomerulonephritis (AGN) in parallel with normal controls and individuals without nephritis who showed evidence of pharyngeal or skin-sore beta-haemolytic streptococcal infection. Numbers of T gamma cells were similar in AGN and normal controls but were significantly lower (P less than 0.05) than those in skin-sore culture-positive streptococcal infection controls. Numbers of T mu cells were similar in AGN and normal controls but were lower (P less than 0.05) than those observed in streptococcal controls. Percentages of T mu cells were similar in AGN and normal controls but were lower (P less than 0.05) than those recorded in streptococcal infection control groups. Proportions of T cells were reduced during AGN (P less than 0.05). Lymphocytes capable of binding type 12 group A streptococcal membranes were increased (30.4%) in patients with AGN as compared to normal controls (4.1%). Subjects with streptococcal infection alone showed elevated but intermediate relative numbers (10.5%) of lymphocytes binding group A membranes. Increased relative numbers of both B and T lymphocytes binding group A streptococcal membranes were present in both AGN and non-nephritogenic streptococcal infection controls. PMID:7039887

Williams, R C; Van de Rijn, I; Reid, H; Poon-King, T; Zabriskie, J B

1981-01-01

5

Evidence of streptococcal origin of acute non-necrotising cellulitis: a serological study.  

PubMed

Bacteriological diagnosis is rarely achieved in acute cellulitis. Beta-haemolytic streptococci and Staphylococcus aureus are considered the main pathogens. The role of the latter is, however, unclear in cases of non-suppurative cellulitis. We conducted a serological study to investigate the bacterial aetiology of acute non-necrotising cellulitis. Anti-streptolysin O (ASO), anti-deoxyribonuclease B (ADN) and anti-staphylolysin (ASTA) titres were measured from acute and convalescent phase sera of 77 patients hospitalised because of acute bacterial non-necrotising cellulitis and from the serum samples of 89 control subjects matched for age and sex. Antibiotic treatment decisions were also reviewed. Streptococcal serology was positive in 53 (69 %) of the 77 cases. Furthermore, ten cases without serological evidence of streptococcal infection were successfully treated with penicillin. Positive ASO and ADN titres were detected in ten (11 %) and three (3 %) of the 89 controls, respectively, and ASTA was elevated in three patients and 11 controls. Our findings suggest that acute non-necrotising cellulitis without pus formation is mostly of streptococcal origin and that penicillin can be used as the first-line therapy for most patients. PMID:25403372

Karppelin, M; Siljander, T; Haapala, A-M; Aittoniemi, J; Huttunen, R; Kere, J; Vuopio, J; Syrjänen, J

2014-11-18

6

Does group B streptococcal infection contribute significantly to neonatal sepsis in Antigua and Barbuda?  

PubMed

Group B streptococcus is the most common cause of neonatal sepsis in the United States of America (USA). This study was undertaken to determine the contribution of group B streptococcus to neonatal septicaemia in Antigua and Barbuda. From 1994 to 2002, there were about 12,000 births, with 2500 Special Care Nursery admissions, 1100 (44%) with potential neonatal septicaemia. Blood cultures were done in 433/1100 (39%) and cerebrospinal fluid cultures in 52/1100 (5%). Positive cultures were seen in 41/433 (9.5%) with group B streptococcus in 1/41 (2.4%), streptococcus "species" in 3/41 (7.4%) and positive cerebrospinal fluid cultures were seen in 2/52 (one group B streptococcus) giving 5 per 12,000 or 0.4 cases per 1000 babies. Vaginal cultures from 1994 to 2002 revealed group B streptococcus in 14/163 (8.6%) of positive bacterial cultures. A sample of pregnant women from a private office had positive culture for group B streptococcus in 2/120 (1.7%). The prevalence rate of carriage (15 to 40%) and infection (1.7 to 4 per 1000 babies) was much higher in the USA in the same period Universal screening of mothers for group B streptococcus may not be as necessary or cost-effective in Antigua and Barbuda. PMID:18646492

Martin, T C; Adamson, J; Dickson, T; DiGiantomasso, E; Nesbitt, C

2007-12-01

7

Ethyl pyruvate decreases sepsis-induced acute renal failure and multiple organ damage in aged mice  

Microsoft Academic Search

Ethyl pyruvate decreases sepsis-induced acute renal failure and multiple organ damage in aged mice.BackgroundSepsis is a common cause of acute renal failure (ARF). The incidence of sepsis increases dramatically after 50 years of age; however, most ARF studies are performed in young mice.MethodsWe performed two common sepsis models, lipopolysaccharide (LPS) administration and cecal ligation puncture (CLP) in aged mice. We

Takehiko Miyaji; Xuzhen Hu; Peter S. T. Yuen; Yasunari Muramatsu; Swarnalatha Iyer; Stephen M. Hewitt; Robert A. Star

2003-01-01

8

Cannabinoid Receptor 2 Protects against Acute Experimental Sepsis in Mice  

PubMed Central

The systemic inflammatory response syndrome can be self-limited or can progress to severe sepsis and septic shock. Despite significant advances in the understanding of the molecular and cellular mechanisms of septic shock, it is still one of the most frequent and serious problems confronting clinicians in the treatments. And the effects of cannabinoid receptor 2 (CB2R) on the sepsis still remain undefined. The present study was aimed to explore the role and mechanism of CB2R in acute sepsis model of mice. Here, we found that mice were more vulnerable for lipopolysaccharide- (LPS-) induced death and inflammation after CB2R deletion (CB2R?/?). CB2R agonist, GW405833, could significantly extend the survival rate and decrease serum proinflammatory cytokines in LPS-treated mice. GW405833 dose-dependently inhibits proinflammatory cytokines release in splenocytes and peritoneal macrophages as well as splenocytes proliferation, and these effects were partly abolished in CB2R?/? splenocytes but completely abolished in CB2R?/? peritoneal macrophages. Further studies showed that GW405833 inhibits LPS-induced phosphorylation of ERK1/2 and STAT3 and blocks I?B? degradation and NF-?B p65 nuclear translocation in macrophages. All data together showed that CB2R provides a protection and is a potential therapeutic target for the sepsis. PMID:23781122

Gui, Huan; Sun, Yang; Luo, Zhu-Min; Dai, Sheng-Ming; Liu, Xia

2013-01-01

9

Sepsis  

PubMed Central

Sepsis represents a major challenge in medicine. It begins as a systemic response to infection that can affect virtually any organ system, including the central and peripheral nervous systems. Akin to management of stroke, early recognition and treatment of sepsis are just as crucial to a successful outcome. Sepsis can precipitate myasthenic crisis and lead to encephalopathy and critical illness neuropathy. Stroke and traumatic brain injury can predispose a patient to develop sepsis, whereas Guillain-Barré syndrome is similarly not uncommon following infection. This review article will first describe the essential principles of sepsis recognition, pathophysiology, and management and will then briefly cover the neurologic aspects associated with sepsis. Vigilant awareness of the clinical features of sepsis and timeliness of intervention can help clinicians prevent progression of this disease to a multisystem organ failure, which can be difficult to reverse even after the original source of infection is under control. PMID:23983879

Karnatovskaia, Lioudmila V.; Festic, Emir

2012-01-01

10

[Juvenile dermatomyositis--acute recidivism or sepsis?].  

PubMed

A 22-year-old male with juvenile dermatomyositis presented with fever up to 40 degrees C and acute pain in his right thigh accompanied by muscle weakness, a skin rash and a tender swelling. Serum aspartate aminotransferase (AST) and aldolase were mildly elevated. C-reactive protein (CRP) and fibrinogen were markedly increased. The differential white blood cell count revealed relative lymphopenia. Radiography showed diffuse calcifications particularly around the thighs and knees of both legs. Magnetic resonance imaging (MRI) demonstrated inflammatory infiltrates in the right thigh. The lesions were identified as phlegmone by immunoszintigraphy with 99mTc-labelled antigranulocyte antibodies. On the 10th day of treatment Staphylococcus aureus was cultured from blood. Patients with juvenile dermatomyositis and calcinosis may develop bacterial infections of soft tissue which sometimes mimic a disease flare. For differential diagnosis plain radiographs, CT scans and MRI are of limited value. Immunoszintigraphy is able to differentiate between infiltrates caused by granulocytes and lymphocytes. PMID:10412700

Bahner, D; Meller, J; Stiefel, M; Nau, R

1999-06-01

11

Antioxidant protection of statins in acute kidney injury induced by sepsis.  

PubMed

Objective Evaluating the effect of preconditioning with simvastatin in acute kidney injury induced by sepsis. Method Male adult Wistar rats were divided into the following groups: SHAM (control); SHAM+Statin (0.5 mg/kg simvastatin, orally); Sepsis (cecal puncture ligation - CPL); Sepsis+Statin. Physiological parameters, peritoneal fluid culture, renal function, oxidative metabolites, severity of acute kidney injury and animal survival were evaluated. Results The treatment with simvastatin in induced sepsis showed elevation of creatinine clearance with attenuation of generation of oxidative metabolites, lower severity of acute kidney injury and reduced mortality. Conclusion This investigation confirmed the renoprotection with antioxidant principle of the simvastatin in acute kidney injury induced by sepsis in an experimental model. PMID:25493485

Santos, Franciele do Nascimento; Watanabe, Mirian; Vasco, Carolina Ferreira; Fonseca, Cassiane Dezoti da; Vattimo, Maria de Fatima Fernandes

2014-10-01

12

Rosuvastatin for Sepsis-Associated Acute Respiratory Distress Syndrome  

PubMed Central

BACKGROUND In the acute respiratory distress syndrome (ARDS), inflammation in the lungs and other organs can cause life-threatening organ failure. Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase (statins) can modulate inflammatory responses. Previous observational studies suggested that statins improved clinical outcomes in patients with sepsis. We hypothesized that rosuvastatin therapy would improve clinical outcomes in critically ill patients with sepsis-associated ARDS. METHODS We conducted a multicenter trial in which patients with sepsis-associated ARDS were randomly assigned to receive either enteral rosuvastatin or placebo in a double-blind manner. The primary outcome was mortality before hospital discharge home or until study day 60 if the patient was still in a health care facility. Secondary outcomes included the number of ventilator-free days (days that patients were alive and breathing spontaneously) to day 28 and organ-failure–free days to day 14. RESULTS The study was stopped because of futility after 745 of an estimated 1000 patients had been enrolled. There was no significant difference between study groups in 60-day in-hospital mortality (28.5% with rosuvastatin and 24.9% with placebo, P = 0.21) or in mean (±SD) ventilator-free days (15.1±10.8 with rosuvastatin and 15.1±11.0 with placebo, P = 0.96). The groups were well matched with respect to demographic and key physiological variables. Rosuvastatin therapy, as compared with placebo, was associated with fewer days free of renal failure to day 14 (10.1±5.3 vs. 11.0±4.7, P = 0.01) and fewer days free of hepatic failure to day 14 (10.8±5.0 vs. 11.8±4.3, P = 0.003). Rosuvastatin was not associated with an increased incidence of serum creatine kinase levels that were more than 10 times the upper limit of the normal range. CONCLUSIONS Rosuvastatin therapy did not improve clinical outcomes in patients with sepsis-associated ARDS and may have contributed to hepatic and renal organ dysfunction. PMID:24835849

2014-01-01

13

Group A streptococcal puerperal sepsis preceded by positive surveillance cultures 1 1 We gratefully acknowledge the contributions of Diane Davis, RN, BS, CIC, and Carole Eberle, MT, in investigating these cases; Piotr Kramarz, MD, PhD, for translating Polish-language literature; Bernard Beall, PhD, and Alma Franklin, for the isolate typing; and John A. Elliott, PhD, for subjecting the isolates to pulsed-field gel electrophoresis  

Microsoft Academic Search

BACKGROUND:Screening of pregnant women for vaginal and rectal carriage of group B streptococci may also identify group A streptococcal carriers. The clinical significance of prenatal group A streptococcal carriage is unknown.CASES:Two women developed group A streptococcal puerperal sepsis after delivery at one hospital 15 months apart. The first patient required hysterectomy and suffered complications including subcapsular hepatic hematoma, pleural effusion,

Karen R Stefonek; Linda L Maerz; Michael P Nielsen; Richard E Besser; Paul R Cieslak

2001-01-01

14

High prevalence of streptococcal or Epstein-Barr virus infections in children with acute non-septic monoarthritis.  

PubMed

To investigate associations between infections and acute monoarthritis, we performed a prospective study on 32 children consecutively hospitalized and 32 age-matched controls. Among 26 (81%) children having infections, the most frequent agents were Group A ?-hemolytic Streptococcus (GAS: 53%) and Epstein-Barr virus (EBV: 37.5%). Among controls, only 5 (16%) were infected with GAS and 2 (6%) with EBV (P<0.005). The most frequently involved joints were hip in 15 children and ankle in 10 children. Our study showed that acute monoarthritis in children may be frequently associated with streptococcal or EBV infections. PMID:24531174

Di Loreto, Simona; Fabiano, Cecilia; Nigro, Giovanni

2014-01-01

15

Update on the Immunological Pathway of Negative Regulation in Acute Insults and Sepsis  

PubMed Central

Sepsis with subsequent multiple organ dysfunction is a distinctly systemic inflammatory response to concealed or known infection and is a leading cause of death in intensive care units. In the initial stage of sepsis, a phase of immune activation can be evident, but a marked apoptosis-induced depletion of lymphocytes and a nonspecific anergy of immune function after severe trauma and burns might be responsible for the increased susceptibility of the host to subsequent septic complications. Recent studies indicated that negative regulation of immune function plays a pivotal role in the maintenance of peripheral homeostasis and regulation of immune responses; therefore, an understanding of the basic pathways might give rise to novel insights into the mechanisms of sepsis and immune homeostasis. This review is an attempt to provide a summary of the different pathways of negative regulation that are involved in the pathogenesis of sepsis, secondary to acute insults. PMID:22509978

Luan, Ying-yi; Sheng, Zhi-yong

2012-01-01

16

Sepsis screening.  

PubMed

NHS Education for Scotland has, in collaboration with the Scottish Patient Safety Programme, made the national early warning score (NEWS) and sepsis screening tool available as a smartphone app. The app provides: a NEWS calculator to alert clinicians to deteriorating patients and acute illness; a sepsis screening tool for the prompt recognition and initiation of treatment of patients with sepsis; an outline of the Sepsis 6 care bundle; and an algorithm to help identify organ dysfunction, severe sepsis, septic shock and when to escalate care. Go to tinyurl.com/sepsis-screening to download the app. PMID:25355121

2014-10-30

17

Effects of anabolic steroids on acute phase responses in intra-abdominal sepsis  

PubMed Central

The acute phase response is an important adaptive response to sepsis and injury. As anabolic steroids increase protein synthesis we postulated that these agents might also increase hepatic acute phase protein synthesis. Male Wistar rats were pretreated with testosterone or danazol for 48 h prior to caecal ligation and puncture (CLP). Thirty-six h following surgery the animals were killed and blood taken for full blood count, total protein, albumin, ?, ? and ? globulin fractions on serum electrophoresis, complement C3 and transferrin levels. Danazol increased the ?1, ?2 and ?1 globulin serum protein fractions in comparison with no surgery and CLP alone groups. These results indicate that danazol increases plasma acute phase proteins, as measured by electrophoresis, in this model of intra-abdominal sepsis. PMID:18472837

Clooney, A.; Marks, P.; Hennessy, T.; Jackson, J.

1997-01-01

18

An acute phase protein ready to go therapeutic for sepsis  

PubMed Central

The so-called Acute Phase Response (APR) begins between 12 and 48 h after the initiation of inflammation. This conserved response mainly involves the production of a set of Acute Phase Proteins (APPs) and the downregulation of other proteins (negative APPs) by hepatocytes. Although the precise identity of the APPs may differ between species, some APPs are common in all mammals. PMID:24408964

Vandevyver, Sofie; Dejager, Lien; Vandenbroucke, Roosmarijn E; Libert, Claude

2014-01-01

19

Acute kidney injury in sepsis: transient or intrinsic?  

PubMed Central

The negative prediction of intrinsic versus transient acute kidney injury (AKI) in septic patients may be facilitated by combined assessment of fractional excretion of sodium and urea. If both excretions are high this would signal the presence of transient AKI and suggest that successful restoration of diuresis by conservative therapy is likely, thus supporting a wait-and-watch approach regarding the initiation of acute renal replacement therapy. PMID:24252543

2013-01-01

20

Energy crisis: the role of oxidative phosphorylation in acute inflammation and sepsis.  

PubMed

Mitochondrial dysfunction is increasingly recognized as an accomplice in most of the common human diseases including cancer, neurodegeneration, diabetes, ischemia/reperfusion injury as seen in myocardial infarction and stroke, and sepsis. Inflammatory conditions, both acute and chronic, have recently been shown to affect mitochondrial function. We here discuss the role of oxidative phosphorylation (OxPhos), focusing on acute inflammatory conditions, in particular sepsis and experimental sepsis models. We discuss mitochondrial alterations, specifically the suppression of oxidative metabolism and the role of mitochondrial reactive oxygen species in disease pathology. Several signaling pathways including metabolic, proliferative, and cytokine signaling affect mitochondrial function and appear to be important in inflammatory disease conditions. Cytochrome c oxidase (COX) and cytochrome c, the latter of which plays a central role in apoptosis in addition to mitochondrial respiration, serve as examples for the entire OxPhos system since they have been studied in more detail with respect to cell signaling. We propose a model in which inflammatory signaling leads to changes in the phosphorylation state of mitochondrial proteins, including Tyr304 phosphorylation of COX catalytic subunit I. This results in an inhibition of OxPhos, a reduction of the mitochondrial membrane potential, and consequently a lack of energy, which can cause organ failure and death as seen in septic patients. PMID:24905734

Lee, Icksoo; Hüttemann, Maik

2014-09-01

21

Chitinase-like Proteins are Candidate Biomarkers for Sepsis-induced Acute Kidney Injury*  

PubMed Central

Sepsis-induced acute kidney injury (AKI) is a frequent complication of critically ill patients and leads to high mortality rates. The specificity of currently available urinary biomarkers for AKI in the context of sepsis is questioned. This study aimed to discover urinary biomarkers for septic AKI by contemporary shotgun proteomics in a mouse model for sepsis and to validate these in individual urine samples of mice and human septic patients with and without AKI. At 48 h after uterine ligation and inoculation of Escherichia coli, aged mice (48 weeks) became septic. A subgroup developed AKI, defined by serum creatinine, blood urea nitrogen, and renal histology. Separate pools of urine from septic mice with and without AKI mice were collected during 12 h before and between 36–48 h after infection, and their proteome compositions were quantitatively compared. Candidate biomarkers were validated by Western blot analysis of urine, plasma, and renal tissue homogenates from individual mice, and a limited number of urine samples from human septic patients with and without AKI. Urinary neutrophil gelatinase-associated lipocalin, thioredoxin, gelsolin, chitinase 3-like protein 1 and -3 (CHI3L3) and acidic mammalian chitinase were the most distinctive candidate biomarkers selected for septic AKI. Both neutrophil gelatinase-associated lipocalin and thioredoxin were detected in urine of septic mice and increased with severity of AKI. Acidic mammalian chitinase was only present in urine of septic mice with AKI. Both urinary chitinase 3-like protein 1 and -3 were only detected in septic mice with severe AKI. The human homologue chitinase 3-like protein 1 was found to be more excreted in urine from septic patients with AKI than without. In summary, urinary chitinase 3-like protein 1 and -3 and acidic mammalian chitinase discriminated sepsis from sepsis-induced AKI in mice. Further studies of human chitinase proteins are likely to lead to additional insights in septic AKI. PMID:22233884

Maddens, B.; Ghesquière, B.; Vanholder, R.; Demon, D.; Vanmassenhove, J.; Gevaert, K.; Meyer, E.

2012-01-01

22

Chitinase-like proteins are candidate biomarkers for sepsis-induced acute kidney injury.  

PubMed

Sepsis-induced acute kidney injury (AKI) is a frequent complication of critically ill patients and leads to high mortality rates. The specificity of currently available urinary biomarkers for AKI in the context of sepsis is questioned. This study aimed to discover urinary biomarkers for septic AKI by contemporary shotgun proteomics in a mouse model for sepsis and to validate these in individual urine samples of mice and human septic patients with and without AKI. At 48 h after uterine ligation and inoculation of Escherichia coli, aged mice (48 weeks) became septic. A subgroup developed AKI, defined by serum creatinine, blood urea nitrogen, and renal histology. Separate pools of urine from septic mice with and without AKI mice were collected during 12 h before and between 36-48 h after infection, and their proteome compositions were quantitatively compared. Candidate biomarkers were validated by Western blot analysis of urine, plasma, and renal tissue homogenates from individual mice, and a limited number of urine samples from human septic patients with and without AKI. Urinary neutrophil gelatinase-associated lipocalin, thioredoxin, gelsolin, chitinase 3-like protein 1 and -3 (CHI3L3) and acidic mammalian chitinase were the most distinctive candidate biomarkers selected for septic AKI. Both neutrophil gelatinase-associated lipocalin and thioredoxin were detected in urine of septic mice and increased with severity of AKI. Acidic mammalian chitinase was only present in urine of septic mice with AKI. Both urinary chitinase 3-like protein 1 and -3 were only detected in septic mice with severe AKI. The human homologue chitinase 3-like protein 1 was found to be more excreted in urine from septic patients with AKI than without. In summary, urinary chitinase 3-like protein 1 and -3 and acidic mammalian chitinase discriminated sepsis from sepsis-induced AKI in mice. Further studies of human chitinase proteins are likely to lead to additional insights in septic AKI. PMID:22233884

Maddens, B; Ghesquière, B; Vanholder, R; Demon, D; Vanmassenhove, J; Gevaert, K; Meyer, E

2012-06-01

23

Role of surfactant proteins a and d in sepsis-induced acute kidney injury.  

PubMed

Sepsis is a major cause of acute kidney injury (AKI) with high rates of morbidity and mortality. Surfactant proteins A and D (SP-A, SP-D) play a critical role in host defense and regulate inflammation during infection. Recent studies indicate SP-A and SP-D are expressed in the kidney. The current study examines the role of SP-A and SP-D in the pathogenesis of sepsis-induced AKI. Wild-type (WT) and SP-A/SP-D double-knockout (KO) C57BL/6 mice were treated by cecal ligation and puncture (CLP) or sham surgery. Histological, cellular, and molecular indices of kidney injury were investigated in septic mice 6 and 24 h after CLP. Twenty-four hours after CLP, kidney injury was more severe, renal function was decreased, and blood creatinine and blood urea nitrogen were higher in septic SP-A/SP-D KO mice (P < 0.05, versus septic WT mice). Kidney edema and vascular permeability were increased in septic SP-A/SP-D KO mice (P < 0.01, versus septic WT mice). Apoptotic cells increased significantly (P < 0.01) in the kidney of septic SP-A/SP-D KO mice compared with septic WT mice. Molecular analysis revealed levels of Bcl-2 (an inhibitor of apoptosis) were lower and levels of caspase 3 (a biomarker of apoptosis) were higher in the kidney of septic SP-A/SP-D KO mice (P < 0.01, versus septic WT mice). Furthermore, levels of nuclear factor ?B and phosphorylated I?B-? increased significantly in the kidney of septic SP-A/SP-D KO mice compared with septic WT mice, suggesting SP-A/SP-D KO mice have a more pronounced inflammatory response to sepsis. We conclude SP-A and SP-D attenuate kidney injury by modulating inflammation and apoptosis in sepsis-induced AKI. PMID:25255378

Liu, Jiao; Abdel-Razek, Osama; Liu, Zhiyong; Hu, Fengqi; Zhou, Qingshan; Cooney, Robert N; Wang, Guirong

2015-01-01

24

Pre-existing Renal Disease Promotes Sepsis-induced Acute Kidney Injury and Worsens Sepsis Outcome via Multiple Pathways  

PubMed Central

Patients with chronic kidney disease (CKD) are at significantly higher risk of death from sepsis, although the mechanism by which CKD increases mortality has not been investigated. We established a mouse two-stage model of pre-existing renal disease with subsequent sepsis by combining folic acid (FA) injection and sub-lethal cecal ligation and puncture (CLP) surgery. Mice were injected with FA then made septic (FA-CLP) or were injected with vehicle then made septic (Veh-CLP). FA-CLP mice had significantly higher mortality than Veh-CLP mice. Sepsis increased serum creatinine in the FA-CLP but not in the Veh-CLP group. FA-CLP mice had more severe septic shock and significantly increased vascular permeability, plasma vascular endothelial growth factor (VEGF), bacteremia, serum IL-10 and splenocyte apoptosis compared to Veh-CLP. To evaluate the contribution of vascular and immunological dysfunction, we treated FA-CLP mice with soluble Flt-1 and chloroquine. Mice treated with combination therapy showed a significant improvement in kidney injury, hemodynamics, and survival. In conclusion, the sequential FA-CLP model mimics human sepsis that is frequently complicated with pre-existing conditions including CKD. This animal model would be useful to evaluate preventative and therapeutic strategies under conditions more typical of human sepsis. PMID:18633340

Doi, Kent; Leelahavanichkul, Asada; Hu, Xuzhen; Sidransky, Karen L.; Qin, Yan; Eisner, Christoph; Schnermann, Jurgen; Yuen, Peter S. T.; Star, Robert A.

2008-01-01

25

Important issues in the design and reporting of clinical trials in severe sepsis and acute lung injury  

Microsoft Academic Search

Severe sepsis and acute lung injury are challenging diagnoses as they relate to designing and reporting of clinical trials. The limited success in bringing forward new therapies in these areas is likely proof of that premise. The ability to use preclinical and phase I and II trial data to predict which patients and which dosing regimens are more likely to

R. Phillip Dellinger; Jean-Louis Vincent; John Marshall; Konrad Reinhart

2008-01-01

26

Low molecular weight heparin may prevent acute lung injury induced by sepsis in rats.  

PubMed

The purpose of this study was to assess the protective effect of low molecular weight heparin (LMWH) on acute lung injury (ALI) in rats induced by sepsis. Rat ALI model was reproduced by cecal ligation and puncture (CLP). All rats were randomly divided into three groups (n=50): control group (A), ALI group (B), and LMWH-treated group (C). Group A received a sham operation and the other groups underwent CLP operation. Groups A and B accepted intraperitoneal injection (i.p.) of normal saline (NS) at a dose of 2.0mlkg(-1) and ceftriaxone (30mgkg(-1)), group C was intraperitoneally injected with additional LMWH (150Ukg(-1)) except saline and ceftriaxone. Blood was collected and lung tissue was harvested at the designated time points for analysis. The lung specimens were harvested for morphological studies, immunohistochemistry examination. Lung tissue edema was evaluated by tissue water content. The levels of lung tissue myeloperoxidase (MPO) were determined. Meanwhile, the nuclear factor-kappa B (NF-?B) activation, tumor necrosis factor-? (TNF-?), interleukin-1? (IL-1?) levels, high mobility group box 1 (HMGB1) and intercellular adhesion molecule-1 (ICAM-1) protein levels in the lung were studied. There was a significant difference in each index between groups A and B (P<0.05). Treatment with LMWH significantly decreased the expression of TNF-?, IL-1?, HMGB1 and ICAM-1 in the lungs of ALI rats. Similarly, treatment with LMWH dramatically diminished sepsis-induced neutrophil sequestration and markedly reduced the enhanced lung permeability. In the present study, LMWH administration inhibited the nuclear translocation of NF-?B in the lungs. These data suggest that LMWH attenuates inflammation and ameliorates lung pathology in CLP-induced sepsis in a rat model. PMID:25497831

Ning, Fangyu; Wang, Xiaozhi; Shang, Li; Wang, Tao; Lv, Changjun; Qi, Zhijiang; Wu, Dawei

2015-02-15

27

Penicillin V, loracarbef and clindamycin in tonsillar surface fluid during acute group A streptococcal pharyngotonsillitis.  

PubMed

Patients with acute group A- strepotococcal pharyngotonsillitis were randomly assigned to treatment for 10 d with either phenoxymethylpenicillin (PcV), loracarbef or clindamycin. The concentrations of the drugs, respectively, were determined in tonsillar surface fluid (TSF), serum and the saliva in each patient on altogether 5 occasions; before, during and 4 d after end of therapy. On the same occasions blood was drawn for analysis of C-reactive protein (CRP) and orosomucoid. On the last d of treatment PcV could be detected in TSF in 1 of 6 patients only. Loracarbef had a slower decrease in TSF during therapy and measurable levels did occur 2 d after end of therapy corresponding to MIC 100 for GAS. This may be related to the somewhat better clinical results of the cephalosporins than of PcV, and possibly indicates that an extended therapy with these drugs in primary GAS pharyngotonsillitis for more than the arbitrarily chosen 10 d could reduce the number of recurrent episodes. PcV and loracarbef were not detected in serum after the end of treatment. The concentration of clindamycin in both TSF and the saliva was fairly longstanding during therapy and reached levels exceeding MIC 100 for GAS, in both TSF and serum 2 d after the end of treatment. Several investigations have shown that GAS, especially in the stationary phase may invade respiratory epithelial cells and are present intracellularly in patients with acute pharyngotonsillitis as well as in asymptomatic carriers. The same T-type, identical DNA fingerprints and arbitrarily primed patterns are found in GAS before and after treatment failure indicating that the primary episode and the failures are caused by the same strain. The longstanding concentrations of clindamycin in TSF, roughly independent of the degree of the local inflammation combined with its intracellular accumulation and activity against resting GAS seem to explain the efficiency of the drug in recurrent GAS pharyngotonsillitis. CRP and orosomucoid were of limited value in differing between bacterial and viral pharyngtonsillitis and a correlation between antibiotic concentration and CRP/orosomucoid levels was not found. PMID:16012002

Orrling, Arne; Kamme, Carl; Stjernquist-Desatnik, Anna

2005-01-01

28

Involvement of Rho kinase (ROCK) in sepsis-induced acute lung injury  

PubMed Central

Indirect acute lung injury is associated with high morbidity and mortality. We investigated the link between Rho kinase (ROCK) activation and apoptotic cell death in sepsis induced acute lung injury. This hypothesis was tested by administering a specific, selective inhibitor of ROCK (Y-27632) to rats subjected to cecal ligation and puncture (CLP). Rats were randomly divided into 4 groups as; sham-operated, sham + Y-27632, CLP and CLP + Y-27632. Twenty-four hours later, each experiment was terminated and lungs analyzed. Histopathology was assessed by hematoxylin-eosin staining and the presence of apoptosis was evaluated through the TUNEL assay. Pulmonary activity of caspase 3 and ROCK 1 & 2 were measured by western blot. Interstitial edema, severely damaged pulmonary architecture with massive infiltration of the inflammatory cells and an increase in lung tissue TBARS levels as well as 3-NT to total tyrosine ratios were observed in untreated CLP animals. Pretreatment of animals with Y-27632, reduced lung injury in the CLP induced septic rats in each of these parameters of lung injury (p<0.05). Western immunoblot revealed active caspase cleavage and increased expression of active fragment of ROCK 1 & 2 in the CLP group. TUNEL assay showed an increase in percentage of apoptotic cells when comparing the CLP group with the CLP + Y-27632 group. These results suggest an important role of Rho kinase in sepsis induced lung injury by a mechanism that might be related to oxidative and/or nitrosative stress mediated caspase cleavage leading to apoptosis. PMID:22295165

Cinel, Ismail; Ark, Mustafa; Dellinger, Phillip; Karabacak, Tuba; Tamer, Lulufer; Cinel, Leyla; Michael, Paul; Hussein, Shaimaa; Parrillo, Joseph E.; Kumar, Anand; Kumar, Aseem

2012-01-01

29

Alpha1-microglobulin as an early biomarker of sepsis-associated acute kidney injury: a prospective cohort study  

PubMed Central

Background: Sepsis emerges as the leading risk factor for acute kidney injury (AKI) development in critically ill patients. Much effort has been invested so far on early diagnosis of AKI using promising biomarkers. This study aimed to determine whether urine alpha1-microglobulin (?1m), a lipocaline member previously used as an indicator of proximal tubular dysfunction, can early predict the development of sepsis-associated AKI (SAAKI) in critically ill patients. Methods: A prospective, observational study was conducted in a single center Intensive Care Unit (ICU). Patients with normal renal function admitted to the ICU followed for sepsis and AKI development. Urine ?1m levels were analyzed in pooled samples from 24-hour urine collections on sepsis onset and at various time points thereafter. The diagnostic performance of urine ?1m was assessed using thenonparametriccalculation of the area under the curve (AUC) of the receiver operating characteristic (ROC) curve. Results: Among 286 critically ill patients admitted to our ICU in a year, 45 patients with sepsis met the inclusion criteria. SAAKI developed in 16 septic patients (35.6%). Urine ?1m levels were significantly elevated in all septic patients (average value of all samples on the day of sepsis: 46.02 ± 7.17 mg/l) and showed a trend to increase in patients who finally developed SAAKI. The AUC for SAAKI prediction according to ?1m urine levels 24-hours before SAAKI onset was 0.739 (sensitivity 87.5%, specificity 62.07%, cutoff level 47.9 mg/l). Urine ?1m 24-hours before SAAKI, serum creatinine on sepsis onset and Acute Physiology and Chronic Health Evaluation II (APACHE II) score on sepsis onset emerged as the most powerful independent predictors of SAAKI. The combination of these three parameters improved the AUC for SAAKI prediction to 0.944. Conclusion: Urine ?1m levels might help in the early prediction of SAAKI development and may prove useful biomarker. The pathogenetic implications of ?1m in sepsis and SAAKI need further investigation. Hippokratia 2014; 18 (3): 262-268. PMID:25694763

Terzi, I; Papaioannou, V; Papanas, N; Dragoumanis, C; Petala, A; Theodorou, V; Gioka, T; Vargemezis, V; Maltezos, E; Pneumatikos, I

2014-01-01

30

THE EPIDEMIOLOGY OF ACUTE RESPIRATORY DISTRESS SYNDROME IN PATIENTS PRESENTING TO THE EMERGENCY DEPARTMENT WITH SEVERE SEPSIS  

PubMed Central

Background Acute respiratory distress syndrome (ARDS) is a serious complication of sepsis and sepsis-associated ARDS is associated with significant morbidity and mortality. To date, no study has directly examined the epidemiology of ARDS in severe sepsis from the earliest presentation to the health care system, the Emergency Department (ED). Methods Single-center retrospective, observational cohort study of 778 adults with severe sepsis presenting to the ED. The primary outcome was the development of ARDS requiring mechanical ventilation during the first 5 hospital days. ARDS was defined using the Berlin definition. We used multivariable logistic regression to identify risk factors associated independently with ARDS development. Results The incidence of ARDS was 6.2% (48 of 778 patients) in the entire cohort. ARDS development varied across the continuum of care: 0.9% of patients fulfilled criteria for ARDS in the ED, 1.4% admitted to the ward developed ARDS, and 8.9% admitted to the ICU developed ARDS. ARDS developed a median of 1 day after admission and was associated with a four-fold higher risk of in-hospital mortality (14% vs. 60%, p<0.001). Independent risk factors associated with increased risk of ARDS development included: intermediate (2–3.9 mmol/L) (p=0.04) and high (? 4) serum lactate levels (p=0.008), lung injury prediction score (LIPS) (p<0.001) and microbiologically-proven infection (p=0.01). Conclusions In patients presenting to the ED with severe sepsis, the rate of sepsis-associated ARDS development varied across the continuum of care. ARDS developed rapidly and was associated with significant mortality. Elevated serum lactate levels in the ED and a recently validated clinical prediction score were independently associated with the development of ARDS in severe sepsis. PMID:23903852

Mikkelsen, Mark E.; Shah, Chirag V.; Meyer, Nuala J.; Gaieski, David F.; Lyon, Sarah; Miltiades, Andrea N.; Goyal, Munish; Fuchs, Barry D.; Bellamy, Scarlett L.; Christie, Jason D.

2013-01-01

31

Can neutrophil-lymphocyte ratio be independent risk factor for predicting acute kidney injury in patients with severe sepsis?  

PubMed

Abstract Aim: Neutrophil-lymphocyte ratio (NLR) is an easily calculated, sensitive, and accurate marker for prognosis and diagnosing sepsis, cardiovascular disease and cancer. As sepsis and septic shock are main causes of acute kidney injury (AKI) intensive care unit (ICU), we investigated whether NLR is an early predictor of AKI in patients with severe sepsis. We compared NLR's predictive power with that of other inflammation-related variables. Methods: Between December 2011 and November 2013, we enrolled 118 consecutive cases with severe sepsis admitted to ICU in this retrospective study. Levels of C-reactive protein (CRP), NLR, and white blood cell count (WBC) were recorded on admission and patients' renal function was monitored for seven consecutive days. Results: The rate of AKI occurrence 7 days after enrollment was 57.6%. NLR levels were higher in the AKI group (Group 1) than in the non-AKI group (Group 2) on the day of ICU admission (p?Acute Physiology and Chronic Health Evaluation II (APACHE II) and duration of invasive mechanical ventilation (MV) in multivariate logistic regression analysis. The area under the receiver-operating characteristic (ROC) curve of NLR for predicting AKI was 0.986, which was superior to WBC and CRP (p?sepsis. The sensitivity, specificity, negative-predictive value (NPV), and positive-predictive value (PPV), for this cut-off value was 90.2%, 92.9%, 90.4%, and 92.7%, respectively. Conclusion: NLR is superior to CRP, and WBC for predicting the development of AKI in patients with severe sepsis. PMID:25394529

Yilmaz, Hakki; Cakmak, Muzaffer; Inan, Osman; Darcin, Tahir; Akcay, Ali

2014-11-14

32

Role of C3, C5 and Anaphylatoxin Receptors in Acute Lung Injury and in Sepsis  

PubMed Central

The complement system plays a major role in innate immune defenses against infectious agents, but exaggerated activation of complement can lead to severe tissue injury. Systemic (intravascular) activation of complement can, via C5a, lead to neutrophil (PMN) activation, sequestration and adhesion to the pulmonary capillary endothelium, resulting in damage and necrosis of vascular endothelial cells and acute lung injury (ALI). Intrapulmonary (intraalveolar) activation of complement can cause ALI that is complement and PMN-dependent, resulting in a cytokine/chemokine storm that leads to intense ALI. Surprisingly, C3?/? mice develop the full intensity of ALI in a C5a-dependent manner due to the action of thrombin that generates C5a directly from C5. There is conflicting evidence on the role of the second C5a receptor, C5L2 in development of ALI. There is accumulating evidence that C5a may suppress inflammatory responses or divert them from Th1 to Th2 responses, impacting the innate immune system. Finally, in experimental polymicrobial sepsis, there is evidence that many of the adverse outcomes can be linked to the roles of C5a and engagement of its two receptors, C5aR and C5L2. These observations underscore the diversity of effects of C5a in a variety of inflammatory settings. PMID:21948367

Bosmann, Markus

2012-01-01

33

[Acute renal failure and sepsis : Just an organ dysfunction due to septic multiorgan failure?].  

PubMed

Acute renal failure (ARF) is clinically defined as an abrupt, but in principle reversible deterioration of glomerular and tubular function. Regarding pathophysiology, ARF is caused by ischemic renal conditions and toxic mediators. Sepsis is the most common cause of ARF in the intensive care unit and ARF is an independent risk factor for lethality of septic patients. Interventions to protect the kidneys against ARF include preliminary optimization of renal perfusion by volume load with cristalloid solutions and the administration of vasopressors. Daily maximum permissible dosages for colloids should not be exceeded and hyperoncotic colloid solutions should be generally avoided. Dopamine in "renal dosage" is nowadays obsolete. Loop diuretics produce diuresis and can be beneficial to extrarenal organs by improving fluid homeostasis, however diuretics do not improve kidney function and outcome. Therefore, diuretics are not indicated for patients with imminent or existing ARF. Septic patients with ARF can be treated by intermittent and continuous forms of renal replacement therapy, whereas continuous convective and intermittent diffusive methods are equivalent when utilizing an ultrafiltration rate > or =20 ml/h*kg body weight or a therapeutic interval > or =3 times/week. PMID:20694713

Schmidt, C; Steinke, T; Moritz, S; Graf, B M; Bucher, M

2010-08-01

34

Diagnostic value of urine sCD163 levels for sepsis and relevant acute kidney injury: a prospective study  

PubMed Central

Background Sepsis is a common syndrome in critically ill patients and easily leads to the occurrence of acute kidney injury (AKI), with high mortality rates. This study aimed to investigate the diagnostic value of urine soluble CD163 (sCD163) for identification of sepsis, severity of sepsis, and for secondary AKI, and to assess the patients’ prognosis. Methods We enrolled 20 cases with systemic inflammatory response syndrome (SIRS), 40 cases with sepsis (further divided into 17 sepsis cases and 23 severe sepsis cases) admitted to the intensive care unit (ICU), and 20 control cases. Results for urine sCD163 were recorded on the day of admission to the ICU, and AKI occurrence was noted. Results On the day of ICU admission, the sepsis group exhibited higher levels of urine sCD163 (74.8 ng/ml; range: 47.9-148.3 ng/ml) compared with those in the SIRS group (31.9 ng/ml; 16.8-48.0, P?sepsis group appeared to have a higher level of sCD163 compared with that in the sepsis group (76.2; 47.2-167.5 ng/ml vs. 74.2; 46.2-131.6 ng/ml), but this was not significant. For 15 patients with AKI, urine sCD163 levels at AKI diagnosis were significantly higher than those of the remaining 35 sepsis patients upon ICU admission (121.0; 74.6-299.1 ng/ml vs. 61.8; 42.8-128.3 ng/ml, P?=?0.049). The AUC for urine sCD163 was 0.688 (95% CI: 0.51-0.87, P?=?0.049). Sepsis patients with a poor prognosis showed a higher urine sCD163 level at ICU admission (98.6; 50.3-275.6 ng/ml vs. 68.0; 44.8-114.5 ng/ml), but this was not significant. Patients with AKI with a poor prognosis had higher sCD163 levels than those in patients with a better prognosis (205.9; 38.6-766.0 ng/ml vs. 80.9; 74.9-141.0 ng/ml), but this was not significant. Conclusions This study shows, for the first time, the potential value of urine sCD163 levels for identifying sepsis and diagnosing AKI, as well as for assessment of patients’ prognosis. Trial Registration ChiCTR-ONC-10000812 PMID:23013330

2012-01-01

35

Immunomodulatory clarithromycin treatment of experimental sepsis and acute pyelonephritis caused by multidrug-resistant Pseudomonas aeruginosa.  

PubMed

Clarithromycin was administered intravenously to 55 rabbits to evaluate its effect on experimental sepsis caused by multidrug-resistant Pseudomonas aeruginosa. Acute pyelonephritis was induced after ligation of the right ureter and injection of 10(8) CFU of the test isolate per kg of body weight into the renal pelvis. The animals were divided into six groups: group A, controls; group B, rabbits that received one intravenous dose of 80 mg of clarithromycin per kg concomitantly with bacterial challenge; group C, rabbits that received two doses of clarithromycin, the second one of which was given 2 h after the first one; group D, rabbits that received 15 mg of amikacin per kg; group E, rabbits that received one dose of clarithromycin and amikacin; and group F, rabbits that received two doses of clarithromycin and amikacin. Serum endotoxin levels were estimated by the QCL-1000 Limulus amoebocyte lysate assay, tumor necrosis factor alpha (TNF-alpha) levels were measured by a bioassay, and malondialdehyde (MDA) levels were measured by the thiobarbiturate assay. Viable bacterial counts in various tissue samples were also assessed. The mean survival times of the animals in groups A, B, C, D, E, and F were 4.50, 7.69, 4.07, 4.55, 11.55, and 11.60 days, respectively (P = 0.033 for group D versus group F, P = 0.006 for group D versus group E, P = not significant for group B versus group E, P = 0.042 for group C versus group F). Serum endotoxin levels were similar between groups at all sampling times; TNF-alpha and MDA levels in groups B, C, E, and F decreased significantly over follow-up. The numbers of viable bacterial cells in the infected kidney were similar among the groups; those in the liver, spleen, lungs, and mesenteral lymph nodes were significantly decreased in groups B, E, and F compared to those in groups A and D. It is concluded that a prolongation of survival in animals with experimental sepsis caused by multidrug-resistant P. aeruginosa was achieved after coadministration of clarithromycin and amikacin and that the increased survival was probably attributable to the immunomodulatory properties of clarithromycin. PMID:14693524

Giamarellos-Bourboulis, Evangelos J; Adamis, Theodoros; Laoutaris, George; Sabracos, Lambros; Koussoulas, Vassilios; Mouktaroudi, Maria; Perrea, Despina; Karayannacos, Panayotis E; Giamarellou, Helen

2004-01-01

36

Acute lung inflammation in Klebsiella pneumoniae B5055-induced pneumonia and sepsis in BALB/c mice: a comparative study.  

PubMed

Lungs play an important role in the body's defense against a variety of pathogens, but this network of immune system-mediated defense can be deregulated during acute pulmonary infections. The present study compares acute lung inflammation occurring during Klebsiella pneumoniae B5055-induced pneumonia and sepsis in BALB/c mice. Pneumonia was induced by intranasal instillation of bacteria (10(4) cfu), while sepsis was developed by placing the fibrin-thrombin clot containing known amount of bacteria (10(2) cfu) into the peritoneal cavity of animals. Mice with sepsis showed 100% mortality within five post-infection days, whereas all the animals with pneumonia survived. In animals suffering from K. pneumoniae B5055-induced pneumonia, all the inflammatory parameters (TNF-?, IL-1?, MPO, MDA, and NO) were found to be maximum till third post-infection day, after that, a decline was observed, whereas in septic animals, all the above-mentioned markers of inflammation kept on increasing. Histopathological study showed presence of alternatively activated alveolar macrophages (or foam cells) in lungs of mice with pneumonia after third post-infection day, which might have contributed to the induction of resolution of inflammation, but no such observation was made in lungs of septic mice. Hence, during pneumonia, controlled activation of macrophages may lead to resolution of inflammation. PMID:20890649

Kumar, Vijay; Chhibber, Sanjay

2011-10-01

37

Effect of siRNA against NF-?B on sepsis-induced acute lung injury in a mouse model  

PubMed Central

The aim of the present study was to explore the protective effect of small interfering RNA (siRNA) against nuclear factor ?B (NF-?B) p65 on sepsis-induced acute lung injury (ALI) in mice. In total, 70 male Kunming mice were randomly divided into a healthy control group, a sepsis group, a specific interfering group and a scrambled control group (Sc), and the latter three groups were divided into post-operational 6 and 12 h subgroups, each of which consisted of 10 mice. The mice were administered with NF-?B siRNA, scrambled siRNA and normal saline via tail vein injection. Following 1 h, a mouse model of septic ALI was produced by cecal ligation and puncture (CLP) in the two siRNA groups and the sepsis control group. At 6 and 12 h post-operation, the experimental mice were sacrificed and the lung tissue samples were collected. Histopathological changes, wet/dry ratio of lung weight, NF-?B protein and NF-?B p65 mRNA levels, matrix metalloproteinase-9 (MMP-9) mRNA and protein activity were detected. Compared with the sepsis group and the Sc at the corresponding time, the expression levels of NF-?B p65 mRNA, the lung injury of experimental mice, the wet/dry ratio and the levels of MMP-9 mRNA and protein activity decreased, and significant differences were observed at 6 h post-operation (P<0.05). RNA interference against NF-?B p65 was able to decrease the expression of NF-?B and further inhibit the early phasic excessive inflammatory reaction in sepsis, which may alleviate ALI. PMID:24913772

JIN, LI-YAN; LI, CONG-FENG; ZHU, GUANG-FA; WU, CHUN-TING; WANG, JUN; YAN, SHU-FENG

2014-01-01

38

Superantigens Are Critical for Staphylococcus aureus Infective Endocarditis, Sepsis, and Acute Kidney Injury  

PubMed Central

ABSTRACT Infective endocarditis and kidney infections are serious complications of Staphylococcus aureus sepsis. We investigated the role of superantigens (SAgs) in the development of lethal sepsis, infective endocarditis, and kidney infections. SAgs cause toxic shock syndrome, but it is unclear if SAgs contribute to infective endocarditis and kidney infections secondary to sepsis. We show in the methicillin-resistant S. aureus strain MW2 that lethal sepsis, infective endocarditis, and kidney infections in rabbits are critically dependent on high-level SAgs. In contrast, the isogenic strain lacking staphylococcal enterotoxin C (SEC), the major SAg in this strain, is attenuated in virulence, while complementation restores disease production. SAgs’ role in infective endocarditis appears to be both superantigenicity and direct endothelial cell stimulation. Maintenance of elevated blood pressure by fluid therapy significantly protects from infective endocarditis, possibly through preventing bacterial accumulation on valves and increased SAg elimination. These data should facilitate better methods to manage these serious illnesses. PMID:23963178

Salgado-Pabón, Wilmara; Breshears, Laura; Spaulding, Adam R.; Merriman, Joseph A.; Stach, Christopher S.; Horswill, Alexander R.; Peterson, Marnie L.; Schlievert, Patrick M.

2013-01-01

39

Acute-phase protein ?-1-acid glycoprotein mediates neutrophil migration failure in sepsis by a nitric oxide-dependent mechanism  

PubMed Central

The reduction of circulating neutrophil migration to infection sites is associated with a poor outcome of severe sepsis. ?-1-Acid glycoprotein (AGP) was isolated from the sera of severely septic patients by HPLC and acrylamide gel electrophoresis and identified by mass spectrometry. Both the isolated protein and commercial AGP inhibited carrageenin-induced neutrophil migration into the rat peritoneal cavity when administered i.v. at a dose of 4.0 ?g per rat (95 pmol per rat). Analysis by intravital microscopy demonstrated that both proteins inhibited the rolling and adhesion of leukocytes in the mesenteric microcirculation. The inhibitory activity was blocked by 50 mg/kg aminoguanidine, s.c., and was not demonstrable in inducible nitric oxide synthase (iNOS) knockout mice. Incubation of AGP with neutrophils from healthy subjects induced the production of NO and inhibited the neutrophil chemotaxis by an iNOS/NO/cyclic guanosine 3,5-monophosphate-dependent pathway. In addition, AGP induced the l-selectin shedding by neutrophils. The administration of AGP to rats with mild cecal ligation puncture sepsis inhibited neutrophil migration and reduced 7-day survival from ?80% to 20%. These data demonstrate that AGP, an acute-phase protein, inhibits neutrophil migration by an NO-dependent process and suggest that AGP also participates in human sepsis. PMID:18048324

Mestriner, F. L. A. C.; Spiller, F.; Laure, H. J.; Souto, F. O.; Tavares-Murta, B. M.; Rosa, J. C.; Basile-Filho, A.; Ferreira, S. H.; Greene, L. J.; Cunha, F. Q.

2007-01-01

40

Comparison of serum creatinine and serum cystatin C as biomarkers to detect sepsis-induced acute kidney injury and to predict mortality in CD-1 mice.  

PubMed

Acute kidney injury (AKI) dramatically increases sepsis mortality, but AKI diagnosis is delayed when based on serum creatinine (SCr) changes, due in part, to decreased creatinine production. During experimental sepsis, we compared serum cystatin C (sCysC), SCr, and blood urea nitrogen (BUN) to inulin glomerular filtration rate (iGFR) before or 3-18 h after cecal ligation and puncture (CLP)-induced sepsis in CD-1 mice. sCysC had a faster increase and reached peak levels more rapidly than SCr in both sepsis and bilateral nephrectomy (BiNx) models. sCysC was a better surrogate of iGFR than SCr during sepsis. Combining sCysC with SCr values into a composite biomarker improved correlation with iGFR better than any biomarker alone or any other combination. We determined the renal contribution to sCysC handling with BiNx. sCysC and SCr were lower post-BiNx/CLP than post-BiNx alone, despite increased inflammatory and nonrenal organ damage biomarkers. Sepsis decreased CysC production in nephrectomized mice without changing body weight or CysC space. Sepsis decreased sCysC production and increased nonrenal clearance, similar to effects of sepsis on SCr. sCysC, SCr, and BUN were measured 6 h postsepsis to link AKI with mortality. Mice with above-median sCysC, BUN, or SCr values 6 h postsepsis died earlier than mice with below-median values, corresponding to a substantial AKI association with sepsis mortality in this model. sCysC performs similarly to SCr in classifying mice at risk for early mortality. We conclude that sCysC detects AKI early and better reflects iGFR in CLP-induced sepsis. This study shows that renal biomarkers need to be evaluated in specific contexts. PMID:25143457

Leelahavanichkul, Asada; Souza, Ana Carolina P; Street, Jonathan M; Hsu, Victor; Tsuji, Takayuki; Doi, Kent; Li, Lingli; Hu, Xuzhen; Zhou, Hua; Kumar, Parag; Schnermann, Jürgen; Star, Robert A; Yuen, Peter S T

2014-10-15

41

Polyarthritis following a streptococcal infection, a doctor's dilemma in treatment: a case report  

Microsoft Academic Search

INTRODUCTION: Acute Rheumatic Fever and Post Streptococcal Reactive Arthritis in adults can present in a similar manner. CASE PRESENTATION: A 25 year old Caucasian male developed a transient crippling polyarthritis one month following treatment of a sore throat. The patient was found to meet criteria for both Acute Rheumatic Fever and Post Streptococcal Reactive Arthritis, leading to the question of

Vanya Grover; Robin Dibner

2009-01-01

42

Pharmacological targets in the renal peritubular microenvironment: implications for therapy for sepsis-induced acute kidney injury  

PubMed Central

One of the most frequent and serious complications to develop in septic patients is acute kidney injury (AKI), a disorder characterized by a rapid failure of the kidneys to adequately filter the blood, regulate ion and water balance, and generate urine. AKI greatly worsens the already poor prognosis of sepsis and increases cost of care. To date, therapies have been mostly supportive; consequently there has been little change in the mortality rates over the last decade. This is due, at least in part, to the delay in establishing clinical evidence of an infection and the associated presence of the systemic inflammatory response syndrome and thus, a delay in initiating therapy. A second reason is a lack of understanding regarding the mechanisms leading to renal injury, which has hindered the development of more targeted therapies. In this review, we summarize recent studies, which have examined the development of renal injury during sepsis and propose how changes in the peritubular capillary microenvironment lead to and then perpetuate microcirculatory failure and tubular epithelial cell injury. We also discuss a number of potential therapeutic targets in the renal peritubular microenvironment, which may prevent or lessen injury and/or promote recovery. PMID:22274552

Mayeux, Philip R.; MacMillan-Crow, Lee Ann

2012-01-01

43

Hemin inhibits NLRP3 inflammasome activation in sepsis-induced acute lung injury, involving heme oxygenase-1.  

PubMed

NLRP3 inflammasome activation contributes to acute lung injury (ALI), accelerating caspase-1 maturation, and resulting in IL-1? and IL-18 over-production. Heme oxygenase-1 (HO-1) plays a protective role in ALI. This study investigated the effect of hemin (a potent HO-1 inducer) on NLRP3 inflammasome in sepsis-induced ALI. The sepsis model of cecal ligation and puncture (CLP) was used in C57BL6 mice. In vivo induction and suppression of HO-1 were performed by pretreatment with hemin and zinc protoporphyrin IX (ZnPP, a HO-1 competitive inhibitor) respectively. CLP triggered significant pulmonary damage, neutrophil infiltration, increased levels of IL-1? and IL-18, and edema formation in the lung. Hemin pretreatment exerted inhibitory effect on lung injury and attenuated IL-1? and IL-18 secretion in serum and lung tissue. In lung tissues, hemin down-regulated mRNA and protein levels of NLRP3, ASC and caspase-1. Moreover, hemin reduced malondialdehyde and reactive oxygen species production, and inhibited NF-?B and NLRP3 inflammasome activity. Meanwhile, hemin significantly increased HO-1 mRNA and protein expression and HO-1 enzymatic activity. In contrast, no significant differences were observed between the CLP and ZnPP groups. Our study suggests that hemin-inhibited NLRP3 inflammasome activation involved HO-1, reducing IL-1? and IL-18 secretion and limiting the inflammatory response. PMID:24583148

Luo, Yun-peng; Jiang, Lei; Kang, Kai; Fei, Dong-sheng; Meng, Xiang-lin; Nan, Chuan-chuan; Pan, Shang-ha; Zhao, Ming-ran; Zhao, Ming-yan

2014-05-01

44

TNF-mediated damage to glomerular endothelium is an important determinant of acute kidney injury in sepsis.  

PubMed

Severe sepsis is often accompanied by acute kidney injury (AKI) and albuminuria. Here we studied whether the AKI and albuminuria associated with lipopolysaccharide (LPS) treatment in mice reflects impairment of the glomerular endothelium with its associated endothelial surface layer. LPS treatment decreased the abundance of endothelial surface layer heparan sulfate proteoglycans and sialic acid, and led to albuminuria likely reflecting altered glomerular filtration permselectivity. LPS treatment decreased the glomerular filtration rate (GFR), while also causing significant ultrastructural alterations in the glomerular endothelium. The density of glomerular endothelial cell fenestrae was 5-fold lower, whereas the average fenestrae diameter was 3-fold higher in LPS-treated than in control mice. The effects of LPS on the glomerular endothelial surface layer, endothelial cell fenestrae, GFR, and albuminuria were diminished in TNF receptor 1 (TNFR1) knockout mice, suggesting that these LPS effects are mediated by TNF-? activation of TNFR1. Indeed, intravenous administration of TNF decreased GFR and led to loss of glomerular endothelial cell fenestrae, increased fenestrae diameter, and damage to the glomerular endothelial surface layer. LPS treatment decreased kidney expression of vascular endothelial growth factor (VEGF). Thus, our findings confirm the important role of glomerular endothelial injury, possibly by a decreased VEGF level, in the development and progression of AKI and albuminuria in the LPS model of sepsis in the mouse. PMID:23903370

Xu, Chang; Chang, Anthony; Hack, Bradley K; Eadon, Michael T; Alper, Seth L; Cunningham, Patrick N

2014-01-01

45

The expression of Toll-like receptors and development of severe sepsis in patients with acute myeloid leukemias after induction chemotherapy.  

PubMed

Toll-like receptors play an important role in the host defense against microorganisms. Sepsis remains a common cause of mortality in patients with acute myeloid leukemia (AML) treated with intensive induction chemotherapy. The expression of TLRs and their association with the development of sepsis in patients with acute myeloid leukemia remains unclear. The aim of this study was to investigate the associations between expression of TLR2, TLR4 and TLR9 and occurrence of sepsis in patients treated with intensive induction chemotherapy for AML. A total of 103 patients with newly diagnosed AML were evaluated. Bone marrow samples were taken before induction therapy. Using quantitative reverse transcriptase PCR, the mRNA expression of genes TLR2, TLR4 and TLR9 was measured. Neutropenic fever occurred in 98 patients. We identified 20 episodes of severe sepsis (20%). In patients with neutropenic fever, the mRNA expression of TLR2 and TLR4 was significant higher in septic patients than in patients without sepsis symptoms (?Ct TLR2 0.93 ± 0.82 vs 0.78 ± 0.85 and ?Ct TLR4 0.38 ± 0.29 vs 0.34 ± 0.25). Moreover, we observed that expression of TLR2 and TLR4 was significantly higher in patients with AML and bacterial infection in comparison with group with separate fungal infection (?Ct TLR2 1.15 ± 1.06 vs 0.66 ± 0.51 and ?Ct TLR4 0.45 ± 0.38 vs 0.21 ± 0.19). Our results suggest that TLRs could be an independent factor for the development of sepsis in patients with acute myeloid leukemias after intensive induction chemotherapy. This observation should be validated by larger study. PMID:25412934

Rybka, Justyna; Butrym, Aleksandra; Wróbel, Tomasz; Ja?wiec, Bo?ena; Stefanko, Ewa; Dobrzy?ska, Olga; Por?ba, Rafa?; Kuliczkowski, Kazimierz

2014-12-01

46

Zinc Regulates the Acute Phase Response and Serum Amyloid A Production in Response to Sepsis through JAK-STAT3 Signaling  

PubMed Central

Sepsis rapidly activates the host inflammatory response and acute phase response. Severe sepsis, complicated by multiple organ failure, is associated with overwhelming inflammation and high mortality. We previously observed that zinc (Zn) deficiency significantly increases mortality in a mouse model of polymicrobial sepsis due to over-activation of the inflammatory response. In order to identify potential mechanisms that account for Zn-responsive effects, we generated whole exome expression profiles from the lung tissue of septic mice that were maintained on Zn modified diets. Based on systems analysis, we observed that Zn deficiency enhances the acute phase response and particularly the JAK-STAT3 pathway, resulting in increased serum amyloid A production. In vitro studies of primary hepatocytes and HepG2 cells substantiated that Zn-deficiency augments serum amyloid A production through up-regulation of the JAK-STAT3 and NF-?B pathways. In contrast, Zn inhibited STAT3 activation through the up-regulation of SHP1 activity. Collectively, these findings demonstrate that Zn deficiency enhances the acute phase response through up-regulation of the JAK-STAT3 pathway, thereby perpetuating increased inflammation that may lead to increased morbidity and mortality in response to sepsis. PMID:24732911

Liu, Ming-Jie; Bao, Shengying; Napolitano, Jessica R.; Burris, Dara L.; Yu, Lianbo; Tridandapani, Susheela; Knoell, Daren L.

2014-01-01

47

Group A Streptococcal Infections  

MedlinePLUS

... Share this: Main Content Area Group A streptococcal (GAS) infections can range from a mild skin infection ... mild infections (throat and skin) occur every year. GAS infections include Cellulitis and Erysipelas Impetigo Scarlet Fever ...

48

Scavenger Receptor B and CD36 Targeting Improves Sepsis Survival and Acute Outcomes in Mice*  

PubMed Central

Class B scavenger receptors, such as SR-BI/II or CD36, bind lipoproteins, but also mediate bacterial recognition and phagocytosis. In evaluating whether blocking receptors can prevent intracellular bacterial proliferation, phagocyte cytotoxicity and proinflammatory signaling in bacterial infection/sepsis, we found that SR-BI/II- or CD36-deficient phagocytes are characterized by a reduced intracellular bacterial survival, a lower cytokine response, and were protected from bacterial cytotoxicity in the presence of antibiotics. Mice deficient in either SR-BI/II or CD36 are protected from antibiotic-treated cecal ligation and puncture (CLP)-induced sepsis, with greatly increased peritoneal granulocytic phagocyte survival (8-fold), a drastic diminution in peritoneal bacteria counts and 50 to 70% reduction in systemic inflammation (serum levels of IL-6, TNF-? and IL-10) and organ damage relative to CLP in wild-type mice. CD36-deficient mice survival after CLP was 58% compared to 17% in control mice. When compensated for mineralocorticoid and glucocorticoid deficiency, SR-BI/II-deficient mice had almost a 50% survival rate vs. 5% in mineralo-/glucocorticoid-treated controls. Targeting SR-B receptors with L-37pA, a peptide that functions as an antagonist of SR-BI/II and CD36 receptors, also increased peritoneal granulocyte counts, reduced peritoneal bacteria and bacterium-induced cytokine secretion. In the CLP mouse sepsis model L-37pA improved survival from 6% to 27%, reduced multiple organ damage, and improved kidney function. These results demonstrate that the reduction of both SR-BI/II- and CD36-dependent bacterial invasion and inflammatory response in the presence of antibiotic treatment results in granulocyte survival, local bacterial containment, and also reduces systemic inflammation, organ damage and improve animal survival during severe infections. PMID:22327076

Leelahavanichkul, Asada; Bocharov, Alexander V.; Kurlander, Roger; Baranova, Irina N.; Vishnyakova, Tatyana G.; Souza, Ana C.P.; Hu, Xuzhen; Doi, Kent; Vaisman, Boris; Amar, Marcelo; Sviridov, Denis; Chen, Zhigang; Remaley, Alan T.; Csako, Gyorgy; Patterson, Amy P.; Yuen, Peter S. T.; Star, Robert A; Eggerman, Thomas L.

2013-01-01

49

Streptococcal Toxic Shock Syndrome Caused by Streptococcus suis Serotype 2  

Microsoft Academic Search

BackgroundStreptococcus suis serotype 2 ( S. suis 2, SS2) is a major zoonotic pathogen that causes only sporadic cases of meningitis and sepsis in humans. Most if not all cases of Streptococcal toxic shock syndrome (STSS) that have been well-documented to date were associated with the non-SS2 group A streptococcus (GAS). However, a recent large-scale outbreak of SS2 in Sichuan

Jiaqi Tang; Changjun Wang; Youjun Feng; Weizhong Yang; Huaidong Song; Zhihai Chen; Hongjie Yu; Xiuzhen Pan; Xiaojun Zhou; Huaru Wang; Bo Wu; Haili Wang; Huamei Zhao; Ying Lin; Jianhua Yue; Zhenqiang Wu; Xiaowei He; Feng Gao; Abdul Hamid Khan; Jian Wang; Guo-Ping Zhao; Yu Wang; Xiaoning Wang; Zhu Chen; George F Gao

2006-01-01

50

Outcome of patients with acute kidney injury in severe sepsis and septic shock treated with early goal-directed therapy in an intensive care unit.  

PubMed

Acute kidney injury (AKI) in the intensive care unit (ICU) is commonly caused by severe sepsis and septic shock. There is limited data regarding the incidence and outcomes of patients developing AKI treated with early goal-directed therapy (EGDT). Our aim was to observe the incidence and outcomes of patients with AKI in severe sepsis and septic shock, treated with EGDT as compared with historic controls. Study subjects included all adults admitted to the ICU with a diagnosis of severe sepsis and septic shock prior to (historic controls) and after introduction of EGDT (intervention group). Two groups were compared for incidence of AKI, length of ICU and hospital stay, incidence and requirement for renal replacement therapy, serum creatinine at discharge, maximum RIFLE (Risk, injury, failure, loss, end stage) in each group and 28-day mortality. Two groups were well matched for age, sex, (April 16, 2014) and acute physiological and chronic health evaluation (APACHE) II scores. We found no significant difference in the incidence of AKI (51% vs. 46%). There was no statistical difference in any of the above outcomes, including 28-day mortality in historic controls versus patients treated with EGDT. Septic AKI is a complex syndrome. The incidence and outcomes have not improved despite advances in sepsis management and EGDT. Very early detection of septic AKI and targeted therapies may improve outcomes. PMID:24821150

Ahmed, Wasim; Memon, Ahmed I; Rehmani, Rifat; Al Juhaiman, Abdulmajeed

2014-05-01

51

Exogenous Glucose Administration Impairs Glucose Tolerance and Pancreatic Insulin Secretion during Acute Sepsis in Non-Diabetic Mice  

PubMed Central

Objectives The development of hyperglycemia and the use of early parenteral feeding are associated with poor outcomes in critically ill patients. We therefore examined the impact of exogenous glucose administration on the integrated metabolic function of endotoxemic mice using our recently developed frequently sampled intravenous glucose tolerance test (FSIVGTT). We next extended our findings using a cecal ligation and puncture (CLP) sepsis model administered early parenteral glucose support. Methods Male C57BL/6J mice, 8-12 weeks, were instrumented with chronic indwelling arterial and venous catheters. Endotoxemia was initiated with intra-arterial lipopolysaccharide (LPS; 1 mg/kg) in the presence of saline or glucose infusion (100 µL/hr), and an FSIVGTT was performed after five hours. In a second experiment, catheterized mice underwent CLP and the impact of early parenteral glucose administration on glucose homeostasis and mortality was assessed over 24 hrs. Measurements And MAIN RESULTS: Administration of LPS alone did not impair metabolic function, whereas glucose administration alone induced an insulin sensitive state. In contrast, LPS and glucose combined caused marked glucose intolerance and insulin resistance and significantly impaired pancreatic insulin secretion. Similarly, CLP mice receiving parenteral glucose developed fulminant hyperglycemia within 18 hrs (all > 600 mg/dl) associated with increased systemic cytokine release and 40% mortality, whereas CLP alone (85 ± 2 mg/dL) or sham mice receiving parenteral glucose (113 ± 3 mg/dL) all survived and were not hyperglycemic. Despite profound hyperglycemia, plasma insulin in the CLP glucose-infused mice (3.7 ± 1.2 ng/ml) was not higher than sham glucose infused mice (2.1 ± 0.3 ng/ml). Conclusions The combination of parenteral glucose support and the systemic inflammatory response in the acute phase of sepsis induces profound insulin resistance and impairs compensatory pancreatic insulin secretion, leading to the development of fulminant hyperglycemia. PMID:23826335

Zou, Baobo; Guo, Lanping; Stefanovski, Darko; Alonso, Laura C.; Garcia-Ocana, Adolfo; O’Donnell, Christopher P.; McVerry, Bryan J.

2013-01-01

52

Functional promoter variants in sphingosine 1-phosphate receptor 3 associate with susceptibility to sepsis-associated acute respiratory distress syndrome  

PubMed Central

The genetic mechanisms underlying the susceptibility to acute respiratory distress syndrome (ARDS) are poorly understood. We previously demonstrated that sphingosine 1-phosphate (S1P) and the S1P receptor S1PR3 are intimately involved in lung inflammatory responses and vascular barrier regulation. Furthermore, plasma S1PR3 protein levels were shown to serve as a biomarker of severity in critically ill ARDS patients. This study explores the contribution of single nucleotide polymorphisms (SNPs) of the S1PR3 gene to sepsis-associated ARDS. S1PR3 SNPs were identified by sequencing the entire gene and tagging SNPs selected for case-control association analysis in African- and ED samples from Chicago, with independent replication in a European case-control study of Spanish individuals. Electrophoretic mobility shift assays, luciferase activity assays, and protein immunoassays were utilized to assess the functionality of associated SNPs. A total of 80 variants, including 29 novel SNPs, were identified. Because of limited sample size, conclusive findings could not be drawn in African-descent ARDS subjects; however, significant associations were found for two promoter SNPs (rs7022797 ?1899T/G; rs11137480 ?1785G/C), across two ED samples supporting the association of alleles ?1899G and ?1785C with decreased risk for sepsis-associated ARDS. In addition, these alleles significantly reduced transcription factor binding to the S1PR3 promoter; reduced S1PR3 promoter activity, a response particularly striking after TNF-? challenge; and were associated with lower plasma S1PR3 protein levels in ARDS patients. These highly functional studies support S1PR3 as a novel ARDS candidate gene and a potential target for individualized therapy. PMID:23911438

Sun, Xiaoguang; Ma, Shwu-Fan; Wade, Michael S.; Acosta-Herrera, Marialbert; Villar, Jesús; Pino-Yanes, Maria; Zhou, Tong; Liu, Bin; Belvitch, Patrick; Moitra, Jaideep; Han, Yoo-Jeong; Machado, Roberto; Noth, Imre; Natarajan, Viswanathan; Dudek, Steven M.; Jacobson, Jeffrey R.; Flores, Carlos

2013-01-01

53

Polyarthritis following a streptococcal infection, a doctor's dilemma in treatment: a case report  

PubMed Central

Introduction Acute Rheumatic Fever and Post Streptococcal Reactive Arthritis in adults can present in a similar manner. Case Presentation A 25 year old Caucasian male developed a transient crippling polyarthritis one month following treatment of a sore throat. The patient was found to meet criteria for both Acute Rheumatic Fever and Post Streptococcal Reactive Arthritis, leading to the question of the role of antibiotic prophylaxis long term. Conclusion Due to overlap in the diagnostic criteria for Acute Rheumatic Fever and Post Streptococcal Reactive Arthritis in adults, the need for penicillin prophylaxis should be individualized based on exposure risk. PMID:20062657

2009-01-01

54

Gut origin sepsis, macrophage function, and oxygen extraction associated with acute pancreatitis in the rat.  

PubMed

It has been suggested that the gut plays a role in the development of bacterial complications, which are important contributors to morbidity and mortality in patients with acute pancreatitis. The present study evaluated the enteric bacterial translocation, bacterial homeostasis, and reticuloendothelial system function in experimental acute pancreatitis induced by intraductal injection of 5% sodium taurodeoxycholate in the rat. The incidence of bacterial translocation from the gut to mesenteric lymph nodes (MLNs) and lungs significantly increased after 12 hours and to the systemic circulation, ascites, and pancreas at 24 hours. The number of anaerobic bacteria and lactobacilli decreased in the colon and distal ileum from 6 or 12 hours, whereas the number of Escherichia coli increased from 12 hours. The systemic uptake rate of radiolabeled bacteria decreased from 6 hours after induction of acute pancreatitis. The uptake of radiolabeled bacteria by Kupffer cells decreased from 6 hours, whereas the uptake by macrophages from blood, lungs, and the intestine increased. A decrease in macrophage killing capacity was noted, reflected by an increase in the number of cultured viable bacteria from isolated macrophages. The whole-body oxygen extraction rate increased 4 to 24 hours after induction of pancreatitis, whereas the gut oxygen extraction rate decreased at 2 and 4 hours, followed by an increase at 12 to 24 hours. These data show that translocation of enteric bacteria occurs during the early stage of acute pancreatitis and that the MLN-thoracic duct-circulation may be a major route of bacterial dissemination. Compromised gut oxygen metabolism, overexaggerated intestinal macrophages, and impaired host immune function may be involved in the development of infectious complications associated with acute pancreatitis. PMID:8661835

Wang, X; Andersson, R; Soltesz, V; Leveau, P; Ihse, I

1996-01-01

55

Predicting Sepsis Severity from Limited Temporal Observations  

E-print Network

Predicting Sepsis Severity from Limited Temporal Observations Xi Hang Cao, Ivan Stojkovic. Sepsis, an acute systemic inflammatory response syndrome caused by severe infection, is one of the leading causes of in-hospital mor- tality. Our recent work provides evidence that mortality rate in sepsis

Obradovic, Zoran

56

Genetic variation in the TNF receptor-associated factor 6 gene is associated with susceptibility to sepsis-induced acute lung injury  

PubMed Central

Background Recent studies showed that overwhelming inflammatory response mediated by the toll-like receptor (TLR)-related pathway was important in the development of acute lung injury (ALI). The aim of this study was to determine whether common genetic variation in four genes of the TLR signaling pathway were associated with sepsis-induced ALI susceptibility and risk of death in Chinese Han population. Methods Fourteen tag single nucleotide polymorphisms (tagSNPs) in MyD88, IRAK1, IRAK4 and TRAF6 were genotyped in samples of sepsis-induced ALI (n?=?272) and sepsis alone patients (n?=?276), and tested for association in this case-control collection. Then, we investigated correlation between the associated SNP and the mRNA expression level of the corresponding gene. And we also investigated correlation between the associated SNP and tumor necrosis factor alpha (TNF-?) as well as interleukin-6 (IL-6) concentrations in peripheral blood mononuclear cells (PBMCs) exposed to lipopolysaccharides (LPS) ex vivo. The mRNA expression level was determined using real-time quantitative Polymerase Chain Reaction (PCR) assays, and concentrations of TNF-? and IL-6 were measured by enzyme-linked immunosorbent assay (ELISA). Results The association analysis revealed that rs4755453, an intronic SNP of TRAF6, was significantly associated with susceptibility to sepsis-induced ALI. The C allele frequency of rs4755453 in the sepsis alone group was significantly higher than that in the sepsis-induced ALI group (P?=?0.00026, odds ratio (OR) = 0.52, 95% confidence interval (CI) 0.37–0.74). These associations remained significant after adjustment for covariates in multiple logistic regression analysis and for multiple comparisons. TRAF6 mRNA expression levels in PBMCs from homozygotes of the rs4755453G allele were significantly higher than that in heterozygotes and homozygotes of the rs4755453C allele at baseline (P?=?0.012 and P?=?0.003, respectively) as well as after LPS stimulation (P?=?0.009 and P?=?0.005). Moreover, the concentrations of TNF-? and IL-6 in cell culture supernatants were also significantly higher in the subjects with rs4755453GG genotype than in subjects with CG and CC genotype. None of the 14 tagSNPs showed associations with risk of death and severity among ALI cases. Conclusions Our findings indicated that common genetic variants in TRAF6 were significantly associated with susceptibility to sepsis-induced ALI in Chinese Han population. This was the first genetic evidence supporting a role for TRAF6 in ALI. PMID:22901274

2012-01-01

57

The Effects of Dexmedetomidine on Secondary Acute Lung and Kidney Injuries in the Rat Model of Intra-Abdominal Sepsis  

PubMed Central

In the present study, the effects of dexmedetomidine on secondary lung and kidney injuries were studied in the rat model of intra-abdominal sepsis by immunohistological and biochemical examinations. We measured serum creatinine, kidney tissue malondialdehide and plasma neutrophil gelatinase-associated lipocalin levels. In order to evaluate tissue injury we determined kidney tissue mononuclear cell infiltration score, alveolar macrophage count, histological kidney and lung injury scores and kidney and lung tissue immunoreactivity scores. We demonstrated that dexmedetomidine attenuates sepsis-induced lung and kidney injuries and apoptosis in the rat model of sepsis. There is still need for comparative studies in order to determine the effects of dexmedetomidine on organ functions in early human sepsis. PMID:23476127

Olguner, Çimen Gülben; Ergür, Bekir U?ur; Altekin, Emel; Ta?dö?en, Ayd?n; Duru, Seden; Girgin, Pelin; Gündüz, Kerim; Cilaker M?c?l?, Serap; Güzelda?, Seda; Akku?, Muhammed

2013-01-01

58

A Unified Theory of Sepsis-Induced Acute Kidney Injury: Inflammation, microcirculatory dysfunction, bioenergetics and the tubular cell adaptation to injury  

PubMed Central

Given that the leading clinical conditions associated with Acute kidney injury (AKI), namely, sepsis, major surgery, heart failure and hypovolemia, are all associated with shock, it is tempting to attribute all AKI to ischemia on the basis of macro-hemodynamic changes. However, an increasing body of evidence has suggested that in many patients, AKI can occur in the absence of overt signs of global renal hypoperfusion. Indeed, sepsis-induced AKI can occur in the setting of normal or even increased renal blood flow. Accordingly, renal injury may not be entirely explained solely on the basis of the classic paradigm of hypoperfusion, and thus other mechanisms must come into play. Herein, we put forward a “unifying theory” to explain the interplay between inflammation and oxidative stress, microvascular dysfunction, and the adaptive response of the tubular epithelial cell to the septic insult. We propose that this response is mostly adaptive in origin, that it is driven by mitochondria and that it ultimately results in and explains the clinical phenotype of sepsis induced AKI. PMID:24346647

Gomez, Hernando; Ince, Can; De Backer, Daniel; Pickkers, Peter; Payen, Didier; Hotchkiss, John; Kellum, John A.

2014-01-01

59

A multicenter, prospective validation study of the Japanese Association for Acute Medicine disseminated intravascular coagulation scoring system in patients with severe sepsis  

PubMed Central

Introduction To validate the Japanese Association for Acute Medicine (JAAM) disseminated intravascular coagulation (DIC) scoring system in patients with severe sepsis, we conducted a multicenter, prospective study at 15 critical care centers in tertiary care hospitals. Methods This study included 624 severe sepsis patients. JAAM DIC was scored on the day of diagnosis of severe sepsis (day 1) and day 4. Scores for disease severity and organ dysfunction were also evaluated. Results The prevalence of JAAM DIC was 46.8% (292/624), and 21% of the DIC patients were scored according to the reduction rate of platelets. The JAAM DIC patients were more seriously ill and exhibited more severe systemic inflammation, a higher prevalence of multiple organ dysfunction syndrome (MODS) and worse outcomes than the non-DIC patients. Disease severity, systemic inflammation, MODS and the mortality rate worsened in accordance with an increased JAAM DIC score on day 1. The Kaplan-Meier curves demonstrated lower 1-year survival in the JAAM DIC patients than in those without DIC (log-rank test P <0.001). The JAAM DIC score on day 1 (odds ratio = 1.282, P <0.001) and the Delta JAAM DIC score (odds ratio = 0.770, P <0.001) were independent predictors of 28-day death. Dynamic changes in the JAAM DIC score from days 1 to 4 also affected prognoses. The JAAM DIC scoring system included all patients who met the International Society on Thrombosis and Haemostasis overt DIC criteria on day 1. The International Society on Thrombosis and Haemostasis scoring system missed a large number of nonsurvivors recognized by the JAAM scoring system. Conclusions The JAAM DIC scoring system exhibits good prognostic value in predicting MODS and poor prognosis in patients with severe sepsis and can detect more patients requiring treatment. Conducting repeated daily JAAM scoring increases the ability to predict the patient's prognosis. PMID:23787004

2013-01-01

60

Effects of Fluid Resuscitation With 0.9% Saline Versus a Balanced Electrolyte Solution on Acute Kidney Injury in a Rat Model of Sepsis*  

PubMed Central

Objective To compare the acute effects of 0.9% saline versus a balanced electrolyte solution on acute kidney injury in a rat model of sepsis. Design Controlled laboratory experiment. Setting University laboratory. Subjects Sixty adult, male Sprague-Dawley rats. Interventions We induced sepsis by cecal ligation and puncture and randomized animals to receive fluid resuscitation with either 0.9% saline or Plasma-Lyte solution for 4 hours after 18 hours of cecal ligation and puncture (10 mL/kg in the first hour and 5 mL/kg in the next 3 hr). Blood and urine specimens were obtained from baseline, 18 hours after cecal ligation and puncture, immediately after 4 hours fluid resuscitation, and 24 hours later. We measured blood gas, plasma electrolytes, creatinine, interleukin-6, cystatin C, and neutrophil gelatinase-associated lipocalin concentrations. We also analyzed urine for cystatin C and neutrophil gelatinase-associated lipocalin. We used Risk, Injury, Failure, Loss and End-stage criteria for creatinine to assess severity of acute kidney injury. We observed all animals for survival up to 1 day after resuscitation. Surviving animals were killed for kidney histology. Finally, we carried out an identical study in 12 healthy animals. Measurements and Main Results Compared with Plasma-Lyte, 0.9% saline resuscitation resulted in significantly greater blood chloride concentrations (p < 0.05) and significantly decreased pH and base excess. Acute kidney injury severity measured by RIFLE criteria was increased with 0.9% saline compared with Plasma-Lyte resuscitation (p < 0.05), and these results were consistent with kidney histology and biomarkers of acute kidney injury. Twenty-four-hour survival favored Plasma-Lyte resuscitation (76.6% vs 53.3%; p = 0.03). Finally, in healthy animals, we found no differences between fluids and no evidence of acute kidney injury. Conclusion Volume resuscitation with Plasma-Lyte resulted in less acidosis and less kidney injury and improved short-term survival when compared with 0.9% saline in this experimental animal model of sepsis. PMID:24335444

Zhou, Feihu; Peng, Zhi-Yong; Bishop, Jeffery V.; Cove, Matthew E.; Singbartl, Kai; Kellum, John A.

2014-01-01

61

The Role of Whole Blood Impedance Aggregometry and Its Utilisation in the Diagnosis and Prognosis of Patients with Systemic Inflammatory Response Syndrome and Sepsis in Acute Critical Illness  

PubMed Central

Objective To assess the prognostic and diagnostic value of whole blood impedance aggregometry in patients with sepsis and SIRS and to compare with whole blood parameters (platelet count, haemoglobin, haematocrit and white cell count). Methods We performed an observational, prospective study in the acute setting. Platelet function was determined using whole blood impedance aggregometry (multiplate) on admission to the Emergency Department or Intensive Care Unit and at 6 and 24 hours post admission. Platelet count, haemoglobin, haematocrit and white cell count were also determined. Results 106 adult patients that met SIRS and sepsis criteria were included. Platelet aggregation was significantly reduced in patients with severe sepsis/septic shock when compared to SIRS/uncomplicated sepsis (ADP: 90.7±37.6 vs 61.4±40.6; p<0.001, Arachadonic Acid 99.9±48.3 vs 66.3±50.2; p?=?0.001, Collagen 102.6±33.0 vs 79.1±38.8; p?=?0.001; SD ± mean)). Furthermore platelet aggregation was significantly reduced in the 28 day mortality group when compared with the survival group (Arachadonic Acid 58.8±47.7 vs 91.1±50.9; p<0.05, Collagen 36.6±36.6 vs 98.0±35.1; p?=?0.001; SD ± mean)). However haemoglobin, haematocrit and platelet count were more effective at distinguishing between subgroups and were equally effective indicators of prognosis. Significant positive correlations were observed between whole blood impedance aggregometry and platelet count (ADP 0.588 p<0.0001, Arachadonic Acid 0.611 p<0.0001, Collagen 0.599 p<0.0001 (Pearson correlation)). Conclusions Reduced platelet aggregometry responses were not only significantly associated with morbidity and mortality in sepsis and SIRS patients, but also correlated with the different pathological groups. Whole blood aggregometry significantly correlated with platelet count, however, when we adjust for the different groups we investigated, the effect of platelet count appears to be non-significant. PMID:25269018

Davies, Gareth R.; Mills, Gavin M.; Lawrence, Matthew; Battle, Ceri; Morris, Keith; Hawkins, Karl; Williams, Phylip Rhodri; Davidson, Simon; Thomas, Dafydd; Evans, Phillip Adrian

2014-01-01

62

Neonatal sepsis  

MedlinePLUS

... coli ( E.coli ), Listeria , and some strains of streptococcus. The herpes virus can also cause a severe ... infant's risk of early-onset sepsis: Group B streptococcus infection during pregnancy Preterm delivery Water breaking (rupture ...

63

Pediatric sepsis  

PubMed Central

Sepsis is the leading cause of death in children worldwide. Although the diagnosis and management of sepsis in infants and children is largely influenced by studies done in adults, there are important considerations relevant for pediatrics. This article highlights pediatric-specific issues related to the definition of sepsis and its epidemiology and management. We review how the capacity of the immune system to respond to infection develops over early life. We also bring attention to primary immune deficiencies that should be considered in children recurrently infected with specific types of organisms. The management of pediatric sepsis must be tailored to the child’s age and immune capacity, and to the site, severity, and source of the infection. It is important for clinicians to be aware of infection-related syndromes that primarily affect children. Although children in developed countries are more likely to survive severe infections than adults, many survivors have chronic health impairments. PMID:24225404

Randolph, Adrienne G; McCulloh, Russell J

2014-01-01

64

Hemodynamic variables and progression of acute kidney injury in critically ill patients with severe sepsis: data from the prospective observational FINNAKI study  

PubMed Central

Introduction Knowledge of the association of hemodynamics with progression of septic acute kidney injury (AKI) is limited. However, some recent data suggest that mean arterial pressure (MAP) exceeding current guidelines (60–65 mmHg) may be needed to prevent AKI. We hypothesized that higher MAP during the first 24 hours in the intensive care unit (ICU), would be associated with a lower risk of progression of AKI in patients with severe sepsis. Methods We identified 423 patients with severe sepsis and electronically recorded continuous hemodynamic data in the prospective observational FINNAKI study. The primary endpoint was progression of AKI within the first 5 days of ICU admission defined as new onset or worsening of AKI by the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. We evaluated the association of hemodynamic variables with this endpoint. We included 53724 10-minute medians of MAP in the analysis. We analysed the ability of time-adjusted MAP to predict progression of AKI by receiver operating characteristic (ROC) analysis. Results Of 423 patients, 153 (36.2%) had progression of AKI. Patients with progression of AKI had significantly lower time-adjusted MAP, 74.4 mmHg [68.3-80.8], than those without progression, 78.6 mmHg [72.9-85.4], P?sepsis. PMID:24330815

2013-01-01

65

Group A Streptococcal (GAS) Disease  

MedlinePLUS

... Cancel Submit Search The CDC Group A Streptococcal (GAS) Disease Note: Javascript is disabled or is not ... Share Compartir Group A Streptococcus (group A strep, GAS) bacteria can live in a person's nose and ...

66

Puerperal sepsis.  

PubMed

Infections during pregnancy are relatively prevalent, and the majority of cases are managed well in the community. Occasionally, however, infections may be life-threatening. Sepsis may be associated with multiple organ dysfunction and a high mortality. The treatment of sepsis is time critical and requires early fluid resuscitation and antibiotics. Early involvement of other specialties and allied health-care professionals to provide a multidisciplinary approach to patient care is important. Continuous monitoring of maternal vital signs and provision of supportive care for multiple organ dysfunction are best done within the intensive care unit. Despite advances in patient care, the mortality rate associated with maternal sepsis remains high. Health-care services in low-income countries face particular problems that account for an increased incidence of puerperal sepsis and maternal mortality. These include lack of access to health care, septic abortions and a greater incidence of human immunodeficiency virus. The key to management of sepsis is early recognition, aggressive resuscitation, antibiotic administration and source control. PMID:23993724

Arulkumaran, N; Singer, M

2013-12-01

67

Understanding brain dysfunction in sepsis  

PubMed Central

Sepsis often is characterized by an acute brain dysfunction, which is associated with increased morbidity and mortality. Its pathophysiology is highly complex, resulting from both inflammatory and noninflammatory processes, which may induce significant alterations in vulnerable areas of the brain. Important mechanisms include excessive microglial activation, impaired cerebral perfusion, blood–brain-barrier dysfunction, and altered neurotransmission. Systemic insults, such as prolonged inflammation, severe hypoxemia, and persistent hyperglycemia also may contribute to aggravate sepsis-induced brain dysfunction or injury. The diagnosis of brain dysfunction in sepsis relies essentially on neurological examination and neurological tests, such as EEG and neuroimaging. A brain MRI should be considered in case of persistent brain dysfunction after control of sepsis and exclusion of major confounding factors. Recent MRI studies suggest that septic shock can be associated with acute cerebrovascular lesions and white matter abnormalities. Currently, the management of brain dysfunction mainly consists of control of sepsis and prevention of all aggravating factors, including metabolic disturbances, drug overdoses, anticholinergic medications, withdrawal syndromes, and Wernicke’s encephalopathy. Modulation of microglial activation, prevention of blood–brain-barrier alterations, and use of antioxidants represent relevant therapeutic targets that may impact significantly on neurologic outcomes. In the future, investigations in patients with sepsis should be undertaken to reduce the duration of brain dysfunction and to study the impact of this reduction on important health outcomes, including functional and cognitive status in survivors. PMID:23718252

2013-01-01

68

Experimental Sepsis Impairs Humoral Memory in Mice  

PubMed Central

Patients with sepsis are often immune suppressed, and experimental mouse models of sepsis also display this feature. However, acute sepsis in mice is also characterized by a generalized B cell activation and plasma cell differentiation, resulting in a marked increase in serum antibody concentration. Its effects on humoral memory are not clearly defined. We measured the effects of experimental sepsis on long-term immunological memory for a defined antigen: we induced colon ascendens stent peritonitis (CASP) 8 weeks after 2 rounds of immunization with ovalbumin. Four weeks later, the antigen-specific bone marrow plasma cell count had doubled in immunized non-septic animals, but remained unchanged in immunized septic animals. Sepsis also caused a decrease in antigen-specific serum antibody concentration. We conclude that sepsis weakens humoral memory by impeding the antigen-specific plasma cell pool’s development, which is not complete 8 weeks after secondary immunization. PMID:24312349

Pötschke, Christian; Kessler, Wolfram; Maier, Stefan; Heidecke, Claus-Dieter; Bröker, Barbara M.

2013-01-01

69

Staphylococcal and Streptococcal Superantigen Exotoxins  

PubMed Central

SUMMARY This review begins with a discussion of the large family of Staphylococcus aureus and beta-hemolytic streptococcal pyrogenic toxin T lymphocyte superantigens from structural and immunobiological perspectives. With this as background, the review then discusses the major known and possible human disease associations with superantigens, including associations with toxic shock syndromes, atopic dermatitis, pneumonia, infective endocarditis, and autoimmune sequelae to streptococcal illnesses. Finally, the review addresses current and possible novel strategies to prevent superantigen production and passive and active immunization strategies. PMID:23824366

Spaulding, Adam R.; Salgado-Pabón, Wilmara; Kohler, Petra L.; Horswill, Alexander R.; Leung, Donald Y. M.

2013-01-01

70

Myeloid-Derived Suppressor Cells in Sepsis  

PubMed Central

Sepsis is a systemic, deleterious host response to widespread infection. Patients with sepsis will have documented or suspected infection which can progress to a state of septic shock or acute organ dysfunction. Since sepsis is responsible for nearly 3 million cases per year in China and severe sepsis is a common, expensive fatal condition in America, developing new therapies becomes a significant and worthwhile challenge. Clinical research has shown that sepsis-associated immunosuppression plays a central role in patient mortality, and targeted immune-enhancing therapy may be an effective treatment approach in these patients. As part of the inflammatory response during sepsis, there are elevations in the number of myeloid-derived suppressor cells (MDSCs). MDSCs are a heterogeneous population of immature myeloid cells that possess immunosuppressive activities via suppressing T-cell proliferation and activation. The role of MDSCs in sepsis remains uncertain. Some believe activated MDSCs are beneficial to the sepsis host by increasing innate immune responses and antimicrobial activities, while others think expansion of MDSCs leads to adaptive immune suppression and secondary infection. Herein, we discuss the complex role of MDSCs in immune regulation during sepsis, as well as the potential to target these cells for therapeutic benefit. PMID:24995313

Qin, Chaojin; Shu, Qiang

2014-01-01

71

Demonstration of circulating group B streptococcal immune complexes in neonates with meningitis.  

PubMed Central

Group B streptococci are the major cause of sepsis and fatal shock in neonates in the United States. Although a number of clinical features have been associated with enhanced severity of disease, the role of soluble immune complex formation in group B streptococcal infection has not been evaluated. We determined the frequency with which circulating immune complexes occurred in 16 infants with nonfatal type III, group B streptococcal meningitis, using an immunoglobulin-specific C1q enzyme immunoassay. Ten healthy, age-matched infants served as a control group. Elevated levels of immunoglobulin M (IgM)-containing immune complexes were present in the sera of four (25%) patients with group B streptococcal meningitis. Group B antigen was detected in precipitated IgM immune complexes from each of these four infants by competitive enzyme-linked immunosorbent assay. In addition, IgG-containing immune complexes were present in 56% of sick and 60% of control infants. Group B antigen was demonstrated in the serum of a sick neonate containing only IgG immune complexes but not in controls. Our findings indicate that a subset of infants with type III, group B streptococcal meningitis develop IgM immune complexes containing group B-specific antigen, and these may persist for up to 3 months in some patients. PMID:7814522

Vallejo, J G; Baker, C J; Edwards, M S

1994-01-01

72

Jack of all trades: Pleiotropy and the application of chemically modified tetracycline-3 in sepsis and the acute respiratory distress syndrome (ARDS)  

Microsoft Academic Search

Sepsis is a disease process that has humbled the medical profession for centuries with its resistance to therapy, relentless mortality, and pathophysiologic complexity. Despite 30 years of aggressive, concerted, well-resourced efforts the biomedical community has been unable to reduce the mortality of sepsis from 30%, nor the mortality of septic shock from greater than 50%. In the last decade only

Shreyas K. Roy; Daniel Kendrick; Benjamin D. Sadowitz; Louis Gatto; Kathleen Snyder; Joshua M. Satalin; Lorne M. Golub; Gary Nieman

2011-01-01

73

Properdin Levels in Human Sepsis  

PubMed Central

Properdin is a normal serum protein that increases the production of complement activation products by binding C3b integral to convertase complexes and amplifying their activity at the site of activation. Thereby, it not only can aid in the resolution of infection but also contribute to tissue damage. In human sepsis, circulating complement C3 concentrations are decreased, though C3 is described as a positive acute phase reactant. However, properdin levels in human sepsis have not been reported. In this study, serum from 81 critically ill patients (predominately abdominal and respiratory sepsis) were analyzed for properdin levels at defined points of their stay in the intensive care unit (ICU) and compared with 61 age and sex-matched healthy volunteers. Properdin concentrations were significantly decreased in patients with sepsis on admission to ICU, but increased after clinical recovery to exceed levels observed in healthy volunteers. Properdin concentrations at ICU admission were decreased in non-survivors of sepsis compared to survivors, but this did not correlate with APACHE II score. However, pathologically low properdin levels (<7 ?g/ml) were related to increased duration of treatment.

Stover, Cordula M.; McDonald, John; Byrne, Simon; Lambert, David G.; Thompson, Jonathan P.

2015-01-01

74

Streptococcal toxic shock syndrome: report of two cases.  

PubMed

Two Japanese cases of streptococcal toxic shock syndrome (STSS) are reported. The first patient was a 45-year-old male who developed necrotizing fasciitis and myositis of the left thigh, refractory hypotension, hepatic dysfunction and acute renal failure; the patient died despite treatment. Streptococcus pyogenes was isolated from the inflamed fascia. The second patient was a 69-year-old female who had coagulopathy, polymyositis and hepatic function abnormality. Streptococcus pyogenes was isolated from blood culture. She was immediately placed on high-dose ampicillin as well as other supportive measures, and she survived. PMID:7496075

Kaneita, Y; Takata, C; Itobayashi, E; Miyauchi, Y; Asada, M; Irabu, N; Yoshida, S

1995-07-01

75

STREPTOCOCCAL L-FORMS IV.  

PubMed Central

Panos, Charles (University of Illinois College of Medicine, Chicago, and Albert Einstein Medical Center, Philadelphia, Pa.). Streptococcal L-forms. IV. Comparison of the metabolic rates of a Streptococcus and derived L-form. J. Bacteriol. 84:921–928. 1962.—Glycolytic rates of hexoses, amino sugars, pentoses, two-carbon compounds, and certain intermediates of glycolysis and the adaptive response to glucose of a group A Streptococcus and its derived L-form were compared. It was found that removal of the streptococcal cell wall did not result in the loss of the homolactic characteristic of the parent coccus or in a marked increase in the metabolism of certain glycolytic intermediates by the L-form. It was shown that (i) a major difference exists between the coccus and its L-form in the metabolism of glucosamine and N-acetylglucosamine; (ii) apparently, a loss of selectivity and internal control occurred in the transformation to the L-form; and (iii) this form, unlike the parent coccus, displayed an adaptive response to glucose. These data were not the result of an internal loss of essential cofactors or enzymes by diffusion from within the L-form. Nor could they be accounted for by dry-weight differences due to loss of the streptococcal cell wall. Finally, it was observed that the sonically disintegrated L-form in 0.5 m NaCl was capable of a glycolytic activity of 46% of that of the total intact culture. These data suggest that the conversion of a streptococcus to the L-form is accompanied by an alteration in carbohydrate metabolism as well as the loss of the cell wall. Previously reported data are in agreement with these findings and support the conclusion that the resulting form is not merely a bacterial cell without a rigid cell wall. PMID:16561973

Panos, Charles

1962-01-01

76

Divergent Signaling Pathways in Phagocytic Cells during Sepsis1  

Microsoft Academic Search

Neutrophil accumulation in the lung plays a pivotal role in the pathogenesis of acute lung injury during sepsis. Directed movement of neutrophils is mediated by a group of chemoattractants, especially CXC chemokines. Local lung production of CXC chemokines is intensified during experimental sepsis induced by cecal ligation and puncture (CLP), as reflected by rising levels of MIP-2 and cytokine-induced neutrophil

Ren-Feng Guo; Niels C. Riedemann; Lei Sun; Hongwei Gao; Kevin X. Shi; Jayne S. Reuben; Vidya J. Sarma; Firas S. Zetoune; Peter A. Ward

77

The enigma of sepsis.  

PubMed

Sepsis remains a serious cause of morbidity and mortality, and the pathophysiology of the disease is not clear. The definition of the clinical manifestations of sepsis is ever evolving. This review discusses the search for effective therapeutic interventions, hurdles in translational sepsis research, and new therapies in development in current clinical trials. PMID:12925683

Riedemann, Niels C; Guo, Ren-Feng; Ward, Peter A

2003-08-01

78

Diagnosis of streptococcal pharyngotonsillitis in children and adolescents: clinical picture limitations?  

PubMed Central

OBJECTIVE: To assess the utility of clinical features for diagnosis of streptococcal pharyngotonsillitis in pediatrics. METHODS: A total of 335 children aged 1-18 years old and presenting clinical manifestations of acute pharyngotonsillitis (APT) were subjected to clinical interviews, physical examinations, and throat swab specimen collection to perform cultures and latex particle agglutination tests (LPATs) for group A streptococcus (GAS) detection. Signs and symptoms of patients were compared to their throat cultures and LPATs results. A clinical score was designed based on the multivariate logistic regression analysis and also was compared to throat cultures and LPATs results. Positive throat cultures and/or LPATs results were used as a reference standard to establish definitive streptococcal APT diagnosis. RESULTS: 78 children (23.4%) showed positivity for GAS in at least one of the two diagnostic tests. Coryza absence (odds ratio [OR]=1.80; p=0.040), conjunctivitis absence (OR=2.47; p=0.029), pharyngeal erythema (OR=3.99; p=0.006), pharyngeal exudate (OR=2.02; p=0.011), and tonsillar swelling (OR=2.60; p=0.007) were significantly associated with streptococcal pharyngotonsilitis. The highest clinical score, characterized by coryza absense, pharyngeal exudate, and pharyngeal erythema had a 45.6% sensitivity, a 74.5% especificity, and a likelihood ratio of 1.79 for streptococcal pharyngotonsilitis. CONCLUSIONS: Clinical presentation should not be used to confirm streptococcal pharyngotonsilitis, because its performance as a diagnostic test is low. Thus, it is necessary to enhance laboratory test availability, especially of LPATs that allow an acurate and fast diagnosis of streptococcal pharyngotonsilitis. PMID:25510990

Barbosa, Aurelino Rocha; Oliveira, Cláudia Di Lorenzo; Fontes, Maria Jussara Fernandes; Lasmar, Laura Maria de Lima Bezário Facury; Camargos, Paulo Augusto Moreira

2014-01-01

79

Group B streptococcal septicemia of the newborn  

MedlinePLUS

... B streptococcal septicemia is caused by the bacterium Streptococcus agalactiae , which is commonly called "group B strep" ... F) during labor Mother who has group B streptococcus in her gastrointestinal, reproductive, or urinary tract Rupture ...

80

Streptococcal toxic shock syndrome complicating a peritonsillar abscess.  

PubMed

Abstract A 68-year-old man was admitted to hospital in an acute confusional state with a 2-week history of fever, influenza-like illness and sore throat. He quickly developed coagulation disturbances, hypotension and renal function impairment. Despite broad-spectrum antibiotic therapy, he deteriorated. Group A streptococcus (GAS) was recovered from blood cultures, which gave the diagnosis streptococcal toxic shock syndrome (STSS). A computed tomography scan showed a right-sided peritonsillar abscess (PTA). Acute tonsillectomy was carried out and the patient recovered. STSS complicating PTA has not previously been described in the literature, but GAS is a common pathogen in PTA. Clinicians should be aware that STSS can develop secondary to tonsillar infections and that abscess development should be suspected in STSS patients who do not respond to antibiotic treatment. PMID:25342572

Aalling, Mathilde; Klug, Tejs Ehlers

2015-02-01

81

Biomarkers of Sepsis  

PubMed Central

Sepsis remains a leading cause of death in critically ill patients, despite efforts to improve patient outcome. Thus far, no magic drugs exist for severe sepsis and septic shock. Instead, early diagnosis and prompt initial management such as early goal-directed therapy are key to improve sepsis outcome. For early detection of sepsis, biological markers (biomarkers) can help clinicians to distinguish infection from host response to inflammation. Ideally, biomarkers can be used for risk stratification, diagnosis, monitoring of treatment responses, and outcome prediction. More than 170 biomarkers have been identified as useful for evaluating sepsis, including C-reactive protein, procalcitonin, various cytokines, and cell surface markers. Recently, studies have reported on the usefulness of biomarker-guided antibiotic stewardships. However, the other side of these numerous biomarkers is that no novel single laboratory marker can diagnose, predict, and track the treatment of sepsis. The purpose of this review is to summarize several key biomarkers from recent sepsis studies. PMID:24693464

Cho, Sung-Yeon

2014-01-01

82

HMGB1 Mediates Cognitive Impairment in Sepsis Survivors  

PubMed Central

Severe sepsis, a syndrome that complicates infection and injury, affects 750,000 annually in the United States. The acute mortality rate is approximately 30%, but, strikingly, sepsis survivors have a significant disability burden: up to 25% of survivors are cognitively and physically impaired. To investigate the mechanisms underlying persistent cognitive impairment in sepsis survivors, here we developed a murine model of severe sepsis survivors following cecal ligation and puncture (CLP) to study cognitive impairments. We observed that serum levels of high mobility group box 1 (HMGB1), a critical mediator of acute sepsis pathophysiology, are increased in sepsis survivors. Significantly, these levels remain elevated for at least 4 wks after CLP. Sepsis survivors develop significant, persistent impairments in learning and memory, and anatomic changes in the hippocampus associated with a loss of synaptic plasticity. Administration of neutralizing anti-HMGB1 antibody to survivors, beginning 1 wk after onset of peritonitis, significantly improved memory impairments and brain pathology. Administration of recombinant HMGB1 to naïve mice recapitulated the memory impairments. Together, these findings indicate that elevated HMGB1 levels mediate cognitive decline in sepsis survivors, and suggest that it may be possible to prevent or reverse cognitive impairments in sepsis survivors by administration of anti-HMGB1 antibodies. PMID:22634723

Chavan, Sangeeta S; Huerta, Patricio T; Robbiati, Sergio; Valdes-Ferrer, SI; Ochani, Mahendar; Dancho, Meghan; Frankfurt, Maya; Volpe, Bruce T; Tracey, Kevin J; Diamond, Betty

2012-01-01

83

Severe Sepsis in Pre-Hospital Emergency Care  

PubMed Central

Rationale: Severe sepsis is common and highly morbid, yet the epidemiology of severe sepsis at the frontier of the health care system—pre-hospital emergency care—is unknown. Objectives: We examined the epidemiology of pre-hospital severe sepsis among emergency medical services (EMS) encounters, relative to acute myocardial infarction and stroke. Methods: Retrospective study using a community-based cohort of all nonarrest, nontrauma King County EMS encounters from 2000 to 2009 who were transported to a hospital. Measurements and Main Results: Overall incidence rate of hospitalization with severe sepsis among EMS encounters, as well as pre-hospital characteristics, admission diagnosis, and outcomes. Among 407,176 EMS encounters, we identified 13,249 hospitalizations for severe sepsis, of whom 2,596 died in the hospital (19.6%). The crude incidence rate of severe sepsis was 3.3 per 100 EMS encounters, greater than for acute myocardial infarction or stroke (2.3 per 100 and 2.2 per 100 EMS encounters, respectively). More than 40% of all severe sepsis hospitalizations arrived at the emergency department after EMS transport, and 80% of cases were diagnosed on admission. Pre-hospital care intervals, on average, exceeded 45 minutes for those hospitalized with severe sepsis. One-half or fewer of patients with severe sepsis were transported by paramedics (n = 7,114; 54%) or received pre-hospital intravenous access (n = 4,842; 37%). Conclusions: EMS personnel care for a substantial and increasing number of patients with severe sepsis, and spend considerable time on scene and during transport. Given the emphasis on rapid diagnosis and intervention for sepsis, the pre-hospital interval may represent an important opportunity for recognition and care of sepsis. PMID:23087028

Rea, Thomas D.; Kahn, Jeremy M.; Walkey, Allan J.; Yealy, Donald M.; Angus, Derek C.

2012-01-01

84

The doripenem serum concentrations in intensive care patients suffering from acute kidney injury, sepsis, and multi organ dysfunction syndrome undergoing continuous renal replacement therapy slow low-efficiency dialysis  

PubMed Central

Doripenem is a novel wide-spectrum antibiotic, and a derivate of carbapenems. It is an ideal antibiotic for treatment of serious nosocomial infections and severe sepsis for its exceptionally high efficiency and broad antibacterial spectrum of action. Doripenem is eliminated mainly by the kidneys. In cases of acute kidney injury, dosing of doripenem depends on creatinine clearance and requires adjustments. Doripenem is eliminated during hemodialysis because its molecular weight is 300–400 Da. The aim of this study was to establish the impact of continuous renal replacement therapy (CRRT) slow low-efficiency dialysis (SLED) on doripenem serum concentrations in a population of intensive-therapy patients with life-threatening infections and severe sepsis. Ten patients were enrolled in this observational study. Twelve blood samples were collected during the first administration of doripenem in a 1-hour continuous infusion while CRRT SLED was provided. Fluid chromatography was used for measurement of the concentration of doripenem in serum. In all collected samples, concentration of doripenem was above the minimum inhibition concentration of this antibiotic. Based on these results, we can draw the conclusion that doripenem concentration is above the minimum inhibition concentration throughout all of CRRT. The dosing pattern proposed by the manufacturer can be used in patients receiving CRRT SLED without necessary modifications. PMID:25364230

Wieczorek, Andrzej; Tokarz, Andrzej; Gaszynski, Wojciech; Gaszynski, Tomasz

2014-01-01

85

Host response in sepsis.  

E-print Network

??Sepsis is a serious condition characterized by a systemic inflammatory response to an infection. Increased vascular leakage, vasodilation and heart failure cause circulatory disturbances challenging… (more)

Berkestedt, Ingrid

2009-01-01

86

Superantigen gene profile diversity among clinical group A streptococcal isolates.  

PubMed

This study examines the diversity of superantigen gene profiles between and within emm-genotypes of 92 clinical group A streptococcal isolates (30 STSS, 24 sepsis, 25 erysipelas, and 12 tonsillitis) collected in Sweden between 1986 and 2001. The emm-genotype and the distribution of smeZ, speG, speJ, speA, speC, speH, speI, speK/L, speL/M, speM, and ssa genes, and the smeZ allelic variant were determined using PCR and DNA sequencing. Forty-five emm1 isolates revealed 10 superantigen gene profiles. One profile dominated and was identified in 22 isolates collected over 14 years. The results indicate that a selective advantage maintained this genotype in circulation. The superantigen content among the emm1 isolates ranged from three to seven, with smeZ-1, speG, and speA present in all but one profile. The 47 isolates of 27 other emm-genotypes exhibited 29 superantigen gene profiles. Thus, the distribution of superantigen genes was highly variable within isolates regardless of emm-genotype. Two novel emm1 subtypes and 14 novel smeZ allelic variants were identified. The 22 smeZ alleles were generally linked to the emm-genotype. The results of the investigation show that superantigen gene profiling is useful for tracking spread of clones in the community. PMID:18754783

Maripuu, Linda; Eriksson, Anna; Norgren, Mari

2008-11-01

87

Adult Zebrafish model of streptococcal infection  

PubMed Central

Streptococcal pathogens cause a wide array of clinical syndromes in humans, including invasive systemic infections resulting in high mortality rates. Many of these pathogens are human specific, and therefore difficult to analyze in vivo using typical animal models, as these models rarely replicate what is observed in human infections. This unit describes the use of the zebrafish (Danio rerio) as an animal model for streptococcal infection to analyze multiple disease states. This model closely mimics the necrotizing fasciitis/myositis pathology observed in humans from a Streptococcus pyogenes infection. The use of a zoonotic pathogen, Streptococcus iniae, which replicates systemic infections caused by many streptococcal pathogens, including dissemination to the brain, is also described. Included protocols describe both intraperitoneal and intramuscular infections, as well as methods for histological and quantitative measurements of infection. PMID:19412913

Phelps, Hilary A.; Runft, Donna L.

2009-01-01

88

Group A ?-hemolytic streptococcal pharyngotonsillitis outbreak  

PubMed Central

The aim was to describe an outbreak of group A ?-hemolytic streptococcal pharyngotonsillitis in health care professionals. This is a cross-sectional descriptive study of 17 clients who dined at the same table in a restaurant in Barcelona in July 2012. The frequency, timing and severity of symptoms were analyzed, as were demographic variables and others concerning the food ingested. The attack rate was 58.8%. Six of the 10 clients were positive for group A ?-hemolytic streptococcal. Six of the 13 individuals who handled the food involved in the dinner had symptoms. No association was identified with the food consumed. There is epidemiological evidence of foodborne group A ?-hemolytic streptococcal transmission, but respiratory transmission could not be ruled out. PMID:24897054

Culqui, Dante R; Manzanares-Laya, Sandra; Van Der Sluis, Sarah Lafuente; Fanlo, Albert Anton; Comas, Rosa Bartolomé; Rossi, Marcello; Caylá, Joán A

2014-01-01

89

Sepsis-induced myopathy  

PubMed Central

Sepsis is a major cause of morbidity and mortality in critically ill patients, and despite advances in management, mortality remains high. In survivors, sepsis increases the risk for the development of persistent acquired weakness syndromes affecting both the respiratory muscles and the limb muscles. This acquired weakness results in prolonged duration of mechanical ventilation, difficulty weaning, functional impairment, exercise limitation, and poor health-related quality of life. Abundant evidence indicates that sepsis induces a myopathy characterized by reductions in muscle force-generating capacity, atrophy (loss of muscle mass), and altered bioenergetics. Sepsis elicits derangements at multiple subcellular sites involved in excitation contraction coupling, such as decreasing membrane excitability, injuring sarcolemmal membranes, altering calcium homeostasis due to effects on the sarcoplasmic reticulum, and disrupting contractile protein interactions. Muscle wasting occurs later and results from increased proteolytic degradation as well as decreased protein synthesis. In addition, sepsis produces marked abnormalities in muscle mitochondrial functional capacity and when severe, these alterations correlate with increased death. The mechanisms leading to sepsis-induced changes in skeletal muscle are linked to excessive localized elaboration of proinflammatory cytokines, marked increases in free-radical generation, and activation of proteolytic pathways that are upstream of the proteasome including caspase and calpain. Emerging data suggest that targeted inhibition of these pathways may alter the evolution and progression of sepsis-induced myopathy and potentially reduce the occurrence of sepsis-mediated acquired weakness syndromes. PMID:20046121

Callahan, Leigh Ann; Supinski, Gerald S.

2014-01-01

90

Higher rates of streptococcal colonization among children in the Pacific Rim Region correlates with higher rates of group A streptococcal disease and sequelae  

PubMed Central

Group A streptococcal (GAS) pharyngeal colonization rates were determined among 1061 asymptomatic students in Hawaii and American Samoa where acute rheumatic fever rates are high. All GAS isolates were emm sequence typed. Although pharyngeal colonization rates were low in Hawaii (3.4%), Pacific Islander children had significantly higher colonization rates (5.7% versus 1.2% in other ethnic groups, p<0.05). The colonization rate was higher in American Samoa (13%). Few emm types that were infrequently observed in symptomatic infections in Hawaii were repeatedly identified in both sites. These emm types were previously described among asymptomatic children suggesting a type-specific association with pharyngeal colonization. PMID:19681949

Erdem, G.; Sinclair, S.; Marrone, J. R.; I’atala, T. F.; Tuua, A.; Tuua, B.; Tuumua, F.; Dodd, A.; Mizumoto, C.; Medina, L.

2009-01-01

91

Targeting neutrophils in sepsis.  

PubMed

Sepsis continues to have a high mortality rate worldwide. The multi-step effects of this syndrome make it difficult to develop a comprehensive understanding of its pathophysiology and to identify a direct treatment. Neutrophils play a major role in controlling infection. Interestingly, the recruitment of these cells to an infection site is markedly reduced in severe sepsis. The systemic activation of Toll-like receptors and high levels of TNF-? and nitric oxide are involved in the reduction of neutrophil recruitment due to down-regulation of CXCR2 in neutrophils. By contrast, CCR2 is expressed in neutrophils after sepsis induction and contributes to their recruitment to organs far from the infection site, which contributes to organ damage. This review provides an overview of the recent advances in the understanding of the role of neutrophils in sepsis, highlighting their potential as a therapeutic target. PMID:24867165

Sônego, Fabiane; Alves-Filho, José Carlos; Cunha, Fernando Queiróz

2014-08-01

92

SEPSIS, APOPTOSIS AND COMPLEMENT  

PubMed Central

Programmed cell death (apoptosis) is a prominent feature in human and experimental sepsis, especially as it involves the lymphoid system with resulting immunoparalysis. In addition, sepsis is associated with strong activation of the complement system, resulting in generation of the powerful anaphylatoxin, C5a, as well as the upregulation of the C5a receptor (C5aR) in a variety of different organs. The consequences of C5a interactions with C5aR can be directly linked to apoptosis of thymocytes and adrenal medullary cells after cecal ligation and puncture (CLP) -induced sepsis in rodents, as well as with other accompanying complications of CLP: cardiac dysfunction, consumptive coagulopathy, organ dysfunction, and lethality. This communication reviews the evidence for the adverse roles of C5a and C5aR in the setting of experimental sepsis and linkages to the various complications of sepsis, especially apoptosis as well as the roles of the two C5a receptors (C5aR AND C5L2) in experimental sepsis. PMID:18848819

Ward, P. A.

2008-01-01

93

Use of Streptococcus salivarius K12 in the prevention of streptococcal and viral pharyngotonsillitis in children  

PubMed Central

Background Streptococcus salivarius K12 is an oral probiotic strain releasing two lantibiotics (salivaricin A2 and salivaricin B) that antagonize the growth of S. pyogenes, the most important bacterial cause of pharyngeal infections in humans also affected by episodes of acute otitis media. S. salivarius K12 successfully colonizes the oral cavity, and is endowed with an excellent safety profile. We tested its preventive role in reducing the incidence of both streptococcal and viral pharyngitis and/or tonsillitis in children. Materials and methods We enrolled 61 children with a diagnosis of recurrent oral streptococcal disorders. Thirty-one of them were enrolled to be treated daily for 90 days with a slow-release tablet for oral use, containing no less than 1 billion colony-forming units/tablet of S. salivarius K12 (Bactoblis®), and the remaining 30 served as the untreated control group. During treatment, they were all examined for streptococcal infection. Twenty children (ten per group) were also assessed in terms of viral infection. Secondary end points in both groups were the number of days under antibiotic and antipyretic therapy and the number of days off school (children) and off work (parents). Results The 30 children who completed the 90-day trial with Bactoblis® showed a significant reduction in their episodes of streptococcal pharyngeal infection (>90%), as calculated by comparing the infection rates of the previous year. No difference was observed in the control group. The treated group showed a significant decrease in the incidence (80%) of oral viral infections. Again, there was no difference in the control group. With regard to secondary end points, the number of days under antibiotic treatment of the treated and control groups were 30 and 900 respectively, days under antipyretic treatment 16 and 228, days of absence from school 16 and 228, and days of absence from work 16 and 228. The product was well tolerated by the subjects, with no side effects, and only one individual reported bad product palatability and dropped out. Conclusion Prophylactic administration of S. salivarius K12 to children with a history of recurrent oral streptococcal disease resulted in a considerable reduction of episodes of both streptococcal and viral infections and reduced the number of days under antibiotic and/or antipyretic therapy and days of absence from school or work. PMID:24600248

Di Pierro, Francesco; Colombo, Maria; Zanvit, Alberto; Risso, Paolo; Rottoli, Amilcare S

2014-01-01

94

Isolated B-cell non-Hodgkin's lymphoma of the parotid gland presenting as an ulcerating facial mass and sepsis during an acute medical take  

PubMed Central

Lymphoma presenting as a parotid gland tumour without systemic involvement is rare, especially with respect to a non-Hodgkin's lymphoma. Furthermore, when such cases present there is often a low degree of clinical suspicion as there may be few clinical features to suggest the diagnosis. We describe an unexpected case that presented during an acute medical intake. The case was an 84-year-old man presenting acutely unwell with an ulcerating mass over the right side of the face, septicaemia and acute kidney injury. Following aggressive initial management the patient improved. Later cytological examination of a fine needle aspiration from the mass confirmed a B-cell non-Hodgkin's lymphoma. He had no evidence of other systemic involvement or of B-symptoms. We report on the case and briefly review the available literature relating to the prevalence of non-Hodgkin's lymphoma of the parotid gland. PMID:23355582

Anthony, Victoria Angharad; Rees, David Owen; Stephens, Jeffrey W

2013-01-01

95

Harmful molecular mechanisms in sepsis  

PubMed Central

Sepsis and sepsis-associated multi-organ failure are major challenges for scientists and clinicians and are a tremendous burden for health-care systems. Despite extensive basic research and clinical studies, the pathophysiology of sepsis is still poorly understood. We are now beginning to understand that sepsis is a heterogeneous, dynamic syndrome caused by imbalances in the ‘inflammatory network’. In this Review, we highlight recent insights into the molecular interactions that occur during sepsis and attempt to unravel the nature of the dysregulated immune response during sepsis. PMID:18802444

Rittirsch, Daniel; Flierl, Michael A.; Ward, Peter A.

2009-01-01

96

Medical treatment of multiple streptococcal liver abscesses  

SciTech Connect

We describe four cases of multiple, cryptogenic, and streptococcal liver abscesses which were cured with antibiotic therapy. Two of the patients were referred for medical management as a last resort after open surgical drainage failed to eradicate the suppurative process. The other two patients were treated from the time of diagnosis with antimicrobial agents alone. Blood cultures or needle aspirates of the abscesses yielded a pure growth of streptococci in all instances. All isolates were susceptible to penicillin G. Cryptogenic streptococcal abscesses may represent a subset of multiple hepatic abscesses particularly amenable to successful medical therapy consisting of a minimum of 6 weeks parenteral antibiotic therapy followed by a period of oral antibiotics until clinical, biochemical, and radiological resolution of the abscesses has occurred.

Matlow, A.; Vellend, H.

1983-04-01

97

Diagnostic utility of biomarkers for neonatal sepsis - a systematic review.  

PubMed

Abstract Neonatal sepsis is a major cause of morbidity and mortality. Early diagnosis and treatment of the neonate with suspected sepsis are essential to prevent life-threatening complications. Diagnosis of neonatal sepsis is a challenge due to non-specific clinical signs and the fact that infection markers are difficult to interpret in the first and critical phase of neonatal sepsis. The objective of the present study was to systematically evaluate existing evidence of the diagnostic utility of biomarkers for prediction of sepsis in neonates. We conducted a systematic literature search performed in PubMed and Embase. The study population was neonates with gestation age > 24 weeks in their first 28 days of life with suspected sepsis. The included manuscripts were rated due to criteria from a modified rating scale developed by Douglas Altman. Of 292 potentially relevant manuscripts, 77 fulfilled the inclusion and exclusion criteria; 16 (21%) were rated as high-quality studies. C-reactive protein (CRP) was the most extensively studied biomarker evaluated. The high-quality studies indicated that the acute phase protein serum amyloid A had high sensitivity, both at onset of symptoms and 2 days after. The studies evaluating serum amyloid A presented a variable positive predictive value (PPV, 0.67 and 0.92) with a high negative predictive value (NPV, 0.97 and 1.00). The existing evidence of the diagnostic value of serum amyloid A for neonatal sepsis showed promising results, and should be further investigated in clinical settings. PMID:25522182

Hedegaard, Sofie Sommer; Wisborg, Kirsten; Hvas, Anne-Mette

2015-03-01

98

Group a streptococcal antigens cross-reactive with myocardium. Purification of heart-reactive antibody and isolation and characterization of the streptococcal antigen  

PubMed Central

Heart-reactive antibody (HRA) appears in the sera of experimental animals inoculated with group A streptococci as well as patients with acute rheumatic fever. Adsorption of either serum with group A streptococcal membranes will remove the HRA. Blocking experiments between these two types of HRAs have demonstrated that the antibodies are directed towards different antigenic determinants on either the same or different molecules. To isolate and purify the antigen from the group A streptococcus cross-reactive with sarcolemmal sheaths of cardiac myofibers, it became necessary to purify the HRA from rheumatic fever patients’ sera. Isolated gamma globulin containing all of the HRA was adsorbed onto human sarcolemmal sheaths. The specific HRA was released by using potassium iodide. Over 99 percent of the purified HRA was shown to bind the sarcolemmal sheath whereas less than 1 percent of the antibody would bind nonspecifically to other material. Preparations of group A streptococcal membrane will bind HRA purified from the sera of acute rheumatic patients at levels of 97 percent or greater. The cross-reactive antigen solubilized by nonionic detergent was purified 120-fold by column chromatography. On sodium dodecyl sulfate polyacrylamide electrophoresis, the antigen was demonstrated to be composed of four polypeptides with mol wt of 32,000, 28,000, 26,000, and 22,000 daltons, respectively. Only proteolytic enzymes could destroy the antigenic determinant whereas glycosidases and lipases had no effect. The purified antigen blocked the binding of purified HRA to normal human heart sections. PMID:327018

Van De Rijn, I; Sabriskie, JB; McCarty, M

1977-01-01

99

Biomarkers for sepsis.  

PubMed

Bloodstream infections are a major concern because of high levels of antibiotic consumption and of the increasing prevalence of antimicrobial resistance. Bacteraemia is identified in a small percentage of patients with signs and symptoms of sepsis. Biomarkers are widely used in clinical practice and they are useful for monitoring the infectious process. Procalcitonin (PCT) and C-reactive protein (CRP) have been most widely used, but even these have limited abilities to distinguish sepsis from other inflammatory conditions or to predict outcome. PCT has been used to guide empirical antibacterial therapy in patients with respiratory infections and help to determine if antibacterial therapy can be stopped. New biomarkers such as those in this review will discuss the major types of biomarkers of bloodstream infections/sepsis, including soluble triggering receptor expressed on myeloid cells-1 (sTREM-1), soluble urokinase-type plasminogen receptor (suPAR), proadrenomedullin (ProADM), and presepsin. PMID:24800240

Henriquez-Camacho, Cesar; Losa, Juan

2014-01-01

100

Harmful molecular mechanisms in sepsis  

Microsoft Academic Search

Sepsis and sepsis-associated multi-organ failure are major challenges for scientists and clinicians and are a tremendous burden for health-care systems. Despite extensive basic research and clinical studies, the pathophysiology of sepsis is still poorly understood. We are now beginning to understand that sepsis is a heterogeneous, dynamic syndrome caused by imbalances in the 'inflammatory network'. In this Review, we highlight

Daniel Rittirsch; Michael A. Flierl; Peter A. Ward

2008-01-01

101

The diagnosis of sepsis revisited - a challenge for young medical scientists in the 21st century  

PubMed Central

In 1991, a well-meaning consensus group of thought leaders derived a simple definition for sepsis which required the breach of only a few static thresholds. More than 20 years later, this simple definition has calcified to become the gold standard for sepsis protocols and research. Yet sepsis clearly comprises a complex, dynamic, and relational distortion of human life. Given the profound scope of the loss of life worldwide, there is a need to disengage from the simple concepts of the past. There is an acute need to develop 21st century approaches which engage sepsis in its true form, as a complex, dynamic, and relational pattern of death. PMID:24383420

2014-01-01

102

Nutrition and sepsis.  

PubMed

The effect of nutritional support in critically ill patients with sepsis has received much attention in recent years. However, many of the studies have produced conflicting results. As for all critically ill patients, nutritional support, preferably via the enteral route, should be commenced once initial resuscitation and adequate perfusion pressure is achieved. Where enteral feeding is impossible or not tolerated, parenteral nutrition (either as total or complimentary therapy) may safely be administered. Most positive studies relating to nutritional support and sepsis have been in the setting of sepsis prevention. Thus, the administration of standard nutrition formulas to critically ill patients within 24 h of injury or intensive care unit admission may decrease the incidence of pneumonia. Both arginine-supplemented enteral diets, given in the perioperative period, and glutamine-supplemented parenteral nutrition have been shown to decrease infections in surgical patients. Parenteral fish oil lipid emulsions as well as probiotics given in the perioperative period may also reduce infections in patients undergoing major abdominal operations, such as liver transplantation. There is little support at the present time for the positive effect of specific pharmaconutrients, in particular fish oil, probiotics, or antioxidants, in the setting of established sepsis. More studies are clearly required on larger numbers of more homogeneous groups of patients. PMID:23075593

Cohen, Jonathan; Chin, w Dat N

2013-01-01

103

Revisiting caspases in sepsis  

PubMed Central

Sepsis is a life-threatening illness that occurs due to an abnormal host immune network which extends through the initial widespread and overwhelming inflammation, and culminates at the late stage of immunosupression. Recently, interest has been shifted toward therapies aimed at reversing the accompanying periods of immune suppression. Studies in experimental animals and critically ill patients have demonstrated that increased apoptosis of lymphoid organs and some parenchymal tissues contributes to this immune suppression, anergy and organ dysfunction. Immediate to the discoveries of the intracellular proteases, caspases for the induction of apoptosis and inflammation, and their striking roles in sepsis have been focused elaborately in a number of original and review articles. Here we revisited the different aspects of caspases in terms of apoptosis, pyroptosis, necroptosis and inflammation and focused their links in sepsis by reviewing several recent findings. In addition, we have documented striking perspectives which not only rewrite the pathophysiology, but also modernize our understanding for developing novel therapeutics against sepsis. PMID:25412304

Aziz, M; Jacob, A; Wang, P

2014-01-01

104

Coagulation in sepsis  

Microsoft Academic Search

Coagulation abnormalities, ranging from a simple fall in platelet count to full-blown disseminated intravascular coagulation, are a common occurrence in critically ill patients and have been associated with increased mortality. In sepsis, activation of the extrinsic coagulation pathway by tissue factor induces increased coagulation, and simultaneous depression of the inhibitory mechanisms of coagulation, and suppression of the fibrinolytic system results

André Amaral; Steven M. Opal; Jean-Louis Vincent

2004-01-01

105

Clinical Microbiology of Bacterial and Fungal Sepsis in Very-Low-Birth-Weight Infants  

PubMed Central

Twenty percent of very-low-birth-weight (<1500 g) preterm infants experience a serious systemic infection, and despite advances in neonatal intensive care and antimicrobials, mortality is as much as threefold higher for these infants who develop sepsis than their counterparts without sepsis during their hospitalization. Outcomes may be improved by preventative strategies, earlier and accurate diagnosis, and adjunct therapies to combat infection and protect the vulnerable preterm infant during an infection. Earlier diagnosis on the basis of factors such as abnormal heart rate characteristics may offer the ability to initiate treatment prior to the onset of clinical symptoms. Molecular and adjunctive diagnostics may also aid in diagnosing invasive infection when clinical symptoms indicate infection but no organisms are isolated in culture. Due to the high morbidity and mortality, preventative and adjunctive therapies are needed. Prophylaxis has been effective in preventing early-onset group B streptococcal sepsis and late-onset Candida sepsis. Future research in prophylaxis using active and passive immunization strategies offers prevention without the risk of resistance to antimicrobials. Identification of the differences in neonatal intensive care units with low and high infection rates and implementation of infection control measures remain paramount in each neonatal intensive care unit caring for preterm infants. PMID:15258097

Kaufman, David; Fairchild, Karen D.

2004-01-01

106

Vitamin D Level and Risk of Community-Acquired Pneumonia and Sepsis  

PubMed Central

Previous research has reported reduced serum 25-hydroxyvitamin D (25(OH)D) levels is associated with acute infectious illness. The relationship between vitamin D status, measured prior to acute infectious illness, with risk of community-acquired pneumonia (CAP) and sepsis has not been examined. Community-living individuals hospitalized with CAP or sepsis were age-, sex-, race-, and season-matched with controls. ICD-9 codes identified CAP and sepsis; chest radiograph confirmed CAP. Serum 25(OH)D levels were measured up to 15 months prior to hospitalization. Regression models adjusted for diabetes, renal disease, and peripheral vascular disease evaluated the association of 25(OH)D levels with CAP or sepsis risk. A total of 132 CAP patients and controls were 60 ± 17 years, 71% female, and 86% Caucasian. The 25(OH)D levels <37 nmol/L (adjusted odds ratio (OR) 2.57, 95% CI 1.08–6.08) were strongly associated with increased odds of CAP hospitalization. A total of 422 sepsis patients and controls were 65 ± 14 years, 59% female, and 91% Caucasian. The 25(OH)D levels <37 nmol/L (adjusted OR 1.75, 95% CI 1.11–2.77) were associated with increased odds of sepsis hospitalization. Vitamin D status was inversely associated with risk of CAP and sepsis hospitalization in a community-living adult population. Further clinical trials are needed to evaluate whether vitamin D supplementation can reduce risk of infections, including CAP and sepsis. PMID:24918697

Jovanovich, Anna J.; Ginde, Adit A.; Holmen, John; Jablonski, Kristen; Allyn, Rebecca L.; Kendrick, Jessica; Chonchol, Michel

2014-01-01

107

Group A streptococcal puerperal sepsis: initial characterization of virulence factors in association with clinical parameters  

Microsoft Academic Search

Group A ?-hemolytic streptococcus (GAS) is an uncommon but potentially fatal source of postpartum infection. Pathogenesis in invasive GAS infections has been linked to bacterial virulence factors. In this study, we sought to provide an initial description of potential virulence factors in association with puerperal morbidity by virtue of specific M-protein type antigens. Women with confirmed GAS puerperal infection in

Janice L. B. Byrne; Kjersti M. Aagaard-Tillery; Jason L. Johnson; Larry J. Wright; Robert M. Silver

2009-01-01

108

Invasive Group A Streptococcal Infections, Israel  

PubMed Central

We conducted a prospective, nationwide, population-based study of invasive group A streptococcal infections in Israel. We identified 409 patients (median age 27 years; range <1-92), for an annual incidence of 3.7/100,000 (11/100,000 in Jerusalem). The mortality rate was 5%. Bacteremia occurred in 125 cases (31%). The most common illnesses were soft-tissue infection (63%) and primary bacteremia (14%). Thirty percent of patients had no identifiable risk factors for infection. Eighty-seven percent of pharyngeal carriers had the same serotype as the index patient. M types included M3 (25%), M28 (10%), and M-nontypable (33%). A marked paucity of M1 serotype (1.2%) was detected. The results highlighted concentrated pockets of invasive disease in the Jewish orthodox community (annual incidence 16/100,000). PMID:11971778

Goldberg, Sara; Korenman, Zinaida; Ravins, Miriam; Hanski, Emanuel; Shapiro, Mervyn

2002-01-01

109

Programmed cell death receptor ligand 1 modulates the regulatory T cells' capacity to repress shock/sepsis-induced indirect acute lung injury by recruiting phosphatase SRC homology region 2 domain-containing phosphatase 1.  

PubMed

We recently reported that adoptively transferred (AT) exogenous CD4+ CD25+ regulatory T cells (Tregs) to wild-type (WT) mice can directly act to repress shock/sepsis-induced experimental indirect acute lung injury (iALI), and this is mediated in part by programmed cell death receptor 1 (PD-1). In this study, we further determine whether recipient mouse lacking PD-L1, one of the primary ligands for PD-1, contributes to the manipulation of the Tregs' capacity to repress lung injury. To do this, Tregs isolated from the spleen of WT mice were AT into PD-L1 mice subjected to hemorrhagic shock and subsequent to cecal ligation and puncture to induce iALI. Samples were collected for analyses 24 h after cecal ligation and puncture. We found that in PD-L1-recipient mice, AT WT-Tregs lost the ability to reverse the development of iALI seen in WT recipient mice (i.e., no reduction of lung injury indices assessed by histology and vascular leakage, failure to decrease the lung neutrophil influx [myeloperoxidase activity], or the rise in lung apoptosis [caspase 3 activity]). Also, a significant increase in interleukin 1? (IL-1?) and keratinocyte-derived chemokine, but no changes in IL-6, IL-10, and IL-17A levels in lung tissues were seen in these mice compared with iALI mice without AT of Tregs. Furthermore, we noted that the lung tissue tyrosine phosphatase Src homology region 2 domain-containing phosphatase 1 (SHP-1), but not SHP-2, was activated with the AT of Tregs in PD-L1(-/-) iALI mice. Finally, through local depletion of CD4+ T cells or CD25+ (Tregs) in the lung, prior to inducing iALI, we found that SHP-1 activation was associated with the loss of Tregs' protective effects in vivo. Collectively, our data reveal that PD-L1 is a critical modulator of Tregs' ability to suppress iALI, and this appears to involve SHP-1 activation. PMID:25057927

Tang, Lunxian; Bai, Jianwen; Chung, Chun-Shiang; Lomas-Neira, Joanne; Chen, Yaping; Huang, Xin; Ayala, Alfred

2015-01-01

110

Streptococcal endocarditis in a captive southern white rhinoceros (Ceratotherium simum simum).  

PubMed

Postmortem examination of a 43-yr-old male southern white rhinoceros (Ceratotherium simum simum) revealed gross lesions and histopathologic findings consistent with endocarditis. The animal was born in Umfolozi National Park, South Africa, and then it was moved at 2 yr of age to two successive European zoologic collections. For several weeks prior to death, the animal was increasingly recumbent or assuming a dog-sitting position. Postmortem examination revealed cutaneous pressure sores and multiple rough nodular structures on the mitral valve and left ventricular endocardium. Histopathologic examination revealed vegetative endocarditis, myocardial and hepatocellular degeneration, hepatic fibrosis, and chronic nephritis. Bacterial culture from the oral cavity, trachea, lung, skin, and heart isolated beta hemolytic Streptococcus dysgalactiae subsp. equisimilis and Streptococcus ovis. The cause of death was acute cardiopulmonary failure due mainly to endocarditis and moderate myocardial degeneration. Streptococcal infections are not uncommon causes of morbidity and mortality in rhinoceros. This is the first detailed report of streptococcal endocarditis in a rhinoceros. PMID:25314832

Houszka, Marek; Dzimira, Stanislaw; Krol, Jaroslaw; Kandefer-Gola, Malgorzata; Ciaputa, Rafal; Sobieraj, Leslaw; Podkowik, Magdalena

2014-09-01

111

Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2008  

PubMed Central

Objective To provide an update to the original Surviving Sepsis Campaign clinical management guidelines, “Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock,” published in 2004. Design Modified Delphi method with a consensus conference of 55 international experts, several subsequent meetings of subgroups and key individuals, teleconferences, and electronic-based discussion among subgroups and among the entire committee. This process was conducted independently of any industry funding. Methods We used the GRADE system to guide assessment of quality of evidence from high (A) to very low (D) and to determine the strength of recommendations. A strong recommendation [1] indicates that an intervention's desirable effects clearly outweigh its undesirable effects (risk, burden, cost), or clearly do not. Weak recommendations [2] indicate that the tradeoff between desirable and undesirable effects is less clear. The grade of strong or weak is considered of greater clinical importance than a difference in letter level of quality of evidence. In areas without complete agreement, a formal process of resolution was developed and applied. Recommendations are grouped into those directly targeting severe sepsis, recommendations targeting general care of the critically ill patient that are considered high priority in severe sepsis, and pediatric considerations. Results Key recommendations, listed by category, include: early goal-directed resuscitation of the septic patient during the first 6 hrs after recognition (1C); blood cultures prior to antibiotic therapy (1C); imaging studies performed promptly to confirm potential source of infection (1C); administration of broad-spectrum antibiotic therapy within 1 hr of diagnosis of septic shock (1B) and severe sepsis without septic shock (1D); reassessment of antibiotic therapy with microbiology and clinical data to narrow coverage, when appropriate (1C); a usual 7–10 days of antibiotic therapy guided by clinical response (1D); source control with attention to the balance of risks and benefits of the chosen method (1C); administration of either crystalloid or colloid fluid resuscitation (1B); fluid challenge to restore mean circulating filling pressure (1C); reduction in rate of fluid administration with rising filing pressures and no improvement in tissue perfusion (1D); vasopressor preference for norepinephrine or dopamine to maintain an initial target of mean arterial pressure ? 65 mm Hg (1C); dobutamine inotropic therapy when cardiac output remains low despite fluid resuscitation and combined inotropic/vasopressor therapy (1C); stress-dose steroid therapy given only in septic shock after blood pressure is identified to be poorly responsive to fluid and vasopressor therapy (2C); recombinant activated protein C in patients with severe sepsis and clinical assessment of high risk for death (2B except 2C for post-operative patients). In the absence of tissue hypoperfusion, coronary artery disease, or acute hemorrhage, target a hemoglobin of 7–9 g/dL (1B); a low tidal volume (1B) and limitation of inspiratory plateau pressure strategy (1C) for acute lung injury (ALI)/acute respiratory distress syndrome (ARDS); application of at least a minimal amount of positive end-expiratory pressure in acute lung injury (1C); head of bed elevation in mechanically ventilated patients unless contraindicated (1B); avoiding routine use of pulmonary artery catheters in ALI/ARDS (1A); to decrease days of mechanical ventilation and ICU length of stay, a conservative fluid strategy for patients with established ALI/ARDS who are not in shock (1C); protocols for weaning and sedation/analgesia (1B); using either intermittent bolus sedation or continuous infusion sedation with daily interruptions or lightening (1B); avoidance of neuromuscular blockers, if at all possible (1B); institution of glycemic control (1B) targeting a blood glucose < 150 mg/dL after initial stabilization ( 2C );

Levy, Mitchell M.; Carlet, Jean M.; Bion, Julian; Parker, Margaret M.; Jaeschke, Roman; Reinhart, Konrad; Angus, Derek C.; Brun-Buisson, Christian; Beale, Richard; Calandra, Thierry; Dhainaut, Jean-Francois; Gerlach, Herwig; Harvey, Maurene; Marini, John J.; Marshall, John; Ranieri, Marco; Ramsay, Graham; Sevransky, Jonathan; Thompson, B. Taylor; Townsend, Sean; Vender, Jeffrey S.; Zimmerman, Janice L.; Vincent, Jean-Louis

2007-01-01

112

Targeting mitochondrial oxidants may facilitate recovery of renal function during infant sepsis  

PubMed Central

Sepsis-induced acute kidney injury (SAKI) is a frequent complication of infant sepsis that approximately doubles the mortality rate. The poor prognosis of these patients is a result of care that is mainly supportive, nontargeted, and usually begun only after symptoms of the systemic inflammatory response syndrome are observed. Preclinical studies from relevant rodent models of SAKI suggest that mitochondria-targeted antioxidants may be a new mode of therapy that could promote recovery. PMID:25148376

Sims, CR; MacMillan-Crow, LA; Mayeux, PR

2014-01-01

113

Targeting mitochondrial oxidants may facilitate recovery of renal function during infant sepsis.  

PubMed

Sepsis-induced acute kidney injury (SAKI) is a frequent complication of infant sepsis that approximately doubles the mortality rate. The poor prognosis of these patients is a result of care that is mainly supportive, nontargeted, and usually begun only after symptoms of the systemic inflammatory response syndrome are observed. Preclinical studies from relevant rodent models of SAKI suggest that mitochondria-targeted antioxidants may be a new mode of therapy that could promote recovery. PMID:25148376

Sims, C R; MacMillan-Crow, L A; Mayeux, P R

2014-12-01

114

Interactions of the streptococcal C5a peptidase with human fibronectin  

PubMed Central

Group B streptococci (GBS) is a leading cause of sepsis and meningitis in neonates and immunocompromised adults in western countries. GBS do not bind to fibronectin (Fn) in solution, but will bind to Fn adsorbed onto a solid surface. The reason for the specificity of this binding is unknown. Single molecule force spectroscopy was used to test the hypothesis that GBS, through streptococcal C5a peptidase (ScpB) molecules present on the surface of the bacteria, binds to a motif created by the juxtaposition of multiple adjacent Fn molecules. Atomic force microscopy (AFM) topographical images of adsorbed Fn deposited from various Fn coating concentrations were used to determine the Fn surface concentration. ScpB was tethered to an AFM tip with all surface modifications characterized by X-ray photoelectron spectroscopy and time-of-flight secondary ion mass spectrometry. At the lowest Fn coverages the probability of observing a ScpB–Fn binding event increased linearly with Fn surface coverage. As an Fn monolayer was reached the probability of a ScpB–Fn binding event occurring increased markedly (~50 fold), with a concomitant increase in the rupture force from 17 pN to 33 pN. These results are consistent with the hypothesis that ScpB binds to a motif created by the juxtaposition of multiple Fn molecules. PMID:18313373

Hull, James R.; Tamura, Glen S.; Castner, David G.

2008-01-01

115

Humanized In Vivo Model for Streptococcal Impetigo  

PubMed Central

An in vivo model for group A streptococcal (GAS) impetigo was developed, whereby human neonatal foreskin engrafted onto SCID mice was superficially damaged and bacteria were topically applied. Severe infection, indicated by a purulent exudate, could be induced with as few as 1,000 CFU of a virulent strain. Early findings (48 h) showed a loss of stratum corneum and adherence of short chains of gram-positive cocci to the external surface of granular keratinocytes. This was followed by an increasing infiltration of polymorphonuclear leukocytes (neutrophils) of mouse origin, until a thick layer of pus covered an intact epidermis, with massive clumps of cocci accumulated at the outer rim of the pus layer. By 7 days postinoculation, the epidermis was heavily eroded; in some instances, the dermis contained pockets (ulcers) filled with cocci, similar to that observed for ecthyma. Importantly, virulent GAS underwent reproduction, resulting in a net increase in CFU of 20- to 14,000-fold. The majority of emm pattern D strains had a higher gross pathology score than emm pattern A, B, or C (A–C) strains, consistent with epidemiological findings that pattern D strains have a strong tendency to cause impetigo, whereas pattern A–C strains are more likely to cause pharyngitis. PMID:10768985

Scaramuzzino, Dominick A.; McNiff, Jennifer M.; Bessen, Debra E.

2000-01-01

116

Effects of selective ß1-adrenoceptor blockade on cardiovascular and renal function and circulating cytokines in ovine hyperdynamic sepsis.  

PubMed

IntroductionActivation of the sympathetic nervous system has beneficial cardiovascular effects in sepsis, but there is also evidence that sympatholytics have beneficial actions in sepsis. We therefore determined the effect of selective ß1-adrenoceptor blockade on cardiac and renal function and cytokine release in ovine hyperdynamic sepsis.MethodsHyperdynamic sepsis was induced by infusion of live E. Coli for 24 hours in 9 conscious sheep instrumented with flow probes on the pulmonary and left renal artery. Cardiovascular and renal function and levels of plasma cytokines were determined in a control group and during selective ß1-adrenoceptor blockade with atenolol (10 mg intravenous bolus then 0.125 mg/Kg/h) from 8 to 24 hours of sepsis.ResultsHyperdynamic sepsis was characterized by hypotension with increases in cardiac output (CO), heart rate (HR) and renal blood flow (RBF), and acute kidney injury. Atenolol caused a sustained reductions in HR (P <0.001) and CO (P <0.001). Despite the lower CO the sepsis-induced fall in mean arterial pressure (MAP) was similar in both groups. The sepsis-induced increase in RBF, decrease in renal function and increase in arterial lactate were unaffected by atenolol. Sepsis increased plasma levels of tumour necrosis factor-¿ (TNF-¿), interleukin-6 (IL-6) and IL-10. Atenolol caused a further increase in IL-10, but did not affect levels of TNF-¿ or IL-6.ConclusionsIn sepsis, selective ß1-adrenoceptor blockade reduced CO, but not MAP. During sepsis, atenolol did not alter the development of acute kidney injury or the levels of pro-inflammatory cytokines, but enhanced the release of IL-10. Atenolol appears safe in sepsis, has no deleterious cardiovascular or renal effects, and has an anti-inflammatory effect. PMID:25413250

Calzavacca, Paolo; Lankadeva, Yugeesh R; Bailey, Simon R; Bailey, Michael; Bellomo, Rinaldo; May, Clive N

2014-11-21

117

Synergistic inhibition of Streptococcal biofilm by ribose and xylitol.  

PubMed

Streptococcus mutans and Streptococcus sobrinus are the major causative agents of human dental caries. Therefore, the removal or inhibition of these streptococcal biofilms is essential for dental caries prevention. In the present study, we evaluated the effects of ribose treatment alone or in combination with xylitol on streptococcal biofilm formation for both species. Furthermore, we examined the expression of genes responsible for dextran-dependent aggregation (DDAG). In addition, we investigated whether ribose affects the biofilm formation of xylitol-insensitive streptococci, which results from long-term exposure to xylitol. The viability of streptococci biofilms formed in a 24-well polystyrene plate was quantified by fluorescent staining with the LIVE/DEAD bacterial viability and counting kit, which was followed by fluorescence activated cell sorting analysis. The effects of ribose and/or xylitol on the mRNA expression of DDAG-responsible genes, gbpC and dblB, was evaluated by RT-qPCR. Our data showed that ribose and other pentose molecules significantly inhibited streptococcal biofilm formation and the expression of DDAG-responsible genes. In addition, co-treatment with ribose and xylitol decreased streptococcal biofilm formation to a further extent than ribose or xylitol treatment alone in both streptococcal species. Furthermore, ribose attenuated the increase of xylitol-insensitive streptococcal biofilm, which results in the reduced difference of biofilm formation between S. mutans that are sensitive and insensitive to xylitol. These data suggest that pentose may be used as an additive for teeth-protective materials or in sweets. Furthermore, ribose co-treatment with xylitol might help to increase the anti-cariogenic efficacy of xylitol. PMID:25463908

Lee, Heon-Jin; Kim, Se Chul; Kim, Jinkyung; Do, Aejin; Han, Se Yeong; Lee, Bhumgey David; Lee, Hyun Ho; Lee, Min Chan; Lee, So Hui; Oh, Taejun; Park, Sangbin; Hong, Su-Hyung

2015-02-01

118

Neonatal Sepsis and Inflammatory Mediators  

PubMed Central

Neonatal sepsis is a major cause of morbidity and mortality and its signs and symptoms are nonspecific, which makes the diagnosis difficult. The routinely used laboratory tests are not effective methods of analysis, as they are extremely nonspecific and often cause inappropriate use of antibiotics. Sepsis is the result of an infection associated with a systemic inflammatory response with production and release of a wide range of inflammatory mediators. Cytokines are potent inflammatory mediators and their serum levels are increased during infections, so changes from other inflammatory effector molecules may occur. Although proinflammatory and anti-inflammatory cytokines have been identified as probable markers of neonatal infection, in order to characterize the inflammatory response during sepsis, it is necessary to analyze a panel of cytokines and not only the measurement of individual cytokines. Measurements of inflammatory mediators bring new options for diagnosing and following up neonatal sepsis, thus enabling early treatment and, as a result, increased neonatal survival. By taking into account the magnitude of neonatal sepsis, the aim of this review is to address the role of cytokines in the pathogenesis of neonatal sepsis and its value as a diagnostic criterion.

Reis Machado, Juliana; Soave, Danilo Figueiredo; da Silva, Marcos Vinícius; de Menezes, Liliana Borges; Etchebehere, Renata Margarida; Monteiro, Maria Luiza Gonçalves dos Reis; Antônia dos Reis, Marlene; Corrêa, Rosana Rosa Miranda; Celes, Mara Rúbia Nunes

2014-01-01

119

The Systemic Pro-Inflammatory Response in Sepsis  

Microsoft Academic Search

The systemic inflammatory response syndrome (SIRS) is the predominantly cytokine-mediated, pro-inflammatory response of the host to invading pathogens and is considered the hallmark sign of sepsis. Molecular components of this response can be divided into cytokines, plasma cascades and acute phase proteins while the predominant cellular components are leukocytes and the endothelium. High-throughput genetic profiling studies have led to increased

Hanna Katrien de Jong; Tom van der Poll; Willem Joost Wiersinga

2010-01-01

120

Heparanase mediates renal dysfunction during early sepsis in mice  

PubMed Central

Heparanase, a heparan sulfate-specific glucuronidase, mediates the onset of pulmonary neutrophil adhesion and inflammatory lung injury during early sepsis. We hypothesized that glomerular heparanase is similarly activated during sepsis and contributes to septic acute kidney injury (AKI). We induced polymicrobial sepsis in mice using cecal ligation and puncture (CLP) in the presence or absence of competitive heparanase inhibitors (heparin or nonanticoagulant N-desulfated re-N-acetylated heparin [NAH]). Four hours after surgery, we collected serum and urine for measurement of renal function and systemic inflammation, invasively determined systemic hemodynamics, harvested kidneys for histology/protein/mRNA, and/or measured glomerular filtration by inulin clearance. CLP-treated mice demonstrated early activation of glomerular heparanase with coincident loss of glomerular filtration, as indicated by a >twofold increase in blood urea nitrogen (BUN) and a >50% decrease in inulin clearance (P < 0.05) in comparison to sham mice. Administration of heparanase inhibitors 2 h prior to CLP attenuated sepsis-induced loss of glomerular filtration rate, demonstrating that heparanase activation contributes to early septic renal dysfunction. Glomerular heparanase activation was not associated with renal neutrophil influx or altered vascular permeability, in marked contrast to previously described effects of pulmonary heparanase on neutrophilic lung injury during sepsis. CLP induction of renal inflammatory gene (IL-6, TNF-?, IL-1?) expression was attenuated by NAH pretreatment. While serum inflammatory indices (KC, IL-6, TNF-?, IL-1?) were not impacted by NAH pretreatment, heparanase inhibition attenuated the CLP-induced increase in serum IL-10. These findings demonstrate that glomerular heparanase is active during sepsis and contributes to septic renal dysfunction via mechanisms disparate from heparanase-mediated lung injury. PMID:24400155

Lygizos, Melissa I; Yang, Yimu; Altmann, Christopher J; Okamura, Kayo; Hernando, Ana Andres; Perez, Mario J; Smith, Lynelle P; Koyanagi, Daniel E; Gandjeva, Aneta; Bhargava, Rhea; Tuder, Rubin M; Faubel, Sarah; Schmidt, Eric P

2013-01-01

121

Fluid overload in patients with severe sepsis and septic shock treated with early goal-directed therapy is associated with increased acute need for fluid-related medical interventions and hospital death.  

PubMed

Early goal-directed therapy (EGDT) consists of early, aggressive fluid resuscitation and is known to improve survival in sepsis. It is unknown how often EGDT leads to subsequent fluid overload and whether post-EGDT fluid overload affects patients' outcomes. Our hypothesis was that patients with sepsis treated with EGDT were at risk for fluid overload and that fluid overload would be associated with adverse outcomes. We conducted a retrospective cohort of 405 consecutive patients admitted with severe sepsis and septic shock to the medical intensive care unit of a tertiary care academic hospital from January 2008 to December 2009. Baseline demographics, daily weights, fluid status, clinical or radiographic evidence of fluid overload, and medical interventions (thoracentesis, paracentesis, diuretic use, and ultrafiltration) were abstracted, and associations explored using univariate and multivariate logistic and linear regression analyses. At day 1, 67% of patients developed evidence of fluid overload, and in 48%, fluid overload persisted to day 3. Interrater agreement for presence of fluid overload was substantial (? = 0.7). An increased trend in weight was noted in those with persistent clinical and radiologic evidence of fluid overload, but not with recorded positive fluid balance. When adjusted for baseline severity of illness, fluid overload was associated with increased use of fluid-related medical interventions (thoracentesis and diuretics) and hospital mortality (odds ratio, 1.92; confidence interval, 1.16-3.22). In patients with severe sepsis and septic shock treated with EGDT, clinical evidence of persistent fluid overload is common and is associated with increased use of medical interventions and hospital mortality. PMID:25247784

Kelm, Diana J; Perrin, Jared T; Cartin-Ceba, Rodrigo; Gajic, Ognjen; Schenck, Louis; Kennedy, Cassie C

2015-01-01

122

Structure of a streptococcal adhesion carbohydrate receptor  

SciTech Connect

Interactions between complementary protein and carbohydrate structures on different genera of human oral bacteria have been implicated in the formation of dental plaque. The carbohydrate receptor on Streptococcus sanguis H1 that is specific for the adhesion on Capnocytophaga ochracea ATCC 33596 has been isolated from the streptococcal cell wall, purified, and structurally characterized. The hexasaccharide repeating unit of the polysaccharide was purified by reverse-phase, amino-bonded silica, and gel permeation high performance liquid chromatography. Earlier studies established that the repeating unit was a hexasaccharide composed of rhamnose, galactose, and glucose in the ration of 2:3:1, respectively. In the present study, determination of absolute configuration by gas chromatography of the trimethylsilyl (+)-2-butyl glycosides revealed that the rhamnose residues were of the L configuration while the hexoses were all D. 252Californium plasma desorption mass spectrometry of the native, the acetylated and the reduced and acetylated hexasaccharide determined that the molecular mass of the native hexasaccharide was 959, and that the 2 rhamnose residues were linked to each other at the nonreducing terminus of the linear molecule. Methylation analysis revealed the positions of the glycosidic linkages in the hexasaccharide and showed that a galactose residue was present at the reducing end. The structural characterization of the hexasaccharide was completed by one and two dimensional 1H and 13C NMR spectroscopy. Complete 1H and 13C assignments for each glycosyl residue were established by two-dimensional (1H,1H) correlation spectroscopy, homonuclear Hartmann-Hahn, and (13C,1H) correlation experiments. The configurations of the glycosidic linkages were inferred from the chemical shifts and coupling constants of the anomeric 1H and 13C resonances.

Cassels, F.J.; Fales, H.M.; London, J.; Carlson, R.W.; van Halbeek, H. (National Institute of Dental Research, Bethesda, MD (USA))

1990-08-25

123

Functional Polymorphisms of Interferon-gamma Affect Pneumonia-Induced Sepsis  

PubMed Central

Objective Sepsis is an inflammatory syndrome caused by infection, and both its incidence and mortality are high. Because interferon-gamma (IFN-?) plays an important role in inflammation, this work assessed IFN-? single nucleotide polymorphism (SNPs) that may be associated with sepsis. Methods A total of 196 patients with pneumonia-induced sepsis and 213 age- and sex-matched healthy volunteers participated in our study from July 2012 to July 2013 in Guangzhou, China. Patient clinical information was collected. Clinical pathology was assessed in subgroups defined based on clinical criteria, APACHE II (acute physiology and chronic health evaluation) and SOFA (sepsis-related organ failure assessment) scores and discharge rate. Four functional SNPs, ?1616T/C (rs2069705), ?764G/C (rs2069707), +874A/T (rs2430561) and +3234C/T (rs2069718), were genotyped by Snapshot in both sepsis patients and healthy controls. Pearson’s chi-square test or Fisher’s exact test were used to analyze the distribution of the SNPs, and the probability values (P values), odds ratios (OR) and 95% confidence intervals (CIs) were calculated. Results No mutations in the IFN-? ?764G/C SNP were detected among the participants in our study. The +874A/T and +3234C/T SNPs were in strong linkage disequilibrium (LD) (r2?=?0.894). The ?1616 TC+TT, +874 AT+AA genotype and the TAC haplotype were significantly associated with sepsis susceptibility, while the CTT haplotype was associated with protection against sepsis incidence. Genotype of ?1616 TT wasn’t only protective against severity of sepsis, but also against higher APACHE II and SOFA scores as +874 AA and +3234 CC. The TAC haplotype was was protective against progression to severe sepsis either. Conclusion Our results suggest that functional IFN-? SNPs and their haplotypes are associated with pneumonia-induced sepsis. PMID:24475220

Huang, Dongjian; Chen, Rui; Bai, Guibin; Li, Qing; Yu, Bolan; Fan, Yong; Sun, Xiaofang

2014-01-01

124

Angiopoietin 2 mediates microvascular and hemodynamic alterations in sepsis  

PubMed Central

Septic shock is characterized by increased vascular permeability and hypotension despite increased cardiac output. Numerous vasoactive cytokines are upregulated during sepsis, including angiopoietin 2 (ANG2), which increases vascular permeability. Here we report that mice engineered to inducibly overexpress ANG2 in the endothelium developed sepsis-like hemodynamic alterations, including systemic hypotension, increased cardiac output, and dilatory cardiomyopathy. Conversely, mice with cardiomyocyte-restricted ANG2 overexpression failed to develop hemodynamic alterations. Interestingly, the hemodynamic alterations associated with endothelial-specific overexpression of ANG2 and the loss of capillary-associated pericytes were reversed by intravenous injections of adeno-associated viruses (AAVs) transducing cDNA for angiopoietin 1, a TIE2 ligand that antagonizes ANG2, or AAVs encoding PDGFB, a chemoattractant for pericytes. To confirm the role of ANG2 in sepsis, we i.p. injected LPS into C57BL/6J mice, which rapidly developed hypotension, acute pericyte loss, and increased vascular permeability. Importantly, ANG2 antibody treatment attenuated LPS-induced hemodynamic alterations and reduced the mortality rate at 36 hours from 95% to 61%. These data indicate that ANG2-mediated microvascular disintegration contributes to septic shock and that inhibition of the ANG2/TIE2 interaction during sepsis is a potential therapeutic target. PMID:23863629

Ziegler, Tilman; Horstkotte, Jan; Schwab, Claudia; Pfetsch, Vanessa; Weinmann, Karolina; Dietzel, Steffen; Rohwedder, Ina; Hinkel, Rabea; Gross, Lisa; Lee, Seungmin; Hu, Junhao; Soehnlein, Oliver; Franz, Wolfgang M.; Sperandio, Markus; Pohl, Ulrich; Thomas, Markus; Weber, Christian; Augustin, Hellmut G.; Fässler, Reinhard; Deutsch, Urban; Kupatt, Christian

2013-01-01

125

Immunosuppression after Sepsis: Systemic Inflammation and Sepsis Induce a Loss of Naïve T-Cells but No Enduring Cell-Autonomous Defects in T-Cell Function  

PubMed Central

Sepsis describes the life-threatening systemic inflammatory response (SIRS) of an organism to an infection and is the leading cause of mortality on intensive care units (ICU) worldwide. An acute episode of sepsis is characterized by the extensive release of cytokines and other mediators resulting in a dysregulated immune response leading to organ damage and/or death. This initial pro-inflammatory burst often transits into a state of immune suppression characterised by loss of immune cells and T-cell dysfunction at later disease stages in sepsis survivors. However, despite these appreciations, the precise nature of the evoked defect in T-cell immunity in post-acute phases of SIRS remains unknown. Here we present an in-depth functional analysis of T-cell function in post-acute SIRS/sepsis. We document that T-cell function is not compromised on a per cell basis in experimental rodent models of infection-free SIRS (LPS or CpG) or septic peritonitis. Transgenic antigen-specific T-cells feature an unaltered cytokine response if challenged in vivo and ex vivo with cognate antigens. Isolated CD4+/CD8+ T-cells from post-acute septic animals do not exhibit defects in T-cell receptor-mediated activation at the the level of receptor-proximal signalling, activation marker upregulation or expansion. However, SIRS/sepsis induced transient lymphopenia and gave rise to an environment of immune attenuation at post acute disease stages. Thus, systemic inflammation has an acute impact on T-cell numbers and adaptive immunity, but does not cause major cell-autonomous enduring functional defects in T-cells. PMID:25541945

Markwart, Robby; Condotta, Stephanie A.; Requardt, Robert P.; Borken, Farina; Schubert, Katja; Weigel, Cynthia; Bauer, Michael; Griffith, Thomas S.; Förster, Martin; Brunkhorst, Frank M.; Badovinac, Vladimir P.; Rubio, Ignacio

2014-01-01

126

Case of intraperitoneal sepsis secondary to rupture of the appendix on the background of pseudomyxoma peritonei  

PubMed Central

Introduction Pseudomyxoma peritonei (PMP) is characterised by gelatinous ascites and pools of mucin associated with neoplastic mucinous epithelium within the peritoneal cavity. It can rarely present as acute intraperitoneal sepsis, requiring urgent medical attention. Presentation of case A 59-year old male was referred to our centre in February 2014 following a diagnostic laparotomy, which showed jelly-like material with occasional epithelial cells. He was listed for peritonectomy in a month's time at our centre. Three weeks later, he was admitted urgently to our hospital due to generalised abdominal pain and watery diarrhoea. Examination at admission was unremarkable. On the following day, he became haemodynamically unstable and was suspected to have intraperitoneal sepsis due to infected PMP. At emergency laparotomy, we found gross intraperitoneal sepsis and did extensive debulking of tumour, appendectomy and extensive division of adhesions. Another laparotomy was done 24 h later for washout. He was discharged three weeks after. Discussion Although we have done 780 peritonectomy procedures, this was the first patient with this presentation of widerspread intraperitoneal sepsis. Continuous mucous production of appendiceal adenoma can lead to appendiceal rupture. The appendix may decompress by perforation and then reseal. However, one episode of appendiceal rupture can cause bacterial contamination of PMP, leading to sepsis. Conclusion Intraperitoneal sepsis secondary to appendiceal rupture is rare. Hence surgeons may face an emergency of intraperitoneal sepsis during waiting period of planned CRS or as a primary presentation. With combined therapy of CRS and PIC, the prognosis of mucinous appendiceal adenoma is excellent.

Huang, Y.; Alzahrani, N.A.; Liauw, W.; Morris, D.L.

2014-01-01

127

Transfusion-associated bacterial sepsis.  

PubMed Central

The incidence of sepsis caused by transfusion of bacterially contaminated blood components is similar to or less than that of transfusion-transmitted hepatitis C virus infection, yet significantly exceeds those currently estimated for transfusion-associated human immunodeficiency and hepatitis B viruses. Outcomes are serious and may be fatal. In addition, transfusion of sterile allogenic blood can have generalized immunosuppressive effects on recipients, resulting in increased susceptibility to postoperative infection. This review examines the frequency of occurrence of transfusion-associated sepsis, the organisms implicated, and potential sources of bacteria. Approaches to minimize the frequency of sepsis are discussed, including the benefits and disadvantages of altering the storage conditions for blood. In addition, the impact of high levels of bacteria on the gross characteristics of erythrocyte and platelet concentrates is described. The potentials and limitations of current tests for detecting bacteria in blood are also discussed. PMID:7923050

Wagner, S J; Friedman, L I; Dodd, R Y

1994-01-01

128

Altered Neutrophil Trafficking During Sepsis1  

Microsoft Academic Search

In sepsis, dysregulation of the inflammatory system is well known, as reflected in excessive inflammatory mediator production, complement activation, and appearance of defects in phagocytic cells. In the current study sepsis was induced in rats by cecal ligation\\/puncture. Early in sepsis the 1 and 2 integrin content on blood neutrophils increased in a nontranscriptional manner, and the increase in 2,

Ren-Feng Guo; Niels C. Riedemann; Ines J. Laudes; Vidya J. Sarma; Robin G. Kunkel; Kari A. Dilley; Joseph D. Paulauskis; Peter A. Ward

2002-01-01

129

Sepsis and Disseminated Intravascular Coagulation  

Microsoft Academic Search

Sepsis almost invariably leads to hemostatic abnormalities, ranging from insignificant laboratory changes to severe disseminated intravascular coagulation (DIC). There is compelling evidence from clinical and experimental studies that DIC is involved in the pathogenesis of microvascular dysfunction and contributes to organ failure. In addition, the massive and ongoing activation of coagulation, may deplete platelets and coagulation factors, which may in

Marcel Levi; Evert de Jonge; Tom van der Poll

2003-01-01

130

Altered neutrophil trafficking during sepsis.  

PubMed

In sepsis, dysregulation of the inflammatory system is well known, as reflected in excessive inflammatory mediator production, complement activation, and appearance of defects in phagocytic cells. In the current study sepsis was induced in rats by cecal ligation/puncture. Early in sepsis the beta(1) and beta(2) integrin content on blood neutrophils increased in a nontranscriptional manner, and the increase in beta(2), but not beta(1), integrin content was C5a dependent. Similar changes could be induced in vitro on blood neutrophils following contact with phorbol ester or C5a. Direct injury of lungs of normal rats induced by deposition of IgG immune complexes (IgG-IC) caused 5-fold increases in the myeloperoxidase content that was beta(2), but not beta(1), dependent. In contrast, in cecal ligation/puncture lungs myeloperoxidase increased 10-fold after IgG immune complex deposition and was both beta(1) and beta(2) integrin dependent. These data suggest that sepsis causes enhanced neutrophil trafficking into the lung via mechanisms that are not engaged in the nonseptic state. PMID:12077259

Guo, Ren-Feng; Riedemann, Niels C; Laudes, Ines J; Sarma, Vidya J; Kunkel, Robin G; Dilley, Kari A; Paulauskis, Joseph D; Ward, Peter A

2002-07-01

131

Office diagnosis and management of group A streptococcal pharyngitis employing the rapid antigen detecting test. A 1-year prospective study of reliability and cost in primary care centres.  

PubMed

The impact of introducing the rapid antigen detecting test for the diagnosis of group A streptococcal pharyngitis in primary care centres and the direct and comprehensive cost-effectiveness of four alternative strategies for the management of group A streptococcal pharyngitis and the prevention of rheumatic fever were assessed in a 1-year prospective randomized study, carried out in children between the ages of 5 and 14 years. Data from the study showed that the test was easy to perform and reliable when introduced as a service in primary care. The strategy of using the rapid antigen detecting test and a 10-day oral penicillin course for diagnosis and treatment proved to be the safest and most cost-effective. If compliance with a 10-day course of oral penicillin is unlikely to be achieved, the strategy of introducing the test and treatment by intramuscular benzathin penicillin G proved to be the second best cost-effective alternative. In developing countries, where acute rheumatic fever is still common and the cost of the test and a 10-day course of penicillin may prove to be formidable, a strategy of treating all children with pharyngitis with intramuscular benzathin penicillin G seems to be the most cost-effective. The strategy of diagnosing group A streptococcal pharyngitis on clinical grounds proved to be the worst. PMID:7681647

Majeed, H A; al-Doussary, L; Moussa, M M; Yusuf, A R; Suliman, A H

1993-01-01

132

Group A Hemolytic Streptococcal Osteomyelitis in Children  

Microsoft Academic Search

Objective Little attention has been given to acute hematogenous osteomyelitis (AHO) caused by group A -hemolytic Streptococcus (GABHS), although up to 10% of cases are caused by this microorganism. The objective of this study was to define the clinical and laboratory characteristics of AHO caused by GABHS. Methods. Between January 1983 and June 1999, 29 patients were treated at Children's

Ekopimo O. Ibia; Menfo Imoisili; Andreas Pikis

2010-01-01

133

Intrauterine Group A Streptococcal Infections are Exacerbated by Prostaglandin E2  

PubMed Central

Streptococcus pyogenes(Group A Streptococcus; GAS) is a major cause of severe postpartum sepsis, a reemerging cause of maternal morbidity and mortality worldwide. Immunological alterations occur during pregnancy to promote maternofetal tolerance, which may increase the risk for puerperal infection. Prostaglandin E2 (PGE2) is an immunomodulatory lipid that regulates maternofetal tolerance, parturition, and innate immunity. The extent to which PGE2 regulates host immune responses to GAS infections in the context of endometritis is unknown. To address this, both an in vivo mouse intrauterine (i.u.) GAS infection model and an in vitro human macrophage-GAS interaction model were utilized. In C57BL/6 mice, i.u. GAS inoculation resulted in local and systemic inflammatory responses and triggered extensive changes in the expression of eicosanoid pathway genes. The i.u. administration of PGE2 increased the mortality of infected mice, suppressed local IL-6 and IL-17A levels, enhanced neutrophilic inflammation, reduced uterine macrophage populations, and increased bacterial dissemination. A role for endogenous PGE2 in modulating anti-streptococcal host defense was suggested because mice lacking the genes encoding the microsomal PGE2 synthase-1 or the EP2 receptor were protected from death, as were mice treated with the EP4 receptor antagonist GW627368X. PGE2 also regulated GAS-macrophage interactions. In GAS-infected human THP-1 (macrophage-like) cells, PGE2 inhibited the production of MCP-1 and TNF-? while augmenting IL-10 expression. PGE2 also impaired the phagocytic ability of human placental macrophages, THP-1 cells, and mouse peritoneal macrophages in vitro. Exploring the targeted disruption of PGE2 synthesis and signaling to optimize existing antimicrobial therapies against GAS may be warranted. PMID:23913961

Mason, Katie L.; Rogers, Lisa M.; Soares, Elyara M.; Bani-Hashemi, Tara; Downward, John Erb; Agnew, Dalen; Peters-Golden, Marc; Weinberg, Jason B.; Crofford, Leslie J.; Aronoff, David M.

2013-01-01

134

GENETIC BASIS OF MURINE ANTIBACTERIAL DEFENSE TO STREPTOCOCCAL LUNG INFECTION  

EPA Science Inventory

To evaluate the effect of genetic background and toll-like receptor 2 on antibacterial defense to streptococcal infection, eight genetically diverse strains of mice (A/J, DBA/2J, CAST/Ei, FVB/NJ, BALB/cJ, C57BL/6J, 129/SvImJ, and C3H/HeJ) and tlr2-deficient mice (C57BL/6...

135

Beyond single-marker analyses: mining whole genome scans for insights into treatment responses in severe sepsis.  

PubMed

Management of severe sepsis, an acute illness with high morbidity and mortality, suffers from the lack of effective biomarkers and largely empirical predictions of disease progression and therapeutic responses. We conducted a genome-wide association study using a large randomized clinical trial cohort to discover genetic biomarkers of response to therapy and prognosis utilizing novel approaches, including combination markers, to overcome limitations of single-marker analyses. Sepsis prognostic models were dominated by clinical variables with genetic markers less informative. In contrast, evidence for gene-gene interactions were identified for sepsis treatment responses with genetic biomarkers dominating models for predicting therapeutic responses, yielding candidates for replication in other cohorts. PMID:22310353

Man, M; Close, S L; Shaw, A D; Bernard, G R; Douglas, I S; Kaner, R J; Payen, D; Vincent, J-L; Fossceco, S; Janes, J M; Leishman, A G; O'Brien, L; Williams, M D; Garcia, J G N

2013-06-01

136

Heterogeneity of group A streptococcal pyrogenic exotoxin type B.  

PubMed Central

Streptococcal pyrogenic exotoxin type B purified from culture filtrates of either the NY-5 or T-19 strain of group A streptococcus was found to be heterogeneous in charge. Three protein fractions with isoelectric points of 8.0, 8.4, and 9.0 were isolated by differential solubility in ethanol and acetate-buffered saline followed by isoelectric focusing and shown to be antigenically identical to streptococcal pyrogenic exotoxin type B. The molecular weights of all three fractions were approximately 17,500, as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, with aggregates forming in the presence of hyaluronic acid. Only the pI 8.4 fraction showed the characteristic activities of streptococcal pyrogenic exotoxin in rabbits: pyrogenicity and ability to enhance susceptibility to lethal endotoxin shock. The pI 8.0 and pI 9.0 fractions were not pyrogenic, but could be used to immunize against pyrogenicity. These two fractions failed either to enhance lethal endotoxin shock or to immunize against enhancement activity. When the isolated fractions were electrofocused again they appeared heterogeneous, suggesting an instability of the B toxin molecular forms. Images PMID:352946

Barsumian, E L; Cunningham, C M; Schlievert, P M; Watson, D W

1978-01-01

137

Comparison of dirithromycin and penicillin for treatment of streptococcal pharyngitis.  

PubMed Central

In the treatment of group A beta-hemolytic streptococcal pharyngitis, penicillin is the drug of choice and erythromycin is the alternative. In a double-blind, randomized study, dirithromycin, a new macrolide, was compared with penicillin for the treatment of streptococcal pharyngitis. Of 121 patients who were treated with dirithromycin, 96.7% manifested a favorable clinical response, and of 136 patients treated with penicillin, 94.2% manifested a favorable clinical response. Streptococci were eradicated from the pharynges of 85.3% of 116 dirithromycin-treated patients and 82.5% of 126 penicillin-treated patients who returned for follow-up. There were no statistically significant differences in efficacy between the two groups. The incidence of abdominal symptoms was higher in dirithromycin-treated patients. Being as efficacious as penicillin and having the advantages over erythromycin of once-daily dosing and the lack of drug interactions, dirithromycin is an alternative to penicillin in the treatment of streptococcal pharyngitis for patients 12 years of age and older. PMID:8980757

Watkins, V S; Smietana, M; Conforti, P M; Sides, G D; Huck, W

1997-01-01

138

Ras regulates alveolar macrophage formation of CXC chemokines and neutrophil activation in streptococcal M1 protein-induced lung injury.  

PubMed

Streptococcal toxic shock syndrome (STSS) is associated with a high mortality rate. The M1 serotype of Streptococcus pyogenes is most frequently associated with STSS. Herein, we examined the role of Ras signaling in M1 protein-induced lung injury. Male C57BL/6 mice received the Ras inhibitor (farnesylthiosalicylic acid, FTS) prior to M1 protein challenge. Bronchoalveolar fluid and lung tissue were harvested for quantification of neutrophil recruitment, edema and CXC chemokine formation. Neutrophil expression of Mac-1 was quantified by use of flow cytometry. Quantitative RT-PCR was used to determine gene expression of CXC chemokines in alveolar macrophages. Administration of FTS reduced M1 protein-induced neutrophil recruitment, edema formation and tissue damage in the lung. M1 protein challenge increased Mac-1 expression on neutrophils and CXC chemokine levels in the lung. Inhibition of Ras activity decreased M1 protein-induced expression of Mac-1 on neutrophils and secretion of CXC chemokines in the lung. Moreover, FTS abolished M1 protein-provoked gene expression of CXC chemokines in alveolar macrophages. Ras inhibition decreased chemokine-mediated neutrophil migration in vitro. Taken together, our novel findings indicate that Ras signaling is a potent regulator of CXC chemokine formation and neutrophil infiltration in the lung. Thus, inhibition of Ras activity might be a useful way to antagonize streptococcal M1 protein-triggered acute lung injury. PMID:24704370

Zhang, Songen; Hwaiz, Rundk; Rahman, Milladur; Herwald, Heiko; Thorlacius, Henrik

2014-06-15

139

Full Activation of CD4+ T Cells Early During Sepsis Requires Specific Antigen  

PubMed Central

ABSTRACT During sepsis, CD4+ T cells express activation markers within the first 24 h. In the present study, the mechanisms of T-cell activation and its consequences were addressed in an acute peritonitis model in mice. The response of CD4+ T cells to sepsis induction was compared between OTII mice, characterized by ovalbumin-specific T-cell receptor–transgenic T cells, and C57BL/6 controls (wild type [WT] mice). Because ovalbumin was absent during peritonitis, the OTII CD4+ T cells could not be activated by canonical antigen recognition. In both OTII and WT control mice, CD4+ T effector cells and CD4+ Foxp3+ regulatory T cells (Tregs) expressed the activation marker CD69 early after sepsis onset. However, full activation with upregulation of CD25 and proliferation took place only in the presence of the antigen. Besides this, the fraction of Tregs was lower in OTII than that in WT mice. Sepsis mortality was increased in OTII mice. Our data show that, in sepsis, partial activation of CD4+ T cells is induced by a T-cell receptor–independent pathway, whereas full stimulation and proliferation require a specific antigen. Antigen-dependent T-cell effector functions as well as Treg activity may contribute to sepsis survival. PMID:25243429

Schmoeckel, Katrin; Traffehn, Sarah; Eger, Christin; Pötschke, Christian; Bröker, Barbara M.

2015-01-01

140

Neuropsychiatric Disorders Associated with Streptococcal Infection: A Case-Control Study among Privately Insured Children  

ERIC Educational Resources Information Center

The link between streptococcal infections and the onset of a variety of neuropsychiatric disorders is studied using a national sample of privately insured children. Findings suggest that patients with new-onset of obsessive-compulsive disorder, Tourette syndrome or tic orders were more likely to have been diagnosed with streptococcal infections in…

Leslie, Douglas L.; Kozma, Laura; Martin, Andres; Landeros, Angeli; Katsovich, Liliya; King, Robert A.; Leckman, James F.

2008-01-01

141

Invasive Group A Streptococcal Infection in High School Football Players, New York City, 2003  

PubMed Central

After being notified that 2 high school football teammates were hospitalized with confirmed or suspected invasive group A streptococcal infections, we conducted an investigation of possible spread among other team members. This investigation highlights a need for guidelines on management of streptococcal and other infectious disease outbreaks in team sport settings. PMID:15705342

Lee, Elsie; Bambino, Maribeth; Ackelsberg, Joel; Weiss, Don; Sathyakumar, Chiminyan; Kornblum, John; Barbot, Oxiris; Johnson, Dwight; Kaplan, Edward L.; Layton, Marcelle

2005-01-01

142

Increased expression of the interleukin 1 receptor on blood neutrophils of humans with the sepsis syndrome.  

PubMed Central

Because of the potential importance of interleukin 1 (IL-1) in modulating inflammation and the observations that human blood neutrophils (PMN) express IL-1 receptors (IL-1R) and synthesize IL-1 alpha and IL-1 beta, we studied the IL-1R on blood PMN from a group of patients with the sepsis syndrome. We report a marked enhancement in the sites per cell of IL-1R expressed on sepsis-PMN of 25 consecutively studied patients compared to 20 controls (patient mean = 9,329 +/- 2,212 SE; control mean = 716 +/- 42 SE, respectively). There was no demonstrable difference in the Kd of IL-1R on sepsis-PMN (approximately 1 nM) as determined by saturation curves of 125I-IL-1 alpha binding and the IL-1R on sepsis-PMN had an apparent Mr approximately 68,000, a value like that of normal PMN. Cytofluorographic analysis indicated that the sepsis-PMN phenotype is a single homogeneous population with respect to IL-1R expression. In contrast, expression of the membrane complement receptor CR3 is not increased on sepsis-PMN. Similar increases in expression of IL-1R were not observed in various other inflammatory processes, including acute disseminated inflammation and organ failure not caused by infection, acute infection without organ failure, and immunopathologies such as active systemic lupus erythematosus and rheumatoid arthritis. Enhanced expression of IL-1R was not related simply to the state of myeloid stimulation. Increased expression of IL-1R on normal PMN was induced in vitro by incubating cells with recombinant human granulocyte-macrophage/colony-stimulating factor for 18 h and this response was inhibited by cycloheximide, suggesting the possibility that de novo synthesis of IL-1R might occur in PMN during the sepsis syndrome. Images PMID:1834697

Fasano, M B; Cousart, S; Neal, S; McCall, C E

1991-01-01

143

Clinical review: Corticotherapy in sepsis  

PubMed Central

The use of glucocorticoids (corticotherapy) in severe sepsis is one of the main controversial issues in critical care medicine. These agents were commonly used to treat sepsis until the end of the 1980s, when several randomized trials casted serious doubt on any benefit from high-dose glucocorticoids. Later, important progress in our understanding of the role played by the hypothalamic–pituitary–adrenal axis in the response to sepsis, and of the mechanisms of action of glucocorticoids led us to reconsider their use in septic shock. The present review summarizes the basics of the physiological response of the hypothalamic–pituitary–adrenal axis to stress, including regulation of glucocorticoid synthesis, the cellular mechanisms of action of glucocorticoids, and how they influence metabolism, cardiovascular homeostasis and the immune system. The concepts of adrenal insufficiency and peripheral glucocorticoid resistance are developed, and the main experimental and clinical data that support the use of low-dose glucocorticoids in septic shock are discussed. Finally, we propose a decision tree for diagnosis of adrenal insufficiency and institution of cortisol replacement therapy. PMID:15025773

Prigent, Helene; Maxime, Virginie; Annane, Djillali

2004-01-01

144

Neonatal sepsis: the gut connection.  

PubMed

Colonization of the neonatal gut takes place immediately after birth. Bacteria that get colonized are considered to be "normal" flora derived principally from the mother and the immediate environment. However, for some neonates, the colonization of the gut, particularly with potential pathogens, may lead to subsequent infections or sepsis. The immune system and the gut barrier in neonates is vulnerable, with decreased acid secretion, low levels of protective mucous, and decreased motility, particularly in those who are premature and of low birth weight. This makes the neonatal gut especially prone to colonization with aerobic Gram-negative bacilli (GNB). And these GNB may later, under circumstances favorable to them, cause disease in the neonates. In developing countries, it is the GNB that cause the majority of the infections. In addition, the use of antibiotics in the neonatal intensive care unit also triggers colonization with antibiotic-resistant bacteria. This review discusses various aspects of neonatal gut colonization, neonatal sepsis, and tries to gather support to understand the connection between the gut and subsequent sepsis in neonates. PMID:25213719

Basu, S

2015-02-01

145

Early-Onset Neonatal Sepsis  

PubMed Central

SUMMARY Early-onset sepsis remains a common and serious problem for neonates, especially preterm infants. Group B streptococcus (GBS) is the most common etiologic agent, while Escherichia coli is the most common cause of mortality. Current efforts toward maternal intrapartum antimicrobial prophylaxis have significantly reduced the rates of GBS disease but have been associated with increased rates of Gram-negative infections, especially among very-low-birth-weight infants. The diagnosis of neonatal sepsis is based on a combination of clinical presentation; the use of nonspecific markers, including C-reactive protein and procalcitonin (where available); blood cultures; and the use of molecular methods, including PCR. Cytokines, including interleukin 6 (IL-6), interleukin 8 (IL-8), gamma interferon (IFN-?), and tumor necrosis factor alpha (TNF-?), and cell surface antigens, including soluble intercellular adhesion molecule (sICAM) and CD64, are also being increasingly examined for use as nonspecific screening measures for neonatal sepsis. Viruses, in particular enteroviruses, parechoviruses, and herpes simplex virus (HSV), should be considered in the differential diagnosis. Empirical treatment should be based on local patterns of antimicrobial resistance but typically consists of the use of ampicillin and gentamicin, or ampicillin and cefotaxime if meningitis is suspected, until the etiologic agent has been identified. Current research is focused primarily on development of vaccines against GBS. PMID:24396135

Simonsen, Kari A.; Anderson-Berry, Ann L.; Delair, Shirley F.

2014-01-01

146

High-Sensitivity C-Reactive Protein and Risk of Sepsis  

PubMed Central

Background Conventional C-reactive protein assays have been used to detect or guide the treatment of acute sepsis. The objective of this study was to determine the association between elevated baseline high-sensitivity C-reactive protein (hsCRP) and the risk of future sepsis events. Methods We studied data from 30,239 community dwelling, black and white individuals, age ?45 years old enrolled in the REasons for Geographic and Racial Differences in Stroke (REGARDS) cohort. Baseline hsCRP and participant characteristics were determined at the start of the study. We identified sepsis events through review of hospital records. Elevated hsCRP was defined as values >3.0 mg/L. Using Cox regression, we determined the association between elevated hsCRP and first sepsis event, adjusting for sociodemographic factors (age, sex, race, region, education, income), health behaviors (tobacco and alcohol use), chronic medical conditions (coronary artery disease, diabetes, dyslipidemia, hypertension, chronic kidney disease, chronic lung disease) and statin use. Results Over the mean observation time of 5.7 years (IQR 4.5–7.1), 974 individuals experienced a sepsis event, and 11,447 (37.9%) had elevated baseline hsCRP (>3.0 mg/L). Elevated baseline hsCRP was independently associated with subsequent sepsis (adjusted HR 1.56; 95% CI 1.36–1.79), adjusted for sociodemographics, health behaviors, chronic medical conditions and statin use. Conclusion Elevated baseline hsCRP was associated with increased risk of future sepsis events. hsCRP may help to identify individuals at increased risk for sepsis. PMID:23935961

Wang, Henry E.; Shapiro, Nathan I.; Safford, Monika M.; Griffin, Russell; Judd, Suzanne; Rodgers, Joel B.; Warnock, David G.; Cushman, Mary; Howard, George

2013-01-01

147

Surviving sepsis: going beyond the guidelines  

PubMed Central

The Surviving Sepsis Campaign is a global effort to improve the care of patients with severe sepsis and septic shock. The first Surviving Sepsis Campaign Guidelines were published in 2004 with an updated version published in 2008. These guidelines have been endorsed by many professional organizations throughout the world and come regarded as the standard of care for the management of patients with severe sepsis. Unfortunately, most of the recommendations of these guidelines are not evidence-based. Furthermore, the major components of the 6-hour bundle are based on a single-center study whose validity has been recently under increasing scrutiny. This paper reviews the validity of the Surviving Sepsis Campaign 6-hour bundle and provides a more evidence-based approach to the initial resuscitation of patients with severe sepsis. PMID:21906348

2011-01-01

148

Mast cells aggravate sepsis by inhibiting peritoneal macrophage phagocytosis  

PubMed Central

Controlling the overwhelming inflammatory reaction associated with polymicrobial sepsis remains a prevalent clinical challenge with few treatment options. In septic peritonitis, blood neutrophils and monocytes are rapidly recruited into the peritoneal cavity to control infection, but the role of resident sentinel cells during the early phase of infection is less clear. In particular, the influence of mast cells on other tissue-resident cells remains poorly understood. Here, we developed a mouse model that allows both visualization and conditional ablation of mast cells and basophils to investigate the role of mast cells in severe septic peritonitis. Specific depletion of mast cells led to increased survival rates in mice with acute sepsis. Furthermore, we determined that mast cells impair the phagocytic action of resident macrophages, thereby allowing local and systemic bacterial proliferation. Mast cells did not influence local recruitment of neutrophils and monocytes or the release of inflammatory cytokines. Phagocytosis inhibition by mast cells involved their ability to release prestored IL-4 within 15 minutes after bacterial encounter, and treatment with an IL-4–neutralizing antibody prevented this inhibitory effect and improved survival of septic mice. Our study uncovers a local crosstalk between mast cells and macrophages during the early phase of sepsis development that aggravates the outcome of severe bacterial infection. PMID:25180604

Dahdah, Albert; Gautier, Gregory; Attout, Tarik; Fiore, Frédéric; Lebourdais, Emeline; Msallam, Rasha; Daëron, Marc; Monteiro, Renato C.; Benhamou, Marc; Charles, Nicolas; Davoust, Jean; Blank, Ulrich; Malissen, Bernard; Launay, Pierre

2014-01-01

149

Mast cells aggravate sepsis by inhibiting peritoneal macrophage phagocytosis.  

PubMed

Controlling the overwhelming inflammatory reaction associated with polymicrobial sepsis remains a prevalent clinical challenge with few treatment options. In septic peritonitis, blood neutrophils and monocytes are rapidly recruited into the peritoneal cavity to control infection, but the role of resident sentinel cells during the early phase of infection is less clear. In particular, the influence of mast cells on other tissue-resident cells remains poorly understood. Here, we developed a mouse model that allows both visualization and conditional ablation of mast cells and basophils to investigate the role of mast cells in severe septic peritonitis. Specific depletion of mast cells led to increased survival rates in mice with acute sepsis. Furthermore, we determined that mast cells impair the phagocytic action of resident macrophages, thereby allowing local and systemic bacterial proliferation. Mast cells did not influence local recruitment of neutrophils and monocytes or the release of inflammatory cytokines. Phagocytosis inhibition by mast cells involved their ability to release prestored IL-4 within 15 minutes after bacterial encounter, and treatment with an IL-4-neutralizing antibody prevented this inhibitory effect and improved survival of septic mice. Our study uncovers a local crosstalk between mast cells and macrophages during the early phase of sepsis development that aggravates the outcome of severe bacterial infection. PMID:25180604

Dahdah, Albert; Gautier, Gregory; Attout, Tarik; Fiore, Frédéric; Lebourdais, Emeline; Msallam, Rasha; Daëron, Marc; Monteiro, Renato C; Benhamou, Marc; Charles, Nicolas; Davoust, Jean; Blank, Ulrich; Malissen, Bernard; Launay, Pierre

2014-10-01

150

Divergent signaling pathways in phagocytic cells during sepsis.  

PubMed

Neutrophil accumulation in the lung plays a pivotal role in the pathogenesis of acute lung injury during sepsis. Directed movement of neutrophils is mediated by a group of chemoattractants, especially CXC chemokines. Local lung production of CXC chemokines is intensified during experimental sepsis induced by cecal ligation and puncture (CLP), as reflected by rising levels of MIP-2 and cytokine-induced neutrophil chemoattractant-1 in bronchoalveolar lavage fluids. Alveolar macrophages are primed and blood neutrophils are down-regulated for production of MIP-2 and cytokine-induced neutrophil chemoattractant production in response to LPS and C5a. Under these conditions of stimulation, activation of MAPKs (p38, p42/p44) occurs in sham neutrophils but not in CLP neutrophils, while under the same conditions phosphorylation of p38 and p42/p44 occurs in both sham and CLP alveolar macrophages. These data indicate that, under septic conditions, there is impaired signaling in neutrophils and enhanced signaling in alveolar macrophages, resulting in CXC chemokine production, and C5a appears to play a pivotal role in this process. As a result, CXC chemokines increase in lung, setting the stage for neutrophil accumulation in lung during sepsis. PMID:16818791

Guo, Ren-Feng; Riedemann, Niels C; Sun, Lei; Gao, Hongwei; Shi, Kevin X; Reuben, Jayne S; Sarma, Vidya J; Zetoune, Firas S; Ward, Peter A

2006-07-15

151

Clinical aspects of sepsis: an overview.  

PubMed

Sepsis is one of the oldest and most elusive syndromes in medicine. With the confirmation of germ theory by Semmelweis, Pasteur, and others, sepsis was considered as a systemic infection by a pathogenic organism. Although the germ is probably the beginning of the syndrome and one of the major enemies to be identified and fought, sepsis is something wider and more elusive. In this chapter clinically relevant themes of sepsis will be approached to provide an insight of everyday clinical practice for healthcare workers often not directly involved in the patient's management. PMID:25319776

Monti, Giacomo; Landoni, Giovanni; Taddeo, Daiana; Isella, Francesca; Zangrillo, Alberto

2015-01-01

152

Presepsin as a powerful monitoring tool for the prognosis and treatment of sepsis: a multicenter prospective study.  

PubMed

Presepsin is a protein whose levels increase specifically in the blood of patients with sepsis. It is proposed as a diagnostic and prognostic marker for assessing the degree of sepsis severity. The present multicenter prospective study compared the clinical utility of presepsin with other conventional sepsis biomarkers including procalcitonin, interleukin-6, and C-reactive protein for evaluating the severity of sepsis during follow-up. Patients with sepsis (n = 103) admitted to the emergency room or intensive care unit were enrolled in this study and classified into 3 diagnostic groups: sepsis, severe sepsis, and septic shock. Blood samples were obtained from each patient on admission and after 1, 3, 5, and 7 days. The patients were further divided into the favorable and unfavorable prognosis groups on the basis of several indicators of sepsis severity (i.e., Sequential Organ Failure Assessment score, and Acute Physiology and Chronic Health Evaluation II score). The patients in the favorable prognosis group exhibited significant decreases in all biomarker levels on days 3 and 7 after admission. In the unfavorable prognosis group, only presepsin levels did not decrease significantly during follow-up. The period of antibiotics treatment in the unfavorable prognosis group was significantly longer than those in the favorable prognosis group (P < 0.05). The unfavorable prognosis group had significantly higher 28-day mortality than the favorable prognosis group (P < 0.05). Therefore, the results suggest that presepsin levels correlated with the severity of sepsis during follow-up in comparison with other conventional sepsis biomarkers. PMID:24462421

Endo, Shigeatsu; Suzuki, Yasushi; Takahashi, Gaku; Shozushima, Tatsuyori; Ishikura, Hiroyasu; Murai, Akira; Nishida, Takeshi; Irie, Yuhei; Miura, Masanao; Iguchi, Hironobu; Fukui, Yasuo; Tanaka, Kimiaki; Nojima, Tsuyoshi; Okamura, Yoshikazu

2014-01-01

153

Brachial artery reactivity in patients with severe sepsis: an observational study  

PubMed Central

Introduction Ultrasound measurements of brachial artery reactivity in response to stagnant ischemia provide estimates of microvascular function and conduit artery endothelial function. We hypothesized that brachial artery reactivity would independently predict severe sepsis and severe sepsis mortality. Methods This was a combined case-control and prospective cohort study. We measured brachial artery reactivity in 95 severe sepsis patients admitted to the medical and surgical intensive care units of an academic medical center and in 52 control subjects without acute illness. Measurements were compared in severe sepsis patients versus control subjects and in severe sepsis survivors versus nonsurvivors. Multivariable analyses were also conducted. Results Hyperemic velocity (centimeters per cardiac cycle) and flow-mediated dilation (percentage) were significantly lower in severe sepsis patients versus control subjects (hyperemic velocity: severe sepsis = 34 (25 to 48) versus controls = 63 (52 to 81), P < 0.001; flow-mediated dilation: severe sepsis = 2.65 (0.81 to 4.79) versus controls = 4.11 (3.06 to 6.78), P < 0.001; values expressed as median (interquartile range)). Hyperemic velocity, but not flow-mediated dilation, was significantly lower in hospital nonsurvivors versus survivors (hyperemic velocity: nonsurvivors = 25 (16 to 28) versus survivors = 39 (30 to 50), P < 0.001; flow-mediated dilation: nonsurvivors = 1.90 (0.68 to 3.41) versus survivors = 2.96 (0.91 to 4.86), P = 0.12). Lower hyperemic velocity was independently associated with hospital mortality in multivariable analysis (odds ratio = 1.11 (95% confidence interval = 1.04 to 1.19) per 1 cm/cardiac cycle decrease in hyperemic velocity; P = 0.003). Conclusions Brachial artery hyperemic blood velocity is a noninvasive index of microvascular function that independently predicts mortality in severe sepsis. In contrast, brachial artery flow-mediated dilation, reflecting conduit artery endothelial function, was not associated with mortality in our severe sepsis cohort. Brachial artery hyperemic velocity may be a useful measurement to identify patients who could benefit from novel therapies designed to reverse microvascular dysfunction in severe sepsis and to assess the physiologic efficacy of these treatments. PMID:22390813

2012-01-01

154

Studie av prehospitalt forløp hos pasienter med sepsis .  

E-print Network

??Bakgrunn: Sepsis er en potensielt livstruende følgetilstand etter infeksjon. En rekke studier etter årtusenskiftet har vist at tidlig antibiotika- og væskebehandling øker overlevelsen av sepsis.… (more)

Antonsen, Linn-Kristin

2014-01-01

155

Vastasyntyneen varsan sepsis, osa I - sepsiksen diagnosointi ja sepsisasteikko.  

E-print Network

??Sepsis tarkoittaa elimistön tulehduksellista vastetta, johon liittyy infektio. Sepsis on yksi yleisimmistä sairauksista vastasyntyneillä varsoilla. Taudinkuva on vakava ja vaatii usein akuuttia tehohoitoa. Halusimme kartoittaa… (more)

Koikkalainen, Krisse

2008-01-01

156

Hemodynamics and metabolic studies on septic shock in patients with acute liver failure  

Microsoft Academic Search

BackgroundsAcute liver failure is often accompanied by hyperdynamic circulation, which is also a characteristic of septic shock. Pre-existing acute liver failure may worsen the hemodynamic impairment and prognosis in sepsis.

Ming-Hung Tsai; Yung-Chang Chen; Jau-Min Lien; Ya-Chung Tian; Yun-shing Peng; Ji-Tseng Fang; Chun Yang; Jui-Hsiang Tang; Yun-Yi Chu; Pang-Chi Chen; Cheng-Shyong Wu

2008-01-01

157

[Micromethod for the identification of streptococcal, enterococcal and staphylococcal species].  

PubMed

The aim of this study was to set accurate and reliable methods in the identification of streptococcal, enterococcal and staphylococcal species. Micro CSB Strep and Staph system consists each of a strip with cupules containing dehydrated substrates for biochemical identification of bacterial species. Baye's theorem was used to validate tests. Reactions from micromethods were clear and easily read. Identification of 229 strains of streptococci and enterococci was correct for most species with 98.7% species with 99.3% sensitivity. 41 strains of staphylococci were also correctly identified with 85.2% of specificity and 97.68% of sensitivity. PMID:10797992

Gassama, A; Boye, C S; Ndao, S K; Kairé, O; Coly, I; Macondo, E A; Sow, A I; Diaw, L; Diop-Diop, M; Mboup, S

1999-01-01

158

Post-streptococcal vasculopathy with evolution to Degos' disease.  

PubMed

Degos' disease or malignant atrophic papulosis is a rare disseminated occlusive vasculopathy affecting the skin, gastrointestinal tract, central nervous system, and less often other organ systems. The exact etiology of this vasculopathy has not been established. Infections, autoimmune disease and coagulation defects have been proposed as underlying pathogenic mechanisms, but none have been confirmed. Here, we report the clinical, radiological and histopathologic features of Degos' disease in a 41-year-old man following streptococcal throat infection. Prior postulated hypothesis as post-infectious immunologic mechanism may be further supported by this case. PMID:21035145

Pati, Sandipan; Muley, Suraj A; Grill, Marie F; Coons, Stephen; Walker, Russell

2011-01-15

159

Probing sepsis and sepsis-like conditions using untargeted SPIO nanoparticles.  

PubMed

Sepsis is the leading cause of death in critically ill patients in the United States. Current diagnosis of sepsis relies heavily on the patient's manifestation of septic symptoms, which occur at life-threatening late stage of sepsis. Because the underlying biological changes of sepsis occur hours to days before the clinical presentation of symptoms, early detection of the biological changes will provide crucial opportunities for early diagnosis and effective treatment of sepsis. As an candidate for early sepsis detection, we propose using a novel quantitative susceptibility mapping (QSM) MRI that quantifiably measure the activity of the immune system during sepsis progression. It has been observed that Kupffer cells, comprising 80% of the liver's macrophages, play a pivotal role in the early response to system infection, a condition characteristic of sepsis. Further, it has been observed that phagocytosis by Kupffer cells is a major mechanism by which nanoparticle-based contrast agents, such as Feridex, are cleared from the body. By quantifying the amount of superparamagnetic iron-oxide nanoparticles uptaken by these macrophages and correlating this result to immune system response and the progression of sepsis, we can utilize commonly used contrast agents as markers in monitoring and diagnosing sepsis condition. This study offers an in vitro proof of concept; RAW264.7 murine monocytes were treated with lipopolysaccharide to induce a sepsis-like cell condition, incubated with the FDA-approved contrast agent Feridex IV, and imaged using QSM MRI for the quantification of iron. PMID:21095733

Wong, Richard; Shou, Jian; Wang, Yi

2010-01-01

160

Novel strategies for the treatment of sepsis.  

PubMed

The history of therapeutic interventions in clinical trials for sepsis has been referred to as the "graveyard for pharmaceutical companies." That is now set to change, as research provides hope for new approaches that will be therapeutically effective in humans with sepsis. PMID:12724763

Riedemann, Niels C; Guo, Ren-Feng; Ward, Peter A

2003-05-01

161

Mobilization in severe sepsis: An integrative review.  

PubMed

Severe sepsis is a leading cause of long-term morbidity in the United States. Up to half of severe sepsis is treated in non-intensive care unit (ICU) settings, making it applicable to hospitalist practice. Evidence has demonstrated benefits from physical therapy (PT) in myriad conditions; whether PT may benefit severe sepsis patients either within or outside the ICU is unknown. Therefore, we conducted a review of the literature to understand whether early mobilization improves outcomes in patients with severe sepsis in non-ICU settings. We summarized the pathophysiology of functional decline in severe sepsis, the efficacy of PT in other patient populations, and the potential rationale for PT interventions in patients with severe sepsis. Multiple databases were searched for keywords including length of stay, mortality, costs, mobilization, and PT. Two authors (S.G. and V.C.) independently determined the eligibility of each study. A secondary review including studies of any infectious pathology with PT interventions or sepsis patients within the ICU was also conducted. Our search did not yield any primary literature regarding the impact of mobilization on severe sepsis outcomes in non-ICU settings. Only 1 retrospective study showed potential benefit of therapy in sepsis patients in the ICU. Similarly, in non-ICU settings, only 1 study that included patients with bacterial pneumonia reported outcomes after implementing an intervention consisting of early mobilization. These findings suggest that scant data regarding the efficacy of early mobilization following severe sepsis exist. Because hospitalists often care for this patient population, an opportunity for research in this area exists. Journal of Hospital Medicine 2014. © 2014 Society of Hospital Medicine. PMID:25393649

Govindan, Sushant; Iwashyna, Theodore J; Odden, Andrew; Flanders, Scott A; Chopra, Vineet

2014-11-13

162

Chronic Filarial Infection Provides Protection against Bacterial Sepsis by Functionally Reprogramming Macrophages  

PubMed Central

Helminths immunomodulate their hosts and induce a regulatory, anti-inflammatory milieu that prevents allergies and autoimmune diseases. Helminth immunomodulation may benefit sepsis outcome by preventing exacerbated inflammation and severe pathology, but the influence on bacterial clearance remains unclear. To address this, mice were chronically infected with the filarial nematode Litomosoides sigmodontis (L.s.) and the outcome of acute systemic inflammation caused by i.p. Escherichia coli injection was determined. L.s. infection significantly improved E. coli-induced hypothermia, bacterial clearance and sepsis survival and correlated with reduced concentrations of associated pro-inflammatory cytokines/chemokines and a less pronounced pro-inflammatory macrophage gene expression profile. Improved sepsis outcome in L.s.-infected animals was mediated by macrophages, but independent of the alternatively activated macrophage subset. Endosymbiotic Wolbachia bacteria that are present in most human pathogenic filariae, as well as L.s., signal via TLR2 and modulate macrophage function. Here, gene expression profiles of peritoneal macrophages from L.s.-infected mice revealed a downregulation of genes involved in TLR signaling, and pulsing of macrophages in vitro with L.s. extract reduced LPS-triggered activation. Subsequent transfer improved sepsis outcome in naïve mice in a Wolbachia- and TLR2-dependent manner. In vivo, phagocytosis was increased in macrophages from L.s.-infected wild type, but not TLR2-deficient animals. In association, L.s. infection neither improved bacterial clearance in TLR2-deficient animals nor ameliorated E. coli-induced hypothermia and sepsis survival. These results indicate that chronic L.s. infection has a dual beneficial effect on bacterial sepsis, reducing pro-inflammatory immune responses and improving bacterial control. Thus, helminths and their antigens may not only improve the outcome of autoimmune and allergic diseases, but may also present new therapeutic approaches for acute inflammatory diseases that do not impair bacterial control. PMID:25611587

Gondorf, Fabian; Berbudi, Afiat; Buerfent, Benedikt C.; Ajendra, Jesuthas; Bloemker, Dominique; Specht, Sabine; Schmidt, David; Neumann, Anna-Lena; Layland, Laura E.; Hoerauf, Achim; Hübner, Marc P.

2015-01-01

163

Chronic Filarial Infection Provides Protection against Bacterial Sepsis by Functionally Reprogramming Macrophages.  

PubMed

Helminths immunomodulate their hosts and induce a regulatory, anti-inflammatory milieu that prevents allergies and autoimmune diseases. Helminth immunomodulation may benefit sepsis outcome by preventing exacerbated inflammation and severe pathology, but the influence on bacterial clearance remains unclear. To address this, mice were chronically infected with the filarial nematode Litomosoides sigmodontis (L.s.) and the outcome of acute systemic inflammation caused by i.p. Escherichia coli injection was determined. L.s. infection significantly improved E. coli-induced hypothermia, bacterial clearance and sepsis survival and correlated with reduced concentrations of associated pro-inflammatory cytokines/chemokines and a less pronounced pro-inflammatory macrophage gene expression profile. Improved sepsis outcome in L.s.-infected animals was mediated by macrophages, but independent of the alternatively activated macrophage subset. Endosymbiotic Wolbachia bacteria that are present in most human pathogenic filariae, as well as L.s., signal via TLR2 and modulate macrophage function. Here, gene expression profiles of peritoneal macrophages from L.s.-infected mice revealed a downregulation of genes involved in TLR signaling, and pulsing of macrophages in vitro with L.s. extract reduced LPS-triggered activation. Subsequent transfer improved sepsis outcome in naïve mice in a Wolbachia- and TLR2-dependent manner. In vivo, phagocytosis was increased in macrophages from L.s.-infected wild type, but not TLR2-deficient animals. In association, L.s. infection neither improved bacterial clearance in TLR2-deficient animals nor ameliorated E. coli-induced hypothermia and sepsis survival. These results indicate that chronic L.s. infection has a dual beneficial effect on bacterial sepsis, reducing pro-inflammatory immune responses and improving bacterial control. Thus, helminths and their antigens may not only improve the outcome of autoimmune and allergic diseases, but may also present new therapeutic approaches for acute inflammatory diseases that do not impair bacterial control. PMID:25611587

Gondorf, Fabian; Berbudi, Afiat; Buerfent, Benedikt C; Ajendra, Jesuthas; Bloemker, Dominique; Specht, Sabine; Schmidt, David; Neumann, Anna-Lena; Layland, Laura E; Hoerauf, Achim; Hübner, Marc P

2015-01-01

164

Positive effect of septimeb™ on mortality rate in severe sepsis: a novel non antibiotic strategy  

PubMed Central

Background Septimeb is a new herbal-derived remedy, recently approved for its potential immunomodulatory effects. Regarding the key role of immune system in the pathogenesis of severe sepsis and lack of any standard treatment for improving survival of these patients; we evaluated the effect of Septimeb -as an adjutant to standard treatment-on inflammatory biomarkers and mortality rates in patients with severe sepsis. Methods In this multicenter, randomized, single-blind trial, we assigned patients with severe sepsis and Acute Physiology and Chronic Health Evaluation (APACHE II) score of more than 20 to receive standard treatment of severe sepsis (control group) or standard treatment plus Septimeb. This group was treated with Septimeb for 14 days then followed up for another14 days. APACHE score, Sequential Organ Failure Assessment (SOFA) and Simplified Acute Physiology Score (SAPS) were calculated daily. Blood samples were analyzed for interleukin 2 tumor necrosis factor-?, total antioxidant power, platelet growth factor and matrix metalloproteinase 2. Results A total of 29 patients underwent randomization (13 in control group and 16 in Septimeb group). There was significant difference between the Septimeb and control group in the 14 days mortality rate (18.8% vs. 53.85 respectively, P=0.048). Compared to control group, Septimeb was significantly effective in improving SAPS (P= 0.029), SOFA (P=0.003) and APACHE II (P=0.008) scores. Inflammatory biomarkers didn’t change significantly between the two groups (P>0.05). Conclusion Septimeb reduces mortality rates among patients with severe sepsis and it could be added as a safe adjutant to standard treatment of sepsis. PMID:23351964

2012-01-01

165

Actinonin, a meprin A inhibitor, protects the renal microcirculation during sepsis  

PubMed Central

Sepsis-induced acute renal injury (AKI) occurs in 20%–50% of septic patients and nearly doubles the mortality rate of sepsis. Since treatment in the septic patient is usually only begun after the onset of symptoms, therapy that is effective even when delayed would have the greatest impact on patient survival. The metalloproteinase meprin A, an oligomeric complex made of ?- and ?- subunits, is highly expressed at the brush-border membranes of the kidney and capable of degrading numerous substrates including extracellular matrix proteins and cytokines. The goal of the present study was to compare the therapeutic potential of actinonin, an inhibitor of meprin A when administered before and after the onset of sepsis. Mice were treated with actinonin at 30 min prior to or 7 h post induction of sepsis by cecal ligation and puncture (CLP). Intravital videomicroscopy was utilized to image renal peritubular capillary perfusion and reactive nitrogen species. Actinonin treatment 30 min before CLP reduced IL1-? levels and prevented the fall in renal capillary perfusion at 7 h and 18 h. Actinonin also prevented the fall in renal capillary perfusion even when administered at 7 h post CLP. In addition, even late administration of actinonin preserved renal morphology and lowered blood urea nitrogen and serum creatinine concentrations. These data suggest that agents like actinonin should be evaluated further as possible therapeutic agents because targeting both the early systemic and later organ-damaging effects of sepsis should have the highest likelihood of success. PMID:20577148

Wang, Zhen; Herzog, Christian; Kaushal, Gur P.; Gokden, Neriman; Mayeux, Philip R.

2012-01-01

166

Clarithromycin co-administered with amikacin attenuates systemic inflammation in experimental sepsis with Escherichia coli.  

PubMed

To assess the efficacy of clarithromycin as an immunomodulator in experimental sepsis with Escherichia coli, acute pyelonephritis was induced after ligation of the right ureter and injection of the test isolate into the renal pelvis in 40 rabbits. Four groups of treatment were applied with administration of therapy on advent of sepsis-associated pulmonary oedema, as follows: A: controls; B: clarithromycin; C: amikacin, D: both agents. Survival was recorded along with estimation of serum levels of endotoxins (LPS), of tumour necrosis factor-alpha (TNFalpha), malondialdehyde (MDA) and of bacterial counts. Mean survival of groups A, B, C and D was 2.51, 7.60, 10.25 and 11.40 days, respectively. Serum levels of TNFalpha and of MDA of group A increased over-time. Pulmonary oedema at 6 h after bacterial challenge was accompanied by increase of TNFalpha and MDA; administration of clarithromycin decreased their values. It is concluded that intravenous clarithromycin might constitute a promising immunomodulatory agent for the management of sepsis since its efficacy was proved after administration on presentation of sepsis-associated pulmonary oedema. The presented findings emphasise the need for further clinical research of the use of clarithromycin for the therapy of Gram-negative sepsis. PMID:15664488

Giamarellos-Bourboulis, Evangelos J; Baziaka, Fotini; Antonopoulou, Anastasia; Koutoukas, Pantelis; Kousoulas, Vassilios; Sabracos, Lambros; Panagou, Charalambos; Perrea, Despina; Giamarellou, Helen

2005-02-01

167

Calpain activity and muscle wasting in sepsis  

PubMed Central

Muscle wasting in sepsis reflects activation of multiple proteolytic mechanisms, including lyosomal and ubiquitin-proteasome-dependent protein breakdown. Recent studies suggest that activation of the calpain system also plays an important role in sepsis-induced muscle wasting. Perhaps the most important consequence of calpain activation in skeletal muscle during sepsis is disruption of the sarcomere, allowing for the release of myofilaments (including actin and myosin) that are subsequently ubiquitinated and degraded by the 26S proteasome. Other important consequences of calpain activation that may contribute to muscle wasting during sepsis include degradation of certain transcription factors and nuclear cofactors, activation of the 26S proteasome, and inhibition of Akt activity, allowing for downstream activation of Foxo transcription factors and GSK-3?. The role of calpain activation in sepsis-induced muscle wasting suggests that the calpain system may be a therapeutic target in the prevention and treatment of muscle wasting during sepsis. Furthermore, because calpain activation may also be involved in muscle wasting caused by other conditions, including different muscular dystrophies and cancer, calpain inhibitors may be beneficial not only in the treatment of sepsis-induced muscle wasting but in other conditions causing muscle atrophy as well. PMID:18492780

Smith, Ira J.; Lecker, Stewart H.; Hasselgren, Per-Olof

2008-01-01

168

[Epidemiology of invasive group A streptococcal infections in developed countries : the Canadian experience with necrotizing fasciitis].  

PubMed

In industrialized countries, group A streptococcal infections were a source of concern, mainly due to the occurrence of rheumatic fever and its cardiac complications. At present, the incidence of rheumatic fever is decreasing in these countries, giving way to an increasing occurrence of invasive streptococcal group A infections with high level of morbidity and mortality. Streptococcal necrotizing fasciitis, a specific entity, emerged these last decades, often in association with chickenpox. The introduction of the varicella vaccine in the province of Quebec routine immunization program, was followed by a significant decrease in the number of necrotizing fasciitis or other skin and soft-tissues infections in our pediatric population. However, in our experience at the CHU Sainte-Justine, this immunization program has not been helpful to reduce the overall incidence of invasive group A streptococcal infections. Conversely, an increase in the number of pleuro-pulmonary and osteo-articular infections was observed. PMID:25456684

Ovetchkine, Ph; Bidet, Ph; Minodier, Ph; Frère, J; Bingen, E

2014-11-01

169

A pilot study of penicillin prophylaxis for neuropsychiatric exacerbations triggered by streptococcal infections  

Microsoft Academic Search

Background: Some children with obsessive-compulsive disorder (OCD) and tic disorders appear to have symptom exacerbations triggered by group A beta-hemolytic streptococcal infections in a manner that is similar to rheumatic fever and its neurologic variant, Sydenham’s chorea. Because penicillin prophylaxis has proven to be effective in preventing recurrences of rheumatic fever, it was postulated that it might also prevent streptococcal-triggered

Marjorie A. Garvey; Susan J. Perlmutter; Albert J. Allen; Susan Hamburger; Lorraine Lougee; Henrietta L. Leonard; M. Elizabeth Witowski; Billinda Dubbert; Susan E. Swedo

1999-01-01

170

Sepsis after autologous fat grafting.  

PubMed

Autologous fat grafting is an increasingly popular technique, with numerous examples of excellent results. Adherence to key principles, including sterile technique and low-volume injection throughout layers of tissue, appears to be critical to obtaining good results. Reports of adverse outcomes are infrequent, but several case reports document both infectious and aesthetic complications. This case report represents an extreme complication, including abscess formation, life-threatening sepsis, and residual deformity. It serves as yet another reminder that early adoption of surgical procedures by those without a sound understanding of the underlying principles and techniques can have disastrous consequences. Furthermore, physicians operating on any patient must understand the potential for complications and be able to manage these appropriately when they occur. PMID:20885205

Talbot, Simon G; Parrett, Brian M; Yaremchuk, Michael J

2010-10-01

171

Targeting Rac1 signaling inhibits streptococcal M1 protein-induced CXC chemokine formation, neutrophil infiltration and lung injury.  

PubMed

Infections with Streptococcus pyogenes exhibit a wide spectrum of infections ranging from mild pharyngitis to severe Streptococcal toxic shock syndrome (STSS). The M1 serotype of Streptococcus pyogenes is most commonly associated with STSS. In the present study, we hypothesized that Rac1 signaling might regulate M1 protein-induced lung injury. We studied the effect of a Rac1 inhibitor (NSC23766) on M1 protein-provoked pulmonary injury. Male C57BL/6 mice received NSC23766 prior to M1 protein challenge. Bronchoalveolar fluid and lung tissue were harvested for quantification of neutrophil recruitment, edema and CXC chemokine formation. Neutrophil expression of Mac-1 was quantified by use of flow cytometry. Quantitative RT-PCR was used to determine gene expression of CXC chemokines in alveolar macrophages. Treatment with NSC23766 decreased M1 protein-induced neutrophil infiltration, edema formation and tissue injury in the lung. M1 protein challenge markedly enhanced Mac-1 expression on neutrophils and CXC chemokine levels in the lung. Inhibition of Rac1 activity had no effect on M1 protein-induced expression of Mac-1 on neutrophils. However, Rac1 inhibition markedly decreased M1 protein-evoked formation of CXC chemokines in the lung. Moreover, NSC23766 completely inhibited M1 protein-provoked gene expression of CXC chemokines in alveolar macrophages. We conclude that these novel results suggest that Rac1 signaling is a significant regulator of neutrophil infiltration and CXC chemokine production in the lung. Thus, targeting Rac1 activity might be a potent strategy to attenuate streptococcal M1 protein-triggered acute lung damage. PMID:23951087

Zhang, Songen; Rahman, Milladur; Zhang, Su; Song, Lei; Herwald, Heiko; Thorlacius, Henrik

2013-01-01

172

Targeting Rac1 Signaling Inhibits Streptococcal M1 Protein-Induced CXC Chemokine Formation, Neutrophil Infiltration and Lung Injury  

PubMed Central

Infections with Streptococcus pyogenes exhibit a wide spectrum of infections ranging from mild pharyngitis to severe Streptococcal toxic shock syndrome (STSS). The M1 serotype of Streptococcus pyogenes is most commonly associated with STSS. In the present study, we hypothesized that Rac1 signaling might regulate M1 protein-induced lung injury. We studied the effect of a Rac1 inhibitor (NSC23766) on M1 protein-provoked pulmonary injury. Male C57BL/6 mice received NSC23766 prior to M1 protein challenge. Bronchoalveolar fluid and lung tissue were harvested for quantification of neutrophil recruitment, edema and CXC chemokine formation. Neutrophil expression of Mac-1 was quantified by use of flow cytometry. Quantitative RT-PCR was used to determine gene expression of CXC chemokines in alveolar macrophages. Treatment with NSC23766 decreased M1 protein-induced neutrophil infiltration, edema formation and tissue injury in the lung. M1 protein challenge markedly enhanced Mac-1 expression on neutrophils and CXC chemokine levels in the lung. Inhibition of Rac1 activity had no effect on M1 protein-induced expression of Mac-1 on neutrophils. However, Rac1 inhibition markedly decreased M1 protein-evoked formation of CXC chemokines in the lung. Moreover, NSC23766 completely inhibited M1 protein-provoked gene expression of CXC chemokines in alveolar macrophages. We conclude that these novel results suggest that Rac1 signaling is a significant regulator of neutrophil infiltration and CXC chemokine production in the lung. Thus, targeting Rac1 activity might be a potent strategy to attenuate streptococcal M1 protein-triggered acute lung damage. PMID:23951087

Zhang, Songen; Rahman, Milladur; Zhang, Su; Song, Lei; Herwald, Heiko; Thorlacius, Henrik

2013-01-01

173

Induced expression and functional effects of aquaporin-1 in human leukocytes in sepsis  

PubMed Central

Introduction Gene expression profiling was performed via DNA microarrays in leukocytes from critically ill trauma patients nonseptic upon admission to the ICU, who subsequently developed either sepsis (n = 2) or severe sepsis and acute respiratory distress syndrome (n = 3). By comparing our results with published expression profiling studies in animal models of sepsis and lung injury, we found aquaporin-1 to be differentially expressed across all studies. Our aim was to determine how the water channel aquaporin-1 is involved in regulating the immune response in critically ill patients during infection acquired in the ICU. Methods Following the results of the initial genetic screening study, we prospectively followed aquaporin-1 leukocyte expression patterns in patients with ICU-acquired sepsis who subsequently developed septic shock (n = 16) versus critically ill patients who were discharged without developing sepsis (n = 13). We additionally determined aquaporin-1 expression upon lipopolysaccharide (LPS) exposure and explored functional effects of aquaporin-1 induction in polymorphonuclear granulocytes (PMNs). Results Leukocyte aquaporin-1 expression was induced at the onset of sepsis (median 1.71-fold increase; interquartile range: 0.99 to 2.42, P = 0.012 from baseline) and was further increased upon septic shock (median 3.00-fold increase; interquartile range: 1.20 to 5.40, P = 0.023 from sepsis, Wilcoxon signed-rank test); no difference was observed between baseline and discharge in patients who did not develop sepsis. Stimulation of PMNs by LPS led to increased expression of aquaporin-1 in vitro, which could be abrogated by the NF-?B inhibitor EF-24. PMN hypotonic challenge resulted in a transient increase of the relative cell volume, which returned to baseline after 600 seconds, while incubation in the presence of LPS resulted in persistently increased cell volume. The latter could be abolished by blocking aquaporin-1 with mercury and restored by incubation in ?-mercaptoethanol, which abrogated the action of mercury inhibition. Conclusions Aquaporin-1 is induced in leukocytes of patients with ICU-acquired sepsis and exhibits higher expression in septic shock. This phenomenon may be due to LPS-triggered NF-?B activation that can also lead to alterations in plasma membrane permeability. PMID:24028651

2013-01-01

174

Sepsis-Associated Disseminated Intravascular Coagulation and Thromboembolic Disease  

PubMed Central

Sepsis is almost invariably associated with haemostatic abnormalities ranging from subclinical activation of blood coagulation (hypercoagulability), which may contribute to localized venous thromboembolism, to acute disseminated intravascular coagulation (DIC), characterized by massive thrombin formation and widespread microvascular thrombosis, partly responsible of the multiple organ dysfunction syndrome (MODS), and subsequent consumption of platelets and coagulation proteins causing, in most severe cases, bleeding manifestations. There is general agreement that the key event underlying this life-threatening sepsis complication is the overwhelming inflammatory host response to the infectious agent leading to the overexpression of inflammatory mediators. Mechanistically, the latter, together with the micro-organism and its derivatives, causes DIC by 1) up-regulation of procoagulant molecules, primarily tissue factor (TF), which is produced mainly by stimulated monocytes-macrophages and by specific cells in target tissues; 2) impairment of physiological anticoagulant pathways (antithrombin, protein C pathway, tissue factor pathway inhibitor), which is orchestrated mainly by dysfunctional endothelial cells (ECs); and 3) suppression of fibrinolysis due to increased plasminogen activator inhibitor-1 (PAI-1) by ECs and likely also to thrombin-mediated activation of thrombin-activatable fibrinolysis inhibitor (TAFI). Notably, clotting enzymes non only lead to microvascular thrombosis but can also elicit cellular responses that amplify the inflammatory reactions. Inflammatory mediators can also cause, directly or indirectly, cell apoptosis or necrosis and recent evidence indicates that products released from dead cells, such as nuclear proteins (particularly extracellular histones), are able to propagate further inflammation, coagulation, cell death and MODS. These insights into the pathogenetic mechanisms of DIC and MODS may have important implications for the development of new therapeutic agents that could be potentially useful particularly for the management of severe sepsis. PMID:21415977

Semeraro, Nicola; Ammollo, Concetta T.; Semeraro, Fabrizio; Colucci, Mario

2010-01-01

175

Antibiotic resistance patterns in invasive group B streptococcal isolates.  

PubMed

Antibiotics are used for both group B streptococcal (GBS) prevention and treatment. Active population-based surveillance for invasive GBS disease was conducted in four states during 1996-2003. Of 3813 case-isolates, 91.0% (3471) were serotyped, 77.1% (2937) had susceptibility testing, and 46.6% (3471) had both. All were sensitive to penicillin, ampicillin, cefazolin, cefotaxime, and vancomycin. Clindamycin and erythromycin resistance was 12.7% and 25.6%, respectively, and associated with serotype V (P < .001). Clindamycin resistance increased from 10.5% to 15.0% (X(2) for trend 12.70; P < .001); inducible clindamycin resistance was associated with the erm genotype. Erythromycin resistance increased from 15.8% to 32.8% (X(2) for trend 55.46; P < .001). While GBS remains susceptible to beta-lactams, resistance to alternative agents such as erythromycin and clindamycin is an increasing concern. PMID:19223967

Castor, Mei L; Whitney, Cynthia G; Como-Sabetti, Kathryn; Facklam, Richard R; Ferrieri, Patricia; Bartkus, Joanne M; Juni, Billie A; Cieslak, Paul R; Farley, Monica M; Dumas, Nellie B; Schrag, Stephanie J; Lynfield, Ruth

2008-01-01

176

Genetic polymorphisms and sepsis in premature neonates.  

PubMed

Identifying single nucleotide polymorphisms (SNPs) in the genes involved in sepsis may help to clarify the pathophysiology of neonatal sepsis. The aim of this study was to evaluate the relationships between sepsis in pre-term neonates and genes potentially involved in the response to invasion by infectious agents. The study involved 101 pre-term neonates born between June 2008 and May 2012 with a diagnosis of microbiologically confirmed sepsis, 98 pre-term neonates with clinical sepsis and 100 randomly selected, otherwise healthy pre-term neonates born during the study period. During the study, 47 SNPs in 18 candidate genes were genotyped on Guthrie cards using an ABI PRISM 7900 HT Fast real-time and MAssARRAY for nucleic acids instruments. Genotypes CT and TT of rs1143643 (the IL1? gene) and genotype GG of rs2664349GG (the MMP-16 gene) were associated with a significantly increased overall risk of developing sepsis (p?=?0.03, p?=?0.05 and p?=?0.03), whereas genotypes AG of rs4358188 (the BPI gene) and CT of rs1799946 (the DEF?1 gene) were associated with a significantly reduced risk of developing sepsis (p?=?0.05 for both). Among the patients with bacteriologically confirmed sepsis, only genotype GG of rs2664349 (the MMP-16 gene) showed a significant association with an increased risk (p?=?0.02). Genotypes GG of rs2569190 (the CD14 gene) and AT of rs4073 (the IL8 gene) were associated with a significantly increased risk of developing severe sepsis (p?=?0.05 and p?=?0.01). Genotype AG of rs1800629 (the LTA gene) and genotypes CC and CT of rs1341023 (the BPI gene) were associated with a significantly increased risk of developing Gram-negative sepsis (p?=?0.04, p?=?0.04 and p?=?0.03). These results show that genetic variability seems to play a role in sepsis in pre-term neonates by influencing susceptibility to and the severity of the disease, as well as the risk of having disease due to specific pathogens. PMID:25000179

Esposito, Susanna; Zampiero, Alberto; Pugni, Lorenza; Tabano, Silvia; Pelucchi, Claudio; Ghirardi, Beatrice; Terranova, Leonardo; Miozzo, Monica; Mosca, Fabio; Principi, Nicola

2014-01-01

177

Genetic Polymorphisms and Sepsis in Premature Neonates  

PubMed Central

Identifying single nucleotide polymorphisms (SNPs) in the genes involved in sepsis may help to clarify the pathophysiology of neonatal sepsis. The aim of this study was to evaluate the relationships between sepsis in pre-term neonates and genes potentially involved in the response to invasion by infectious agents. The study involved 101 pre-term neonates born between June 2008 and May 2012 with a diagnosis of microbiologically confirmed sepsis, 98 pre-term neonates with clinical sepsis and 100 randomly selected, otherwise healthy pre-term neonates born during the study period. During the study, 47 SNPs in 18 candidate genes were genotyped on Guthrie cards using an ABI PRISM 7900 HT Fast real-time and MAssARRAY for nucleic acids instruments. Genotypes CT and TT of rs1143643 (the IL1? gene) and genotype GG of rs2664349GG (the MMP-16 gene) were associated with a significantly increased overall risk of developing sepsis (p?=?0.03, p?=?0.05 and p?=?0.03), whereas genotypes AG of rs4358188 (the BPI gene) and CT of rs1799946 (the DEF?1 gene) were associated with a significantly reduced risk of developing sepsis (p?=?0.05 for both). Among the patients with bacteriologically confirmed sepsis, only genotype GG of rs2664349 (the MMP-16 gene) showed a significant association with an increased risk (p?=?0.02). Genotypes GG of rs2569190 (the CD14 gene) and AT of rs4073 (the IL8 gene) were associated with a significantly increased risk of developing severe sepsis (p?=?0.05 and p?=?0.01). Genotype AG of rs1800629 (the LTA gene) and genotypes CC and CT of rs1341023 (the BPI gene) were associated with a significantly increased risk of developing Gram-negative sepsis (p?=?0.04, p?=?0.04 and p?=?0.03). These results show that genetic variability seems to play a role in sepsis in pre-term neonates by influencing susceptibility to and the severity of the disease, as well as the risk of having disease due to specific pathogens. PMID:25000179

Esposito, Susanna; Zampiero, Alberto; Pugni, Lorenza; Tabano, Silvia; Pelucchi, Claudio; Ghirardi, Beatrice; Terranova, Leonardo; Miozzo, Monica; Mosca, Fabio; Principi, Nicola

2014-01-01

178

Endothelial activation and dysfunction in sepsis  

Microsoft Academic Search

\\u000a Severe sepsis is a major cause of morbidity and mortality worldwide. Recent advances in our understanding of the pathophysiology\\u000a of sepsis have emphasized the pivotal role of the innate immune system in the development of a deleterious host response to\\u000a bacterial infection. It is now recognized that the endothelium is an important effector cell of the innate immune system.\\u000a This

John M. Harlan

179

Pseudomonas sepsis with Noma: an association?  

PubMed

We report here a 2.5-year-old male child with community-acquired Pseudomonal sepsis showing the characteristic lesions of ecthyma gangrenosum. The child had development of gangrenous changes of the nose and face - the 'cancrum oris' or 'Noma'. We highlight the possible association of Pseudomonas sepsis and Noma, with malnutrition playing a central role in causing both the diseases. PMID:16129930

Vaidyanathan, S; Tullu, M S; Lahiri, K R; Deshmukh, C T

2005-08-01

180

Alterations in antigen-specific naive CD4 T cell precursors after sepsis impairs their responsiveness to pathogen challenge.  

PubMed

Patients surviving the acute stages of sepsis develop compromised T cell immunity and increased susceptibility to infection. Little is known about the decreased CD4 T cell function after sepsis. We tracked the loss and recovery of endogenous Ag-specific CD4 T cell populations after cecal ligation and puncture-induced sepsis and analyzed the CD4 T cell response to heterologous infection during or after recovery. We observed that the sepsis-induced early loss of CD4 T cells was followed by thymic-independent numerical recovery in the total CD4 T cell compartment. Despite this numerical recovery, we detected alterations in the composition of naive CD4 T cell precursor pools, with sustained quantitative reductions in some populations. Mice that had experienced sepsis and were then challenged with epitope-bearing, heterologous pathogens demonstrated significantly reduced priming of recovery-impaired Ag-specific CD4 T cell responses, with regard to both magnitude of expansion and functional capacity on a per-cell basis, which also correlated with intrinsic changes in V? clonotype heterogeneity. Our results demonstrate that the recovery of CD4 T cells from sepsis-induced lymphopenia is accompanied by alterations to the composition and function of the Ag-specific CD4 T cell repertoire. PMID:25595784

Cabrera-Perez, Javier; Condotta, Stephanie A; James, Britnie R; Kashem, Sakeen W; Brincks, Erik L; Rai, Deepa; Kucaba, Tamara A; Badovinac, Vladimir P; Griffith, Thomas S

2015-02-15

181

Meningoencephalitis due to adenovirus in a healthy infant mimicking severe bacterial sepsis.  

PubMed

We present the case of a previously healthy 15-month-old girl with acute adenovirus infection who had features of severe bacterial sepsis and meningitis. Real-time qPCR done on cerebrospinal fluid identified adenovirus as the causative agent allowing stopping antibiotic treatment. The patient subsequently recovered without sequelae. An overview of published and unpublished data on adenovirus central nervous system infection in immunocompetent children is presented. PMID:24632664

Reyes-Andrade, Joaquin; Sánchez-Céspedes, Javier; Olbrich, Peter; Falcon, Lola; Sanchez-Ganfornina, Inmaculada; Tebruegge, Marc; Pérez-Romero, Pilar; Neth, Olaf

2014-04-01

182

Another step in improving the diagnosis of disseminated intravascular coagulation in sepsis  

PubMed Central

The diagnosis of disseminated intravascular coagulation (DIC) based on composite scoring systems using routinely available coagulation tests has been greatly facilitated. Such scoring instruments not only adequately assess the presence of DIC but also have strong prognostic power for morbidity and mortality. In this issue of Critical Care, Gando and colleagues report on the prospective validation of the Japanese Association of Acute Medicine score for DIC in patients with severe sepsis. PMID:24103584

2013-01-01

183

Sepsis and Organ(s) Dysfunction — Key Points, Reflections, and Perspectives  

Microsoft Academic Search

Sepsis is one of the main problems in medicine due to its complexity from pathophysiology, clinical, and therapeutic standpoints.\\u000a Although several definitions have been proposed for this syndrome, it can in general be assumed that it represents the clinical\\u000a manifestation of a system response of the body to infection or to an inflammatory-associated acute disease [1,2]. Despite advances in medical

A. Gullo; F. Iscra; F. Rubulotta

184

Leukotriene B4 enhances innate immune defense against the puerperal sepsis agent Streptococcus pyogenes  

PubMed Central

Puerperal sepsis is a leading cause of maternal mortality worldwide. Streptococcus pyogenes (Group A Streptococcus; GAS) is a major etiologic agent of severe postpartum sepsis yet little is known regarding the pathogenesis of these infections. Tissue macrophages provide innate defense against GAS and their actions are highly regulated. The intracellular second messenger cAMP can negatively regulate macrophage actions against GAS. Because leukotriene (LT) B4 has been shown to suppress intracellular cAMP in macrophages, we hypothesized that it could enhance innate defenses against GAS. We assessed the capacity of LTB4 to modulate anti-streptococcal actions of human macrophages, including placental and decidual macrophages and used a novel intrauterine infection model of GAS in mice lacking the 5-lipoxygenase (5LO) enzyme to determine the role of endogenous LTs in host defense against this pathogen. Animals lacking 5LO were significantly more vulnerable to intrauterine GAS infection than wild-type mice and showed enhanced dissemination of bacteria out of the uterus and a more robust inflammatory response compared to wild-type mice. Additionally, LTB4 reduced intracellular cAMP levels via the BLT1 receptor and was a potent stimulant of macrophage phagocytosis and NADPH oxidase-dependent intracellular killing of GAS. Importantly, interference was observed between the macrophage immunomodulatory actions of LTB4 and the cAMP-inducing lipid prostaglandin E2, suggesting that interplay between pro- and anti-inflammatory compounds may be important in vivo. This work underscores the potential for pharmacological targeting of lipid mediator signaling cascades in the treatment of invasive GAS infections. PMID:23325886

Soares, Elyara M.; Mason, Katie L.; Rogers, Lisa M.; Serezani, Carlos H.; Faccioli, Lucia H.; Aronoff, David M.

2012-01-01

185

Staphylococcus aureus Sepsis Induces Early Renal Mitochondrial DNA Repair and Mitochondrial Biogenesis in Mice  

PubMed Central

Acute kidney injury (AKI) contributes to the high morbidity and mortality of multi-system organ failure in sepsis. However, recovery of renal function after sepsis-induced AKI suggests active repair of energy-producing pathways. Here, we tested the hypothesis in mice that Staphyloccocus aureus sepsis damages mitochondrial DNA (mtDNA) in the kidney and activates mtDNA repair and mitochondrial biogenesis. Sepsis was induced in wild-type C57Bl/6J and Cox-8 Gfp-tagged mitochondrial-reporter mice via intraperitoneal fibrin clots embedded with S. aureus. Kidneys from surviving mice were harvested at time zero (control), 24, or 48 hours after infection and evaluated for renal inflammation, oxidative stress markers, mtDNA content, and mitochondrial biogenesis markers, and OGG1 and UDG mitochondrial DNA repair enzymes. We examined the kidneys of the mitochondrial reporter mice for changes in staining density and distribution. S. aureus sepsis induced sharp amplification of renal Tnf, Il-10, and Ngal mRNAs with decreased renal mtDNA content and increased tubular and glomerular cell death and accumulation of protein carbonyls and 8-OHdG. Subsequently, mtDNA repair and mitochondrial biogenesis was evidenced by elevated OGG1 levels and significant increases in NRF-1, NRF-2, and mtTFA expression. Overall, renal mitochondrial mass, tracked by citrate synthase mRNA and protein, increased in parallel with changes in mitochondrial GFP-fluorescence especially in proximal tubules in the renal cortex and medulla. Sub-lethal S. aureus sepsis thus induces widespread renal mitochondrial damage that triggers the induction of the renal mtDNA repair protein, OGG1, and mitochondrial biogenesis as a conspicuous resolution mechanism after systemic bacterial infection. PMID:24988481

Bartz, Raquel R.; Fu, Ping; Suliman, Hagir B.; Crowley, Stephen D.; MacGarvey, Nancy Chou; Welty-Wolf, Karen; Piantadosi, Claude A.

2014-01-01

186

CECAL LIGATION AND PUNCTURE INDUCED MURINE SEPSIS DOES NOT CAUSE LUNG INJURY  

PubMed Central

Objective The cause of death in murine models of sepsis remains unclear. The primary purpose of this study was to determine if significant lung injury develops in mice predicted to die following cecal ligation and puncture induced sepsis compared to those predicted to live. Design Prospective, laboratory controlled experiments. Setting University research laboratory. Subjects Adult, female, outbred ICR mice. Interventions Mice underwent cecal ligation and puncture (CLP) to induce sepsis. Two groups of mice were sacrificed at 24 and 48 hours post-CLP and samples were collected. These mice were further stratified into groups predicted to die (Die-P) and predicted to live (Live-P) based on plasma interleukin 6 (IL-6) levels obtained 24 hours post-CLP. Multiple measures of lung inflammation and lung injury were quantified in these two groups. Results from a group of mice receiving intratracheal normal saline without surgical intervention were also included as a negative control. As a positive control, bacterial pneumonia was induced with Pseudomonas aeruginosa to cause definitive lung injury. Separate mice were followed for survival until day 28 post-CLP. These mice were used to verify the IL-6 cut-offs for survival prediction. Measurements and Main Results Following sepsis, both the Die-P and Live-P mice had significantly suppressed measures of respiratory physiology but maintained normal levels of arterial oxygen saturation. Bronchoalveolar lavage (BAL) levels of pro and anti-inflammatory cytokines were not elevated in the Die-P mice compared to the Live-P. Additionally, there was no increase in the recruitment of neutrophils to the lung, pulmonary vascular permeability, or histological evidence of damage. In contrast, all of these pulmonary injury and inflammatory parameters were increased in mice with Pseudomonas pneumonia. Conclusions These data demonstrate that mice predicted to die during sepsis have no significant lung injury. In murine intra-abdominal sepsis, pulmonary injury cannot be considered the etiology of death in the acute phase. PMID:23222255

Iskander, Kendra N.; Craciun, Florin L.; Stepien, David M.; Duffy, Elizabeth R.; Kim, Jiyoun; Moitra, Rituparna; Vaickus, Louis J.; Osuchowski, Marcin F.; Remick, Daniel G.

2012-01-01

187

Use of intravenous immunoglobulin therapy in the treatment of septic shock, in particular severe invasive group A streptococcal disease  

PubMed Central

Group A streptococcus (GAS) is a ?-hemolytic bacterium often found in the throat and skin. The two most severe clinical manifestations of GAS are streptococcal toxic shock syndrome and necrotizing fasciitis. Intravenous immunoglobulin (IVIg) is a gamma globulin made from purified pooled plasma of thousands of donors, consisting mainly of IgG. We report the case of a 40-year-old man admitted after 2 days of vomiting and severe right-sided chest pain. He was hypotensive with a sinus tachycardia, pyrexial, and vasodilated. The only other positive finding was a swollen and erythematous chest wall. Muscle layer biopsies and blood cultures soon grew extensive GAS, and an initial diagnosis of necrotizing fasciitis was made. The clinical syndrome was of severe septic shock secondary to invasive GAS. The patient quickly deteriorated with a worsening metabolic acidosis. Despite maximal intensive care therapy including fluids, vasoactive agents, and also activated protein C, the patient continued to remain profoundly hypotensive. A decision was made to commence IVIg, with the aim of immunomodulation of the inflammatory cascade seen in sepsis. Over the next 24 hours the patient improved, was extubated 3 days later, and subsequently discharged from hospital after 2 weeks. Although the evidence for the use of IVIg in severe invasive GAS disease is limited, we feel that on reviewing the available literature its use in this case was justified. The limited worldwide supply and high costs, together with a limited evidence base, warrant restricting its use to cases in which conventional therapy has failed. The literature for use of intravenous immunoglobulin in invasive GAS infection will be reviewed in this article. PMID:22557832

Raithatha, Ajay H.; Bryden, Daniele C.

2012-01-01

188

Rolipram Improves Renal Perfusion and Function during Sepsis in the Mouse  

PubMed Central

Microcirculatory dysfunction is correlated with increased mortality among septic patients and is believed to be a major contributor to the development of acute kidney injury (AKI). Rolipram, a selective phosphodiesterase 4 (PDE4) inhibitor, has been shown to reduce microvascular permeability and in the kidney, increase renal blood flow (RBF). This led us to investigate its potential to improve the renal microcirculation and preserve renal function during sepsis using a murine cecal ligation and puncture (CLP) model to induce sepsis. Rolipram, tested at doses of 0.3–10 mg/kg i.p., acutely restored capillary perfusion in a bell-shaped dose-response effect with 1 mg/kg being the lowest most efficacious dose. This dose also acutely increased RBF despite transiently decreasing mean arterial pressure. Rolipram also reduced renal microvascular permeability. It is noteworthy that delayed treatment with rolipram at 6 hours after CLP restored the renal microcirculation, reduced blood urea nitrogen and serum creatinine, and increased glomerular filtration rate at 18 hours. However, delayed treatment with rolipram did not reduce serum nitrate/nitrite levels, a marker of nitric oxide production, nor reactive nitrogen species generation in renal tubules. These data show that restoring the microcirculation with rolipram, even with delayed treatment, is enough to improve renal function during sepsis despite the generation of oxidants and suggest that PDE4 inhibitors should be evaluated further for their ability to treat septic-induced AKI. PMID:24018639

Holthoff, Joseph H.; Wang, Zhen; Patil, Naeem K.; Gokden, Neriman

2013-01-01

189

Identification of four novel serum protein biomarkers in sepsis patients encoded by target genes of sepsis-related miRNAs  

PubMed Central

The goal of the present study was to identify novel protein biomarkers from the target genes of six serum miRNAs that we identified previously in patients with sepsis. The target genes were predicted by bioinformatics analysis; the levels of the respective proteins in the sera of patients with sepsis were detected by ELISA. ACVR2A (activin A receptor, type IIA), FOXO1 (forkhead box O1), IHH (Indian hedgehog), STK4 (serine/threonine kinase 4) and DUSP3 (dual specificity phosphatase 3) were predicted to be the targets of the six miRNAs, and their encoded proteins were used for biomarker identification. Levels of ACVR2A (P<0.01) and FOXO1 (P<0.01) were significantly different among normal controls, patients with sepsis, patients with severe sepsis and patients with septic shock. Furthermore, levels of ACVR2A (P=0.025), FOXO1 (P<0.001), IHH (P=0.001) and STK4 (P=0.001) were differentially expressed in survivors and non-survivors. DUSP3 levels were not significantly different between any groups. Conjoin analysis of the four differentially expressed proteins showed that the area under the curve of the predictive probabilities was 0.875 [95% CI (confidence interval): 0.785–0.965], which was higher than the SOFA (Sequential Organ Failure Assessment) and APACHE II (Acute Physiology and Chronic Health Evaluation II) scores. When the value of predictive probabilities was 0.449, the four proteins yielded a sensitivity of 68% and a specificity of 91%. Dynamic changes in ACVR2A, FOXO1 and IHH levels showed differential expression between survivors and non-survivors at all time points. On the basis of a combined analysis of the four identified proteins, their predictive value of 28-day mortality of patients with sepsis was better than the SOFA or APACHE II scores. PMID:24303815

Wang, Hui-juan; Wang, Bao-zeng; Zhang, Peng-jun; Deng, Jie; Zhao, Zhi-rui; Zhang, Xin; Xiao, Kun; Feng, Dan; Jia, Yan-hong

2013-01-01

190

Burkholderia cepacia sepsis among neonates.  

PubMed

Burkholderia cepacia is a rare cause of sepsis in newborns and its transmission involves human contact with heavily contaminated medical devices and disinfectants. The authors aimed to determine epidemiology, clinical features, antibiotic sensitivity pattern, complications and outcome of blood culture proven B. cepacia infections in 12 neonates. All neonates were outborn, 5 preterm and 7 term. B. cepacia was isolated from blood in all and concurrently from CSF in three neonates. Lethargy and respiratory distress (41.7 %) were major presenting features. Five newborns (41.7 %) required mechanical ventilation for 3-7 d. Highest bacterial susceptibility was observed for meropenem (100 %), followed by cefoperazone-sulbactam, piperacillin-tazobactam, sulfamethoxazole-trimethoprim (all 83 %), ceftazidime (75 %) and ciprofloxacin (42 %). Piperacillin-tazobactam, ciprofloxacin and cotrimoxazole either singly or in combination led to complete recovery of 11 (91.7 %) newborns; one developed hydrocephalus. Eight of nine infants who completed 6 mo follow up were normal. Prompt recognition and appropriate antibiotic therapy for B. cepacia infection results in complete recovery in majority. PMID:24871076

Patra, Saikat; Bhat Y, Ramesh; Lewis, Leslie Edward; Purakayastha, Jayashree; Sivaramaraju, V Vamsi; Kalwaje E, Vandana; Mishra, Swathi

2014-11-01

191

Chronic Medical Conditions and Risk of Sepsis  

PubMed Central

Background We sought to determine the associations between baseline chronic medical conditions and future risk of sepsis. Methods Longitudinal cohort study using the 30,239 community-dwelling participants of the REGARDS cohort. We determined associations between baseline chronic medical conditions and incident sepsis episodes, defined as hospitalization for an infection with the presence of infection plus two or more systemic inflammatory response syndrome criteria. Results Over the mean observation time of 4.6 years (February 5, 2003 through October 14, 2011), there were 975 incident cases of sepsis. Incident sepsis episodes were associated with older age (p<0.001), white race (HR 1.39; 95% CI: 1.22–1.59), lower education (p<0.001) and income (p<0.001), tobacco use (p<0.001), and alcohol use (p?=?0.02). Incident sepsis episodes were associated with baseline chronic lung disease (adjusted HR 2.43; 95% CI: 2.05–2.86), peripheral artery disease (2.16; 1.58–2.95), chronic kidney disease (1.99; 1.73–2.29), myocardial infarction 1.79 (1.49–2.15), diabetes 1.78 (1.53–2.07), stroke 1.67 (1.34–2.07), deep vein thrombosis 1.63 (1.29–2.06), coronary artery disease 1.61 (1.38–1.87), hypertension 1.49 (1.29–1.74), atrial fibrillation 1.48 (1.21–1.81) and dyslipidemia 1.16 (1.01–1.34). Sepsis risk increased with the number of chronic medical conditions (p<0.001). Conclusions Individuals with chronic medical conditions are at increased risk of future sepsis events. PMID:23118977

Wang, Henry E.; Shapiro, Nathan I.; Griffin, Russell; Safford, Monika M.; Judd, Suzanne; Howard, George

2012-01-01

192

Comparing the effect of hydroxyethyl starch 130\\/0.4 with balanced crystalloid solution on mortality and kidney failure in patients with severe sepsis (6S - Scandinavian Starch for Severe Sepsis\\/Septic Shock trial): Study protocol, design and rationale for a double-blinded, randomised clinical trial  

Microsoft Academic Search

BACKGROUND: By tradition colloid solutions have been used to obtain fast circulatory stabilisation in shock, but high molecular weight hydroxyethyl starch (HES) may cause acute kidney failure in patients with severe sepsis. Now lower molecular weight HES 130\\/0.4 is the preferred colloid in Scandinavian intensive care units (ICUs) and 1st choice fluid for patients with severe sepsis. However, HES 130\\/0.4

Anders Perner; Nicolai Haase; Jørn Wetterslev; Anders Åneman; Jyrki Tenhunen; Anne Berit Guttormsen; Gudmundur Klemenzson; Frank Pott; Karen Doris Bødker; Per Martin Bådstøløkken; Asger Bendtsen; Peter Søe-Jensen; Hamid Tousi; Morten Bestle; Malgorzata Pawlowicz; Robert Winding; Hans-Henrik Bülow; Claude Kancir; Morten Steensen; Jonas Nielsen; Bjarne Fogh; Kristian R Madsen; Nils H Larsen; Marcela Carlsson; Jørgen Wiis; John Asger Petersen; Susanne Iversen; Ole Schøidt; Siv Leivdal; Pawel Berezowicz; Ville Pettilä; Esko Ruokonen; Pål Klepstad; Sari Karlsson; Maija Kaukonen; Juha Rutanen; Sigurbergur Karason; Anne Lene Kjældgaard; Lars Broksø Holst; Jan Wernerman

2011-01-01

193

Brazilian Sepsis Epidemiological Study (BASES study)  

PubMed Central

Introduction Consistent data about the incidence and outcome of sepsis in Latin American intensive care units (ICUs), including Brazil, are lacking. This study was designed to verify the actual incidence density and outcome of sepsis in Brazilian ICUs. We also assessed the association between the Consensus Conference criteria and outcome Methods This is a multicenter observational cohort study performed in five private and public, mixed ICUs from two different regions of Brazil. We prospectively followed 1383 adult patients consecutively admitted to those ICUs from May 2001 to January 2002, until their discharge, 28th day of stay, or death. For all patients we collected the following data at ICU admission: age, gender, hospital and ICU admission diagnosis, APACHE II score, and associated underlying diseases. During the following days, we looked for systemic inflammatory response syndrome (SIRS), sepsis, severe sepsis, and septic shock criteria, as well as recording the sequential organ failure assessment score. Infection was diagnosed according to CDC criteria for nosocomial infection, and for community-acquired infection, clinical, radiological and microbiological parameters were used. Results For the whole cohort, median age was 65.2 years (49–76), median length of stay was 2 days (1–6), and the overall 28-day mortality rate was 21.8%. Considering 1383 patients, the incidence density rates for sepsis, severe sepsis and septic shock were 61.4, 35.6 and 30.0 per 1000 patient-days, respectively. The mortality rate of patients with SIRS, sepsis, severe sepsis and septic shock increased progressively from 24.3% to 34.7%, 47.3% and 52.2%, respectively. For patients with SIRS without infection the mortality rate was 11.3%. The main source of infection was lung/respiratory tract. Conclusion Our preliminary data suggest that sepsis is a major public health problem in Brazilian ICUs, with an incidence density about 57 per 1000 patient-days. Moreover, there was a close association between ACCP/SCCM categories and mortality rate. PMID:15312226

Silva, Eliézer; Pedro, Marcelo de Almeida; Sogayar, Ana Cristina Beltrami; Mohovic, Tatiana; Silva, Carla Lika de Oliveira; Janiszewski, Mariano; Cal, Ruy Guilherme Rodrigues; de Sousa, Érica Fernandes; Abe, Thereza Phitoe; de Andrade, Joel; de Matos, Jorge Dias; Rezende, Ederlon; Assunção, Murillo; Avezum, Álvaro; Rocha, Patrícia CS; de Matos, Gustavo Faissol Janot; Bento, André Moreira; Corrêa, Alice Danielli; Vieira, Paulo Cesar Bastos; Knobel, Elias

2004-01-01

194

Elevated Cardiac Troponin I in Sepsis and Septic Shock: No Evidence for Thrombus Associated Myocardial Necrosis  

PubMed Central

Background Elevated cardiac troponin I (cTnI) is frequently observed in patients with severe sepsis and septic shock. However, the mechanisms underlying cTnI release in these patients are still unknown. To date no data regarding coagulation disturbances as a possible mechanism for cTnI release during sepsis are available. Methodology/Principal Findings Consecutive patients with systemic inflammatory response syndrome (SIRS), sepsis or septic shock without evidence of an acute coronary syndrome were analyzed. Coagulation parameters (clotting time (CT), clot formation time (CFT), maximum clot firmness (MCF), ?-angle) were assessed in native whole blood samples, and using specific activators to evaluate the extrinsic and intrinsic as well as the fibrin component of the coagulation pathway with the use of rotational thrombelastometry (ROTEM). Thirty-eight patients were included and 22 (58%) were cTnI-positive. Baseline characteristics between TnI-positive and -negative patients were similar. The CT, CFT, MCF and the ?-angle were similar between the groups with trends towards shorter CT in the extrinsic and fibrin activation. Conclusions/Significance We found no differences in coagulation parameters analyzed with rotational thrombelastometry between cTnI-positive and -negative patients with SIRS, severe sepsis, and septic shock. These findings suggest that pathophysiological mechanisms other than thrombus-associated myocardial damage might play a major role, including reversible myocardial membrane leakage and/or cytokine mediated apoptosis in these patients. PMID:20140242

Altmann, David R.; Korte, Wolfgang; Maeder, Micha T.; Fehr, Thomas; Haager, Philipp; Rickli, Hans; Kleger, Gian-Reto; Rodriguez, Regulo; Ammann, Peter

2010-01-01

195

Novel targets for sepsis-induced kidney injury: the glomerular arterioles and the sympathetic nervous system.  

PubMed

Sepsis and septic shock are the most common causes of acute kidney injury (AKI) in the intensive care unit, and mortality remains high despite improvements in our ability to support vital organs. The lack of development of effective treatments is partly because there has been little advance in our understanding of the pathophysiology of septic AKI, owing to the difficulty in conducting experiments on critically ill patients and use of inappropriate experimental models. Recently, however, a number of new concepts have emerged that challenge existing dogma and give insights into the causes of AKI. Traditionally, renal ischaemia has been proposed as the main cause of AKI, but it is becoming apparent that in sepsis with a hyperdynamic circulation, the most common situation in septic patients, there is an increase or at least no decrease in renal blood flow. In this review, the possible role of changes in pre- and postglomerular resistance in setting the increased level of renal blood flow in the presence of a decreased glomerular filtration rate is discussed. New evidence also indicates that the increased sympathetic nerve activity that occurs in sepsis may contribute to the induction of organ failure. Experimental studies indicate that inhibition of central sympathetic outflow with ?(2)-adrenoceptor agonists or treatment with ?(1)-adrenoceptor antagonists might reduce mortality in experimental endotoxaemia and sepsis. The possibility that these beneficial actions are partly dependent on a reduction in the excessive cytokine release caused by marked and prolonged sympathetic activation is discussed. PMID:22689445

May, Clive N; Calzavacca, Paolo; Ishikawa, Ken; Langenberg, Christoph; Wan, Li; Ramchandra, Rohit; Bellomo, Rinaldo

2012-11-01

196

Effects of sepsis on neonatal thrombopoiesis.  

PubMed

We serially evaluated the effects of sepsis and/or necrotizing enterocolitis (NEC) on neonatal thrombopoiesis, using a panel of tests that included platelet counts, thrombopoietin concentrations (Tpo), circulating megakaryocyte progenitor concentrations (CMPs), and reticulated platelets (RPs). Variables analyzed included sepsis type, time after onset of sepsis, platelet counts, and gestational (GA) and postconceptional ages (PCA). Twenty neonates were enrolled. Ten had Gram-negative, six had Gram-positive, and four had presumed sepsis. Four neonates had NEC stage II or higher, and six developed thrombocytopenia. Overall, septic neonates had significantly elevated Tpo concentrations and circulating megakaryocyte progenitors. The highest Tpo levels were associated with Gram-negative or presumed sepsis. RP percentages were increased only in neonates with low platelet counts, while RP counts (RP% x platelet count) were elevated in neonates with high platelet counts. Our findings suggest that septic neonates up-regulate Tpo production, leading to increased megakaryocytopoiesis and platelet release, although the degree of upregulation is moderate. The changes in RP% and RP count most likely reflect increased thrombopoiesis with variable degrees of platelet consumption. In addition, our findings suggest that different factors, likely including level of illness and/or specific platelet or bacterial products, can down-regulate the magnitude of the thrombopoietic response. PMID:18552713

Brown, Rachel E; Rimsza, Lisa M; Pastos, Karen; Young, Linda; Saxonhouse, Matthew A; Bailey, Matthew; Lawrence, Robert M; Sola-Visner, Martha C

2008-10-01

197

Role of immunoglobulins in neonatal sepsis  

PubMed Central

Neonates, especially VLBW, are at high risk for sepsis related morbidity and mortality for immaturity of their immune system and invasive NICU practices. The paucity of immunoglobulins in preterm neonates consequently to the immaturity of immune system contributes to their high risk for systemic infection. The use of intravenous IgM enriched immunoglobulins, with higher antimicrobial activity than standard IgG, has been demonstrated in a retrospective study to reduce short term mortality in VLBW infant with proven sepsis. Larger, randomized prospective trials given the enormous burden of morbidity and mortality imposed by neonatal sepsis should urgently be addressed not only to validate this results but also to tailor the optimal scheme of treatment. PMID:25674546

Capasso, L; Borrelli, AC; Cerullo, J; Pisanti, R; Figliuolo, C; Izzo, F; Paccone, M; Ferrara, T; Lama, S; Raimondi, F

2015-01-01

198

Nociceptin system as a target in sepsis?  

PubMed

The nociceptin system comprises the nociceptin receptor (NOP) and the ligand nociceptin/orphanin FQ (N/OFQ) that binds to the receptor. The archetypal role of the system is in pain processing but the NOP receptor is also expressed on immune cells. Activation of the NOP receptor is known to modulate inflammatory responses, such as mast-cell degranulation, neutrophil rolling, vasodilation, increased vascular permeability, adhesion molecule regulation and leucocyte recruitment. As there is a loss of regulation of inflammatory responses during sepsis, the nociceptin system could be a target for therapies aimed at modulating sepsis. This review details the known effects of NOP activation on leucocytes and the vascular endothelium and discusses the most recent human and animal data on the role of the nociceptin system in sepsis. PMID:24728719

Thomas, Róisín; Stover, Cordula; Lambert, David G; Thompson, Jonathan P

2014-10-01

199

Hepatic Fibrosis in a Long-term Murine Model of Sepsis.  

PubMed

Chronic sequelae of sepsis represent a major, yet underappreciated clinical problem, contributing to long-term mortality and quality-of-life impairment. In chronic liver disease, inflammation perpetuates fibrogenesis, but development of fibrosis in the post-acute phase of systemic inflammation has not been studied. Therefore, a mouse model of post-acute sequelae of sepsis was established based on polymicrobial peritonitis under antibiotic protection. Survival decreased to approximately 40% within 7 days and remained constant until day 28 (post-acute phase). In survivors, clinical recovery was observed within 1 week, whereas white blood cell and platelet count, as well as markers of liver injury, remained elevated until day 28. Macroscopically, inflammation and abscess formation were detected in the peritoneal space and on/in the liver. Microscopically, acute-chronic inflammation with ductular proliferation, focal granuloma formation in the parenchyma, and substantial hepatic fibrosis were observed. Increased numbers of potentially pathogenetic macrophages and ?-smooth muscle actin-positive cells, presumably activated hepatic stellate cells, were detected in the vicinity of fibrotic areas. Fibrosis was associated with the presence of elastin and an augmented production/deposition of collagen types I and III. Microarray analyses revealed early activation of canonical and noncanonical pathways of hepatic stellate cell transdifferentiation. Thus, chronic sequelae of experimental sepsis were characterized by abscess formation, persistent inflammation, and substantial liver injury and fibrosis, the latter associated with increased numbers of macrophages/?-smooth muscle actin-positive cells and deposition of collagen types I and III. This suggests persistent activation of stellate cells, with consecutive fibrosis-a hallmark of chronic liver disease-as a result of acute life-threatening infection. PMID:22266973

Gonnert, Falk A; Kunisch, Elke; Gajda, Mieczyslaw; Lambeck, Sandro; Weber, Martina; Claus, Ralf A; Bauer, Michael; Kinne, Raimund W

2012-04-01

200

Nonspecific complement activation by streptococcal structures. I. Re- evaluation of HLA cytotoxicity inhibition  

PubMed Central

A number of experiments have suggested that there is an antigenic relationship between the HLA complex and streptococcal bacterial structures. Using inhibition of cytotoxicity of HLA antisera as our assay system, it was demonstrated that the inhibitory effect on HLA cytotoxicity by streptococcal antigens is, in reality, due to activation and consumption of components of the alternate complement pathway. In addition, antisera prepared against streptococcal membrane antigens had no cytotoxic effect on a large panel of human lymphocytes, nor did these antisera exhibit immunofluorescent staining of lymphocytes directly. These experiments are compatible with our concept that the HLA complex may have evolved through selective evolutionary pressure as a means of escaping bacterial mimicry. PMID:818334

1976-01-01

201

Fluid Resuscitation in Sepsis: Reexamining the Paradigm  

PubMed Central

Sepsis results in widespread inflammatory responses altering homeostasis. Associated circulatory abnormalities (peripheral vasodilation, intravascular volume depletion, increased cellular metabolism, and myocardial depression) lead to an imbalance between oxygen delivery and demand, triggering end organ injury and failure. Fluid resuscitation is a key part of treatment, but there is little agreement on choice, amount, and end points for fluid resuscitation. Over the past few years, the safety of some fluid preparations has been questioned. Our paper highlights current concerns, reviews the science behind current practices, and aims to clarify some of the controversies surrounding fluid resuscitation in sepsis. PMID:25180196

Tirupakuzhi Vijayaraghavan, Bharath Kumar; Cove, Matthew Edward

2014-01-01

202

Hemofiltration, adsorption, sieving and the challenge of sepsis therapy design  

Microsoft Academic Search

Circulating inflammatory mediators spilling into the circulation from sites of active inflammation are considered the source of remote tissue injury and associated organ dysfunction in sepsis. Hemofiltration has been proposed as a therapy for sepsis based on its ability to remove circulating inflammatory mediators by sieving or by adsorption, or both. Designing devices and methods for sepsis therapy will require

Patrick M Honoré; James R Matson

2002-01-01

203

Science review: The brain in sepsis – culprit and victim  

Microsoft Academic Search

On one side, brain dysfunction is a poorly explored complication of sepsis. On the other side, brain dysfunction may actively contribute to the pathogenesis of sepsis. The current review aimed at summarizing the current knowledge about the reciprocal interaction between the immune and central nervous systems during sepsis. The immune-brain cross talk takes part in circumventricular organs that, being free

Tarek Sharshar; Nicholas S Hopkinson; David Orlikowski; Djillali Annane

2005-01-01

204

Model for predicting short-term mortality of severe sepsis  

Microsoft Academic Search

INTRODUCTION: To establish a prognostic model for predicting 14-day mortality in ICU patients with severe sepsis overall and according to place of infection acquisition and to sepsis episode number. METHODS: In this prospective multicentre observational study on a multicentre database (OUTCOMEREA) including data from 12 ICUs, 2268 patients with 2737 episodes of severe sepsis were randomly divided into a training

Christophe Adrie; Adrien Francais; Antonio Alvarez-Gonzalez; Roman Mounier; Elie Azoulay; Jean-Ralph Zahar; Christophe Clec'h; Dany Goldgran-Toledano; Laure Hammer; Adrien Descorps-Declere; Samir Jamali; Jean-Francois Timsit

2009-01-01

205

Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections: an overview.  

PubMed

The acronym PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections) has been used to describe a syndrome characterized by various obsessions, compulsions, tics, hyperactivity, motor stereotypies, and paroxysmal movement disorders that are correlated with prior infection by group A beta-hemolytic Streptococcus pyogenes (GABHS) infections. Five clinical criteria can be used to diagnose PANDAS: (1) the presence of obsessive-compulsive disorder (OCD) and/or any other tic disorders; (2) prepuberal onset (between 3 years of age and the start of puberty); (3) abrupt onset and relapsing-remitting symptom course; (4) a distinct association with GABHS infection; and (5) association with neurological abnormalities during exacerbations (adventitious movements or motoric hyperactivity). The exact pathogenesis of PANDAS remains unclear, and several theories that focus on multiple etiologic or contributive factors have emerged. PANDAS appears to be a neurobiological disorder that potentially complicates GABHS infections in genetically susceptible individuals. The current standard of care for PANDAS patients remains symptomatic, and cognitive behavioral therapy, such as exposure and response prevention, combined with family counseling and psychoeducation, should be the first approach for treating PANDAS. This review examines current theories of PANDAS pathogenesis, identifies possible treatments for managing this complex condition, and highlights areas for future research. Moving forward, developing more standardized diagnostic criteria and identifying specific laboratory markers to facilitate PANDAS diagnoses are crucial. PMID:24953744

Esposito, S; Bianchini, S; Baggi, E; Fattizzo, M; Rigante, D

2014-12-01

206

Use of antiplatelet agents in sepsis: a glimpse into the future.  

PubMed

As mechanisms of sepsis pathophysiology have been elucidated with time, sepsis may be considered nowadays, as an uncontrolled inflammatory and pro-coagulant response to a pathogen. In this cascade of events, platelets play a key role, via interaction with endothelial cells and modulation of both innate and adaptive immune system. In that manner, inhibition of platelet function could represent a useful tool for attenuating inflammatory response and improving outcomes. Data on current antiplatelet agents, including acetylsalicylic acid, P2Y12 inhibitors and GPIIb/IIIa antagonists, in animal models are promising. Clinical data in patients hospitalized for pneumonia, at risk for acute lung injury, and/or critically ill revealed an association between antiplatelet therapy and reduction in both short-term mortality and prevalence of acute lung injury, as well as, the need for intensive care unit admission, without a concomitant increased bleeding risk. In need of innovative approach in the treatment of sepsis, further prospective, interventional, randomized trials are pivotal to establish potential use of antiplatelet agents in this context. PMID:24103487

Akinosoglou, Karolina; Alexopoulos, Dimitrios

2014-02-01

207

Plasma adrenomedullin is associated with short-term mortality and vasopressor requirement in patients admitted with sepsis  

PubMed Central

Introduction The incidence of death among patients admitted for severe sepsis or septic shock is high. Adrenomedullin (ADM) plays a central role in initiating the hyperdynamic response during the early stages of sepsis. Pilot studies indicate an association of plasma ADM with the severity of the disease. In the present study we utilized a novel sandwich immunoassay of bioactive plasma ADM in patients hospitalized with sepsis in order to assess the clinical utility. Methods We enrolled 101 consecutive patients admitted to the emergency department with suspected sepsis in this study. Sepsis was defined by fulfillment of at least two systemic inflammatory response syndrome (SIRS) criteria plus clinical suspicion of infection. Plasma samples for ADM measurement were obtained on admission and for the next four days. The 28-day mortality rate was recorded. Results ADM at admission was associated with severity of disease (correlation with Acute Physiology and Chronic Health Evaluation II (APACHE II) score: r?=?0.46; P <0.0001). ADM was also associated with 28-day mortality (ADM median (IQR): survivors: 50 (31 to 77) pg/mL; non-survivors: 84 (48 to 232) pg/mL; P <0.001) and was independent from and additive to APACHE II (P?=?0.02). Cox regression analysis revealed an additive value of serial measurement of ADM over baseline assessment for prediction of 28-day mortality (P?sepsis, severe sepsis or septic shock plasma ADM is strongly associated with severity of disease, vasopressor requirement and 28-day mortality. PMID:24533868

2014-01-01

208

Clinical diagnosis of sepsis and the combined use of biomarkers and culture- and non-culture-based assays.  

PubMed

Sepsis is among the most common causes of death in hospitalized patients, and early recognition followed by immediate initiation of therapy is an important concept to improve survival in these patients. According to the definition of sepsis, diagnosis of sepsis requires the recognition of the systemic inflammatory response syndrome (SIRS) caused by infection as well as recognition of possible infection-related organ dysfunctions for diagnosis of severe sepsis or septic shock. Both SIRS and organ dysfunctions may occur frequently in hospitalized patients for various reasons. However, the fast recognition of acute infection as a cause of SIRS and newly developed organ dysfunction may be a demanding task since culture-based results of microbiological samples will be available only days after onset of symptoms. Biomarkers and PCR-based pathogen detection may help the physician in differentiating SIRS from sepsis. Procalcitonin (PCT) is the best investigated biomarker for this purpose. Furthermore, the current data support the usage of PCT for guidance of antimicrobial therapy. C-reactive protein (CRP) may be used to monitor the course of infection but has only limited discriminative capabilities. Interleukin-6 is widely used for its fast response to the infectious stimulus, but conclusive data for the application of this biomarker are missing. None of the available biomarkers can by itself reliably differentiate SIRS from sepsis but can aid and shorten the decision process. PCR-based pathogen detection can theoretically shorten the recognition of the underlying pathogen to about 8 h. However, this technique is expensive and requires additional staff in the laboratory; controlled prospective studies are missing. Although current studies suggest that PCR-based pathogen detection may be useful to shorten time to adequate antimicrobial therapy and diagnose invasive Candida infections, no general recommendations about the application of PCR for the diagnosis of sepsis can be given. PMID:25319792

Bloos, Frank

2015-01-01

209

New diagnostic strategy for sepsis-induced disseminated intravascular coagulation: a prospective single-center observational study  

PubMed Central

Introduction Inflammation and coagulation are closely interrelated pathophysiologic processes in the pathogenesis of sepsis. However, the diagnostic criteria of sepsis and disseminated intravascular coagulation (DIC) are different. This study aimed to define a biomarker panel to predict sepsis-induced DIC in emergency department patients. Methods Eighty-two patients who were admitted to the emergency department of a tertiary university hospital were included in this study. The inclusion criteria were as follows: (1) age >18 years; (2) ?1 systemic inflammatory response syndrome (SIRS) criteria. Patients were excluded if they lacked biomarker data or apparent clinical manifestations. Eleven biomarkers were assayed from blood drawn on ED admission. Receiver operating curve (ROC) analysis including the area under the ROC and multivariable logistic regression were used to identify an optimal combination of biomarkers to create a diagnostic panel. The derived formula for weighting biomarker values was used to determine the severity of sepsis-induced DIC, which was divided into three categories: mild, moderate, and severe. We also investigated the ability of this classification to predict secondary outcome measures of rates of sepsis and DIC, DIC score, acute physiology and chronic health evaluation (APACHE) II score, sequential organ failure score (SOFA) score, and 28-day all-cause mortality. Results Among the 11 biomarkers tested, the optimal 2-marker panel comprised presepsin and protein C. The area under the curve for the accuracies of predicting sepsis and DIC from these two biomarkers were 0.913 and 0.880, respectively. When patients were divided according to the severity of sepsis-induced DIC, all secondary outcomes except for mortality were significantly higher depending on the severity (P?sepsis-induced DIC were 7.14%, 15.4%, and 28.6%, respectively (P?=?.0994). Conclusions A biomarker panel of presepsin and protein C is predictive of the severity of sepsis-induced DIC in suspected ED patients. These criteria for sepsis-induced DIC are very simple, easy to implement, and can be used in intensive care units as a point-of-care test. PMID:24443891

2014-01-01

210

Group G streptococcal arthritis and bowel disease: a rare enteropathic arthropathy.  

PubMed

Group G streptococci may be seen as normal flora in many parts of the body, including the gastrointestinal tract. They are rarely pathogens in humans, but they have been isolated from septic joints in debilitated patients. Three patients with group G streptococcal arthritis were further evaluated using contrast studies of the colon. Abnormalities, including an occult carcinoma and a colocutaneous fistula, were found. We conclude that group G streptococcal arthritis may be associated with gastrointestinal abnormalities that allow a portal of entry for an otherwise innocuous organism, and that this represents a rare enteropathic arthropathy. PMID:3596149

Trenkner, S W; Braunstein, E M; Lynn, M D; Ike, R W

1987-01-01

211

The role of microglia activation in the development of sepsis-induced long-term cognitive impairment.  

PubMed

Oxidative stress and inflammation is likely to be a major step in the development of sepsis-associated encephalopathy (SAE) and long-term cognitive impairment. To date, it is not known whether brain inflammation and oxidative damage are a direct consequence of systemic inflammation or whether these events are driven by brain resident cells, such as microglia. Therefore, the aim of this study is to evaluate the effect of minocycline on behavioral and neuroinflammatory parameters in rats submitted to sepsis. Male Wistar rats were subjected to sepsis by cecal ligation and puncture (CLP). The animals were divided into sham-operated (Sham+control), sham-operated plus minocycline (sham+MIN), CLP (CLP+control) and CLP plus minocycline (CLP+MIN) (100?g/kg, administered as a single intracerebroventricular (ICV) injection). Some animals were killed 24h after surgery to assess the breakdown of the blood brain barrier, cytokine levels, oxidative damage to lipids (TBARS) and proteins in the hippocampus. Some animals were allowed to recover for 10days when step-down inhibitory avoidance and open-field tasks were performed. Treatment with minocycline prevented an increase in markers of oxidative damage and inflammation in the hippocampus after sepsis. This was associated with an improvement in long-term cognitive performance. In conclusion, we demonstrated that the inhibition of the microglia by an ICV injection of minocycline was able to decrease acute brain oxidative damage and inflammation as well as long-term cognitive impairment in sepsis survivors. PMID:25019583

Michels, Monique; Vieira, Andriele S; Vuolo, Francieli; Zapelini, Hugo Galvane; Mendonça, Bruna; Mina, Francielle; Dominguini, Diogo; Steckert, Amanda; Schuck, Patrícia Fernanda; Quevedo, João; Petronilho, Fabrícia; Dal-Pizzol, Felipe

2015-01-01

212

A qualitative study of GP, NP and patient views about the use of rapid streptococcal antigen detection tests (RADTs) in primary care: ‘swamped with sore throats?’  

PubMed Central

Objective To explore patient and healthcare professionals’ (HCP) views of clinical scores and rapid streptococcal antigen detection tests (RADTs) for acute sore throat. Design Qualitative semistructured interview study. Setting UK primary care. Participants General practitioners (GPs), nurse practitioners (NPs) and patients from general practices across Hampshire, Oxfordshire and the West Midlands who were participating in the Primary Care Streptococcal Management (PRISM) study. Method Semistructured, face-to-face and phone interviews were conducted with GPs, NPs and patients from general practices across Hampshire, Oxfordshire and the West Midlands. Results 51 participants took part in the study. Of these, 42 were HCPs (29 GPs and 13 NPs) and 9 were patients. HCPs could see a positive role for RADTs in terms of reassurance, as an educational tool for patients, and for aiding inexperienced practitioners, but also had major concerns about RADT use in clinical practice. Particular concerns included the validity of the tests (the role of other bacteria, and carrier states), the tension and possible disconnect with clinical assessment and intuition, the issues of time and resource use and the potential for medicalisation of self-limiting illness. In contrast, however, experience of using RADTs over time seemed to make some participants more positive about using the tests. Moreover, patients were much more positive about the place of RADTs in providing reassurance and in limiting their antibiotic use. Conclusions It is unlikely that RADTs will have a (comfortable) place in clinical practice in the near future until health professionals’ concerns are met, and they have direct experience of using them. The routine use of clinical scoring systems for acute upper respiratory illness also face important barriers related to clinicians’ perceptions of their utility in the face of clinician experience and intuition. PMID:23558734

Leydon, Gerry M; McDermott, Lisa; Moore, Mike; Williamson, Ian; Hobbs, F D Richard; Lambton, Tessa; Cooper, Rebecca; Henderson, Hugo; Little, Paul

2013-01-01

213

Postsplenectomy sepsis: Historical background and current concepts  

Microsoft Academic Search

Although most common in infancy and early childhood, susceptibility to postsplenectomy infection is not limited by age or underlying pathological condition. Postsplenectomy sepsis is a fulminant, rapid process which often begins with vague symptoms. Death may follow in hours unless appropriate fluid resuscitation and antibiotic therapy is promptly instituted. Experimental evidence suggests that spienectomy results in a loss of both

Karen W. West; Jay L. Grosfeld

1985-01-01

214

Immunological aspects of severe bacterial sepsis  

Microsoft Academic Search

In spite of discovery of new antibiotics and regular progress in intensive care, mortality from severe bacterial sepsis remains high. In this review the importance of cellular and humoral immunity in the pathogenesis and the outcome of severe infection is delineated. Immunological evaluation of patients in Intensive Care Units should be performed almost routinely in order to detect “high risk”

N. Clumeck; C. George

1981-01-01

215

Role of biomarkers in sepsis care  

PubMed Central

Sepsis is one of the leading causes of mortality and morbidity, even with the current availability of extended spectrum antibiotics and advanced medical care. Biomarkers offer a tool in facilitating early diagnosis, in identifying patient populations at high risk of complications, and in monitoring progression of the disease, which are critical assessments for appropriate therapy and improvement in patient outcomes. Several biomarkers are already available for clinical use in sepsis; however, their effectiveness in many instances is limited by the lack of specificity and sensitivity to characterize the presence of an infection and the complexity of the inflammatory and immune processes, and to stratify patients into homogenous groups for specific treatments. Current advances in molecular techniques have provided new tools facilitating the discovery of novel biomarkers, which can vary from metabolites and chemical products present in body fluids to genes and proteins in circulating blood cells. The purpose of this review is to examine the current status of sepsis biomarkers, with special emphasis on emerging markers, which are undergoing validation and may transition into clinical practice for their informative value in diagnosis, prognosis or response to therapy. We will also discuss the new concept of combination biomarkers and biomarker risk models, their existing challenges, and their potential use in the daily management of the sepsis patients. PMID:24088989

Samraj, Ravi S.; Zingarelli, Basilia; Wong, Hector R.

2013-01-01

216

Pharmacokinetic and pharmacodynamic considerations when treating patients with sepsis and septic shock.  

PubMed

Sepsis and septic shock are accompanied by profound changes in the organism that may alter both the pharmacokinetics and the pharmacodynamics of drugs. This review elaborates on the mechanisms by which sepsis-induced pathophysiological changes may influence pharmacological processes. Drug absorption following intramuscular, subcutaneous, transdermal and oral administration may be reduced due to a decreased perfusion of muscles, skin and splanchnic organs. Compromised tissue perfusion may also affect drug distribution, resulting in a decrease of distribution volume. On the other hand, the increase in capillary permeability and interstitial oedema during sepsis and septic shock may enhance drug distribution. Changes in plasma protein binding, body water, tissue mass and pH may also affect drug distribution. For basic drugs that are bound to the acute phase reactant alpha(1)-acid glycoprotein, the increase in plasma concentration of this protein will result in a decreased distribution volume. The opposite may be observed for drugs that are extensively bound to albumin, as the latter protein decreases during septic conditions. For many drugs, the liver is the main organ for metabolism. The determinants of hepatic clearance of drugs are liver blood flow, drug binding in plasma and the activity of the metabolic enzymes; each of these may be influenced by sepsis and septic shock. For high extraction drugs, clearance is mainly flow-dependent, and sepsis-induced liver hypoperfusion may result in a decreased clearance. For low extraction drugs, clearance is determined by the degree of plasma binding and the activity of the metabolic enzymes. Oxidative metabolism via the cytochrome P450 enzyme system is an important clearance mechanism for many drugs, and has been shown to be markedly affected in septic conditions, resulting in decreased drug clearance. The kidneys are an important excretion pathway for many drugs. Renal failure, which often accompanies sepsis and septic shock, will result in accumulation of both parent drug and its metabolites. Changes in drug effect during septic conditions may theoretically result from changes in pharmacodynamics due to changes in the affinity of the receptor for the drug or alterations in the intrinsic activity at the receptor. The lack of valid pharmacological studies in patients with sepsis and septic shock makes drug administration in these patients a difficult challenge. The patient's underlying pathophysiological condition may guide individual dosage selection, which may be guided by measuring plasma concentration or drug effect. PMID:12405864

De Paepe, Peter; Belpaire, Frans M; Buylaert, Walter A

2002-01-01

217

Factors associated with severe sepsis: prospective study of 94 neutropenic febrile episodes.  

PubMed

Severe sepsis defined as infection-induced organ dysfunction or hypoperfusion abnormalities predispose to septic shock and increased mortality in neutropenic setting. We aimed at determining predictors of severe sepsis in neutropenic patients. Between 1 October and 31 December 2007, 41 patients (21 with acute myeloid leukemia, 19 with acute lymphoid leukemia and one with autologous stem cell transplantation for a mantle cell lymphoma) with chemotherapy-induced neutropenia (<0.5 x 10(9)/l) lasting for more than 7 days were included in this study. The median age was 28 years (range: 3-58 years). All patients were on oral antibacterial (colistin and gentamicin) and anti-fungal (amphotericin B) prophylaxis. The first neutropenic febrile episode was treated with piperacillin/tazobactam and colistin IV; if the patient remains febrile at 48 h from the start of this first line of treatment, amphotericin B i.v. is added. Imipenem was introduced in the case of non-response and finally glycopeptides were introduced according to the IDSA criteria. Severe sepsis and septic shock are defined according to the criteria of the consensus conference of the ACCP/SCCM excluding the leukocyte count since all the patients were neutropenic. Ninety-four febrile episodes were observed: 27 microbiologically documented (28.7%), six clinically documented (6.3%) and 61 fever of unknown origin (65%). Microbiologically documented infections were: 13 Gram-negative organisms, 11 Gram-positive organisms and three combined (Gram+ and -). Clinically documented infections were pneumonia (two), neutropenic enterocolitis (one), sinuses infection (one) and cutaneous infection (two). Severe sepsis accounted for 22 febrile episodes. Factors associated with the occurrence of severe sepsis were: hypophosphatemia (<0.8 mmol/l; p=0.05, OR=3.9, 95% CI: 1.3-45.7), hypoproteinemia (<62 g/l; p=0.006, OR=4.1, 95% CI: 1.4-11.4) and non-adapted antibiotherapy at the onset of severe sepsis (p=0.019, OR=2.7, 95% CI: 1.02-7.39). However, heart rate/systolic blood pressure ratio <1.1 (p<0.001, OR=0.1, 95% CI: 0.03-0.31) and Creactive protein <80 mg (p=0.001, OR=0.14, 95% CI: 0.04-0.54) were not predictive. PMID:20132659

Jeddi, Ramzi; Achour, Mériem; Amor, Ramzi Ben; Aissaoui, Lamia; Bouterâa, Walid; Kacem, Karima; Lakhal, Raihane Ben; Abid, Héla Ben; BelHadjAli, Zaher; Turki, Amel; Meddeb, Balkis

2010-02-01

218

Redox therapy in neonatal sepsis: reasons, targets, strategy, and agents.  

PubMed

Neonatal sepsis is one of the most fulminating conditions in neonatal intensive care units. Antipathogen and supportive care are administered routinely, but do not deliver satisfactory results. In addition, the efforts to treat neonatal sepsis with anti-inflammatory agents have generally shown to be futile. The accumulating data imply that intracellular redox changes intertwined into neonatal sepsis redox cycle represent the main cause of dysfunction of mitochondria and cells in neonatal sepsis. Our aim here is to support the new philosophy in neonatal sepsis treatment, which involves the integration of mechanisms that are responsible for cellular dysfunction and organ failure, the recognition of the most important targets, and the selection of safe agents that can stop the neonatal sepsis redox cycle by hitting the hot spots. Redox-active agents that could be beneficial for neonatal sepsis treatment according to these criteria include lactoferrin, interleukin 10, zinc and selenium supplements, ibuprofen, edaravone, and pentoxifylline. PMID:24827393

Baj?eti?, Milica; Spasi?, Snežana; Spasojevi?, Ivan

2014-09-01

219

New insights into thrombopoiesis in neonatal sepsis.  

PubMed

Thrombocytopenia is one of the most frequent hematologic abnormalities in the neonatal period, affecting about 18-35% of all patients admitted to the Neonatal Intensive Care Unit (NICU), with sepsis being among the most common causes of severe neonatal thrombocytopenia. It is unclear whether decreased platelet production or increased platelet consumption contributes to thrombocytopenia of septic neonates. To answer this question, we evaluated the effects of sepsis on neonatal thrombopoiesis using a panel of tests. This prospective case-control study was conducted on 50 neonates with culture-proven sepsis admitted to NICU at the Pediatrics Department, Ain Shams University Hospitals. Thirty healthy newborns were included as controls. The enrolled neonates were subjected to detailed history taking, thorough clinical examination, and laboratory investigations including complete blood count, C-reactive protein, blood cultures, and tests of thrombopoiesis; namely serum thrombopoietin (TPO) assay, flow cytometric analysis of reticulated platelet percentage (RP%), and calculation of absolute RP counts. Septic neonates comprised 24 males and 26 females with a mean gestational age of 36.0?±?3.1 weeks. Twenty-eight (56%) of the septic neonates were thrombocytopenic (platelets?sepsis had the lowest platelet and RP counts and the highest TPO and RP% followed by those with fungal septicemia. Platelet counts showed inverse correlations with TPO and RP% and direct correlation with RP count. Our findings suggest that neonates respond to sepsis by up-regulating thrombopoiesis, where thrombocytopenia ensues when the rate of platelet consumption exceeds the rate of platelet production. Simultaneous measurements of serum TPO levels and RP% are helpful in discriminating hyperdestructive from hypoplastic thrombocytopenia among septic neonates. PMID:22746320

Eissa, Deena S; El-Farrash, Rania A

2013-01-01

220

IDIOTYPIC SPECIFICITY OF RABBIT ANTIBODIES TO STREPTOCOCCAL GROUP POLYSACCHARIDES  

PubMed Central

Anti-idiotypic antisera against six restricted rabbit streptococcal group specific antibodies have been raised in rabbits matched for allotypes. All these antisera reacted specifically with their homologous idiotypes on double-diffusion tests in agarose gel. In addition, they showed a high incidence of cross-specificities with group-specific hyperimmune sera induced in both closely related and unrelated individuals. These precipitating cross-specificities could be explained for two systems by the interference of rheumatoid factor. Two idiotypic antibody systems have been analyzed in detail; these were restricted antibodies produced in a father and in one of his offspring. The methods employed included binding inhibition of radio-labeled homologous Fab fragments and hemagglutination inhibition with homologous idiotypic coat. The data demonstrated that only related rabbits produced, besides non-cross-reacting antibodies, idiotypically similar antibodies raised to the same antigen. About one-third of the cross-reactive idiotypes showed binding inhibition between 31 and 92%. Inhibition of binding above 50% in the paternal idiotypic system was only achieved by one offspring antibody whereas the F1 progeny idiotypic system was inhibited to this extent by seven antibodies of related rabbits. In contrast, 87.5% and 91.7% of antibodies of unrelated rabbits were less than 20% inhibitory. Within this study two idiotypically identical antibodies have not been found. This implies that A-variant-specific antibodies of related rabbits which produced antipolysaccharide antibodies were structurally different. Cross-reaction, even if greater than 90% by binding inhibition, appears to involve only part and not all of the variable regions. PMID:4200777

Braun, Dietmar G.; Kelus, Andrew S.

1973-01-01

221

Automated electronic medical record sepsis detection in the emergency department  

PubMed Central

Background. While often first treated in the emergency department (ED), identification of sepsis is difficult. Electronic medical record (EMR) clinical decision tools offer a novel strategy for identifying patients with sepsis. The objective of this study was to test the accuracy of an EMR-based, automated sepsis identification system. Methods. We tested an EMR-based sepsis identification tool at a major academic, urban ED with 64,000 annual visits. The EMR system collected vital sign and laboratory test information on all ED patients, triggering a “sepsis alert” for those with ?2 SIRS (systemic inflammatory response syndrome) criteria (fever, tachycardia, tachypnea, leukocytosis) plus ?1 major organ dysfunction (SBP ? 90 mm Hg, lactic acid ?2.0 mg/dL). We confirmed the presence of sepsis through manual review of physician, nursing, and laboratory records. We also reviewed a random selection of ED cases that did not trigger a sepsis alert. We evaluated the diagnostic accuracy of the sepsis identification tool. Results. From January 1 through March 31, 2012, there were 795 automated sepsis alerts. We randomly selected 300 cases without a sepsis alert from the same period. The true prevalence of sepsis was 355/795 (44.7%) among alerts and 0/300 (0%) among non-alerts. The positive predictive value of the sepsis alert was 44.7% (95% CI [41.2–48.2%]). Pneumonia and respiratory infections (38%) and urinary tract infection (32.7%) were the most common infections among the 355 patients with true sepsis (true positives). Among false-positive sepsis alerts, the most common medical conditions were gastrointestinal (26.1%), traumatic (25.7%), and cardiovascular (20.0%) conditions. Rates of hospital admission were: true-positive sepsis alert 91.0%, false-positive alert 83.0%, no sepsis alert 5.7%. Conclusions. This ED EMR-based automated sepsis identification system was able to detect cases with sepsis. Automated EMR-based detection may provide a viable strategy for identifying sepsis in the ED. PMID:24765577

Nguyen, Su Q.; Mwakalindile, Edwin; Booth, James S.; Hogan, Vicki; Morgan, Jordan; Prickett, Charles T.; Donnelly, John P.

2014-01-01

222

Group A streptococcal infections and tic disorders in an Italian pediatric population  

Microsoft Academic Search

Background: The relationship between childhood tic disorders and group A streptococcal (GAS) infections has been recently investigated by several research groups, but no systematic evaluation of laboratory indicators of GAS infections has been provided. Objective: The aim of our study was to seek clinical and laboratory evidence of GAS infections in a large population of children affected with tic disorders.

Francesco Cardona; Graziella Orefici

2001-01-01

223

The natural history of streptococcal skin infection: prevention with topical antibiotics.  

PubMed

An investigation on the natural history of streptococcal skin infection was done in fifty-nine children in a rural day care setting. A double-blind study for prevention of streptococcal pyoderma was done during the peak season for skin infection. Triple antibiotic ointment, containing bacitracin, polysporin, and neomycin, was compared to placebo ointment. Ointments were applied thrice daily for minor skin trauma; mosquito bites and abrasions were predominant. Cultures of normal skin surfaces were taken for group A streptococci each week of the 15-week study period. Skin lesions were cultured whenever present. Eighty-one percent of the fifty-nine patients had positive normal skin cultures on one or more occasions. Nineteen children (32%) developed streptococcal pyoderma. Infection occurred significantly more often in children using placebo ointment than in those using topical antibiotic (47% vs 15%; p = 0.01). The infecting strain was first recovered from normal skin surfaces in 67% of placebo patients and in two of the four patients using antibiotic ointment. This study further confirms the importance of skin carriage of group A streptococci as a precursor to pyoderma and demonstrates the importance of minor skin trauma as a predisposing factor. Topical antibiotics may be useful in preventing streptococcal pyoderma, especially in children known to be at increased risk for such infection. PMID:2995463

Maddox, J S; Ware, J C; Dillon, H C

1985-08-01

224

Paedatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal Infection in an Indian Adolescent--A Case Report  

ERIC Educational Resources Information Center

Pediatric Autoimmune Neuropsychiatric Disorders associated with Streptococcal infection (PANDAS) is a unique constellation of signs and symptoms that exist in a subset of children with rapid onset or exacerbation of obsessive-compulsive disorder (OCD) and/or tic disorders due to an initial autoimmune reaction to a Group A Beta Hemolytic…

Sharma, Sachin; Vaish, Supriya; Chopra, Saurabh; Singh, Vindyaprakash; Sharma, Priyanka

2012-01-01

225

ARTICLE doi:10.1038/nature09967 Streptococcal M1 protein constructs a  

E-print Network

invasive strain of group A Streptococcus, is sufficient to induce toxic-shock-like vascular leakage toxic shock. The M protein1 is the major surface-associated virulence factor of Streptococcus pyogenes invasive diseases with high mortality rates (,30%), such as streptococcal toxic shock syndrome (STSS)2

Nizet, Victor

226

A single streptococcal gene can confer innate immune resistance and virulence to a  

E-print Network

­ streptococcal shuttle vector pDCerm for complementation and heterologous expression. Bacterial phagocyte resistance was assessed by co-incubation with human neutrophils or murine macrophages for 2 h before plating determined as described [7]. The interaction of AMP with bacteria was assessed by co-incubation of strains

Nizet, Victor

227

Milk fat globule EGF factor 8 attenuates sepsis-induced apoptosis and organ injury in alcohol-intoxicated rats  

PubMed Central

Background Despite advances in our understanding of excessive alcohol intake-related tissue injury and modernization of the management of septic patients, high morbidity and mortality due to infectious diseases in alcohol abusers remain a prominent challenge. Our previous studies have shown that milk fat globule epidermal growth factor-factor VIII (MFG-E8), a protein required to opsonize apoptotic cells for phagocytosis, is protective in inflammation. However, it remains unknown whether MFG-E8 ameliorates sepsis-induced apoptosis and organ injury in alcohol-intoxicated rats. The purpose of this study was to determine whether recombinant murine MFG-E8 (rmMFG-E8) attenuates organ injury after acute alcohol exposure and subsequent sepsis. Methods Acute alcohol intoxication was induced in male adult rats by a bolus injection of intravenous alcohol at 1.75 g/kg BW, followed by an intravenous infusion of 300 mg/kg BW/h of alcohol for 10h. Sepsis was induced at the end of 10-h alcohol infusion by cecal ligation and puncture (CLP). rmMFG-E8 or vehicle (normal saline) was administered intravenously three times (i.e., at the beginning of alcohol injection, the beginning of CLP, and 10h post-CLP) at a dose of 20 ?g/kg BW each. Blood and tissue samples were collected 20h after CLP in alcoholic animals for various measurements. Results Acute alcohol exposure per se did not affect the production of MFG-E8; however, it primed the animal and enhanced sepsis-induced MFG-E8 downregulation in the spleen. Administration of rmMFG-E8 reduces alcohol/sepsis-induced apoptosis in the spleen, lungs, and liver. In addition, administration of rmMFG-E8 after alcohol exposure and subsequent sepsis decreases circulating levels of TNF-? and IL-6 and attenuates organ injury. Conclusions rmMFG-E8 attenuates sepsis-induced apoptosis and organ injury in alcohol-intoxicated rats. PMID:20586751

Wu, Rongqian; Chaung, Wayne W.; Zhou, Mian; Ji, Youxin; Dong, Weifeng; Wang, Zhimin; Qiang, Xiaoling; Wang, Ping

2010-01-01

228

Inverse Relation between Disease Severity and Expression of the Streptococcal Cysteine Protease, SpeB, among Clonal M1T1 Isolates Recovered from Invasive Group A Streptococcal Infection Cases  

Microsoft Academic Search

The streptococcal cysteine protease (SpeB) is one of the major virulence factors produced by group A streptococci (GAS). In this study we investigated if differences exist in SpeB production by clonally related M1T1 clinical isolates derived from patients with invasive infections. Twenty-nine of these isolates were from nonsevere cases and 48 were from severe cases, including streptococcal toxic shock syndrome

RITA G. KANSAL; ALLISON MCGEER; DONALD E. LOW; ANNA NORRBY-TEGLUND; MALAK KOTB

2000-01-01

229

Myocardial Depression in Sepsis and Septic Shock  

Microsoft Academic Search

Myocardial dysfunction is an important component in the hemodynamic collapse induced by sepsis and septic shock. A series\\u000a of inflammatory cascades triggered by the inciting infection generate circulatory myocardial depressant substances, including\\u000a TNF-?, IL-1?, PAF and lysozyme. Current evidence suggests that septic myocardial depression in humans is characterized by\\u000a reversible biventricular dilatation, decreased systolic contractile function, and decreased response to

A. Kumar; J. E. Parrillo

230

Pathogenesis, therapy, and prevention of meningococcal sepsis  

Microsoft Academic Search

Neisseria meningitidis (meningococcus), an exclusive pathogen of humans, is the cause of sepsis (meningococcemia) and meningitis, often in otherwise\\u000a healthy individuals. Several hundred thousand cases of meningococcal disease occur worldwide each year, a number that is frequently\\u000a accentuated by epidemic outbreaks. In recent years, significant advances, fueled by new molecular approaches and genome sequencing\\u000a projects, have improved our understanding of

David S. Stephens; Shanta M. Zimmer

2002-01-01

231

Dermatomyositis following chronic staphylococcal joint sepsis.  

PubMed

A young man is reported with recurrent Staphylococcus aureus joint sepsis associated with dermatomyositis. His dermatomyositis failed to resolve on treatment with antimicrobial agents alone, indicating that if staphylococcal infection was the triggering event for the dermatomyositis then the subsequent process was apparently self perpetuating, requiring cytotoxic agents for its control. This case can be interpreted as possible further evidence for the triggering of autoimmune disease by infective agents. PMID:2383066

Lane, S; Doherty, M; Powell, R J

1990-06-01

232

Inactivation of renal mitochondrial respiratory complexes and manganese superoxide dismutase during sepsis: mitochondria-targeted antioxidant mitigates injury.  

PubMed

Acute kidney injury (AKI) is a complication of sepsis and leads to a high mortality rate. Human and animal studies suggest that mitochondrial dysfunction plays an important role in sepsis-induced multi-organ failure; however, the specific mitochondrial targets damaged during sepsis remain elusive. We used a clinically relevant cecal ligation and puncture (CLP) murine model of sepsis and assessed renal mitochondrial function using high-resolution respirometry, renal microcirculation using intravital microscopy, and renal function. CLP caused a time-dependent decrease in mitochondrial complex I and II/III respiration and reduced ATP. By 4 h after CLP, activity of manganese superoxide dismutase (MnSOD) was decreased by 50% and inhibition was sustained through 36 h. These events were associated with increased mitochondrial superoxide generation. We then evaluated whether the mitochondria-targeted antioxidant Mito-TEMPO could reverse renal mitochondrial dysfunction and attenuate sepsis-induced AKI. Mito-TEMPO (10 mg/kg) given at 6 h post-CLP decreased mitochondrial superoxide levels, protected complex I and II/III respiration, and restored MnSOD activity by 18 h. Mito-TEMPO also improved renal microcirculation and glomerular filtration rate. Importantly, even delayed therapy with a single dose of Mito-TEMPO significantly increased 96-h survival rate from 40% in untreated septic mice to 80%. Thus, sepsis causes sustained inactivation of three mitochondrial targets that can lead to increased mitochondrial superoxide. Importantly, even delayed therapy with Mito-TEMPO alleviated kidney injury, suggesting that it may be a promising approach to treat septic AKI. PMID:24500690

Patil, Naeem K; Parajuli, Nirmala; MacMillan-Crow, Lee Ann; Mayeux, Philip R

2014-04-01

233

Reduction in maternal mortality due to sepsis.  

PubMed

The present study was undertaken at a rural medical institute in India to analyse the trends in maternal mortality due to sepsis and the factors associated with change, if any. During the study period of 20 years, a total of 37,155 women delivered, 192 deaths occurred and forty deaths (20.83%) were due to sepsis and it's sequlae. It was revealed that there is a definite decrease in the proportion of deaths due to sepsis, to 10% in the last five years from 35% in earlier years. The change seems to be due to the advocacy of clean deliveries and reduction in case fatality because of alterations in medication and earlier surgical intervention. However the percentage contribution of septic abortion has remained the same. Septic abortion continues to exist inspite of all the current laws and discussion about the availability of a liberal law, which permits abortion almost on request. Most of the women who had died due to septic abortion were married (65%). Deaths due to septic abortion, are persisting even in married women and it is a matter of concern for health providers, policy makers and governments. PMID:15814392

Chhabra, S; Kaipa, A; Kakani, A

2005-02-01

234

Sepsis and Meningitis due to Listeria Monocytogenes  

PubMed Central

Purpose This study focused on the effect of immuno-compromising conditions on the clinical presentation of severe listerial infection. Patients and Methods Nine human listeriosis cases seen from 1991-2002 were reviewed. All adult patients, from whose blood, peritoneal fluid or cerebrospinal fluid (CSF) the L. monocytogenes was isolated, were included in this retrospective study. Results Listeriosis presented as primary sepsis with positive blood cultures in 5 cases and meningitis with positive CSF cultures in 4 cases. All of these patients had at least one underlying disease, most commonly, hematologic malignancy, diabetes mellitus, amyloidosis and hepatic cirrhosis; 55.6% had received immunosuppressive or corticosteroid therapy within a week before the onset of listeriosis. The patients were adults with a mean age of 60 years. Fever, night sweats, chills and lethargy were the most common symptoms; high temperature (> 38?), tachycardia, meningeal signs and poor conditions in general were the most common findings on admission. The mortality rate was 33.3% and was strictly associated with the severity of the underlying disease. Mortality differences were significant between sepsis (20%) and meningitis (50%) patients. Conclusion Listeriosis as an uncommon infection in our region and that immuno-suppressive therapy is an important pre-disposing factor of listeriosis. Sepsis and meningitis were more common in this group of patients and had the highest case-fatality rate for food-borne illnesses. PMID:17594151

Aygen, Bilgehan; Esel, Duygu; Kayabas, Uner; Alp, Emine; Sumerkan, Bulent; Doganay, Mehmet

2007-01-01

235

Anti-complement strategies in experimental sepsis.  

PubMed

Using the cecal ligation/puncture (CLP) model of sepsis in rodents, evidence was obtained for excessive activation of the complement system, which leads to nearly total loss of innate immune protective functions of blood neutrophils. These defects are associated with profound defects in chemotaxis, respiratory burst (H2O2 production) and phagocytosis. The molecular mechanisms of these defects are linked to the complement activation product C5a. In CLP rats and mice, the C5a receptor (C5aR) is widely up-regulated in organs, in part owing to the production of interleukin-6 (IL-6). The up-regulation of C5aR in the thymus is linked to C5a-dependent induction of apoptosis in thymocytes, as revealed by caspase activation, increased binding of C5a and DNA laddering. Such events in thymocytes are prevented if rats first are treated with anti-C5a or with anti-C5aR at the time of CLP. Treatment of CLP rats and mice with anti-C5a, anti-IL-6 or anti-C5aR dramatically improves survival rates after CLP, indicating a linkage between C5a and C5aR in the harmful outcomes of sepsis in rodents. Studies are underway in humans with sepsis to determine whether similar mechanisms are in play. PMID:14620141

Ward, Peter A; Riedemann, Niels C; Guo, Ren-Feng; Huber-Lang, Markus; Sarma, J Vidya; Zetoune, Firas S

2003-01-01

236

A VLU complicated by severe group a streptococcal infection resulting in necrotising fasciitis and septic shock: a case report.  

PubMed

This case study outlines the management of a patient with a venous leg ulcer whose swabs cultured Staphylococcus aureus and beta-haemolytic streptococcus group A while in hospital with cellulitis, which was treated with antibiotics as per sensitivities. However, the patient presented at the emergency department five weeks later with a diagnosis of invasive group A streptococcal disease resulting in necrotising fasciitis and streptococcal toxic shock syndrome. This paper describes the holistic care and wound management that the patient received. PMID:25289649

Meagher, H; Corkery, M; Concannon, L; Kavanagh, E

2014-10-01

237

The effects of moderate-dose steroid therapy in sepsis: A placebo-controlled, randomized study  

PubMed Central

BACKGROUND: Despite the new developments in sepsis treatment, mortality rate is still high. In this study, we aimed to investigate endocrinologic changes and the effects of moderate dosage steroid treatment in patients with sepsis. METHODS: Fifty-five patients were included in the study. Basal hormonal evaluation and adrenocorticotropin hormone (ACTH) stimulation test were performed within 24 h in all patients. Both groups received standard treatment for sepsis. However, one group (steroid group) was also given intravenous prednisolone (20 mg/day). All-cause mortality was assessed during the first 28 days. RESULTS: Analysis of the findings revealed a 59.3% mortality rate in steroid group compared with a 53.6% mortality rate in placebo group (p = 0.787). Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) scores, and peak cortisol and ACTH levels were significant factors related to mortality. The incidence of adrenal insufficiency (AI) was 10.9% and relative adrenal insufficiency (RAI) 36.4%. It was also found that steroid treatment did not have any effects on the mortality of patients with AI and RAI (p = 0.075 and p = 0.999, respectively). CONCLUSIONS: Moderate-dose steroid therapy has no effect on mortality. Higher basal cortisol and peak cortisol levels were found more reliable mortality indicators compared to RAI. In addition, the study revealed that ACTH level was a significant indicator of mortality. PMID:22973341

Yildiz, Orhan; Tanriverdi, Fatih; Simsek, Serap; Aygen, Bilgehan; Kelestimur, Fahrettin

2011-01-01

238

Sore throat progressing to embolic sepsis: A case of Lemierre’s syndrome  

PubMed Central

Lemierre’s syndrome is a rare clinical syndrome defined as oropharyngeal sepsis, thrombophlebitis of the internal jugular vein and septic thombo-emboli. It is typically encountered in young, immunocompetent individuals, with a mean incident age of 20 years. The organism that is most commonly associated is an anaerobic Gram-negative bacterium: Fusobacterium species. The defined treatment course is at least six weeks of antibiotics, with the role of anticoagulation being unclear. The present article documents a case of Lemierre’s syndrome complicated by acute renal failure and loculated pleural effusion in an otherwise healthy 16-year-old patient. PMID:20186362

Dirks, Jacquelyn; Bowie, Dennis

2010-01-01

239

Redox regulation of mitophagy in the lung during murine Staphylococcus aureus sepsis.  

PubMed

Oxidative mitochondrial damage is closely linked to inflammation and cell death, but low levels of reactive oxygen and nitrogen species serve as signals that involve mitochondrial repair and resolution of inflammation. More specifically, cytoprotection relies on the elimination of damaged mitochondria by selective autophagy (mitophagy) during mitochondrial quality control. This aim of this study was to identify and localize mitophagy in the mouse lung as a potentially upregulatable redox response to Staphylococcus aureus sepsis. Fibrin clots loaded with S. aureus (1×10(7) CFU) were implanted abdominally into anesthetized C57BL/6 and B6.129X1-Nfe2l2tm1Ywk/J (Nrf2(-/-)) mice. At the time of implantation, mice were given vancomycin (6mg/kg) and fluid resuscitation. Mouse lungs were harvested at 0, 6, 24, and 48h for bronchoalveolar lavage (BAL), Western blot analysis, and qRT-PCR. To localize mitochondria with autophagy protein LC3, we used lung immunofluorescence staining in LC3-GFP transgenic mice. In C57BL/6 mice, sepsis-induced pulmonary inflammation was detected by significant increases in mRNA for the inflammatory markers IL-1? and TNF-? at 6 and 24h, respectively. BAL cell count and protein also increased. Sepsis suppressed lung Beclin-1 protein, but not mRNA, suggesting activation of canonical autophagy. Notably sepsis also increased the LC3-II autophagosome marker, as well as the lung?s noncanonical autophagy pathway as evidenced by loss of p62, a redox-regulated scaffolding protein of the autophagosome. In LC3-GFP mouse lungs, immunofluorescence staining showed colocalization of LC3-II to mitochondria, mainly in type 2 epithelium and alveolar macrophages. In contrast, marked accumulation of p62, as well as attenuation of LC3-II in Nrf2-knockout mice supported an overall decrease in autophagic turnover. The downregulation of canonical autophagy during sepsis may contribute to lung inflammation, whereas the switch to noncanonical autophagy selectively removes damaged mitochondria and accompanies tissue repair and cell survival. Furthermore, mitophagy in the alveolar region appears to depend on activation of Nrf2. Thus, efforts to promote mitophagy may be a useful therapeutic adjunct for acute lung injury in sepsis. PMID:25450328

Chang, Alan L; Ulrich, Allison; Suliman, Hagir B; Piantadosi, Claude A

2015-01-01

240

Mikrobizide und zytotoxische Funktionen polymorphkerniger Leukozyten bei Patienten mit Sepsis.  

E-print Network

??Reagible Sauerstoffradikale sind wichtige Bestandteile mikrobizider als auch zytotoxischer Funktionen polymorphkerniger neutrophiler Leukozyten (PMNL). Da dieser ambivalenten Stellung im Verlauf einer Sepsis große Bedeutung zukommt,… (more)

Schliephake, Florian

2006-01-01

241

Systemic inflammatory response syndrome and sepsis in major vascular surgery.  

E-print Network

??This study aimed to identify relationships between post-operative systemic inflammatory response syndrome (SIRS) and sepsis, and markers of immunological, neuroendocrine, nutritional and psychological status ;… (more)

Hassen, Tiffany Alicia

2006-01-01

242

Bacterial Sepsis in Patients with Visceral Leishmaniasis in Northwest Ethiopia  

PubMed Central

Background and Objectives. Visceral leishmaniasis (VL) is one of the neglected diseases affecting the poorest segment of world populations. Sepsis is one of the predictors for death of patients with VL. This study aimed to assess the prevalence and factors associated with bacterial sepsis, causative agents, and their antimicrobial susceptibility patterns among patients with VL. Methods. A cross-sectional study was conducted among parasitologically confirmed VL patients suspected of sepsis admitted to the University of Gondar Hospital, Northwest Ethiopia, from February 2012 to May 2012. Blood cultures and other clinical samples were collected and cultured following the standard procedures. Results. Among 83 sepsis suspected VL patients 16 (19.3%) had culture confirmed bacterial sepsis. The most frequently isolated organism was Staphylococcus aureus (68.8%; 11/16), including two methicillin-resistant isolates (MRSA). Patients with focal bacterial infection were more likely to have bacterial sepsis (P < 0.001). Conclusions. The prevalence of culture confirmed bacterial sepsis was high, predominantly due to S. aureus. Concurrent focal bacterial infection was associated with bacterial sepsis, suggesting that focal infections could serve as sources for bacterial sepsis among VL patients. Careful clinical evaluation for focal infections and prompt initiation of empiric antibiotic treatment appears warranted in VL patients. PMID:24895569

Takele, Yegnasew; Woldeyohannes, Desalegn; Tiruneh, Moges; Mohammed, Rezika; Lynen, Lutgarde; van Griensven, Johan

2014-01-01

243

Application of the C3-Binding Motif of Streptococcal Pyrogenic Exotoxin B to Protect Mice from Invasive Group A Streptococcal Infection  

PubMed Central

Group A streptococcus (GAS) is an important human pathogen that produces several extracellular exotoxins to facilitate invasion and infection. Streptococcal pyrogenic exotoxin B (SPE B) has been demonstrated to be an important virulence factor of GAS. Our previous studies indicate that SPE B cleaves complement 3 (C3) and inhibits the activation of complement pathways. In this study, we constructed and expressed recombinant fragments of SPE B to examine the C3-binding site of SPE B. Using enzyme-linked immunosorbent assays and pull-down assays, we found that the C-terminal domain, containing amino-acid residues 345–398, of SPE B was the major binding site of human serum C3. We further identified a major, Ala376-Pro398, and a minor C3-binding motif, Gly346-Gly360, that both mediated the binding of C3 complement. Immunization with the C3-binding motifs protected mice against challenge with a lethal dose of non-invasive M49 strain GAS but not invasive M1 strains. To achieve higher efficiency against invasive M1 GAS infection, a combination of synthetic peptides derived from C-terminal epitope of streptolysin S (SLSpp) and from the major C3-binding motif of SPE B (PP6, Ala376-Pro398) was used to elicit specific immune response to those two important streptococcal exotoxins. Death rates and the severity of skin lesions decreased significantly in PP6/SLSpp-immunized mice that were infected with invasive M1 strains of GAS. These results indicate a combination of the C3-binding motif of SPE B and the protective epitope of SLS could be used as a subunit vaccine against invasive M1 strains group A streptococcal infection. PMID:25629609

Kuo, Chih-Feng; Tsao, Nina; Cheng, Miao-Hui; Yang, Hsiu-Chen; Wang, Yu-Chieh; Chen, Ying-Pin; Lin, Kai-Jen

2015-01-01

244

PD-L1 Blockade Attenuated Sepsis-Induced Liver Injury in a Mouse Cecal Ligation and Puncture Model  

PubMed Central

Liver plays a major role in hypermetabolism and produces acute phase proteins during systemic inflammatory response syndrome and it is of vital importance in host defense and bacteria clearance. Our previous studies indicated that programmed death-1 (PD-1) and its ligand programmed death ligand-1 (PD-L1) are crucial modulators of host immune responses during sepsis. Our current study was designed to investigate the role of PD-L1 in sepsis-induced liver injury by a mouse cecal ligation and puncture (CLP) model. Our results indicated that there was a significant increase of PD-L1 expression in liver after CLP challenge compared to sham-operated controls, in terms of levels of mRNA transcription and immunohistochemistry. Anti-PD-L1 antibody significantly alleviated the morphology of liver injury in CLP mice. Anti-PD-L1 antibody administration decreased ALT and AST release in CLP mice, decreased the levels of tumor necrosis factor (TNF)-?, interleukin (IL)-6, and IL-10 mRNA in liver after sepsis challenge. Thus, anti-PD-L1 antibody might have a therapeutic potential in attenuating liver injury in sepsis. PMID:24324295

Bao, Rui; Zhu, Jiali; Wang, Jiafeng; Li, Jinbao

2013-01-01

245

Understanding of Sepsis among Emergency Medical Services: A Survey Study  

PubMed Central

Background Emergency medical services (EMS) personnel commonly encounter sepsis, yet little is known about their understanding of sepsis. Study Objectives To determine the awareness, knowledge, current practice, and attitudes about sepsis among EMS personnel. Methods We performed an anonymous, multi-agency, online survey of emergency medical technicians (EMTs), firefighter-emergency medical technicians (FF-EMTs), and paramedics in a metropolitan, 2-tier EMS system. We compared responses according to the level of EMS training, and used multivariable logistic regression to determine the odds of correctly identifying the definition of sepsis, independent of demographic and professional factors. Results Overall response rate of study participants was 57% (786/1390), and greatest among EMTs (78%; 276/350). A total of 761 respondents (96%) had heard of the term sepsis. EMTs and FF-EMTs were at significantly reduced odds of correctly defining sepsis compared to paramedics, independent of age, sex, and years of experience (EMTs, OR=0.44, 95%CI:0.3,0.8; FF-EMTs, OR=0.32, 95%CI:0.2,0.6,). Overall, knowledge of the clinical signs and symptoms and recommended treatments for sepsis was typically greater than 75%, though best among paramedics than EMTs or FF-EMTs (p<0.01). The majority of respondents believed sepsis is not recognized by EMS “some” or “a lot” of the time (76%, 596/786). Conclusions EMS personnel demonstrated an overall sound awarenessof sepsis. Knowledge of sepsis was less among firefighter-EMTs and EMTs compared to paramedics. These results suggest that paramedics could be integrated into strategies of early identification and treatment of sepsis while EMTs may benefit from focused education and training. PMID:22070877

Seymour, Christopher W.; Carlbom, David; Engelberg, Ruth A.; Larsen, Jonathan; Bulger, Eileen M.; Copass, Michael K.; Rea, Thomas D.

2011-01-01

246

Tolerability of inhaled N-chlorotaurine in an acute pig streptococcal lower airway inflammation model  

PubMed Central

Background Inhalation of N-chlorotaurine (NCT), an endogenous new broad spectrum non-antibiotic anti-infective, has been shown to be very well tolerated in the pig model recently. In the present study, inhaled NCT was tested for tolerability and efficacy in the infected bronchopulmonary system using the same model. Methods Anesthetized pigs were inoculated with 20 ml of a solution containing approximately 108 CFU/ml Streptococcus pyogenes strain d68 via a duodenal tube placed through the tracheal tube down to the carina. Two hours later, 5 ml of 1% NCT aqueous solution (test group, n = 15) or 5 ml of 0.9% NaCl (control group, n = 16) was inhaled via the tracheal tube connected to a nebulizer. Inhalation was repeated every hour, four times in total. Lung function and haemodynamics were monitored. Bronchoalveolar lavage samples were removed for determination of colony forming units (CFU), and lung samples for histology. Results Arterial pressure of oxygen (PaO2) decreased rapidly after instillation of the bacteria in all animals and showed only a slight further decrease at the end of the experiment without a difference between both groups. Pulmonary artery pressure increased to a peak 1-1.5 h after application of the bacteria, decreased in the following hour and remained constant during treatment, again similarly in both groups. Histology demonstrated granulocytic infiltration in the central parts of the lung, while this was absent in the periphery. Expression of TNF-alpha, IL-8, and haemoxygenase-1 in lung biopsies was similar in both groups. CFU counts in bronchoalveolar lavage came to 170 (10; 1388) CFU/ml (median and 25 and 75 percentiles) for the NCT treated pigs, and to 250 (10; 5.5 × 105) CFU/ml for NaCl treated pigs (p = 0.4159). Conclusions Inhaled NCT at a concentration of 1% proved to be very well tolerated also in the infected bronchopulmonary system. This study confirms the tolerability in this delicate body region, which has been proven in healthy pigs previously. Regarding efficacy, no conclusions can be drawn, mainly because of the limited test period of the model. PMID:21875435

2011-01-01

247

Comparing the effect of hydroxyethyl starch 130/0.4 with balanced crystalloid solution on mortality and kidney failure in patients with severe sepsis (6S - Scandinavian Starch for Severe Sepsis/Septic Shock trial): Study protocol, design and rationale for a double-blinded, randomised clinical trial  

PubMed Central

Background By tradition colloid solutions have been used to obtain fast circulatory stabilisation in shock, but high molecular weight hydroxyethyl starch (HES) may cause acute kidney failure in patients with severe sepsis. Now lower molecular weight HES 130/0.4 is the preferred colloid in Scandinavian intensive care units (ICUs) and 1st choice fluid for patients with severe sepsis. However, HES 130/0.4 is largely unstudied in patients with severe sepsis. Methods/Design The 6S trial will randomise 800 patients with severe sepsis in 30 Scandinavian ICUs to masked fluid resuscitation using either 6% HES 130/0.4 in Ringer's acetate or Ringer's acetate alone. The composite endpoint of 90-day mortality or end-stage kidney failure is the primary outcome measure. The secondary outcome measures are severe bleeding or allergic reactions, organ failure, acute kidney failure, days alive without renal replacement therapy or ventilator support and 28-day and 1/2- and one-year mortality. The sample size will allow the detection of a 10% absolute difference between the two groups in the composite endpoint with a power of 80%. Discussion The 6S trial will provide important safety and efficacy data on the use of HES 130/0.4 in patients with severe sepsis. The effects on mortality, dialysis-dependency, time on ventilator, bleeding and markers of resuscitation, metabolism, kidney failure, and coagulation will be assessed. Trial Registration ClinicalTrials.gov: NCT00962156 PMID:21269526

2011-01-01

248

Mechanisms of tissue hypercarbia in sepsis.  

PubMed

Intramucosal acidosis, that it is to say, an increased intramucosal-arterial PCO2 difference, is a common finding in clinical and experimental sepsis. Nevertheless, the physiologic significance of increases in tissue PCO2 is controversial, since CO2 can be generated by both aerobic and anaerobic biochemical processes. PCO2 can rise after buffering of protons produced in the hydrolysis of high-energy phosphate compounds by bicarbonate, or after the anaerobic production of acids, like lactate. In this case, it could represent tissue dysoxia. Alternatively, an increase in tissue PCO2 could denote hypoperfusion and diminished removal of the CO2 produced during the oxidation of pyruvate. In this last situation, aerobic metabolism might be preserved. In the present review, we discuss the physiologic mechanisms that determine tissue and venous hypercarbia during the three classic forms of hypoxia: stagnant, hypoxic and anemic hypoxia. The results of experimental studies suggest that tissue minus arterial and venoarterial PCO2 gradients primarily reflect alterations in tissue perfusion. These conclusions are further confirmed by a mathematical model of CO2 transport. In sepsis, however, tissue hypercarbia might develop despite normal or high cardiac output. This phenomenon has been initially interpreted as secondary to alterations in energetic metabolism, the so-called cytopathic hypoxia. Yet, new evidences show that the underlying mechanism to tissue hypercarbia in sepsis might be due to severe microcirculatory derangements. In summary, experimental results support the hypothesis that increases in tissue and venous CO2 are insensitive markers of tissue dysoxia, and merely reflect vascular hypoperfusion. PMID:17981634

Dubin, Arnaldo; Estenssoro, Elisa

2008-01-01

249

Psoriasis: a T-cell-mediated autoimmune disease induced by streptococcal superantigens?  

Microsoft Academic Search

Psoriasis is a T-cell-mediated disease that can be triggered by infection with group A ?-haemolytic streptococci. It is proposed that psoriatic skin lesions are initiated by exotoxin-activated T cells, and persist because of specific T cells that react both with streptococcal M protein and a skin determinant, possibly a variant of keratin. As discussed here by Helgi Valdimarsson and colleagues,

Helgi Valdimarsson; Barbara S. Baker; Ingileif Jónsdóttir; Ann Powles; Lionel Fry

1995-01-01

250

Influences of Linezolid, Penicillin, and Clindamycin, Alone and in Combination, on Streptococcal Pyrogenic Exotoxin A Release  

PubMed Central

An in vitro model was used to compare the effects of linezolid, clindamycin, and penicillin, alone and in combination, on streptococcal pyrogenic exotoxin A (SPE A) release against virulent group A streptococci (GAS). All regimens exhibited lower (P < 0.05) SPE A release at 1 h than those with penicillin alone. Linezolid and clindamycin, alone or in combination with penicillin, may optimize the treatment of GAS infections by reducing bacterial burden and exotoxin release. PMID:12709354

Coyle, Elizabeth A.; Cha, Raymond; Rybak, Michael J.

2003-01-01

251

Beta-Hemolytic Streptococcal Erythroderma Syndrome: A Clinical and Pathogenic Analysis  

PubMed Central

The syndrome of erythroderma due to beta-hemolytic streptococci is rarely seen and should be distinguished from cellulitis and toxic shock-like syndrome. We describe a novel syndrome of non-group A, beta-hemolytic streptococcal infection truncal erythroderma. The characteristics of this syndrome suggest that local factors were likely operative in the cutaneous manifestations of an exotoxin-associated erythroderma. PMID:21841465

Tyner, Harmony L; Schlievert, M; Baddour

2011-01-01

252

A case of invasive group A streptococcal infection associated with chronic granulomatous interstitial pneumonitis  

Microsoft Academic Search

A 52-year-old man with chronic granulomatous interstitial pneumonitis suffered from invasive group A streptococcal infection.\\u000a His chest x-ray showed bilateral interstitial shadows in the lower lung fields since childhood. He was admitted to Keio University\\u000a Hospital because of fever, productive cough, and necrosis of the distal extremity. The chest radiographic appearance worsened\\u000a and he developed low blood pressure, liver dysfunction,

Akira Umeda; Kyohko Nomura; Kohichi Sayama; Akitoshi Ishizaka; Kazuhiro Yamaguchi; Minoru Kanazawa; Momoko Miyaji; Yoshio Kobayashi; Hitoshi Sugiura

1995-01-01

253

Burkholderia contaminans: unusual cause of biliary sepsis.  

PubMed

We report a case of biliary tract infection caused by a strain of Burkholderia contaminans, a member of the Burkholderia cepacia complex. The patient developed sepsis after endoscopic retrograde cholangiopancreatography (ERCP). Gram-negative bacilli were isolated from blood and bile cultures. Automated bacterial identification systems identified the organism as Burkholderia cepacia, whereas DNA sequence analysis revealed that the recA gene isolate was identical to that of B. contaminans. The patient responded to therapy with the antibiotics trimethoprim/sulfamethoxazole and biliary tract decompression. This case suggests that B. contaminans can be a causative agent of healthcare-associated biliary tract infections such as ERCP-related cholangitis. PMID:23292160

Ohji, Goh; Ohkusu, Kiyofumi; Toguchi, Akihiro; Otsuka, Yoshihito; Hosokawa, Naoto; Iwata, Kentaro

2013-10-01

254

Noninvasive Hemodynamic Monitoring in Emergency Patients with Suspected Heart Failure, Sepsis and Stroke: The Premium Registry  

PubMed Central

Introduction Noninvasive hemodynamic (HD) assessments in the emergency department (ED) might assist in the diagnosis, therapeutic plan development and risk stratification of acutely ill patients. This multinational observational study was designed to initiate noninvasive HD measurements prior to any ED patient therapeutic interventions and broadly evaluate them for potential diagnostic, therapeutic and predictive value. Methods We enrolled patients with suspected acute heart failure (AHF), sepsis or stroke. Continuous noninvasive HD monitoring was begun using the Nexfin finger cuff device (Edwards LifeSciences, BMEYE, Amsterdam, Netherlands). Beat-to-beat HD measurements were averaged for the initial 15 minutes, prior to therapeutic intervention. We performed suspected disease group comparisons and evaluated HD predictors of 30-day mortality. Results Of 510 patients enrolled: 185 (36%) AHF, 194 (38%) sepsis and 131 (26%) stroke. HD variables were significantly different (p<0.05) amongst the groups. Cardiac output and index and stroke volume index (SVI) were highest in sepsis (6.5, 3.5, 36), followed by stroke (5.5, 2.7, 35.8), and lowest in AHF (5.4, 2.7, 33.6). The in-group HD standard deviations and ranges measurements were large, indicating heterogeneous underlying HD profiles. Presenting SVI predicted 30-day mortality for all groups. Conclusion Presenting ED noninvasive HD data has not been previously reported in any large patient population. Our data suggest a potential role for early noninvasive HD assessments aiding in diagnosing of patients, individualizing therapy based on each person’s unique HD values and predicting 30-day mortality. Further studies and analyses are needed to determine how HD assessments should be best used in the ED. PMID:25493119

Nowak, Richard M.; Nanayakkara, Prabath; DiSomma, Salvatore; Levy, Phillip; Schrijver, Edmée; Huyghe, Rebecca; Autunno, Alessandro; Sherwin, Robert L.; Divine, George; Moyer, Michele

2014-01-01

255

Prevention and Treatment of Nosocomial Sepsis in the NICU  

Microsoft Academic Search

Nosocomial sepsis is a serious problem for neonates who are admitted for intensive care. It is associated with an increase in mortality, morbidity, and prolonged length of hospital stay. Thus, both the human and fiscal costs of these infections are high. Although the rate of nosocomial sepsis increases with the degree of both prematurity and low birth weight, no specific

Reese Clark; Richard Powers; Robert White; Barry Bloom; Pablo Sanchez; Daniel K Benjamin

2004-01-01

256

Microcirculatory dysfunction in sepsis: a pathogenetic basis for therapy?  

Microsoft Academic Search

Sepsis is a frequent complication of multiple organ dysfunction syndrome and remains a major problem of intensive care medicine. It is also a common factor in the final cause of death in hospital populations. Clinical observations, assisted by invasive monitoring techniques as well as pathological-anatomical studies, clearly indicate that microcirculatory dysfunction lies at the centre of sepsis pathogenesis. Numerous animal

Fernando Bittinger; C. James Kirkpatrick

2000-01-01

257

Severe sepsis and septic shock in the elderly: An overview.  

PubMed

The incidence of severe sepsis and septic shock is increasing in the older population leading to increased admissions to the intensive care units (ICUs). The elderly are predisposed to sepsis due to co-existing co-morbidities, repeated and prolonged hospitalizations, reduced immunity, functional limitations and above all due to the effects of aging itself. A lower threshold and a higher index of suspicion is required to diagnose sepsis in this patient population because the initial clinical picture may be ambiguous, and aging increases the risk of a sudden deterioration in sepsis to severe sepsis and septic shock. Management is largely based on standard international guidelines with a few modifications. Age itself is an independent risk factor for death in patients with severe sepsis, however, many patients respond well to timely and appropriate interventions. The treatment should not be limited or deferred in elderly patients with severe sepsis only on the grounds of physician prejudice, but patient and family preferences should also be taken into account as the outcomes are not dismal. Future investigations in the management of sepsis should not only target good functional recovery but also ensure social independence and quality of life after ICU discharge. PMID:24701398

Nasa, Prashant; Juneja, Deven; Singh, Omender

2012-02-01

258

Severe sepsis and septic shock in the elderly: An overview  

PubMed Central

The incidence of severe sepsis and septic shock is increasing in the older population leading to increased admissions to the intensive care units (ICUs). The elderly are predisposed to sepsis due to co-existing co-morbidities, repeated and prolonged hospitalizations, reduced immunity, functional limitations and above all due to the effects of aging itself. A lower threshold and a higher index of suspicion is required to diagnose sepsis in this patient population because the initial clinical picture may be ambiguous, and aging increases the risk of a sudden deterioration in sepsis to severe sepsis and septic shock. Management is largely based on standard international guidelines with a few modifications. Age itself is an independent risk factor for death in patients with severe sepsis, however, many patients respond well to timely and appropriate interventions. The treatment should not be limited or deferred in elderly patients with severe sepsis only on the grounds of physician prejudice, but patient and family preferences should also be taken into account as the outcomes are not dismal. Future investigations in the management of sepsis should not only target good functional recovery but also ensure social independence and quality of life after ICU discharge. PMID:24701398

Nasa, Prashant; Juneja, Deven; Singh, Omender

2012-01-01

259

Translocation of indigenous microflora in an experimental model of sepsis.  

PubMed

Translocation of viable bacteria from gut to bloodstream and other sterile body sites during shock has been demonstrated in several experimental and clinical studies. The factors causing translocation and its incidence at different stages of shock are not known. The aim of the study was to evaluate the importance of several factors causing translocation of indigenous microflora in an experimental model of septic shock based on intraperitoneal Escherichia coli sepsis in rats. Counts of inoculated E. coli and translocated bacteria in different locations, gut morphology and haematological values were evaluated at different stages of sepsis. Sepsis developed in all animals and E. coli achieved the highest counts in blood 6 h after inoculation. Translocation was commonest at 6 and 12 h after inoculation. Frequently translocating bacteria were lactobacilli, bifidobacteria, bacteroides and peptostreptococci. In early sepsis, translocation was associated with high E. coli counts in blood, yet in late sepsis the opposite correlation was present. Low infiltration by neutrophils in the ileum and decreased mitotic activity in the colon were associated with a high translocation rate. In early sepsis, translocation was associated with low lymphocyte counts, but in late sepsis, with low neutrophil counts. Translocation of bacteria (including anaerobes) that colonise the gut in high counts takes place during sepsis. Putative influencing factors such as activity of the primary disease (bacterial counts in blood), gut morphology or haematological values seem to have different impacts on translocation, depending on the stage of the disease. PMID:10798556

Naaber, P; Smidt, I; Tamme, K; Liigant, A; Tapfer, H; Mikelsaar, M; Talvik, R

2000-05-01

260

Group A streptococcal toxic shock syndrome developing in the third trimester of pregnancy.  

PubMed Central

BACKGROUND: Group A streptococcal (GAS) toxic shock syndrome (TSS) is an uncommon, but life-threatening infection during pregnancy and should be considered in rapid onset of shock. Most cases described in the literature have occurred in the puerperium. We report a case of GAS TSS occurring during the third trimester of pregnancy in a previously healthy woman. CASE: A 31-year-old female, who was 34 weeks pregnant, presented with fevers and a prodromal 'flu-like' illness. She rapidly developed shock and multiorgan failure. Blood cultures revealed GAS bacteremia and the patient met criteria for streptococcal TSS. Despite her eventual recovery, her infant died on postpartum day 15 as a consequence of the mother's TSS. CONCLUSIONS: This case is unusual in that there were no identifiable initiating events or source of the streptococcal infection, and the TSS developed during pregnancy rather than after delivery. Early recognition of GAS infections is important given the rapid onset and high morbidity and mortality associated with these infections. This is the first reported case utilizing intravenous immunoglobulin for GAS TSS in the puerperium. PMID:12648315

Crum, Nancy F; Chun, Helen M; Gaylord, Thomas G; Hale, Braden R

2002-01-01

261

Sepsis-induced immunosuppression: from cellular dysfunctions to immunotherapy  

PubMed Central

Sepsis — severe life-threatening infection with organ dysfunction — initiates a complex interplay of host pro- and anti-inflammatory processes. In a real sense, sepsis can be considered a race to the death between the pathogens and the host immune system. It is the proper balance between the often competing pro- and anti-inflammatory pathways that determines the fate of the individual. Although the field of sepsis research has witnessed the failure of many highly-touted clinical trials, a better understanding of the pathophysiological basis of the disorder and the mechanisms responsible for the associated pro- and anti-inflammatory responses is leading to a novel approach to treat this highly lethal condition. Biomarker-guided immunotherapy administered to patients at the proper immune phase of sepsis represents a potential major advance in the treatment of sepsis and more broadly in the field of infectious disease. PMID:24232462

Hotchkiss, Richard S.; Monneret, Guillaume; Payen, Didier

2014-01-01

262

Anti-inflammatory strategies for the treatment of sepsis.  

PubMed

Sepsis leads to an overwhelming inflammatory response of the host and is usually accompanied by well-known clinical symptoms (fever, tachycardia, leukocytosis, and so on) and the accompanying systemic inflammatory response syndrome (SIRS). Accordingly, most efforts to develop treatment strategies for sepsis have focused on those designed to counteract overactivation of the inflammatory system. Despite intensive research into identifying targets in sepsis, most of the resulting clinical trials have been based on experimental data and have resulted in no beneficial effects (i.e., survival). Recombinant activated protein C (APC) represents the first treatment that has led to restricted approval for use in sepsis in the USA and worldwide. This article reviews approaches to anti-inflammatory treatment in sepsis and provides an outlook into ongoing clinical trials as well as new treatments that have not yet been evaluated in the clinical setting. PMID:12662146

Riedemann, Niels C; Ward, Peter A

2003-04-01

263

Therapeutic potential of HMGB1-targeting agents in sepsis  

PubMed Central

Sepsis refers to a systemic inflammatory response syndrome resulting from a microbial infection. The inflammatory response is partly mediated by innate immune cells (such as macrophages, monocytes and neutrophils), which not only ingest and eliminate invading pathogens but also initiate an inflammatory response upon recognition of pathogen-associated molecular patterns (PAMPs). The prevailing theories of sepsis as a dysregulated inflammatory response, as manifested by excessive release of inflammatory mediators such as tumour necrosis factor and high-mobility group box 1 protein (HMGB1), are supported by extensive studies employing animal models of sepsis. Here we review emerging evidence that support extracellular HMGB1 as a late mediator of experimental sepsis, and discuss the therapeutic potential of several HMGB1-targeting agents (including neutralising antibodies and steroid-like tanshinones) in experimental sepsis. PMID:18980707

Wang, Haichao; Zhu, Shu; Zhou, Rongrong; Li, Wei; Sama, Andrew E.

2008-01-01

264

Sepsis in Old Age: Review of Human and Animal Studies  

PubMed Central

Sepsis is a serious problem among the geriatric population as its incidence and mortality rates dramatically increase with advanced age. Despite a large number of ongoing clinical and basic research studies, there is currently no effective therapeutic strategy that rescues elderly patients with severe sepsis. Recognition of this problem is relatively low as compared to other age-associated diseases. The disparity between clinical and basic studies is a problem, and this is likely due, in part, to the fact that most laboratory animals used for sepsis research are not old while the majority of sepsis cases occur in the geriatric population. The objective of this article is to review recent epidemiological studies and clinical observations, and compare these with findings from basic laboratory studies which have used aged animals in experimental sepsis. PMID:24729938

Starr, Marlene E; Saito, Hiroshi

2014-01-01

265

Lactoferrin for prevention of neonatal sepsis.  

PubMed

Preterm neonates are at risk to acquire infections. In addition to the high mortality associated with sepsis, these patients are at risk for long-term disabilities, particularly neurodevelopment impairment. Several interventions have been evaluated to reduce rates of infections in neonates but have not proven efficacy. Lactoferrin (LF), a milk glycoprotein with anti-inflammatory, immunomodulatory and anti-microbial properties, has the potential to prevent infections in young children. We performed a review of current and ongoing clinical trials of LF for prevention of neonatal sepsis, and found eleven registered clinical trials that include more than 6,000 subjects. Few of these trials have finished; despite their small sample size, the preliminary results show a trend towards a positive protective effect of LF on neonatal infections. Larger trials are underway to confirm the findings of these initial studies. This information will help to define LF's role in clinical settings and, if proven effective, would profoundly affect the treatment of low birth weight neonates as a cost-effective intervention worldwide. PMID:24935001

Turin, Christie G; Zea-Vera, Alonso; Pezo, Alonso; Cruz, Karen; Zegarra, Jaime; Bellomo, Sicilia; Cam, Luis; Llanos, Raul; Castañeda, Anne; Tucto, Lourdes; Ochoa, Theresa J

2014-10-01

266

The gene for type A streptococcal exotoxin (erythrogenic toxin) is located in bacteriophage T12.  

PubMed Central

The infection of Streptococcus pyogenes T25(3) with the temperate bacteriophage T12 results in the conversion of the nontoxigenic strain to type A streptococcal exotoxin (erythrogenic toxin) production. Although previous research has established that integration of the bacteriophage genome into the host chromosome is not essential for exotoxin production, the location of the gene on the bacteriophage or bacterial chromosome had not been determined. In the present investigation, recombinant DNA techniques were used to determine whether the gene specifying type A streptococcal exotoxin (speA) production is located on the bacteriophage chromosome. Bacteriophage T12 was obtained from S. pyogenes T25(3)(T12) by induction with mitomycin C, and after isolation of bacteriophage DNA by phenol-chloroform extraction, the DNA was digested with restriction enzymes and ligated with Escherichia coli plasmid pHP34 or the Streptococcus-E. coli shuttle vector pSA3. Transformation of E. coli HB101 with the recombinant molecules allowed selection of E. coli clones containing bacteriophage T12 genes. Immunological assays with specific antibody revealed the presence of type A streptococcal exotoxin in sonicates of E. coli transformants. Subcloning experiments localized the speA gene to a 1.7-kilobase segment of the bacteriophage T12 genome flanked by SalI and HindIII sites. Introduction of the pSA3 vector containing the speA gene into Streptococcus sanguis (Challis) resulted in transformants that secreted the type A exotoxin. Immunological analysis showed that the type A streptococcal exotoxin produced by E. coli and S. sanguis transformants was identical to the type A exotoxin produced by S. pyogenes T25(3)(T12). Southern blot hybridizations with the cloned fragment confirmed its presence in the bacteriophage T12 genome and its absence in the T25(3) nonlysogen. Therefore, the gene for type A streptococcal exotoxin is located in the bacteriophage genome, and conversion of S. pyogenes T25(3) to toxigenicity occurs in a manner similar to the conversion of Corynebacterium diphtheriae to toxigenicity by bacteriophage beta. Images PMID:6389348

Weeks, C R; Ferretti, J J

1984-01-01

267

Pulse high-volume haemofiltration for treatment of severe sepsis: effects on hemodynamics and survival  

Microsoft Academic Search

INTRODUCTION: Severe sepsis is the leading cause of mortality in critically ill patients. Abnormal concentrations of inflammatory mediators appear to be involved in the pathogenesis of sepsis. Based on the humoral theory of sepsis, a potential therapeutic approach involves high-volume haemofiltration (HVHF), which has exhibited beneficial effects in severe sepsis, improving haemodynamics and unselectively removing proinflammatory and anti-inflammatory mediators. However,

Ranistha Ratanarat; Alessandra Brendolan; Pasquale Piccinni; Maurizio Dan; Gabriella Salvatori; Zaccaria Ricci; Claudio Ronco

2005-01-01

268

Is neuroimmunomodulation a future therapeutic approach for sepsis?  

PubMed

Sepsis is considered as a disease of profoundly and uncontrollably activated innate immune response against bacterial infection or their products. Thus, regulation of innate immune response plays a critical role in controlling exaggerated systemic inflammation responsible for sepsis development. However, treatment of patients suffering from sepsis or its more severe form (i.e. severe sepsis or septic shock) with available antibiotics or immunomodulatory agents did not prove effective in controlling multi organ damage and mortality. Therefore it is important to explore cascades of mechanisms associated with pathogenesis of sepsis causing high mortality. The nervous system via peripheral nervous system (PNS) or sympathetic nervous system (SNS) along with hypothalamic pituitary axis (HPA) regulates the innate immune response. Thus the nervous system may play an important role in fine tuning and precise regulation of exaggerated innate immune response via different pathways (i.e. cholinergic pathway activated by vagus nerve stimulation, alpha- or beta-adrenergic receptor activation etc.) in sepsis. Hence neuroimmunomodulation can be a future approach to treat sepsis. PMID:19840870

Kumar, V; Sharma, A

2010-01-01

269

Challenges in the diagnosis and management of neonatal sepsis.  

PubMed

Neonatal sepsis is the third leading cause of neonatal mortality and a major public health problem, especially in developing countries. Although recent medical advances have improved neonatal care, many challenges remain in the diagnosis and management of neonatal infections. The diagnosis of neonatal sepsis is complicated by the frequent presence of noninfectious conditions that resemble sepsis, especially in preterm infants, and by the absence of optimal diagnostic tests. Since neonatal sepsis is a high-risk disease, especially in preterm infants, clinicians are compelled to empirically administer antibiotics to infants with risk factors and/or signs of suspected sepsis. Unfortunately, both broad-spectrum antibiotics and prolonged treatment with empirical antibiotics are associated with adverse outcomes and increase antimicrobial resistance rates. Given the high incidence and mortality of sepsis in preterm infants and its long-term consequences on growth and development, efforts to reduce the rates of infection in this vulnerable population are one of the most important interventions in neonatal care. In this review, we discuss the most common questions and challenges in the diagnosis and management of neonatal sepsis, with a focus on developing countries. PMID:25604489

Zea-Vera, Alonso; Ochoa, Theresa J

2015-02-01

270

Autoantibody germ-line gene segment encodes V{sub H} and V{sub L} regions of a human anti-streptococcal monoclonal antibody recognizing streptococcal M protein and human cardiac myosin epitopes  

SciTech Connect

Cross-reactivity of anti-streptococcal Abs with human cardiac myosin may result in sequelae following group A streptococcal infections. Molecular mimicry between group A streptococcal M protein and cardiac myosin may be the basis for the immunologic cross-reactivity. In this study, a cross-reactive human anti-streptococcal/antimyosin mAb (10.2.3) was characterized, and the myosin epitopes were recognized by the Ab identified. mAb 10.2.3 reacted with four peptides from the light meromyosin (LMM) tail fragment of human cardiac myosin, including LMM-10 (1411-1428), LMM-23 (1580-1597), LMM-27 (1632-1649), and LMM-30 (1671-1687). Only LMM-30 inhibited binding of mAb 10.2.3 to streptococcal M protein and human cardiac myosin. Human mAb 10.2.3 labeled cytoskeletal structures within rat heart cells in indirect immunofluorescence, and reacted with group A streptococci expressing various M protein serotypes, PepM5, and recombinant M protein. The nucleotide sequence of gene segments encoding the Ig heavy and light chain V region of mAb 10.2.3 was determined. The light chain V segment was encoded by a VK1 gene segment that was 98.5% identical with germ-line gene humig{sub K}Vi5. The V segment of the heavy chain was encoded by a V{sub H}3a gene segment that differed from the V{sub H}26 germ-line gene by a single base change. V{sub H}26 is expressed preferentially in early development and encodes autoantibodies with anti-DNA and rheumatoid factor specificities. Anti-streptococcal mAb 10.2.3 is an autoantibody encoded by V{sub H} and V{sub L} genes, with little or no somatic mutation. 63 refs., 11 figs.

Quinn, A.; Cunningham, M.W. [Univ. of Oklahoma Health Sciences Center, Oklahoma City, OK (United States); Adderson, E.E. [Univ. of Utah, Salt Lake City, UT (United States)] [and others

1995-04-15

271

Sepsis in Canadian children: a national analysis using administrative data  

PubMed Central

Background Severe infection resulting in sepsis is recognized as a leading cause of morbidity and mortality worldwide. The purpose of this study is to use longitudinal, population-based data to report national-level hospital metrics, providing a current assessment of the status of sepsis hospitalizations in Canadian children. Methods We performed an analysis of previously abstracted data from the Canadian Institute for Health Information (CIHI) Discharge Abstract Database (DAD). Children aged 0–17 years at the time of hospital admission were identified from a cohort of patients with sepsis or severe sepsis using the International Classification of Diseases and Related Health Problems, 10th Revision (ICD-10-CA) and the Canadian Classification of Health Interventions (CCI). Descriptive population-based statistics are reported. Results Hospitalization data for 20,130 children admitted over 5 years were reviewed. The majority of children were young, with neonates (56.3%) and infants under 2 months (18.8%) representing the majority of cases. A decline in age-adjusted hospitalization rates was demonstrated in both overall and non-severe sepsis across the study period; however, no change was demonstrated for severe sepsis. While overall in-hospital crude mortality rates did not change significantly across the study period (range 5.1%–5.4%), a significant decrease was found in children aged 3–23 months and adolescents. Multi-organ failure was reported in more than one-quarter of children with severe sepsis. Odds of mortality increased significantly with number of organs failed. Conclusion Sepsis remains an important cause of morbidity and mortality in Canadian children, posing a significant burden on health care resources. Age continues to be associated with the incidence and severity of illness. Overall hospitalization rates have declined over time, as has mortality in severe sepsis. This report provides baseline metrics for future outcome-based research in Canada targeting prevention strategies and early diagnosis, as well as therapies preventing and managing organ failure. PMID:25525390

Thompson, Graham C; Kissoon, Niranjan

2014-01-01

272

Enzyme-linked immunosorbent assay for detection of type A streptococcal exotoxin: kinetics and regulation during growth of Streptococcus pyogenes.  

PubMed Central

We describe the detection and quantitation of type A streptococcal exotoxin (erythrogenic toxin, streptococcal pyrogenic exotoxin) by an enzyme-linked immunosorbent assay. This sensitive and specific technique detected microgram amounts of type A exotoxin and was useful for studying the kinetics and regulation of type A exotoxin production during the growth of Streptococcus pyogenes NY5. Maximum production of type A exotoxin was observed during the mid-log phase of growth, similar to the production of other streptococcal extracellular products. When S. pyogenes NY5 was grown at 42 degrees C, decreases in both growth and type A exotoxin production were observed. The results obtained when we studied the influence of nutrient additives and metal ions on the production of type A exotoxin led to the conclusion that none of these factors significantly affected type A exotoxin synthesis and that regulation was constitutive. Images PMID:7026447

Houston, C W; Ferretti, J J

1981-01-01

273

Pediatric Severe Sepsis in US Children’s Hospitals  

PubMed Central

Objective To compare the prevalence, resource utilization, and mortality for pediatric severe sepsis identified using two established identification strategies. Design Observational cohort study from 2004–2012. Setting Forty-four pediatric hospitals contributing data to the Pediatric Health Information Systems database. Patients Children ?18 years of age. Measurements and Main Results We identified patients with severe sepsis or septic shock by using two International Classification of Diseases, 9th edition-Clinical Modification (ICD9-CM) based coding strategies: 1) combinations of ICD9-CM codes for infection plus organ dysfunction (combination code cohort); 2) ICD9-CM codes for severe sepsis and septic shock (sepsis code cohort). Outcomes included prevalence of severe sepsis, as well as hospital and intensive care unit (ICU) length of stay (LOS), and mortality. Outcomes were compared between the two cohorts examining aggregate differences over the study period and trends over time. The combination code cohort identified, 176,124 hospitalizations (3.1% of all hospitalizations), while the sepsis code cohort identified 25,236 hospitalizations (0.45%), a 7-fold difference. Between 2004 and 2012, the prevalence of sepsis increased from 3.7% to 4.4% using the combination code cohort and from 0.4% to 0.7% using the sepsis code cohort (p<0.001 for trend in each cohort). LOS (hospital and ICU) and costs decreased in both cohorts over the study period (p<0.001). Overall hospital mortality was higher in the sepsis code cohort than the combination code cohort (21.2%, (95% CI: 20.7–21.8 vs. 8.2%,(95% CI: 8.0–8.3). Over the 9 year study period, there was an absolute reduction in mortality of 10.9% (p<0.001) in the sepsis code cohort and 3.8% (p<0.001) in the combination code cohort. Conclusions Prevalence of pediatric severe sepsis increased in the studied US children’s hospitals over the past 9 years, though resource utilization and mortality decreased. Epidemiologic estimates of pediatric severe sepsis varied up to 7-fold depending on the strategy used for case ascertainment. PMID:25162514

Balamuth, Fran; Weiss, Scott L.; Neuman, Mark I.; Scott, Halden; Brady, Patrick W.; Paul, Raina; Farris, Reid W.D.; McClead, Richard; Hayes, Katie; Gaieski, David; Hall, Matt; Shah, Samir S.; Alpern, Elizabeth R.

2014-01-01

274

[Use of biomarkers in sepsis. Update and perspectives].  

PubMed

Sepsis and related complications are a challenge for intensive care medicine. Despite many advances in antibiotic therapy sepsis remains one of the most common diseases of patients in intensive care units and is designated as the main cause of death in critically ill patients. Persisting sepsis leads to impaired immunity, resulting in immunosuppression. Unspecific predictive signs complicate an early diagnosis; however, an early initiation of adequate therapy is of crucial importance for the prognosis. Scoring systems can be applied for the initial evaluation but are controversially discussed concerning the monitoring of disease progression and therapy as well as outcome prediction. Biomarkers are considered as a complementary approach. PMID:25002138

Siegler, B H; Weiterer, S; Lichtenstern, C; Stumpp, D; Brenner, T; Hofer, S; Weigand, M A; Uhle, F

2014-09-01

275

Manipulation of the complement system for benefit in sepsis.  

PubMed

There is evidence in sepsis, both in rodents and in humans, that activation of the complement system results in excessive production of C5a, which triggers a series of events leading to septic shock, multiorgan failure, and lethality. In rodents following cecal ligation and puncture (CLP), which induces polymicrobial sepsis, in vivo blockade of C5a using neutralizing antibodies dramatically improved survival, reduced apoptosis of lymphoid cells, and attenuated the ensuing coagulopathy. Based on these data, it seems reasonable to consider therapeutic blockade of C5a in humans entering into sepsis and septic shock. Strategies for the development of such an antibody for use in humans are presented. PMID:22482043

Ward, Peter A; Guo, Ren-Feng; Riedemann, Niels C

2012-01-01

276

Manipulation of the Complement System for Benefit in Sepsis  

PubMed Central

There is evidence in sepsis, both in rodents and in humans, that activation of the complement system results in excessive production of C5a, which triggers a series of events leading to septic shock, multiorgan failure, and lethality. In rodents following cecal ligation and puncture (CLP), which induces polymicrobial sepsis, in vivo blockade of C5a using neutralizing antibodies dramatically improved survival, reduced apoptosis of lymphoid cells, and attenuated the ensuing coagulopathy. Based on these data, it seems reasonable to consider therapeutic blockade of C5a in humans entering into sepsis and septic shock. Strategies for the development of such an antibody for use in humans are presented. PMID:22482043

Ward, Peter A.; Guo, Ren-Feng; Riedemann, Niels C.

2012-01-01

277

Potential of surface acoustic wave biosensors for early sepsis diagnosis.  

PubMed

Early diagnosis of sepsis is a difficult problem for intensivists and new biomarkers for early diagnosis have been difficult to come by. Here we discuss the potential of adapting a technology from the electronics industry, surface acoustic wave (SAW) sensors, for diagnosis of multiple markers of sepsis in real time, using non-invasive assays of exhaled breath condensate. The principles and advantages of the SAW technology are reviewed as well as a proposed plan for adapting this flexible technology to early sepsis detection. PMID:23471596

Csete, Marie; Hunt, William D

2013-08-01

278

Plasma dia-filtration for severe sepsis.  

PubMed

The mortality rate in severe sepsis is 30-50%, and independent liver and renal dysfunction impacts significantly on hospital and intensive care mortality. If 4 or more organs fail, mortality is > 90%. Recently, we reported a novel plasmapheresis--plasma diafiltration (PDF)--the concept of which is plasma filtration with dialysis. PDF employs a plasma separator that has a sieving coefficient of 0.3 for albumin and which requires flowing dialysate outside the hollow fiber. For substitute liquid, 1,200 ml of fresh frozen plasma followed by 50 ml of 25% albumin solution is used for 8 h as 1 session. In a single-center study, 24 patients with septic shock were admitted to the ICU, then 37.7 +/- 30.0 h later, 7 patients received PDF. The patients' Sequential Organ Failure Assessment (SOFA) scores had increased from 14.9 +/- 3.6 on ICU admission to 17.1 +/- 3.0 before PDF procedure. PDF was performed, with an average of 7.4 +/- 4.4 sessions (range 3-15) per patient. Five patients survived after day 28, thus the 28-day mortality rate was 29%. In our multicenter study, 33 patients with severe sepsis who simultaneously suffered from liver dysfunction were enrolled and received PDF. On average, 12.0 +/- 16.4 sessions (range 2-70) per patient were performed. The 28-day mortality rate was 36.4%, while the predicted death rate was 68.0 +/- 17.7%. These findings suggest that PDF is a simple modality and may become a useful strategy for treatment of patients with septic multiple organ failure. PMID:20473002

Eguchi, Yutaka

2010-01-01

279

Hydrogen sulfide reduces kidney injury due to urinary-derived sepsis by inhibiting NF-?B expression, decreasing TNF-? levels and increasing IL-10 levels  

PubMed Central

The present study aimed to investigate the effect of hydrogen sulfide (H2S) on kidney injury induced by urinary-derived sepsis. Rabbits were randomly divided into control, sham, sepsis, NaHS 2.8 ?mol/kg and NaHS 8.4 ?mol/kg groups, with six rabbits in each group. Upper urinary tract obstruction and acute infection was induced to establish the sepsis model. Blood was collected to carry out a white blood cell (WBC) count, and creatinine (Cr) and blood urea nitrogen (BUN) analysis. Morphological changes were observed by hematoxylin and eosin (H&E) staining and transmission electron microscopy. Immunohistochemical staining was used to detect the expression levels of tumor necrosis factor (TNF)-?, interleukin (IL)-10 and nuclear factor ?-light-chain-enhancer of activated B cells (NF-?B). Cystathionine-?-lyase (CSE) activity was measured by the spectrophotometric methylene blue method and the blood H2S concentration was measured by deproteinization. WBC, Cr and BUN levels were significantly elevated in the sepsis group compared with those in the control group (P<0.05). Following treatment with NaHS, the WBC, Cr and BUN levels were significantly decreased in the NaHS groups compared with those in the sepsis group (P<0.05). The pathological features of kidney injury were also alleviated by NaHS. In the sepsis group, the levels of TNF-?, IL-10 and NF-?B were significantly increased compared with those in the control group (P<0.05). In the NaHS groups, the TNF-? and NF-?B levels were significantly reduced whereas the IL-10 level was significantly increased compared with the respective levels in the sepsis group (P<0.05). The H2S concentration was significantly decreased in the sepsis group and this reduction was attenuated in the NaHS groups (P<0.05). Furthermore, the NaHS 8.4 ?mol/kg dose revealed a more potent effect than the NaHS 2.8 ?mol/kg dose. Thus, exogenous H2S reduced kidney injury from urinary-derived sepsis by decreasing the levels of NF-?B and TNF-?, and increasing the level of IL-10. PMID:25009602

CHEN, XIAN; XU, WUJUN; WANG, YI; LUO, HONGMEI; QUAN, SUQIN; ZHOU, JING; YANG, NING; ZHANG, TAO; WU, LEI; LIU, JUN; LONG, XIANGYANG; ZHU, NENG; XIE, HUANG; LUO, ZHIGANG

2014-01-01

280

Government introduces action plan to reduce deaths from sepsis.  

PubMed

Tackling sepsis - the potentially fatal over-reaction of the immune system to infection - must be given the same priority as reducing Clostridium difficile and MRSA infections, the government has said. PMID:25585729

Kleebauer, Alistair

2015-01-14

281

Inflammatory Response in Microvascular Endothelium in Sepsis: Role of Oxidants  

PubMed Central

Sepsis, as a severe systemic inflammatory response to bacterial infection, represents a major clinical problem. It is characterized by the excessive production of reactive oxygen species (ROS) both in the circulation and in the affected organs. The excessive generation of ROS inevitably leads to oxidative stress in the microvasculature and has been implicated as a causative event in a number of pathologies including sepsis. In this review, we focus on the role of oxidative and nitrosative stress during the early onset of sepsis. Changes in microvascular endothelial cells, the cell type that occurs in all organs, are discussed. The mechanisms underlying septic induction of oxidative and nitrosative stresses, the functional consequences of these stresses, and potential adjunct therapies for microvascular dysfunction in sepsis are identified. PMID:18545638

Cepinskas, Gediminas; Wilson, John X

2008-01-01

282

Mechanical ventilation drives pneumococcal pneumonia into lung injury and sepsis in mice: protection by adrenomedullin  

PubMed Central

Introduction Ventilator-induced lung injury (VILI) contributes to morbidity and mortality in acute respiratory distress syndrome (ARDS). Particularly pre-injured lungs are susceptible to VILI despite protective ventilation. In a previous study, the endogenous peptide adrenomedullin (AM) protected murine lungs from VILI. We hypothesized that mechanical ventilation (MV) contributes to lung injury and sepsis in pneumonia, and that AM may reduce lung injury and multiple organ failure in ventilated mice with pneumococcal pneumonia. Methods We analyzed in mice the impact of MV in established pneumonia on lung injury, inflammation, bacterial burden, hemodynamics and extrapulmonary organ injury, and assessed the therapeutic potential of AM by starting treatment at intubation. Results In pneumococcal pneumonia, MV increased lung permeability, and worsened lung mechanics and oxygenation failure. MV dramatically increased lung and blood cytokines but not lung leukocyte counts in pneumonia. MV induced systemic leukocytopenia and liver, gut and kidney injury in mice with pneumonia. Lung and blood bacterial burden was not affected by MV pneumonia and MV increased lung AM expression, whereas receptor activity modifying protein (RAMP) 1–3 expression was increased in pneumonia and reduced by MV. Infusion of AM protected against MV-induced lung injury (66% reduction of pulmonary permeability p?sepsis by aggravating lung injury and systemic hyperinflammation leading to liver, kidney and gut injury. AM may be a promising therapeutic option to protect against development of lung injury, sepsis and extrapulmonary organ injury in mechanically ventilated individuals with severe pneumonia. PMID:24731244

2014-01-01

283

Anti-inflammatory effect of Momordica charantia in sepsis mice.  

PubMed

Wild bitter gourd (Momordica charantia L. var. abbreviate Seringe), a common vegetable in Asia, is used in traditional medicine to treat various diseases, including inflammation. Extant literature indicates that wild bitter gourds have components that activate PPAR? and PPAR?. This research probed the influence of adding wild bitter gourd to diets on inflammation responses in mice with sepsis induced by intraperitoneal injection of LPS. Male BALB/c mice were divided normal, sepsis, positive control, and three experimental groups. The latter ate diets with low (1%), moderate (2%), and high (10%) ratios of wild bitter gourd lyophilized powder. Before mice were sacrificed, with the exception of the normal group, intraperitoneal injection of LPS induced sepsis in each group; positive control group was injected with LPS after PDTC. This experiment revealed starkly lower weights in groups with added wild bitter gourd than those of the remaining groups. Blood lipids (TG, cholesterol, and NEFA) were also lower in comparison to the sepsis group, and blood glucose concentrations recovered and approached normal levels. Blood biochemistry values related to inflammation reactions indicated GOT, GPT, C-RP, and NO concentrations of groups with added wild bitter gourd were all lower than those of the sepsis group. Secretion levels of the spleen pro-inflammatory cytokines IL-1, IL-6, and TNF-? tallied significantly lower in comparison to the sepsis group, whereas secretion levels of IL-10 anti-inflammatory cytokine increased. Expression level of proteins NF-?B, iNOS, and COX-2 were significantly inhibited. Results indicate wild bitter gourd in diets promoted lipid metabolism, reducing fat accumulation, and improving low blood glucose in sepsis. Addition of wild bitter gourd can reduce inflammation biochemical markers or indicators and pro-inflammatory cytokines in the body, hence improving the inflammation responses in mice with sepsis. PMID:25153878

Chao, Che-Yi; Sung, Ping-Jyun; Wang, Wei-Hsien; Kuo, Yueh-Hsiung

2014-01-01

284

Sepsis Syndrome in Children: Can We Do Better?  

Microsoft Academic Search

\\u000a Sepsis is a significant healthcare problem both in industrialized and developing countries. In the United States the incidence\\u000a of disease is 56 and 240 per 100,000 per year in children and adults respectively. In adults underlying disease is present\\u000a in 83%. Approximately 50% of the children have underlying diseases. Annual total costs of sepsis in the United States are\\u000a estimated

Marieke Emonts; Ronald de Groot

2004-01-01

285

C5a receptor and thymocyte apoptosis in sepsis  

Microsoft Academic Search

In sepsis, apoptosis occurs in many different organs. The mediators responsible for induction of apoptosis are not clearly known, although there are some suggestions that C5a and the C5a receptor (C5aR) might be directly linked to apoptosis. In the cecal ligation\\/puncture (CLP) model of sepsis in rats, apoptosis occurs early in a variety of organs, especially in the thymus. We

Niels C. Riedemann; Ren-Feng Guo; Ines J. Laudes; Katie Keller; Vidya J. Sarma; Vaishalee Padgaonkar; Firas S. Zetoune; Peter A. Ward

2002-01-01

286

Molecular diagnosis of sepsis: New aspects and recent developments  

PubMed Central

By shortening the time to pathogen identification and allowing for detection of organisms missed by blood culture, new molecular methods may provide clinical benefits for the management of patients with sepsis. While a number of reviews on the diagnosis of sepsis have recently been published we here present up-to-date new developments including multiplex PCR, mass spectrometry and array techniques. We focus on those techniques that are commercially available and for which clinical studies have been performed and published. PMID:24678402

Lehman, L.; Hunfeld, K.-P.; Kost, G.

2014-01-01

287

New approaches to sepsis: molecular diagnostics and biomarkers.  

PubMed

Sepsis is among the most common causes of death in hospitals. It arises from the host response to infection. Currently, diagnosis relies on nonspecific physiological criteria and culture-based pathogen detection. This results in diagnostic uncertainty, therapeutic delays, the mis- and overuse of antibiotics, and the failure to identify patients who might benefit from immunomodulatory therapies. There is a need for new sepsis biomarkers that can aid in therapeutic decision making and add information about screening, diagnosis, risk stratification, and monitoring of the response to therapy. The host response involves hundreds of mediators and single molecules, many of which have been proposed as biomarkers. It is, however, unlikely that one single biomarker is able to satisfy all the needs and expectations for sepsis research and management. Among biomarkers that are measurable by assays approved for clinical use, procalcitonin (PCT) has shown some usefulness as an infection marker and for antibiotic stewardship. Other possible new approaches consist of molecular strategies to improve pathogen detection and molecular diagnostics and prognostics based on transcriptomic, proteomic, or metabolic profiling. Novel approaches to sepsis promise to transform sepsis from a physiologic syndrome into a group of distinct biochemical disorders and help in the development of better diagnostic tools and effective adjunctive sepsis therapies. PMID:23034322

Reinhart, Konrad; Bauer, Michael; Riedemann, Niels C; Hartog, Christiane S

2012-10-01

288

New Approaches to Sepsis: Molecular Diagnostics and Biomarkers  

PubMed Central

Summary: Sepsis is among the most common causes of death in hospitals. It arises from the host response to infection. Currently, diagnosis relies on nonspecific physiological criteria and culture-based pathogen detection. This results in diagnostic uncertainty, therapeutic delays, the mis- and overuse of antibiotics, and the failure to identify patients who might benefit from immunomodulatory therapies. There is a need for new sepsis biomarkers that can aid in therapeutic decision making and add information about screening, diagnosis, risk stratification, and monitoring of the response to therapy. The host response involves hundreds of mediators and single molecules, many of which have been proposed as biomarkers. It is, however, unlikely that one single biomarker is able to satisfy all the needs and expectations for sepsis research and management. Among biomarkers that are measurable by assays approved for clinical use, procalcitonin (PCT) has shown some usefulness as an infection marker and for antibiotic stewardship. Other possible new approaches consist of molecular strategies to improve pathogen detection and molecular diagnostics and prognostics based on transcriptomic, proteomic, or metabolic profiling. Novel approaches to sepsis promise to transform sepsis from a physiologic syndrome into a group of distinct biochemical disorders and help in the development of better diagnostic tools and effective adjunctive sepsis therapies. PMID:23034322

Bauer, Michael; Riedemann, Niels C.; Hartog, Christiane S.

2012-01-01

289

Spontaneous Neutrophil Migration Patterns during Sepsis after Major Burns  

PubMed Central

Finely tuned to respond quickly to infections, neutrophils have amazing abilities to migrate fast and efficiently towards sites of infection and inflammation. Although neutrophils ability to migrate is perturbed in patients after major burns, no correlations have yet been demonstrated between altered migration and higher rate of infections and sepsis in these patients when compared to healthy individuals. To probe if such correlations exist, we designed microfluidic devices to quantify the neutrophil migration phenotype with high precision. Inside these devices, moving neutrophils are confined in channels smaller than the neutrophils and forced to make directional decisions at bifurcations and around posts. We employed these devices to quantify neutrophil migration across 18 independent parameters in 74 blood samples from 13 patients with major burns and 3 healthy subjects. Blinded, retrospective analysis of clinical data and neutrophil migration parameters revealed that neutrophils isolated from blood samples collected during sepsis migrate spontaneously inside the microfluidic channels. The spontaneous neutrophil migration is a unique phenotype, typical for patients with major burns during sepsis and often observed one or two days before the diagnosis of sepsis is confirmed. The spontaneous neutrophil migration phenotype is rare in patients with major burns in the absence of sepsis, and is not encountered in healthy individuals. Our findings warrant further studies of neutrophils and their utility for early diagnosing and monitoring sepsis in patients after major burns. PMID:25489947

Jones, Caroline N.; Moore, Molly; Dimisko, Laurie; Alexander, Andrew; Ibrahim, Amir; Hassell, Bryan A.; Warren, H. Shaw; Tompkins, Ronald G.; Fagan, Shawn P.; Irimia, Daniel

2014-01-01

290

Clinicomicrobiological profile of children with acute pharyngitis with special reference to streptococcol grouping.  

PubMed

A total of 100 patients of acute pharyngitis were evaluated clinically and investigated microbiologically. Eighty patients proved culture positive acute pharyngitis, among them 17 patients proved positive for beta-haemolytic streptococci, 14 patients for Staphylococcus aureus, 24 for pneumococci, 13 patients for Streptococcus viridans, 3 for Brahmanella catarrhalis, 4 for coagulase negative staphylococci, 5 had mixed infection. Further streptococcal grouping was carried out on these isolates. Out of 17 isolates of beta-haemolytic streptococci 13 (76.47%) belonged to group A and 2 each (11.76%) belonged to group C and group G. PMID:23469573

Patil, Harsha B; Shahapur, Praveen R

2011-12-01

291

Purification of group C streptococcal extracellular antigens detected with naturally occurring human antibodies: isolation of streptokinase and two previously undescribed antigens.  

PubMed Central

Twelve antigens were detected in crude group C streptococcal extracellular concentrates, using naturally occurring antibodies in normal human gamma globulin. These group C streptococcal antigens all appeared to be present in crude group A streptococcal extracellular concentrates, although the latter contained additional antigens reactive with the human antibodies. Systematic purification procedures were established for the isolation of the group C streptococcal antigens by a sequence of salting out, hydroxylapatite chromatography, Sephadex G-100 gel filtration, and isoelectric focusing. With such procedures, three of the group C streptococcal antigens were isolated in a relatively pure state. One of the purified antigens was identified as streptokinase on the basis of its fibrinolytic potency, its reaction of identity with two purified streptokinase fractions obtained from other sources, and its high titer in immunodiffusion assays. The most highly purified streptokinase fractions, derived from the 0.1 M sodium phosphate hydroxylapatite eluate, revealed a plasmin-inhibiting effect at high concentrations of streptokinase. This was not seen in the purified streptokinase of equivalent functional and immunological purity that was derived from the 0.2 M sodium phosphate hydroxylapatite peak. Two other streptococcal antigens were also isolated to a high degree during the course of the above study. These were designated antigens X and Y and were found to be unrelated immunologically to each other or to streptokinase. Their isoelectric points were 6.7 and 8.8, respectively, and both were present in group A streptococcal concentrates. Esterase activity was found to be widely distributed in almost all of the fractions obtained in the various purification steps, indicating a high degree of heterogeneity of the streptococcal enzyme. Histochemical staining techniques applied to the immune precipitates formed with human antibodies indicated that none of the antigens detected in crude group C and group A streptococcal concentrates possessed catalase, glucuronidase, glucosaminidase, acid or alkaline phosphatase, arylsulfatase, leucineaminopeptidase, or chymotrypsin enzymatic activities. Images PMID:131108

Kiefer, D; Halbert, S P

1976-01-01

292

IL6 Plasma Concentrations in Patients with Sepsis Receiving SLED and Antibiotics: A Predictor for Survival.  

PubMed

Background: The present study evaluated interleukin-6 (IL6) as a predictor of mortality in patients and sepsis with acute kidney injury (AKI) receiving sustained low-efficiency dialysis (SLED) and antibiotic therapy. Patients and Methods: Seven patients with sepsis receiving antibiotics and SLED for AKI were studied. Blood was obtained at baseline prior to SLED and antibiotics, during SLED, and then after stopping SLED. IL6 concentrations were measured using an enzyme-linked immunosorbent assay (ELISA). Results: Mean plasma IL6 concentrations ranged between 700 and 900 pg/ml for the first 8 h after starting SLED but was significantly lower after discontinuation of SLED (200-250 pg/ml) (p=0.0044). Three out of seven patients survived to be discharged from the hospital and all three had significantly lower concentrations of IL6 during the first 8 h compared to those who died in the hospital (p<0.0001). Conclusion: The combination of SLED and antibiotic therapy was unable to lower the initial high plasma IL6 concentrations, and high initial IL6 concentrations predicted in-hospital mortality. PMID:25398811

McGuire, Timothy R; Reardon, Nicole T; Bogard, Kimberly; Plumb, Troy J; Bultsma, Chris J; Nissen, Steve W; Fuller, Patrick D; Olsen, Keith M

293

Complement Factor B is the Downstream Effector of Toll-Like Receptors and Plays an Important Role in a Mouse Model of Severe Sepsis  

PubMed Central

Severe sepsis involves massive activation of the innate immune system and leads to high mortality. Previous studies have demonstrated that various types of Toll-like receptors (TLRs) mediate a systemic inflammatory response and contribute to organ injury and mortality in animal models of severe sepsis. However, the downstream mechanisms responsible for TLR-mediated septic injury are poorly understood. Here, we show that activation of TLR2, TLR3 and TLR4 markedly enhanced complement factor B (cfB) synthesis and release by macrophages and cardiac cells. Polymicrobial sepsis, created by cecal ligation and puncture (CLP) in a mouse model, augmented cfB levels in the serum, peritoneal cavity and major organs including the kidney and heart. CLP also led to the alternative pathway (AP) activation, C3 fragment deposition in the kidney and heart, and cfB-dependent C3dg elevation. Bacteria isolated from septic mice activated the serum AP via a factor D-dependent manner. MyD88 deletion attenuated cfB/C3 up-regulation as well as cleavage induced by polymicrobial infection. Importantly, during sepsis, absence of cfB conferred a protective effect with improved survival and cardiac function, and markedly attenuated acute kidney injury. cfB deletion also led to increased neutrophil migratory function during the early phase of sepsis, decreased local and systemic bacterial load, attenuated cytokine production and reduced neutrophil reactive oxygen species production. Together, our data indicate that cfB acts as a downstream effector of TLR signaling and plays a critical role in the pathogenesis of severe bacterial sepsis. PMID:24154627

Zou, Lin; Feng, Yan; Li, Yan; Zhang, Ming; Chen, Chan; Cai, Jiayan; Gong, Yu; Wang, Larry; Thurman, Joshua M.; Wu, Xiaobo; Atkinson, John P.; Chao, Wei

2013-01-01

294

Complement factor B is the downstream effector of TLRs and plays an important role in a mouse model of severe sepsis.  

PubMed

Severe sepsis involves massive activation of the innate immune system and leads to high mortality. Previous studies have demonstrated that various types of TLRs mediate a systemic inflammatory response and contribute to organ injury and mortality in animal models of severe sepsis. However, the downstream mechanisms responsible for TLR-mediated septic injury are poorly understood. In this article, we show that activation of TLR2, TLR3, and TLR4 markedly enhanced complement factor B (cfB) synthesis and release by macrophages and cardiac cells. Polymicrobial sepsis, created by cecal ligation and puncture in a mouse model, augmented cfB levels in the serum, peritoneal cavity, and major organs including the kidney and heart. Cecal ligation and puncture also led to the alternative pathway activation, C3 fragment deposition in the kidney and heart, and cfB-dependent C3dg elevation. Bacteria isolated from septic mice activated the serum alternative pathway via a factor D-dependent manner. MyD88 deletion attenuated cfB/C3 upregulation as well as cleavage induced by polymicrobial infection. Importantly, during sepsis, absence of cfB conferred a protective effect with improved survival and cardiac function and markedly attenuated acute kidney injury. cfB deletion also led to increased neutrophil migratory function during the early phase of sepsis, decreased local and systemic bacterial load, attenuated cytokine production, and reduced neutrophil reactive oxygen species production. Together, our data indicate that cfB acts as a downstream effector of TLR signaling and plays a critical role in the pathogenesis of severe bacterial sepsis. PMID:24154627

Zou, Lin; Feng, Yan; Li, Yan; Zhang, Ming; Chen, Chan; Cai, Jiayan; Gong, Yu; Wang, Larry; Thurman, Joshua M; Wu, Xiaobo; Atkinson, John P; Chao, Wei

2013-12-01

295

Early sepsis does not increase the risk of late sepsis in very low birth weight neonates  

PubMed Central

Objective To examine whether preterm very low birth weight (VLBW) infants have an increased risk of late-onset sepsis (LOS) following early-onset sepsis (EOS). Study design Retrospective analysis of VLBW infants (401-1500 g) born September 1998 through December 2009 who survived >72 hours and were cared for within the NICHD Neonatal Research Network. Sepsis was defined by growth of bacteria or fungi in a blood culture obtained ?72 hr of birth (EOS) or >72 hr (LOS) and antimicrobial therapy for ?5 days or death <5 d while receiving therapy. Regression models were used to assess risk of death or LOS by 120d and LOS by 120d among survivors to discharge or 120d, adjusting for gestational age and other covariates. Results Of 34,396 infants studied 504 (1.5%) had EOS. After adjustment, risk of death or LOS by 120d did not differ overall for infants with EOS compared with those without EOS [RR:0.99 (0.89-1.09)] but was reduced in infants born at <25wk gestation [RR:0.87 (0.76-0.99), p=0.048]. Among survivors, no difference in LOS risk was found overall for infants with versus without EOS [RR:0.88 (0.75-1.02)], but LOS risk was shorter in infants with BW 401-750 g who had EOS [RR:0.80 (0.64-0.99), p=0.047]. Conclusions Risk of LOS after EOS was not increased in VLBW infants. Surprisingly, risk of LOS following EOS appeared to be reduced in the smallest, most premature infants, underscoring the need for age-specific analyses of immune function. PMID:23295144

Wynn, James L.; Hansen, Nellie I.; Das, Abhik; Cotten, C. Michael; Goldberg, Ronald N.; Sánchez, Pablo J.; Bell, Edward F.; Van Meurs, Krisa P.; Carlo, Waldemar A.; Laptook, Abbot R.; Higgins, Rosemary D.; Benjamin, Daniel K.; Stoll, Barbara J.

2012-01-01

296

Low-dose heparin as treatment for early disseminated intravascular coagulation during sepsis: A prospective clinical study  

PubMed Central

The present study aimed to investigate whether low-dose heparin improves the condition of patients suffering from early disseminated intravascular coagulation (pre-DIC) during sepsis. In total, 37 patients were randomly divided into low-dose heparin intervention and control groups. The heparin group received a low-dose of heparin for 5–7 days, while the other group received only saline. The two groups were treated for sepsis. Blood samples were collected at various times and acute physiology and chronic health evaluation (APACHE)-II scores were recorded at day 1 and 7. In addition, the number of days applying mechanical ventilation and in the intensive care unit (ICU) were recorded, as well as the 28-day mortality rate. APACHE-II scores in the two groups decreased following treatment, however, scores in the heparin group decreased more significantly. Prothrombin fragment and thrombin-antithrombin complex levels in the heparin group were significantly decreased. In addition, the number of days applying a ventilator was fewer and the total stay in ICU was significantly shorter compared with the control group. Significantly fewer complications were observed in the heparin group, however, there was no significant difference in the 28-day mortality rate. In conclusion, low-dose heparin improves the hypercoagulable state of sepsis, which subsequently reduces the incidence of DIC or multiple organ dysfunction syndrome, decreasing the number of days of mechanical ventilation and hospitalization. PMID:24520253

LIU, XIAO-LI; WANG, XIAO-ZHI; LIU, XIU-XIANG; HAO, DONG; JALADAT, YASAMAN; LU, FENG; SUN, TING; LV, CHANG-JUN

2014-01-01

297

Time course of nitric oxide synthases, nitrosative stress, and poly(ADP ribosylation) in an ovine sepsis model  

Microsoft Academic Search

Introduction  Different isoforms of nitric oxide synthases (NOS) and determinants of oxidative\\/nitrosative stress play important roles in\\u000a the pathophysiology of pulmonary dysfunction induced by acute lung injury (ALI) and sepsis. However, the time changes of these\\u000a pathogenic factors are largely undetermined.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  Twenty-four chronically instrumented sheep were subjected to inhalation of 48 breaths of cotton smoke and instillation of\\u000a live Pseudomonas aeruginosa

Matthias Lange; Rhykka Connelly; Daniel L Traber; Atsumori Hamahata; Yoshimitsu Nakano; Aimalohi Esechie; Collette Jonkam; Sanna von Borzyskowski; Lillian D Traber; Frank C Schmalstieg; David N Herndon; Perenlei Enkhbaatar

2010-01-01

298

Streptococcal Upper Respiratory Tract Infections and Exacerbations of Tic and Obsessive-Compulsive Symptoms: A Prospective Longitudinal Study  

ERIC Educational Resources Information Center

Objective: The objective of this blinded, prospective, longitudinal study was to determine whether new group A beta hemolytic streptococcal (GABHS) infections are temporally associated with exacerbations of tic or obsessive-compulsive (OC) symptoms in children who met published criteria for pediatric autoimmune neuropsychiatric disorders…

Leckman, James F.; King, Robert A.; Gilbert, Donald L.; Coffey, Barbara J.; Singer, Harvey S.; Dure, Leon S., IV; Grantz, Heidi; Katsovich, Liliya; Lin, Haiqun; Lombroso, Paul J.; Kawikova, Ivana; Johnson, Dwight R.; Kurlan, Roger M.; Kaplan, Edward L.

2011-01-01

299

GENES, IN ADDITION TO TOLL-LIKE RECEPTOR 2, PLAY A ROLE IN ANTIBACTERIAL DEFENSE TO STREPTOCOCCAL PNEUMONIA  

EPA Science Inventory

Streptococcus infection in human populations continues to be a major cause of morbidity and mortality. To evaluate the effect of genetic background and toll-like receptor 2 (TLR2) on antibacterial defense to streptococcal infection, eight genetically diverse strains of mic...

300

Alterations of leptin in the course of inflammation and severe sepsis  

PubMed Central

Background The adipokine leptin regulates energy expenditure, vascular function, bone and cartilage growth as well as the immune system and systemic inflammatory response. Several activating effects towards T cells, monocytes, endothelium cells and cytokine production have been reported suggesting a protective role of leptin in the setting of an acute systemic inflammation. However, the pathophysiological role of leptin during severe sepsis is currently not elucidated in detail. This study aims to investigate leptin expression in cultured human adipocytes within an inflammatory model and in patients suffering from severe sepsis and evaluates treatment effects of drotrecogin alpha (activated) (DAA), the recombinant form of human activated protein C. Methods In an in-vitro inflammatory model of adipocyte cell-culture the effect of DAA on leptin mRNA expression was evaluated. Synthesis of mRNA was measured by quantitative polymerase chain reaction (qPCR). Additionally, supernatants of these adipocytes as well as serum levels of adiponectin were measured in blood of 104 severe septic patients by ELISA-method. 26 patients were treated with DAA (DAA+), 78 patients were not treated with DAA (DAA-). Results Stimulation of human adipocytes with TNF alpha over 6 and 24?hours resulted in a significant decrease by 46% and 59% of leptin mRNA transcripts compared to un-stimulated controls (p?sepsis, leptin levels increased in DAA+ compared to DAA- patients (p<0.10). Conclusions Leptin appears to be involved in the pathogenesis of a systemic inflammatory response during sepsis. Administration of DAA significantly increased leptin expression. The specific mechanism or even benefit of DAA towards leptin needs further ongoing research. PMID:22973876

2012-01-01

301

Necrotizing fasciitis and streptococcal toxic shock syndrome secondary to varicella in a healthy child  

PubMed Central

Varicella is usually considered to be a benign disease in healthy children; however, serious complications can occur such as necrotizing fasciitis and toxic shock syndrome. We describe a 38-month-old girl with necrotizing fasciitis and streptococcal toxic shock syndrome following varicella. She was previously healthy and vaccinated against varicella at 12 months of age. She had been diagnosed with varicella three days prior to presenting at our facility; she developed fever, vomiting, and painful swelling on her left flank. Her skin lesions worsened, she became lethargic, and had episodes of hypotension and coagulopathy. Necrotizing fasciitis on the left abdominal wall, buttocks, and left thigh was diagnosed by magnetic resonance imaging, and group A Streptococcus was isolated from a tissue culture. She was diagnosed as necrotizing fasciitis and streptococcal toxic shock syndrome, and successfully treated with repeated surgical debridement and fasciotomy, in addition to intensive antibiotics. Our experience suggests that necrotizing fasciitis in patients with varicella should be considered to be a rare complication even with widespread vaccine use. Early diagnosis and intensive treatment are required to prevent a fatal outcome. PMID:25653688

Kwak, Byung Ok; Lee, Min Jung; Park, Hye Won; Song, Min Kyung; Chung, Sochung

2014-01-01

302

The effect of a silver nanoparticle polysaccharide system on streptococcal and saliva-derived biofilms.  

PubMed

In this work, we studied the antimicrobial properties of a nanocomposite system based on a lactose-substituted chitosan and silver nanoparticles: Chitlac-nAg. Twofold serial dilutions of the colloidal Chitlac-nAg solution were both tested on Streptococcus mitis, Streptococcus mutans, and Streptococcus oralis planktonic phase and biofilm growth mode as well as on saliva samples. The minimum inhibitory and bactericidal concentrations of Chitlac-nAg were evaluated together with its effect on sessile cell viability, as well as both on biofilm formation and on preformed biofilm. In respect to the planktonic bacteria, Chitlac-nAg showed an inhibitory/bactericidal effect against all streptococcal strains at 0.1% (v/v), except for S. mitis ATCC 6249 that was inhibited at one step less. On preformed biofilm, Chitlac-nAg at a value of 0.2%, was able to inhibit the bacterial growth on the supernatant phase as well as on the mature biofilm. For S. mitis ATCC 6249, the biofilm inhibitory concentration of Chitlac-nAg was 0.1%. At sub-inhibitory concentrations, the Streptococcal strains adhesion capability on a polystyrene surface showed a general reduction following a concentration-dependent-way; a similar effect was obtained for the metabolic biofilm activity. From these results, Chitlac-nAg seems to be a promising antibacterial and antibiofilm agent able to hinder plaque formation. PMID:23812080

Di Giulio, Mara; Di Bartolomeo, Soraya; Di Campli, Emanuela; Sancilio, Silvia; Marsich, Eleonora; Travan, Andrea; Cataldi, Amelia; Cellini, Luigina

2013-01-01

303

The Effect of a Silver Nanoparticle Polysaccharide System on Streptococcal and Saliva-Derived Biofilms  

PubMed Central

In this work, we studied the antimicrobial properties of a nanocomposite system based on a lactose-substituted chitosan and silver nanoparticles: Chitlac-nAg. Twofold serial dilutions of the colloidal Chitlac-nAg solution were both tested on Streptococcus mitis, Streptococcus mutans, and Streptococcus oralis planktonic phase and biofilm growth mode as well as on saliva samples. The minimum inhibitory and bactericidal concentrations of Chitlac-nAg were evaluated together with its effect on sessile cell viability, as well as both on biofilm formation and on preformed biofilm. In respect to the planktonic bacteria, Chitlac-nAg showed an inhibitory/bactericidal effect against all streptococcal strains at 0.1% (v/v), except for S. mitis ATCC 6249 that was inhibited at one step less. On preformed biofilm, Chitlac-nAg at a value of 0.2%, was able to inhibit the bacterial growth on the supernatant phase as well as on the mature biofilm. For S. mitis ATCC 6249, the biofilm inhibitory concentration of Chitlac-nAg was 0.1%. At sub-inhibitory concentrations, the Streptococcal strains adhesion capability on a polystyrene surface showed a general reduction following a concentration-dependent-way; a similar effect was obtained for the metabolic biofilm activity. From these results, Chitlac-nAg seems to be a promising antibacterial and antibiofilm agent able to hinder plaque formation. PMID:23812080

Di Giulio, Mara; Di Bartolomeo, Soraya; Di Campli, Emanuela; Sancilio, Silvia; Marsich, Eleonora; Travan, Andrea; Cataldi, Amelia; Cellini, Luigina

2013-01-01

304

Polymorphisms in the SUFU gene are Associated with Organ Injury Protection and Sepsis Severity in Patients with Enterobacteriacea Bacteremia  

PubMed Central

Background Organ injury including acute kidney injury (AKI) and acute lung Injury (ALI) are major contributors to mortality and morbidity in the setting of sepsis. Hedgehog pathway has been recognized as an important mediator in repair of organ injury. There are some clinical predictors associated with the development of organ injury in sepsis; however few host genetic risk factors have been identified and candidate genes for organ injury susceptibility and severity are largely unknown. Methods A prospective cohort study in a tertiary care hospital included 250 adult hospitalized patients with Enterobacteriacea bacteremia. We selected a panel of 69 tagging SNPs for genes in the Hedgehog signaling pathway using the TagSNP functionality of the SNPInfo web server and designed a panel on the GoldenGate Veracode genotyping assay (Illumina). We confirmed Illumina data using Taqman allelic discrimination assays. We assessed SNPs in combination with clinical variables for associations with outcomes and organ injury. Results Significant associations were identified using logistic regression models, controlling for age, race and gender. From the 69 tagging SNPs, 5 SNPs were associated with renal function and 2 with APACHEII score after false discovery rate correction. After multivariate analysis SNPs rs10786691 (p=0.03), rs12414407 (p=0.026), rs10748825 (p=0.01), and rs7078511 (p=0.006), all in the suppressor of fused homolog (SUFU) gene, correlated with renal function. Likewise, SUFU SNPs rs7907760 (p=0.009) and rs10748825 (p=0.029) were associated with APACHEII score. SNPs rs12414407 and rs1078825 are in linkage disequilibrium (LD) with rs2296590, a SNP in the 5?-UTR region that is within a predicted transcription factor bind site for CCAAT-enhancer-binding proteins. In multivariate analyses functional SNP rs2296590 was correlated with renal function (p=0.004) and APACHEII score (p=0.049). Conclusions Host susceptibility factors play an important role in sepsis development and sepsis related organ injury. Polymorphisms in the SUFU gene (encoding for a negative regulator of the hedgehog signaling pathway) are associated with protection from Enterobacteriacea bacteremia related organ injury and sepsis severity. PMID:23538333

Henao-Martínez, Andrés F.; Agler, Anne Hermetet; LaFlamme, Daniel; Schwartz, David A.; Yang, Ivana V.

2013-01-01

305

Impact of sepsis on CD4 T cell immunity.  

PubMed

Sepsis remains the primary cause of death from infection in hospital patients, despite improvements in antibiotics and intensive-care practices. Patients who survive severe sepsis can display suppressed immune function, often manifested as an increased susceptibility to (and mortality from) nosocomial infections. Not only is there a significant reduction in the number of various immune cell populations during sepsis, but there is also decreased function in the remaining lymphocytes. Within the immune system, CD4 T cells are important players in the proper development of numerous cellular and humoral immune responses. Despite sufficient clinical evidence of CD4 T cell loss in septic patients of all ages, the impact of sepsis on CD4 T cell responses is not well understood. Recent findings suggest that CD4 T cell impairment is a multipronged problem that results from initial sepsis-induced cell loss. However, the subsequent lymphopenia-induced numerical recovery of the CD4 T cell compartment leads to intrinsic alterations in phenotype and effector function, reduced repertoire diversity, changes in the composition of naive antigen-specific CD4 T cell pools, and changes in the representation of different CD4 T cell subpopulations (e.g., increases in Treg frequency). This review focuses on sepsis-induced alterations within the CD4 T cell compartment that influence the ability of the immune system to control secondary heterologous infections. The understanding of how sepsis affects CD4 T cells through their numerical loss and recovery, as well as function, is important in the development of future treatments designed to restore CD4 T cells to their presepsis state. PMID:24791959

Cabrera-Perez, Javier; Condotta, Stephanie A; Badovinac, Vladimir P; Griffith, Thomas S

2014-11-01

306

HLA-DR expression, cytokines and bioactive lipids in sepsis  

PubMed Central

Sepsis accounts for more than 200,000 deaths annually in the USA alone. Both inflammatory and anti-inflammatory responses occur simultaneously in sepsis, the early phase dominated by the hyperinflammatory response and the late phase by immunosuppression. This late immunosuppression phase leads to loss of the delayed type hypersensitivity response, failure to clear the primary infection and development of secondary infections. Based on the available data, I hypothesize that failure to produce adequate amounts of inflammation resolving lipid mediators may be at the centre of both the hyperinflammatory response and late immunosuppression seen in sepsis. These proresolving lipids – lipoxins, resolvins and protectins – suppress exacerbated activation of leukocytes and macrophages, inhibit excess production of pro-inflammatory cytokines, initiate resolution of inappropriate inflammation, augment clearance of bacteria and other pathogens, and restore homeostasis. If true, this implies that administration of naturally occurring lipoxins, resolvins, protectins, maresins and nitrolipids by themselves or their more stable synthetic analogues such as 15-epi-16-(para-fluorophenoxy)-lipoxin A4-methyl ester, a synthetic analogue of 15-epi-lipoxin A4, and 15(R/S)-methyl-LXA4 may form a new approach in the prevention (in the high-risk subjects), management of sepsis and in resolving the imbalanced inflammatory process such that sepsis is ameliorated early. In addition, recent studies have suggested that nociceptin and cold inducible RNA binding protein (CIRBP) also have a role in the pathobiology of sepsis. It is suggested that both nociceptin and CIRBP inhibit the production of lipoxins, resolvins, protectins, maresins, and nitrolipids and thus play a role in sepsis and septic shock. PMID:24904669

2014-01-01

307

Physiological-dose steroid therapy in sepsis [ISRCTN36253388  

PubMed Central

Introduction The aim of the study was to assess the prognostic importance of basal cortisol concentrations and cortisol response to corticotropin, and to determine the effects of physiological dose steroid therapy on mortality in patients with sepsis. Methods Basal cortisol level and corticotropin stimulation test were performed within 24 hours in all patients. One group (20 patients) received standard therapy for sepsis and physiological-dose steroid therapy for 10 days; the other group (20 patients) received only standard therapy for sepsis. Basal cortisol level was measured on the 14th day in patients who recovered. The outcome of sepsis was compared. Results Only Sequential Organ Failure Assessment (SOFA) score was found related to mortality, independent from other factors in multivariate analysis. No significant difference was found between the changes in the percentage of SOFA scores of the steroid therapy group and the standard therapy group in survivors, nor between the groups in basal and peak cortisol levels, cortisol response to corticotropin test and mortality. The mortality rates among patients with occult adrenal insufficiencies were 40% in the steroid therapy group and 55.6% in the standard therapy group. Discussion There was a trend towards a decrease in the mortality rates of the patients with sepsis who received physiological-dose steroid therapy. In the advancing process from sepsis to septic shock, adrenal insufficiency was not frequent as supposed. There was a trend (that did not reach significance) towards a decrease in the mortality rates of the patients with sepsis who received physiological-dose steroid therapy. PMID:12133187

Yildiz, Orhan; Do?anay, Mehmet; Aygen, Bilgehan; Güven, Muhammet; Kele?timur, Fahrettin; Tutu?, Ahmet

2002-01-01

308

Serum Procalcitonine Levels as an Early Diagnostic Indicator of Sepsis  

PubMed Central

Introduction: Prompt and accurate diagnosis of sepsis is of high importance for clinicians. Procalcitonine (PCT) and C-reactive protein (CRP) have been proposed as markers for this purpose. Our aim was to evaluate the levels of PCT and CRP in early sepsis and its correlation with severity of sepsis. Methods: Levels of PCT and CRP were taken from 60 patients with sepsis criteria and 39 patients with SIRS symptoms from the University Hospital Center “Mother Teresa” in Tirana, Albania during 2010-2012. Sensitivity, specificity and predictive values for PCT and CRP were calculated. Results: PCT and CRP levels increased in parallel with the severity of the clinical conditions of the patients. The mean PCT level in patients with sepsis was 11.28 ng/ml versus 0.272 ng/ml in patients with SIRS symptoms, with a sensitivity of 97.4% and a specificity of 96.6% for PCT >0.5ng/ml. The mean CRP level in septic patients was 146.58 mg/l vs. 34.4 mg/l in patients with SIRS, with a sensitivity of 98.6% for sepsis and a specificity of 75 % for CRP >11mg/l. Conclusion: PCT and CRP values are useful markers to determine early diagnosis and severity of an infection. In the present study, PCT was found to be a more accurate diagnostic parameter for differentiating SIRS from sepsis and may be helpful in the follow-up of critically ill patients. PMID:23687457

Beqja-Lika, Anila; Bulo-Kasneci, Anyla; Refatllari, Etleva; Heta-Alliu, Nevila; Rucaj-Barbullushi, Alma; Mone, Iris; Mitre, Anila

2013-01-01

309

Evaluation of Vitamin C for Adjuvant Sepsis Therapy  

PubMed Central

Abstract Significance: Evidence is emerging that parenteral administration of high-dose vitamin C may warrant development as an adjuvant therapy for patients with sepsis. Recent Advances: Sepsis increases risk of death and disability, but its treatment consists only of supportive therapies because no specific therapy is available. The characteristics of severe sepsis include ascorbate (reduced vitamin C) depletion, excessive protein nitration in microvascular endothelial cells, and microvascular dysfunction composed of refractive vasodilation, endothelial barrier dysfunction, and disseminated intravascular coagulation. Parenteral administration of ascorbate prevents or even reverses these pathological changes and thereby decreases hypotension, edema, multiorgan failure, and death in animal models of sepsis. Critical Issues: Dehydroascorbic acid appears to be as effective as ascorbate for protection against microvascular dysfunction, organ failure, and death when injected in sepsis models, but information about pharmacodynamics and safety in human subjects is only available for ascorbate. Although the plasma ascorbate concentration in critically ill and septic patients is normalized by repletion protocols that use high doses of parenteral ascorbate, and such doses are tolerated well by most healthy subjects, whether such large amounts of the vitamin trigger adverse effects in patients is uncertain. Future Directions: Further study of sepsis models may determine if high concentrations of ascorbate in interstitial fluid have pro-oxidant and bacteriostatic actions that also modify disease progression. However, the ascorbate depletion observed in septic patients receiving standard care and the therapeutic mechanisms established in models are sufficient evidence to support clinical trials of parenteral ascorbate as an adjuvant therapy for sepsis. Antioxid. Redox Signal. 19, 2129–2140. PMID:23682970

2013-01-01

310

Early and Late Onset Sepsis in Late Preterm Infants  

PubMed Central

Background Preterm birth is increasing worldwide, and late preterm births, which comprise more than 70% of all preterm births, account for much of the increase. Early and late onset sepsis results in significant mortality in extremely preterm infants, but little is known about sepsis outcomes in late preterm infants. Methods This is an observational cohort study of infants < 121 days of age (119,130 infants less than or equal to 3 days of life and 106,142 infants between 4 and 120 days of life) with estimated gestational age at birth between 34 and 36 weeks, admitted to 248 neonatal intensive care units in the United States between 1996 and 2007. Results During the study period, the cumulative incidence of early and late onset sepsis was 4.42 and 6.30 episodes per 1000 admissions, respectively. Gram-positive organisms caused the majority of early and late onset sepsis episodes. Infants with early onset sepsis caused by Gram-negative rods and infants with late onset sepsis were more likely to die than their peers with sterile blood cultures (OR 4.39, 95% CI 1.71–11.23, P=0.002; and OR 3.37, 95% CI 2.35–4.84, P<0.001, respectively). Conclusion Late preterm infants demonstrate specific infection rates, pathogen distribution, and mortality associated with early and late onset sepsis. The results of this study are generalizable to late preterm infants admitted to the special care nursery or neonatal intensive care unit. PMID:19953725

Cohen-Wolkowiez, Michael; Moran, Cassandra; Benjamin, Daniel K.; Cotten, C. Michael; Clark, Reese H.; Benjamin, Daniel K.; Smith, P. Brian

2009-01-01

311

A New Cecal Slurry Preparation Protocol with Improved Long-Term Reproducibility for Animal Models of Sepsis  

PubMed Central

Sepsis, a life-threatening systemic inflammatory response syndrome induced by infection, is widely studied using laboratory animal models. While cecal-ligation and puncture (CLP) is considered the gold standard model for sepsis research, it may not be preferable for experiments comparing animals of different size or under different dietary regimens. By comparing cecum size, shape, and cecal content characteristics in mice under different experimental conditions (aging, diabetes, pancreatitis), we show that cecum variability could be problematic for some CLP experiments. The cecal slurry (CS) injection model, in which the cecal contents of a laboratory animal are injected intraperitoneally to other animals, is an alternative method for inducing polymicrobial sepsis; however, the CS must be freshly prepared under conventional protocols, which is a major disadvantage with respect to reproducibility and convenience. The objective of this study was to develop an improved CS preparation protocol that allows for long-term storage of CS with reproducible results. Using our new CS preparation protocol we found that bacterial viability is maintained for at least 6 months when the CS is prepared in 15% glycerol-PBS and stored at -80°C. To test sepsis-inducing efficacy of stored CS stocks, various amounts of CS were injected to young (4–6 months old), middle-aged (12–14 months old), and aged (24–26 months old) male C57BL/6 mice. Dose- and age-dependent mortality was observed with high reproducibility. Circulating bacteria levels strongly correlated with mortality suggesting an infection-mediated death. Further, injection with heat-inactivated CS resulted in acute hypothermia without mortality, indicating that CS-mediated death is not due to endotoxic shock. This new CS preparation protocol results in CS stocks which are durable for freezing preservation without loss of bacterial viability, allowing experiments to be performed more conveniently and with higher reproducibility than before. PMID:25531402

Starr, Marlene E.; Steele, Allison M.; Saito, Mizuki; Hacker, Bill J.; Evers, B. Mark; Saito, Hiroshi

2014-01-01

312

Epidemiological and Clinical Characteristics of Community-Acquired Severe Sepsis and Septic Shock: A Prospective Observational Study in 12 University Hospitals in Korea  

PubMed Central

A prospective multicenter observational study was performed to investigate the epidemiology and outcomes of community-acquired severe sepsis and septic shock. Subjects included 1,192 adult patients admitted to the 22 participating intensive care units (ICUs) of 12 university hospitals in the Korean Sepsis Registry System from April, 2005 through February, 2009. Male accounted for 656 (55%) patients. Mean age was 65.0 ± 14.2 yr. Septic shock developed in 740 (62.1%) patients. Bacteremia was present in 422 (35.4%) patients. The 28-day and in-hospital mortality rates were 23.0% and 28.0%, respectively. Men were more likely to have comorbid illnesses and acute organ dysfunctions, and had higher mortality and clinical severity compared to women. While respiratory sources of sepsis were common in men, urinary sources were predominant in women. In the multivariate logistic regression analysis, cancer (odds ratio 1.89; 95% confidence interval 1.13-3.17), urinary tract infection (0.25; 0.13-0.46), APACHE II score (1.05; 1.02-1.09), SOFA score on day 1 (1.13; 1.06-1.21) and metabolic dysfunction (2.24, 1.45-3.45) were independent clinical factors for gender-related in-hospital mortality. This study provided epidemiological and clinical characteristics of community-acquired severe sepsis and septic shock in ICUs in Korea, and demonstrated the impact of clinical factors on gender difference in mortality. PMID:23166410

Park, Dae Won; Chun, Byung Chul; Kim, June Myung; Sohn, Jang Wook; Peck, Kyong Ran; Kim, Yang Soo; Choi, Young Hwa; Choi, Jun Yong; Kim, Sang Il; Eom, Joong Sik; Kim, Hyo Youl; Song, Joon Young; Song, Young Goo; Choi, Hee Jung

2012-01-01

313

Molecular microbiological methods in the diagnosis of neonatal sepsis  

PubMed Central

Neonatal sepsis is a major cause of neonatal mortality and morbidity. The current gold standard for diagnosis of sepsis, namely blood culture, suffers from low sensitivity and a reporting delay of approximately 48–72 h. Rapid detection of sepsis and institution of antimicrobial therapy may improve patient outcomes. Rapid and sensitive tests that can inform clinicians regarding the institution or optimization of antimicrobial therapy are urgently needed. The ideal diagnostic test should have adequate specificity and negative predictive value to reliably exclude sepsis and avoid unnecessary antibiotic therapy. We comprehensively searched for neonatal studies that evaluated molecular methods for diagnosis of sepsis. We identified 19 studies that were assessed with respect to assay methodology and diagnostic characteristics. In addition, we also reviewed newer molecular microbiological assays of relevance that have not been fully evaluated in neonates. Molecular methods offer distinct advantages over blood cultures, including increased sensitivity and rapid diagnosis. However, diagnostic accuracy and cost–effectiveness should be established before implementation in clinical practice. PMID:20818947

Venkatesh, Mohan; Flores, Angela; Luna, Ruth Ann; Versalovic, James

2010-01-01

314

Proteome changes in mesenteric lymph induced by sepsis  

PubMed Central

The present study aimed to examine the changes in mesenteric lymph during the development of sepsis and to identify the distinct proteins involved, as targets for further study. The sepsis animal model was constructed by cecal ligation and puncture (CLP). The mesenteric lymph was collected from 28 adult male Sprague-Dawley rats, which were randomly divided into the following four groups (n=7 per group): CLP-6 h, CLP-24 h, sham-6 h and sham-24 h groups. Capillary high performance liquid chromatography-tandem mass spectrometry was performed to analyze the proteome in mesenteric lymph. A comprehensive bioinformatic analysis was then conducted to investigate the distinct proteins. Compared with the sham group, 158 distinct proteins were identified in the lymph samples from the CLP group. Five of these proteins associated with the same lipid metabolism pathway were selected, apolipoprotein E (ApoE), annexin A1 (Anxa1), neutrophil gelatinase-associated lipocalin (NGAL), S100a8 and S100a9. The expression of ApoE, Anxa1, NGAL, S100a8 and S100a9 were all elevated in the progression of sepsis. The five proteins were reported to be closely associated with disease development and may be a potential target for the diagnosis and treatment of sepsis. In conclusion, identifying proteome changes in mesenteric lymph provides a novel perspective to understand the pathological mechanisms underlying sepsis. PMID:25242054

ZHANG, PING; LI, YAN; ZHANG, LIAN-DONG; WANG, LIANG-HUA; WANG, XI; HE, CHAO; LIN, ZHAO-FEN

2014-01-01

315

Role of Pore-Forming Toxins in Neonatal Sepsis  

PubMed Central

Protein toxins are important virulence factors contributing to neonatal sepsis. The major pathogens of neonatal sepsis, group B Streptococci, Escherichia coli, Listeria monocytogenes, and Staphylococcus aureus, secrete toxins of different molecular nature, which are key for defining the disease. Amongst these toxins are pore-forming exotoxins that are expressed as soluble monomers prior to engagement of the target cell membrane with subsequent formation of an aqueous membrane pore. Membrane pore formation is not only a means for immediate lysis of the targeted cell but also a general mechanism that contributes to penetration of epithelial barriers and evasion of the immune system, thus creating survival niches for the pathogens. Pore-forming toxins, however, can also contribute to the induction of inflammation and hence to the manifestation of sepsis. Clearly, pore-forming toxins are not the sole factors that drive sepsis progression, but they often act in concert with other bacterial effectors, especially in the initial stages of neonatal sepsis manifestation. PMID:23710203

Sonnen, Andreas F.-P.

2013-01-01

316

Genetic polymorphisms associated with acute lung injury  

PubMed Central

Acute lung injury and acute respiratory distress syndrome are the result of intense inflammation in the lungs leading to respiratory failure. The causes of acute lung injury/acute respiratory distress syndrome are numerous (e.g., pneumonia, sepsis and trauma) but the reasons why certain individuals develop lung injury in response to these stimuli and others do not are not well understood. There is ample evidence in the literature that gene–host and gene–environment interactions may play a large role in the morbidity and mortality associated with this syndrome. In this review, we initially discuss methods for identification of candidate acute lung injury/acute respiratory distress syndrome susceptibility genes using a number of model systems including in vitro cell systems and inbred mice. We then describe examples of polymorphisms in genes that have been associated with the pathogenesis of acute lung injury/acute respiratory distress syndrome in human case–control studies. Systematic bench to bedside approaches to understand the genetic contribution to acute lung injury/acute respiratory distress syndrome have provided important insight to this complex disease and continuation of these investigations could lead to the development of novel prevention or intervention strategies. PMID:19761373

Reddy, Anita J; Kleeberger, Steven R

2009-01-01

317

Antibodies against neural, nuclear, cytoskeletal, and streptococcal epitopes in children and adults with Tourette’s syndrome, Sydenham’s chorea, and autoimmune disorders  

Microsoft Academic Search

Background: Some cases of Tourette’s syndrome (TS) are hypothesized to be caused by autoantibodies that develop in response to a preceding group A beta hemolytic streptococcal infection.Methods: To test this hypothesis, we looked for the presence ot total and IgG antibodies against neural, nuclear, cytoskeletal and streptococcal epitopes using indirect immunofluorescent assays and Western blot techniques in three patient groups:

Syed A. Morshed; Salina Parveen; James F. Leckman; Marcos T. Mercadante; Maria H. Bittencourt Kiss; Euripedes C. Miguel; Ayse Arman; Yanki Yazgan; Takao Fujii; Surojit Paul; Bradley S. Peterson; Heping Zhang; Robert A. King; Lawrence Scahill; Paul J. Lombroso

2001-01-01

318

[Current aspects of sepsis caused by bacterial translocation].  

PubMed

Bacterial translocation has been put forward as a concept to explain sepsis without an infectious focus, but it has been difficult to prove in humans. Dysfunction of the intestinal barrier, which is composed of physical, biochemical and immunological factors, is the pathophysiological prerequisite for bacterial translocation. Recent findings indicate that not only viable bacteria but also pathogen associated molecular patterns may translocate and cause sepsis. Molecular detection methods for bacteria or their components have been developed to address these new concepts, but they have not yet become widely available. Specific therapeutic interventions within the sepsis cascades and signaling pathways of the innate and specific immune system so far have not been successful. Selective oral decontamination (SOD) und selective digestive tract decontamination (SDD) are efficacious prophylactic measures against nosocomial septic complications. An increased incidence of resistant pathogens has not been encountered. The use of probiotics as prophylaxis against septic complications is controversial and has led in some studies to a worse prognosis. PMID:22711326

Lamprecht, G; Heininger, A

2012-06-01

319

Hydrogen gas presents a promising therapeutic strategy for sepsis.  

PubMed

Sepsis is characterized by a severe inflammatory response to infection. It remains a major cause of morbidity and mortality in critically ill patients despite developments in monitoring devices, diagnostic tools, and new therapeutic options. Recently, some studies have found that molecular hydrogen is a new therapeutic gas. Our studies have found that hydrogen gas can improve the survival and organ damage in mice and rats with cecal ligation and puncture, zymosan, and lipopolysaccharide-induced sepsis. The mechanisms are associated with the regulation of oxidative stress, inflammatory response, and apoptosis, which might be through NF- ? B and Nrf2/HO-1 signaling pathway. In this paper, we summarized the progress of hydrogen treatment in sepsis. PMID:24829918

Xie, Keliang; Liu, Lingling; Yu, Yonghao; Wang, Guolin

2014-01-01

320

Relationship between gut and sepsis: Role of ghrelin.  

PubMed

Ghrelin is a growth hormone secretagogue produced by the gut, and is expressed in the hypothalamus and other tissues as well. Ghrelin not only plays an important role in the regulation of appetite, energy balance and glucose homeostasis, but also shows anti-bacterial activity, suppresses pro-inflammatory cytokine production and restores gut barrier function. In experimental animals, ghrelin has shown significant beneficial actions in preventing mortality from sepsis. In the critically ill, corticosteroid insufficiency as a result of dysfunction of the hypothalamic-pituitary-adrenal axis is known to occur. It is therefore possible that both gut and hypothalamus play an important role in the pathogenesis of sepsis by virtue of their ability to produce ghrelin, which, in turn, could be a protective phenomenon to suppress inflammation. It remains to be seen whether ghrelin and its analogues are of benefit in treating patients with sepsis. PMID:21537444

Das, Undurti N

2011-01-15

321

Relationship between gut and sepsis: Role of ghrelin  

PubMed Central

Ghrelin is a growth hormone secretagogue produced by the gut, and is expressed in the hypothalamus and other tissues as well. Ghrelin not only plays an important role in the regulation of appetite, energy balance and glucose homeostasis, but also shows anti-bacterial activity, suppresses pro-inflammatory cytokine production and restores gut barrier function. In experimental animals, ghrelin has shown significant beneficial actions in preventing mortality from sepsis. In the critically ill, corticosteroid insufficiency as a result of dysfunction of the hypothalamic-pituitary-adrenal axis is known to occur. It is therefore possible that both gut and hypothalamus play an important role in the pathogenesis of sepsis by virtue of their ability to produce ghrelin, which, in turn, could be a protective phenomenon to suppress inflammation. It remains to be seen whether ghrelin and its analogues are of benefit in treating patients with sepsis. PMID:21537444

Das, Undurti N

2011-01-01

322

Hydrogen Gas Presents a Promising Therapeutic Strategy for Sepsis  

PubMed Central

Sepsis is characterized by a severe inflammatory response to infection. It remains a major cause of morbidity and mortality in critically ill patients despite developments in monitoring devices, diagnostic tools, and new therapeutic options. Recently, some studies have found that molecular hydrogen is a new therapeutic gas. Our studies have found that hydrogen gas can improve the survival and organ damage in mice and rats with cecal ligation and puncture, zymosan, and lipopolysaccharide-induced sepsis. The mechanisms are associated with the regulation of oxidative stress, inflammatory response, and apoptosis, which might be through NF-?B and Nrf2/HO-1 signaling pathway. In this paper, we summarized the progress of hydrogen treatment in sepsis. PMID:24829918

Liu, Lingling; Yu, Yonghao; Wang, Guolin

2014-01-01

323

Lower mortality following pulmonary adverse events and sepsis with ticagrelor compared to clopidogrel in the PLATO study.  

PubMed

In the PLATelet inhibition and patient Outcomes (PLATO) study of patients with acute coronary syndromes, ticagrelor reduced mortality compared to clopidogrel but the mechanisms for this mortality reduction remain uncertain. We analysed adverse events (AEs) consistent with either pulmonary infection or sepsis, and subsequent mortality, in 18,421 PLATO patients treated with ticagrelor or clopidogrel. AEs occurring within 7 days of last dose of study medication were defined as "on-treatment". Serial measurements of blood leukocyte counts, C-reactive protein and interleukin-6 were performed. Fewer on-treatment pulmonary AEs occurred in the ticagrelor compared to the clopidogrel group (275 vs. 331 respectively; p?=?0.019), with fewer deaths following these AEs (33 vs. 71; p?sepsis in the ticagrelor group (7 vs. 23; p?=?0.003). Leukocyte counts were lower in the clopidogrel group during treatment (p?sepsis in acute coronary syndrome patients appears to be lower during ticagrelor compared to clopidogrel therapy. Further work should assess whether ticagrelor and clopidogrel have differential effects on immune signalling. PMID:24127651

Storey, Robert F; James, Stefan K; Siegbahn, Agneta; Varenhorst, Christoph; Held, Claes; Ycas, Joseph; Husted, Steen E; Cannon, Christopher P; Becker, Richard C; Steg, Ph Gabriel; Åsenblad, Nils; Wallentin, Lars

2014-01-01

324

Neutrophil C5a receptor and the outcome in a rat model of sepsis  

Microsoft Academic Search

Complement fragment 5a (C5a)-C5a receptor (C5aR) signaling plays an essential role in neutrophil innate immunity. Blockade of either the ligand or the receptor improves survival rates in experimental sepsis. In the current study, sepsis was induced in rats by cecal ligation\\/puncture. Early in sepsis C5aR content on neutrophils significantly dropped, reached the nadir at 24 h after onset of sepsis,

Ren-Feng Guo; Niels C. Riedemann; Kurt D. Bernacki; Vidya J. Sarma; Ines J. Laudes; Jayne S. Reuben; Ellen M. Younkin; Thomas A. Neff; Joseph D. Paulauskis; Firas S. Zetoune; Peter A. Ward

2003-01-01

325

The role of obesity in the immune response during sepsis  

PubMed Central

Background/Objectives: Sepsis is one of the most important causes of mortality in the developed world, where almost two-thirds of the population suffer from obesity. Therefore, the coexistence of both conditions has become frequent in clinical practice and a growing number of clinical studies attempts to examine the potential effect of obesity on sepsis with controversial results up to now. The present study investigates how obesity influences the immune response of septic patients, by assessing the number and activation state of adipose tissue macrophages, serum and adipose tissue tumor necrosis factor-alpha (TNF?) levels and plasma oxidative stress markers. Subjects/methods: The study included 106 patients, divided into four groups (control n=26, obesity n=27, sepsis n=27 and sepsis and obesity n=26). The number of macrophages in subcutaneous and visceral adipose tissue (SAT and VAT) and their subtypes (M1 and M2) were defined with immunohistochemical staining techniques under light microscopy. TNF? mRNA levels were determined in SAT and VAT using real-time reverse transcription-PCR. Serum levels of TNF? were determined with sandwich enzyme-linked immunosorbent assay. Plasma oxidative stress was evaluated using selective biomarkers (thiobarbituric acid-reactive substances (TBARS), protein carbonyls and total antioxidant capacity (TAC)). Results: Sepsis increased the total number of macrophages and their M2 subtype in (VAT), whereas obesity did not seem to affect the concentration of macrophages in fat. Obesity increased TNF? mRNA levels (P<0.05) in VAT as well as the plasma TBARS (P<0.001) and protein carbonyls (P<0.001) in septic patients. The plasma TAC levels were decreased and the serum TNF? levels were increased in sepsis although they were not influenced by obesity. Conclusions: Obesity is associated with elevated TNF? adipose tissue production and increased oxidative stress biomarkers, promoting the proinflammatory response in septic patients. PMID:25244356

Kolyva, A S; Zolota, V; Mpatsoulis, D; Skroubis, G; Solomou, E E; Habeos, I G; Assimakopoulos, S F; Goutzourelas, N; Kouretas, D; Gogos, C A

2014-01-01

326

Increased C5a receptor expression in sepsis.  

PubMed

Excessive production of the complement activation product C5a appears to be harmful during the development of sepsis in rodents. Little is known about the role of the C5a receptor (C5aR) and its presence in different organs during sepsis. Using the cecal ligation/puncture (CLP) model in mice, we show here that C5aR immunoreactivity was strikingly increased in lung, liver, kidney, and heart early in sepsis in both control and neutrophil-depleted mice. C5aR mRNA expression in these organs was also significantly increased during sepsis. Immunohistochemical analysis revealed patterns of increased C5aR expression in parenchymal cells in all four organs following CLP. Mice injected at the start of CLP with a blocking IgG to C5aR (alphaC5aR) showed dramatically improved survival when compared with animals receiving nonspecific IgG, as did mice injected with alphaC5a. In alphaC5aR-treated mice, serum levels of IL-6 and TNF-alpha and bacterial counts in various organs were significantly reduced during CLP when compared with control CLP animals. These studies demonstrate for the first time that C5aR is upregulated in lung, liver, kidney, and heart during the early phases of sepsis and that blockade of C5aR is highly protective from the lethal outcome of sepsis. PMID:12093893

Riedemann, Niels C; Guo, Ren-Feng; Neff, Thomas A; Laudes, Ines J; Keller, Katie A; Sarma, Vidya J; Markiewski, Maciej M; Mastellos, Dimitrios; Strey, Christoph W; Pierson, Carl L; Lambris, John D; Zetoune, Firas S; Ward, Peter A

2002-07-01

327

Genome-wide transcription profiling of human sepsis: a systematic review  

Microsoft Academic Search

INTRODUCTION: Sepsis is thought to be an abnormal inflammatory response to infection. However, most clinical trials of drugs that modulate the inflammatory response of sepsis have been unsuccessful. Emerging genomic evidence shows that the host response in sepsis does not conform to a simple hyper-inflammatory\\/hypo-inflammatory model. We, therefore, synthesized current genomic studies that examined the host response of circulating leukocytes

Benjamin M Tang; Stephen J Huang; Anthony S McLean

2010-01-01

328

What are the latest recommendations for managing severe sepsis and septic shock?  

PubMed

Severe sepsis is a continuum of physiologic stages characterized by infection, systemic inflammation, and hypoperfusion leading to tissue injury and organ failure. The primary goal of sepsis treatment is to prevent morbidity and mortality. Crystalloids are now recommended over colloids for volume resuscitation, one of the key interventions for patients with sepsis. PMID:25251649

Bland, Christopher M; Sutton, S Scott; Dunn, Brianne L

2014-10-01

329

The acute respiratory distress syndrome  

PubMed Central

The acute respiratory distress syndrome (ARDS) is an important cause of acute respiratory failure that is often associated with multiple organ failure. Several clinical disorders can precipitate ARDS, including pneumonia, sepsis, aspiration of gastric contents, and major trauma. Physiologically, ARDS is characterized by increased permeability pulmonary edema, severe arterial hypoxemia, and impaired carbon dioxide excretion. Based on both experimental and clinical studies, progress has been made in understanding the mechanisms responsible for the pathogenesis and the resolution of lung injury, including the contribution of environmental and genetic factors. Improved survival has been achieved with the use of lung-protective ventilation. Future progress will depend on developing novel therapeutics that can facilitate and enhance lung repair. PMID:22850883

Matthay, Michael A.; Ware, Lorraine B.; Zimmerman, Guy A.

2012-01-01

330

Fast folding of a prototypic polypeptide: the immunoglobulin binding domain of streptococcal protein G.  

PubMed Central

The folding of the small (56 residues) highly stable B1 immunoglobulin binding domain (GB1) of streptococcal protein G has been investigated by quenched-flow deuterium-hydrogen exchange. This system represents a paradigm for the study of protein folding because it exhibits no complicating features superimposed upon the intrinsic properties of the polypeptide chain. Collapse to a semicompact state exhibiting partial order, reflected in protection factors for ND-NH exchange up to 10-fold higher than that expected for a random coil, occurs within the dead time (< or = 1 ms) of the quenched flow apparatus. This is followed by the formation of the fully native state, as monitored by the fractional proton occupancy of 26 backbone amide groups spread throughout the protein, in a single rapid concerted step with a half-life of 5.2 ms at 5 degrees C. PMID:7703841

Kuszewski, J.; Clore, G. M.; Gronenborn, A. M.

1994-01-01

331

Lyme disease and pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS): an overview  

PubMed Central

Lyme disease (LD) is a complex, multisystemic illness. As the most common vector- borne disease in the United States, LD is caused by bacterial spirochete Borrelia burgdorferi sensu stricto, with potential coinfections from agents of anaplasmosis, babesiosis, and ehrlichiosis. Persistent symptoms and clinical signs reflect multiorgan involvement with episodes of active disease and periods of remission, not sparing the coveted central nervous system. The capability of microorganisms to cause and exacerbate various neuropsychiatric pathology is also seen in pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS), a recently described disorder attributed to bacterium Streptococcus pyogenes of group A beta-hemolytic streptococcus in which neurologic tics and obsessive-compulsive disorders are sequelae of the infection. In the current overview, LD and PANDAS are juxtaposed through a review of their respective infectious etiologies, clinical presentations, mechanisms of disease development, courses of illness, and treatment options. Future directions related to immunoneuropsychiatry are also discussed. PMID:22393303

Rhee, Hanna; Cameron, Daniel J

2012-01-01

332

Synthesis of group A streptococcal virulence factors is controlled by a regulatory RNA molecule.  

PubMed

The capacity of pathogens to cause disease depends strictly on the regulated expression of their virulence factors. In this study, we demonstrate that the untranslated mRNA of the recently described streptococcal pleiotropic effect locus (pel), which incidentally contains sagA, the structural gene for streptolysin S, is an effector of virulence factor expression in group A beta-haemolytic streptococci (GAS). Our data suggest that the regulation by pel RNA occurs at both transcriptional (e.g. emm, sic, nga) and post-transcriptional (e.g. SpeB) levels. We could exclude the possibility that the pel phenotype was linked to a polar effect on downstream genes (sagB-I). Remarkably, the RNA effector is regulated in a growth phase-dependent fashion and we provide evidence that pel RNA expression is induced by conditioned media. PMID:15387826

Mangold, Monika; Siller, Maria; Roppenser, Bernhard; Vlaminckx, Bart J M; Penfound, Tom A; Klein, Reinhard; Novak, Rodger; Novick, Richard P; Charpentier, Emmanuelle

2004-09-01

333

[Diagnostic value of rapid streptococcal antigen test provided by Abbott "test pack strep A": current report].  

PubMed

The upper respiratory tract infections are the most frequent infectious diseases in human. Beta haemolytic streptococcus group A is the most common etiologic factor of bacterial pharyngitis. Delayed or inadequate treatment of streptococcal pharyngitis can cause serious subsequent complications. Only a part of patients show typical features of the disease so that the diagnosis can be based on clinical appearance alone. For this reason we propose direct antigen test as a rapid useful method which allows detection of group A streptococci in throat swabs. The aim of the study is to estimate clinical value of rapid antigen test in differential diagnosis of pharyngitis in children and adults. We have performed 50 tests using commercial kit--Abbott Test Pack Strep A. Simultaneously conventional bacterial throat cultures were performed. The comparison of results acquired by both methods did not revealed any differences. PMID:9757684

Gajos, A; Janeczek, T; Wilczy?ski, K; Bogdan, P; Winiewicz, A; Szychowska, Z; Bany?, D

1997-01-01

334

Cloning of the gene encoding streptococcal immunoglobulin A protease and its expression in Escherichia coli.  

PubMed Central

We have identified and cloned a 6-kilobase-pair segment of chromosomal DNA from Streptococcus sanguis ATCC 10556 that encodes immunoglobulin A (IgA) protease activity when cloned into Escherichia coli. The enzyme specified by the iga gene in plasmid pJG1 accumulates in the periplasm of E. coli MM294 cells and has a substrate specificity for human IgA1 identical to that of native S. sanguis protease. Hybridization experiments with probes from within the encoding DNA showed no detectable homology at the nucleotide sequence level with chromosomal DNA of gram-negative bacteria that excrete IgA protease. Moreover, the S. sanguis iga gene probes showed no detectable hybridization with chromosomal DNA of S. pneumoniae, although the IgA proteases of these two streptococcal species cleaved the identical peptide bond in the human IgA1 heavy-chain hinge region. Images PMID:3294181

Gilbert, J V; Plaut, A G; Fishman, Y; Wright, A

1988-01-01

335

Identification and Structural Basis of Binding to Host Lung Glycogen by Streptococcal Virulence Factors  

SciTech Connect

The ability of pathogenic bacteria to recognize host glycans is often essential to their virulence. Here we report structure-function studies of previously uncharacterized glycogen-binding modules in the surface-anchored pullulanases from Streptococcus pneumoniae (SpuA) and Streptococcus pyogenes (PulA). Multivalent binding to glycogen leads to a strong interaction with alveolar type II cells in mouse lung tissue. X-ray crystal structures of the binding modules reveal a novel fusion of tandem modules into single, bivalent functional domains. In addition to indicating a structural basis for multivalent attachment, the structure of the SpuA modules in complex with carbohydrate provides insight into the molecular basis for glycogen specificity. This report provides the first evidence that intracellular lung glycogen may be a novel target of pathogenic streptococci and thus provides a rationale for the identification of the streptococcal {alpha}-glucan-metabolizing machinery as virulence factors.

Lammerts van Bueren,A.; Higgins, M.; Wang, D.; Burke, R.; Boraston, A.

2007-01-01

336

Characterization of the human cellular immune response to purified group A streptococcal blastogen A1.  

PubMed

The human mononuclear cell response to purified extracellular streptococcal protein, blastogen A, was compared to the response of these cells to PHA and tetanus antigen. Blastogen A induced peak uptake of thymidine during day 6 of tissue culture whereas PHA induced peak uptake during day 5 and tetanus during day 8. Like PHA, blastogen A transformed human umbilical cord lymphocytes and those of nonimmune animals. Also like PHA, blastogen A transformed primarily T lymphocytes. However, unlike PHA, the ability of T lymphocytes to respond to blastogen A was almost completely dependent on the presence of viable non-T lymphocytes. Monocytes were not as effective in facilitating the response to blastogen A as they were for PHA. Thus, blastogen A behaves most like a polyclonal T lymphocyte mitogen, although the degree of dependence of the transformation response on the presence of non-T lymphocytes is much greater than that of PHA. PMID:7037952

Regelmann, W E; Gray, E D; Wannamaker, L W

1982-04-01

337

Effect of type III group B streptococcal capsular polysaccharide on invasion of respiratory epithelial cells.  

PubMed Central

Group B streptococcal (GBS) capsular polysaccharide is an important virulence factor, and its role in invasion of cultured respiratory epithelial cells was investigated. A type III GBS clinical isolate, COH1, and asialo and unencapsulated isogenic transposon capsule mutants of it were compared in an in vitro invasion assay. The results demonstrated that capsule attenuated the invasion process. Invasion was not affected when the A549 epithelial cells were preincubated with purified type III GBS capsular polysaccharide. Polyclonal type III GBS capsule antibody inhibited invasion by COH1 but did not affect invasion by the capsule mutants. Serotypes Ia, Ib, Ia/c, II, and III all invaded respiratory epithelial cells but demonstrated some strain variation in magnitude of invasion. These observations led us to conclude that type III capsular polysaccharide was not essential for invasion of respiratory epithelial cells by GBS and that bacterial factors other than capsule were responsible for respiratory epithelial cell invasion. Images PMID:8406885

Hulse, M L; Smith, S; Chi, E Y; Pham, A; Rubens, C E

1993-01-01

338

Mucin model for group B type III streptococcal infection in mice.  

PubMed Central

An experimental murine infection was established by the intraperitoneal injection of a log-phase culture of a laboratory reference strain of Streptococcus agalactiae, Lancefield group B, type III (strain SS620), suspended in sterile hog gastric mucin. The enhancement of streptococcal virulence was measured by a significantly increased mortality in outbred ICR Swiss mice. An inbred C57BL6 strain of mice was resistant to the mucin-bacterial combination. Mucin, treated with Desferal to chelate the iron, did not lose the capacity to enhance the virulence of group B, type III streptococci in ICR Swiss mice. Iron-dextran was not a suitable substitute for mucin and failed to enhance the virulence of group B, type III streptococci. The results of these studies indicate that iron is not the resistance-lowering factor in this group B, type III streptococci-mucin model. PMID:6155334

Fleming, D O

1980-01-01

339

Direct molecular detection of pathogens in blood as specific rule-in diagnostic biomarker in patients with presumed sepsis: our experience on a heterogeneous cohort of patients with signs of infective systemic inflammatory response syndrome.  

PubMed

The practical value of blood cultures in the diagnosis of sepsis is impaired by a delay in the turnaround time to result and by the fact that blood culture positive can be found for only about 30% of these patients. Conventional laboratory signs of sepsis and acute phase protein biomarkers are sensitive and easy to use, but often also very nonspecific. Molecular diagnostic reflects currently the most promising avenue to decrease time to result and to influence decision making for antibiotic therapy in the septic host. In this study, we wish to highlight the impact of the LightCycler SeptiFast, a multipathogen probe-based real-time polymerase chain reaction, in the rapid etiological diagnosis of sepsis in patients with clinical and laboratory signs of bloodstream infections. We have evaluated prospectively 830 adult patients with suspected bloodstream infection and at least two criteria of systemic inflammatory response syndrome. In more than 50% of critically ill patients strongly suspected of having sepsis, we arrived to an etiological diagnosis only by the molecular method in a median time of 15 h, with specificity and predictive positive values of 96% and 94%, respectively. We highlight the role of DNAemia as time-critical, high-specificity, etiological, non-culture-based rule-in diagnostic biomarker in patients with presumed sepsis. PMID:24727869

Avolio, Manuela; Diamante, Paola; Modolo, Maria Luisa; De Rosa, Rita; Stano, Paola; Camporese, Alessandro

2014-08-01

340

Lemierre Syndrome: A Case of Postanginal Sepsis  

PubMed Central

Lemierre syndrome is a rare disease that's characterized by internal jugular vein thrombosis and septic emboli. These symptoms typically develop after acute oropharyngeal infection by Fusobacterium necrophorum1). Although this syndrome is less frequently seen in modern times due to the availability of antibiotics, physicians must be aware of the syndrome in order to initiate prompt antibiotics therapy, including coverage of the anerobic organisms. We discuss here the case of an 18-year-old female with Lemierre syndrome and we review the relevant literature on this syndrome. PMID:17939341

Seo, Young Tak; Kim, Ji Hoon; Ha, Byung Wook; Choi, Hyo Sun; Kim, Yong Tai; Ham, Young Hwan

2007-01-01

341

Recombinant human soluble thrombomodulin administration improves sepsis-induced disseminated intravascular coagulation and mortality: a retrospective cohort study  

PubMed Central

Background Early treatment of disseminated intravascular coagulation (DIC) can be associated with improved patient outcomes. The Japanese Ministry of Health and Welfare (JMHW) and the International Society on Thrombosis and Haemostasis (ISTH) criteria are the most specific for diagnosis of septic DIC. The revised Japanese Association for Acute Medicine (JAAM) criteria are able to diagnose sepsis-induced DIC in the early stage. Recombinant human soluble thrombomodulin (rhTM) has recently been used for treating DIC. Previous studies have shown a benefit of using rhTM for D,IC diagnosed by the JMHW or ISTH criteria, but not the JAAM criteria. The purpose of this study was to sequentially evaluate coagulation biomarkers and the DIC score after giving rhTM treatment to patients with sepsis-induced DIC diagnosed according to the JAAM criteria. Methods We performed a retrospective cohort study. Critically ill patients were included if diagnosed with sepsis-induced DIC according to the JAAM criteria. They were either treated without rhTM (control group) or with rhTM (treatment group). The primary outcome was the DIC score on day 7. The secondary outcome was 28-day mortality from the start of DIC treatment. Changes in the results of coagulation tests were assessed over time from the start of treatment to day 7. Results Twelve and 23 patients were assigned to the treatment and control groups, respectively. The DIC score on day 7 was significantly higher in the treatment group (3.3 ± 1.4) than in the control group (4.9 ± 1.8, p < 0.05). Estimated survival showed lower in treatment group than control group. There was significant difference between the control group and the treatment group (p < 0.05). The D-dimer level on day 7 was significantly lower in the treatment group (7.5 ± 4.1 ?g/mL) than in the control group (30.9 ± 33.6 ?g/mL, p < 0.05). Life-threatening bleeding did not occur. Our results indicated that rhTM improved sepsis-induced DIC and mortality. Conclusions Recombinant human soluble thrombomodulin may improve sepsis-induced DIC diagnosed according to the JAAM criteria without an increased bleeding risk. PMID:23414216

2013-01-01

342

Correlation between protection against sepsis by probiotic therapy and stimulation of a novel bacterial phylotype.  

PubMed

Prophylactic probiotic therapy has shown beneficial effects in an experimental rat model for acute pancreatitis on the health status of the animals. Mechanisms by which probiotic therapy interferes with severity of acute pancreatitis and associated sepsis, however, are poorly understood. The aims of this study were to identify the probiotic-induced changes in the gut microbiota and to correlate these changes to disease outcome. Duodenum and ileum samples were obtained from healthy and diseased rats subjected to pancreatitis for 7 days and prophylactically treated with either a multispecies probiotic mixture or a placebo. Intestinal microbiota was characterized by terminal-restriction fragment length polymorphism (T-RFLP) analyses of PCR-amplified 16S rRNA gene fragments. These analyses showed that during acute pancreatitis the host-specific ileal microbiota was replaced by an "acute pancreatitis-associated microbiota." This replacement was not reversed by administration of the probiotic mixture. An increase, however, was observed in the relative abundance of a novel bacterial phylotype most closely related to Clostridium lituseburense and referred to as commensal rat ileum bacterium (CRIB). Specific primers targeting the CRIB 16S rRNA gene sequence were developed to detect this phylotype by quantitative PCR. An ileal abundance of CRIB 16S rRNA genes of more than 7.5% of the total bacterial 16S rRNA gene pool was correlated with reduced duodenal bacterial overgrowth, reduced bacterial translocation to remote organs, improved pancreas pathology, and reduced proinflammatory cytokine levels in plasma. Our current findings and future studies involving this uncharacterized bacterial phylotype will contribute to unraveling one of the potential mechanisms of probiotic therapy. PMID:21926217

Gerritsen, Jacoline; Timmerman, Harro M; Fuentes, Susana; van Minnen, L Paul; Panneman, Henk; Konstantinov, Sergey R; Rombouts, Frans M; Gooszen, Hein G; Akkermans, Louis M A; Smidt, Hauke; Rijkers, Ger T

2011-11-01

343

[Peculiarities of clinical and laboratory characteristics of the activity of streptococcal infection in the patients presenting with tonsillar pathology].  

PubMed

The objective of the present study was to characterize peculiar clinical and laboratory features of trivial tonsillitis for the substantiation of the necessity of prescription of antibacterial therapy. A total of 386 patients presenting with various forms of trivial tonsillitis were available for the determination of anti-streptococcal antibody (ASLO, anti-DN-ase B, ASPH) levels. The results of the measurement were compared based on the Centor scale generally used to estimate the necessity of prescribing antibacterial therapy for the treatment of sore throat. It is concluded that laboratory studies of characteristics of S. ?yogenes activity are needed in all the patients presenting with tonsillitis in order to elucidate the etiological factors responsible for pharyngalgia and the necessity of prescription of antibacterial therapy for the prevention of pyogenic systemic complications of streptococcal infection. PMID:23887368

Kriukov, A I; Aksenova, A V; Shostak, N A; Briko, N I; Gurov, A V; Kle?menov, D A; Guseva, O A; Nabieva, T T

2013-01-01

344

Diagnosis of Adrenal Insufficiency in Severe Sepsis and Septic Shock  

Microsoft Academic Search

Rationale: Diagnosis of adrenal insufficiency in critically ill patients has relied on random or cosyntropin-stimulated cortisol levels, and has not been corroborated by a more accurate diagnostic standard. Objective: We used the overnight metyrapone stimulation test to investigate the diagnostic value of the standard cosyntropin stimu- lation test, and the prevalence of sepsis-associated adrenal insufficiency. Methods: This was an inception

Djillali Annane; Virginie Maxime; Fidaa Ibrahim; Jean Claude Alvarez; Emuri Abe; Philippe Boudou

2006-01-01

345

Sepsis associated with central vein catheters in critically ill patients  

Microsoft Academic Search

In 440 critically ill patients, the association between different central vein catheter insertion sites, the duration of catheter insertion and catheter-associated sepsis was examined. Of 780 catheter tips studied, 19% were colonized by microorganisms. The incidence of colonization varied with the different insertion sites. The lowest percentage of colonized catheters occurred with catheters inserted via the subclavian vein (15%) and

P. Collignon; N. Soni; I. Pearson; T. Sorrell; P. Woods

1988-01-01

346

Cellular origin and procoagulant properties of microparticles in meningococcal sepsis  

Microsoft Academic Search

Patients with meningococcal sepsis gen- erally suffer from disseminated intravas- cular coagulation (DIC). The aim of this study was to address whether these patients have elevated numbers of circu- lating microparticles that contribute to the development of DIC. Plasma samples from 5 survivors, 2 nonsurvivors, and 5 healthy volunteers were analyzed for the presence of microparticles by flow cytom- etry.

Rienk Nieuwland; R. J. Berckmans; S. McGregor; A. N. Boing; F. P. H. Th. M Romijn; Rudi G. J. Westendorp; C. Erik Hack; Augueste Sturk

2000-01-01

347

Sepsis in Older Patients: An Emerging Concern in Critical Care  

Microsoft Academic Search

Severe sepsis is a common problem associated with substantial mortality and a significant consumption of healthcare resources. The number of cases per year, currently estimated at 750 000 in the US alone, is expected to increase at a rate of 1.5% per year, and an increasingly significant proportion of these patients will be elderly. Older persons are more prone to

Luis A Destarac; E Wesley Ely

2002-01-01

348

Early-onset neonatal sepsis due to Cellulosimicrobium cellulans.  

PubMed

Cellulosimicrobium cellulans represents a rare human pathogen. Infections have been reported in immunocompromised hosts or in patients with an underlying disease. The authors describe a rare case of early-onset neonatal sepsis due to Cellulosimicrobium cellulans in an infant without any underlying disease. The infant was successfully treated with vancomycin. PMID:20376528

Casanova-Román, M; Sanchez-Porto, A; Gomar, J L; Casanova-Bellido, M

2010-08-01

349

Therapeutic interventions in sepsis: current and anticipated pharmacological agents.  

PubMed

Sepsis is a clinical syndrome characterized by a multisystem response to a pathogenic assault due to underlying infection that involves a combination of interconnected biochemical, cellular and organ-organ interactive networks. After the withdrawal of recombinant human-activated protein C (rAPC), researchers and physicians have continued to search for new therapeutic approaches and targets against sepsis, effective in both hypo- and hyperinflammatory states. Currently, statins are being evaluated as a viable option in clinical trials. Many agents that have shown favourable results in experimental sepsis are not clinically effective or have not been clinically evaluated. Apart from developing new therapeutic molecules, there is great scope for for developing a variety of drug delivery strategies, such as nanoparticulate carriers and phospholipid-based systems. These nanoparticulate carriers neutralize intracorporeal LPS as well as deliver therapeutic agents to targeted tissues and subcellular locations. Here, we review and critically discuss the present status and new experimental and clinical approaches for therapeutic intervention in sepsis. PMID:24977655

Shukla, Prashant; Rao, G Madhava; Pandey, Gitu; Sharma, Shweta; Mittapelly, Naresh; Shegokar, Ranjita; Mishra, Prabhat Ranjan

2014-11-01

350

Laparoscopic cholecystostomy for acute acalculous cholecystitis.  

PubMed

Acute acalculous cholecystitis (AAC) can occur in up to 18% of severely injured patients. Diagnosis is made by positive ultrasound findings of gallbladder sludge, hydrox, and wall thickening. There may also be recent-onset jaundice, positive ultrasound induced Murphy's sign, and unexplained sepsis. Mortality can be as high as 50%. Laparoscopic confirmation was obtained in six ICU trauma patients when omentum was drawn up over a distended gallbladder. Laparoscopic cholecystectomy (LC) was done by first directly decompressing the gallbladder through the fundus. This trocar was replaced by a 16 French Foley catheter passed through an Endoloop into the gallbladder and secured by tightening the loop around a cuff of gallbladder. Sepsis resolved in all cases. Only one required subsequent laparoscopic cholecystectomy. LC has a low morbidity and may be life saving during the early stages of AAC. It is not indicated in gangrene or perforation of the gallbladder. PMID:8662413

Yang, H K; Hodgson, W J

1996-06-01

351

[Group A streptococcal meningitis: Streptococcus pneumoniae is not the only one to seep into the CSF fluid leak!].  

PubMed

We reported a case of group A streptococcal meningitis in a patient with a CSF fluid leak. This case underlined several relevant points: (i) an unfrequent cause of bacterial meningitis; (ii) the main diagnosis to evoke when the direct examination of CSF shows Gram+ cocci with a negative pneumococcal antigen; (iii) that bacteria other than Streptococcus pneumoniae are possible in front of a meningitis associated with a CSF fluif leak. PMID:24161291

Zappella, N; Barrelet, A; Pangon, B; Laurent, V; Bruneel, F

2013-11-01

352

Gluten ataxia and post-streptococcal central nervous system syndromes: Emerging immune-mediated disorders of the central nervous system?  

Microsoft Academic Search

Opinion statement  There is an “emerging concept” that central nervous system dysfunction can be caused by an aberrant immune response triggered\\u000a by exogenous antigens such as the food allergen gluten or streptococcal infection. The hypothesis of a gluten sensitive ataxia\\u000a remains unproven, but is worthy of consideration. The data in support of this hypothesis require critical review before any\\u000a treatment recommendations

Adrian Wills; Russell Dale; Gavin Giovannoni

2005-01-01

353

Streptococcal preparation OK432: a new maturation factor of monocyte-derived dendritic cells for clinical use  

Microsoft Academic Search

For vaccinations based on dendritic cells (DCs), maturation of DCs is critical to the induction of T-cell responses. We tested the efficacy of streptococcal preparation OK-432 as a Good Manufacturing Practice (GMP)–grade maturation agent. OK-432 is currently used in Japan as a cancer immunotherapy drug. Immature monocyte-derived dendritic cells (imMo-DCs) isolated from human peripheral blood monocytes stimulated with granulocyte-macrophage colony

Hideo Kuroki; Takashi Morisaki; Kotaro Matsumoto; Hideya Onishi; Eishi Baba; Masao Tanaka; Mitsuo Katano

2003-01-01

354

Cystitis - acute  

MedlinePLUS

Uncomplicated urinary tract infection; UTI - acute; Acute bladder infection; Acute bacterial cystitis ... The symptoms of a bladder infection include: Cloudy or bloody urine, which may have a foul or strong odor Low fever (not everyone will have a ...

355

SEPSIS-INDUCED ALTERATIONS IN PROTEIN-PROTEIN INTERACTIONS WITHIN mTOR COMPLEX 1 AND THE MODULATING EFFECT OF LEUCINE ON MUSCLE PROTEIN SYNTHESIS  

PubMed Central

Sepsis-induced muscle atrophy is produced in part by decreased protein synthesis mediated by inhibition of mTOR (mammalian target of rapamycin). The present study tests the hypothesis that alteration of specific protein-protein interactions within the mTORC1 (mTOR complex 1) contributes to the decreased mTOR activity observed after cecal ligation and puncture in rats. Sepsis decreased in vivo translational efficiency in gastrocnemius and reduced the phosphorylation of eukaryotic initiation factor (eIF) 4E-binding protein (BP) 1, S6 kinase (S6K) 1, and mTOR, compared with time-matched pair-fed controls. Sepsis decreased T246-phosphorylated PRAS40 (proline-rich Akt substrate 40) and reciprocally increased S792-phosphorylated raptor (regulatory associated protein of mTOR). Despite these phosphorylation changes, sepsis did not alter PRAS40 binding to raptor. The amount of the mTOR-raptor complex did not differ between groups. In contrast, the binding and retention of both 4E-BP1 and S6K1 to raptor were increased, and, conversely, the binding of raptor with eIF3 was decreased in sepsis. These changes in mTORC1 in the basal state were associated with enhanced 52032-AMP activated kinase activity. Acute in vivo leucine stimulation increased muscle protein synthesis in control, but not septic rats. This muscle leucine resistance was associated with coordinated changes in raptor-eIF3 binding and 4E-BP1 phosphorylation. Overall, our data suggest the sepsis-induced decrease in muscle protein synthesis may be mediated by the inability of 4E-BP1 and S6K1 to be phosphorylated and released from mTORC1 as well as the decreased recruitment of eIF3 necessary for a functional 48S complex. These data provide additional mechanistic insight into the molecular mechanisms by which sepsis impairs both basal protein synthesis and the anabolic response to the nutrient signal leucine in skeletal muscle. PMID:20577146

Kazi, Abid A.; Pruznak, Anne M.; Frost, Robert A.; Lang, Charles H.

2010-01-01

356

Acute Peritoneal Dialysis in Neonates with Acute Kidney Injury and Hypernatremic Dehydration  

PubMed Central

? Objective: We aimed to evaluate the efficacy of acute peritoneal dialysis (PD) and clinical outcomes in neonates with acute kidney injury (AKI) and hypernatremic dehydration. ? Methods: The medical records of 15 neonates with AKI and hypernatremic dehydration who were treated with acute PD were reviewed. The diagnoses were AKI with hypernatremic dehydration with or without sepsis in 13 patients and AKI with hypernatremia and congenital nephropathy in 2 patients. The main indications for PD were AKI with some combination of oligoanuria, azotemia, hyperuricemia, and metabolic acidosis unresponsive to initial intensive medical treatment. ? Results: The mean age of the patients at dialysis initiation was 11.9 ± 9 days, and the mean duration of PD was 6.36 ± 4.8 days. In 7 patients (46.7%), hypotension required the use of vasopressors, and in 6 patients (40%), mechanical ventilation was required. Peritoneal dialysis-related complications occurred in 7 patients (46.7%), the most common being catheter malfunction (n = 6). Four episodes of peritonitis occurred in the 15 patients (26.7%), 2 episodes in patients with congenital renal disease and 2 episodes in patients with sepsis and multiorgan failure, who did not survive. Congenital renal disease, septicemia, and the need for mechanical ventilation were important factors influencing patient survival. All patients with no pre-existing renal disease or sepsis recovered their renal function and survived. ? Conclusions: In neonates with AKI and hypernatremic dehydration, PD is safe and successful, and in patients without congenital renal disease or sepsis, the prognosis is good. Peritoneal dialysis should be the treatment of choice in neonates with AKI and hypernatremic dehydration who do not respond to appropriate med ical treatment. PMID:23123669

Yildiz, Nurdan; Erguven, Müferet; Yildiz, Metin; Ozdogan, Tutku; Turhan, Pinar

2013-01-01

357

Pro- and Synbiotics to Prevent Sepsis in Major Surgery and Severe Emergencies  

PubMed Central

Septic morbidity associated with advanced surgical and medical treatments is unacceptably high, and so is the incidence of complications occurring in connection with acute emergencies such as severe trauma and severe acute pancreatitis. Only considering the US, it will annually affect approximately (app) 300 million (mill) of a population of almost one million inhabitants and cause the death of more than 200,000 patients, making sepsis the tenth most common cause of death in the US. Two major factors affect this, the lifestyle-associated increased weakness of the immune defense systems, but more than this the artificial environment associated with modern treatments such as mechanical ventilation, use of tubes, drains, intravascular lines, artificial nutrition and extensive use of synthetic chemical drugs, methods all known to reduce or eliminate the human microbiota and impair immune functions and increase systemic inflammation. Attempts to recondition the gut by the supply of microorganisms have sometimes shown remarkably good results, but too often failed. Many factors contribute to the lack of success: unsuitable choice of probiotic species, too low dose, but most importantly, this bio-ecological treatment has never been given the opportunity to be tried as an alternative treatment. Instead it has most often been applied as complementary to all the other treatments mentioned above, including antibiotic treatment. The supplemented lactic acid bacteria have most often been killed already before they have reached their targeted organs. PMID:22413064

Bengmark, Stig

2012-01-01

358

Pro- and synbiotics to prevent sepsis in major surgery and severe emergencies.  

PubMed

Septic morbidity associated with advanced surgical and medical treatments is unacceptably high, and so is the incidence of complications occurring in connection with acute emergencies such as severe trauma and severe acute pancreatitis. Only considering the US, it will annually affect approximately (app) 300 million (mill) of a population of almost one million inhabitants and cause the death of more than 200,000 patients, making sepsis the tenth most common cause of death in the US. Two major factors affect this, the lifestyle-associated increased weakness of the immune defense systems, but more than this the artificial environment associated with modern treatments such as mechanical ventilation, use of tubes, drains, intravascular lines, artificial nutrition and extensive use of synthetic chemical drugs, methods all known to reduce or eliminate the human microbiota and impair immune functions and increase systemic inflammation. Attempts to recondition the gut by the supply of microorganisms have sometimes shown remarkably good results, but too often failed. Many factors contribute to the lack of success: unsuitable choice of probiotic species, too low dose, but most importantly, this bio-ecological treatment has never been given the opportunity to be tried as an alternative treatment. Instead it has most often been applied as complementary to all the other treatments mentioned above, including antibiotic treatment. The supplemented lactic acid bacteria have most often been killed already before they have reached their targeted organs. PMID:22413064

Bengmark, Stig

2012-02-01

359

Activity of lung neutrophils and matrix metalloproteinases in cyclophosphamide-treated mice with experimental sepsis  

PubMed Central

Sepsis in patients receiving chemotherapy may result in acute respiratory distress syndrome, despite decreased number of blood neutrophils [polymorphonuclear neutrophils (PMNs)]. In the present study, we investigated the correlation of cyclophosphamide (CY)-induced neutropenia with the destructive potential of lung PMN in respect to formation of septic acute lung injury (ALI). Mice were treated with 250 mg/kg of CY or saline (control) and subjected to cecal ligation and puncture (CLP) or sham operation. ALI was verified by histological examination. Lung PMNs and matrix metalloproteinases (MMPs) were assessed by flow cytometry and gelatin zymography. CLP in CY-treated mice induced a typical lung injury. Despite profound neutropenia, CY treatment did not attenuate CLP-induced ALI. This might relate to only a partial suppression of PMN: CY has significantly reduced PMN influx into the lungs (P = 0.008) and suppressed their oxidative metabolism, but had no suppressive effect on degranulation (P = 0.227) and even induced MMP-9 activity (P = 0.0003). In CY-untreated animals, peak of CLP-induced ALI coincided with massive PMN influx (P = 0.013), their maximal degranulation (P = 0.014) and activation of lung MMP-9 (P = 0.002). These findings may indicate an important role of the residual lung PMN and activation of MMP-9 in septic lung injury during CY chemotherapy. PMID:15255968

Hirsh, Mark; Carmel, Julie; Kaplan, Viktoria; Livne, Erella; Krausz, Michael M

2004-01-01

360

Elevated expression of IL-23/IL-17 pathway-related mediators correlates with exacerbation of pulmonary inflammation during polymicrobial sepsis.  

PubMed

Sepsis is a leading cause of death in the United States, claiming more than 215,000 lives every year. A primary condition observed in septic patients is the incidence of acute respiratory distress syndrome, which is characterized by the infiltration of neutrophils into the lung. Prior studies have shown differences in pulmonary neutrophil accumulation in C57BL/6J (B6) and A/J mice after endotoxic and septic shock. However, the mechanism by which neutrophils accumulate in the lung after polymicrobial sepsis induced by cecal ligation and puncture still remains to be fully elucidated. We show in this study that lung inflammation, characterized by neutrophil infiltration and expression of inflammatory cytokines, was aggravated in B6 as compared with A/J mice and correlated with a high expression of p19, the interleukin 23 (IL-23)-specific subunit. Furthermore, lipopolysaccharide stimulation of B6- and A/J-derived macrophages, one of the main producers of IL-23 and IL-12, revealed that B6 mice favored the production of IL-23, whereas A/J-derived macrophages expressed higher levels of IL-12. In addition, expression of IL-17, known to be upregulated by IL-23, was also more elevated in the lung of B6 mice when compared with that in the lung of A/J mice. In contrast, pulmonary expression of interferon-? was much more pronounced in A/J than that in B6 mice, which was most likely a result of a higher production of IL-12. The expression of the IL-17-dependent neutrophil recruitment factors chemokine (CXC motif) ligand 2 and granulocyte colony-stimulating factor was also higher in B6 mice. Altogether, these results suggest that increased activation of the IL-23/IL-17 pathway has detrimental effects on sepsis-induced lung inflammation, whereas activation of the IL-12/interferon-? pathway may lead, in contrast, to less pronounced inflammatory events. These two pathways may become possible therapeutic targets for the treatment of sepsis-induced acute respiratory distress syndrome. PMID:24978886

Cauvi, David M; Williams, Michael R; Bermudez, Jose A; Armijo, Gabrielle; De Maio, Antonio

2014-09-01

361

Streptococcal toxic shock syndrome from necrotizing soft-tissue infection of the breast caused by a mucoid type strain.  

PubMed

Streptococcal toxic shock syndrome is a severe infectious disease. We report a Japanese case of Streptococcal toxic shock syndrome caused by a highly mucoid strain of Streptococcus pyogenes. A 31-year old female with shock vital sign presented at a tertiary medical center. Her left breast was necrotizing and S. pyogenes was detected by Immunochromatographic rapid diagnostic kits. Intensive care, including administration of antibiotics and skin debridement, was performed. After 53 days in our hospital, she was discharged. The blood cultures and skin swab cultures all grew S. pyogenes which displayed a highly mucoid morphology on culture media. In her course of the disease, the Streptococcus strain had infected two other family members. All of the strains possessed the T1 and M1 antigens, as well as the emm1.0 gene. As for fever genes, the strains were all positive for speA, speB, and speF, but negative for speC. All of the strains exhibited and the same pattern in PFGE with the SfiI restriction enzyme. The strain might have spread in the local area by the data from the Japanese Infectious Disease Surveillance Center. Immunochromatographic rapid diagnostic kits are very useful for detecting S. pyogenes. However, they can not be used to diagnose severe streptococcul disease by highly mucoid strain alone. Careful observation of patients and colony morphology are useful methods for diagnosing severe streptococcal disease by highly mucoid strain. PMID:25260866

Kohayagawa, Yoshitaka; Ishitobi, Natsuko; Yamamori, Yuji; Wakuri, Miho; Sano, Chiaki; Tominaga, Kiyoshi; Ikebe, Tadayoshi

2015-02-01

362

Streptococcal Infections  

MedlinePLUS

... throat. It causes a red rash on the body. Impetigo - a skin infection Toxic shock syndrome Cellulitis and necrotizing fasciitis (flesh-eating disease) Group B strep can cause blood infections, pneumonia ...

363

Membrane TLR Signaling Mechanisms in the Gastrointestinal Tract during Sepsis  

PubMed Central

Our bacterial residents are deadly Janus-faced indwellers which can lead to a septic-induced systemic inflammatory response syndrome and multiple organ failure. Over half of ICU patients suffer from infections and sepsis remains among the top ten causes of death in the United States. Severe ileus frequently accompanies sepsis setting up an insidious cycle of gut-derived microbial translocation and the copious intestinal production of potent systemic inflammatory mediators. Few therapeutic advances have occurred to prevent/treat the sequelae of sepsis. Here, we selectively review studies on cellular membrane bound Toll-like receptor (TLR) mechanisms of ileus. Virtually no data exists on Gram-positive/TLR2 signaling mechanisms of ileus, however, TLR2 is highly inducible by numerous inflammatory mediators and studies using clinically relevant scenarios of Gram-positive sepsis are needed. Specific Gram-negative/TLR4 signaling pathways are being elucidated using a “reverse engineering” approach and have revealed that endotoxin induced ileus is dually mediated by classical leukocyte inflammatory signaling and by a MyD88-dependent non-bone marrow derived mechanism, but the specific roles of individual cell populations are still unknown. Like TLR2, little is also know of the role of flagellin/TLR5 signaling in ileus. But, much can be learned by understanding TLR signaling in other systems. Clearly, the use of polymicrobial models provide important clinical relevancy but simultaneous activation of virtually all pattern recognition receptors make it impossible to discretely study specific signaling pathways. We believe that dissection of individual TLR pathways, which can then be intelligently re-assembled in a meaningful manner, will provide insight into treatments for sepsis induced ileus. PMID:20377787

Buchholz, Bettina M.; Bauer, Anthony J.

2010-01-01

364

Ischemic preconditioning attenuates lipid peroxidation and apoptosis in the cecal ligation and puncture model of sepsis  

PubMed Central

Sepsis and septic shock are are among the major causes of mortality in intensive care units. The lung and kidney are the organs most affected by sepsis. Evidence exists that lipid peroxidation and apoptosis may be responsible for the high mortality due to sepsis. Ischemic preconditioning (IP) is a method for the protection of tissues and organs against ischemia/reperfusion injury by reducing reactive oxygen species levels, lipid peroxidation and apoptosis. In the present study, the effects of IP were investigated in cecal ligation and puncture (CLP)-induced sepsis in rats. The three groups of animals used in the present controlled study were the sham-operated group (sham, n=7), which only underwent a laparotomy; the sepsis group (sepsis, n=7), which underwent cecal ligation and perforation; and the IP + sepsis group (IP+sepsis, n=7), which underwent CLP immediately prior to the application of three cycles of IP to the hind limb. The study was terminated at 6 h after the induction of CLP. Blood, kidney and lung tissue samples were collected for the determination of serum creatinine, blood urea nitrogen (BUN), neutrophil gelatinase-associated lipocalin (NGAL) and lung tissue malondialdehyde (MDA) levels, as well as histological examination. The serum creatinine, plasma NGAL and lung tissue MDA levels in the sepsis group were significantly increased compared with those in the sham and the IP+sepsis groups (P<0.05). Alveolar macrophage counts, histological kidney and lung injury scores, kidney (caspase 3) and lung tissue immuonreactivity (M30) scores in the sepsis group were also significantly increased compared with those in the sham and IP+sepsis groups (P<0.05). The alveolar macrophage count in the IP+sepsis group was increased compared with that in the sham group (P<0.05). In conclusion, IP inhibits lipid peroxidation and attenuates histological injury and apoptosis in the lung and kidney during sepsis. PMID:23837035

OLGUNER, ÇIMEN GÜLBEN; KOCA, U?UR; ALTEKIN, EMEL; ERGÜR, BEKIR U?UR; DURU, SEDEN; GIRGIN, PELIN; TA?DÖ?EN, AYDIN; GÜNDÜZ, KERIM; GÜZELDA?, SEDA; AKKU?, MUHAMMED; MICILI, SERAP CILAKER

2013-01-01

365

Current patterns of acute respiratory disease in the United States Navy and Marine Corps.  

PubMed Central

During 1974 there was an apparent decrease in the reported amount of acute respiratory illness in the Navy and Marine Corps. Streptococcal infections continued to be controlled by the selective use of prophylactic benzathine penicillin in recruit training centers. Influenza immunization limited the impact of that illness, and serogroup C polysaccharide vaccine reduced the amount of meningococcal disease among recruits. Although some of the data are contradictory there are indications that fully potent live adenovirus vaccines lessen the frequency and severity of respiratory illness in recruit populations. Continued epidemiologic study will be required to fill the gaps in our knowledge. PMID:808911

Hoeffler, D. F.

1975-01-01

366

A randomized, controlled, multicenter trial of the effects of antithrombin on disseminated intravascular coagulation in patients with sepsis  

PubMed Central

Introduction To test the hypothesis that the administration of antithrombin concentrate improves disseminated intravascular coagulation (DIC), resulting in recovery from DIC and better outcomes in patients with sepsis, we conducted a prospective, randomized controlled multicenter trial at 13 critical care centers in tertiary care hospitals. Methods We enrolled 60 DIC patients with sepsis and antithrombin levels of 50 to 80% in this study. The participating patients were randomly assigned to an antithrombin arm receiving antithrombin at a dose of 30 IU/kg per day for three days or a control arm treated with no intervention. The primary efficacy end point was recovery from DIC on day 3. The analysis was conducted with an intention-to-treat approach. DIC was diagnosed according to the Japanese Association for Acute Medicine (JAAM) scoring system. The systemic inflammatory response syndrome (SIRS) score, platelet count and global markers of coagulation and fibrinolysis were measured on day 0 and day 3. Results Antithrombin treatment resulted in significantly decreased DIC scores and better recovery rates from DIC compared with those observed in the control group on day 3. The incidence of minor bleeding complications did not increase, and no major bleeding related to antithrombin treatment was observed. The platelet count significantly increased; however, antithrombin did not influence the sequential organ failure assessment (SOFA) score or markers of coagulation and fibrinolysis on day 3. Conclusions Moderate doses of antithrombin improve DIC scores, thereby increasing the recovery rate from DIC without any risk of bleeding in DIC patients with sepsis. Trial registration UMIN Clinical Trials Registry (UMIN-CTR) UMIN000000882 PMID:24342495

2013-01-01

367

Association of the immature platelet fraction with sepsis diagnosis and severity  

PubMed Central

Management of Sepsis would greatly benefit from the incorporation of simple and informative new biomarkers in clinical practice. Ideally, a sepsis biomarker should segregate infected from non-infected patients, provide information about prognosis and organ-specific damage, and be accessible to most healthcare services. The immature platelet fraction (IPF) and immature reticulocyte fraction (IRF) are new analytical parameters of the complete blood count, that have been studied as biomarkers of several inflammatory conditions. Recently, a study performed in critically-ill patients suggested that IPF could be a more accurate sepsis biomarker than C-reactive protein (CRP) and procalcitonin. In this retrospective study we evaluated the performance of IPF and IRF as biomarkers of sepsis diagnosis and severity. 41 patients admitted to two intensive care units were evaluated, 12 of which with severe sepsis or septic shock, and 11 with non-complicated sepsis. Significantly higher IPF levels were observed in patients with severe sepsis/septic shock. IPF correlated with sepsis severity scores and presented the highest diagnostic accuracy for the presence of sepsis of all studied clinical and laboratory parameters. No significant differences were observed in IRF levels. Our results suggest that IPF levels could be used as a biomarker of sepsis diagnosis and severity. PMID:25620275

Hubert, Rodolfo Monteiro Enz; Rodrigues, Melina Veiga; Andreguetto, Bruna Dolci; Santos, Thiago M.; de Fátima Pereira Gilberti, Maria; de Castro, Vagner; Annichino-Bizzacchi, Joyce M.; Dragosavac, Desanka; Carvalho-Filho, Marco Antonio; De Paula, Erich Vinicius

2015-01-01

368

Identification of sepsis subtypes in critically ill adults using gene expression profiling  

PubMed Central

Introduction Sepsis is a syndromic illness that has traditionally been defined by a set of broad, highly sensitive clinical parameters. As a result, numerous distinct pathophysiologic states may meet diagnostic criteria for sepsis, leading to syndrome heterogeneity. The existence of biologically distinct sepsis subtypes may in part explain the lack of actionable evidence from clinical trials of sepsis therapies. We used microarray-based gene expression data from adult patients with sepsis in order to identify molecularly distinct sepsis subtypes. Methods We used partitioning around medoids (PAM) and hierarchical clustering of gene expression profiles from neutrophils taken from a cohort of septic patients in order to identify distinct subtypes. Using the medoids learned from this cohort, we then clustered a second independent cohort of septic patients, and used the resulting class labels to evaluate differences in clinical parameters, as well as the expression of relevant pharmacogenes. Results We identified two sepsis subtypes based on gene expression patterns. Subtype 1 was characterized by increased expression of genes involved in inflammatory and Toll receptor mediated signaling pathways, as well as a higher prevalence of severe sepsis. There were differences between subtypes in the expression of pharmacogenes related to hydrocortisone, vasopressin, norepinephrine, and drotrecogin alpha. Conclusions Sepsis subtypes can be identified based on different gene expression patterns. These patterns may generate hypotheses about the underlying pathophysiology of sepsis and suggest new ways of classifying septic patients both in clinical practice, and in the design of clinical trials. PMID:23036193

2012-01-01

369

Interleukin 6 increases dysfunction of organs in sepsis rats through sirtuin 1  

PubMed Central

Sepsis-induced organ failure is the major cause of death, and is characterized by a massive dysregulated inflammatory response. The present study was to determine whether interleukin 6 (IL-6) expression was increased in sepsis rats and the roles of IL-6 in the damage of cardiac, liver and renal function in the sepsis rats. Sepsis rat models were elicited by intravenous injection of LPS. The mRNA and protein of IL-6 levels were increased in the sepsis rats. The Left ventricular developed pressure (LVDP) and average ±dP/dt were significantly reduced in sepsis rats compare with sham group. ALT and AST activities and creatinine level were increased in the sepsis rats. IL-6 significantly reduced LVDP and average ±dP/dt, increased the activities of ALT and AST, and increased the concentration of creatinine in the sepsis rats. EX527, a sirtuin 1 (SIRT 1) inhibitor, blocked the effects of IL-6 in the sepsis rats. These results indicate that IL-6 plays important roles in the damage of cardiac, liver and renal function in the sepsis rats through SIRT 1. PMID:25356114

Ding, Ying; Lin, Yongjun; Zhu, Tao; Huang, Man; Xu, Qiuping

2014-01-01

370

Outcome and predictive factors of acute renal failure in the intensive care unit  

Microsoft Academic Search

The development of acute renal failure (ARF) in the ICU setting carries a high morbidity and mortality. To assess the outcomes and its predictive factors in our ICU, we analyzed the data of patients with ARF treated during 18 months. The 33 patients included 21 men and 12 women of mean age 51 ± 21.7 years (13 to 87). Sepsis

B. Bernieh; M. Al Hakim; Y. Boobes; E. Siemkovics; H. El Jack

2004-01-01

371

Morphological response to positive end expiratory pressure in acute respiratory failure. Computerized tomography study  

Microsoft Academic Search

Ten patients with acute respiratory failure (ARF), (4 pneumonia, 4 sepsis, 2 polytrauma), underwent computerized tomography (CT) of the lungs, (apex, hilum, base), at 5, 10, 15 cm H2O positive end expiratory pressure (PEEP). The ARF lungs, on CT scan, appeared as a patchwork of normal and dense areas with generally well defined boundaries. Most of the densities were found

L. Gattinoni; D. Mascheroni; A. Torresin; R. Marcolin; R. Fumagalli; S. Vesconi; G. P. Rossi; F. Rossi; S. Baglioni; F. Bassi; G. Nastri; A. Pesenti

1986-01-01

372

Sepsis-induced purpura fulminans caused by Pasteurella multocida.  

PubMed

A 52-year-old man was admitted with a cutaneous rash associated with septic shock and multiorganic failure, 6 days after a dog bite. He was started on empiric antibiotherapy and supportive measures. The patient's condition aggravated, with need for invasive mechanical ventilation and intermittent haemodialysis, and evolution from a petechiae-like rash to purpura and gangrene, culminating in bilateral lower limb amputation. The blood cultures revealed only Pasteurella multocida, after 10 days of incubation. P multocida infection is a rare cause of soft tissue infection that subsides with oral antibiotherapy. Infections causing sepsis are rare and appear in immunocompromised patients. Purpura fulminans induced by sepsis is a rare, life-threatening disorder. This syndrome should be recognised promptly, so early treatment is instituted. We found no case reports of purpura fulminans caused by Pasteurella infections in our literature review. PMID:24554680

Borges, Lisa; Oliveira, Nelson; Cássio, Isabel; Costa, Humberto

2014-01-01

373

Commercial Multiplex Technologies for the Microbiological Diagnosis of Sepsis  

PubMed Central

In patients with suspected sepsis, rapid and accurate diagnosis of the causative infectious agent is critical. Although clinicians often use empiric antimicrobial therapy until the blood cultures are available to potentially adjust treatment, this approach is often not optimum for patient care. Recently, several commercial molecular multiplex technologies have shown promise for fast and comprehensive diagnosis of microorganisms and their antimicrobial resistance signatures. While one class of multiplex technologies is directed at improving the speed and diagnostic information obtained from positive blood cultures, the other identifies the causative microorganisms directly from clinical blood samples. The goal of this review is to provide an overview of these molecular technologies and describe their performance capabilities compared to standard blood cultures and in some cases to each other. We discuss the current clinical impact, limitations, and likely futures advances these multiplex technologies may have in guiding the management of patients with sepsis. PMID:23636778

Lebovitz, Evan E.; Burbelo, Peter D.

2013-01-01

374

Regulation by C5a of neutrophil activation during sepsis.  

PubMed

In sepsis, there is evidence that excessive C5a generation leads to compromised innate immune functions, being associated with poor outcome. We now report that in vitro exposure of neutrophils to C5a causes increased levels of IkappaBalpha, decreased NF-kappaB-dependent gene transcription of TNFalpha, and decreased lipopolysaccharide (LPS)-induced TNFalpha production. Similar findings were obtained with neutrophils from cecal ligation/puncture (CLP)-induced septic rats. Such changes were reversed by antibody-induced in vivo blockade of C5a. In contrast, in vitro exposure of alveolar macrophages to C5a and LPS resulted in enhanced production of TNFalpha and no increase in IkappaBalpha. These data suggest that CLP-induced sepsis causes a C5a-dependent dysfunction of neutrophils, which is characterized by altered signaling associated with NF-kappaB activation. PMID:12932353

Riedemann, Niels C; Guo, Ren-Feng; Bernacki, Kurt D; Reuben, Jayne S; Laudes, Ines J; Neff, Thomas A; Gao, Hongwei; Speyer, Cecilia; Sarma, Vidya J; Zetoune, Firas S; Ward, Peter A

2003-08-01

375

Roger C. Bone, MD and the evolving paradigms of sepsis.  

PubMed

Severe sepsis and septic shock are frequent causes of ICU admission, commonly encountered complications during the course of hospitalization, and among the most common causes of death in the noncoronary ICU. Dr. Roger C. Bone was a pioneer in our struggles to improve the early recognition and management of severe sepsis and septic shock. Through his leadership and guidance, great strides were made to develop a uniform definition and to ensure the comparability of clinical research trials to evaluate new therapeutic strategies and antimediator agents. Dr. Bone also helped shape our understanding of the various stages or physiologic alterations that occur in the septic patient which also drove forward the development of new therapeutic strategies. This chapter briefly reviews the impact Roger Bone has had on our current understanding and approach to the septic patient. PMID:21659744

Balk, Robert

2011-01-01

376

The role of imaging in adult acute urinary tract infection  

Microsoft Academic Search

.   Imaging is required in only a minority of patients with urinary tract infection. Some patients who present with severe loin\\u000a pain are imaged because ureteric colic is suspected. If urinary tract infection does not respond normally to antibiotics,\\u000a imaging is undertaken to check for evidence of renal obstuction or sepsis. Finally, after the acute infection has been treated,\\u000a imaging

J. A. W. Webb

1997-01-01

377

Burden of illness imposed by severe sepsis in Germany  

Microsoft Academic Search

s  \\u000a Sepsis is a systemic response to severe infection in critically ill patients and is among the most frequent causes of death\\u000a in intensive care medicine. Every year between 44,000 and 95,000 persons suffer from this illness in Germany. With the help\\u000a of a retrospective electronic chart analysis in three adult ICUs of three university hospitals we calculated by a

A. Schmid; H. Burchardi; J. Clouth; H. Schneider

2002-01-01

378

Role of Immunosenescence in Infections and Sepsis in the Elderly  

Microsoft Academic Search

It is well-known that infections and sepsis are increased in elderly subjects, and that the immune system changes with age.\\u000a The question arises whether dysfunctionality of the immune system, or immunosenescence, contributes to this increased incidence\\u000a of infections and if so, how. As the immune system evolved to protect against infection, the role of aging is likely to be\\u000a important

Tamas Fulop; Steven Castle; Anis Larbi; Carl Fortin; Olivier Lesur; Graham Pawelec

379

Regulation by C5a of Neutrophil Activation during Sepsis  

Microsoft Academic Search

In sepsis, there is evidence that excessive C5a generation leads to compromised innate immune functions, being associated with poor outcome. We now report that in vitro exposure of neutrophils to C5a causes increased levels of I?B?, decreased NF-?B-dependent gene transcription of TNF?, and decreased lipopolysaccharide (LPS)-induced TNF? production. Similar findings were obtained with neutrophils from cecal ligation\\/puncture (CLP)-induced septic rats.

Niels C. Riedemann; Ren-Feng Guo; Kurt D. Bernacki; Jayne S. Reuben; Ines J. Laudes; Thomas A. Neff; Hongwei Gao; Cecilia Speyer; Vidya J. Sarma; Firas S. Zetoune; Peter A. Ward

2003-01-01

380

Sepsis of the cheek over a subcutaneous forehead flap.  

PubMed

In two cases, a temporal flap was folded medially and passed through a subcutaneous tunnel superficial to the parotid gland. In both cases sepsis developed at the point at which the flap entered the mouth. In one case a spontaneous perforation occurred and the other required drainage. If one elects to fold the flap medially and pass it superficial to the zygomatic arch, the route described by Lewis and Remensnyder, i.e., deep to the masseter, is preferable. PMID:7355171

Cohen, D J; Jones, R F; Engrav, L H

1980-03-01

381

C5a receptor and thymocyte apoptosis in sepsis.  

PubMed

In sepsis, apoptosis occurs in many different organs. The mediators responsible for induction of apoptosis are not clearly known, although there are some suggestions that C5a and the C5a receptor (C5aR) might be directly linked to apoptosis. In the cecal ligation/puncture (CLP) model of sepsis in rats, apoptosis occurs early in a variety of organs, especially in the thymus. We demonstrate that thymocytes from normal rats show specific, saturable, and high affinity binding of 125I-labeled recombinant rat C5a. C5a binding to thymocytes was significantly increased 3 h after CLP and also when thymocytes from normal rats were first incubated in vitro with lipopolysaccharide (LPS) or IL-6. The expression of C5aR mRNA in thymocytes was markedly increased 3, 6, and 12 h after CLP and increased similarly when normal thymocytes were first exposed to LPS or IL-6 in vitro. Thymocytes obtained 2 or 3 h after CLP and exposed in vitro to C5a, but not normal thymocytes, underwent increased apoptosis, as demonstrated by annexin-V binding, coinciding with increased activation of caspases 3, 6, and 8. These data provide the first direct evidence that in the early onset of sepsis, increased expression of C5aR occurs in thymocytes, which increases their susceptibility to C5a-induced apoptosis. PMID:12039868

Riedemann, Niels C; Guo, Ren-Feng; Laudes, Ines J; Keller, Katie; Sarma, Vidya J; Padgaonkar, Vaishalee; Zetoune, Firas S; Ward, Peter A

2002-06-01

382

Reduced motoneuron excitability in a rat model of sepsis  

PubMed Central

Many critically ill patients in intensive care units suffer from an infection-induced whole body inflammatory state known as sepsis, which causes severe weakness in patients who survive. The mechanisms by which sepsis triggers intensive care unit-acquired weakness (ICUAW) remain unclear. Currently, research into ICUAW is focused on dysfunction of the peripheral nervous system. During electromyographic studies of patients with ICUAW, we noticed that recruitment was limited to few motor units, which fired at low rates. The reduction in motor unit rate modulation suggested that functional impairment within the central nervous system contributes to ICUAW. To understand better the mechanism underlying reduced firing motor unit firing rates, we moved to the rat cecal ligation and puncture model of sepsis. In isoflurane-anesthetized rats, we studied the response of spinal motoneurons to injected current to determine their capacity for initiating and firing action potentials repetitively. Properties of single action potentials and passive membrane properties of motoneurons from septic rats were normal, suggesting excitability was normal. However, motoneurons exhibited striking dysfunction during repetitive firing. The sustained firing that underlies normal motor unit activity and smooth force generation was slower, more erratic, and often intermittent in septic rats. Our data are the first to suggest that reduced excitability of neurons within the central nervous system may contribute to ICUAW. PMID:23303860

Nardelli, Paul; Khan, Jaffar; Powers, Randall; Cope, Tim C.

2013-01-01

383

Properties and type antigen patterns of group B streptococcal isolates from pigs and nutrias.  

PubMed

All 59 group B streptococcal cultures isolated from pigs and nutrias reacted with group B-specific antiserum and gave a positive CAMP reaction in the zone of staphylococcal beta-lysin. Most of the cultures were pigmented; all cultures hydrolyzed Na hippurate and utilized salicin, maltose, and saccharose but not esculin, mannitol, or inulin. Fifty-three percent of the group B streptococci from pigs and none of those from nutrias were lactose positive. Serotyping revealed that most of the group B streptococci from pigs were of serotype III and most of those from nutrias were of type Ia/c. Protein c was present as c beta antigen. All group B streptococci were susceptible to penicillin and bacitracin (10 U), and most of the porcine cultures were resistant to tetracycline. According to these results, group B streptococci from pigs and nutrias differ from bovine and human group B streptococci and seem to play no role in cross-infections between animals or between animals and humans. PMID:8458981

Wibawan, I W; Lämmler, C; Smola, J

1993-03-01

384

A Glimpse of Streptococcal Toxic Shock Syndrome from Comparative Genomics of S. suis 2 Chinese Isolates  

PubMed Central

Background Streptococcus suis serotype 2 (SS2) is an important zoonotic pathogen, causing more than 200 cases of severe human infection worldwide, with the hallmarks of meningitis, septicemia, arthritis, etc. Very recently, SS2 has been recognized as an etiological agent for streptococcal toxic shock syndrome (STSS), which was originally associated with Streptococcus pyogenes (GAS) in Streptococci. However, the molecular mechanisms underlying STSS are poorly understood. Methods and Findings To elucidate the genetic determinants of STSS caused by SS2, whole genome sequencing of 3 different Chinese SS2 strains was undertaken. Comparative genomics accompanied by several lines of experiments, including experimental animal infection, PCR assay, and expression analysis, were utilized to further dissect a candidate pathogenicity island (PAI). Here we show, for the first time, a novel molecular insight into Chinese isolates of highly invasive SS2, which caused two large-scale human STSS outbreaks in China. A candidate PAI of ?89 kb in length, which is designated 89K and specific for Chinese SS2 virulent isolates, was investigated at the genomic level. It shares the universal properties of PAIs such as distinct GC content, consistent with its pivotal role in STSS and high virulence. Conclusions To our knowledge, this is the first PAI candidate from S. suis worldwide. Our finding thus sheds light on STSS triggered by SS2 at the genomic level, facilitates further understanding of its pathogenesis and points to directions of development on some effective strategies to combat highly pathogenic SS2 infections. PMID:17375201

Wang, Jing; Zheng, Feng; Pan, Xiuzhen; Liu, Di; Li, Ming; Song, Yajun; Zhu, Xinxing; Sun, Haibo; Feng, Tao; Guo, Zhaobiao; Ju, Aiping; Ge, Junchao; Dong, Yaqing; Sun, Wen; Jiang, Yongqiang; Wang, Jun; Yan, Jinghua; Yang, Huanming; Wang, Xiaoning; Gao, George F.; Yang, Ruifu; Wang, Jian; Yu, Jun

2007-01-01

385

Group A Streptococcal Cysteine Protease Cleaves Epithelial Junctions and Contributes to Bacterial Translocation*  

PubMed Central

Group A Streptococcus (GAS) is an important human pathogen that possesses an ability to translocate across the epithelial barrier. In this study, culture supernatants of tested GAS strains showed proteolytic activity against human occludin and E-cadherin. Utilizing various types of protease inhibitors and amino acid sequence analysis, we identified SpeB (streptococcal pyrogenic exotoxin B) as the proteolytic factor that cleaves E-cadherin in the region neighboring the calcium-binding sites within the extracellular domain. The cleaving activities of culture supernatants from several GAS isolates were correlated with the amount of active SpeB, whereas culture supernatants from an speB mutant showed no such activities. Of note, the wild type strain efficiently translocated across the epithelial monolayer along with cleavage of occludin and E-cadherin, whereas deletion of the speB gene compromised those activities. Moreover, destabilization of the junctional proteins was apparently relieved in cells infected with the speB mutant, as compared with those infected with the wild type. Taken together, our findings indicate that the proteolytic efficacy of SpeB in junctional degradation allows GAS to invade deeper into tissues. PMID:23532847

Sumitomo, Tomoko; Nakata, Masanobu; Higashino, Miharu; Terao, Yutaka; Kawabata, Shigetada

2013-01-01

386

Direct inoculation of food as the cause of an outbreak of group A streptococcal pharyngitis.  

PubMed

An investigation was conducted of a food-related outbreak of group A streptococcal pharyngitis following an elementary school banquet. Of 166 surveyed banquet attendees, 71 (43%) reported outbreak-associated pharyngitis, and 21 (88%) of 24 tested attendees had evidence of group A streptococcus (GAS) in the throat. Attendees who ate macaroni and cheese were three times more likely to develop pharyngitis than those who did not (66/132 [50%] vs. 5/30 [17%], P = .002). None of the food handlers had GAS recovered by throat culture. However, the cook who prepared the macaroni and cheese had a hand wound; a wound culture grew GAS with the same T agglutination pattern and M- and/or opacity factor type as that of all available GAS strains from ill attendees. Under laboratory conditions, macaroni and cheese supported rapid growth of the outbreak-associated strain of GAS. To the authors' knowledge, this is the first documented foodborne outbreak of GAS pharyngitis in which the only apparent source of contamination was a food handler's skin lesion. PMID:8486961

Farley, T A; Wilson, S A; Mahoney, F; Kelso, K Y; Johnson, D R; Kaplan, E L

1993-05-01

387

[An elderly case with group B streptococcal bacteremia, subcutaneous abscess and reactive polyarthritis].  

PubMed

We report a 77-year-old woman with Group B streptococcal bacteremia, subcutaneous abscess and reactive polyarthritis. Two years previously she suffered from atrial fibrillation and osteoarthritis of the knee. After she was admitted for treatment of the knee joint with hyaluronate sodium, she complained of pain in the left shoulder and both knees. Pyogenic arthritis was suspected and administration of cefazolin was started immediately after blood culture. One set of blood cultures showed Group B streptococcus. Therefore the antibiotic was changed to ampicillin. To investigate the cause of polyarthritis, enhanced CT of the left shoulder and both knees was performed and demonstrated fluid collection with marginal enhancement, suggesting a bacterial abscess. However, findings of arthrocentesis and synovial fluid culture were incompatible with bacterial arthritis. A subcutaneous abscess, which appeared at 5 days after admission to the hospital, was not connected to the synovial fluid, suggesting reactive arthritis was the main cause of her polyarthritis. We performed drainage surgery and one week later, the clinical symptoms and inflammatory findings mostly disappeared. Several microbes are able to cause reactive arthritis, however, cases with Group B streptococcus are very rare. Group B streptococcus infection should be taken into consideration not only in patients with diabetes and cerebrovascular disease but also in elderly patients. PMID:18198461

Ota, Hidetaka; Yamaguchi, Yasuhiro; Kojima, Taro; Ohike, Yumiko; Eto, Masato; Akishita, Masahiro; Ouchi, Yasuyoshi

2007-11-01

388

Site-restricted plasminogen activation mediated by group A streptococcal streptokinase variants.  

PubMed

SK (streptokinase) is a secreted plasminogen activator and virulence factor of GAS (group A Streptococcus). Among GAS isolates, SK gene sequences are polymorphic and are grouped into two sequence clusters (cluster type-1 and cluster type-2) with cluster type-2 being further classified into subclusters (type-2a and type-2b). In the present study, we examined the role of bacterial and host-derived cofactors in SK-mediated plasminogen activation. All SK variants, apart from type-2b, can form an activator complex with Glu-Plg (Glu-plasminogen). Specific ligand-binding-induced conformational changes in Glu-Plg mediated by fibrinogen, PAM (plasminogen-binding group A streptococcal M protein), fibrinogen fragment D or fibrin, were required for type-2b SK to form a functional activator complex with Glu-Plg. In contrast with type-1 and type-2a SK, type-2b SK activator complexes were inhibited by ?2-antiplasmin unless bound to fibrin or to the GAS cell-surface via PAM in combination with fibrinogen. Taken together, these data suggest that type-2b SK plasminogen activation may be restricted to specific microenvironments within the host such as fibrin deposits or the bacterial cell surface through the action of ?2-antiplasmin. We conclude that phenotypic SK variation functionally underpins a pathogenic mechanism whereby SK variants differentially focus plasminogen activation, leading to specific niche adaption within the host. PMID:24266842

Cook, Simon M; Skora, Amanda; Walker, Mark J; Sanderson-Smith, Martina L; McArthur, Jason D

2014-02-15

389

An unusual case of hematochezia: acute ischemic proctosigmoiditis.  

PubMed

Acute ischemia of the rectum is uncommon and usually occurs after aorto-iliac surgery. In this report, we present a case of acute ischemic proctosigmoiditis that developed from a brief episode of hypotension. An 85-year-old male presented to the emergency room with hypotension, mental confusion, and passage of maroon-colored stool. He was resuscitated and treated for presumed sepsis. Computerized tomography of the abdomen and pelvis displayed signs of acute inflammation of the distal colon and rectum. Endoscopic findings and microscopic examination of the rectal biopsy revealed changes consistent with acute ischemic proctosigmoiditis. An evaluation for infectious etiologies was negative. The patient's clinical condition improved over the next 24 h with supportive care. Involvement of the rectum is rare in ischemic colitis because of its abundant collateral blood supply. Acute ischemic proctosigmoiditis should be considered in the differential diagnosis of elderly patients with multiple co-morbidities presenting with hematochezia. PMID:18521689

Abhishek, Kumar; Kaushik, Shivu; Kazemi, Mehdi M; El-Dika, Samer

2008-09-01

390

An Unusual Case of Hematochezia: Acute Ischemic Proctosigmoiditis  

PubMed Central

Acute ischemia of the rectum is uncommon and usually occurs after aorto-iliac surgery. In this report, we present a case of acute ischemic proctosigmoiditis that developed from a brief episode of hypotension. An 85-year-old male presented to the emergency room with hypotension, mental confusion, and passage of maroon-colored stool. He was resuscitated and treated for presumed sepsis. Computerized tomography of the abdomen and pelvis displayed signs of acute inflammation of the distal colon and rectum. Endoscopic findings and microscopic examination of the rectal biopsy revealed changes consistent with acute ischemic proctosigmoiditis. An evaluation for infectious etiologies was negative. The patient's clinical condition improved over the next 24 h with supportive care. Involvement of the rectum is rare in ischemic colitis because of its abundant collateral blood supply. Acute ischemic proctosigmoiditis should be considered in the differential diagnosis of elderly patients with multiple co-morbidities presenting with hematochezia. PMID:18521689

Abhishek, Kumar; Kaushik, Shivu; Kazemi, Mehdi M.

2008-01-01

391

The burden of sepsis in the Emergency Department: an observational snapshot.  

PubMed

The primary aim of our study was to establish what proportion of patients in the Emergency Department (ED) fulfill the criteria for sepsis. All adult patients presenting to ED in two 1-week periods, 6 months apart, were included. Notes were reviewed retrospectively to identify which patients fulfilled the criteria for sepsis and severe sepsis. The proportion of patients with sepsis was 4.3% (95% confidence interval 3.3-5.2%) and the proportion with severe sepsis was 2.2% (95% confidence interval 1.5-2.8%). In conclusion our results suggest that sepsis is more common than previously reported and this represents a significant burden on ED. PMID:25485968

Cowan, Sarah L; Holland, Jonathon A A; Kane, Andrew D; Frost, Ian; Boyle, Adrian A

2014-12-01

392

Role of human recombinant activated protein C and low dose corticosteroid therapy in sepsis  

PubMed Central

Despite advances in modern medicine, sepsis remains a complex syndrome that has been associated with significant morbidity and mortality. Multiple organ failure associated with sepsis leads to high mortality and morbidity. About 28 – 50% deaths have been reported in patients with sepsis. The number of sepsis patients is increasing, with considerable burden on healthcare facilities. Various factors leading to a rise in the incidence of sepsis are (1) Improvement of diagnostic procedures (2) Increase in the number of immunocompromised patients taking treatment for various autoimmune disease, carcinomas, organ transplantation (3) Advances in intensive procedures (4) Nosocomial infections (5) Extensive use of antibiotics. With the better understanding of sepsis various modalities to modify pathophysiological response of septic patients have developed. Activated protein C and low-dose corticosteroid therapy have been tried in patients, with variable results. PMID:21224965

Shukla, Aparna; Awasthi, Shilpi

2010-01-01

393

Postadmission sepsis as a screen for quality problems: a case-control study.  

PubMed

The present on admission (POA) indicator used with diagnosis codes listed in hospital discharge abstracts makes it possible to screen for possible in-hospital complications, which may in turn point to quality of care problems. A case-control study was performed among 382 patients from 30 New York State hospitals to see if lapses in quality were associated with the development of postadmission sepsis. Cases with hospital-acquired sepsis (labeled not POA) were compared with matched controls without sepsis. The authors found that central venous catheters and emergently inserted peripheral intravenous catheters were associated with subsequent development of sepsis. Urethral catheters were associated with sepsis for medical patients but not for surgical patients. Adherence to several process of care guidelines was incomplete but none occurred statistically significantly more frequently among sepsis cases than controls. Using discharge abstract diagnosis codes to determine the presence of postadmission complications shows promise for identifying areas for quality improvement. PMID:24226649

Hughes, John S; Eisenhandler, Jon; Goldfield, Norbert; Weinberg, Patti G; Averill, Richard

2014-01-01

394

Regulation of the Transcription Factor C\\/EBP? Following Peritoneal Sepsis  

Microsoft Academic Search

The transcription factors C\\/EBP? and C\\/EBP? belong to the leucine-zipper C\\/EBP (CCAAT\\/enhancer binding protein) family of DNA-binding proteins. C\\/EBP? and C\\/EBP? are expressed in the liver and are implicated in the control of transcriptional events following sepsis. It is hypothesized that inhibition of C\\/EBP? gene expression following sepsis may lead to some of the phenotypic features we recognize as sepsis

Rebecca B. Chapin; Sabita Roy; Richard Charboneau; Kelly Cain; Paul S. Brady; Linda J. Brady; Roderick A. Barke

1995-01-01

395

Hypotransferrinemia and changes in plasma lipid and metabolic patterns in sepsis  

Microsoft Academic Search

This study was performed to obtain a characterization of the changes in plasma transferrin (Tf, g\\/L) in sepsis. More than\\u000a four hundred determinations of Tf, and of a large series of simultaneously collected blood and hemodynamic variables, were\\u000a obtained in 17 patients with post-traumatic sepsis. Tf during sepsis was consistently low (mean ± SD = 1.46 ± 0.46) however\\u000a fluctuated markedly according to changes in metabolic

Carlo Chiarla; Ivo Giovannini; John H. Siegel

2009-01-01

396

Adjuvant selenium supplementation in the form of sodium selenite in postoperative critically ill patients with severe sepsis  

PubMed Central

Introduction Plasma selenium (Se) concentrations are reduced in critically ill surgical patients, and lower plasma Se concentrations are associated with worse outcomes. We investigated whether adjuvant Se supplementation in the form of sodium selenite could improve outcomes in surgical patients with sepsis. Methods In this retrospective study, all adult patients admitted to a 50-bed surgical ICU with severe sepsis between January 2004 and April 2010 were included and analysed according to whether they had received adjuvant Se supplementation, which was given at the discretion of the attending physician. When prescribed, Se was administered in the form of sodium selenite pentahydrate (Na2SeO3?5H2O), in which 100 ?g of Se corresponds to 333 ?g of sodium selenite. A bolus of sodium selenite corresponding to 1,000 ?g of Se was injected intravenously through a central venous line for 30 minutes, followed by infusion of 1,000 ?g/day for 24 hours for 14 days until ICU discharge or death. We performed logistic regression analysis to investigate the impact of adjuvant Se supplementation on hospital mortality. Results Adjuvant Se was administered to 413 (39.7%) of the 1,047 patients admitted with severe sepsis. Age and sex were similar between patients who received adjuvant Se and those who did not. Compared with patients who did not receive adjuvant Se supplementation, patients who did had higher scores on the Simplified Acute Physiology Score II, a greater prevalence of cancer upon admission to the ICU and were more commonly admitted after abdominal surgery. Compared with patients who did not receive adjuvant Se, patients who did had higher hospital mortality rates (46% versus 39.1%; P?=?0.027), and longer median (interquartile range (IQR)) ICU stays (15 days (6 to 24) versus 11 days (4 to 24); P?=?0.01) and hospital lengths of stay (33 days (21 to 52) versus 28 days (17 to 46); P?=?0.001). In multivariable analysis, adjuvant Se supplementation was not independently associated with favourable outcome (odds ratio?=?1.19, 95% confidence interval?=?0.86 to 1.65; P?=?0.288). Conclusions In this retrospective analysis of a large cohort of surgical ICU patients with severe sepsis, adjuvant Se supplementation in the form of sodium selenite had no impact on in-hospital death rates after adjustment for confounders. PMID:24716537

2014-01-01

397

Inadequate Exercise as a Risk Factor for Sepsis Mortality  

PubMed Central

Objective Test whether inadequate exercise is related to sepsis mortality. Research Design and Methods Mortality surveillance of an epidemiological cohort of 155,484 National Walkers' and Runners' Health Study participants residing in the United States. Deaths were monitored for an average of 11.6-years using the National Death index through December 31, 2008. Cox proportional hazard analyses were used to compare sepsis mortality (ICD-10 A40-41) to inadequate exercise (<1.07 METh/d run or walked) as measured on their baseline questionnaires. Deaths occurring within one year of the baseline survey were excluded. Results Sepsis was the underlying cause in 54 deaths (sepsisunderlying) and a contributing cause in 184 deaths (sepsiscontributing), or 238 total sepsis-related deaths (sepsistotal). Inadequate exercise was associated with 2.24-fold increased risk for sepsisunderlying (95%CI: 1.21 to 4.07-fold, P?=?0.01), 2.11-fold increased risk for sepsiscontributing (95%CI: 1.51- to 2.92-fold, P<10?4), and 2.13-fold increased risk for sepsistotal (95%CI: 1.59- to 2.84-fold, P<10?6) when adjusted for age, sex, race, and cohort. The risk increase did not differ significantly between runners and walkers, by sex, or by age. Sepsistotal risk was greater in diabetics (P?=?10?5), cancer survivors (P?=?0.0001), and heart attack survivors (P?=?0.003) and increased with waist circumference (P?=?0.0004). The sepsistotal risk associated with inadequate exercise persisted when further adjusted for diabetes, prior cancer, prior heart attack and waist circumference, and when excluding deaths with cancer, or cardiovascular, respiratory, or genitourinary disease as the underlying cause. Inadequate exercise also increased sepsistotal risk in 2163 baseline diabetics (4.78-fold, 95%CI: 2.1- to 13.8-fold, P?=?0.0001) when adjusted, which was significantly greater (P?=?0.03) than the adjusted risk increase in non-diabetics (1.80-fold, 95%CI: 1.30- to 2.46-fold, P?=?0.0006). Conclusion Inadequate exercise is a risk factor for sepsis mortality, particular in diabetics. PMID:24324580

Williams, Paul T.

2013-01-01

398

PRESENCE OF PRE-EXISTING ANTIBODIES MEDIATE SURVIVAL IN SEPSIS  

PubMed Central

Sepsis is one of the leading causes of death in hospitals worldwide. Even with optimal therapy, severe sepsis results in 50% mortality, indicating variability in the response of individuals towards treatment. We hypothesize that the presence of pre-existing antibodies present in the blood before the onset of sepsis induced by cecal ligation and puncture (CLP) in mice, accounts for the differences in their survival. A Plasma Enhanced Killing (PEK) assay was performed to calculate the PEK capacity of plasma i.e. the ability of plasma to augment PMN killing of bacteria. PEK was calculated as PEK= (1/log (N)) × 100; where N= number of surviving bacteria; a higher PEK indicated better bacterial killing. A range of PEK in plasma collected from mice prior to CLP was observed, documenting individual differences in bacterial killing capacity. Mortality was predicted based on plasma IL-6 levels at 24 hr post CLP. Mice predicted to die (Die-P) had a lower PEK (<14) and higher peritoneal bacterial counts 24 hr post sepsis compared to those predicted to live (Live-P) with a PEK>16. Mice with PEK<14 were 3.1 times more likely to die compared to the PEK>16 group. To understand the mechanism of defense conferred by the pre-existing antibodies, binding of IgM or IgG to enteric bacteria was documented by flow cytometry. To determine the relative contribution of IgM or IgG, the immunoglobulins were specifically immuno-depleted from the naïve plasma samples and the PEK of the depleted plasma measured. Compared to naïve plasma, depletion of IgM had no effect on the PEK. However, depletion of IgG increased PEK suggesting that an inhibitory IgG binds to antigenic sites on bacteria preventing optimal opsonization of the bacteria. These data demonstrate that prior to CLP; circulating inhibitory IgG antibodies exist that prevent bacterial killing by PMNs in a CLP model of sepsis. PMID:21921828

Moitra, Rituparna; Beal, Dominic R.; Belikoff, Bryan G.; Remick, Daniel G.

2011-01-01

399

Thymus-dependent and -independent regulation of Ia antigen expression in situ by cells in the synovium of rats with streptococcal cell wall-induced arthritis. Differences in site and intensity of expression in euthymic, athymic, and cyclosporin A-treated LEW and F344 rats.  

PubMed Central

Euthymic LEW rats, when injected with streptococcal cell walls, exhibited rapid onset development of acute exudative arthritis coincident with enhanced synovial expression of Ia antigen. By 21 d after injection, the expression of Ia was markedly increased compared with basal conditions and paralleled the severity of the later developing proliferative and erosive disease. Immunodeficient athymic and cyclosporin A-treated LEW rats developed only the early phase arthritis, which was again paralleled by synovial Ia expression. Chronic expression of high levels of Ia antigen was not observed. Histocompatible F344 rats, both athymic and euthymic, developed minimal, if any, clinically significant arthritis and did not exhibit the enhanced Ia expression demonstrated in the LEW rats. Our results indicate that enhanced synovial Ia expression parallels clinical disease severity and varies by rat strain, and that the rapid onset enhanced synovial Ia expression is thymus independent, whereas the markedly enhanced chronic phase Ia expression is thymus dependent. Images PMID:3494045

Wilder, R L; Allen, J B; Hansen, C

1987-01-01

400

Angiopoietin-1, Angiopoietin-2 and Bicarbonate as Diagnostic Biomarkers in Children with Severe Sepsis  

PubMed Central

Severe pediatric sepsis continues to be associated with high mortality rates in children. Thus, an important area of biomedical research is to identify biomarkers that can classify sepsis severity and outcomes. The complex and heterogeneous nature of sepsis makes the prospect of the classification of sepsis severity using a single biomarker less likely. Instead, we employ machine learning techniques to validate the use of a multiple biomarkers scoring system to determine the severity of sepsis in critically ill children. The study was based on clinical data and plasm