These are representative sample records from Science.gov related to your search topic.
For comprehensive and current results, perform a real-time search at Science.gov.
1

Streptococcal acute pharyngitis.  

PubMed

Acute pharyngitis/tonsillitis, which is characterized by inflammation of the posterior pharynx and tonsils, is a common disease. Several viruses and bacteria can cause acute pharyngitis; however, Streptococcus pyogenes (also known as Lancefield group A ?-hemolytic streptococci) is the only agent that requires an etiologic diagnosis and specific treatment. S. pyogenes is of major clinical importance because it can trigger post-infection systemic complications, acute rheumatic fever, and post-streptococcal glomerulonephritis. Symptom onset in streptococcal infection is usually abrupt and includes intense sore throat, fever, chills, malaise, headache, tender enlarged anterior cervical lymph nodes, and pharyngeal or tonsillar exudate. Cough, coryza, conjunctivitis, and diarrhea are uncommon, and their presence suggests a viral cause. A diagnosis of pharyngitis is supported by the patient's history and by the physical examination. Throat culture is the gold standard for diagnosing streptococcus pharyngitis. However, it has been underused in public health services because of its low availability and because of the 1- to 2-day delay in obtaining results. Rapid antigen detection tests have been used to detect S. pyogenes directly from throat swabs within minutes. Clinical scoring systems have been developed to predict the risk of S. pyogenes infection. The most commonly used scoring system is the modified Centor score. Acute S. pyogenes pharyngitis is often a self-limiting disease. Penicillins are the first-choice treatment. For patients with penicillin allergy, cephalosporins can be an acceptable alternative, although primary hypersensitivity to cephalosporins can occur. Another drug option is the macrolides. Future perspectives to prevent streptococcal pharyngitis and post-infection systemic complications include the development of an anti-Streptococcus pyogenes vaccine. PMID:25229278

Anjos, Lais Martins Moreira; Marcondes, Mariana Barros; Lima, Mariana Ferreira; Mondelli, Alessandro Lia; Okoshi, Marina Politi

2014-07-01

2

Acute streptococcal myopericarditis mimicking myocardial infarction.  

PubMed

A 25-year-old man who had recurrent sore throats presented with sharp central chest pain 5 hours after starting penicillin for tonsillitis. Electrocardiogram (ECG) revealed ST-segment elevation in leads I and aVL with reciprocal ST depression in lead III (Fig. 1). Troponin I was measured as 33 microg/L (normal range, b0.1 microg/L), and C-reactive protein (CRP) was 127 (normal range b10). Echocardiogram revealed a nondilated well-contracting left ventricle, and cardiac catheterization revealed normal coronary arteries. A diagnosis of acute myopericarditis was made, and he was treated with moxifloxacin. Throat swabs grew Lancefield group A Streptococcus. Over subsequent days, his symptoms and ECG changes resolved, and he was discharged on longterm prophylactic penicillin. PMID:18534319

Khavandi, Ali; Whitaker, John; Elkington, Andrew; Probert, Jo; Walker, Paul R

2008-06-01

3

Group B Streptococcal b-Hemolysin Induces Mortality and Liver Injury in Experimental Sepsis  

E-print Network

-hemolysin plays a crucial role in the pathophysiology of GBS sepsis by inducing liver failure and high mortality. The incidence of gram- positive sepsis has risen since the 1980s, and, today, gram-positive organisms cause 50% of all cases of sepsis [1]. Group B strep- tococci (GBS; Streptococcus agalactiae ) are a major etiologic

Nizet, Victor

4

Evidence for a streptococcal superantigen-driven process in acute guttate psoriasis.  

PubMed Central

Recent studies have suggested that T cells play a critical role in the pathogenesis of psoriasis. Guttate psoriasis is a well-defined form of psoriasis frequently associated with streptococcal throat infection. This study tested the hypothesis that T cells in acute guttate psoriasis skin lesions may be activated by streptococcal superantigens. Peripheral blood as well as lesional and perilesional skin biopsies were analyzed for T cell receptor V beta repertoire using monoclonal antibodies against 10 different V beta families. Skin biopsies from all patients with acute guttate psoriasis, but not skin biopsies from patients with acute atopic dermatitis or inflammatory skin lesions induced in normal subjects with sodium lauryl sulfate, demonstrated selective accumulation of V beta 2+ T cells (P < 0.05). The expansion of V beta 2+ T cells occurred in both the CD4+ and the CD8+ T cell subsets. Sequence analysis of T cell receptor beta chain genes of V beta 2-expressing T cells from skin biopsies of patients with guttate psoriasis showed extensive junctional region diversity that is more compatible with a superantigen rather than a conventional (nominal) antigen-driven T cell response. All streptococcal isolates from patients with guttate psoriasis secreted streptococcal pyrogenic exotoxin C, a superantigen known to stimulate marked V beta 2+ T cell expansion. These data support the concept that acute guttate psoriasis is associated with superantigenic stimulation of T cells triggered by streptococcal superantigen(s). Images PMID:7593594

Leung, D Y; Travers, J B; Giorno, R; Norris, D A; Skinner, R; Aelion, J; Kazemi, L V; Kim, M H; Trumble, A E; Kotb, M

1995-01-01

5

Lymphocyte surface markers in acute rheumatic fever and post-streptococcal acute glomerulonephritis.  

PubMed Central

Lymphocyte cell-surface markers were examined in forty children with acute rheumatic fever (ARF) and twelve with acute post-streptococal glomerulonephritis (AGN) and compared to thirty-six normal controls of similar age. Cell-surface-marker studies included surface Ig using fluorescein-labelled F(ab)2 anti-F(AB')2, IgG aggregate binding cells, and EAC rosettes. T cells were identified both as 'active' rosettes and total E-binding cells. Proportions and absolute numbers of cells bearing surface Ig and Fc receptors were elevated in subjects with AGN (Pless than0-01-0-5), whereas proportions of cells producing EAC rosettes were diminished. Patients with acute rheumatic carditis or chorea showed a substantial elevation in proportions and numbers of active T-cell rosettes (Pless than0-01). Streptococcal antigen binding cells capable of forming rosettes with autologous cells coated with group A streptococcal membranes were elevated in the acute phase of both rheumatic fever and acute glomerulonephritis(Pless than0-01). The majority of such cells were removed by passage over insolubilized Ig-anti-IgG columns and appeared to be B cells. PMID:300301

Williams, R C; Zabriskie, J B; Mahros, F; Hassaballa, F; Abdin, Z H

1977-01-01

6

Neonatal sepsis  

PubMed Central

Neonatal sepsis continues to be a common and significant health care burden, especially in very-low-birth-weight infants (VLBW <1500 g). Though intrapartum antibiotic prophylaxis has decreased the incidence of early-onset group B streptococcal infection dramatically, it still remains a major cause of neonatal sepsis. Moreover, some studies among VLBW preterm infants have shown an increase in early-onset sepsis caused by Escherichia coli. As the signs and symptoms of neonatal sepsis are nonspecific, early diagnosis and prompt treatment remains a challenge. There have been a myriad of studies on various diagnostic markers like hematological indices, acute phase reactants, C-reactive protein, procalcitonin, cytokines, and cell surface markers among others. Nonetheless, further research is needed to identify a biomarker with high diagnostic accuracy and validity. Some of the newer markers like inter ? inhibitor proteins have shown promising results thereby potentially aiding in early detection of neonates with sepsis. In order to decrease the widespread, prolonged use of unnecessary antibiotics and improve the outcome of the infants with sepsis, reliable identification of sepsis at an earlier stage is paramount. PMID:24185532

Shah, Birju A; Padbury, James F

2014-01-01

7

Post-streptococcal acute glomerulonephritis in children: clinical features and pathogenesis  

Microsoft Academic Search

Post-streptococcal acute glomerulonephritis (PSAGN) is one of the most important and intriguing conditions in the discipline\\u000a of pediatric nephrology. Although the eventual outcome is excellent in most cases, PSAGN remains an important cause of acute\\u000a renal failure and hospitalization for children in both developed and underdeveloped areas. The purpose of this review is to\\u000a describe both the typical and less

T. Matthew Eison; Bettina H. Ault; Deborah P. Jones; Russell W. Chesney; Robert J. Wyatt

2011-01-01

8

Purpura Fulminans and Late Onset Group B Streptococcal Sepsis in a Premature Twin  

PubMed Central

Introduction:?Purpura fulminans (PF) is a skin manifestation due to hemorrhagic infarction caused by intravascular thrombosis secondary to bacterial infections or deficiency of anticoagulants such as protein C and protein S. Neonatal PF is a rare but potentially disabling disorder associated with a high mortality and severe long term morbidity in those who survive. Case description:?We report a case of a premature infant who developed extensive PF due to late onset group B streptococcus sepsis. Despite early identification and initiation of antibiotic therapy in our patient, PF progressed rapidly, leading to autoamputation of fingers and toes and severe brain injury. Conclusion:?In conclusion, our case highlights the severe sequelae of PF due to late onset GBS sepsis in a premature infant.

Elayappen, Avanikkha; Jain, Sunil K.; Loeffelholz, Michael J.; Patel, Janak

2014-01-01

9

Lipid peroxidation, osmotic fragility and antioxidant status in children with acute post-streptococcal glomerulonephritis  

Microsoft Academic Search

Plasma and erythrocyte samples from acute post-streptococcal glomerulonephritis (APSGN) children and control children were enrolled in this study. Lipid peroxidation (LPO), measured in terms of thiobarbituric acid-reactive substances (TBARS) was found to be significantly increased in plasma and RBCs of APSGN children (P<0.05) than in control children. Osmotic fragility of erythrocytes was examined. RBCs of APSGN patients were found to

T. Devasena; S. Lalitha; K. Padma

2001-01-01

10

Prognostic factors in acute renal failure due to sepsis. Results of a prospective multicentre study  

Microsoft Academic Search

Background. Sepsis is a major cause of acute renal failure in hospital patients, but its incidence and the associated prognostic factors have rarely been assessed prospectively by multivariate analysis. Methods. We conducted a prospective 6-month study in 20 multidisciplinary intensive care units to assess the prognosis of patients hospitalized with acute renal failure due to sepsis. Sepsis syndrome and septic

H. Neveu; D. Kleinknecht; F. Brivet; Ph. Loirat; P. Landais; CMC Foch

11

Neutrophil apoptosis: a marker of disease severity in sepsis and sepsis-induced acute respiratory distress syndrome  

PubMed Central

Introduction Apoptosis of neutrophils (polymorphonuclear neutrophils [PMNs]) may limit inflammatory injury in sepsis and acute respiratory distress syndrome (ARDS), but the relationship between the severity of sepsis and extent of PMN apoptosis and the effect of superimposed ARDS is unknown. The objective of this study was to correlate neutrophil apoptosis with the severity of sepsis and sepsis-induced ARDS. Methods A prospective cohort study was conducted in intensive care units of three tertiary hospitals in Porto Alegre, southern Brazil. Fifty-seven patients with sepsis (uncomplicated sepsis, septic shock, and sepsis-induced ARDS) and 64 controls were enrolled. Venous peripheral blood was collected from patients with sepsis within 24 hours of diagnosis. All surgical groups, including controls, had their blood drawn 24 hours after surgery. Control patients on mechanical ventilation had blood collected within 24 hours of initiation of mechanical ventilation. Healthy controls were blood donors. Neutrophils were isolated, and incubated ex vivo, and apoptosis was determined by light microscopy on cytospun preparations. The differences among groups were assessed by analysis of variance with Tukeys. Results In medical patients, the mean percentage of neutrophil apoptosis (± standard error of the mean [SEM]) was lower in sepsis-induced ARDS (28% ± 3.3%; n = 9) when compared with uncomplicated sepsis (57% ± 3.2%; n = 8; p < 0.001), mechanical ventilation without infection, sepsis, or ARDS (53% ± 3.0%; n = 11; p < 0.001) and healthy controls (69% ± 1.1%; n = 33; p < 0.001) but did not differ from septic shock (38% ± 3.7%; n = 12; p = 0.13). In surgical patients with sepsis, the percentage of neutrophil apoptosis was lower for all groups when compared with surgical controls (52% ± 3.6%; n = 11; p < 0.001). Conclusion In medical patients with sepsis, neutrophil apoptosis is inversely proportional to the severity of sepsis and thus may be a marker of the severity of sepsis in this population. PMID:17092345

Fialkow, Lea; Fochesatto Filho, Luciano; Bozzetti, Mary C; Milani, Adriana R; Rodrigues Filho, Edison M; Ladniuk, Roberta M; Pierozan, Paula; de Moura, Rafaela M; Prolla, Joao C; Vachon, Eric; Downey, Gregory P

2006-01-01

12

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

13

[The clinico-laboratory characteristics and diagnosis of acute stomatogenic sepsis].  

PubMed

Thirty-four patients with acute stomatogenic sepsis developing in grave ulcerative necrotic stomatitis (including that in Stevens-Johnson's and Lyell's syndromes) were examined. Homeostasis parameters were shifted in these patients. To facilitate timely diagnosis of acute stomatogenic sepsis, the authors offer a differential diagnostic table. Patients with grave forms of stomatitis are recommended to be referred for examination and treatment to specialized dentistry hospitals in order to early diagnose the disease and prevent the development of acute sepsis. PMID:8754538

El'kova, N L; Korchinova, L D; Kobtseva, T M

1996-01-01

14

Scrub Typhus with Sepsis and Acute Respiratory Distress Syndrome  

PubMed Central

Scrub typhus is a major infectious threat in the Asia-Pacific region. We report an unusual case of scrub typhus in a patient in Singapore who presented with sepsis and acute respiratory distress syndrome but lacked the pathognomonic eschar. The patient recovered after appropriate diagnosis and doxycycline treatment. Rickettsial diseases should be included in the differential diagnosis of febrile illnesses in regions where the diseases are endemic, and absence of eschar should not be the criterion used to rule out scrub typhus. PMID:23761149

Kurup, Asok; Issac, Aneesh; Loh, Jin Phang; Lee, Too Bou; Chua, Robert; Bist, Pradeep; Chao, Chien-Chung; Lewis, Michael; Gubler, Duane J.; Ching, Wei Mei; Ooi, Eng Eong

2013-01-01

15

Sepsis  

MedlinePLUS

... bacteria, some of which normally live on the skin's surface, to get inside the baby's body and cause an infection. In some cases of sepsis in newborns, bacteria enter the baby's body from the mother during pregnancy, labor, or delivery. Some pregnancy complications that can increase the risk ...

16

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

17

Effects of honokiol on sepsis-induced acute kidney injury in an experimental model of sepsis in rats.  

PubMed

Acute kidney injury (AKI) is a severe complication of sepsis, which largely contributes to the high mortality rate of sepsis. Honokiol, a natural product isolated from Magnolia officinalis (Houpo), has been shown to exhibit anti-inflammatory and antioxidant properties. Here, we investigated the effects of honokiol on sepsis-associated AKI in rats subjected to cecal ligation and puncture (CLP). We found that the administration of honokiol improved the survival of septic rats. Periodic acid-Schiff stain revealed that the morphological changes of kidney tissues in CLP rats were restored after honokiol treatment. Furthermore, honokiol reduced CLP-induced oxidative stress and inflammatory cytokine production. The levels of nitric oxide (NO) and inducible NO synthetase (iNOS) were attenuated by honokiol in septic rats. Finally, honokiol inhibited CLP-induced activation of NF-?B signaling in CLP rats. Our findings suggest that honokiol might be used as a potential therapeutic agent for complications of sepsis, especially for sepsis-induced AKI. PMID:24531855

Li, Nan; Xie, Hua; Li, Longkai; Wang, Jing; Fang, Ming; Yang, Ning; Lin, Hongli

2014-08-01

18

Compliance with a protocol for intrapartum antibiotic prophylaxis against neonatal group B streptococcal sepsis in women with clinical risk factors.  

PubMed Central

OBJECTIVE: The aim of this study was to determine the prevalence of clinical risk factors (CRF) for neonatal sepsis in laboring women and to evaluate clinician compliance with a CRF-based protocol for intrapartum antibiotic prophylaxis (IAP). METHODS: A retrospective chart audit was undertaken at a district hospital (A) and a tertiary obstetric hospital (B) in Sydney, Australia between 1996 and 1998, to determine compliance with IAP in women with defined CRF. RESULTS: Eighty-five (12%) women at Hospital A and 117 (19%) at Hospital B had one or more CRF. Overall compliance rates with the IAP protocols were 65 and 50% at Hospitals A and B respectively, but varied according to maternal, obstetric and sepsis-related risk factors. We postulate that differences between the hospitals were related to protocol implementation. CONCLUSIONS: Compliance with a CRF-based protocol was lower than previously reported. Improvements in protocol development, implementation and maintenance are required to enhance compliance with IAP based on CRF. PMID:12648317

Sanders, Toni R; Roberts, Christine L; Gilbert, Gwendolyn L

2002-01-01

19

Knockdown of Burton's tyrosine kinase confers potent protection against sepsis-induced acute lung injury.  

PubMed

Sepsis is a common and critical complication in surgical patients that often leads to multiple organ failure syndrome (MOFS), including acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Despite intensive supportive care and treatment modalities, the mortality of these patients remains high. In this study, we investigated the role of Burton's tyrosine kinase (BTK), a member of the Btk/Tec family of cytoplasmic tyrosine kinases, in the pathogenesis of sepsis, and evaluated the protective effect of in vivo Btk RNA interference in a mouse model of cecal ligation and puncture (CLP)-induced sepsis. After intratracheal injection of Btk siRNA, the mice were then subjected to CLP to induce sepsis. The results demonstrated that this approach conferred potent protection against sepsis-induced ALI, as evidenced by a significant reduction in pathological scores, epithelial cell apoptosis, pulmonary edema, vascular permeability, and the expression of inflammatory cytokines and neutrophil infiltration in the lung tissues of septic mice. In addition, RNA interference of Btk significantly suppressed p-38 and iNOS signaling pathways in transduced alveolar macrophages in vitro. These results identify a novel role for BTK in lethal sepsis and provide a potential new therapeutic approach to sepsis and ALI. PMID:24906236

Zhou, Panyu; Ma, Bing; Xu, Shuogui; Zhang, Shijie; Tang, Hongtai; Zhu, Shihui; Xiao, Shichu; Ben, Daofeng; Xia, Zhaofan

2014-11-01

20

Effect of Resident Physician Education Regarding Selective Chemoprophylaxis for the Prevention of Early Onset Group B Streptococcal Sepsis: An Outcome Study  

PubMed Central

Objective: The aim of this study was to evaluate the effect of a voluntary protocol for selective intrapartum chemoprophylaxis on the incidence of early onset group B streptococcal sepsis (GBS EOS). Methods: Cases of GBS EOS were defined as a positive GBS culture from a normally sterile fluid obtained during the first 7 days of life. All cases of GBS EOS at an urban, university-affiliated community hospital were reviewed during 2 time periods. The 2-year period before instituting a resident education program to promote selective chemoprophylaxis (1988–89) was retrospectively reviewed; the 2-year period after the education program was introduced (1990–91) was prospectively recorded. The outcome measure was the incidence of GBS EOS. Results: The rate of GBS EOS was 7/14,335 deliveries (0.05%) before and 9/13,999 (0.064%) after the introduction of the education program (observed difference between proportions 0.016%, 95% confidence interval [CI] for the difference between the proportions –0.071% to 0.04%, P = not significant [NS]). The rate of GBS EOS in preterm infants was 5/1,331 (0.376%) before and 3/1,297 (0.23%) afterward (observed difference between proportions 0.14%, 95% CI –0.28% to 0.56%, P = NS). The incidence of GBS EOS did not decrease during the latter period due to failure of antepartum cultures to predict intrapartum GBS colonization (2 cases); non-compliance with voluntary recommendations to administer chemoprophylaxis (2 cases); failure of chemoprophylaxis or therapy for intraamniotic infection to prevent neonatal infection (3 cases); and occurrence of GBS EOS in infants without risk factors (2 cases). Conclusions: An education program for resident physicians regarding chemoprophylaxis for GBS EOS did not significantly reduce the absolute incidence of disease. Alternative strategies are needed that redress the causes of failure inherent in the current guidelines. Some cases of GBS EOS are not preventable because the parturient does not have risk factors that indicate chemoprophylaxis. PMID:18472876

Rosen, Doron J. D.; Sumen, Anita P.

1994-01-01

21

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

22

Management of Acute Pharyngitis in Adults Reliability of Rapid Streptococcal Tests and Clinical Findings  

Microsoft Academic Search

otic use, in 38% of patients with streptococcal pharyn- gitis. Systematic RSAT led to nearly optimal treatment (94%) and antibiotic prescription (37%), with minimal antibiotic overuse (3%) and underuse (3%). Empirical antibiotictreatmentinpatientswith3or4clinicalsymp- toms or signs resulted in a lower rate of appropriate therapy (59%) but higher rates of antibiotic use (60%), overuse(32%),andunderuse(9%).SystematicRSATwas more cost-effective than strategies based on empirical treatment

Jean-Paul Humair; Sylvie Antonini Revaz; Patrick Bovier; Hans Stalder

23

The use of corticosteroids in severe sepsis and acute respiratory distress syndrome.  

PubMed

During sepsis or acute respiratory distress syndrome, the hypothalamic pituitary adrenal axis is rapidly activated through a systemic pathway, i.e. by circulating pro-inflammatory cytokines and through the vagus nerve. Subsequently, the adrenal glands release cortisol, a hormone which will likely counteract the inflammatory process and restore cardiovascular homeostasis. Both experimental models and studies in humans suggest that inadequate hypothalamic pituitary adrenal axis response to stress accounts, at least partly, for the genesis of shock and organ dysfunction in sepsis and acute respiratory distress syndrome. Relative adrenal insufficiency and peripheral glucocorticoid resistance syndrome are the two main features of the inappropriate hormonal response and provide the grounds for cortisol replacement in these diseases. In practice, a high dose of corticosteroids (i.e. one to four boluses of 30 mg/kg of methylprednisolone, or equivalent) had no effects on survival in severe sepsis or acute respiratory distress syndrome. There are at least seven randomised controlled trials reporting the benefits and risks of low dose corticosteroids (i.e. 200 to 300 mg daily of hydrocortisone or equivalent) given for a prolonged period in severe sepsis or in the late phase of acute respiratory distress syndrome. These trials showed consistently that, in these patients, the use of low dose of corticosteroids alleviated inflammation, restored cardiovascular homeostasis, reduced organ dysfunction, improved survival and was safe. Further studies are ongoing to better identify the target population. In the meantime, cortisol replacement (i.e. 200 to 300 mg daily of hydrocortisone or equivalent) should be considered as standard care for these patients. PMID:12553498

Chadda, Karim; Annane, Djillali

2002-01-01

24

Management of acute perianal sepsis in neutropenic patients with hematological malignancy.  

PubMed

In neutropenic patients with acute perianal sepsis in the setting of hematological malignancy, the classical clinical features of abscess formation are lacking. Additionally, the role of surgical intervention is not well established. In this review, we discuss the challenges and controversy regarding diagnosis and optimal management when clear surgical guidelines are absent. In the literature, there is great diversity in the surgical approach to these patients, which leads to a high percentage of diagnostic errors, risks of complications, and unnecessary interventions. We review the literature and assess whether surgical intervention produces better outcomes than a non-surgical approach. Studies published on perianal sepsis in neutropenic cancer patients were identified by searching PubMed using the following key words: "perianal sepsis/abscesses, anorectal sepsis/abscess, neutropenia, hematological malignancy, cancer". No randomized or prospective studies on the management of acute perianal sepsis in hematological malignancies were found. The largest retrospective study and most comprehensive clinical data demonstrated that 42% of patients were treated successfully without surgical intervention and without morbidity or mortality related to treatment chosen. Small retrospective studies advocated surgical intervention, while the majority of successes were in a non-operative treatment. It is difficult to formulate a conclusion given the small retrospective series on management of neutropenic patients with hematological malignancies. While there is no evidence mandating a routine surgical approach in this category of patients, non-surgical management including careful follow-up to determine whether the patient's condition is deteriorating or treatment has failed is an acceptable approach in selected patients without pathognomonic features of abscess. Comprehensive and well-designed prospective studies are needed to firmly establish the guidelines of treatment protocols. PMID:24276114

Baker, B; Al-Salman, M; Daoud, F

2014-04-01

25

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

26

Sepsis-Induced Acute Lung Injury (ALI) Is Milder in Diabetic Rats and Correlates with Impaired NFkB Activation  

PubMed Central

Acute lung injury (ALI) develops in response to a direct insult to the lung or secondarily to a systemic inflammatory response, such as sepsis. There is clinical evidence that the incidence and severity of ALI induced by direct insult are lower in diabetics. In the present study we investigated whether the same occurs in ALI secondarily to sepsis and the molecular mechanisms involved. Diabetes was induced in male Wistar rats by alloxan and sepsis by caecal ligation and puncture surgery (CLP). Six hours later, the lungs were examined for oedema and cell infiltration in bronchoalveolar lavage. Alveolar macrophages (AMs) were cultured in vitro for analysis of I?B and p65 subunit of NF?B phosphorylation and MyD88 and SOCS-1 mRNA. Diabetic rats were more susceptible to sepsis than non-diabetics. In non-diabetic rats, the lung presented oedema, leukocyte infiltration and increased COX2 expression. In diabetic rats these inflammatory events were significantly less intense. To understand why diabetic rats despite being more susceptible to sepsis develop milder ALI, we examined the NF?B activation in AMs of animals with sepsis. Whereas in non-diabetic rats the phosphorylation of I?B and p65 subunit occurred after 6 h of sepsis induction, this did not occur in diabetics. Moreover, in AMs from diabetic rats the expression of MyD88 mRNA was lower and that of SOCS-1 mRNA was increased compared with AMs from non-diabetic rats. These results show that ALI secondary to sepsis is milder in diabetic rats and this correlates with impaired activation of NF?B, increased SOCS-1 and decreased MyD88 mRNA. PMID:23024779

Filgueiras, Jr., Luciano R.; Martins, Joilson O.; Serezani, Carlos H.; Capelozzi, Vera L.; Montes, Marlise B. A.; Jancar, Sonia

2012-01-01

27

Type 2 Deiodinase and Host Responses of Sepsis and Acute Lung Injury  

PubMed Central

The role of thyroid hormone metabolism in clinical outcomes of the critically ill remains unclear. Using preclinical models of acute lung injury (ALI), we assessed the gene and protein expression of type 2 deiodinase (DIO2), a key driver for synthesis of biologically active triiodothyronine, and addressed potential association of DIO2 genetic variants with ALI in a multiethnic cohort. DIO2 gene and protein expression levels in murine lung were validated by microarrays and immunoblotting. Lung injury was assessed by levels of bronchoalveolar lavage protein and leukocytes. Single-nucleotide polymorphisms were genotyped and ALI susceptibility association assessed. Significant increases in both DIO2 gene and D2 protein expression were observed in lung tissues from murine ALI models (LPS- and ventilator-induced lung injury), with expression directly increasing with the extent of lung injury. Mice with reduced levels of DIO2 expression (by silencing RNA) demonstrated reduced thyroxine levels in plasma and increased lung injury (increased bronchoalveolar lavage protein and leukocytes), suggesting a protective role for DIO2 in ALI. The G (Ala) allele of the Thr92Ala coding single-nucleotide polymorphism (rs225014) was protective in severe sepsis and severe sepsis–associated ALI after adjustments for age, sex, and genetic ancestry in a logistic regression model in European Americans. Our studies indicate that DIO2 is a novel ALI candidate gene, the nonsynonymous Thr92Ala coding variant of which confers ALI protection. Increased DIO2 expression may dampen the ALI inflammatory response, thereby strengthening the premise that thyroid hormone metabolism is intimately linked to the integrated response to inflammatory injury in critically ill patients. PMID:21685153

Ma, Shwu-Fan; Xie, Lishi; Pino-Yanes, Maria; Sammani, Saad; Wade, Michael S.; Letsiou, Eleftheria; Siegler, Jessica; Wang, Ting; Infusino, Giovanni; Kittles, Rick A.; Flores, Carlos; Zhou, Tong; Prabhakar, Bellur S.; Moreno-Vinasco, Liliana; Villar, Jesus; Jacobson, Jeffrey R.; Dudek, Steven M.

2011-01-01

28

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

PubMed

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

2014-08-01

29

Effects of early administration of a novel anticholinergic drug on acute respiratory distress syndrome induced by sepsis  

PubMed Central

Summary Background Acute respiratory distress syndrome (ARDS) is the inflammatory disorder of the lung most commonly caused by sepsis. It was hypothesized that treating the lung with penehyclidine hydrochloride (PHC), a new type of hyoscyamus drug, early in the development of sepsis could diminish the lung dysfunction. Material/Methods Sprague-Dawley rats were divided into 4 groups: 1) a control group; 2) a sham-operated group; 3) a cecal ligation and puncture (CLP) group; 4) a PHC-treated group. One hour after CLP surgery, rats were either untreated or treated with PHC via intraperitoneal injection. Lung wet/dry weight ratio, bronchoalveolar lavage fluid (BALF), serum tumor necrosis factor (TNF-?), interleukin 6 (IL-6), interleukin 10 (IL-10), total nitrite/nitrate (NOx), superoxide dismutase (SOD), malondialdehyde (MDA) in lung tissues, and pulmonary functions were examined 24 hour after surgery. Another 60 rats were randomly assigned to 4 equal groups to observe survival status 96 hours after surgery. Results Treatment of PHC markedly decreased TNF-?, IL-6, NOx, SOD, MDA content, protein concentration in BALF, and lung wet/dry weight ratio and enhanced SOD activity (p<0.05), which are indicative of PHC-induced suppression in the pathogenesis of ARDS caused by sepsis. In comparison to group CLP/saline, plasma IL-10 level markedly increased in group CLP/PHC. In PHC-treated groups, the administered PHC had a significant protective effect on the lung dysfunction induced by sepsis. Conclusions We conclude that administration of PHC at the time of a systemic insult can protect the lung from the damaging effects of sepsis. PMID:22037734

Li, Hao; Qian, Zhaoxin; Li, Jianmin; Han, Xiaotong; Liu, Min

2011-01-01

30

Cellular Reactivity Studies to Streptococcal Antigens MIGRATION INHIBITION STUDIES IN PATIENTS WITH STREPTOCOCCAL INFECTIONS AND REHEUMATIC FEVER  

PubMed Central

The question of whether hypersensitivity to streptococcal antigens plays a role in the pathogenesis of the nonsuppurative sequelae of streptococcal infections remains at present unclear. As a first step in the approach to this question, the degree of cellular reactivity of peripheral blood leucocytes to streptococcal antigens was investigated in a number of rheumatic fever patients, patients with uncomplicated streptococcal infections, as well as normal healthy subjects. Using the in vitro technique for the inhibition of capillary migration of peripheral blood leucocytes as an index of the degree of sensitivity to streptococcal antigens, the results indicate that patients with acute rheumatic fever exhibit an exaggerated cellular reactivity to these antigens and in particular to streptococcal cell membrane antigens. This abnormal response to streptococcal membrane antigens appears to persist in rheumatic subjects for at least 5 yr after the initial attack of rheumatic fever. Only Group A streptococcal membrane antigens elicited this unusual response in rheumatic subjects, since the cellular reactivity to Group C and D streptococcal membranes was the same in all groups. Patients with evidence of valvular disease exhibited the same degree of cellular reactivity to these antigens as did patients without clinical evidence of rheumatic heart disease. The nature of the antigens responsible for the observed cellular response remains unknown. Enzymatic treatment of streptococcal cell walls and membranes designed to remove type-specific M proteins did not alter the observed cellular reactivity to the streptococcal antigens. The finding that an abnormal cellular response to certain streptococcal antigens is present only in rheumatic patients suggests that cell-mediated factors may play an important role in the disease process. PMID:4603169

Read, Stanley E.; Fischetti, Vincent A.; Utermohlen, Virginia; Falk, Rudolf E.; Zabriskie, John B.

1974-01-01

31

Phenotyping community-acquired pneumonia according to the presence of acute respiratory failure and severe sepsis  

PubMed Central

Background Acute respiratory failure (ARF) and severe sepsis (SS) are possible complications in patients with community-acquired pneumonia (CAP). The aim of the study was to evaluate prevalence, characteristics, risk factors and impact on mortality of hospitalized patients with CAP according to the presence of ARF and SS on admission. Methods This was a multicenter, observational, prospective study of consecutive CAP patients admitted to three hospitals in Italy, Spain, and Scotland between 2008 and 2010. Three groups of patients were identified: those with neither ARF nor SS (Group A), those with only ARF (Group B) and those with both ARF and SS (Group C) on admission. Results Among the 2,145 patients enrolled, 45% belonged to Group A, 36% to Group B and 20% to Group C. Patients in Group C were more severe than patients in Group B. Isolated ARF was correlated with age (p?

2014-01-01

32

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) prevents lipopolysaccharide (LPS)-induced, sepsis-related severe acute lung injury in mice  

PubMed Central

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is an energy metabolism-related enzyme in the glycolytic pathway. Recently, it has been reported that GAPDH has other physiological functions, such as apoptosis, DNA repair and autophagy. Some in vitro studies have indicated immunological aspects of GAPDH function, although there is no definite study discussing the advantage of GAPDH as a therapeutic target. Here, we show that GAPDH has an anti-inflammatory function by using a lipopolysaccharide (LPS)-induced, sepsis-related severe acute lung injury (ALI) mouse model, which is referred to as acute respiratory distress syndrome (ARDS) in humans. GAPDH pre-injected mice were protected from septic death, and their serum levels of proinflammatory cytokines were significantly suppressed. In lung tissue, LPS-induced acute injury and neutrophil accumulation were strongly inhibited by GAPDH pre-injection. Pulmonary, proinflammatory cytokine gene expression and serum chemokine expression in GAPDH pre-injected mice were also reduced. These data suggest the therapeutic potential of GAPDH for sepsis-related ALI/ARDS. PMID:24902773

Takaoka, Yuki; Goto, Shigeru; Nakano, Toshiaki; Tseng, Hui-Peng; Yang, Shih-Ming; Kawamoto, Seiji; Ono, Kazuhisa; Chen, Chao-Long

2014-01-01

33

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

34

The effects of post-treatment with lisofylline, a phosphatidic acid generation inhibitor, on sepsis-induced acute lung injury in pigs.  

PubMed

The effects of lisofylline [(R)-1-(5-hydroxyhexyl)-3,7-dimethylxanthine] (LSF), an inhibitor of de novo phosphatidic acid (PA) generation, on sepsis-induced acute lung injury was studied using Hanford minipigs weighing 18 to 25 kg. Sepsis was induced by an intravenous infusion of Pseudomonas aeruginosa (1 x 10(6)/colony-forming units/kg/min over 2 h). Saline was used as the control vehicle. Six groups were studied: saline control group (SALINE: n = 5); sepsis control group (SEPSIS: n = 5); LSF control group (LSF: n = 5), which received a 25-mg/kgbolus of LSF 30 min before time zero followed by continuous infusion of 10 mg/kg/h throughout the study; LSF-treated septic groups, which were treated with LSF 30 min prior to sepsis (Pre: n = 5), 1 h postonset (Post-1 h: n = 8) or h postonset (Post-2 h: n = 8) of the bacterial infusion. Hemodynamics PaO2, neutrophil counts, and plasma porcine tumor necrosis factor-alpha concentrations were monitored for 6 h. After the minipigs were killed, lung tissue was sampled to measured wet-to-dry weight ratio (W/D), tissue albumin index (TAI), thiobarbituric acid-reactive material content (TBARM), and myeloperoxidase (MPO) activity. Compared with the SALINE group, the SEPSIS group showed significant systemic hypotension, pulmonary hypertension, arterial hypoxemia, neutropenia, and increase in TNF-alpha, MPO activity, W/D, TBARM, and TAI. LSF treatment attenuated sepsis-induced pulmonary hypertension, neutropenia, and hypoxemia, and increased MPO activity and lung injury measurements in the Pre and Post-1 h groups, but its efficacy was blunted in the Post-2 h group. Plasma TNF-alpha was decreased only in the Pre group. Thus, inhibition of intracellular PA generation through de novo pathways attenuates sepsis-induced acute lung injury. PMID:9117028

Hasegawa, N; Oka, Y; Nakayama, M; Berry, G J; Bursten, S; Rice, G; Raffin, T A

1997-03-01

35

The Acute Immunological Response to Blood Transfusion is Influenced by Polymicrobial Sepsis  

PubMed Central

Blood transfusion is a well-established risk factor for adverse outcomes during sepsis. The specific mechanisms responsible for this effect remain elusive, and few studies have investigated this phenomenon in a model that reflects not only the clinical circumstances in which blood is transfused, but also how packed red blood cells (PRBC) are created and stored. Using a cecal ligation and puncture model of polymicrobial sepsis as well as creating murine allogeneic and stored PRBC in a manner that replicates the clinical process, we have demonstrated that transfusion of PRBCs induces numerous effects on leukocyte subpopulations. In polymicrobial sepsis, these responses are profoundly dissimilar to the pro-inflammatory effects of PRBC transfusion observed in the healthy mouse. Transfused septic mice, as opposed to mice receiving crystalloid resuscitation, had a significant loss of blood, spleen and bone marrow lymphocytes, especially those with an activated phenotype. Myeloid cells behaved similarly, although they were able to produce more reactive oxygen species. Overall, transfusion in the septic mouse may contribute to the persistent immune dysfunction known to be associated with this process, rather than simply promote pro- or anti-inflammatory effects on the host. Thus, it is possible that blood transfusion contributes to the multiple known effects of sepsis on leukocyte populations that have been shown to result in increased morbidity and mortality. PMID:23143057

Nacionales, Dina C.; Cuenca, Alex G.; Ungaro, Ricardo; Gentile, Lori F.; Joiner, Dallas; Satoh, Minoru; Lomas-Neira, Joanne; Ayala, Alfred; Bihorac, Azra; Delano, Matthew J.; Ang, Darwin N.; Efron, Philip A.

2012-01-01

36

Biomarker and Drug Target Discovery Using Proteomics in a New Rat Model of Sepsis-Induced Acute Renal Failure  

PubMed Central

Background Sepsis is one of the common causes of acute renal failure (ARF). The objective of this study was to identify new biomarkers and therapeutic targets. We present a new rat model of sepsis-induced ARF based on cecal ligation and puncture (CLP). We used this model to find urinary proteins which may be potential biomarkers and/or drug targets. Methods Aged rats were treated with fluids and antibiotics after CLP. Urinary proteins from septic rats without ARF and urinary proteins from septic rats with ARF were compared by difference in-gel electrophoresis (DIGE). Results CLP surgery elevated IL-6 and IL-10 serum cytokines and blood nitrite compared with sham-operated rats. However there was a range of serum creatinine values at 24 hrs (0.4–2.3 mg/dL) and only 24% developed ARF. Histology confirmed renal injury in these rats. 49% of rats did not develop ARF. Rats without ARF also had less liver injury. The mortality rate at 24 hrs was 27% but was increased by housing the post-surgery rats in metabolic cages. Creatinine clearance and urine output 2–8 hours after CLP was significantly reduced in rats which died within 24 hours. Using DIGE we identified changes in a number of urinary proteins including albumin, brush-border enzymes (eg., meprin-1-alpha) and serine protease inhibitors. The meprin-1-alpha inhibitor actinonin prevented ARF in aged mice. Conclusion In summary we describe a new rat model of sepsis-induced ARF which has a heterogeneous response similar to humans. This model allowed us to use DIGE to find changes in urinary proteins and this approach identified a potential biomarker and drug target – meprin-1-alpha. PMID:16760904

Holly, Mikaela K.; Dear, James W.; Hu, Xuzhen; Schechter, Alan N.; Gladwin, Mark T.; Hewitt, Stephen M.; Yuen, Peter S.T.; Star, Robert A.

2008-01-01

37

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

38

The effect of PEEP on oxygenating capacity in acute respiratory failure with sepsis.  

PubMed

We report an evaluation of the effect of postive-end-expiratory-pressure (PEEP) on improving pulmonary oxygenating capacity in the adult respiratory distress syndrome (ARDS), when the latter is associated with generalized gram-negative sepsis. Fifty-seven cases treated in our RICU with PEEP ventilation (April 1972 to January 1975) were retrospectively reviewed. Oxygenating capacity improvement was evaluated in terms of the changes in PaO2/FIO2 and AaDO2 (FIO2 = 1.0). Both the short term (2-3 hours from the initiation of PEEP) and the overall effects of PEEP were evaluated. A mean PEEP of 5.6 cm H2O initially increased PaO2/FIO2 by a mean of 94 torr and decreased AaDO2 (FIO2 = 1.0) by 105 torr in the 28 nonseptic patients. In the 29 septic patients, 5.1 cm H2O PEEP initially increased PaO2/FIO2 by 32 torr and decreased AsDO2 (FIO2 = 1.0) by 38 torr. The differences between the septic and nonseptic patients were statistically significant (P less than 0.001). Likewise, the long-term effect of similar levels of PEEP was in increasing PaO2/FIO2 by 142 torr and by 75 torr in the nonseptic and septic patients, respectively. The final reduction in AaDO2 (FIO2 = 1.0) was 163 torr and 87 torr in the nonseptic and septic patients, respectively. These differences between patient groups were also statistically significant (P less than 0.02). Mortality during PEEP was 15/29 and 3/28 in the septic and nonseptic patients, respectively. Overall mortality in the septic and nonseptic groups was 18/29 and 5/28, respectively. We conclude that ARDS with sepsis constitutes a more severe pulmonary insult than ARDS without sepsis, and/or that generalized sepsis creates a more prolonged pulmonary insult that makes it less amenable to PEEP. Thus, high levels of PEEP may be needed to treat ARDS associated with sepsis. PMID:780054

Cotev, S; Perel, A; Katzenelson, R; Eimerl, D

1976-01-01

39

Puerperal group A streptococcal infection: beyond Semmelweis.  

PubMed

Ignaz Semmelweiss made one of the most important contributions to modern medicine when he instituted handwashing in an obstetric clinic in Austria in 1847, decreasing mortality there from more than 10% to 2%. Unfortunately, puerperal sepsis remains a leading cause of maternal mortality throughout the world. Group A streptococcus (GAS), Streptococcus pyogenes, is an organism associated with high rates of morbidity and mortality from puerperal infections. When associated with sepsis, known as streptococcal toxic shock syndrome, mortality rates approach 30-50%. Group A streptococcus can cause invasive infections in the form of endometritis, necrotizing fasciitis, or streptococcal toxic shock syndrome. The clinical presentation of women with puerperal GAS infections is often atypical with extremes of temperature, unusual and vague pain, and pain in extremities. Toxin production by the organism may allow GAS to spread across tissue planes and cause necrosis while evading containment by the maternal immune system in the form of a discrete abscess. Endometrial aspiration in addition to blood cultures may be a useful rapid diagnostic tool. Imaging may appear normal and should not dissuade the clinician from aggressive management. When suspected, invasive GAS infections should be treated emergently with fluid resuscitation, antibiotic administration, and source control. The optimal antibiotic regimen contains penicillin and clindamycin. Source control may require extensive wound or vulvar debridement, hysterectomy, or a combination of these, which may be life-saving. The benefit of immunoglobulins in management of puerperal GAS infections is unclear. PMID:24785617

Anderson, Brenna L

2014-04-01

40

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

41

Epidemiology of severe sepsis  

PubMed Central

Severe sepsis is a leading cause of death in the United States and the most common cause of death among critically ill patients in non-coronary intensive care units (ICU). Respiratory tract infections, particularly pneumonia, are the most common site of infection, and associated with the highest mortality. The type of organism causing severe sepsis is an important determinant of outcome, and gram-positive organisms as a cause of sepsis have increased in frequency over time and are now more common than gram-negative infections. Recent studies suggest that acute infections worsen pre-existing chronic diseases or result in new chronic diseases, leading to poor long-term outcomes in acute illness survivors. People of older age, male gender, black race, and preexisting chronic health conditions are particularly prone to develop severe sepsis; hence prevention strategies should be targeted at these vulnerable populations in future studies. PMID:24335434

Mayr, Florian B; Yende, Sachin; Angus, Derek C

2014-01-01

42

Melatonin augments apoptotic adipose-derived mesenchymal stem cell treatment against sepsis-induced acute lung injury  

PubMed Central

This study investigated whether combining melatonin and apoptotic adipose-derived mesenchymal stem cells (A-ADMSC) was superior to ADMSC alone in ameliorating sepsis-induced acute lung injury. Adult male Sprague-Dawley rats (n=50) were randomized equally into five groups: sham controls (SC), sepsis induced by cecal-ligation and puncture (CLP), CLP-melatonin, CLP-A-ADMSC, and CLP-melatonin-A-ADMSC. Circulating interleukin (IL)-6 at 6, 18, and 72 hrs, were highest in CLP and lowest in SC groups, higher in CLP-melatonin than CLP-A-ADMSC and CLP-melatonin-A-ADMSC groups, higher in CLP-A-ADMSC than CLP-melatonin-A-ADMSC groups (all p<0.001). Immune reactivity (indicated by circulating cytotoxic-, and regulatory-T cells) and WBC count at 72 h exhibited the same pattern as that of circulating IL-6 (all p<0.001). Changes in histological scoring of lung parenchyma and the number of CD68+ and CD14+ cells showed a similar pattern compared to that of IL-6 level in all groups (all p<0.001). Changes in protein expressions of inflammatory (oxidative stress, RANTES, TNF-?, NF-?B, MMP-9, MIP-1, IL-1?), apoptotic (cleaved caspase 3 and PARP, mitochondrial Bax), fibrotic (Smad3, TGF-?) markers and those of reactive-oxygen-species (NOX-1, NOX-2) displayed an identical pattern compared to that of circulating IL-6 in all groups (all p<0.001). Anti-oxidative capacities (GR+, GPx+, HO-1, NQO-1+) and angiogenesis marker (CXCR4+ cells) were lowest in SC group but highest in CLP-melatonin-A-ADMSC group, lower in CLP than CLP-melatonin and CLP-A-ADMSC groups, and lower in CLP-melatonin than CLP-A-ADMSC groups (all p<0.001). In conclusion, combined melatonin and A-ADMSC were superior to A-ADMSC alone in protecting the lung from sepsis-induced injury. PMID:25360211

Chen, Hong-Hwa; Chang, Chia-Lo; Lin, Kun-Chen; Sung, Pei-Hsun; Chai, Han-Tan; Zhen, Yen-Yi; Chen, Yi-Ching; Wu, Ying-Chung; Leu, Steve; Tsai, Tzu-Hsien; Chen, Chih-Hung; Chang, Hsueh-Wen; Yip, Hon-Kan

2014-01-01

43

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, Jesus; 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

44

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

45

Role of skeletal muscle Na +–K + ATPase activity in increased lactate production in sub–acute sepsis  

Microsoft Academic Search

Bacterial sepsis is frequently accompanied by increased blood concentration of lactic acid, which traditionally is attributed to poor tissue perfusion, hypoxia and anaerobic glycolysis. Therapy aimed at improving oxygen delivery to tissues often does not correct the hyperlactatemia, suggesting that high blood lactate in sepsis is not due to hypoxia. Various tissues, including skeletal muscle, demonstrate increased lactate production under

Freda D McCarter; S. Renee Nierman; J. Howard James; Li Wang; Jy-Kung King; Lou Ann Friend; Josef E Fischer

2002-01-01

46

Renal Vascular Resistance in Sepsis  

Microsoft Academic Search

Aims: To assess changes in renal vascular resistance (RVR) in human and experimental sepsis and to identify determinants of RVR. Methods: We performed a systematic interrogation of two electronic reference libraries using specific search terms. Subjects were animals and patients involved in experimental and human studies of sepsis and septic acute renal failure, in which the RVR was assessed. We

Christoph Langenberg; Rinaldo Bellomo; Clive N. May; Moritoki Egi; Li Wan; Stanislao Morgera

2006-01-01

47

Acute and long-term dysphagia in critically ill patients with severe sepsis: results of a prospective controlled observational study.  

PubMed

Dysphagia is a major risk factor for morbidity and mortality in critically ill patients treated in intensive care units (ICUs). Structured otorhinolaryngological data on dysphagia in ICU survivors with severe sepsis are missing. In a prospective study, 30 ICU patients with severe sepsis and thirty without sepsis as control group were examined using bedside fiberoptic endoscopic evaluation of swallowing after 14 days in the ICU (T1) and 4 months after onset of critical illness (T2). Swallowing dysfunction was assessed using the Penetration-Aspiration Scale (PAS). The Functional Oral Intake Scale was applied to evaluate the diet needed. Primary endpoint was the burden of dysphagia defined as PAS score >5. At T1, 19 of 30 severe sepsis patients showed aspiration with a PAS score >5, compared to 7 of 30 in critically ill patients without severe sepsis (p = 0.002). Severe sepsis and tracheostomy were independent risk factors for severe dysphagia with aspiration (PAS > 5) at T1 (p = 0.042 and 0.006, respectively). 4-month mortality (T2) was 57 % in severe sepsis patients compared to 20 % in patients without severe sepsis (p = 0.006). At T2, more severe sepsis survivors were tracheostomy-dependent and needed more often tube or parenteral feeding (p = 0.014 and p = 0.040, respectively). Multivariate analysis revealed tracheostomy at T1 as independent risk factor for severe dysphagia at T2 (p = 0.030). Severe sepsis appears to be a relevant risk factor for long-term dysphagia. An otorhinolaryngological evaluation of dysphagia at ICU discharge is mandatory for survivors of severe critical illness to plan specific swallowing rehabilitation programs. PMID:24970291

Zielske, Joerg; Bohne, Silvia; Brunkhorst, Frank M; Axer, Hubertus; Guntinas-Lichius, Orlando

2014-11-01

48

Antioxidants that protect mitochondria reduce interleukin-6 and oxidative stress, improve mitochondrial function, and reduce biochemical markers of organ dysfunction in a rat model of acute sepsis  

PubMed Central

Background Sepsis-induced organ failure is the major cause of death in critical care units, and is characterized by a massive dysregulated inflammatory response and oxidative stress. We investigated the effects of treatment with antioxidants that protect mitochondria (MitoQ, MitoE, or melatonin) in a rat model of lipopolysaccharide (LPS) plus peptidoglycan (PepG)-induced acute sepsis, characterized by inflammation, mitochondrial dysfunction and early organ damage. Methods Anaesthetized and ventilated rats received an i.v. bolus of LPS and PepG followed by an i.v. infusion of MitoQ, MitoE, melatonin, or saline for 5 h. Organs and blood were then removed for determination of mitochondrial and organ function, oxidative stress, and key cytokines. Results MitoQ, MitoE, or melatonin had broadly similar protective effects with improved mitochondrial respiration (P<0.002), reduced oxidative stress (P<0.02), and decreased interleukin-6 levels (P=0.0001). Compared with control rats, antioxidant-treated rats had lower levels of biochemical markers of organ dysfunction, including plasma alanine amino-transferase activity (P=0.02) and creatinine concentrations (P<0.0001). Conclusions Antioxidants that act preferentially in mitochondria reduce mitochondrial damage and organ dysfunction and decrease inflammatory responses in a rat model of acute sepsis. PMID:23381720

Lowes, D. A.; Webster, N. R.; Murphy, M. P.; Galley, H. F.

2013-01-01

49

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, Cimen Gulben; Ergur, Bekir Ugur; Altekin, Emel; Tasdogen, Ayd?n; Duru, Seden; Girgin, Pelin; Gunduz, Kerim; Cilaker M?c?l?, Serap; Guzeldag, Seda; Akkus, Muhammed

2013-01-01

50

Maternal sepsis.  

PubMed

Maternal sepsis is relatively common. Most of these infections are the result of tissue damage during labor and delivery and physiologic changes normally occurring during pregnancy. These infections, whether directly pregnancy-related or simply aggravated by normal pregnancy physiology, ultimately have the potential to progress to severe sepsis and septic shock. This article discusses commonly encountered entities and septic shock. The expeditious recognition of common maternal sepsis and meticulous attention to appropriate management to prevent the progression to severe sepsis and septic shock are emphasized. Also discussed are principles and new approaches for the management of septic shock. PMID:23466138

Morgan, Jamie; Roberts, Scott

2013-03-01

51

Optical immunoassay for streptococcal pharyngitis: evaluation of accuracy with routine and mucoid strains associated with acute rheumatic fever outbreak in the intermountain area of the United States.  

PubMed Central

The Strep A OIA (BioStar, Inc., Boulder, Colo.) rapid detection system is an intriguing technology that utilizes an immunoassay relying on changes in reflected light to directly detect group A streptococcal antigen from specimens. In this evaluation, 424 routine pediatric throat specimens and 20 simulated oropharyngeal specimens with added mucoid (M type 3, 18) strains were cultured and tested by the Strep A OIA. The respective sensitivities and specificities were as follows: Strep A OIA versus enhanced broth culturing, 84.2 and 95.7%; and streptococcus-SXT agar (BBL Microbiology Systems, Cockeysville, Md.) culturing versus enhanced broth culturing, 82.9 and 98.6%. The Strep A OIA is an 8-min, technologist-friendly, accurate technique with an 89.4% agreement with traditional culturing. PMID:8150968

Daly, J A; Korgenski, E K; Munson, A C; Llausas-Magana, E

1994-01-01

52

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

53

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 ...

54

Animal models of sepsis and sepsis-induced kidney injury  

PubMed Central

Sepsis is characterized by a severe inflammatory response to infection, and its complications, including acute kidney injury, can be fatal. Animal models that correctly mimic human disease are extremely valuable because they hasten the development of clinically useful therapeutics. Too often, however, animal models do not properly mimic human disease. In this Review, we outline a bedside-to-bench-to-bedside approach that has resulted in improved animal models for the study of sepsis — a complex disease for which preventive and therapeutic strategies are unfortunately lacking. We also highlight a few of the promising avenues for therapeutic advances and biomarkers for sepsis and sepsis-induced acute kidney injury. Finally, we review how the study of drug targets and biomarkers are affected by and in turn have influenced these evolving animal models. PMID:19805915

Doi, Kent; Leelahavanichkul, Asada; Yuen, Peter S.T.; Star, Robert A.

2009-01-01

55

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

56

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

57

Clinical sepsis  

Microsoft Academic Search

\\u000a Clinical sepsis has been a fundamental issue in the practice of intensive care medicine since the specialty’s inception in\\u000a the early 1950s (1). Severe community-acquired and hospital-acquired infection presenting as clinical sepsis remain the ‘bread\\u000a and butter’ of modern intensive care (2). Yet despite the availability of a wide range of antimicrobial agents, it continues\\u000a to be associated with a

David Bihari

58

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

59

Urinary output and fractional excretion of sodium and urea as indicators of transient versus intrinsic acute kidney injury during early sepsis  

PubMed Central

Introduction The pathophysiology of acute kidney injury (AKI) in sepsis is ill defined. We investigated parameters associated with low glomerular filtration, and their predictive value to discriminate transient from intrinsic septic AKI. Methods In 107 sepsis patients, AKI was defined by the Risk, Injury, Failure, Loss of Kidney Function, End-stage renal disease (RIFLE) urinary output or serum creatinine criterion, or both. Transient AKI (TAKI) versus intrinsic AKI was defined as RIFLE R, I, or F on the first day evolving to no AKI or not, respectively, over the following 5 days. Fractional excretion of sodium (FENa), urea (FEUrea), and NGAL (FENGAL) at admission (d0t0), 4 (d0t4), and 24 hours (d1) was determined. Results Including versus not including the urinary-output criterion of RIFLE increased AKI from 43% to 64.5%. Median uNGAL levels and FENGAL were lower in no AKI versus transient AKI when AKI was defined based on creatinine (P = 0.002 and P = 0.04, respectively), but not when based on urinary output (P = 0.9 and P = 0.49, respectively). FENa < 1% and FEUrea <35% was present in 77.3% and 63.2% of patients. Urinary NGAL was higher (P < 0.001) in those with high versus low fractional sodium excretion, but this was only in patients with transient or intrinsic AKI (P < 0.001 in subgroups), and not in patients without AKI. The negative predictive value for either intrinsic AKI or not restoring diuresis in patients with FENa > 0.36% and FEUrea > 31.5% was 92% and 94.5% respectively. Conclusions A low FENa and FEUrea is highly prevalent in the first hours of sepsis. In sepsis, oliguria is an earlier sign of impending AKI than increase in serum creatinine. A combination of a high FENa and a low FEUrea is associated with intrinsic AKI, whereas a combined high FENa and FEUrea is strongly predictive of transient AKI. PMID:24119730

2013-01-01

60

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

61

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-Pabon, Wilmara; Kohler, Petra L.; Horswill, Alexander R.; Leung, Donald Y. M.

2013-01-01

62

An efficacy and mechanism evaluation study of Levosimendan for the Prevention of Acute oRgan Dysfunction in Sepsis (LeoPARDS): protocol for a randomized controlled trial  

PubMed Central

Background Organ dysfunction consequent to infection (‘severe sepsis’) is the leading cause of admission to an intensive care unit (ICU). In both animal models and early clinical studies the calcium channel sensitizer levosimendan has been demonstrated to have potentially beneficial effects on organ function. The aims of the Levosimendan for the Prevention of Acute oRgan Dysfunction in Sepsis (LeoPARDS) trial are to identify whether a 24-hour infusion of levosimendan will improve organ dysfunction in adults who have septic shock and to establish the safety profile of levosimendan in this group of patients. Methods/Design This is a multicenter, randomized, double-blind, parallel group, placebo-controlled trial. Adults fulfilling the criteria for systemic inflammatory response syndrome due to infection, and requiring vasopressor therapy, will be eligible for inclusion in the trial. Within 24 hours of meeting these inclusion criteria, patients will be randomized in a 1:1 ratio stratified by the ICU to receive either levosimendan (0.05 to 0.2 ?g.kg-1.min-1 or placebo for 24 hours in addition to standard care. The primary outcome measure is the mean Sequential Organ Failure Assessment (SOFA) score while in the ICU. Secondary outcomes include: central venous oxygen saturations and cardiac output; incidence and severity of renal failure using the Acute Kidney Injury Network criteria; duration of renal replacement therapy; serum bilirubin; time to liberation from mechanical ventilation; 28-day, hospital, 3 and 6 month survival; ICU and hospital length-of-stay; and days free from catecholamine therapy. Blood and urine samples will be collected on the day of inclusion, at 24 hours, and on days 4 and 6 post-inclusion for investigation of the mechanisms by which levosimendan might improve organ function. Eighty patients will have additional blood samples taken to measure levels of levosimendan and its active metabolites OR-1896 and OR-1855. A total of 516 patients will be recruited from approximately 25 ICUs in the United Kingdom. Discussion This trial will test the efficacy of levosimendan to reduce acute organ dysfunction in adult patients who have septic shock and evaluate its biological mechanisms of action. Trial registration Current controlled trials ISRCTN12776039 (19 September 2013) PMID:24894386

2014-01-01

63

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

Potschke, Christian; Kessler, Wolfram; Maier, Stefan; Heidecke, Claus-Dieter; Broker, Barbara M.

2013-01-01

64

Group A Streptococcal Infections  

MedlinePLUS

... geographical locations. See Protocols for Surveillance of Streptococcus pyogenes Infections and their Sequelae . One protocol focused on ... for Surveillance of Acute Diseases Caused by Streptococcus pyogenes : Pharyngitis, Impetigo and Invasive Diseases”. The following publications ...

65

Streptococcal mimicry and antibody-mediated cell signaling in the pathogenesis of Sydenham's chorea  

Microsoft Academic Search

Recent evidence suggests that the pathogenesis of Sydenham's chorea following group A streptococcal infection is due to antibodies which develop due to the infection and infiltrate the brain and basal ganglia. Antibodies present in acute chorea react with the surface of neuronal cells and signal the induction of calcium calmodulin dependent protein kinase II with elevation of tyrosine hydroxylase and

Christine A. Kirvan; Susan E. Swedo; David Kurahara; Madeleine W. Cunningham

2006-01-01

66

Hypertonic saline up-regulates A3 adenosine receptors expression of activated neutrophils and increases acute lung injury after sepsis  

PubMed Central

Objective Hypertonic saline resuscitation reduces tissue damage by inhibiting polymorphonuclear neutrophils. Hypertonic saline triggers polymorphonuclear neutrophils to release adenosine triphosphate that is converted to adenosine, inhibiting polymorphonuclear neutrophils through A2a adenosine receptors. polymorphonuclear neutrophils also express A3 adenosine receptors that enhance polymorphonuclear neutrophils functions. Here we investigated whether A3 receptors may diminish the efficacy of hypertonic saline in a mouse model of acute lung injury. Design Randomized animal study and laboratory investigation. Setting University research laboratory. Interventions The effect of A3 receptors on the efficacy of hypertonic saline resuscitation was assessed in A3 receptor knockout and wild-type mice. Animals were treated with hypertonic saline (7.5% NaCl, 4 mL/kg) before or after cecal ligation and puncture, and acute lung injury and mortality were determined. The effect of timing of hypertonic saline exposure on A3 receptor expression and degranulation was studied in vitro with isolated human polymorphonuclear neutrophils. Measurements and main results Treatment of human polymorphonuclear neutrophils with hypertonic saline before stimulation with formyl methionyl-leucyl-phenylalanine inhibited A3 receptor expression and degranulation, whereas hypertonic saline-treatment after formyl methionyl-leucyl-phenylalanine-stimulation augmented A3 receptor expression and degranulation. Acute lung injury in wild-type mice treated with hypertonic saline after cecal ligation and puncture was significantly greater than in wild-type mice pretreated with hypertonic saline. This aggravating effect of delayed hypertonic saline-treatment was absent in A3 receptor knockout mice. Similarly, mortality in wild-type mice with delayed hypertonic saline-treatment was significantly higher (88%) than in animals treated with hypertonic saline before cecal ligation and puncture (50%). Mortality in A3 receptor knockout mice remained only 50% regardless of timing of hypertonic saline administration. Conclusions Polymorphonuclear neutrophils A3 receptors expression determines whether hypertonic saline resuscitation inhibits or aggravates polymorphonuclear neutrophils-induced acute lung injury. These findings suggest that A3 antagonists could improve the efficacy of hypertonic saline resuscitation by reducing side effects in patients whose polymorphonuclear neutrophils are activated before hypertonic saline treatment. PMID:18679117

Inoue, Yoshiaki; Chen, Yu; Pauzenberger, Reinhard; Mark, Hirsh I.; Junger, Wolfgang G.

2008-01-01

67

Effect of Hemoperfusion Using Polymyxin B-immobilized Fibers on Acute Lung Injury in a Rat Sepsis Model  

PubMed Central

Direct hemoperfusion using polymyxin B-immobilized column (PMX-DHP) is recognized as an effective treatment for septic shock. However, whether its efficacy is limited to cardiovascular dysfunction remains unknown. Therefore, we planned to examine the effects of PMX-DHP in an acute lung injury model. [Materials and methods] Rats were assigned to either PMX-DHP group or control group (n= 7 in each). A lung injury was created by the intratracheal instillation of LPS. In PMX-DHP group, an arteriovenous extracorporeal circuit using PMX column was applied for three hours. The same procedure using a dummy column was applied in control group. The lung microcirculation was observed, and adherent leukocytes, RBC velocity, and the arterial PaO2 were calculated. Pathological changes and the wet/dry weight ratio of the lungs were examined. [Results] Adherent leukocytes and platelets to the lung venules were recognized at 3 hours, and their numbers increased over time. Treatment with PMX-DHP significantly suppressed these events and helped maintenance of the blood flow and PaO2 levels. The lung edema and the histologic damages were also suppressed. [Conclusions] PMX-DHP improved the microcirculation by suppressing leukocyte and platelet adhesion. PMX-DHP had beneficial effects in a model for acute lung injury. PMID:24516349

Iba, Toshiaki; Nagaoka, Isao; Yamada, Atsushi; Nagayama, Masataka; Miki, Takahiro

2014-01-01

68

Effect of hemoperfusion using polymyxin B-immobilized fibers on acute lung injury in a rat sepsis model.  

PubMed

Direct hemoperfusion using polymyxin B-immobilized column (PMX-DHP) is recognized as an effective treatment for septic shock. However, whether its efficacy is limited to cardiovascular dysfunction remains unknown. Therefore, we planned to examine the effects of PMX-DHP in an acute lung injury model. [Materials and methods] Rats were assigned to either PMX-DHP group or control group (n= 7 in each). A lung injury was created by the intratracheal instillation of LPS. In PMX-DHP group, an arteriovenous extracorporeal circuit using PMX column was applied for three hours. The same procedure using a dummy column was applied in control group. The lung microcirculation was observed, and adherent leukocytes, RBC velocity, and the arterial PaO2 were calculated. Pathological changes and the wet/dry weight ratio of the lungs were examined. [Results] Adherent leukocytes and platelets to the lung venules were recognized at 3 hours, and their numbers increased over time. Treatment with PMX-DHP significantly suppressed these events and helped maintenance of the blood flow and PaO2 levels. The lung edema and the histologic damages were also suppressed. [Conclusions] PMX-DHP improved the microcirculation by suppressing leukocyte and platelet adhesion. PMX-DHP had beneficial effects in a model for acute lung injury. PMID:24516349

Iba, Toshiaki; Nagaoka, Isao; Yamada, Atsushi; Nagayama, Masataka; Miki, Takahiro

2014-01-01

69

Streptococcal mimicry and antibody-mediated cell signaling in the pathogenesis of Sydenham's chorea.  

PubMed

Recent evidence suggests that the pathogenesis of Sydenham's chorea following group A streptococcal infection is due to antibodies which develop due to the infection and infiltrate the brain and basal ganglia. Antibodies present in acute chorea react with the surface of neuronal cells and signal the induction of calcium calmodulin dependent protein kinase II with elevation of tyrosine hydroxylase and subsequent dopamine release which may lead to the movement disorder. The antibodies present in disease recognize lysoganglioside and the group A streptococcal epitope, N-acetyl-glucosamine. Monoclonal antibodies (mAbs) from Sydenham's chorea demonstrated the mimicry between lysoganglioside and the group A streptococcal carbohydrate epitope. A group of antibodies present in pediatric autoimmune neuropsychiatric disorders (PANDAS) were similar but not identical to the antibodies observed in chorea. PMID:16455579

Kirvan, Christine A; Swedo, Susan E; Kurahara, David; Cunningham, Madeleine W

2006-02-01

70

Sepsis and disseminated intravascular coagulation in an eastern spiny softshell turtle (Apalone spinifera spinifera) with acute mycobacteriosis.  

PubMed

An adult, captive eastern spiny softshell turtle (Apalone spinifera spinifera) was examined for a 4-day history of lethargy and plastron discoloration. The turtle was obtunded and had pale mucous membranes, hemorrhagic nasal discharge, and petechiae on all limbs. The turtle was euthanized due to its grave condition. Necropsy revealed hemorrhagic coelomic effusion, petechiae on the serosal surfaces of the intestinal tract, and bilaterally hemorrhagic lungs. Histologic examination revealed numerous emboli of bacteria associated with fibrinocellular thrombi throughout the blood vessels of multiple tissues. The bacteria in the thrombi were slender bacilli that stained intensely acid fast. Culture of the coelomic fluid yielded Mycobacterium chelonae. Although mycobacteriosis in reptiles is typically a chronic, granulomatous disease, this case demonstrates that mycobacteriosis should be considered in reptiles presenting with acute, nongranulomatous disease. This case also describes clinically apparent hemorrhage due to disseminated intravascular coagulation, which is rarely described in chelonians. PMID:19746876

Murray, Maureen; Waliszewski, Nicole T; Garner, Michael M; Tseng, Florina S

2009-09-01

71

Fulminant postsplenectomy sepsis.  

PubMed

The vital role of a normally-functioning spleen in a host's defence against circulating microorganisms has been realized for many years. The fulminant clinical course that characterizes infection with encapsulated microorganisms in asplenic patients is highlighted in these cases of severe pneumococcal sepsis in two patients, 10 and 13 years after splenectomies for idiopathic thrombocytopenic purpura. Approaches to the acute management of septic episodes and preventive measures are discussed. Pneumococcal vaccination reduces the incidence of infection effectively in asplenic patients and has a low complication rate. Penicillin by mouth is also efficacious in this situation, but patient compliance is low. Our current practice is to offer pneumococcal vaccination to all patients who have undergone splenectomy in the past and to administer the vaccine two weeks before elective splenectomies. Asplenic patients should be educated about the potential dangers of a septic episode and should be urged to seek an early medical consultation when this occurs. PMID:3336300

Perkins, A C; Joshua, D E; Gibson, J; Kronenberg, H

1988-01-01

72

Human pathogenic streptococcal proteomics and vaccine development.  

PubMed

Gram-positive streptococci are non-motile, chain-forming bacteria commonly found in the normal oral and bowel flora of warm-blooded animals. Over the past decade, a proteomic approach combining 2-DE and MS has been used to systematically map the cellular, surface-associated and secreted proteins of human pathogenic streptococcal species. The public availability of complete streptococcal genomic sequences and the amalgamation of proteomic, genomic and bioinformatic technologies have recently facilitated the identification of novel streptococcal vaccine candidate antigens and therapeutic agents. The objective of this review is to examine the constituents of the streptococcal cell wall and secreted proteome, the mechanisms of transport of surface and secreted proteins, and describe the current methodologies employed for the identification of novel surface-displayed proteins and potential vaccine antigens. PMID:21136841

Cole, Jason N; Henningham, Anna; Gillen, Christine M; Ramachandran, Vidiya; Walker, Mark J

2008-03-01

73

Scarlet Fever: A Group A Streptococcal Infection  

MedlinePLUS

... What's this? Submit Button CDC Features Scarlet Fever: A Group A Streptococcal Infection Language: English Español (Spanish) Share Compartir Scarlet fever results from group A strep infection. If your child has a sore ...

74

Streptococcal infection, Tourette syndrome, and OCD  

PubMed Central

Background: A causal relationship of common streptococcal infections and childhood neuropsychiatric disorders has been postulated. Objective: To test the hypothesis of an increased rate of streptococcal infections preceding the onset of neuropsychiatric disorders. Methods: Case-control study of a large primary care database comparing the rate of possible streptococcal infections in patients aged 2–25 years with obsessive-compulsive disorder (OCD), Tourette syndrome (TS), and tics with that in controls matched for age, gender, and practice (20 per case). We also examined the influence of sociodemographic factors. Results: There was no overall increased risk of prior possible streptococcal infection in patients with a diagnosis of OCD, TS, or tics. Subgroup analysis showed that patients with OCD had a slightly higher risk than controls of having had possible streptococcal infections without prescription of antibiotics in the 2 years prior to the onset of OCD (odds ratio 2.59, 95% confidence interval 1.18, 5.69; p = 0.02). Cases with TS or tics were not more likely to come from more affluent or urban areas, but more cases lived in areas with a greater proportion of white population (p value for trend = 0.05). Conclusions: The present study does not support a strong relationship between streptococcal infections and neuropsychiatric syndromes such as obsessive-compulsive disorder and Tourette syndrome. However, it is possible that a weak association (or a stronger association in a small susceptible subpopulation) was not detected due to nondifferential misclassification of exposure and limited statistical power. The data are consistent with previous reports of greater rates of diagnosis of Tourette syndrome or tics in white populations. GLOSSARY CI = confidence interval; GP = general practice; OCD = obsessive-compulsive disorder; OR = odds ratio; PANDAS = pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections; SI = streptococcal infection; TS = Tourette syndrome. PMID:19794128

Schrag, A; Gilbert, R; Giovannoni, G; Robertson, M M.; Metcalfe, C; Ben-Shlomo, Y

2009-01-01

75

Variability in the diagnosis and treatment of group a streptococcal pharyngitis by primary care pediatricians.  

PubMed

Objective.?To compare practice patterns regarding the diagnosis and management of streptococcal pharyngitis across pediatric primary care practices. Design.?Retrospective cohort study. Setting.?All encounters to 25 pediatric primary care practices sharing an electronic health record. Methods.?Streptococcal pharyngitis was defined by an International Classification of Diseases, Ninth Revision code for acute pharyngitis, positive laboratory test, antibiotic prescription, and absence of an alternative bacterial infection. Logistic regression models standardizing for patient-level characteristics were used to compare diagnosis, testing, and broad-spectrum antibiotic treatment for children with pharyngitis across practices. Fixed-effects models and likelihood ratio tests were conducted to analyze within-practice variation. Results.?Of 399,793 acute encounters in 1 calendar year, there were 52,658 diagnoses of acute pharyngitis, including 12,445 diagnoses of streptococcal pharyngitis. After excluding encounters by patients with chronic conditions and standardizing for age, sex, insurance type, and race, there was significant variability across and within practices in the diagnosis and testing for streptococcal pharyngitis. Excluding patients with antibiotic allergies or prior antibiotic use, off-guideline antibiotic prescribing for confirmed group A streptococcal pharyngitis ranged from 1% to 33% across practices (P < .001). At the clinician level, 13 of 25 sites demonstrated significant within-practice variability in off-guideline antibiotic prescribing (P ? .05). Only 18 of the 222 clinicians in the network accounted for half of all off-guideline antibiotic prescribing. Conclusions.?Significant variability in the diagnosis and treatment of pharyngitis exists across and within pediatric practices, which cannot be explained by relevant clinical or demographic factors. Our data support clinician-targeted interventions to improve adherence to prescribing guidelines for this common condition. PMID:25222902

Fierro, Julie L; Prasad, Priya A; Localio, A Russell; Grundmeier, Robert W; Wasserman, Richard C; Zaoutis, Theoklis E; Gerber, Jeffrey S

2014-10-01

76

Renal blood flow in sepsis: a complex issue  

Microsoft Academic Search

The clinical complexity of sepsis and the regional variability in renal blood flow present a difficult challenge for the clinician or investigator in understanding the role and clinical importance of reduced blood flow in the pathophysiology of sepsis-induced acute renal failure. Understanding the role of regional microvasculature flow and interactions between endothelium and white blood cells in the local delivery

Bruce A Molitoris

2005-01-01

77

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

78

Acute disseminated encephalomyelitis associated with acute rheumatic fever.  

PubMed

An 8-year-old boy developed acute disseminated encephalomyelitis, 2 weeks after an episode of acute rheumatic fever. The disease was succesfully treated with high-dose methylprednisolone. A wide range of neurologic disorders is associated with streptococcal disease. Poststreptococcal acute disseminated encephalomyelitis was previously reported in children, but to our knowledge, this is the first case report of rheumatic fever complicated by acute disseminated encephalomyelitis. This case supports the hypothesis that rheumatic fever, a late complication of streptococcal infections, may be associated with acute disseminated encephalomyelitis. PMID:21310343

Sayg?, Semra; Olgaç, Asburçe; Üçkarde?, Yasemin; Alehan, Füsun; Varan, Birgül

2011-03-01

79

Biology of sepsis: Its relevance to pediatric nephrology.  

PubMed

Because of its multi-organ involvement, the syndrome of sepsis provides clinical challenges to a wide variety of health care providers. While multi-organ dysfunction triggered by sepsis requires general supportive critical care provided by intensivists, the impact of sepsis on renal function and the ability of renal replacement therapies to modulate its biologic consequences provide a significant opportunity for pediatric nephrologists and related care providers to impact outcomes. In this review, we aim to highlight newer areas of understanding of the pathobiology of sepsis with special emphasis on those aspects of particular interest to pediatric nephrology. As such, we aim to: (1) review the definition of sepsis and discuss advances in our mechanistic understanding of sepsis; (2) review current hypotheses regarding sepsis-induced acute kidney injury (AKI) and describe its epidemiology based on evolving definitions of AKI; (3) review the impact of renal failure on the immune system, highlighting the sepsis risk in this cohort and strategies that might minimize this risk; (4) review how renal replacement therapeutic strategies may impact sepsis-induced AKI outcomes. By focusing the review on these specific areas, we have omitted other important areas of the biology of sepsis and additional interactions with renal function from this discussion; however, we have aimed to provide a comprehensive list of references that provide contemporary reviews of these additional areas. PMID:24408224

Blatt, Neal B; Srinivasan, Sushant; Mottes, Theresa; Shanley, Maureen M; Shanley, Thomas P

2014-12-01

80

Group A ?-hemolytic streptococcal pharyngotonsillitis outbreak.  

PubMed

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

2014-04-01

81

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

82

Introduction to Pediatric Sepsis  

PubMed Central

Sepsis is a significant health problem in both critically ill children and adults. While the mortality rate from sepsis is much lower in children, sepsis is directly responsible for over 4,000 childhood deaths per year in the United States alone. At face value, this number suggests that more children die per year in the United States from sepsis as the primary cause than from cancer. Unfortunately, there are few studies on the epidemiology, pathophysiology, and management of sepsis in children. Moreover, extrapolation of adult data to critically ill children is probably not appropriate due to several key developmental differences in the host response to infection and response to therapy. Therefore, additional studies targeting sepsis in the pediatric population are urgently required.

Wheeler, Derek S.

2012-01-01

83

Increased Resistance Against Acute Polymicrobial Sepsis in Mice Challenged with Immunostimulatory CpG Oligodeoxynucleotides Is Related to an Enhanced Innate Effector Cell Response1  

Microsoft Academic Search

Recent reports support the concept that the major defect in polymicrobial sepsis is an impaired immunologic response to infection. Oligodeoxynucleotides containing CpG sequence motifs (CpG-ODN) were previously shown to induce immune protection in models of chronic infection with intracellular bacteria, parasites, and viruses due to their ability to augment IFN- g-dependent Th1 responses. Here, we demonstrate that challenging mice with

Heike Weighardt; Carolin Feterowski; Martin Veit; Martina Rump; Hermann Wagner; Bernhard Holzmann

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

Immunogenetic study of the response to streptococcal carbohydrate antigen of the cell wall in rheumatic fever.  

PubMed Central

An immunogenetic study of the response to streptococcal carbohydrate antigen of the cell wall was carried out on members of 15 multiplex families each having more than one sib affected with rheumatic heart disease. They comprised 30 parents and 61 sibs (32 with rheumatic disease and 29 without). Fifty healthy unrelated subjects served as controls. A history was taken and clinical examination carried out. Rheumatic activity was determined and HLA typing was carried out for nine A antigens, 15 B antigens, and six DR antigens. The immune response of lymphocytes to streptococcal polysaccharide antigen of the cell wall of group A beta haemolytic streptococci in vitro was studied by tritiated thymidine uptake. The results were statistically and genetically analysed. It was found that (a) all subjects with rheumatic disease were highly responsive to the streptococcal polysaccharide antigen of the cell wall, the sib pairs being mostly HLA identical; (b) all low responders had no rheumatic disease and their phenotypes were mostly different from those of the rheumatic member of their sib pair; (c) correlation of immune responsiveness (high or low) between HLA-identical sibs was significant, but insignificant between haplotype identical and non-identical sibs; (d) the gene responsible for high responsiveness to the streptococcal polysaccharide antigen of the cell wall is recessive and closely linked to HLA. In conclusion, it was found that exposure to pharyngeal infection with group A beta haemolytic streptococci may lead to acute rheumatic fever in those with an inherited recessive gene responsible for high responsiveness to the streptococcal polysaccharide antigen of the cell wall. PMID:2241288

Hafez, M; Abdalla, A; el-Shennawy, F; al-Tonbary, Y; Sheaishaa, A; el-Morsi, Z; Tawfik, S; Settien, A; Abou el-Khair, M

1990-01-01

86

TLR2, TLR4 and the MYD88 Signaling Pathway Are Crucial for Neutrophil Migration in Acute Kidney Injury Induced by Sepsis  

PubMed Central

The aim of this study was to investigate the role of TLR2, TLR4 and MyD88 in sepsis-induced AKI. C57BL/6 TLR2?/?, TLR4?/? and MyD88?/? male mice were subjected to sepsis by cecal ligation and puncture (CLP). Twenty four hours later, kidney tissue and blood samples were collected for analysis. The TLR2?/?, TLR4?/? and MyD88?/? mice that were subjected to CLP had preserved renal morphology, and fewer areas of hypoxia and apoptosis compared with the wild-type C57BL/6 mice (WT). MyD88?/? mice were completely protected compared with the WT mice. We also observed reduced expression of proinflammatory cytokines in the kidneys of the knockout mice compared with those of the WT mice and subsequent inhibition of increased vascular permeability in the kidneys of the knockout mice. The WT mice had increased GR1+low cells migration compared with the knockout mice and decreased in GR1+high cells migration into the peritoneal cavity. The TLR2?/?, TLR4?/?, and MyD88?/? mice had lower neutrophil infiltration in the kidneys. Depletion of neutrophils in the WT mice led to protection of renal function and less inflammation in the kidneys of these mice. Innate immunity participates in polymicrobial sepsis-induced AKI, mainly through the MyD88 pathway, by leading to an increased migration of neutrophils to the kidney, increased production of proinflammatory cytokines, vascular permeability, hypoxia and apoptosis of tubular cells. PMID:22655058

Castoldi, Angela; Braga, Tarcio Teodoro; Correa-Costa, Matheus; Aguiar, Cristhiane Favero; Bassi, Enio Jose; Correa-Silva, Reinaldo; Elias, Rosa Maria; Salvador, Fabia; Moraes-Vieira, Pedro Manoel; Cenedeze, Marcos Antonio; Reis, Marlene Antonia; Hiyane, Meire Ioshie; Pacheco-Silva, Alvaro; Goncalves, Giselle Martins; Camara, Niels Olsen Saraiva

2012-01-01

87

Defensins and Sepsis  

PubMed Central

Sepsis is a leading cause of mortality and morbidity in the critical illness. Multiple immune inflammatory processes take part in the pathogenesis of sepsis. Defensins are endogenous antimicrobial peptides with three disulphide bonds created by six cysteine residues. Besides the intrinsic microbicidal properties, defensins are active players which modulate both innate and adaptive immunity against various infections. Defensins can recruit neutrophils, enhance phagocytosis, chemoattract T cells and dendritic cells, promote complement activation, and induce IL-1? production and pyrotosis. Previous publications have documented that defensins play important roles in a series of immune inflammatory diseases including sepsis. This review aims to briefly summarize in vitro, in vivo, and genetic studies on defensins' effects as well as corresponding mechanisms within sepsis and highlights their promising findings which may be potential targets in future therapies of sepsis.

Xie, Guo-Hao; Chen, Qi-Xing; Cheng, Bao-Li; Fang, Xiang-Ming

2014-01-01

88

Biomarkers of sepsis  

PubMed Central

Sepsis is an unusual systemic reaction to what is sometimes an otherwise ordinary infection, and it probably represents a pattern of response by the immune system to injury. A hyper-inflammatory response is followed by an immunosuppressive phase during which multiple organ dysfunction is present and the patient is susceptible to nosocomial infection. Biomarkers to diagnose sepsis may allow early intervention which, although primarily supportive, can reduce the risk of death. Although lactate is currently the most commonly used biomarker to identify sepsis, other biomarkers may help to enhance lactate’s effectiveness; these include markers of the hyper-inflammatory phase of sepsis, such as pro-inflammatory cytokines and chemokines; proteins such as C-reactive protein and procalcitonin which are synthesized in response to infection and inflammation; and markers of neutrophil and monocyte activation. Recently, markers of the immunosuppressive phase of sepsis, such as anti-inflammatory cytokines, and alterations of the cell surface markers of monocytes and lymphocytes have been examined. Combinations of pro- and anti-inflammatory biomarkers in a multi-marker panel may help identify patients who are developing severe sepsis before organ dysfunction has advanced too far. Combined with innovative approaches to treatment that target the immunosuppressive phase, these biomarkers may help to reduce the mortality rate associated with severe sepsis which, despite advances in supportive measures, remains high. PMID:23480440

2013-01-01

89

Sepsis Questions and Answers  

MedlinePLUS

... prevent infections that could lead to sepsis through promotion of vaccination for diseases like pneumococcus and meningitis, smoking cessation programs to prevent community-acquired pneumonia, and strategies to prevent healthcare-associated infections. Recently, CDC has ...

90

Mitochondrial Mechanisms of Sepsis-Induced Organ Failure  

PubMed Central

Sepsis is the leading cause of death in medical intensive care units. Though progress has been made in the early treatment of sepsis associated with hemodynamic collapse (septic shock), little is known about the pathogenesis of delayed organ dysfunction during sepsis. A growing body of data indicates that sepsis is associated with acute changes in cell metabolism, and that mitochondria are particularly susceptible. The severity of mitochondrial pathology varies according to host and pathogen factors, and appears to correlate with loss of organ dysfunction. In this regard, low levels of cell apoptosis and mitochondrial turnover are normally observed in all metabolically active tissues; however, these homeostatic mechanisms are frequently overwhelmed during sepsis and contribute to cell and tissue pathology. Thus, a better understanding of the mechanisms regulating mitochondrial damage and repair during severe sepsis may provide new treatment options and better outcomes for this deadly disease (30-60% mortality). Herein, we present compelling evidence linking mitochondrial apoptosis pathways to sepsis-induced cell and organ failure and discuss the implications in terms of future sepsis research. PMID:18508567

Exline, Matthew C; Crouser, Elliot D

2014-01-01

91

Pathophysiology of Sepsis  

PubMed Central

Sepsis remains a critical problem with significant morbidity and mortality even in the modern era of critical care management. Multiple derangements exist in sepsis involving several different organs and systems, although controversies exist over their individual contribution to the disease process. Septic patients have substantial, life-threatening alterations in their coagulation system, and currently, there is an approved therapy with a component of the coagulation system (activated protein C) to treat patients with severe sepsis. Previously, it was believed that sepsis merely represented an exaggerated, hyperinflammatory response with patients dying from inflammation-induced organ injury. More recent data indicate that substantial heterogeneity exists in septic patients’ inflammatory response, with some appearing immuno-stimulated, whereas others appear suppressed. Cellular changes continue the theme of heterogeneity. Some cells work too well such as neutrophils that remain activated for an extended time. Other cellular changes become accelerated in a detrimental fashion including lymphocyte apoptosis. Metabolic changes are clearly present, requiring close and individualized monitoring. At this point in time, the literature richly illustrates that no single mediator/system/pathway/pathogen drives the pathophysiology of sepsis. This review will briefly discuss many of the important alterations that account for the pathophysiology of sepsis. PMID:17456750

Remick, Daniel G.

2007-01-01

92

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

93

Sepsis chronically in MARS: systemic cytokine responses are always mixed regardless of the outcome, magnitude, or phase of sepsis.  

PubMed

The paradigm of systemic inflammatory response syndrome-to-compensatory anti-inflammatory response syndrome transition implies that hyperinflammation triggers acute sepsis mortality, whereas hypoinflammation (release of anti-inflammatory cytokines) in late sepsis induces chronic deaths. However, the exact humoral inflammatory mechanisms attributable to sepsis outcomes remain elusive. In the first part of this study, we characterized the systemic dynamics of the chronic inflammation in dying (DIE) and surviving (SUR) mice suffering from cecal ligation and puncture sepsis (days 6-28). In the second part, we combined the current chronic and previous acute/chronic sepsis data to compare the outcome-dependent inflammatory signatures between these two phases. A composite cytokine score (CCS) was calculated to compare global inflammatory responses. Mice were never sacrificed but were sampled daily (20 ?l) for blood. In the first part of the study, parameters from chronic DIE mice were clustered into the 72, 48, and 24 h before death time points and compared with SUR of the same post-cecal ligation and puncture day. Cytokine increases were mixed and never preceded chronic deaths earlier than 48 h (3- to 180-fold increase). CCS demonstrated simultaneous and similar upregulation of proinflammatory and anti-inflammatory compartments at 24 h before chronic death (DIE 80- and 50-fold higher versus SUR). In the second part of the study, cytokine ratios across sepsis phases/outcomes indicated steady proinflammatory versus anti-inflammatory balance. CCS showed the inflammatory response in chronic DIE was 5-fold lower than acute DIE mice, but identical to acute SUR. The systemic mixed anti-inflammatory response syndrome-like pattern (concurrent release of proinflammatory and anti-inflammatory cytokines) occurs irrespective of the sepsis phase, response magnitude, and/or outcome. Although different in magnitude, neither acute nor chronic septic mortality is associated with a predominating proinflammatory and/or anti-inflammatory signature in the blood. PMID:23008446

Osuchowski, Marcin F; Craciun, Florin; Weixelbaumer, Katrin M; Duffy, Elizabeth R; Remick, Daniel G

2012-11-01

94

Immunoinflammatory response in critically ill patients: severe sepsis and/or trauma.  

PubMed

Immunoinflammatory response in critically ill patients is very complex. This review explores some of the new elements of immunoinflammatory response in severe sepsis, tumor necrosis factor-alpha in severe acute pancreatitis as a clinical example of immune response in sepsis, immune response in severe trauma with or without secondary sepsis, and genetic aspects of host immuno-inflammatory response to various insults in critically ill patients. PMID:24371374

Surbatovic, Maja; Veljovic, Milic; Jevdjic, Jasna; Popovic, Nada; Djordjevic, Dragan; Radakovic, Sonja

2013-01-01

95

Immunoinflammatory Response in Critically Ill Patients: Severe Sepsis and/or Trauma  

PubMed Central

Immunoinflammatory response in critically ill patients is very complex. This review explores some of the new elements of immunoinflammatory response in severe sepsis, tumor necrosis factor-alpha in severe acute pancreatitis as a clinical example of immune response in sepsis, immune response in severe trauma with or without secondary sepsis, and genetic aspects of host immuno-inflammatory response to various insults in critically ill patients. PMID:24371374

Popovic, Nada; Djordjevic, Dragan

2013-01-01

96

Seroprevalence of Streptococcal Inhibitor of Complement (SIC) suggests association of streptococcal infection with chronic kidney disease  

PubMed Central

Background Group A streptococcus (GAS) is an etiological agent for the immune mediated sequela post streptococcal glomerulonephritis (PSGN). In some populations PSGN is recognized as a risk factor for chronic kidney disease (CKD) and end-stage renal disease (ESRD). It was found that a significantly greater proportion of subjects with past history of PSGN than without the history exhibited seroreactions to streptococcal antigens called streptococcal inhibitor of complement (SIC) and to distantly related SIC (DRS). These antigens are expressed by major PSGN-associated GAS types. We therefore predicted that in populations such as India, which is endemic for streptococcal diseases and which has high prevalence of CKD and ESRD, greater proportions of CKD and ESRD patients exhibit seroreaction to SIC and DRS than healthy controls. Methods To test this we conducted a SIC and DRS seroprevalence study in subjects from Mumbai area. We recruited 100 CKD, 70 ESRD and 70 healthy individuals. Results Nineteen and 35.7% of CKD and ESRD subjects respectively were SIC antibody-positive, whereas only 7% of healthy cohort was seropositive to SIC. Furthermore, significantly greater proportion of the ESRD patients than the CKD patients is seropositive to SIC (p=0.02; odds ratio 2.37). No association was found between the renal diseases and DRS-antibody-positivity. Conclusions Past infection with SIC-positive GAS is a risk factor for CKD and ESRD in Mumbai population. Furthermore, SIC seropositivity is predictive of poor prognosis of CKD patients. PMID:23642030

2013-01-01

97

Toxoids of Streptococcal Pyrogenic Exotoxin A Are Protective in Rabbit Models of Streptococcal Toxic Shock Syndrome  

Microsoft Academic Search

Streptococcal pyrogenic exotoxins (SPEs) are superantigens that have been implicated in causing strepto- coccal toxic shock syndrome (STSS). Most notably, SPE serotype A is made by nearly all M-protein serotype 1 and 3 streptococci, the M types most associated with the illness (these strains contain one or more other SPEs, and those proteins are likely also to contribute to disease).

MANUELA ROGGIANI; JENNIFER A. STOEHR; STEPHEN B. OLMSTED; YURY V. MATSUKA; SUBRAMONIA PILLAI; DOUGLAS H. OHLENDORF; PATRICK M. SCHLIEVERT

2000-01-01

98

The Surviving Sepsis Campaign sepsis change bundles and clinical practice  

Microsoft Academic Search

The Surviving Sepsis Campaign (SSC) is an international effort to reduce mortality in severe sepsis and septic shock. The campaign included the creation of evidence-based guidelines sponsored and endorsed by 11 international organizations. From these guidelines, sepsis change bundles for initial resuscitation (6 hours) and management (24 hours) were created as a performance improvement tool. In this issue of Critical

R Phillip Dellinger; Jean-Louis Vincent

2005-01-01

99

Construction and management of ARDS/sepsis registry with REDCap  

PubMed Central

Objective The study aimed to construct and manage an acute respiratory distress syndrome (ARDS)/sepsis registry that can be used for data warehousing and clinical research. Methods The workflow methodology and software solution of research electronic data capture (REDCap) was used to construct the ARDS/sepsis registry. Clinical data from ARDS and sepsis patients registered to the intensive care unit (ICU) of our hospital formed the registry. These data were converted to the electronic case report form (eCRF) format used in REDCap by trained medical staff. Data validation, quality control, and database management were conducted to ensure data integrity. Results The clinical data of 67 patients registered to the ICU between June 2013 and December 2013 were analyzed. Of the 67 patients, 45 (67.2%) were classified as sepsis, 14 (20.9%) as ARDS, and eight (11.9%) as sepsis-associated ARDS. The patients’ information, comprising demographic characteristics, medical history, clinical interventions, daily assessment, clinical outcome, and follow-up data, was properly managed and safely stored in the ARDS/sepsis registry. Data efficiency was guaranteed by performing data collection and data entry twice weekly and every two weeks, respectively. Conclusions The ARDS/sepsis database that we constructed and manage with REDCap in the ICU can provide a solid foundation for translational research on the clinical data of interest, and a model for development of other medical registries in the future. PMID:25276372

Pang, Xiaoqing; Kozlowski, Natascha; Wu, Sulong; Jiang, Mei; Huang, Yongbo; Mao, Pu; Liu, Xiaoqing; He, Weiqun; Huang, Chaoyi; Zhang, Haibo

2014-01-01

100

Drotrecogin alfa (activated): a novel therapeutic strategy for severe sepsis  

PubMed Central

Recent studies have highlighted the close link between activation of the coagulation system and the inflammatory response in the pathophysiology of severe sepsis. The protein C anticoagulant pathway plays an integral part in modulating the coagulation and inflammatory responses to infection. In patients with sepsis, endogenous protein C levels are decreased, shifting the balance toward greater systemic inflammation, coagulation, and cell death. On the basis of a single large randomised phase 3 trial, drotrecogin alfa (activated), a recombinant form of human activated protein C, was recently approved for the treatment of adult patients with severe sepsis and a high risk of death. Since its approval, several questions have been raised regarding the appropriate use of this agent. Given the increased risk of serious bleeding and the high cost of treatment, drotrecogin alfa (activated) should be reserved at this time for the most acutely ill patients with severe sepsis who meet the criteria that were used in the phase 3 trial. PMID:12566544

Pastores, S

2003-01-01

101

Sepsis in burned patients.  

PubMed

A prospective study was conducted from June 2001 to May 2002 at the Burns Unit of Hospital Regional da Asa Norte, Brasília, Brazil. During the period of the study, 252 patients were treated at the Burns Unit, 49 (19.4%) developed clinically and microbiologically proven sepsis. Twenty-six (53.1%) were males and 23 (46.9%) females with a mean age of 22 years (range one to 89 years) and mean burned body surface area of 37.7 +/- 18.4% (range 7 to 84%). Forty-three patients had flame burns, five a scald and one an electric burn. These 49 patients had a total of 62 septic episodes. Forty (81.6%) patients had only one and nine (18.4%) had up to three episodes of sepsis. Thirty (61.2%) patients had their first septicemic episode either earlier or by one week postburn. Out of 62 septic episodes, 58 were due to bacteria and four due to Candida sp. The most common bacteria isolated from blood culture were Staphylococccus aureus, coagulase-negative Staphylococcus, Acinetobacter baumannii, Enterobacter cloacae and Klebsiella pneumoniae. Eleven (18.9%) episodes were due to oxacillin resistant Staphylococcus aureus. Acinetobacter baumannii was sensitive to ampicillin/sulbactam in 71.4% and to imipenem in 85.7% of the cases. The primary foci of sepsis were the burn wound in 15 (24.2%) episodes. The most common clinical findings of sepsis in these patients were fever, dyspnea, hypotension and oliguria. The most common laboratory findings of these patients were anemia, leukocytosis, hypoalbuminemia and thrombocytopenia. Twelve (24.5%) patients died. The appropriate knowledge of clinical, epidemiological, laboratorial and microbiological aspects of sepsis in burned patients permits an adequate diagnosis and treatment of this complication. PMID:15049101

de Macedo, Jefferson Lessa; Rosa, Simone C; Castro, Cleudson

2003-01-01

102

Severe sepsis and septic shock  

PubMed Central

Morbidity and mortality from sepsis remains unacceptably high. Large variability in clinical practice, plus the increasing awareness that certain processes of care associated with improved critical care outcomes, has led to the development of clinical practice guidelines in a variety of areas related to infection and sepsis. The Surviving Sepsis Guidelines for Management of Severe Sepsis and Septic Shock were first published in 2004, revised in 2008, and recently revised again and published in 2013. The first part of this manuscript is a summary of the 2013 guidelines with some editorial comment. The second part of the manuscript characterizes hospital based sepsis performance improvement programs and highlights the sepsis bundles from the Surviving Sepsis Campaign as a key component of such a program. PMID:24335487

Schorr, Christa A; Zanotti, Sergio; Dellinger, R Phillip

2014-01-01

103

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

PubMed

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

Lynn, Lawrence A

2014-01-01

104

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

105

Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections  

PubMed Central

Abstract Question I have heard about children who have tic disorders that seem to be exacerbated by group A ?-hemolytic streptococcal infection. Should children presenting with this phenomenon receive treatment with antibiotics, receive prophylactic treatment, or use immunomodulators to treat the symptoms? Answer Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) constitute a condition that includes neuropsychiatric symptoms, mainly obsessive-compulsive disorder or tic disorders, temporally associated with an immune-mediated response to streptococcal infections. The actual existence of PANDAS as a unique clinical entity is still up for debate, as a temporal association between group A ?-hemolytic streptococcal infections and symptom exacerbations has been difficult to prove thus far. Based on only a few studies, positive results have been found using antibiotic prophylaxis and immunomodulatory therapy in children with PANDAS. At this time, however, evidence does not support a recommendation for long-term antibiotic prophylaxis or immunomodulatory therapy. PMID:22972724

Tan, Jason; Smith, Christine H.; Goldman, Ran D.

2012-01-01

106

Immunoprophylaxis Against Bacterial Sepsis  

Microsoft Academic Search

Sepsis can be viewed as toxigenic illness resulting from the release of excess quantities of microbial-derived inflammatory mediators into the systemic circulation. Principal among these microbial mediators is bacterial endotoxin. Endotoxin is an essential component of the outer membrane of gram-negative bacteria. Humans are exquisitely susceptible to endotoxin-induced systemic inflammatory reactions that may prove to be rapidly fatal. Many gram-positive

Steven M. Opal; Alan S. Cross; Apurba K. Bhattacharjee; Kumar Visvanathan; John B. Zabriskie

1999-01-01

107

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

108

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

109

Alcoholic leukopenic pneumococcal sepsis.  

PubMed

Alcohol abuse has been associated with an increased mortality and morbidity due to increased aspiration, delirium tremens, and seizures. The association of pneumococcal lung infections and leukopenia in the setting of alcohol abuse are rarely reported; however, when present, severe lung infections can happen with severe lung injury and poor response to conventional therapy and ultimately, death. We are reporting a case of 55-year-old-man presented with shortness of breath, cough and altered mental status and eventually found with severe pneumococcal lung infection in the setting of leukopenia and long-term alcohol abuse representing alcoholic leukopenic pneumococcal sepsis syndrome. PMID:23930244

Alraiyes, Abdul Hamid; Shaheen, Khaldoon; Alraies, M Chadi

2013-04-01

110

Combinatorial search for the ligands that specifically recognize the streptococcal collagen-like  

E-print Network

Combinatorial search for the ligands that specifically recognize the streptococcal collagen. We employed this combinatorial approach to identify ligands specific for the streptococcal collagen plaques 1. Introduction The streptococcal collagen-like proteins, Scl1 and Scl2, are cell surface proteins

Wojciechowski, Jerzy

111

Model for predicting short-term mortality of severe sepsis  

PubMed Central

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 cohort (n = 1458) and a validation cohort (n = 810). Up to four consecutive severe sepsis episodes per patient occurring within the first 28 ICU days were included. We developed a prognostic model for predicting death within 14 days after each episode, based on patient data available at sepsis onset. Results Independent predictors of death were logistic organ dysfunction (odds ratio (OR), 1.22 per point, P < 10-4), septic shock (OR, 1.40; P = 0.01), rank of severe sepsis episode (1 reference, 2: OR, 1.26; P = 0.10 ? 3: OR, 2.64; P < 10-3), multiple sources of infection (OR; 1.45, P = 0.03), simplified acute physiology score II (OR, 1.02 per point; P < 10-4), McCabe score ([greater than or equal to]2) (OR, 1.96; P < 10-4), and number of chronic co-morbidities (1: OR, 1.75; P < 10-3, ? 2: OR, 2.24, P < 10-3). Validity of the model was good in whole cohorts (AUC-ROC, 0.76; 95%CI, 0.74 to 0.79; and HL Chi-square: 15.3 (P = 0.06) for all episodes pooled). Conclusions In ICU patients, a prognostic model based on a few easily obtained variables is effective in predicting death within 14 days after the first to fourth episode of severe sepsis complicating community-, hospital-, or ICU-acquired infection. PMID:19454002

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

2009-01-01

112

Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS): An Evolving Concept  

PubMed Central

Pediatric autoimmune neuropsychiatric disorders associated with streptococcus infections (PANDAS) originated from the observational work of Swedo and collaborators, who formalized their definition in 1998 in a set of operational criteria. The application of these criteria, which focuses on tics and obsessive-compulsive symptoms as core symptoms, has encountered difficulties, eventually leading to a high rate of misdiagnosis. In particular, the core feature represented by the association between newly diagnosed infections and neuropsychiatric symptom relapses in youths with this diagnosis could not be demonstrated by longitudinal studies. Exploratory studies aiming to identify clinical or cognitive features that could discriminate PANDAS from other pediatric obsessive-compulsive and tic disorders present methodological limitations, and therefore are not conclusive. Other behavioral features, in addition to obsessive-compulsive symptoms and tics, have been included in pediatric acute-onset neuropsychiatric syndromes (PANS) and childhood acute neuropsychiatric syndromes (CANS), two new concepts recently proposed in order to define a much broader clinical spectrum encompassing etiologically diverse entities. Given the uncertainties on the clinical definition of PANDAS, it is not surprising that evidence in support of a post-infectious, immune-mediated pathophysiology is also insufficient. Anti-dopamine receptor antibodies might be relevant to both Sydenham’s chorea (SC)—the prototypical post-streptococcal neuropsychiatric disorder—and some rare forms of encephalitis targeting the basal ganglia specifically, but studies exploring their association with children fulfilling Swedo’s criteria for PANDAS have been inconclusive. Moreover, we lack evidence in favor of the efficacy of antibiotic prophylaxis or tonsillectomy in patients fulfilling Swedo’s criteria for PANDAS, whereas a response to immune-mediated treatments like intravenous immunoglobulins has been documented by one study, but needs replication in larger trials. Overall, the available evidence does not convincingly support the concept that PANDAS are a well-defined, isolated clinical entity subdued by definite pathophysiological mechanisms; larger, prospective studies are necessary to reshape the nosography and disease mechanisms of post-streptococcal acute neuropsychiatric disorders other than SC. Research is also under way to shed further light on a possible relationship between streptococcal infections, other biological and psychosocial stressors, and the complex pathobiology of chronic tic disorders. PMID:24106651

Macerollo, Antonella; Martino, Davide

2013-01-01

113

Role of protein C in renal dysfunction after polymicrobial sepsis.  

PubMed

Protein C (PC) plays an important role in vascular function, and acquired deficiency during sepsis is associated with increased mortality in both animal models and in clinical studies. This study explored the consequences of PC suppression on the kidney in a cecal ligation and puncture model of polymicrobial sepsis. This study shows that a rapid drop in PC after sepsis is strongly associated with an increase in blood urea nitrogen, renal pathology, and expression of known markers of renal injury, including neutrophil gelatinase-associated lipocalin, CXCL1, and CXCL2. The endothelial PC receptor, which is required for the anti-inflammatory and antiapoptotic activity of activated PC (APC), was significantly increased after cecal ligation and puncture as well as in the microvasculature of human kidneys after injury. Treatment of septic animals with APC reduced blood urea nitrogen, renal pathology, and chemokine expression and dramatically reduced the induction of inducible nitric oxide synthase and caspase-3 activation in the kidney. The data demonstrate a clear link between acquired PC deficiency and renal dysfunction in sepsis and suggest a compensatory upregulation of the signaling receptor. Moreover, these data suggest that APC treatment may be effective in reducing inflammatory and apoptotic insult during sepsis-induced acute renal failure. PMID:17301189

Gupta, Akanksha; Berg, David T; Gerlitz, Bruce; Sharma, Ganesh R; Syed, Samreen; Richardson, Mark A; Sandusky, George; Heuer, Josef G; Galbreath, Elizabeth J; Grinnell, Brian W

2007-03-01

114

Maternal and Fetal Death following Group A Streptococcal Meningitis in Mid-Term Pregnancy  

PubMed Central

Background. Group A streptococcal (GAS) meningitis is rarely seen in the antenatal period, but it is associated with significant mortality. We present a case of a mid-trimester woman who developed fulminant meningitis following a rapid onset atypical presentation of infection with this organism. Case. A multiparous 23+5-week woman presented with a 10-day history of a non-productive cough associated with pyrexia. Within minutes of her admission she collapsed and lost consciousness; sepsis was suspected and cross-specialty care was initiated. She was managed empirically in extremis with broad-spectrum antibiotics and mannitol with 3% hypertonic saline for suspected infection and raised intracranial pressure, respectively. Despite intensivist management, a CT head revealed diffuse oedema with coning of the cerebellar tonsils. Brainstem death was certified within 19 hours of admission and fetal death ensued. Postmortem bacteriology confirmed GAS meningitis. Conclusion. Through raising awareness of this patient and her disease course, we hope that future policy decisions, primary care, and hospital level management will be informed accordingly for treatment of pregnant women with suspected GAS infection. PMID:24883215

Kamaledeen, Abderahman; Law, Penelope

2014-01-01

115

Serum sepsis, not sickness.  

PubMed

Rarely taught in medical schools, clinical reasoning is the ability to discern the important from the unimportant and to arrive at accurate and efficient clinical conclusions. Identifying errors in reasoning is difficult; however, undetected clinical reasoning errors can have exponential consequences. As quality and patient safety come into focus, identifying and preventing clinical reasoning errors have become imperative. The authors present a case of a man sent for admission from a subspecialty clinic diagnosed with infliximab-induced serum sickness. Not countering the expert's diagnosis, initial workup failed to diagnose joint abscess and sepsis. Heuristics are mental shortcuts used to make decision making more efficient but can lead to error. The anchoring heuristic, premature closure, confirmation bias and the blind obedience heuristic are examples. Introspective surveillance and interactive hypothesis testing defend against heuristics. The authors conclude by discussing 4 types of hypersensitivity reactions, serum sickness in particular, and the chimeric nature of infliximab. PMID:21273840

Guidry, Michelle M; Drennan, Robert H; Weise, Jeff; Hamm, L Lee

2011-02-01

116

Neonatal Sepsis and Neutrophil Insufficiencies  

PubMed Central

Sepsis has continuously been a leading cause of neonatal morbidity and mortality despite current advances in chemotherapy and patient intensive care facilities. Neonates are at high risk for developing bacterial infections due to quantitative and qualitative insufficiencies of innate immunity, particularly granulocyte lineage development and response to infection. Although antibiotics remain the mainstay of treatment, adjuvant therapies enhancing immune function have shown promise in treating sepsis in neonates. This chapter reviews current strategies for the clinical management of neonatal sepsis and analyzes mechanisms underlying insufficiencies of neutrophil defense in neonates with emphasis on new directions for adjuvant therapy development. PMID:20521927

Melvan, John Nicholas; Bagby, Gregory J.; Welsh, David A.; Nelson, Steve; Zhang, Ping

2011-01-01

117

Group A streptococcal meningitis in a patient with palmoplantar pustulosis.  

PubMed

A 64-year-old man with a 10-year history of palmoplantar pustulosis, a recent history of cranial surgery and a persistent upper airway infection presented with a high fever and deep coma. The patient was diagnosed with Group A Streptococcal meningitis and promptly treated with antibiotics. Although his general condition recovered well, sensorineural hearing loss and facial palsy remained. Group A Streptococcal meningitis is a rare condition, and its typical clinical picture and epidemiological features remain poorly understood. Physicians need to be more aware of this infection, which is extremely rare but frequently causes various complications and yields a high mortality. PMID:24292762

Hagiya, Hideharu; Otsuka, Fumio

2013-01-01

118

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

119

Limb Salvage for Streptococcal Gangrene of the Extremity  

Microsoft Academic Search

Background: Extremity soft tissue infections from group A, ?-hemolytic streptococcus frequently culminate in amputation. This study compares our protocol for limb salvage with expected results.Methods: Patients with extremity streptococcal gangrene treated from 1989 to 1995 were reviewed. The management protocol mandated immediate, radical excision of involved skin and subcutaneous tissue, with preservation of fascia. Patients were managed in the burn

Michael Schurr; Sandra Engelhardt; Richard Helgerson

1998-01-01

120

Cervical pregnancy complicated with group B streptococcal meningitis.  

PubMed

Maternal group B streptococcal infection is an uncommon entity. Herein we describe a case of a 27-year-old-woman who presented life-threateniing group B streptococcus meningitis with an ectopic cervical pregnancy. No other infectious focus have been found. To our knowledge this is the first time that this association has been reported. PMID:17674249

Sabadell, Jordi; Sanchez-Iglesias, Jose Luis; Ferrer, Raquel; Higueras, Teresa; Alijotas, Jaume; Cabero, Luis

2007-05-01

121

SIRT1 inhibition during the hypoinflammatory phenotype of sepsis enhances immunity and improves outcome.  

PubMed

Mechanism-based sepsis treatments are unavailable, and their incidence is rising worldwide. Deaths occur during the early acute phase of hyperinflammation or subsequent postacute hypoinflammatory phase with sustained organ failure. The acute sepsis phase shifts rapidly, and multiple attempts to treat early excessive inflammation have uniformly failed. We reported in a sepsis cell model and human sepsis blood leukocytes that nuclear NAD+ sensor SIRT1 deacetylase remodels chromatin at specific gene sets to switch the acute-phase proinflammatory response to hypoinflammatory. Importantly, SIRT1 chromatin reprogramming is reversible, suggesting that inhibition of SIRT1 might reverse postacute-phase hypoinflammation. We tested this concept in septic mice, using the highly specific SIRT1 inhibitor EX-527, a small molecule that closes the NAD+ binding site of SIRT1. Strikingly, when administered 24 h after sepsis, all treated animals survived, whereas only 40% of untreated mice survived. EX-527 treatment reversed the inability of leukocytes to adhere at the small intestine MVI, reversed in vivo endotoxin tolerance, increased leukocyte accumulation in peritoneum, and improved peritoneal bacterial clearance. Mechanistically, the SIRT1 inhibitor restored repressed endothelial E-selectin and ICAM-1 expression and PSGL-1 expression on the neutrophils. Systemic benefits of EX-527 treatment included stabilized blood pressure, improved microvascular blood flow, and a shift toward proimmune macrophages in spleen and bone marrow. Our findings reveal that modifying the SIRT1 NAD+ axis may provide a novel way to treat sepsis in its hypoinflammatory phase. PMID:25001863

Vachharajani, Vidula T; Liu, Tiefu; Brown, Candice M; Wang, Xianfeng; Buechler, Nancy L; Wells, Jonathan David; Yoza, Barbara K; McCall, Charles E

2014-11-01

122

Paediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS).  

PubMed

The evidence to date, both published and unpublished, which addresses the validity of the proposed unique subgroup of children with early and abrupt onset of obsessive--compulsive disorder (OCD) and/or tic disorders subsequent to streptococcal infections was reviewed. The aetiology of OCD and tic disorders is unknown, although it appears that both disorders may arise from a variety of genetic and environmental factors. Post-streptococcal autoimmunity has been postulated as one possible mechanism for some. The acronym PANDAS (for paediatric autoimmune neuropsychiatric disorders associated with streptococcal infections) has been given to a subgroup of paediatric patients who meet five inclusionary criteria: presence of OCD and/or tic disorder, pre-pubertal symptom onset, sudden onset or episodic course of symptoms, temporal association between streptococcal infections and neuropsychiatric symptom exacerbations, and associated neurological abnormalities. The proposed model of pathophysiology provides for several unique treatment strategies, including the use of antibiotic prophylaxis to prevent streptococcal-triggered exacerbations, and the use of immunomodulatory interventions (such as intravenous immunoglobulin or therapeutic plasma exchange) in the treatment severe neuropsychiatric symptoms. For the latter study group, long-term (2--5 yr) follow-up revealed continued symptom improvement for the majority of patients, particularly when antibiotic prophylaxis had been effective in preventing recurrent streptococcal infections. In addition, the episodic nature of the subgroup's illness provides for opportunities to study brain structure and function during health and disease, as well as allowing for investigations of the aetiologic role of anti-neuronal antibodies and neuroimmune dysfunction in both OCD and tic disorders. Although much research remains to be done, an increasing body of evidence provides support for the postulate that OCD and tic disorders may arise from post-streptococcal autoimmunity. The unique clinical characteristics of the PANDAS subgroup, the presence of volumetric changes in the basal ganglia, and the dramatic response to immunomodulatory treatments, suggest that symptoms arise from a combination of local, regional and systemic dysfunction. Ongoing research is directed at understanding the nature of the abnormal immune response, as well as identifying at-risk children, in order to provide for novel strategies of prevention and treatment. PMID:11466169

Leonard, H L; Swedo, S E

2001-06-01

123

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

124

Increased Resistin Levels in Intra-abdominal Sepsis  

PubMed Central

Objectives: Resistin, a hormone secreted from adipocytes and considered to be a likely cause of insulin resistance, has recently been accepted as a proinflammatory cytokine. This study aimed to determine the correlation between resistin levels in patients with intra-abdominal sepsis and mortality. Methods: Of 45 patients with intra-abdominal sepsis, a total of 35 adult patients were included in the study. This study was undertaken from December 2011 to December 2012 and included patients who had no history of diabetes mellitus and who were admitted to the general surgery intensive care units of Gazi University and Bülent Ecevit University School of Medicine, Turkey. Evaluations were performed on 12 patients with sepsis, 10 patients with severe sepsis, 13 patients with septic shock and 15 healthy controls. The patients’ plasma resistin, interleukin-6 (IL-6), tumour necrosis factor alpha (TNF-?), interleukin-1 beta (IL-1?), procalcitonin, lactate and glucose levels and Acute Physiology and Chronic Health Evaluation (APACHE) II scores were studied daily for the first five days after admission. A correlation analysis of serum resistin levels with cytokine levels and APACHE II scores was performed. Results: Serum resistin levels in patients with sepsis were significantly higher than in the healthy controls (P <0.001). A significant correlation was found between serum resistin levels and APACHE II scores, serum IL-6, IL-1?, TNF-?, procalcitonin, lactate and glucose levels. Furthermore, a significant correlation was found between serum resistin levels and all-cause mortality (P = 0.02). Conclusion: The levels of resistin were significantly positively correlated with the severity of disease and were a possible mediator of a prolonged inflammatory state in patients with intra-abdominal sepsis.

Yilmaz, Tonguc U.; Kerem, Mustafa; Demirtas, Canan Y.; Pasaoglu, Ozge; Tascilar, Oge; Sakrak, Omer; Dikmen, Kursat; Karahan, Tarkan

2014-01-01

125

Sepsis-associated encephalopathy.  

PubMed

Sepsis-associated encephalopathy (SAE) is a diffuse brain dysfunction that occurs secondary to infection in the body without overt CNS infection. SAE is frequently encountered in critically ill patients in intensive care units, and in up to 70% of patients with severe systemic infection. The severity of SAE can range from mild delirium to deep coma. Seizures and myoclonus are infrequent and cranial nerves are almost always spared, but most severe cases have an associated critical illness neuromyopathy. Development of SAE probably involves a number of mechanisms that are not mutually exclusive and vary from patient to patient. Substantial neurological and psychological morbidities often occur in survivors. Mortality is almost always due to multiorgan failure rather than neurological complications, and is almost 70% in patients with severe SAE. Further research into the pathophysiology, management and prevention of SAE is needed. This Review discusses the epidemiology and clinical presentation of SAE. Recent evidence for SAE pathophysiology is outlined and a diagnostic approach to patients with this syndrome is presented. Lastly, prognosis and management of SAE is discussed. PMID:22986430

Gofton, Teneille E; Young, G Bryan

2012-10-01

126

Rheumatic fever, autoimmunity, and molecular mimicry: the streptococcal connection.  

PubMed

The group A streptococcus, Streptococcus pyogenes, and its link to autoimmune sequelae, has acquired a new level of understanding. Studies support the hypothesis that molecular mimicry between the group A streptococcus and heart or brain are important in directing immune responses in rheumatic fever. Rheumatic carditis, Sydenham chorea and a new group of behavioral disorders called pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections are reviewed with consideration of autoantibody and T cell responses and the role of molecular mimicry between the heart, brain and group A streptococcus as well as how immune responses contribute to pathogenic mechanisms in disease. In rheumatic carditis, studies have investigated human monoclonal autoantibodies and T cell clones for their crossreactivity and their mechanisms leading to valve damage in rheumatic heart disease. Although studies of human and animal sera from group A streptococcal diseases or immunization models have been crucial in providing clues to molecular mimicry and its role in the pathogenesis of rheumatic fever, study of human monoclonal autoantibodies have provided important insights into how antibodies against the valve may activate the valve endothelium and lead to T cell infiltration. Passive transfer of anti-streptococcal T cell lines in a rat model of rheumatic carditis illustrates effects of CD4+ T cells on the valve. Although Sydenham chorea has been known as the neurological manifestation of rheumatic fever for decades, the combination of autoimmunity and behavior is a relatively new concept linking brain, behavior and neuropsychiatric disorders with streptococcal infections. In Sydenham chorea, human mAbs and their expression in transgenic mice have linked autoimmunity to central dopamine pathways as well as dopamine receptors and dopaminergic neurons in basal ganglia. Taken together, the studies reviewed provide a basis for understanding streptococcal sequelae and how immune responses against group A streptococci influence autoimmunity and inflammatory responses in the heart and brain. PMID:24892819

Cunningham, Madeleine W

2014-01-01

127

Management of the neonate at risk for early-onset Group B streptococcal disease (GBS EOD): new paediatric guidelines in Belgium.  

PubMed

Despite group B streptococcal (GBS) screening in late pregnancy and intrapartum antimicrobial prophylaxis, early-onset sepsis in neonates remains a common source of neonatal morbidity and mortality especially in preterm neonates. The identification of neonates with early-onset sepsis is usually based on perinatal risk factors. Clinical signs are aspecific and laboratory tests are not sensitive. Therefore, many clinicians will overtreat at-risk infants. Inappropriate treatment with antibiotics increases the risk for late-onset sepsis, necrotizing enterocolitis, mortality, and prolongs hospitalisation and costs. In 2003, the Belgian Health Council published guidelines for the prevention of perinatal GBS infections. This report presents the Belgian paediatric management guidelines, which have been endorsed by the Belgian and Flemish societies of neonatology and paediatrics. The most imported changes in the 2014 guidelines are the following: recommendations for a lumbar puncture; clarification of normal spinal fluid parameters and blood neutrophil indices corrected for gestation age; specific timing for diagnostic testing after birth; no indication for diagnostic testing in asymptomatic newborns unless additional risk factors; a revised algorithm for management of neonates according to maternal and neonatal risk factors; and premature infants described as those below 35 weeks instead of 37 weeks. The guidelines were made on the basis of the best evidence and on expert opinion when inadequate evidence exists. PMID:25056493

Mahieu, L; Langhendries, J-P; Cossey, V; De Praeter, C; Lepage, P; Melin, P

2014-10-01

128

Role of presepsin for the evaluation of sepsis in the emergency department.  

PubMed

Abstract Sepsis, severe sepsis and septic shock are among the most common conditions handled in the emergency department (ED). According to new Sepsis Guidelines, early diagnosis and treatment are the keys to improve survival. Plasma C-reactive protein (CRP) and procalcitonin (PCT) levels, when associated with documented or suspected infection, are now part of the definitions of sepsis. Blood culture is the gold standard method for detecting microorganisms but it requires too much time for results to be known. Sensitive biomarkers are required for early diagnosis and as indexes of prognosis sepsis. CRP is one of the acute phase proteins synthesized by the liver: it has a great sensitivity but a very poor specificity for bacterial infections. Moreover, the evolution of sepsis does not correlate with CRP plasma changes. In recent years PCT has been widely used for sepsis differential diagnosis, because of its close correlation with infections, but it still retains some limitations and false positivity (such as in multiple trauma and burns). Soluble CD14 subtype (sCD14-ST), also known as presepsin, is a novel and promising biomarker that has been shown to increase significantly in patients with sepsis, in comparison to the healthy population. Studies pointed out the capability of this biomarker for diagnosing sepsis, assessing the severity of the disease and providing a prognostic evaluation of patient outcome. In this mini review we mainly focused on presepsin: we evaluate its diagnostic and prognostic roles in patients presenting to the ED with systemic inflammatory response syndrome (SIRS), suspected sepsis or septic shock. PMID:24897403

Pizzolato, Elisa; Ulla, Marco; Galluzzo, Claudia; Lucchiari, Manuela; Manetta, Tilde; Lupia, Enrico; Mengozzi, Giulio; Battista, Stefania

2014-10-01

129

Experimental Cannabinoid 2 Receptor-Mediated Immune Modulation in Sepsis  

PubMed Central

Sepsis is a complex condition that results from a dysregulated immune system in response to a systemic infection. Current treatments lack effectiveness in reducing the incidence and mortality associated with this disease. The endocannabinoid system offers great promise in managing sepsis pathogenesis due to its unique characteristics. The present study explored the effect of modulating the CB2 receptor pathway in an acute sepsis mouse model. Endotoxemia was induced by intravenous injection of lipopolysaccharide (LPS) in mice and intestinal microcirculation was assessed through intravital microscopy. We found that HU308 (CB2 receptor agonist) reduced the number of adherent leukocytes in submucosal venules but did not restore muscular and mucosal villi FCD in endotoxemic mice. AM630 (CB2 receptor antagonist) maintained the level of adherent leukocytes induced by LPS but further reduced muscular and mucosal villi FCD. URB597 (FAAH inhibitor) and JZL184 (MAGL inhibitor) both reduced the number of adherent leukocytes in submucosal venules but did not restore the mucosal villi FCD. Using various compounds we have shown different mechanisms of activating CB2 receptors to reduce leukocyte endothelial interactions in order to prevent further inflammatory damage during sepsis. PMID:24803745

Sardinha, J.; Kelly, M. E. M.; Zhou, J.; Lehmann, C.

2014-01-01

130

Early identification and treatment of sepsis.  

PubMed

Sepsis is a potentially fatal condition and is becoming increasingly frequent, yet health professionals are often unable to recognise its symptoms. It is the body's exaggerated response to infection and, if left untreated, will lead to severe sepsis, multi-organ failure and death. Nurses play a vital role in identifying patients with sepsis and starting essential treatment. This article looks at how sepsis can be identified and effectively treated to improve survival. PMID:24592630

McClelland, Heather; Moxon, Alex

131

Sepsis progression and outcome: a dynamical model  

Microsoft Academic Search

BACKGROUND: Sepsis (bloodstream infection) is the leading cause of death in non-surgical intensive care units. It is diagnosed in 750,000 US patients per annum, and has high mortality. Current understanding of sepsis is predominately observational and correlational, with only a partial and incomplete understanding of the physiological dynamics underlying the syndrome. There exists a need for dynamical models of sepsis

Sergey M Zuev; Stephen F Kingsmore; Damian DG Gessler

2006-01-01

132

[Primary peritonitis combined with streptococcal toxic shock syndrome following an upper respiratory tract infection caused by Streptococcus pyogenes].  

PubMed

A 52-year-old woman with no previous history of major health problems presented with an acute abdomen and symptoms of shock. Three days earlier she had been diagnosed as having acute laryngitis which was treated with steroids. On admission she was suffering from hypotension, renal failure, liver failure and coagulopathy. Emergency laparotomy revealed purulent fluid spread diffusely throughout the abdominal cavity. Streptococcus pyogenes was grown in culture from this fluid, enabling a diagnosis of streptococcal toxic shock syndrome (STSS) with primary peritonitis to be made. This combination is rare, and has been described only a few times. Only one other patient is known in whom this combination was preceded by respiratory symptoms. The treatment consists of abdominal lavage, intravenous administration of antibiotics and immunoglobulins, and support for renal function, liver function, respiration and coagulation. PMID:18512531

Van Den Bossche, M J A; Devriendt, D; Weyne, L; Van Ranst, M

2008-04-12

133

Restless legs syndrome: association with streptococcal or mycoplasma infection.  

PubMed

Group A beta-hemolytic streptococcal infections have been reported to cause neuropsychiatric symptoms, such as chorea, tics, and obsessive-compulsive disorder, presumably through autoimmune damage to basal ganglia. Mycoplasma pneumoniae infections have also been reported to cause damage to the basal ganglia. Restless legs syndrome is a movement disorder with focal restlessness, an irresistible desire to move, and exacerbation by long periods of sitting or lying. We present three children with transient restless legs syndrome-like symptoms possibly associated with group A beta-hemolytic streptococcal infection or Mycoplasma pneumoniae infection. One of three patients had persistently elevated enzyme-linked immunosorbent optical density values against human caudate and putamen. PMID:15301831

Matsuo, Muneaki; Tsuchiya, Katsunori; Hamasaki, Yuhei; Singer, Harvey S

2004-08-01

134

Miliary tuberculosis as a cause of acute empyema.  

PubMed

Adult respiratory distress syndrome (ARDS) and sepsis are known, life-threatening complications of miliary tuberculosis. This report describes a patient with miliary tuberculosis who rapidly developed an acute tuberculous empyema. She had a fulminant course culminating in ARDS, sepsis and subsequent death. This case highlights the rare association of acute empyema with miliary tuberculosis. PMID:14665781

Runo, James R; Welch, Derek C; Ness, Erik M; Robbins, Ivan M; Milstone, Aaron P

2003-01-01

135

Successful Trovafloxacin Prophylaxis against Experimental Streptococcal Aortic Valve Endocarditis  

Microsoft Academic Search

Single-dose trovafloxacin (15 mg\\/kg given intravenously (i.v.)) and ampicillin (40 mg\\/kg given i.v.) protected 38 and 33% of animals challenged with an ampicillin-tolerant strain of Streptococcus oralis, respectively. As a double-dose regimen, trovafloxacin afforded total protection (100%; P < 0.001 versus controls). Trovafloxacin is the first fluoroquinolone effective in preventing experimental streptococcal endocarditis. Trovafloxacin is highly active in vitro against

I. Katsarolis; A. Pefanis; D. Iliopoulos; P. Siaperas; P. Karayiannakos; H. Giamarellou

2000-01-01

136

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...

137

MODELING THERAPEUTIC INTERVENTION IN SEPSIS  

Microsoft Academic Search

Inflammation is the physiological response to infection and tissue injury. It is characterized by release of proteins called cytokines and other mediators produced by cells of the immune system. Sepsis, the systemic inflammatory response to infection, is a public health issue because of its high incidence, mortality and economical cost. Experimental paradigms and therapeutic strategies designed to harness systemic inflammation

Masayoshi Kubo; Mauricio Rosas

138

Which biomarkers reveal neonatal sepsis?  

PubMed

We address the identification of optimal biomarkers for the rapid diagnosis of neonatal sepsis. We employ both canonical correlation analysis (CCA) and sparse support vector machine (SSVM) classifiers to select the best subset of biomarkers from a large hematological data set collected from infants with suspected sepsis from Yale-New Haven Hospital's Neonatal Intensive Care Unit (NICU). CCA is used to select sets of biomarkers of increasing size that are most highly correlated with infection. The effectiveness of these biomarkers is then validated by constructing a sparse support vector machine diagnostic classifier. We find that the following set of five biomarkers capture the essential diagnostic information (in order of importance): Bands, Platelets, neutrophil CD64, White Blood Cells, and Segs. Further, the diagnostic performance of the optimal set of biomarkers is significantly higher than that of isolated individual biomarkers. These results suggest an enhanced sepsis scoring system for neonatal sepsis that includes these five biomarkers. We demonstrate the robustness of our analysis by comparing CCA with the Forward Selection method and SSVM with LASSO Logistic Regression. PMID:24367543

Wang, Kun; Bhandari, Vineet; Chepustanova, Sofya; Huber, Greg; O'Hara, Stephen; O'Hern, Corey S; Shattuck, Mark D; Kirby, Michael

2013-01-01

139

The role of Nox2-derived ROS in the development of cognitive impairment after sepsis  

PubMed Central

Background Sepsis- associated encephalopathy (SAE) is an early and common feature of severe infections. Oxidative stress is one of the mechanisms associated with the pathophysiology of SAE. The goal of this study was to investigate the involvement of NADPH oxidase in neuroinflammation and in the long-term cognitive impairment of sepsis survivors. Methods Sepsis was induced in WT and gp91phox knockout mice (gp91phox-/-) by cecal ligation and puncture (CLP) to induce fecal peritonitis. We measured oxidative stress, Nox2 and Nox4 gene expression and neuroinflammation in the hippocampus at six hours, twenty-four hours and five days post-sepsis. Mice were also treated with apocynin, a NADPH oxidase inhibitor. Behavioral outcomes were evaluated 15 days after sepsis with the inhibitory avoidance test and the Morris water maze in control and apocynin-treated WT mice. Results Acute oxidative damage to the hippocampus was identified by increased 4-HNE expression in parallel with an increase in Nox2 gene expression after sepsis. Pharmacological inhibition of Nox2 with apocynin completely inhibited hippocampal oxidative stress in septic animals. Pharmacologic inhibition or the absence of Nox2 in gp91phox-/- mice prevented glial cell activation, one of the central mechanisms associated with SAE. Finally, treatment with apocynin and inhibition of hippocampal oxidative stress in the acute phase of sepsis prevented the development of long-term cognitive impairment. Conclusions Our results demonstrate that Nox2 is the main source of reactive oxygen species (ROS) involved in the oxidative damage to the hippocampus in SAE and that Nox2-derived ROS are determining factors for cognitive impairments after sepsis. These findings highlight the importance of Nox2-derived ROS as a central mechanism in the development of neuroinflammation associated with SAE. PMID:24571599

2014-01-01

140

Narcolepsy-Cataplexy: Is Streptococcal Infection a Trigger?  

PubMed Central

Narcolepsy-cataplexy is an uncommon sleep disorder which may present in childhood. We report a case of an 8-year-old presenting with narcolepsy-cataplexy following a streptococcal infection. Autoimmune etiology for narcolepsy has been suggested. In our patient increased anti-streptolysin O and anti-DNAse B titers were noted. As suggested by recent cases, the streptococcal infection was likely a trigger for narcolepsy onset in this genetically predisposed child. The patient was initially diagnosed as having Sydenham chorea due to motor movements. However, these transient movements may be due to the narcolepsy onset. Narcolepsy in childhood may present with atypical symptoms; it might be difficult to obtain accurate history and can be misdiagnosed as in the reported case. A high index of clinical suspicion is needed to diagnose these patients. Citation: Natarajan N; Jain SV; Chaudhry H; Hallinan BE; Simakajornboon N. Narcolepsy-cataplexy: is streptococcal infection a trigger? J Clin Sleep Med 2013;9(3):269-270. PMID:23493659

Natarajan, Niranjana; Jain, Sejal V.; Chaudhry, Hina; Hallinan, Barbara E.; Simakajornboon, Narong

2013-01-01

141

Managing the risks of sepsis in pregnancy.  

PubMed

Sepsis is a major cause of maternal mortality and morbidity worldwide. In the UK, sepsis is now the leading cause of direct maternal deaths. Raising awareness among healthcare professionals about the risks of maternal sepsis and the importance of early management is urgently needed. The challenge in the management of maternal sepsis is the translation of the vast knowledge gained from sequential confidential enquiries into maternal death and research findings, into clinical practice, to ensure an improvement in patient quality of care and maternal mortality and morbidity. In this chapter, I give an overview of the management of the risks of sepsis, and discuss implementation strategies that may reduce these risks. PMID:23639681

Bamfo, Jacqueline E A K

2013-08-01

142

Therapeutic effects of compound hypertonic saline on rats with sepsis.  

PubMed

Sepsis is one of the major causes of death and is the biggest obstacle preventing improvement of the success rate in curing critical illnesses. Currently, isotonic solutions are used in fluid resuscitation technique. Several studies have shown that hypertonic saline applied in hemorrhagic shock can rapidly increase the plasma osmotic pressure, facilitate the rapid return of interstitial fluid into the blood vessels, and restore the effective circulating blood volume. Here, we established a rat model of sepsis by using the cecal ligation and puncture approach. We found that intravenous injection of hypertonic saline dextran (7.5% NaCl/6% dextran) after cecal ligation and puncture can improve circulatory failure at the onset of sepsis. We found that the levels of tumor necrosis factor-?, interleukin-1?, interleukin-6 and intracellular adhesion molecule 1 levels in the lung tissue of cecal ligation and puncture rats treated with hypertonic saline dextran were significantly lower than the corresponding levels in the control group. We inferred that hypertonic saline dextran has a positive immunoregulatory effect and inhibits the overexpression of the inflammatory response in the treatment of sepsis. The percentage of neutrophils, lung myeloperoxidase activity, wet to dry weight ratio of lung tissues, histopathological changes in lung tissues, and indicators of arterial blood gas analysis was significantly better in the hypertonic saline dextran-treated group than in the other groups in this study. Hypertonic saline dextran-treated rats had significantly improved survival rates at 9 and 18 h compared to the control group. Our results suggest that hypertonic saline dextran plays a protective role in acute lung injury caused after cecal ligation and puncture. In conclusion, hypertonic/hyperoncotic solutions have beneficial therapeutic effects in the treatment of an animal model of sepsis. PMID:24983672

Dong, Fang; Chen, Wei; Xu, Liang; Wang, Huabing; Lu, Huizhi

2014-01-01

143

Outcomes of Severe Sepsis and Septic Shock Patients on Chronic Antiplatelet Treatment: A Historical Cohort Study  

PubMed Central

Background. Sepsis is characterized by dysfunctional activation of platelets, and antiplatelet therapy could improve the outcomes of septic patients. Methods. We performed a retrospective cohort study of severe sepsis or septic shock adult patients. Outcomes of patients on antiplatelet therapy were compared to those that were not taking antiplatelet therapy by univariate analysis followed by a propensity score analysis based on the probability of receiving antiplatelet therapy. Results. Of 651 patients included in the study 272 (42.8%) were on antiplatelet therapy before the development of severe sepsis or septic shock. After adjusting for important confounding variables antiplatelet therapy was not associated with a decreased risk of hospital mortality (odds ratio 0.73, 95% confidence interval 0.46–1.16). Antiplatelet therapy was associated with a decreased incidence of acute respiratory distress syndrome/acute lung injury (odds ratio 0.50, 95% confidence interval 0.35–0.71) and reduced need of mechanical ventilation (odds ratio 0.62, 95% confidence interval 0.45–87). Incidence of acute kidney injury was similar between both groups (odds ratio 1.08, 95% confidence interval 0.73–1.59). Conclusions. The use of antiplatelet therapy before the diagnosis of severe sepsis or septic shock was not associated with decreased hospital mortality. Antiplatelet therapy was associated with a decreased incidence of acute lung injury/acute respiratory distress syndrome. PMID:23509620

Valerio-Rojas, Juan C.; Jaffer, Insara J.; Kor, Daryl J.; Gajic, Ognjen

2013-01-01

144

Oral Delivery of Group A Streptococcal Cell Walls Augments Circulating TGF-b and Suppresses Streptococcal Cell Wall Arthritis  

Microsoft Academic Search

Oral administration of autoantigens can influence the outcome of experimental autoimmune diseases, yet little is known about nonself Ag-induced tolerance. In this study, we administered group A streptococcal cell wall (SCW) peptidoglycan-polysaccharide complexes orally and monitored the impact on SCW-induced erosive polyarthritis. Oral administration of low dose SCW (3 mg\\/day), initiated 7 days before an arthritogenic dose of systemic SCW,

Wanjun Chen; Wenwen Jin; Melissa Cook; Howard L. Weiner; Sharon M. Wahl

145

Epidemiology of neonatal sepsis in South Korea  

PubMed Central

Background Neonatal sepsis is a severe clinical syndrome characterized by systemic signs of infection, shock and system organ failure; diagnosis is confirmed on positive culture from a normally sterile site(s). There are few reports comparing incidence, mortality, and risk factors between clinically diagnosed sepsis and that confirmed by culture. Methods All infants diagnosed with early- (within first 72 h after birth) or late-onset (72 h–4 weeks after birth) neonatal sepsis between 1997 and 1999 from four neonatal centers in South Korea, were investigated. Results The estimated incidence rate of neonatal sepsis during the 3 years was 30.5 per 1000 live births for clinical sepsis and 6.1 per 1000 live births for sepsis with positive culture, with case-fatality rates of 4.7% and 2.2%, respectively. When only early-onset sepsis was considered, the incidence and fatality rates were 25.1 per 1000 live births and 6.1% for clinical sepsis, and 4.3 per 1000 live births and 2.5% for culture-confirmed sepsis, respectively. For the 179 patients (185 causative organisms) of proven sepsis, Staphylococcus spp. including S. aureus were the most frequent isolates. In early-onset clinical sepsis, having very low birthweight (?1500 g), a low Apgar score at 5 min (?7), and being male were related to higher rates of case-fatality (relative risk: 11.3, 6.8 and 2.5, respectively) Conclusions Clinical sepsis was more common than culture-confirmed sepsis and had a higher case-fatality rate. It seems prudent to take rapid and decisive steps toward better management of the high-risk group whether the sepsis is clinically diagnosed or culture confirmed. PMID:19405921

Shin, Youn-Jeong; Ki, Moran; Foxman, Betsy

2013-01-01

146

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

147

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

148

NONSPECIFIC COMPLEMENT ACTIVATION BY STREPTOCOCCAL STRUCTURES II. Properdin-Indepe ndent Initiation of the Alternate Pathway  

Microsoft Academic Search

The observation (1) that inhibition of HLA cytotoxicity by streptococcal antigens was, in reality, due to consumption of complement (C) by these antigens prompted us to further investigate the mechanism of this consumption. Several possibilities for this anticomplementary activity were considered. Since human sera often contain antibodies to a number of streptococcal antigens, a specific interaction between bacterial structures and

J. W. TAUBER; M. J. POLLEY; J. B. ZABRISKIE

149

Biosensor of endotoxin and sepsis  

NASA Astrophysics Data System (ADS)

To investigate the relation between biosensor of endotoxin and endotoxin of plasma in sepsis. Method: biosensor of endotoxin was designed with technology of quartz crystal microbalance bioaffinity sensor ligand of endotoxin were immobilized by protein A conjugate. When a sample soliton of plasma containing endotoxin 0.01, 0.03, 0.06, 0.1, 0.5, 1.0Eu, treated with perchloric acid and injected into slot of quartz crystal surface respectively, the ligand was released from the surface of quartz crystal to form a more stable complex with endotoxin in solution. The endotoxin concentration corresponded to the weight change on the crystal surface, and caused change of frequency that occurred when desorbed. The result was biosensor of endotoxin might detect endotoxin of plasma in sepsis, measurements range between 0.05Eu and 0.5Eu in the stop flow mode, measurement range between 0.1Eu and 1Eu in the flow mode. The sensor of endotoxin could detect the endotoxin of plasm rapidly, and use for detection sepsis in clinically.

Shao, Yang; Wang, Xiang; Wu, Xi; Gao, Wei; He, Qing-hua; Cai, Shaoxi

2001-09-01

150

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

151

Standardized order sets for the treatment of severe sepsis and septic shock.  

PubMed

Evaluation of: Thiel SW, Asghar MF, Micek ST, Reichley RM, Doherty JA, Kollef MH. Hospital-wide impact of standardized order set for the management of bacteremic severe sepsis. Crit. Care Med. 37(3), 819-824 (2009). Aggressive standardized diagnostic and therapeutic approaches to acute diseases such as acute myocardial infarction, trauma and stroke have led to improved patient survival. A standardized order set for severe sepsis and septic shock represents a similar approach. In 2001, Rivers et al., using a standardized operating procedure to treat severe sepsis and septic shock, showed a relative risk reduction of 0.34 and absolute risk reduction of 16%, with a decrease in healthcare resource consumption for patients presenting to the emergency department. Since then, similar studies have shown similar or better results. This study in particular highlights a hospital-wide initiative that further confirms that standardized order sets and operating procedures for severe sepsis and septic shock result in a significant reduction in morbidity, mortality and healthcare resource consumption. With these robust findings, future emphasis should be placed on overcoming logistical, institutional and professional barriers to the implementation of standardized order sets, which can save the life of one out of every five to six patients presenting with severe sepsis and septic shock. PMID:19883327

Rivers, Emanuel P; Coba, Victor; Rudis, Maria

2009-11-01

152

Sepsis reduces isoflurane MAC in a normotensive animal model of sepsis  

Microsoft Academic Search

Patients with sepsis often require anaesthesia for surgical procedures. Anaesthesia can be unpredictable and the most haemodynamically\\u000a stable agents are used. No data are available for the minimum alveolar concentration (MAC) requirements in such patients or\\u000a in animal models of sepsis. We have characterized the effect of sepsis on the MAC of isoflurane in a normotensive rodent model\\u000a of sepsis.

Ravi Gill; Claudio Martin; Ted McKinnon; Calvin Lain; David Cunningham; William J. Sibbald

1995-01-01

153

Surviving sepsis: going beyond the guidelines  

Microsoft Academic Search

The Surviving Sepsis Campaign is a global effort to improve the care of patients with severe sepsis and septic shock. The\\u000a first Surviving Sepsis Campaign Guidelines were published in 2004 with an updated version published in 2008. These guidelines\\u000a have been endorsed by many professional organizations throughout the world and come regarded as the standard of care for the\\u000a management

Paul E Marik

2011-01-01

154

HOST-PARASITE FACTORS IN GROUP A STREPTOCOCCAL INFECTIONS  

PubMed Central

The factors present in streptococcal lesion extracts (SLE) which enhanced the lethal and tissue-damaging properties of Gram-negative bacterial endotoxins and streptolysin O were identified with the scarlet fever group of toxins. Toxic manifestations attributed to this group of toxins included lethality, cardiotoxic and other tissue damage, enhancement of toxicity, and pyrogenicity. Of these, the measurement of febrile response in American Dutch rabbits was the most useful parameter of toxicity. In rabbits, repeated daily intravenous injections of 0.125 Lf of a purified erythrogenic toxin immunizes specifically against the pyrogenic activity; this technique was used to type the toxins and to distinguish them from exogenous and endogenous pyrogens; non-specific pyrogens, such as streptococcal endotoxin, were not found in SLE. All types of the Lancefield Group A streptococci tested produced one or or more immunologically distinct toxins in vivo in contrast to Groups B and C which did not produce them; toxins A and B, previously distinguished by neutralization of rash-inducing activity in the skin, were produced in vivo. The A toxin was the most common, as indicated by its presence in extracts prepared with Types 28, 12, 17, and 10 (NY-5); B toxin was found in 10 (NY-5) and 19. A new toxin, designated C, was obtained from a Type 18. In American Dutch rabbits, purified toxin at a concentration of 15 Lf (900,000 STD) neither gave a Dick test nor prepared the skin for the local Shwartzman reaction; by this route, however, in contrast to classical endotoxins, they enhance the lethal and tissue-damaging properties of sublethal doses of these and other toxins. These properties of the immunologic distinct exotoxins as demonstrated in American Dutch rabbits suggest by analogy their importance in the pathogenesis of streptococcal disease in man. Evidence that might implicate them in sequelae, in addition to scarlet fever, is discussed. PMID:13783427

Watson, Dennis W.

1960-01-01

155

[Massive intravascular hemolysis secondary to sepsis due to Clostridium perfringens].  

PubMed

Massive hemolysis secondary to sepsis caused by Clostridium perfringens is a rare entity but appears fairly often in the literature. In nearly all published reports, the clinical course is rapid and fatal. We describe the case of a 75-year-old woman with diabetes who was admitted with symptoms consistent with acute cholecystitis. Deteriorating hemodynamics and laboratory findings were consistent with intravascular hemolysis, coagulation disorder, and renal failure. Gram-positive bacilli of the Clostridium species were detected in blood along with worsening indicators of hemolysis. In spite of antibiotic and surgical treatment, hemodynamic support and infusion of blood products, the patient continued to decline and died in the postoperative recovery unit 14 hours after admission. Mortality ranges from 70% to 100% in sepsis due to Clostridium perfringens, and risk of death is greater if massive hemolysis is present, as in the case we report. Only a high degree of clinical suspicion leading to early diagnosis and treatment can improve the prognosis. This bacterium should therefore be considered whenever severe sepsis and hemolysis coincide. PMID:20527348

Pita Zapata, E; Sarmiento Penide, A; Bautista Guillén, A; González Cabano, M; Agulla Budiño, J A; Camba Rodríguez, M A

2010-05-01

156

Diagnosis and treatment of severe sepsis  

PubMed Central

The burden of infection in industrialized countries has prompted considerable effort to improve the outcomes of patients with sepsis. This has been formalized through the Surviving Sepsis Campaign 'bundles', derived from the recommendations of 11 professional societies, which have promoted global improvement in those practices whose primary goal it is to reduce sepsis-related death. However, difficulties remain in implementing all of the procedures recommended by the experts, despite the apparent pragmatism of those procedures. We summarize the main proposals made by the Surviving Sepsis Campaign and focus on the difficulties associated with making a proper diagnosis and supplying adequate treatment promptly to septic patients. PMID:18269689

Claessens, Yann-Erick; Dhainaut, Jean-Francois

2007-01-01

157

Heat incubation inactivates streptococcal exotoxins and recombinant cholesterol-dependent cytolysins: suilysin, pneumolysin and streptolysin o.  

PubMed

Streptococcus species release cholesterol-dependent cytolysins (CDCs), which are a main toxin, and their heat susceptibility is poorly understood. The aim of this study was to clarify the heat susceptibility of streptococcal exotoxins and CDCs. Streptococcal exotoxins were treated with heat incubation at 60 °C for 10 or 30 min. The Streptococcus suis exotoxin of serotypes 1 and 2 exhibited more than 50 % haemolytic activity, and all Streptococcus pneumoniae exotoxins exhibited more than 60 % haemolytic activity. During the thermolabile assay, the virulent streptococcal haemolytic activity remarkably decreased after being heated at 60 °C for 10 m. Then, streptococcal recombinant CDCs were produced and put through a thermolabile assay. The haemolytic activity of suilysin (SLY), pneumolysin (PLY) and streptolysin O (SLO) decreased more than 80 % after heat incubation. We also conducted a TER assay to evaluate the cell monolayer. The cell monolayer of all CDCs broke down, and the FITC-dextran translocated at 1 h post addition, while the CDCs treated with heating did not induce cell disruption. Moreover, the microscopy analysis demonstrated that CDCs treated with heating lost their activity. In conclusion, heat incubation induced the inactivation of streptococcal exotoxins and CDCs. Heat incubation plays a role in the degradation of the streptococcal exotoxin, and this result applies to the inhibition of streptococcal infection. PMID:24974216

Nakayama, T; Ezoe, K

2014-11-01

158

Il1-? involvement in cognitive impairment after sepsis.  

PubMed

Sepsis is defined as the host's reaction to infection and characterised by a systemic inflammatory response with important clinical implications. Central nervous system dysfunction secondary to sepsis is associated with local generation of pro- and anti-inflammatory cytokines, impaired cerebral microcirculation, an imbalance of neurotransmitters, apoptosis and cognitive impairment. It's known that the IL-1? is one of the first cytokines to be altered. Thus, the objective of this study was to evaluate the role of IL-1? in cognitive parameters in brain tissue through the use of an IL-1? (IL-1ra) receptor antagonist up to 10 days and to assess blood-brain barrier permeability, cytokine levels, oxidative parameters and energetic metabolism up to 24 h, after sepsis induction. To this aim, we used sham-operated Wistar rats or submitted to the cecal ligation and perforation (CLP) procedure. Immediately after, the animals received one dose of 10 ?g of IL-1ra. After 24 h, the rats were killed and were evaluated for biochemical parameters in the pre-frontal cortex, hippocampus and striatum. After 10 days, the animals were submitted to the habituation to the open field and step-down inhibitory avoidance task. We observed that the use of IL-1ra reverted the increase of blood-brain barrier permeability in the pre-frontal cortex, hippocampus and striatum; the increase of IL-1?, IL1-6 and TNF-? levels in the pre-frontal cortex and striatum; the decrease of complex I activity in the pre-frontal, hippocampus and striatum; the increase of oxidative parameters in pre-frontal cortex, hippocampus and striatum; and cognitive impairment. In conclusion, the results observed in this study reinforce the role of acute brain inflammatory response, in particular, the IL1? response, in the cognitive impairment associated with sepsis. PMID:24234155

Mina, Francielle; Comim, Clarissa M; Dominguini, Diogo; Cassol-Jr, Omar J; Dall Igna, Dhébora M; Ferreira, Gabriela K; Silva, Milena C; Galant, Leticia S; Streck, Emílio L; Quevedo, João; Dal-Pizzol, Felipe

2014-04-01

159

Anti-brain antibodies in PANDAS versus uncomplicated streptococcal infection.  

PubMed

The objective of this study was to assess brain involvement through the presence of antineuronal antibodies in Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus (PANDAS) and in uncomplicated active Group A streptococcal infection. We compared serum antibrain antibody to human basal ganglia sections assessed by indirect tissue immunofluorescence in two groups: a PANDAS group, comprised of 22 patients (mean age 10.1 years; 20 male, 2 female) who met strict National Institutes of Mental Health diagnostic criteria for PANDAS and had clinically active tics or obsessive-compulsive disorder, or both; and a GABHS control group consisting of 22 patients (mean age 9.1 years; 15 mol/L, 7 female) with clinical evidence of active Group A beta-hemolytic streptococcal (GABHS) infection confirmed by throat culture and elevated antistreptolysin O titers but without history or clinical evidence of tics or obsessive-compulsive disorder. We observed positive anti-basal ganglia staining (defined as detectable staining at 1:10 serum dilution) in 14/22 patients in the PANDAS group (64%) but only 2/22 (9%) in the GABHS control group (P < 0.001, Fisher's exact test). These results suggest that antibrain antibodies are present in children with PANDAS that cannot be explained merely by a history of GABHS infection. PMID:14984902

Pavone, Piero; Bianchini, Rio; Parano, Enrico; Incorpora, Gemma; Rizzo, Renata; Mazzone, Luigi; Trifiletti, Rosario R

2004-02-01

160

Laboratory diagnosis of intravascular catheter associated sepsis  

Microsoft Academic Search

Many different methods have been employed to aid in the laboratory diagnosis of intravascular catheter associated infection. However, because of differences in patient populations, the definition of catheter sepsis and types of catheters, comparison of these studies is difficult. Of even more fundamental importance, the question of the pathogenesis of intravascular catheter associated sepsis (i.e. whether the microorganisms migrate to

P. J. Collignon; R. Munro

1989-01-01

161

Improving the Odds of Surviving Sepsis  

MedlinePLUS

... Improving the Odds of Surviving Sepsis Inside Life Science View All Articles | Inside Life Science Home Page Improving the Odds of Surviving Sepsis ... Threatening Bacterial Infection Remains Mysterious This Inside Life Science article also appears on LiveScience . Learn about related ...

162

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

163

Sepsis  

MedlinePLUS

... updated August 2014 Share Print E-mail House Image Highlight Header Highlight Body Related Links Up to top This page last reviewed on August 18, 2014 Social Media Links Bookmark & Share Free Subscriptions Twitter Facebook YouTube ...

164

Long-term mortality after community-acquired sepsis: a longitudinal population-based cohort study  

PubMed Central

Objective Prior studies have concentrated on the acute short-term outcomes of sepsis, with little focus on its long-term consequences. The objective of this study was to characterise long-term mortality following a sepsis event. Design Population-based data from the 30?239 community-dwelling individuals in the REasons for Geographic and Racial Differences in Stroke (REGARDS) cohort. Setting USA. Participants Community-dwelling adults ?45?years of age. Sepsis was defined as hospitalisation or emergency department treatment for a serious infection with the presence of ?2 systemic inflammatory response syndrome criteria. Outcomes 6-year all-cause mortality. The analysis utilised a time-varying Cox model adjusted for participant's age, demographic factors, health behaviours and chronic medical conditions. Results The participants were observed for a median of 6.1?years (IQR 4.5–7.1). During this period, 975 individuals experienced a sepsis event. Sepsis hospital mortality was 8.9%. One-year, 2-year and 5-year all-cause mortality among individuals with sepsis were 23%, 28.8% and 43.8%, respectively, compared with death rates of 1%, 2.6% and 8.3% among those who never developed sepsis. On multivariable analysis, the association of sepsis with increased all-cause mortality persisted for up to 5?years, after adjustment for confounders; year 0.00–1.00, adjusted HR (aHR) 13.07 (95% CI 10.63 to 16.06); year 1.01–2.00 aHR 2.64 (1.85 to 3.77); year 2.01–3.00 aHR 2.18 (1.43 to 3.33); year 3.01–4.00 aHR 1.97 (1.19 to 3.25); year 4.01–5.00 aHR 2.08 (1.14 to 3.79); year 5.01+ aHR 1.41 (0.67 to 2.98). Conclusions Individuals with sepsis exhibited increased rates of death for up to 5?years after the illness event, even after accounting for comorbidities. Sepsis is independently associated with increased risk of mortality well after hospital treatment. PMID:24441058

Wang, Henry E; Szychowski, Jeff M; Griffin, Russell; Safford, Monika M; Shapiro, Nathan I; Howard, George

2014-01-01

165

Cerebral perfusion in sepsis-associated delirium  

PubMed Central

Introduction The pathophysiology of sepsis-associated delirium is not completely understood and the data on cerebral perfusion in sepsis are conflicting. We tested the hypothesis that cerebral perfusion and selected serum markers of inflammation and delirium differ in septic patients with and without sepsis-associated delirium. Methods We investigated 23 adult patients with sepsis, severe sepsis, or septic shock with an extracranial focus of infection and no history of intracranial pathology. Patients were investigated after stabilisation within 48 hours after admission to the intensive care unit. Sepsis-associated delirium was diagnosed using the confusion assessment method for the intensive care unit. Mean arterial pressure (MAP), blood flow velocity (FV) in the middle cerebral artery using transcranial Doppler, and cerebral tissue oxygenation using near-infrared spectroscopy were monitored for 1 hour. An index of cerebrovascular autoregulation was calculated from MAP and FV data. C-reactive protein (CRP), interleukin-6 (IL-6), S-100?, and cortisol were measured during each data acquisition. Results Data from 16 patients, of whom 12 had sepsis-associated delirium, were analysed. There were no significant correlations or associations between MAP, cerebral blood FV, or tissue oxygenation and sepsis-associated delirium. However, we found a significant association between sepsis-associated delirium and disturbed autoregulation (P = 0.015). IL-6 did not differ between patients with and without sepsis-associated delirium, but we found a significant association between elevated CRP (P = 0.008), S-100? (P = 0.029), and cortisol (P = 0.011) and sepsis-associated delirium. Elevated CRP was significantly correlated with disturbed autoregulation (Spearman rho = 0.62, P = 0.010). Conclusion In this small group of patients, cerebral perfusion assessed with transcranial Doppler and near-infrared spectroscopy did not differ between patients with and without sepsis-associated delirium. However, the state of autoregulation differed between the two groups. This may be due to inflammation impeding cerebrovascular endothelial function. Further investigations defining the role of S-100? and cortisol in the diagnosis of sepsis-associated delirium are warranted. Trial registration ClinicalTrials.gov NCT00410111. PMID:18457586

Pfister, David; Siegemund, Martin; Dell-Kuster, Salome; Smielewski, Peter; Ruegg, Stephan; Strebel, Stephan P; Marsch, Stephan CU; Pargger, Hans; Steiner, Luzius A

2008-01-01

166

Group a streptococcal toxic shock syndrome with severe necrotizing fasciitis following hysterectomy — a case report  

Microsoft Academic Search

In the last 10 years an increasing number of cases of group A streptococcal toxic shock syndrome have appeared in various\\u000a clinical settings. The manifestation of this syndrome includes rapidly progressive multiorgan failure and soft-tissue necrosis.\\u000a \\u000a This report presents a case of streptococcal toxic shock syndrome caused by Streptococcus pyogenes with severe necrotizing fasciitis of the abdominal wall following hysterectomy.

M. Loscar; G. Schelling; M. Haller; J. Polasek; C. Stoll; U. Kreimeier; U. Finsterer; J. Briegel; H. O. Steitz; R. Baumeister; R. Kimmig; B. Grabein

1998-01-01

167

Decreased plasma concentrations of apolipoprotein M in sepsis and systemic inflammatory response syndromes  

PubMed Central

Introduction Apolipoprotein M (apoM) is present in 5% of high-density lipoprotein (HDL) particles in plasma. It is a carrier of sphingosine-1-phosphate (S1P), which is important for vascular barrier protection. The aim was to determine the plasma concentrations of apoM during sepsis and systemic inflammatory response syndrome (SIRS) and correlate them to levels of apolipoprotein A-I (apoA1), apolipoprotein B (apoB), HDL-, and low-density lipoprotein (LDL)-cholesterol. Methods Plasma samples from patients with (1), severe sepsis with shock (n = 26); (2), severe sepsis without shock (n = 44); (3), sepsis (n = 100); (4), infections without SIRS (n = 43); and (5) SIRS without infection (n = 20) were analyzed. The concentrations of apoM, apoA1, and apoB were measured with enzyme-linked immunosorbent assays (ELISAs). Total, HDL-, and LDL-cholesterol concentrations were measured with a commercial HDL/LDL cholesterol test. Results ApoM concentrations correlated negatively to acute-phase markers. Thus, apoM behaved as a negative acute-phase protein. Decreased values were observed in all patient groups (P < 0.0001), with the most drastic decreases observed in the severely sick patients. ApoM levels correlated strongly to those of apoA1, apoB, HDL, and LDL cholesterol. The HDL and LDL cholesterol levels were low in all patient groups, as compared with controls (P < 0.0001), in particular, HDL cholesterol. ApoA1 and apoB concentrations were low only in the more severely affected patients. Conclusions During sepsis and SIRS, the plasma concentrations of apoM decrease dramatically, the degree of decrease reflecting the severity of the disease. As a carrier for barrier-protective S1P in HDL, the decrease in apoM could contribute to the increased vascular leakage observed in sepsis and SIRS. PMID:22512779

2012-01-01

168

Nephrilin peptide modulates a neuroimmune stress response in rodent models of burn trauma and sepsis  

PubMed Central

Sepsis occurs three times more often in burns than in other types of trauma, suggesting an overlap or synergy between underlying immune mechanisms in burn trauma and sepsis. Nephrilin peptide, a designed inhibitor of mTORC2, has previously been shown to modulate a neuroimmune stress response in rodent models of xenobiotic and metabolic stress. Here we investigate the effect of nephrilin peptide administration in different rodent models of burn trauma and sepsis. In a rat scald burn model, daily subcutaneous bolus injection of 4 mg/kg nephrilin significantly reduced the elevation of kidney tissue substance P, S100A9 gene expression, PMN infiltration and plasma inflammatory markers in the acute phase, while suppressing plasma CCL2 and insulin C-peptide, kidney p66shc-S36 phosphorylation and PKC-beta and CGRP in dorsal root ganglia at 14 days (chronic phase). In the mouse cecal ligation and puncture model of sepsis, nephrilin fully protected mice from mortality between surgery and day 7, compared to 67% mortality in saline-treated animals, while significantly reducing elevated CCL2 in plasma. mTORC2 may modulate important neuroimmune responses in both burn trauma and sepsis. PMID:24273694

Mascarenhas, Desmond D; ElAyadi, Amina; Singh, Baljit K; Prasai, Anesh; Hegde, Sachin D; Herndon, David N; Finnerty, Celeste C

2013-01-01

169

An interprofessional process to improve early identification and treatment for sepsis.  

PubMed

The course of sepsis is rapid. Patient outcomes improve when sepsis is diagnosed and treated quickly. The clinical goals of the evidence-based bundled strategies from the International consortium Surviving Sepsis Campaign (SSC) include optimizing timeliness in the delivery of care and creating a continuum for sepsis management that runs from the emergency department (ED) to the acute and critical care settings. Successful implementation of processes that integrate sepsis bundles can improve patient mortality and hospital costs. Improving interprofessional education and collaboration are necessary to facilitate the effective use of bundled strategies. An intervention that included interprofessional education resulted in a statistically significant difference between the three phases studied. There was a statistically significant improvement between the phases for lactate completion X(2) = 16.908 (p < .01) after education. Frequency of blood cultures being obtained before antibiotic administration was nearing statistical significance (p < .054). There was an improvement in time to antibiotic administration between phase 2 (182.09 mean average minutes, SD = 234.06) and phase 3 (91.62 mean average minutes, SD = 167.99). PMID:23534854

Palleschi, Maria Teresa; Sirianni, Susanna; O'Connor, Nancy; Dunn, Deborah; Hasenau, Susan M

2014-01-01

170

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

171

The changing immune system in sepsis  

PubMed Central

Sepsis remains the leading cause of death in most intensive care units. Advances in understanding the immune response to sepsis provide the opportunity to develop more effective therapies. The immune response in sepsis can be characterized by a cytokine-mediated hyper-inflammatory phase, which most patients survive, and a subsequent immune-suppressive phase. Patients fail to eradicate invading pathogens and are susceptible to opportunistic organisms in the hypo-inflammatory phase. Many mechanisms are responsible for sepsis-induced immuno-suppression, including apoptotic depletion of immune cells, increased T regulatory and myeloid-derived suppressor cells, and cellular exhaustion. Currently in clinical trial for sepsis are granulocyte macrophage colony stimulating factor and interferon gamma, immune-therapeutic agents that boost patient immunity. Immuno-adjuvants with promise in clinically relevant animal models of sepsis include anti-programmed cell death-1 and interleukin-7. The future of immune therapy in sepsis will necessitate identification of the immunologic phase using clinical and laboratory parameters as well as biomarkers of innate and adaptive immunity. PMID:24067565

Boomer, Jonathan S; Green, Jonathan M; Hotchkiss, Richard S

2014-01-01

172

Long-term cerebral consequences of sepsis.  

PubMed

Sepsis is a potentially fatal whole-body inflammatory state caused by severe infection, in which a maladaptive, system-wide inflammatory response follows initial attempts to eliminate pathogens, leading to a dangerous and often fatal increase in the permeability of the blood-brain barrier. These changes in the blood-brain barrier might lead to a major symptom of sepsis, sepsis-associated encephalopathy, which manifests as confusion with a rapid decline in cognitive functions, especially memory, or coma. Once presumed to be entirely reversible, research suggests that sepsis-associated encephalopathy could lead to permanent neurocognitive dysfunction and functional impairments, even after the patient has recovered. Sepsis might act as a major inflammatory hit and potentially increase the brain's susceptibility to neurodegenerative disease, further deterioration of cognitive ability, and risk of developing dementia in later life. Key opportunities for neuroprotective interventions and after-care for people who have survived sepsis might be lost because the long-term neurocognitive and functional consequences of sepsis are not fully characterised. PMID:24849863

Widmann, Catherine N; Heneka, Michael T

2014-06-01

173

Autoantibody germ-line gene segment encodes VH and VL regions of a human anti-streptococcal monoclonal antibody recognizing streptococcal M protein and human cardiac myosin epitopes.  

PubMed

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/anti-myosin 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 V kappa 1 gene segment that was 98.5% identical with germ-line gene humig kappa Vi5. The V segment of the heavy chain was encoded by a VH3a gene segment that differed from the VH26 germ-line gene by a single base change. VH26 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 VH and VL genes, with little or no somatic mutation. PMID:7706755

Quinn, A; Adderson, E E; Shackelford, P G; Carroll, W L; Cunningham, M W

1995-04-15

174

[Characteristics of group A streptococcal meningitis in children].  

PubMed

Group A streptococcal (GAS) meningitis in children are rare. The aim of this study was to analyze the clinical, biological and outcome data on GAS meningitis recorded in the Bacterial Meningitis (BM) French Surveillance Network (GPIP/ACTIV). From 2001 through 2012, 4,564 children suffering from proven bacterial meningitis were recorded in the data base. Among them, 0.7 % were GAS infections. The median age was 5.6 years. A history of community acquired infection before the onset of GAS meningitis was frequent. Apart from the identification of the bacterial species, GAS meningitis were clinically and biologically indistinguishable from meningitis caused by other pathogens notably S. pneumoniae. Case fatality rate was 8 %. PMID:25399491

Levy, C; Bidet, Ph; Bonacorsi, S; Béchet, S; Cohen, R

2014-11-01

175

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

176

Incident Stroke and Mortality Associated with New-onset Atrial Fibrillation in Patients Hospitalized with Severe Sepsis  

PubMed Central

Context New-onset fibrillation (AF) has been reported in 6–20% of patients with severe sepsis. Whereas chronic AF is a known risk factor for stroke and death, the clinical significance of new-onset AF in the setting of severe sepsis is uncertain. Objective To determine the in-hospital stroke and in-hospital mortality risks associated with new-onset AF in patients with severe sepsis. Design Retrospective population-based cohort of California State Inpatient Database administrative claims data from 1/1/2007 through 12/31/2007. Setting Non-Federal acute care hospitals. Patients Data was available from 3,144,787 hospitalized adults. Severe sepsis [N=49,082 (1.56%)] was defined by validated ICD-9-CM code 995.92. New-onset AF was defined as AF that occurred during the hospital stay, after excluding AF cases present at admission. Main Outcome Measures A priori outcome measures were in-hospital ischemic stroke (ICD-9-CM codes of 433, 434, or 436) and mortality. Results Patients with severe sepsis were 69±16 years old and 48% were women. New-onset atrial fibrillation occurred in 5.9% of patients with severe sepsis versus 0.6% of patients without severe sepsis [multivariable-adjusted odds ratio (OR), 6.82; 95% confidence interval (CI), 6.54–7.11; P<0.001]. Severe sepsis was present in 14% of all new-onset AF in hospitalized adults. Compared with severe sepsis patients without new-onset AF, patients with new-onset AF during severe sepsis had greater risks of in-hospital stroke (75/2896 (2.6%) vs. 306/46186 (0.6%) strokes, adjusted OR 2.70; 95% CI, 2.05–3.57; P <0.0001) and in-hospital mortality (1629 (56%) vs. 18027 (39%) deaths, adjusted relative risk, 1.07; 95% CI, 1.04–1.11; P <0.0001). Findings were robust across two definitions of severe sepsis, multiple methods of addressing confounding, and multiple sensitivity analyses. Conclusion Among patients with severe sepsis, patients with new-onset AF were at increased risk for in-hospital stroke and death compared with patients with no AF and patients with pre-existing AF. PMID:22081378

Walkey, Allan J.; Wiener, Renda Soylemez; Ghobrial, Joanna M.; Curtis, Lesley H.; Benjamin, Emelia J.

2012-01-01

177

Peptide-based treatment of sepsis  

Microsoft Academic Search

Sepsis (blood poisoning) is a severe infectious disease with high mortality, and no effective therapy is actually known. In\\u000a the case of Gram-negative bacteria, endotoxins (lipopolysaccharides) are known to be responsible for the strong inflammation\\u000a reaction leading to the systemic infection. Peptides based on endotoxin-binding domains of human or animal proteins represent\\u000a a promising approach in sepsis research. Although so

Klaus Brandenburg; Jörg Andrä; Patrick Garidel; Thomas Gutsmann

2011-01-01

178

Procalcitonin as a Predictor of Sepsis and Outcome in Severe Trauma Patients: A Prospective Study  

PubMed Central

Introduction: Despite the advances in medical sciences, the morbidity and mortality due to sepsis in severe trauma patients remains high; hence the need for early and accurate diagnosis. Very few prospective studies are available in a country like India, which tried to analyze the prediction of sepsis using serum procalcitonin (PCT) in such a large scale among trauma patients. This study explores the role of the biomarker PCT in early diagnosis of sepsis and prediction of outcomes in severe trauma cases. Materials and Methods: We studied the patient population prospectively in two different groups. One with acute trauma but no clinical evidence of sepsis and the second group with clinical evidence of sepsis and are followed. Bronchoalveolar lavage, tracheal aspirates, pus, urine, body fluids from sterile body sites, etc., were collected including blood for culture and serum for PCT assays. Such assays were done on samples collected on days 1 and 4 and then compared. Additionally, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) levels were also tested. Antimicrobial sensitivity tests were carried out for all the isolates from the clinical samples and correlated with the clinically suspected cases of sepsis. Outcomes of the patients were noted. Results: Patients with high initial PCT levels (>2 ng/ml) in severe trauma cases had poor outcomes and risk of developing complications. Its correlation with severe outcomes was better marked as compared with CRP and ESR levels. The difference in PCT levels between days 1 and 4 in group two patients was statistically significant (P = 0.006) but were not statistically significant for CRP (P = 0.646) and ESR (P = 0.935). The study also shows that PCT levels fall in response to appropriate antimicrobial treatment. Conclusion: PCT is a useful biomarker for early and accurate prediction of sepsis in severe trauma patients. If used in adjunct to clinical findings, it proves to be a good biomarker for early diagnosis, treatment and for monitoring response to therapy in confirmed cases of sepsis. It will prove to be a good supportive indicator of sepsis in early stages for the trauma patients in a low resource country like India. PMID:24701102

Rajkumari, Nonika; Mathur, Purva; Sharma, Satyapriya; Gupta, Babita; Bhoi, Sanjeev; Misra, Mahesh C

2013-01-01

179

Persistent inflammation and T cell exhaustion in severe sepsis in the elderly  

PubMed Central

Introduction Sepsis is known as a complex immunological response with hyperinflammation in the acute phase followed by immunosuppression. Although aging is crucial in sepsis, the impact of aging on inflammation and immunosuppression is still unclear. The purpose of this study was to investigate the relationship between inflammation and immunosuppression in aged patients and mice after sepsis. Methods Fifty-five patients with severe sepsis and 30 healthy donors were prospectively enrolled, and 90-day survival was compared between elderly (?65 years) and adult (18–64 years) septic patients with serial measurement of serum interleukin (IL)-6. Within 24 h after diagnosis of severe sepsis, peripheral blood mononuclear cells were stimulated ex vivo to measure expression of the activation maker CD25 in T cells, IL-2 levels in the supernatant, and proliferation. In the mouse study, young (6–8 weeks) and aged (20–22 months) C57/B6 mice were subjected to cecal ligation and puncture (CLP), and survival was compared after 7 days with serial measurement of serum IL-6. Expression of the negative co-stimulatory molecules, CD25, and IL-2 in CD4+ T cells was measured. Results The survival rate in elderly sepsis patients and aged septic mice was significantly lower than that in adult patients and young septic mice (60% vs. 93% in septic patients, 0% vs. 63% in septic mice, P?sepsis patients and aged septic mice were persistently higher than those in adult patients and young septic mice. Expression of negative co-stimulatory molecules in CD4+ T cells in the spleen, lymph nodes, and peripheral blood was significantly higher in aged mice than in young mice (P?sepsis (P?sepsis. PMID:24962182

2014-01-01

180

Apolipoprotein M - a new biomarker in sepsis  

PubMed Central

Sepsis is one of the leading causes of mortality in non-cardiac intensive care units, and the need for markers of progression and severity are high. Also, treatment of sepsis is highly debated and potential new targets of treatment are of great interest. In the previous issue of Critical Care Kumaraswamy and colleagues have investigated whether plasma apolipoprotein M (apoM) is affected during different grades of sepsis, septic shock and systemic inflammatory response syndrome. Interestingly, plasma apoM was significantly decreased in all groups of patients with a relationship to severity of disease. This identifies apoM as a potential new biomarker in sepsis. It also underscores the possibility that altered high-density lipoprotein in sepsis patients can affect the course of disease. Thus, since apoM is the carrier of Sphingosine-1-P (S1P), a molecule with great influence on vascular barrier function, the study presented raises the interest and relevance for further studies of apoM and S1P in relation to sepsis and inflammation. PMID:22587809

2012-01-01

181

Target blood pressure in sepsis: between a rock and a hard place  

PubMed Central

The optimal target blood pressure in septic shock is still unknown. Therefore, in a long-term, resuscitated porcine model of fecal peritonitis-induced septic shock, Corrêa and colleagues tested whether different titrations of mean arterial pressure (50 to 60 and 75 to 85 mm Hg) would produce different effects on sepsis-related organ dysfunction. The higher blood pressure window was associated with increased needs for fluid resuscitation and norepinephrine support. However, titrating the lower blood pressure range coincided with an increased incidence of acute kidney injury. In contrast, neither the inflammatory response nor tissue mitochondrial activity showed any difference. This research paper in a clinically relevant model elegantly demonstrates that any standard resuscitation strategy may be a double-edged sword with respect to various therapeutic endpoints. Furthermore, it adds an important piece to the puzzle of the complex pathophysiology of sepsis-related acute kidney injury. PMID:23534963

2013-01-01

182

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

183

Drotrecogin Alfa (Activated) for Adults with Severe Sepsis and a Low Risk of Death  

Microsoft Academic Search

methods We randomly assigned adult patients with severe sepsis and a low risk of death (defined by an Acute Physiology and Chronic Health Evaluation (APACHE II) score <25 or single- organ failure) to receive an intravenous infusion of placebo or DrotAA (24 µ g per kilo- gram of body weight per hour) for 96 hours in a double-blind, placebo-controlled, mul-

Edward Abraham; Pierre-François Laterre; Rekha Garg; Howard Levy; Deepak Talwar; Benjamin L. Trzaskoma; Bruno François; Jeffrey S. Guy; Martina Brückmann; Álvaro Rea-Neto; Rolf Rossaint; Dominique Perrotin; Armin Sablotzki; Nancy Arkins; Barbara G. Utterback; William L. Macias

2005-01-01

184

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

185

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

186

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

187

Clostridium perfringens Sepsis and Fetal Demise after Genetic Amniocentesis  

PubMed Central

Clostridium perfringens is a rare cause of intrauterine infection. There have been five case reports concerning infection associated with invasive procedures. We report a woman who underwent a genetic amniocentesis due to her history of chronic granulomatous disease. She presented to the hospital ?38 hours after the amniocentesis complaining of fever and chills. Due to acute decompensation, she underwent an emergent dilatation and evacuation. During her stay, blood cultures came back positive for C. perfringens. Gradual improvement with intensive monitoring led to hospital discharge 4 days after the procedure. Uterine infection due to C. perfringens leading to maternal sepsis is associated with a high morbidity and mortality rate. Our patient was able to survive without a hysterectomy due to the rapid administration of antibiotics and surgical intervention while being evaluated. PMID:23705080

Hendrix, Nancy W.; Mackeen, A. Dhanya; Weiner, Stuart

2011-01-01

188

Clinical course of sepsis, severe sepsis, and septic shock in a cohort of infected patients from ten Colombian hospitals  

PubMed Central

Background Sepsis has several clinical stages, and mortality rates are different for each stage. Our goal was to establish the evolution and the determinants of the progression of clinical stages, from infection to septic shock, over the first week, as well as their relationship to 7-day and 28-day mortality. Methods This is a secondary analysis of a multicenter cohort of inpatients hospitalized in general wards or intensive care units (ICUs). The general estimating equations (GEE) model was used to estimate the risk of progression and the determinants of stages of infection over the first week. Cox regression with time-dependent covariates and fixed covariates was used to determine the factors related with 7-day and 28-day mortality, respectively. Results In 2681 patients we show that progression to severe sepsis and septic shock increases with intraabdominal and respiratory sources of infection [OR?=?1,32; 95%IC?=?1,20-1,46 and OR?=?1.21, 95%CI?=?1,11-1,33 respectively], as well as according to Acute Physiology and Chronic Health Evaluation II (APACHE II) [OR?=?1,03; 95%CI?=?1,02-1,03] and Sequential Organ Failure Assessment (SOFA) [OR?=?1,16; 95%CI?=?1,14-1,17] scores. The variables related with first-week mortality were progression to severe sepsis [HR?=?2,13; 95%CI?=?1,13-4,03] and septic shock [HR?=?3,00; 95%CI?=?1,50-5.98], respiratory source of infection [HR?=?1,76; 95%IC?=?1,12-2,77], APACHE II [HR?=?1,07; 95% CI?=?1,04-1,10] and SOFA [HR?=?1,09; 95%IC?=?1,04-1,15] scores. Conclusions Intraabdominal and respiratory sources of infection, independently of SOFA and APACHE II scores, increase the risk of clinical progression to more severe stages of sepsis; and these factors, together with progression of the infection itself, are the main determinants of 7-day and 28-day mortality. PMID:23883312

2013-01-01

189

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, Eliezer; Pedro, Marcelo de Almeida; Sogayar, Ana Cristina Beltrami; Mohovic, Tatiana; Silva, Carla Lika de Oliveira; Janiszewski, Mariano; Cal, Ruy Guilherme Rodrigues; de Sousa, Erica Fernandes; Abe, Thereza Phitoe; de Andrade, Joel; de Matos, Jorge Dias; Rezende, Ederlon; Assuncao, Murillo; Avezum, Alvaro; Rocha, Patricia CS; de Matos, Gustavo Faissol Janot; Bento, Andre Moreira; Correa, Alice Danielli; Vieira, Paulo Cesar Bastos; Knobel, Elias

2004-01-01

190

[Management of severe invasive group A streptococcal infections].  

PubMed

The group A streptococcus (GAS) is the 5(th) responsible pathogen of invasive infections in children in France. These particularly severe diseases are dominated in children by soft tissue infection, isolated bacteremia but also osteoarthritis. Other complications are rare in France such as lung infections, necrotizing fasciitis (NF) and streptococcal toxic shock syndrome (STSS). More unusual localizations such as meningitis, neonatal infections, severe ear and throat and gastrointestinal infections and vascular disorders are also described. Based on published series, mortality ranging from 0-8 % of cases, is high but still lower than that observed in adults. Probabilistic antibiotherapy includes a ?-lactam with anti-SGA but also anti-staphylococcal (predominantly methi-S in France) activity such as clavulanic acid- amoxicillin followed by amoxicillin as soon as identification of SGA is performed. The addition of an anti-toxin antibiotic such as clindamycin is recommended particularly in NF or STSS or clinical signs suggestive of toxin production by the SGA (rash, gastrointestinal signs, hemodynamic disorders). The use of intravenous polyvalent immunoglobulins must also be discussed in NF and STSS. In all cases surgery should be discussed. The prognosis of these potentially very severe infections is related to their early diagnosis and treatment. A better understanding of the pathophysiology of these infections may optimize their management but also their prevention. PMID:25399501

Faye, A; Lorrot, M; Bidet, Ph; Bonacorsi, S; Cohen, R

2014-11-01

191

Maternal ?-Hemolytic Streptococcal Pharyngeal Exposure and Colonization in Pregnancy  

PubMed Central

Objectives. To report the pharyngeal colonization rate of ?-hemolytic streptococci and changes in the value of antistreptolysin O (ASO) and anti-DNase B serology titers during pregnancy. Methods. Healthy pregnant women were recruited and blood was drawn in each trimester. The upper limit of normal (ULN) values for ASO and anti-DNase B was calculated for each trimester. Throat swabs were collected for culture and positive cultures were further assessed for the identification of serogroup of the isolated ?-hemolytic streptococcus. Results. Out of a total of 126 pregnant women, 34.1% had positive throat cultures. Group C and group G strains were isolated in 18.2% of throat cultures while group F was detected in 13.5% of cases. The rate of colonization with GAS was 1.6%. There was an overall drop in ASO titer during pregnancy while anti-DNase B titers remained relatively unchanged. ULN values of 164IU, 157IU, and 156IU were calculated for ASO at the first, second, and third trimesters, respectively. Based on the ULN values, 28.6% of patients had recent streptococcal exposure. Conclusions. These results show that pregnant women act as a reservoir for spreading potentially immunogenic (groups C and G) and disease producing (group F) virulent strains of streptococci.

Brar, Anoop K.; Hathcock, Trupti; Cunningham, Madeleine W.; Eghtesady, Pirooz

2014-01-01

192

A novel streptococcal integrative conjugative element involved in iron acquisition  

PubMed Central

In this study, we determined the function of a novel non-ribosomal peptide synthetase (NRPS) system carried by a streptococcal integrative conjugative element (ICE), ICESe2. The NRPS shares similarity with the yersiniabactin system found in the high-pathogenicity island of Yersinia sp. and is the first of its kind to be identified in streptococci. We named the NRPS product ‘equibactin’ and genes of this locus eqbA–N. ICESe2, although absolutely conserved in Streptococcus equi, the causative agent of equine strangles, was absent from all strains of the closely related opportunistic pathogen Streptococcus zooepidemicus. Binding of EqbA, a DtxR-like regulator, to the eqbB promoter was increased in the presence of cations. Deletion of eqbA resulted in a small-colony phenotype. Further deletion of the irp2 homologue eqbE, or the genes eqbH, eqbI and eqbJ encoding a putative ABC transporter, or addition of the iron chelator nitrilotriacetate, reversed this phenotype, implicating iron toxicity. Quantification of 55Fe accumulation and sensitivity to streptonigrin suggested that equibactin is secreted by S. equi and that the eqbH, eqbI and eqbJ genes are required for its associated iron import. In agreement with a structure-based model of equibactin synthesis, supplementation of chemically defined media with salicylate was required for equibactin production. PMID:18990191

Heather, Zoe; Holden, Matthew T G; Steward, Karen F; Parkhill, Julian; Song, Lijiang; Challis, Gregory L; Robinson, Carl; Davis-Poynter, Nicholas; Waller, Andrew S

2008-01-01

193

Identification of conserved antigens from staphylococcal and streptococcal pathogens.  

PubMed

The design of vaccines containing epitopes shared between different human pathogens may lead to cross-species protection. In order to identify potentially conserved bacterial antigens, bacteriophage expression libraries of genomic DNA from Streptococcus agalactiae, Streptococcus pneumoniae and Streptococcus pyogenes were probed with human sera from Staphylococcus aureus-infected and healthy individuals. By comparison with previous screening data from Staphylococcus epidermidis and Staph. aureus, putative antigenic, conserved domains across the genera were identified. In particular, three potentially antigenic conserved regions were identified based on the N-terminal domain of SACOL0609 (SdrD), the C-terminal domain of SACOL0723 (ScaB) and the C-terminus of SACOL1140 (IsdA) from Staph. aureus. The three domains were overexpressed, recombinant proteins were purified and polyclonal antisera raised against them recognized cell surface-located proteins from both staphylococcal and streptococcal species. The antisera were also able to opsonize both Staph. aureus and Strep. agalactiae thereby increasing their phagocytic uptake by human neutrophils. The conserved antigenic domains therefore represent potential cross-protective vaccine candidates. PMID:22345598

Stapleton, Melanie R; Wright, Lynda; Clarke, Simon R; Moseby, Hilde; Tarkowski, Andrej; Vendrengh, Margareta; Foster, Simon J

2012-06-01

194

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

195

Case report: group B streptococcal bacteremia and sacroiliitis after mid-trimester dilation and evacuation.  

PubMed

Group B streptococcal bacteremia with septic arthritis is a rare complication of second trimester dilation and evacuation, and may cause substantial post-operative morbidity. A 37-year-old gravida 4 para 1-0-2-1 presented with fever and right hip pain on post-operative day 11 from a second trimester dilation and evacuation for fetal trisomy 21. She was initially found to have septic arthritis involving the right sacroiliac joint and group B streptococcal bacteremia. Transesophageal echocardiogram showed a tricuspid valve, vegetation consistent with endocarditis. After prolonged parenteral antibiotic therapy, she developed septic pulmonary emboli that were successfully treated with anticoagulation therapy. Group B streptococcal infection is a potentially serious post-abortion complication that can cause sacroiliitis, endocarditis and septic pulmonary emboli. PMID:19710658

McKenna, T; O'Brien, K

2009-09-01

196

[Neonatal group A streptococcal meningitis and portal vein thrombosis: A casual association?].  

PubMed

Invasive group A streptococcal infections are potentially serious. The occurrence in the neonatal period and meningeal location are two unusual situations. The complications reported in the literature vary; we add the risk of thromboembolic events. We report the case of a newborn, admitted to our department at 22 days of life for late neonatal group A streptococcal meningitis and diffuse cerebral infarction lesions. Ultrasound and abdominal CT scan objectified the presence of portal vein thrombosis and cavernoma. Echocardiography, electrocardiogram, as well as coagulation and thrombophilia tests were normal. Progression was marked by the installation of cerebral atrophy and ventricular dilation without the appearance of signs of portal hypertension over 18months. We therefore concluded in neonatal group A streptococcal meningitis complicated by multiple thrombosis that can be explained by the invasive properties and hypercoagulability characterizing group A beta-hemolytic streptococcus. However, the characteristics of the fetal circulation may explain the possibility of paradoxical cerebral embolism from portal thrombosis. PMID:25089040

Hmami, F; Oulmaati, A; Mahmoud, M; Boubou, M; Tizniti, S; Bouharrou, A

2014-09-01

197

The pulmonary endothelial glycocalyx regulates neutrophil adhesion and lung injury during experimental sepsis.  

PubMed

Sepsis, a systemic inflammatory response to infection, commonly progresses to acute lung injury (ALI), an inflammatory lung disease with high morbidity. We postulated that sepsis-associated ALI is initiated by degradation of the pulmonary endothelial glycocalyx, leading to neutrophil adherence and inflammation. Using intravital microscopy, we found that endotoxemia in mice rapidly induced pulmonary microvascular glycocalyx degradation via tumor necrosis factor-? (TNF-?)-dependent mechanisms. Glycocalyx degradation involved the specific loss of heparan sulfate and coincided with activation of endothelial heparanase, a TNF-?-responsive, heparan sulfate-specific glucuronidase. Glycocalyx degradation increased the availability of endothelial surface adhesion molecules to circulating microspheres and contributed to neutrophil adhesion. Heparanase inhibition prevented endotoxemia-associated glycocalyx loss and neutrophil adhesion and, accordingly, attenuated sepsis-induced ALI and mortality in mice. These findings are potentially relevant to human disease, as sepsis-associated respiratory failure in humans was associated with higher plasma heparan sulfate degradation activity; moreover, heparanase content was higher in human lung biopsies showing diffuse alveolar damage than in normal human lung tissue. PMID:22820644

Schmidt, Eric P; Yang, Yimu; Janssen, William J; Gandjeva, Aneta; Perez, Mario J; Barthel, Lea; Zemans, Rachel L; Bowman, Joel C; Koyanagi, Dan E; Yunt, Zulma X; Smith, Lynelle P; Cheng, Sara S; Overdier, Katherine H; Thompson, Kathy R; Geraci, Mark W; Douglas, Ivor S; Pearse, David B; Tuder, Rubin M

2012-08-01

198

Group G streptococcal bacteremia: clinical study and review of the literature.  

PubMed

Patients with group G streptococcal bactermia represented 10.8% of those with beta-hemolytic streptococcal bacteremia and 0.3% of all those with bacteremia between 1970 and 1980 at Mayo Clinic-affiliated hospitals. The most frequent portal of entry was the skin, usually in cases with preexisting edema due to previous surgical removal, irradiation, or tumor infiltration of lymph nodes, or to chronic venous insufficiency. The majority of these patients had underlying hematologic malignancies or solid tumors. Clinical response to therapy with beta-lactam antibiotics was rapid. PMID:6844802

Auckenthaler, R; Hermans, P E; Washington, J A

1983-01-01

199

Current concept of abdominal sepsis: WSES position paper  

PubMed Central

Although sepsis is a systemic process, the pathophysiological cascade of events may vary from region to region. Abdominal sepsis represents the host’s systemic inflammatory response to bacterial peritonitis. It is associated with significant morbidity and mortality rates, and is the second most common cause of sepsis-related mortality in the intensive care unit. The review focuses on sepsis in the specific setting of severe peritonitis. PMID:24674057

2014-01-01

200

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

Microsoft Academic Search

Objective  To provide an update to the original Surviving Sepsis Campaign clinical management guidelines, “Surviving Sepsis Campaign\\u000a guidelines for management of severe sepsis and septic shock,” published in 2004.\\u000a \\u000a \\u000a \\u000a Design  Modified Delphi method with a consensus conference of 55 international experts, several subsequent meetings of subgroups and\\u000a key individuals, teleconferences, and electronic-based discussion among subgroups and among the entire committee. This process\\u000a was

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

2008-01-01

201

Clinical score and rapid antigen detection test to guide antibiotic use for sore throats: randomised controlled trial of PRISM (primary care streptococcal management)  

PubMed Central

Objective To determine the effect of clinical scores that predict streptococcal infection or rapid streptococcal antigen detection tests compared with delayed antibiotic prescribing. Design Open adaptive pragmatic parallel group randomised controlled trial. Setting Primary care in United Kingdom. Patients Patients aged ?3 with acute sore throat. Intervention An internet programme randomised patients to targeted antibiotic use according to: delayed antibiotics (the comparator group for analyses), clinical score, or antigen test used according to clinical score. During the trial a preliminary streptococcal score (score 1, n=1129) was replaced by a more consistent score (score 2, n=631; features: fever during previous 24 hours; purulence; attends rapidly (within three days after onset of symptoms); inflamed tonsils; no cough/coryza (acronym FeverPAIN). Outcomes Symptom severity reported by patients on a 7 point Likert scale (mean severity of sore throat/difficulty swallowing for days two to four after the consultation (primary outcome)), duration of symptoms, use of antibiotics. Results For score 1 there were no significant differences between groups. For score 2, symptom severity was documented in 80% (168/207 (81%) in delayed antibiotics group; 168/211 (80%) in clinical score group; 166/213 (78%) in antigen test group). Reported severity of symptoms was lower in the clinical score group (?0.33, 95% confidence interval ?0.64 to ?0.02; P=0.04), equivalent to one in three rating sore throat a slight versus moderate problem, with a similar reduction for the antigen test group (?0.30, ?0.61 to ?0.00; P=0.05). Symptoms rated moderately bad or worse resolved significantly faster in the clinical score group (hazard ratio 1.30, 95% confidence interval 1.03 to 1.63) but not the antigen test group (1.11, 0.88 to 1.40). In the delayed antibiotics group, 75/164 (46%) used antibiotics. Use of antibiotics in the clinical score group (60/161) was 29% lower (adjusted risk ratio 0.71, 95% confidence interval 0.50 to 0.95; P=0.02) and in the antigen test group (58/164) was 27% lower (0.73, 0.52 to 0.98; P=0.03). There were no significant differences in complications or reconsultations. Conclusion Targeted use of antibiotics for acute sore throat with a clinical score improves reported symptoms and reduces antibiotic use. Antigen tests used according to a clinical score provide similar benefits but with no clear advantages over a clinical score alone. Trial registration ISRCTN32027234 PMID:24114306

2013-01-01

202

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

203

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

204

The mitochondria-targeted antioxidant MitoQ protects against organ damage in a lipopolysaccharide-peptidoglycan model of sepsis.  

PubMed

Sepsis is characterised by a systemic dysregulated inflammatory response and oxidative stress, often leading to organ failure and death. Development of organ dysfunction associated with sepsis is now accepted to be due at least in part to oxidative damage to mitochondria. MitoQ is an antioxidant selectively targeted to mitochondria that protects mitochondria from oxidative damage and which has been shown to decrease mitochondrial damage in animal models of oxidative stress. We hypothesised that if oxidative damage to mitochondria does play a significant role in sepsis-induced organ failure, then MitoQ should modulate inflammatory responses, reduce mitochondrial oxidative damage, and thereby ameliorate organ damage. To assess this, we investigated the effects of MitoQ in vitro in an endothelial cell model of sepsis and in vivo in a rat model of sepsis. In vitro MitoQ decreased oxidative stress and protected mitochondria from damage as indicated by a lower rate of reactive oxygen species formation (P=0.01) and by maintenance of the mitochondrial membrane potential (P<0.005). MitoQ also suppressed proinflammatory cytokine release from the cells (P<0.05) while the production of the anti-inflammatory cytokine interleukin-10 was increased by MitoQ (P<0.001). In a lipopolysaccharide-peptidoglycan rat model of the organ dysfunction that occurs during sepsis, MitoQ treatment resulted in lower levels of biochemical markers of acute liver and renal dysfunction (P<0.05), and mitochondrial membrane potential was augmented (P<0.01) in most organs. These findings suggest that the use of mitochondria-targeted antioxidants such as MitoQ may be beneficial in sepsis. PMID:18845241

Lowes, Damon A; Thottakam, Bensita M V; Webster, Nigel R; Murphy, Michael P; Galley, Helen F

2008-12-01

205

Positive effect of septimeb(TM) 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

206

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

207

Teicoplanin-induced neutropenic sepsis mimicking endocarditis.  

PubMed

Teicoplanin is a less toxic replacement for vancomycin in most situations where resistant organisms are encountered, and is therefore the drug of choice. As a commonly used drug in cardiac surgery, we treated a case of presumptive endocarditis with teicoplanin that caused neutropenic sepsis, unmasked on withdrawal of treatment. PMID:22879557

Booth, Karen; Parissis, Haralambos

2012-08-01

208

[Management of severe sepsis and septic shock].  

PubMed

Severe sepsis and septic shock are systemic manifestations of the host response to infection. Mortality remains high despite advances in pathophysiological knowledge. Hemodynamic and respiratory management is largely supportive, while early antibiotics administration and source of infection's control are crucial for patient outcome. We review the principles guiding the initial management of these patients in emergency situation. PMID:25199223

Cuche, Antoine; Rutz, Paul; Trueb, Lionel

2014-08-13

209

Angiopoietin-1 variant reduces LPS-induced microvascular dysfunction in a murine model of sepsis  

PubMed Central

Introduction Severe sepsis is characterised by intravascular or extravascular infection with microbial agents, systemic inflammation and microcirculatory dysfunction, leading to tissue damage, organ failure and death. The growth factor angiopoietin (Ang-1) has therapeutic potential but recombinant Ang-1 tends to aggregate and has a short half-life in vivo. This study aimed to investigate the acute effects of the more stable Ang-1 variant matrilin-1-angiopoietin-1 (MAT.Ang-1) on the function of the microcirculation in an experimental model of sepsis, and whether any protection by MAT-Ang-1 was associated with modulation of inflammatory cytokines, angiogenic factors or the endothelial nitric oxide synthase (eNOS)-Akt and vascular endothelial (VE)-cadherin pathways. Methods Aluminium window chambers were implanted into the dorsal skinfold of male C3H/HeN mice (7 to 10 weeks old) to expose the striated muscle microcirculation. Endotoxemia was induced by intraperitoneal injection of lipopolysaccharide (LPS, 1 mg/kg at 0 and 19 hours). MAT.Ang-1 was administered intravenously 20 hours after the onset of sepsis. Microcirculatory function was evaluated by intravital microscopy and Doppler fluximetry. Results Endotoxemia resulted in macromolecular leak, which was ameliorated by MAT.Ang-1 post-treatment. LPS induced a dramatic reduction in tissue perfusion, which was improved by MAT.Ang-1. Proteome profiler array analysis of skeletal muscle also demonstrated increased inflammatory and reduced angiogenic factors during endotoxemia. MAT.Ang-1 post-treatment reduced the level of IL-1? but did not significantly induce the expression of angiogenic factors. MAT.Ang-1 alone did not induce leak or increase angiogenic factors but did reduce vascular endothelial growth factor expression in controls. Conclusion Administration of MAT.Ang-1 after the onset of sepsis protects the microcirculation from endotoxemia-induced vascular dysfunction through reducing inflammation but without pro-angiogenic actions, thus representing a novel, potential pharmacotherapeutic agent for the treatment of sepsis. PMID:23036162

2012-01-01

210

Severe sepsis: Low expression of the renin-angiotensin system is associated with poor prognosis  

PubMed Central

Severe sepsis has a high fatality rate, but no clinical indices for prognosis have been established. In recent years, the renin-angiotensin system (RAS) has received considerable attention. However, clinical data on RAS are inconsistent. Therefore, the aim of the present study was to assess the significance of RAS in the prognosis of sepsis. Blood samples were collected from patients, who met the diagnostic criteria of severe sepsis, on day 1 (D1) and 3 (D3). For each sample, the levels of angiotensin II (AngII), angiotensin-converting enzyme (ACE) and additional indices were measured. Patients were monitored for 28 days. On the D1 of inclusion, the average Acute Physiology and Chronic Health Evaluation II (APACHE II) score was 22.2 and the Sepsis-related Organ Failure Assessment (SOFA) score was 6.1. Logistic regression analysis revealed that mortality-associated variables included the APACHE II score on D1, the SOFA score on D1, high lactic acid levels on D3 and low AngII and ACE levels on D1 and D3. AngII levels (<86.1 ng/ml) on D1 had a sensitivity of 88.2% and specificity of 77.3% for predicting mortality. ACE levels (<39.2 ng/ml) on D1 had a sensitivity of 88.2% and specificity of 72.7% for predicting mortality. These two indices were better than the APACHE II and SOFA scores. Therefore, low expression levels of AngII and ACE are valuable in predicting the mortality of patients with severe sepsis. PMID:24940436

ZHANG, WEI; CHEN, XIAOWEI; HUANG, LING; LU, NING; ZHOU, LEI; WU, GUOJIE; CHEN, YUGUO

2014-01-01

211

Traditional Chinese Medicine Diagnosis “Yang-Xu Zheng”: Significant Prognostic Predictor for Patients with Severe Sepsis and Septic Shock  

PubMed Central

Pathogenesis of sepsis includes complex interaction between pathogen activities and host response, manifesting highly variable signs and symptoms, possibly delaying diagnosis and timely life-saving interventions. This study applies traditional Chinese medicine (TCM) Zheng diagnosis in patients with severe sepsis and septic shock to evaluate its adaptability and use as an early predictor of sepsis mortality. Three-year prospective observational study enrolled 126 septic patients. TCM Zheng diagnosis, Acute Physiology and Chronic Health Evaluation (APACHE) II score, and blood samples for host response cytokines measurement (tumor necrosis factor-?, Interleukin-6, Interleukin-8, Interleukin-10, Interleukin-18) were collected within 24 hours after admission to Intensive Care Unit. Main outcome was 28-day mortality; multivariate logistic regression analysis served to determine predictive variables of the sepsis mortality. APACHE II score, frequency of Nutrient-phase heat, and Qi-Xu and Yang-Xu Zhengs were significantly higher in nonsurvivors. The multivariate logistic regression analysis identified Yang-Xu Zheng as the outcome predictor. APACHE II score and levels of five host response cytokines between patients with and without Yang-Xu Zheng revealed significant differences. Furthermore, cool extremities and weak pulse, both diagnostic signs of Yang-Xu Zheng, were also proven independent predictors of sepsis mortality. TCM diagnosis “Yang-Xu Zheng” may provide a new mortality predictor for septic patients. PMID:24282436

Lin, Sunny Jui-Shan; Cheng, Yung-Yen; Chang, Chih-Hung; Huang, Yi-Chia; Su, Yi-Chang

2013-01-01

212

Cloning, sequence analysis, and expression in Escherichia coli of a streptococcal plasmin receptor.  

PubMed Central

Plasmin(ogen) receptors are expressed by many gram-positive and gram-negative bacteria. We previously isolated a plasmin receptor from a pathogenic group A streptococcal strain (C. C. Broder, R. Lottenberg, G. O. von Mering, K. H. Johnston, and M. D. P. Boyle, J. Biol. Chem. 266:4922-4928, 1991). The gene encoding this plasmin receptor, plr, was isolated from a lambda gt11 library of chromosomal DNA from group A streptococcal strain 64/14 by screening plaques with antibodies raised against the purified streptococcal plasmin receptor protein. The gene was subcloned by using a low-copy-number plasmid and stably expressed in Escherichia coli, resulting in the production of an immunoreactive and functional receptor protein. The DNA sequence of the gene contained an open reading frame encoding 335 amino acids with a predicted molecular weight of 35,787. Upstream of the open reading frame, putative promoter and ribosomal binding site sequences were identified. The experimentally derived amino acid sequences of the N terminus and three cyanogen bromide fragments of the purified streptococcal plasmin receptor protein corresponded to the predicted sequence encoded by plr. The deduced amino acid sequence for the plasmin receptor protein revealed significant similarity (39 to 54% identical amino acid residues) to glyceraldehyde 3-phosphate dehydrogenases. Images PMID:1322883

Lottenberg, R; Broder, C C; Boyle, M D; Kain, S J; Schroeder, B L; Curtiss, R

1992-01-01

213

Physicians’ opinions about critical attributes of a potential group A streptococcal vaccine  

Microsoft Academic Search

A group A streptococcal (GAS) vaccine, while not currently available, offers the possibility of a more effective approach; however, barriers to its implementation are likely to exist. The objectives of this study were to describe the attitudes of physicians about the importance of preventing GAS-associated conditions and to identify potential barriers to vaccine implementation. Surveys were sent to randomly selected

Michael A. Gerber; Heidi W. Brown; Grace Lee; Robert R. Tanz; Jonathan L. Temte; Chris A. Van Beneden

2010-01-01

214

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

215

Evidence for the Presence of Streptococcal-Superantigen- Neutralizing Antibodies in Normal Polyspecific Immunoglobulin G  

Microsoft Academic Search

Recently we demonstrated that normal polyspecific immunoglobulin given intravenously (IVIG) and plasma samples from patients treated with IVIG neutralize the mitogenic and cytokine-inducing activities of group A streptococcal (GAS) superantigens. Here we investigated whether this neutralizing activity is mediated by antibodies to these superantigens. IVIG and plasma samples collected from a patient with GAS necrotizing fasciitis post-IVIG infusions markedly inhibited

ANNA NORRBY-TEGLUND; RUPERT KAUL; DONALD E. LOW; ALLISON MCGEER; JAN ANDERSSON; ULF ANDERSSON; ANDMALAK KOTB

1996-01-01

216

Group B Streptococcal b-Hemolysin/Cytolysin Directly Impairs Cardiomyocyte Viability and Function  

E-print Network

Group B Streptococcal b-Hemolysin/Cytolysin Directly Impairs Cardiomyocyte Viability and Function the effects of the GBS pore-forming b-hemolysin/cytolysin (Bh/c) exotoxin on cardiomyocyte viability for viability by trypan blue exclusion and for apoptosis by TUNEL staining. Functionality of exposed

Nizet, Victor

217

IS Sag1 in streptococcal strains of human and animal origin  

Microsoft Academic Search

The chromosomal region of Streptococcus agalactiae harboring the C5a peptidase and the lmb genes displays the structure of a composite transposon. Its presence in a streptococcal strain is associated with the origin of this strain from a human host. In S. agalactiae it is flanked by two copies of the insertion element ISSag2, and the nucleotide sequence for a third

Carmen Franken; Claudia Brandt; Gerd Bröker; Barbara Spellerberg

2004-01-01

218

Impact of a risk-based prevention policy on neonatal group B streptococcal disease  

Microsoft Academic Search

Objective: Neonatal group B streptococcal infections can be prevented by intrapartum antibiotic prophylaxis. Beginning in 1992, women with obstetric risk factors at University of Miami–Jackson Memorial Medical Center were targeted to receive intrapartum antibiotic prophylaxis. We evaluated these preventive efforts. Study Design: A case was defined as isolation of group B streptococci from a sterile site in an infant <7

Stephanie H. Factor; Orin S. Levine; Anwar Nassar; JoNell Potter; Ariana Fajardo; Mary Jo O’Sullivan; Anne Schuchat

1998-01-01

219

Late-Onset Group B Streptococcal Infection in Identical Twins: Insight to Disease Pathogenesis  

E-print Network

are left with permanent neurological sequelae including cerebral palsy, cognitive deficits, deafness INTRODUCTION Group B Streptococcus (GBS) is the leading cause of neonatal pneumonia, sepsis, and meningitis

Nizet, Victor

220

Mental and physical disability after sepsis.  

PubMed

Sepsis remains a major cause of admissions to Intensive Care Units (ICU) and has a high mortality rates and significant morbidity in survivors. There are physical, cognitive and psychological sequelae from severe sepsis that have a negative effect on the patients' health related quality of life in the longer term and a social care and humanitarian impact. Although muscle mass loss during the septic period happens very quickly, recovery takes a considerable time and requires the patient to commit to exercising and eating well to rebuild. Where cognitive impairment has resulted from the septic illness the patients' ability to look after themselves may be affected and this has financial and family implications for future care. Patients may also develop psychological problems such as anxiety, depression or post traumatic stress disorder (PTSD), which can have a profound effect on their everyday functioning and the possibility of returning to work. As yet there are no published studies of rehabilitation with patients surviving severe sepsis, although there is one in progress at the moment. The use of techniques such as ICU diaries to help patients to understand their illness and deal with delusional memories they may have from their ICU stay has been shown to aid psychological recovery in general ICU patients, a percentage of whom will have suffered from sepsis. The use of a self-guided manualised 6 week rehabilitation program, the ICU Recovery Manual, has been shown to accelerate physical recovery in general ICU patients. Considerable amounts of money are spent treating patients with severe sepsis in ICU and not completing the job of returning them to as close as possible to their normal functioning does not make financial sense. PMID:23857443

Jones, C; Griffiths, R D

2013-11-01

221

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

222

How Can the Microbiologist Help in Diagnosing Neonatal Sepsis?  

PubMed Central

Neonatal sepsis can be classified into two subtypes depending upon whether the onset of symptoms is before 72 hours of life (early-onset neonatal sepsis—EONS) or later (late-onset neonatal sepsis—LONS). These definitions have contributed greatly to diagnosis and treatment by identifying which microorganisms are likely to be responsible for sepsis during these periods and the expected outcomes of infection. This paper focuses on the tools that microbiologist can offer to diagnose and eventually prevent neonatal sepsis. Here, we discuss the advantages and limitation of the blood culture, the actual gold standard for sepsis diagnosis. In addition, we examine the utility of molecular techniques in the diagnosis and management of neonatal sepsis. PMID:22319539

Paolucci, Michela; Landini, Maria Paola; Sambri, Vittorio

2012-01-01

223

Cytokines and Signaling Molecules Predict Clinical Outcomes in Sepsis  

PubMed Central

Introduction Inflammatory response during sepsis is incompletely understood due to small sample sizes and variable timing of measurements following the onset of symptoms. The vasopressin in septic shock trial (VASST) compared the addition of vasopressin to norepinephrine alone in patients with septic shock. During this study plasma was collected and 39 cytokines measured in a 363 patients at both baseline (before treatment) and 24 hours. Clinical features relating to both underlying health and the acute organ dysfunction induced by the severe infection were collected during the first 28 days of admission. Hypothesis Cluster analysis of cytokines identifies subgroups of patients at differing risk of death and organ failure. Methods Circulating cytokines and other signaling molecules were measured using a Luminex multi-bead analyte detection system. Hierarchical clustering was performed on plasma values to create patient subgroups. Enrichment analysis identified clinical outcomes significantly different according to these chemically defined patient subgroups. Logistic regression was performed to assess the importance of cytokines for predicting patient subgroups. Results Plasma levels at baseline produced three subgroups of patients, while 24 hour levels produced two subgroups. Using baseline cytokine data, one subgroup of 47 patients showed a high level of enrichment for severe septic shock, coagulopathy, renal failure, and risk of death. Using data at 24 hours, a larger subgroup of 81 patients that largely encompassed the 47 baseline subgroup patients had a similar enrichment profile. Measurement of two cytokines, IL2 and CSF2 and their product were sufficient to classify patients into these subgroups that defined clinical risks. Conclusions A distinct pattern of cytokine levels measured early in the course of sepsis predicts disease outcome. Subpopulations of patients have differing clinical outcomes that can be predicted accurately from small numbers of cytokines. Design of clinical trials and interventions may benefit from consideration of cytokine levels. PMID:24244449

Fjell, Christopher D.; Thair, Simone; Hsu, Joseph L.; Walley, Keith R.; Russell, James A.; Boyd, John

2013-01-01

224

Characterization of group H streptococcal temperate bacteriophage phi 227.  

PubMed Central

phi 227, a temperate phage from a group H streptococcus (Streptococcus sanguis), was propagated vegetatively in group H strain Wicky 4-EryR, and its characteristics were determined. A procedure dependent on multiplicity of infection, incubation time, and treatment of crude lysates with diatomaceous earth was found to optimize phage yield, resulting in titers of 1 X 10(10) to 2 X 10(10) PFU/ml. Without prior treatment with diatomaceous earth, subsequent purification procedures (methanol, ammonium sulfate, polyethylene glycol) gave recoveries of less than 1% of crude lysate titers. Adsorption of phi227 to host cells was relatively unaffected by the medium, but calcium (not substituted by magnesium) was required for formation of infectious centers. The phage receptor was present on purified cell walls, resisted trypsin and heat, and was removed ty hydrochloric acid, trichloracetic acid, and hot formamide: however, formamide-extracted material failed to inactivate phage, and the nature of the receptor is unknown. Single-step growth experiments showed a latent period of 39 min and a burst size of 100 PFU/infectious center; results were unaffected by omission of supplemental Ca2+, by supplementation with Mg2, addition of glucose, or changes of pH between 6.35 and 8.0; but increased temperature (40 to 43 degrees C) shortened the latent period and decreased the burst size. The latent period was prolonged in genetically competent host cells and in chemically defined medium; and in the latter, the burst size was smaller. Phage replication was sensitive to those metabolic inhibitors which inhibited the host streptococcus: these included rifampin, fluorodeoxyuridine, hydroxyurea, dihydrostreptomycin, and 6-P-hydroxyphenylazouracil. The data suggest that phi227 does not code for a rifampin-resistant RNA polymerase. However, in a rifampin-resistant host strain, phage replication and lysogen formation were both decreased suggesting that altered host core polymerase had less affinity for (some) promotors on the phi227 template. In transfection, a Ca2+-dependent stabilization step that was inhibited by Mg2+ was demonstrated; transformation was not affected by either Ca2+ or Mg2+, and the site and nature of the stabilization are unknown. More than one molecule of DNA was required for plaque formation. Biophysical characterization showed a type B phage of buoyant density (CsCl) 1.50, containing five proteins and 54.8% DNA. The duplex linear DNA had a molecular weight (calculated from contour length) of 23.2 X 10(6) and a guanine plus cytosine content (calculated from melting point) of 42.3 mol%. Similar characterizations of streptococcal phages, including biophysical data, have not been previously available. Images PMID:15133

Nugent, K M; Cole, R M

1977-01-01

225

Invasive group A streptococcal infection in the Northern Territory, Australia: Case report and review of the literature.  

PubMed

The increasing incidence of invasive group A streptococcus has been well documented in the temperate climates of North America, Europe and the United Kingdom. Studies also suggest that there are high rates of invasive group A streptococcus infection within the indigenous population of Northern Australia. This review article presents the case of infant Aboriginal twins with invasive group A streptococcal infection complicated by streptococcal toxic shock syndrome, highlighting both the severity and high transmissibility of invasive group A streptococcal disease. We review the epidemiology of group A streptococcal infection and suggest a potential role for chemoprophylaxis of household contacts to reduce the burden of disease within the indigenous population of Northern Australia. PMID:24957474

Middleton, Bianca; Morris, Peter; Carapetis, Jonathan

2014-11-01

226

Psychiatric Disorders in First-Degree Relatives of Children With Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcal Infections (PANDAS)  

Microsoft Academic Search

ObjectiveTo determine the rates of psychiatric disorders in the first-degree relatives of children with infection-triggered obsessive-compulsive disorder (OCD) and\\/or tics (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections; PANDAS).

LORRAINE LOUGEE; SUSAN J. PERLMUTTER; ROB NICOLSON; MARJORIE A. GARVEY; SUSAN E. SWEDO

2000-01-01

227

Prospective Identification and Treatment of Children With Pediatric Autoimmune Neuropsychiatric Disorder Associated With Group A Streptococcal Infection (PANDAS)  

Microsoft Academic Search

Background: The current diagnostic criteria for pedi- atric autoimmune neuropsychiatric disorder associated with group A streptococcal infection (PANDAS) are pe- diatric onset, neuropsychiatric disorder (obsessive- compulsive disorder (OCD)) and\\/or tic disorder; abrupt onset and\\/or episodic course of symptoms; association with group A-hemolytic streptococcal (GABHS) infec- tion; and association with neurological abnormalities (mo- toric hyperactivity or adventitious movements, includ- ing choreiform

Marie Lynd Murphy; Michael E. Pichichero

2002-01-01

228

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

229

Role of immunomodulator therapy in sepsis.  

PubMed

Endotoxin is released from the cell walls of gram-negative bacteria and causes severe systemic effects due to the release of cytokines. Monoclonal antibodies directed at endotoxin may be promising adjuncts to the standard therapeutic interventions of antibiotics and supportive measures used to treat patients with gram-negative sepsis. Monoclonal antibodies interfere with the bacteria's ability to trigger an unfavorable response. In recent clinical trials, two immunoglobulin M monoclonal antibodies have improved survival in certain small patient subgroups, although neither drug improved overall mortality in all septic patients treated. E5 murine monoclonal antibody reduced mortality in patients with gram-negative sepsis who were not in refractory shock. HA-1A human monoclonal antibody reduced mortality in patients with gram-negative infections who were bacteremic or in shock. The statistical significance and clinical importance of these benefits is not yet known. Results of these clinical trials are reviewed. PMID:8438996

Caplan, E S

1993-02-01

230

Macrophage activation syndrome following Acinetobacter baumannii sepsis.  

PubMed

Macrophage activation syndrome (MAS) is a systemic disorder with a high mortality, commonly associated with rheumatological conditions, but which can also occur as a complication of several infections. Here we present a case of MAS following Acinetobacter baumannii sepsis. Early institution of therapy with prednisolone, cyclosporine, colistin, and polymyxin resulted in a prompt clinical recovery. There are very few reported cases of Acinetobacter-related MAS that have been successfully treated. PMID:22285540

John, Teny Mathew; Jacob, Ceena N; Ittycheria, Cherian C; George, Amrutha M; Jacob, Amith G; Subramaniyam, Saji; Puthiyaveettil, Jabbar; Jayaprakash, R

2012-03-01

231

Designing a Pediatric Severe Sepsis Screening Tool  

PubMed Central

We sought to create a screening tool with improved predictive value for pediatric severe sepsis (SS) and septic shock that can be incorporated into the electronic medical record and actively screen all patients arriving at a pediatric emergency department (ED). “Gold standard” SS cases were identified using a combination of coded discharge diagnosis and physician chart review from 7,402 children who visited a pediatric ED over 2?months. The tool’s identification of SS was initially based on International Consensus Conference on Pediatric Sepsis (ICCPS) parameters that were refined by an iterative, virtual process that allowed us to propose successive changes in sepsis detection parameters in order to optimize the tool’s predictive value based on receiver operating characteristics (ROC). Age-specific normal and abnormal values for heart rate (HR) and respiratory rate (RR) were empirically derived from 143,603 children seen in a second pediatric ED over 3?years. Univariate analyses were performed for each measure in the tool to assess its association with SS and to characterize it as an “early” or “late” indicator of SS. A split-sample was used to validate the final, optimized tool. The final tool incorporated age-specific thresholds for abnormal HR and RR and employed a linear temperature correction for each category. The final tool’s positive predictive value was 48.7%, a significant, nearly threefold improvement over the original ICCPS tool. False positive systemic inflammatory response syndrome identifications were nearly sixfold lower. PMID:24982852

Sepanski, Robert J.; Godambe, Sandip A.; Mangum, Christopher D.; Bovat, Christine S.; Zaritsky, Arno L.; Shah, Samir H.

2014-01-01

232

Recent insights into the pathogenesis of bacterial sepsis.  

PubMed

Sepsis is a very heterogeneous clinical syndrome broadly defined as the systemic host response to an infection. Until very recently, the prevailing concept of the pathogenesis of sepsis was that mortality is the consequence of an uncontrolled hyperinf lammatory response of the host. The disappointing results of nearly 40 years of anti-inflammatory strategies and the development of animal models that more closely mimic clinical sepsis have led to the reconsideration of the pathophysiology of sepsis. Sepsis is now considered a misbalance between proinflammatory reactions (designed to kill invading pathogens but at the same time responsible for tissue damage) and anti-inflammatory responses (designed to limit excessive inflammation, but at the same time making the host more vulnerable for secondary infections). This review discusses key components of the pro- and anti-inflammatory response to sepsis, listing potential novel interventional strategies along the way. PMID:20421654

Anas, A A; Wiersinga, W J; de Vos, A F; van der Poll, T

2010-04-01

233

The pediatric sepsis biomarker risk model: potential implications for sepsis therapy and biology.  

PubMed

Sepsis remains a major cause of morbidity and mortality in adult and pediatric intensive care units. Heterogeneity of demographics, comorbidities, biological mechanisms, and severity of illness leads to difficulty in determining which patients are at highest risk of mortality. Determining mortality risk is important for weighing the potential benefits of more aggressive interventions and for deciding whom to enroll in clinical trials. Biomarkers can be used to parse patients into different risk categories and can outperform current methods of patient risk stratification based on physiologic parameters. Here we review the Pediatric Sepsis Biomarker Risk Model that has also been modified and applied to estimate mortality risk in adult patients. We compare the two models and speculate on the biological implications of the biomarkers in patients with sepsis. PMID:24754535

Alder, Matthew N; Lindsell, Christopher J; Wong, Hector R

2014-07-01

234

Complement Depletion Deteriorates Clinical Outcomes of Severe Abdominal Sepsis: A Conspirator of Infection and Coagulopathy in Crime?  

PubMed Central

Background The complement depletion commonly occurred during sepsis, but it was often underestimated compared with severe infection or coagulation dysfunction. Objective This study was designed to investigate the alteration of complement system in patients with severe abdominal sepsis and evaluate the role of complement depletion in prognosis of such patients. The relationship between complement depletion and infection or coagulopathy was also explored. Methods Forty-five patients with severe abdominal sepsis were prospectively conducted among individuals referral to SICU. Currently recommended treatments, such as early goal-directed resuscitation, source control and antibiotics therapy, were performed. Acute physiology and chronic health evaluation II (APACHE II) and sepsis related organ failure assessment (SOFA) scores were employed to evaluate severity. Plasma levels of C3, C4, CRP, PCT, D-dimer and other parameters were detected within eight times of observation. The 28-day mortality, length of stay, and postoperative complications were compared between complement depletion and non-complement depletion groups. Results Within the study period, eight (17.8%) patients died, five of them suffering from complement depletion. The overall incidence of complement depletion was 64.4%. At admission, mean complement C3 and C4 levels were 0.70 and 0.13 mg/mL, respectively. Using ROC analysis for mortality prediction, the area under the curve of C3 was 0.926 (95% CI, 0.845–0.998, P<0.001), with optimal cutpoint value of 0.578 mg/mL. Complement C3 depletion was shown to be no correlation to severity scores, however, strongly correlated with elevated D-dimer, PCT concentrations and increased postoperative complications. Conclusions Complement C3 depletion was found to be connected to poor prognosis in severe abdominal sepsis. This depletion seems to be associated with coagulopathy and aggravated infection during sepsis, which should be paid close attention in critical care. Trial Registration ClinicalTrials.gov NCT01568853 PMID:23091606

Zhao, Yunzhao; Han, Gang; Li, Weiqin; Huang, Qian; Tong, Zhihui; Li, Jieshou

2012-01-01

235

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

236

Protective effects of guanosine against sepsis-induced damage in rat brain and cognitive impairment.  

PubMed

The development of cognitive impairment in sepsis is associated with neurotoxic effects caused by oxidative stress. We have assessed the effects of acute and extended administration of guanosine (GUA) on brain oxidative stress parameters and cognitive impairment in rats submitted to sepsis by cecal ligation and perforation (CLP). To achieve this goal, male Wistar rats underwent either sham operation or CLP with GUA. Rats subjected to CLP were treated with intraperitoneal injection of GUA (8 mg/kg after CLP) or vehicle. Twelve and 24 h after CLP, the rats were sacrificed, and samples from brain (hippocampus, striatum, cerebellum, prefrontal cortex and cortex) were obtained and assayed for thiobarbituric acid reactive species (TBARS) formation and protein carbonyls. On the 10th day, another group of rats was submitted to the behavioral tasks. GUA administration reduced TBARS and carbonyl levels in some brain regions between 12 and 24 h after CLP, and ameliorated cognitive impairment evaluated 10 days after CLP. Our data provide the first experimental demonstration that GUA was able to reduce the consequences of CLP-induced sepsis in rats, by decreasing oxidative stress parameters in the brain and recovering the memory impairment. PMID:22497789

Petronilho, Fabricia; Périco, Susane Raquel; Vuolo, Francieli; Mina, Francielle; Constantino, Larissa; Comim, Clarissa M; Quevedo, João; Souza, Diogo Onofre; Dal-Pizzol, Felipe

2012-08-01

237

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

238

Studies of Streptococcal Cell Walls VII. Carbohydrate Composition of Group B Cell Walls1  

PubMed Central

Wittner, Masako K. (Presbyterian-St. Luke's Hospital, Chicago, Ill.), and James A. Hayashi. Studies of streptococcal cell walls. VII. Carbohydrate composition of group B cell walls. J. Bacteriol. 89:398–402. 1965.—Group B streptococcal cell walls contain 63% protein, 10% rhamnose, 18% hexose (mainly galactose, but also some glucose), 7% hexosamine (mainly glucosamine, but also galactosamine), and 3% muramic acid. The group and type antigens were extracted from isolated cell walls by acid treatment and enzymatic hydrolysis, and fractionated either with ethanol or on a diethylaminoethyl-cellulose column. Serological and chemical analyses of the fractions obtained in the two fractionation methods show that the group antigen is a rhamnose-rich polysaccharide and that the type antigen is rich in galactose and contains hexosamines. PMID:14255706

Wittner, Masako K.; Hayashi, James A.

1965-01-01

239

FURTHER STUDIES ON THE CHEMICAL BASIS FOR SEROLOGICAL SPECIFICITY OF GROUP A STREPTOCOCCAL CARBOHYDRATE  

PubMed Central

Azoproteins prepared with p-aminophenyl-?-N-acetyl-glucosaminide react in precipitin tests with Group A streptococcal antisera. The reaction is nonreciprocal, and antisera to the azoprotein do not react with Group A carbohydrate. Phenyl-N-acetyl-glucosaminides inhibit the reaction of Group A carbohydrate with homologous antisera and with antisera to the azoprotein. The ?-anomer is more effective as an inhibitor than the ?-anomer. Formation by a soil bacillus of the enzyme which removes N-acetyl-glucosamine from Group A carbohydrate is induced by phenyl-?-N-acetyl-glucosaminide but not by the ?-compound. The enzyme, like the glucosaminidase of emulsin, appears to be specific for ?-glucosaminides. Neither the induced enzyme nor emulsin effectively remove all of the N-acetyl-glucosamine from the azoprotein antigens. The findings support the view that ?-N-acetyl-glucosaminide side chains represent the major antigenic determinant of Group A streptococcal carbohydrate. PMID:13575668

McCarty, Maclyn

1958-01-01

240

Radioimmunoassay for measuring antibodies specific for group B streptococcal types Ia, Ib, Ic, II, and III.  

PubMed Central

The object of this study was to develop a test that would measure antibodies directed against group B streptococcal types Ia, Ib, Ic, II, and III. The type-specific carbohydrate antigens were purified, labeled with 125I, and used to develop a radioimmunoassay. This procedure should be particularly useful in testing human sera for group B type-specific antibodies, since it requires very small quantities of antigens and measures primary type antigen-antibody interactions. PMID:58870

Wilkinson, H W; Jones, W L

1976-01-01

241

Making a Point: the Role of DivIVA in Streptococcal Polar Anatomy  

Microsoft Academic Search

Like the cells of other bacteria that are not rod shaped, Streptococcus pneumoniae cells manage to avoid potentially distressing changes in their surface-to-volume ratio as they grow. The work reported by Fadda et al. in this issue (9) on the streptococcal DivIVA protein suggests new ideas on how this protein may contribute to transformation of the midcell into two pointed

Miguel Vicente; M. Garcia-Ovalle

2007-01-01

242

Comparison of cefdinir and penicillin for the treatment of pediatric streptococcal pharyngitis  

Microsoft Academic Search

This multicenter, randomized, controlled, investigator-masked study was performed to assess the efficacy and tolerability of cefdinir for the treatment of Streptococcal pharyngitis. Children aged 1 through 12 years with signs and symptoms of pharyngitis and a positive result on a rapid screening test for Streptococcus pyogenes were randomly assigned to receive cefdinir 14 mg\\/kg QD, cefdinir 7 mg\\/kg BID, or

Mary Anne Nemeth; W GOOCHIII; James Hedrick; Eric Slosberg; Constance H. Keyserling; Kenneth J. Tack

1999-01-01

243

Case report: group B streptococcal bacteremia and sacroiliitis after mid-trimester dilation and evacuation  

Microsoft Academic Search

Group B streptococcal bacteremia with septic arthritis is a rare complication of second trimester dilation and evacuation, and may cause substantial post-operative morbidity. A 37-year-old gravida 4 para 1-0-2-1 presented with fever and right hip pain on post-operative day 11 from a second trimester dilation and evacuation for fetal trisomy 21. She was initially found to have septic arthritis involving

T McKenna; K O'Brien

2009-01-01

244

Identification of DysI, the Immunity Factor of the Streptococcal Bacteriocin Dysgalacticin?  

PubMed Central

DysI is identified as the protein that confers specific immunity to dysgalacticin, a plasmid-encoded streptococcal bacteriocin. dysI is transcribed as part of the copG-repB-dysI replication-associated operon. DysI appears to function at the membrane level to prevent the inhibitory effects of dysgalacticin on glucose transport, membrane integrity, and intracellular ATP content. PMID:20935130

Swe, Pearl M.; Heng, Nicholas C. K.; Cook, Gregory M.; Tagg, John R.; Jack, Ralph W.

2010-01-01

245

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

246

Characterization of group A streptococcal R-28 antigen purified by hydroxyapatite column chromatography.  

PubMed Central

Purified R-28 antigen from an M-protein-poor, R-antigen-rich strain of group A Streptococcus was prepared by sequential treatment of an acid extract of whole cells with ammonium sulfate fractionation and hydroxylapatite (HA) column chromatography. Purified R-28 antigen was eluted only with 0.10 M sodium phosphate, pH 6.7. Findings on quantitative amino acid composition, polyacrylamide gel electrophoresis pattern, and HA column elution pattern were similar but not identical to those previously reported for streptococcal M-proteins. Rabbits immunized with either HA-purified R-28 antigen or heat-killed cells developed two pepsin-sensitive, trypsin-resistant immunodiffusion lines of identity against HA-purified R-28 antigen but failed to form bactericidal antibody. One of these two lines formed a line of identity with R-28 antigen prepared by trypsinization of whole cells. The other line remained undefined, although it appeared not to be either streptococcal group A carbohydrate, M-protein, T-antigen, polyglycerophosphate, E4 antigen, or M-associated protein; by enzymatic criteria it is an R-antigen. Polyacrylamide gel electrophoresis of HA-purified R-28 antigen revealed multiple serologically active charge and size isomers. These findings suggest possible structural similarities between group A streptococcal M-proteins and R-antigens and also indicate that the same purification techniques may be utilized to study these protein antigens if the proper strain of Streptococcus is chosen. Images PMID:1104480

Johnson, R H

1975-01-01

247

Use of tuf Sequences for Genus-Specific PCR Detection and Phylogenetic Analysis of 28 Streptococcal Species  

PubMed Central

A 761-bp portion of the tuf gene (encoding the elongation factor Tu) from 28 clinically relevant streptococcal species was obtained by sequencing amplicons generated using broad-range PCR primers. These tuf sequences were used to select Streptococcus-specific PCR primers and to perform phylogenetic analysis. The specificity of the PCR assay was verified using 102 different bacterial species, including the 28 streptococcal species. Genomic DNA purified from all streptococcal species was efficiently detected, whereas there was no amplification with DNA from 72 of the 74 nonstreptococcal bacterial species tested. There was cross-amplification with DNAs from Enterococcus durans and Lactococcus lactis. However, the 15 to 31% nucleotide sequence divergence in the 761-bp tuf portion of these two species compared to any streptococcal tuf sequence provides ample sequence divergence to allow the development of internal probes specific to streptococci. The Streptococcus-specific assay was highly sensitive for all 28 streptococcal species tested (i.e., detection limit of 1 to 10 genome copies per PCR). The tuf sequence data was also used to perform extensive phylogenetic analysis, which was generally in agreement with phylogeny determined on the basis of 16S rRNA gene data. However, the tuf gene provided a better discrimination at the streptococcal species level that should be particularly useful for the identification of very closely related species. In conclusion, tuf appears more suitable than the 16S ribosomal RNA gene for the development of diagnostic assays for the detection and identification of streptococcal species because of its higher level of species-specific genetic divergence. PMID:15297518

Picard, Francois J.; Ke, Danbing; Boudreau, Dominique K.; Boissinot, Maurice; Huletsky, Ann; Richard, Dave; Ouellette, Marc; Roy, Paul H.; Bergeron, Michel G.

2004-01-01

248

Complement Inhibitors from Scabies Mites Promote Streptococcal Growth – A Novel Mechanism in Infected Epidermis?  

PubMed Central

Background Scabies is highly prevalent in socially disadvantaged communities such as indigenous populations and in developing countries. Generalized itching causes discomfort to the patient; however, serious complications can occur as a result of secondary bacterial pyoderma, commonly caused by Streptococcus pyogenes (GAS) or Staphylococcus aureus. In the tropics, skin damage due to scabies mite infestations has been postulated to be an important link in the pathogenesis of disease associated with acute rheumatic fever and heart disease, poststreptococcal glomerulonephritis and systemic sepsis. Treatment of scabies decreases the prevalence of infections by bacteria. This study aims to identify the molecular mechanisms underlying the link between scabies and GAS infections. Methodology/Principal Findings GAS bacteria were pre-incubated with blood containing active complement, phagocytes and antibodies against the bacteria, and subsequently tested for viability by plate counts. Initial experiments were done with serum from an individual previously exposed to GAS with naturally acquired anti-GAS antibodies. The protocol was optimized for large-scale testing of low-opsonic whole blood from non-exposed human donors by supplementing with a standard dose of heat inactivated human sera previously exposed to GAS. This allowed an extension of the dataset to two additional donors and four proteins tested at a range of concentrations. Shown first is the effect of scabies mite complement inhibitors on human complement using ELISA-based complement activation assays. Six purified recombinant mite proteins tested at a concentration of 50 µg/ml blocked all three complement activation pathways. Further we demonstrate in human whole blood assays that each of four scabies mite complement inhibitors tested increased GAS survival rates by 2–15 fold. Conclusions/Significance We propose that local complement inhibition plays an important role in the development of pyoderma in scabies infested skin. This molecular link between scabies and bacterial infections may provide new avenues to develop alternative treatment options against this neglected disease. PMID:22815998

Mika, Angela; Reynolds, Simone L.; Pickering, Darren; McMillan, David; Sriprakash, Kadaba S.; Kemp, David J.; Fischer, Katja

2012-01-01

249

Oxygen delivery and utilization in sepsis.  

PubMed

Oxygen delivery and utilization is deranged in the setting of sepsis. The most likely cause is an inability of the microvasculature to provide sufficient oxygen to actively metabolize tissue, probably as a result of diminished autoregulatory control and capillary damage. This maldistribution of blood flow results in the development of pathological supply dependency of TO2, which correlates with the development of multiorgan failure and a high mortality. The ability to monitor the adequacy of tissue O2 delivery is limited by technological limitations and evidence that we can increase tissue O2 delivery either by improving TO2 or altering microcirculatory functioning is not yet available. PMID:2647227

Dantzker, D

1989-01-01

250

Damage control for intra-abdominal sepsis.  

PubMed

With the success of damage-control surgery for the treatment of exsanguinating truncal trauma, it has been adapted to other surgical diseases associated with shock states, such as severe secondary peritonitis. The structured approach of damage control is easily adapted to and can incorporate the fundamental elements of the Surviving Sepsis Campaign. It is not meant to replace tried and true surgical principles, such as source control, but is a usable framework in managing the complicated circumstances seen with these patients. PMID:22414411

Waibel, Brett H; Rotondo, Michael F

2012-04-01

251

Group G Beta-Hemolytic Streptococcal Bacteremia Characterized by 16S Ribosomal RNA Gene Sequencing  

PubMed Central

Little is known about the relative importance of the four species of Lancefield group G beta-hemolytic streptococci in causing bacteremia and the factors that determine the outcome for patients with group G beta-hemolytic streptococcal bacteremia. From 1997 to 2000, 75 group G beta-hemolytic streptococcal strains were isolated from the blood cultures of 66 patients. Sequencing of the 16S rRNA genes of the group G beta-hemolytic streptococci showed that all 75 isolates were Streptococcus dysgalactiae subspecies equisimilis. The API system (20 STREP) and Vitek system (GPI) successfully identified 65 (98.5%) and 62 (93.9%) isolates, respectively, as S. dysgalactiae subspecies equisimilis with >95% confidence, whereas the ATB Expression system (ID32 STREP) only successfully identified 49 isolates (74.2%) as S. dysgalactiae subspecies equisimilis with >95% confidence. The median age of the patients was 76 years (range, 33 to 99 years). Fifty-six patients (85%) were over 60 years old. All patients had underlying diseases. No source of the bacteremia was identified (primary bacteremia) in 34 patients (52%), whereas 17 (26%) had cellulitis and 8 (12%) had bed sore or wound infections. Fifty-eight patients (88%) had community-acquired group G streptococcal bacteremia. Sixty-two patients (94%) had group G Streptococcus recovered in one blood culture, whereas 4 patients (6%) had it recovered in multiple blood cultures. Fifty-nine patients (89%) had group G Streptococcus as the only bacterium recovered in their blood cultures, whereas in 7 patients other bacteria were recovered concomitantly with the group G Streptococcus in the blood cultures (Staphylococcus aureus in 3, Clostridium perfringens in 2, Citrobacter freundii in 1, and Bacteroides fragilis in 1). Overall, 10 patients (15%) died. Male sex, diagnosis other than cellulitis, hospital-acquired bacteremia, and multiple positive blood cultures were associated with mortality {P < 0.005 (relative risk [RR] = 7.6), P < 0.05 (RR = 3.7), P < 0.005 (RR = 5.6), and P < 0.05 (RR = 5.6), respectively}. Unlike group C beta-hemolytic streptococcal bacteremia, group G beta-hemolytic streptococcal bacteremia is not a zoonotic infection in Hong Kong. PMID:11526143

Woo, Patrick C. Y.; Fung, Ami M. Y.; Lau, Susanna K. P.; Wong, Samson S. Y.; Yuen, Kwok-Yung

2001-01-01

252

Intensive Insulin Therapy and Pentastarch Resuscitation in Severe Sepsis  

Microsoft Academic Search

A b s t r ac t Background The role of intensive insulin therapy in patients with severe sepsis is uncertain. Fluid resuscitation improves survival among patients with septic shock, but evidence is lacking to support the choice of either crystalloids or colloids. Methods In a multicenter, two-by-two factorial trial, we randomly assigned patients with se- vere sepsis to receive

Frank M. Brunkhorst; Christoph Engel; Frank Bloos; Andreas Meier-Hellmann; Max Ragaller; Norbert Weiler; Onnen Moerer; Matthias Gruendling; Michael Oppert; Stefan Grond; Derk Olthoff; Ulrich Jaschinski; Stefan John; Rolf Rossaint; Tobias Welte; Martin Schaefer; Peter Kern; Evelyn Kuhnt; Michael Kiehntopf; Christiane Hartog; Charles Natanson; Markus Loeffler; Konrad Reinhart

2008-01-01

253

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

254

Which Biomarkers Reveal Neonatal Sepsis? , Vineet Bhandari2  

E-print Network

of increas- ing size that are most highly correlated with sepsis infection. The effectiveness of body temperature, which may be either above or below normal [12,13,26]. The most reliable diagnostic of neonatal sepsis, often referred to as the gold standard, is a blood culture test for bacteria. While

O'Hern, Corey S.

255

Spectral analysis of heart rate variability in the sepsis syndrome  

Microsoft Academic Search

Sympathetic and parasympathetic activity was evaluated on 39 occasions in 17 patients with the sepsis syndrome, by measurement of the variation in resting heart rate using frequency spectrum analysis. Heart rate was recorded by electrocardiography and respiratory rate by impedance plethysmography. The sepsis syndrome was established on the basis of established clinical and physiological criteria. Subjects were studied, whenever possible,

Christopher S. Garrard; Dimitrios A. Kontoyannis; Massimo Piepoli

1993-01-01

256

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

257

Mitochondrial biogenesis restores oxidative metabolism during Staphylococcus aureus sepsis  

Microsoft Academic Search

Rationale: The extent, timing, and significance of mitochondrial injury and recovery in bacterial sepsis are poorly characterized, although oxidative and nitrosative mitochondrial damage have been implicated in the development of organ failure. Objectives: To define the relationships between mitochondrial bio- genesis, oxidative metabolism, and recovery from Staphylococcus aureus sepsis. Methods: We developed a murine model of fibrin clot peritonitis, using

Douglas W. Haden; Hagir B. Suliman; Martha Sue Carraway; Karen E. Welty-Wolf; Abdelwahid S. Ali; Hiroshi Shitara; Hiromichi Yonekawa; Claude A. Piantadosi

2007-01-01

258

Prognosis of AKI in malignant diseases with and without sepsis  

PubMed Central

Background AKI significantly worsens prognosis of hospitalized patients. This is particularly the case in patients with sepsis. The risk for aquiring sepsis is significantly increased in malignant diseases. Aim of the present retrospective study was to analyze outcomes of tumor patients with sepsis and AKI. Methods One-thousand and seventeen patients, treated at the ICU of the Department of Nephrology and Rheumatology of the University Hospital Göttingen from 2009 to 2011 were retrospectively analyzed for mortality, sepsis, AKI, need for renal replacement therapy (dialysis) and malignancies. Results AKI occurred significantly more frequent in septic than in non-septic patients and in tumor as oposed to non-tumor patients. Mortaliy rates were higher in the respective latter groups. Mortality increased even further if patients suffered from a malignant disease with sepsis and AKI. Mortality rates peaked if dialysis treatment became mandatory. In non-solid tumors 100% of the patients died if they suffered drom sepsis and AKI. This was not the case in solid malignancies (mortality rate 56%). Conclusions We conclude that prognosis of tumor patients with AKI and sepsis is very poor. Mortality increases to almost 70% if diaylsis therapy is initiated. Non-solid tumors are associated with a 100% mortality if sepsis and AKI conincide. PMID:24168374

2013-01-01

259

Passive transfer of streptococcus-induced antibodies reproduces behavioral disturbances in a mouse model of pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection  

Microsoft Academic Search

Streptococcal infections can induce obsessive-compulsive and tic disorders. In children, this syndrome, frequently associated with disturbances in attention, learning and mood, has been designated pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS). Autoantibodies recognizing central nervous system (CNS) epitopes are found in sera of most PANDAS subjects, but may not be unique to this neuropsychiatric subset. In support of

K Yaddanapudi; M Hornig; R Serge; J De Miranda; A Baghban; G Villar; W I Lipkin

2010-01-01

260

Behavioral, Pharmacological, and Immunological Abnormalities after Streptococcal Exposure: A Novel Rat Model of Sydenham Chorea and Related Neuropsychiatric Disorders  

PubMed Central

Group A streptococcal (GAS) infections and autoimmunity are associated with the onset of a spectrum of neuropsychiatric disorders in children, with the prototypical disorder being Sydenham chorea (SC). Our aim was to develop an animal model that resembled the behavioral, pharmacological, and immunological abnormalities of SC and other streptococcal-related neuropsychiatric disorders. Male Lewis rats exposed to GAS antigen exhibited motor symptoms (impaired food manipulation and beam walking) and compulsive behavior (increased induced-grooming). These symptoms were alleviated by the D2 blocker haloperidol and the selective serotonin reuptake inhibitor paroxetine, respectively, drugs that are used to treat motor symptoms and compulsions in streptococcal-related neuropsychiatric disorders. Streptococcal exposure resulted in antibody deposition in the striatum, thalamus, and frontal cortex, and concomitant alterations in dopamine and glutamate levels in cortex and basal ganglia, consistent with the known pathophysiology of SC and related neuropsychiatric disorders. Autoantibodies (IgG) of GAS rats reacted with tubulin and caused elevated calcium/calmodulin-dependent protein kinase II signaling in SK-N-SH neuronal cells, as previously found with sera from SC and related neuropsychiatric disorders. Our new animal model translates directly to human disease and led us to discover autoantibodies targeted against dopamine D1 and D2 receptors in the rat model as well as in SC and other streptococcal-related neuropsychiatric disorders. PMID:22534626

Brimberg, Lior; Benhar, Itai; Mascaro-Blanco, Adita; Alvarez, Kathy; Lotan, Dafna; Winter, Christine; Klein, Julia; Moses, Allon E; Somnier, Finn E; Leckman, James F; Swedo, Susan E; Cunningham, Madeleine W; Joel, Daphna

2012-01-01

261

Early management of severe sepsis: concepts and controversies.  

PubMed

Sepsis is among the most common reasons for admission to ICUs throughout the world, and it is believed to be the third most common cause of death in the United States. The pathogenetic mechanism and physiologic changes associated with sepsis are exceedingly complex, but our understanding is evolving rapidly. The major pathophysiologic changes in patients with septic shock include vasoplegic shock (distributive shock), myocardial depression, altered microvascular flow, and a diffuse endothelial injury. These pathophysiologic changes play a central role in the management of sepsis. The early management of patients with severe sepsis and septic shock centers on the administration of antibiotics, IV fluids, and vasoactive agents, followed by source control. However, the specific approach to the resuscitation of patients with septic shock remains highly controversial. This review provides a practical and physiologic-based approach to the early management of sepsis and explores the controversies surrounding the management of this complex condition. PMID:24889440

Marik, Paul E

2014-06-01

262

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

263

Ghrelin-mediated sympathoinhibition and suppression of inflammation in sepsis  

PubMed Central

Sepsis, a systemic inflammatory response to infection, continues to carry a high mortality despite advances in critical care medicine. Elevated sympathetic nerve activity in sepsis has been shown to contribute to early hepatocellular dysfunction and subsequently multiple organ failure, resulting in a poor prognosis, especially in the elderly. Thus, suppression of sympathetic nerve activity represents a novel therapeutic option for sepsis. Ghrelin is a 28-amino acid peptide shown to inhibit sympathetic nerve activity and inflammation in animal models of tissue injury. Age-related ghrelin hyporesponsiveness has also been shown to exacerbate sepsis. However, the mechanistic relationship between ghrelin-mediated sympathoinhibition and suppression of inflammation remains poorly understood. This review assesses the therapeutic potential of ghrelin in sepsis in the context of the neuroanatomical and molecular basis of ghrelin-mediated suppression of inflammation through inhibition of central sympathetic outflow. PMID:22068604

Cheyuo, Cletus; Jacob, Asha

2012-01-01

264

Improving the management and care of people with sepsis.  

PubMed

Many hospitals struggle to implement the full sepsis care bundle, but research suggests that many patients with sepsis are transported to hospital by ambulance. In 2011, the Scottish Ambulance Service introduced a pre-hospital sepsis screening tool (PSST) to expedite sepsis identification and care delivery. However, ambulance clinicians have reported varying degrees of interest and enthusiasm from hospital staff during handover. Therefore, an online survey was set up to investigate medical and nursing staff perceptions and experiences of the introduction of a PSST. This article discusses the results, which show that participants perceive the PSST reduces time to treatment, improves continuity of care, benefits patients and is accurately applied by ambulance clinicians, but which also highlight problems with communication. The delivery of in-hospital and pre-hospital sepsis care is challenging, but simple measures such as improving and standardising communication and alert systems between ambulance services and receiving hospitals could improve the clinical effects of a PSST. PMID:24689480

Fitzpatrick, David; McKenna, Michael; Rooney, Kevin; Beckett, Dan; Pringle, Norma

2014-04-01

265

Intestinal radiation syndrome: sepsis and endotoxin  

SciTech Connect

Rats were whole-body irradiated with 8-MeV cyclotron-produced neutrons and /sup 137/Cs ..gamma.. rays to study the role of enteric bacteria and endotoxin in the intestinal radiation syndrome. Decrease in intestinal weight was used as an index of radiation-induced breakdown of the mucosa. Neutron and ..gamma..-ray doses that were sublethal for intestinal death resulted in a dose-dependent decrease in intestinal weight, reaching minimal values 2 to 3 days after exposure, followed by recovery within 5 days after irradiation. Neutron and photon doses that caused intestinal death resulted in greater mucosal breakdown with little or no evidence of mucosal recovery. The presence of fluid in the intestine and diarrhea, but not bacteremia or endotoxemia, were related to mucosal breakdown and recovery. Neither sepsis nor endotoxin could be detected in liver samples taken at autopsy from animals which died a short time earlier from intestinal injury. These results suggest that overt sepsis and endotoxemia do not play a significant role in the intestinal radiation syndrome.

Geraci, J.P.; Jackson, K.L.; Mariano, M.S.

1985-03-01

266

Sepsis-induced alterations in sleep of rats  

PubMed Central

Sepsis is a systemic immune response to infection that may result in multiple organ failure and death. Polymicrobial infections remain a serious clinical problem, and in the hospital, sepsis is the number-one noncardiac killer. Although the central nervous system may be one of the first systems affected, relatively little effort has been made to determine the impact of sepsis on the brain. In this study, we used the cecal ligation and puncture (CLP) model to determine the extent to which sepsis alters sleep, the EEG, and brain temperature (Tbr) of rats. Sepsis increases the amount of time rats spend in non-rapid eye movement sleep (NREMS) during the dark period, but not during the light period. Rapid eye movements sleep (REMS) of septic rats is suppressed for about 24 h following CLP surgery, after which REMS increases during dark periods for at least three nights. The EEG is dramatically altered shortly after sepsis induction, as evidenced by reductions in slow-frequency components. Furthermore, sleep is fragmented, indicating that the quality of sleep is diminished. Effects on sleep, the EEG, and Tbr persist for at least 84 h after sepsis induction, the duration of our recording period. Immunohistochemical assays focused on brain stem mechanisms responsible for alterations in REMS, as little information is available concerning infection-induced suppression of this sleep stage. Our immunohistochemical data suggest that REMS suppression after sepsis onset may be mediated, in part, by the brain stem GABAergic system. This study demonstrates for the first time that sleep and EEG patterns are altered during CLP-induced sepsis. These data suggest that the EEG may serve as a biomarker for sepsis onset. These data also contribute to our knowledge of potential mechanisms, whereby infections alter sleep and other central nervous system functions. PMID:21900639

Baracchi, Francesca; Ingiosi, Ashley M.; Raymond, Richard M.

2011-01-01

267

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

268

Mortality Predictors in Renal Transplant Recipients with Severe Sepsis and Septic Shock  

PubMed Central

Introduction The growing number of renal transplant recipients in a sustained immunosuppressive state is a factor that can contribute to increased incidence of sepsis. However, relatively little is known about sepsis in this population. The aim of this single-center study was to evaluate the factors associated with hospital mortality in renal transplant patients admitted to the intensive care unit (ICU) with severe sepsis and septic shock. Methods Patient demographics and transplant-related and ICU stay data were retrospectively collected. Multiple logistic regression was conducted to identify the independent risk factors associated with hospital mortality. Results A total of 190 patients were enrolled, 64.2% of whom received kidneys from deceased donors. The mean patient age was 51±13 years (males, 115 [60.5%]), and the median APACHE II was 20 (16–23). The majority of patients developed sepsis late after the renal transplantation (2.1 [0.6–2.3] years). The lung was the most common infection site (59.5%). Upon ICU admission, 16.4% of the patients had ?1 systemic inflammatory response syndrome criteria. Among the patients, 61.5% presented with ?2 organ failures at admission, and 27.9% experienced septic shock within the first 24 hours of ICU admission. The overall hospital mortality rate was 38.4%. In the multivariate analysis, the independent determinants of hospital mortality were male gender (OR?=?5.9; 95% CI, 1.7–19.6; p?=?0.004), delta SOFA 24 h (OR?=?1.7; 95% CI, 1.2–2.3; p?=?0.001), mechanical ventilation (OR?=?30; 95% CI, 8.8–102.2; p<0.0001), hematologic dysfunction (OR?=?6.8; 95% CI, 2.0–22.6; p?=?0.002), admission from the ward (OR?=?3.4; 95% CI, 1.2–9.7; p?=?0.02) and acute kidney injury stage 3 (OR?=?5.7; 95% CI,1.9–16.6; p?=?0.002). Conclusions Hospital mortality in renal transplant patients with severe sepsis and septic shock was associated with male gender, admission from the wards, worse SOFA scores on the first day and the presence of hematologic dysfunction, mechanical ventilation or advanced graft dysfunction. PMID:25369197

de Carvalho, Monica Andrade; Freitas, Flavio Geraldo Rezende; Silva Junior, Helio Tedesco; Bafi, Antonio Toneti; Machado, Flavia Ribeiro; Pestana, Jose Osmar Medina

2014-01-01

269

Bai-Hu-Tang, Ancient Chinese Medicine Formula, May Provide a New Complementary Treatment Option for Sepsis  

PubMed Central

Bai-Hu-Tang (BHT) has been broadly applied to treating the early stage of acute infection with systemic inflammation for two thousand years in Chinese medicine. We explore whether BHT is beneficial in treating sepsis and its effects on proinflammatory cytokine, interleukin-6, and anti-inflammatory cytokine interleukin-10, in which both play key roles in the progress of sepsis. Thirty-six male Sprague-Dawley rats were randomized into six groups, with cecal ligation and puncture (CLP) performed in all but the sham-control group. Rats in CLP + BHT-L6 and CLP + BHT-H6 groups, respectively, received a low (0.45?g/kg) and high doses (0.9?g/kg) of BHT, 6?hrs postoperatively. CLP + BHT-L12 and CLP + BHT-H12 groups, respectively, received low and high doses of BHT, 12?hrs postoperatively. Sham-control and sepsis-control groups received distilled water (1?mL) as vehicle, 6 hrs postoperatively. Serial blood samples were drawn before operation, as baseline, and at 4, 8, and 12?hrs postoperatively for IL-6 and IL-10 assay. All rats were monitored for 3 days for survival study. Rats in the CLP + BHT-H6 group had significantly higher survival rate (80%) and significantly lower levels of both IL-6 and IL-10 at 12?hrs postoperatively than those in the sepsis-control group. Results suggested that BHT may be a new complementary treatment option for sepsis. PMID:23762108

Lin, Chien-Jung; Su, Yi-Chang; Lee, Cheng-Hung; Li, Tsai-Chung; Chen, Yun-An; Lin, Sunny Jui-Shan

2013-01-01

270

Anti-inflammatory effects of mangiferin on sepsis-induced lung injury in mice via up-regulation of heme oxygenase-1.  

PubMed

Sepsis, a serious unbalanced hyperinflammatory condition, is a tremendous burden for healthcare systems, with a high mortality and limited treatment. Increasing evidences indicated that some active components derived from natural foods have potent anti-inflammatory properties. Here we show that mangiferin (MF), a natural glucosyl xanthone found in both mango and papaya, attenuates cecal ligation and puncture-induced mortality and acute lung injury (ALI), as indicated by reduced systemic and pulmonary inflammatory responses. Moreover, pretreatment with MF inhibits sepsis-activated mitogen-activated protein kinases and nuclear factor kappa-light-chain-enhancer of activated B cells signaling, resulting in inhibiting production of proinflammatory mediators. Notably, MF dose-dependently up-regulates the expression and activity of heme oxygenase (HO)-1 in the lung of septic mice. Further, these beneficial effects of MF on the septic lung injury were eliminated by ZnPP IX, a specific HO-1 inhibitor. Our results suggest that MF attenuates sepsis by up-regulation of HO-1 that protects against sepsis-induced ALI through inhibiting inflammatory signaling and proinflammatory mediators. Thereby, MF may be effective in treating sepsis with ALI. PMID:23266284

Gong, Xia; Zhang, Li; Jiang, Rong; Ye, Mengliang; Yin, Xinru; Wan, Jingyuan

2013-06-01

271

The impact of body temperature abnormalities on the disease severity and outcome in patients with severe sepsis: an analysis from a multicenter, prospective survey of severe sepsis  

PubMed Central

Introduction Abnormal body temperatures (Tb) are frequently seen in patients with severe sepsis. However, the relationship between Tb abnormalities and the severity of disease is not clear. This study investigated the impact of Tb on disease severity and outcomes in patients with severe sepsis. Methods We enrolled 624 patients with severe sepsis and grouped them into 6 categories according to their Tb at the time of enrollment. The temperature categories (?35.5°C, 35.6–36.5°C, 36.6–37.5°C, 37.6–38.5°C, 38.6–39.5°C, ?39.6°C) were based on the temperature data of the Acute Physiology and Chronic Health Evaluation II (APACHE II) scoring. We compared patient characteristics, physiological data, and mortality between groups. Results Patients with Tb of ?36.5°C had significantly worse sequential organ failure assessment (SOFA) scores when compared with patients with Tb >37.5°C on the day of enrollment. Scores for APACHE II were also higher in patients with Tb ?35.5°C when compared with patients with Tb >36.5°C. The 28-day and hospital mortality was significantly higher in patients with Tb ?36.5°C. The difference in mortality rate was especially noticeable when patients with Tb ?35.5°C were compared with patients who had Tb of >36.5°C. Although mortality did not relate to Tb ranges of ?37.6°C as compared to reference range of 36.6–37.5°C, relative risk for 28-day mortality was significantly greater in patients with 35.6–36.5°C and ?35.5°C (odds ratio; 2.032, 3.096, respectively). When patients were divided into groups based on the presence (?36.5°C, n?=?160) or absence (>36.5°C, n?=?464) of hypothermia, disseminated intravascular coagulation (DIC) as well as SOFA and APACHE II scores were significantly higher in patients with hypothermia. Patients with hypothermia had significantly higher 28-day and hospital mortality rates than those without hypothermia (38.1% vs. 17.9% and 49.4% vs. 22.6%, respectively). The presence of hypothermia was an independent predictor of 28-day mortality, and the differences between patients with and without hypothermia were observed irrespective of the presence of septic shock. Conclusions In patients with severe sepsis, hypothermia (Tb ?36.5°C) was associated with increased mortality and organ failure, irrespective of the presence of septic shock. Trial registration UMIN-CTR ID UMIN000008195 PMID:24220071

2013-01-01

272

Severity of multiple organ failure (MOF) but not of sepsis correlates with irreversible platelet degranulation  

Microsoft Academic Search

Summary Multiple hemostatic changes occur in sepsis and multiple organ failure (MOF). To evaluate the role of platelets in patients with sepsis and MOF, we examined changes in surface glycoproteins on circulating platelets of 14 patients with suspected sepsis and MOF. The severity of sepsis and MOF was assessed by the Elebute and APACHE II scoring systems, respectively. Using flow

M. Gawaz; Suzanne Fateh-Moghadam; G. Pilz; H. J. Gurland; K. Werdan

1995-01-01

273

Positive Maternal C-Reactive Protein Predicts Neonatal Sepsis  

PubMed Central

Purpose To evaluate the diagnostic performance of maternal inflammatory marker: C-reactive protein (CRP) in predicting early onset neonatal sepsis (that occurring within 72 hours after birth). Materials and Methods 126 low birth weight newborns (gestation 32±3.2 wk, birth weight 1887±623 g) and their mothers were included. Neonates were divided into sepsis group (n=51) including both proven (positive blood culture) and suspected (negative blood culture but with more than 3 abnormal clinical signs), and controls (n=75). Mothers were subgrouped into CRP positive ?1.22 mg/dL (n=48) and CRP negative <1.22 mg/dL (n=78) group, determined by Receiver Operating Characteristic curves, and odds ratio was calculated for neonatal sepsis according to maternal condition. Results Maternal CRP was significantly higher in neonatal sepsis group than in control (3.55±2.69 vs. 0.48±0.31 mg/dL, p=0.0001). Maternal CRP (cutoff value >1.22 mg/dL) had sensitivity 71% and specificity 84% for predicting neonatal sepsis. Maternal CRP positive group had more neonatal sepsis than CRP negative group (71% vs. 29%, p<0.001). Odds ratio of neonatal sepsis in maternal CRP positive group versus CRP negative group was 10.68 (95% confidence interval: 4.313-26.428, p<0.001). Conclusion The risk of early onset neonatal sepsis significantly increased in the case of positive maternal CRP (?1.22 mg/dL). In newborn of CRP positive mother, the clinician may be alerted to earlier evaluation for possible neonatal infection prior to development of sepsis. PMID:24339295

Jeon, Ji Hyun; Park, Min Soo; Park, Koo In; Lee, Chul

2014-01-01

274

Murine monoclonal antibodies reactive with human heart and group A streptococcal membrane antigens.  

PubMed Central

Ten selected murine hybridoma cell lines that produce monoclonal antibodies against M type 5 Streptococcus pyogenes and human heart antigen were isolated. All of the monoclonal antibodies studied were determined to be the immunoglobulin M isotype. The antibodies were characterized on the basis of their reactions with Triton X-100-extracted whole human heart antigens, sodium dodecyl sulfate-extracted sarcolemmal antigens, and whole streptococci or their membranes. Enzyme-linked immunosorbent assays and Western immunoblotting techniques were used to compare the reactivity of the monoclonal antibodies. All 10 of the antibodies were first selected for their reactivity with Triton X-100-extracted heart antigens and whole group A, M type 5 streptococci. These antibodies were then divided into two categories: strong reactors or weak reactors with human sarcolemmal and streptococcal membranes. Among the strong reactors, two different types of monoclonal antibodies were observed on the basis of their immunobanding patterns with sarcolemmal and streptococcal membranes on Western blots. Monoclonal antibodies that were strong reactors with sarcolemmal and group A streptococcal membrane antigen were directed against a determinant on a family of proteins. The major reactants of sarcolemmal extracts were high-molecular-weight proteins near 200,000. Some monoclonal antibodies demonstrated more specificity for the heart than did others when reacted with separated Triton X-100-extracted tissue antigens from the heart, kidney, and skeletal muscle. One of the monoclonal antibodies that reacted with group A streptococci reacted with a Triton X-100-extracted heart antigen ca. 40,000 daltons in size. None of these monoclonal antibodies opsonized type 5 Streptococcus pyogenes, and in enzyme-linked immunosorbent assays most of the antibodies were found to react to a lesser degree with other groups of streptococci. Monoclonal antibody was used to probe normal and rheumatic sarcolemma for differences in reactivity. Although the rheumatic heart reacted more intensely, no major differences between the immunobanding patterns of normal and rheumatic hearts were observed. Images PMID:6384047

Cunningham, M W; Krisher, K; Graves, D C

1984-01-01

275

Management and Treatment Guidelines for Sepsis in Pediatric Patients  

PubMed Central

Sepsis remains one of the leading causes of morbidity and mortality in children despite improved understanding of the pathophysiology leading to better clinical management and survival. Recent studies have identified several areas that must be addressed by the clinician in order to continue to impact the morbidity and mortality associated with sepsis. In this review, we discuss the evidence in several of these areas including initial resuscitation, pathogen eradication, maintenance of oxygen delivery, and directed modifiers of the inflammatory response. Our overall goal is to provide the bedside clinician with an updated systematic approach to treat sepsis in children. PMID:23125881

El-wiher, Nidal; Cornell, Timothy T.; Kissoon, Nranjany; Shanley, Thomas P.

2012-01-01

276

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

277

Non-typhoidal Salmonella septic arthritis in an immunocompetent child with a pharyngeal streptococcal infection.  

PubMed

We report the case of an immunocompetent child who showed monoarticular arthritis and fever, preceded by pharyngitis and arthralgias. Because group A beta-hemolytic Streptococcus had been detected in the pharyngeal swab, erythromycin was given on admission. However, based on ultrasound examination, therapy with ceftriaxone and joint fluid drainage were promptly performed, and a rapid and full recovery followed. Meanwhile, Salmonella enterica infection was revealed in blood and joint fluid. Our case suggests that septic arthritis caused by a non-typhoidal Salmonella infection may occur without gastrointestinal manifestations and concomitantly with a pharyngeal streptococcal infection. PMID:18707909

Pezone, Ilaria; Penna, Maria Rosa Della; Flamini, Stefano; Nigro, Giovanni

2009-01-01

278

A generic pathogen capture technology for sepsis diagnosis  

E-print Network

Sepsis is a systemic inflammatory response that results the presence and persistence of microorganisms or their toxins in the bloodstream and it is diagnosed by detecting the presence of pathogens in blood. Despite ...

Cooper, Ryan Mcomber

2013-01-01

279

Novel Insights for Systemic Inflammation in Sepsis and Hemorrhage  

PubMed Central

The inflammatory responses in sepsis and hemorrhage remain a major cause of death. Clinically, it is generally accepted that shock in sepsis or hemorrhage differs in its mechanisms. However, the recognition of inflammatory cytokines as a common lethal pathway has become consent. Proinflammatory cytokines such as tumor necrosis factor (TNF) or high-mobility group box1 (HMGB1) are fanatically released and cause lethal multiorgan dysfunction. Inhibition of these cytokines can prevent the inflammatory responses and organ damage. In seeking potential anti-inflammatory strategies, we reported that ethyl pyruvate and alpha7 nicotinic acetylcholine receptor (alpha7nAChR) agonists effectively restrained cytokine production to provide therapeutic benefits in both experimental sepsis and hemorrhage. Here, we review the inflammatory responses and the anti-inflammatory strategies in experimental models of sepsis and hemorrhage, as they may have a consistent inflammatory pathway in spite of their different pathophysiological processes. PMID:20628562

Cai, Bolin; Deitch, Edwin A.; Ulloa, Luis

2010-01-01

280

Biomarkers for Sepsis: A Review with Special Attention to India  

PubMed Central

Sepsis is a serious infection and still a common cause of morbidity and mortality in resource-limited settings such as India. Even when microbiologic diagnostics are available, bacteremia is only identified in a proportion of patients who present with sepsis and bloodstream infections. Biomarkers have been used in a variety of disease processes and can help aid in diagnosing bacterial infections. There have been numerous biomarkers investigated to aid with diagnosis and prognostication in sepsis with the majority suffering from lack of sensitivity or specificity. Procalcitonin has been heralded as the biomarker that holds the most promise for bloodstream infections. Data are emerging in India, and in this review, we focus on the current data of biomarkers in sepsis with particular attention to how biomarkers could be used to augment diagnosis and treatment in India. PMID:24772418

Nelson, George E.; Gupta, Amita

2014-01-01

281

Thrombomodulin: A Bifunctional Modulator of Inflammation and Coagulation in Sepsis  

PubMed Central

Deregulated interplay between inflammation and coagulation plays a pivotal role in the pathogenesis of sepsis. Therapeutic approaches that simultaneously target both inflammation and coagulation hold great promise for the treatment of sepsis. Thrombomodulin is an endogenous anticoagulant protein that, in cooperation with protein C and thrombin-activatable fibrinolysis inhibitor, serves to maintain the endothelial microenvironment in an anti-inflammatory and anticoagulant state. A recombinant soluble form of thrombomodulin has been approved to treat patients suffering from disseminated intravascular coagulation (DIC) and has thus far shown greater therapeutic potential than heparin. A phase II clinical trial is currently underway in the USA to study the efficacy of thrombomodulin for the treatment of sepsis with DIC complications. This paper focuses on the critical roles that thrombomodulin plays at the intersection of inflammation and coagulation and proposes the possible existence of interactions with integrins via protein C. Finally, we provide a rationale for the clinical application of thrombomodulin for alleviating sepsis. PMID:22482044

Okamoto, Takayuki; Tanigami, Hironobu; Suzuki, Koji; Shimaoka, Motomu

2012-01-01

282

Mechanisms and regulation of the gene expression response to sepsis  

PubMed Central

Sepsis is defined as the systemic inflammatory response of the human host that is triggered by an invading pathogen. Despite tremendous advances in both our knowledge of and treatment strategies for this syndrome, sepsis remains among the major causes of morbidity and mortality in children worldwide. Thus, we hypothesize that an improved mechanistic understanding obtained via basic and translational science will continue to identify novel therapeutic targets and approaches. As a result, given the central importance of the alterations in gene expression in regulating the human host’s physiologic response to a pathogen, we review those complex factors: genetics, transcriptional expression and epigenetics, which regulate unique gene expression patterns in pediatric sepsis and septic shock. We anticipate that emerging data from genetic, genomic and other translation studies in pediatric sepsis will advance our biologic understanding of this response and undoubtedly identify targets for newer therapies. PMID:20478944

Cornell, Timothy T.; Wynn, James; Shanley, Thomas P.; Wheeler, Derek S.; Wong, Hector R.

2010-01-01

283

Staff training: a key factor in reducing intravascular catheter sepsis.  

PubMed Central

A children's hospital nutritional care team prospectively monitored the frequency of sepsis in central venous catheters used for administering parenteral nutrition. During an initial study period of 12 months, 26/58 (45%) of catheters were removed because of proved sepsis. The possible causes of this alarmingly high rate were examined, with catheter care techniques on the wards coming under particular scrutiny. As a result protocols were modified and an intensive staff training programme implemented throughout the hospital, led by the nutritional care sister. Subsequently, the catheter sepsis rate was significantly reduced with only 9/107 (8%) of consecutive catheters becoming infected. These findings emphasise the key role that education of staff plays in controlling central venous catheter sepsis and the importance and cost effectiveness of special nursing staff in implementing such measures. PMID:1902650

Puntis, J W; Holden, C E; Smallman, S; Finkel, Y; George, R H; Booth, I W

1991-01-01

284

High-density lipoproteins in sepsis and septic shock: metabolism, actions, and therapeutic applications.  

PubMed

Sepsis and septic shock are important causes of morbidity and lethality in noncoronary intensive care units. Circulating levels of high-density lipoproteins (HDLs) are reduced in sepsis/septic shock, and the magnitude of this reduction is positively correlated with the severity of the illness. The mechanisms underlying this phenomenon are incompletely understood, although increased levels of several acute-phase proteins, including serum amyloid A (SAA) and secretory phospholipase A2 (sPLA2), may contribute to the decrease in plasma HDLs. It has been suggested that HDLs possess anti-inflammatory properties and, hence, may play a crucial role in innate immunity by regulating the inflammatory response as well as being capable of reducing the severity of organ injury in animals and patients with septic shock. These protective effects of HDLs are mediated mainly via (a) lipopolysaccharide (LPS) binding and neutralization, (b) the HDL-associated enzymes, plasma paraoxonase (PON1) and platelet-activating factor acetylhydrolase (PAF-AH), which protect low-density lipoproteins against peroxidative damage, (c) inhibition of the expression of endothelial cell adhesion molecules and release of proinflammatory cytokines, which prevents inflammatory cell infiltration and subsequent multiple organ dysfunction, and (d) stimulation of the expression of endothelial nitric oxide synthase (eNOS). Thus, HDL exerts potent anti-inflammatory effects, some of which are independent of endotoxin binding and might be useful in the treatment of patients with not only sepsis/septic shock but also other conditions associated with an uncontrolled inflammatory response, such as ischemia-reperfusion injury and hemorrhagic shock. PMID:14770033

Wu, Aihua; Hinds, Charles J; Thiemermann, Christoph

2004-03-01

285

Defense From the Group A Streptococcus by Active and Passive Vaccination With the Streptococcal Hemoprotein Receptor  

PubMed Central

Background.?The worldwide burden of the Group A Streptococcus (GAS) primary infection and sequelae is considerable, although immunization programs with broad coverage of the hyper variable GAS are still missing. We evaluate the streptococcal hemoprotein receptor (Shr), a conserved streptococcal protein, as a vaccine candidate against GAS infection. Methods.?Mice were immunized intraperitoneally with purified Shr or intranasally with Shr-expressing Lactococcus lactis. The resulting humoral response in serum and secretions was determined. We evaluated protection from GAS infection in mice after active or passive vaccination with Shr, and Shr antiserum was tested for bactericidal activity. Results.?A robust Shr-specific immunoglobulin (Ig) G response was observed in mouse serum after intraperitoneal vaccination with Shr. Intranasal immunization elicited both a strong IgG reaction in the serum and a specific IgA reaction in secretions. Shr immunization in both models allowed enhanced protection from systemic GAS challenge. Rabbit Shr antiserum was opsonizing, and mice that were administrated with Shr antiserum prior to the infection demonstrated a significantly higher survival rate than did mice treated with normal rabbit serum. Conclusions.?Shr is a promising vaccine candidate that is capable of eliciting bactericidal antibody response and conferring immunity against systemic GAS infection in both passive and active vaccination models. PMID:21592989

Huang, Ya-Shu; Fisher, Morly; Nasrawi, Ziyad

2011-01-01

286

THE USE OF PRECIPITIN ANALYSIS IN AGAR FOR THE STUDY OF HUMAN STREPTOCOCCAL INFECTIONS  

PubMed Central

Studies on the purification of group A streptococcal extracellular antigens detectable with naturally occurring human antibodies from normal individuals have been extended. It has been shown that streptococcal electrophoretic fractions intermediate between the most rapidly migrating components are quite complex. In the calcium phosphate chromatography of adjacent electrophoretic fractions, particular antigenic components desorbed at similar buffer elution steps. It is clear from the results obtained that substantially more extracellular antigens than the twelve heretofore recognized are secreted in human beings during infection, as judged by their detection with human antibodies. The precise number is not yet known, but is probably greater than 16. Of the nine components which thus far have been separated rather well from the others, four were previously identified as streptolysin "O," diphosphopyridine nucleotidase, proteinase precursor, and desoxyribonuclease B. The accumulated data substantiated these previous identifications. The identity of a fifth antigen has been made as a possible complex of C carbohydrate and protein. Tentative evidence for the relationship of a sixth component to scarlet fever toxin has been presented. It has been shown that rechromatography of crystalline proteinase precursor and desoxyribonuclease B on calcium phosphate columns resulted in elution principally at the expected stepwise increase in buffer concentration. Attempts to isolate antigens present as mixtures in some calcium phosphate chromatographic peaks, by rechromatography on DEAE or CM cellulose columns resulted in only limited further purifications. PMID:13710679

Halbert, S. P.; Auerbach, T.

1961-01-01

287

Novel Curcumin Diclofenac Conjugate Enhanced Curcumin Bioavailability and Efficacy in Streptococcal Cell Wall-induced Arthritis  

PubMed Central

Curcumin-diclofenac conjugate as been synthesized by esterification of phenolic group of curcumin with the acid moiety of diclofenac, and characterized by mass spectrometry, NMR, FTIR, DSC, thermogravimetric analysis and X-ray diffraction analysis. The relative solubility of curcumin-diclofenac conjugate, curcumin and diclofenac; stability of curcumin-diclofenac conjugate in intestinal extract; permeability study of curcumin-diclofenac conjugate using the everted rat intestinal sac method; stability of curcumin-diclofenac conjugate in gastrointestinal fluids and in vitro efficacy have been evaluated. In vivo bioavailability of curcumin-diclofenac conjugate and curcumin in Sprague-Dawley rats, and antiarthritic activity of curcumin-diclofenac conjugate, curcumin and diclofenac in modified streptococcal cell wall-induced arthritis model in Balb/c mice to mimic rheumatoid arthritis in humans have also been studied. In all of the above studies, curcumin-diclofenac conjugate exhibited enhanced stability as compared to curcumin; its activity was twice that of diclofenac in inhibiting thermal protein denaturation taken as a measure of in vitro antiinflammatory activity; it enhanced the bioavailability of curcumin by more than five folds, and significantly (P<0.01) alleviated the symptoms of arthritis in streptococcal cell wall-induced arthritis model as compared to both diclofenac and curcumin.

Jain, S. K.; Gill, M. S.; Pawar, H. S.; Suresh, Sarasija

2014-01-01

288

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

289

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...

290

Reduction in pediatric hospitalizations for varicella-related invasive group a streptococcal infections in the varicella vaccine era  

Microsoft Academic Search

ObjectivesTo assess changes in hospitalization rates for invasive group A streptococcal (IGAS) and varicella-associated IGAS (VA-IGAS) infections at a pediatric hospital over a period of 9 years, to characterize clinical features of patients with IGAS infections, and to assess frequency of macrolide-resistant IGAS isolates.

Roopal A. Patel; Helen J. Binns; Stanford T. Shulman

2004-01-01

291

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

292

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

293

Current trends in inflammatory and immunomodulatory mediators in sepsis  

PubMed Central

Sepsis refers to severe systemic inflammation in response to invading pathogens. An overwhelming immune response, as mediated by the release of various inflammatory mediators, can lead to shock, multiple organ damage, and even death. Cytokines, proteases, lipid mediators, gaseous substances, vasoactive peptides, and cell stress markers play key roles in sepsis pathophysiology. Various adhesion molecules and chemokines sequester and activate neutrophils into the target organs, further augmenting inflammation and tissue damage. Although the anti-inflammatory substances counterbalance proinflammatory mediators, prolonged immune modulation may cause host susceptibility to concurrent infections, thus reflecting enormous challenge toward developing effective clinical therapy against sepsis. To understand the complex interplay between pro- and anti-inflammatory phenomenon in sepsis, there is still an unmet need to study newly characterized mediators. In addition, revealing the current trends of novel mediators will upgrade our understanding on their signal transduction, cross-talk, and synergistic and immunomodulating roles during sepsis. This review highlights the latest discoveries of the mediators in sepsis linking to innate and adaptive immune systems, which may lead to resolution of many unexplored queries. PMID:23136259

Aziz, Monowar; Jacob, Asha; Yang, Weng-Lang; Matsuda, Akihisa; Wang, Ping

2013-01-01

294

Apolipoprotein M--a new biomarker in sepsis.  

PubMed

Sepsis is one of the leading causes of mortality in non-cardiac intensive care units, and the need for markers of progression and severity are high. Also, treatment of sepsis is highly debated and potential new targets of treatment are of great interest. In the previous issue of Critical Care Kumaraswamy and colleagues have investigated whether plasma apolipoprotein M (apoM) is affected during different grades of sepsis, septic shock and systemic inflammatory response syndrome. Interestingly, plasma apoM was significantly decreased in all groups of patients with a relationship to severity of disease. This identifies apoM as a potential new biomarker in sepsis. It also underscores the possibility that altered high-density lipoprotein in sepsis patients can affect the course of disease. Thus, since apoM is the carrier of Sphingosine-1-P (S1P), a molecule with great influence on vascular barrier function, the study presented raises the interest and relevance for further studies of apoM and S1P in relation to sepsis and inflammation. PMID:22587809

Christoffersen, Christina; Nielsen, Lars Bo

2012-01-01

295

Role of Circulating Lymphocytes in Patients with Sepsis  

PubMed Central

Sepsis is a systemic inflammatory response syndrome due to infection. The incidence rate is estimated to be up to 19 million cases worldwide per year and the number of cases is rising. Infection triggers a complex and prolonged host response, in which both the innate and adaptive immune response are involved. The disturbance of immune system cells plays a key role in the induction of abnormal levels of immunoregulatory molecules. Furthermore, the involvement of effector immune system cells also impairs the host response to the infective agents and tissue damage. Recently, postmortem studies of patients who died of sepsis have provided important insights into why septic patients die and showed an extensive depletion of CD4 and CD8 lymphocytes and they found that circulating blood cells showed similar findings. Thus, the knowledge of the characterization of circulating lymphocyte abnormalities is relevant for the understanding of the sepsis pathophysiology. In addition, monitoring the immune response in sepsis, including circulating lymphocyte subsets count, appears to be potential biomarker for predicting the clinical outcome of the patient. This paper analyzes the lymphocyte involvement and dysfunction found in patients with sepsis and new opportunities to prevent sepsis and guide therapeutic intervention have been revealed. PMID:25302303

de Pablo, Raul; Monserrat, Jorge; Prieto, Alfredo; Alvarez-Mon, Melchor

2014-01-01

296

Towards personalized medicine in sepsis: Quest for Shangri-La?  

PubMed Central

Expanded abstract Citation Boomer JS, To K, Chang KC, Takasu O, Osborne DF, Walton AH, Bricker TL, Jarman SD 2nd, Kreisel D, Krupnick AS, Srivastava A, Swanson PE, Green JM, Hotchkiss RS: Immunosuppression in patients who die of sepsis and multiple organ failure. JAMA 2011, 306:2594-2605. Background Severe sepsis is typically characterized by initial cytokine-mediated hyper-inflammation. Whether this hyper-inflammatory phase is followed by immunosuppression is a subject of controversy. Animal studies suggest that multiple immune defects occur in sepsis, but data from humans remain conflicting. Methods Objectives To determine the association of sepsis with changes in host innate and adaptive immunity and to examine potential mechanisms for putative immunosuppression. Design Rapid prospective postmortem spleen and lung tissue harvest and analysis within 120 minutes of death. Setting Intensive care units (ICUs) of academic medical centers. Subjects A convenience sample of 40 patients who died with active severe sepsis was taken over the course of 2 years to characterize their immune status at the time of death. Control spleens (n = 29) were obtained from patients who were declared brain dead or had emergent splenectomy due to trauma; control lungs (n = 20) were obtained from transplant donors or from lung cancer resections. Interventions None. Outcomes Cytokine secretion assays and immunophenotyping of cell surface receptor-ligand expression profiles were performed to identify potential mechanisms of immune dysfunction. Immunohistochemical staining was performed to evaluate the loss of immune effector cells. Results The mean ages (standard deviations) of patients with sepsis and controls were 71.7 (15.9) and 52.7 (15.0) years, respectively. Patients with sepsis were in the ICU for a median of 8 days (range of 1 to 195 days), whereas control patients were in the ICU for not more than 4 days. The median duration of sepsis was 4 days (range of 1 to 40 days). Anti-CD3/anti-CD28-stimulated splenocytes from patients with sepsis, compared with those from controls, had significant reductions in cytokine secretion at 5 hours: tumor necrosis factor, 5,361 (95% confidence interval (CI) 3,327 to 7,485) pg/mL versus 418 (95% CI 98 to 738) pg/mL; interferon-gamma, 1,374 (95% CI 550 to 2,197) pg/mL versus 37.5 (95% CI -5 to 80) pg/mL; interleukin-6, 3,691 (95% CI 2,313 to 5,070) versus 365 (95% CI 87 to 642) pg/mL; and interleukin-10, 633 (95% CI -269 to 1,534) versus 58 (95% CI -39 to 156) pg/mL (P < 0.001 for all). There were similar reductions in 5-hour lipopolysaccharidestimulated cytokine secretion. Cytokine secretion in patients with sepsis was generally less than 10% of that in controls, independently of age, duration of sepsis, corticosteroid use, and nutritional status. Despite differences between spleen and lung, flow cytometric analysis showed increased expression of selected inhibitory receptors and ligands and expansion of suppressor cell populations in both organs. Unique differences in cellular inhibitory molecule expression existed in immune cells isolated from lungs of patients with sepsis versus patients with cancer and versus transplant donors. Immunohistochemical staining showed extensive depletion of splenic CD4, CD8, and HLA-DR cells and expression of ligands for inhibitory receptors on lung epithelial cells. Conclusions Patients who die in the ICU following sepsis compared with patients who die of non-sepsis etiologies have bio-chemical, flow cytometric, and immunohistochemical findings consistent with those of immunosuppression. Targeted immune-enhancing therapy may be a valid approach in selected patients with sepsis. PMID:23398880

2013-01-01

297

The pediatric sepsis biomarker risk model  

PubMed Central

Introduction The intrinsic heterogeneity of clinical septic shock is a major challenge. For clinical trials, individual patient management, and quality improvement efforts, it is unclear which patients are least likely to survive and thus benefit from alternative treatment approaches. A robust risk stratification tool would greatly aid decision-making. The objective of our study was to derive and test a multi-biomarker-based risk model to predict outcome in pediatric septic shock. Methods Twelve candidate serum protein stratification biomarkers were identified from previous genome-wide expression profiling. To derive the risk stratification tool, biomarkers were measured in serum samples from 220 unselected children with septic shock, obtained during the first 24 hours of admission to the intensive care unit. Classification and Regression Tree (CART) analysis was used to generate a decision tree to predict 28-day all-cause mortality based on both biomarkers and clinical variables. The derived tree was subsequently tested in an independent cohort of 135 children with septic shock. Results The derived decision tree included five biomarkers. In the derivation cohort, sensitivity for mortality was 91% (95% CI 70 - 98), specificity was 86% (80 - 90), positive predictive value was 43% (29 - 58), and negative predictive value was 99% (95 - 100). When applied to the test cohort, sensitivity was 89% (64 - 98) and specificity was 64% (55 - 73). In an updated model including all 355 subjects in the combined derivation and test cohorts, sensitivity for mortality was 93% (79 - 98), specificity was 74% (69 - 79), positive predictive value was 32% (24 - 41), and negative predictive value was 99% (96 - 100). False positive subjects in the updated model had greater illness severity compared to the true negative subjects, as measured by persistence of organ failure, length of stay, and intensive care unit free days. Conclusions The pediatric sepsis biomarker risk model (PERSEVERE; PEdiatRic SEpsis biomarkEr Risk modEl) reliably identifies children at risk of death and greater illness severity from pediatric septic shock. PERSEVERE has the potential to substantially enhance clinical decision making, to adjust for risk in clinical trials, and to serve as a septic shock-specific quality metric. PMID:23025259

2012-01-01

298

Hospital-acquired acute kidney injury in the elderly  

Microsoft Academic Search

Acute kidney injury (AKI) is becoming increasingly common in elderly individuals. The presence of multiple comorbidities as well as age-related changes in the kidney, systemic vasculature and immunological system render older patients more prone to renal injury. Hypovolemia, sepsis, and iatrogenic complications related to drug toxicity, contrast-induced nephropathy, and perioperative complications therefore often occur in older hospitalized patients. Although AKI

Alexandra Chronopoulos; Dinna N. Cruz; Claudio Ronco

2010-01-01

299

Deficiency of protease-activated receptor-1 limits bacterial dissemination during severe Gram-negative sepsis (melioidosis).  

PubMed

Protease-activated receptor-1 (PAR-1) is a G-coupled transmembrane receptor expressed by multiple cell types present in the lungs that can be activated by various proteases generated during acute inflammation. In this study we aimed to investigate the role of PAR-1 during melioidosis, a common cause of (pneumo)sepsis in Southeast Asia in a murine model of intranasal inoculation of the causative pathogen Burkholderia (B.) pseudomallei. Our results show that endogenous PAR-1 facilitates bacterial growth and dissemination during murine melioidosis, which is associated with increased cell influxes. However, these observations have no impact on survival. PMID:24239704

Kager, Liesbeth M; Wiersinga, W Joost; Roelofs, Joris J T H; van 't Veer, Cornelis; van der Poll, Tom

2014-02-01

300

A3 AND P2Y2 RECEPTORS CONTROL THE RECRUITMENT OF NEUTROPHILS TO THE LUNGS IN A MOUSE MODEL OF SEPSIS  

PubMed Central

We have recently shown that A3 adenosine receptors and P2Y2 purinergic receptors play an important role in neutrophil chemotaxis. Chemotaxis of neutrophils to sites of infections is critical for immune defense. However, excessive accumulation of neutrophils in the lungs can cause acute lung tissue damage. Here we assessed the role of A3 and P2Y2 receptors in neutrophil sequestration to the lungs in a mouse model of sepsis. Sepsis was induced by cecal ligation and puncture (CLP) using adult male C57BL/6J mice (wild type [WT]), homozygous A3 receptor knockout (A3KO) mice, and P2Y2 receptor knockout (P2Y2KO) mice. Animals were killed 2, 4, 6, or 8 h after CLP, and peritoneal lavage fluid and blood were collected. Lungs were removed, and neutrophil infiltration was evaluated using elastase as a marker. Leukocyte and bacterial counts in peritoneal lavage fluid and blood samples were determined. Survival after sepsis was determined in a separate group. Leukocyte counts in the peritoneum were lower in A3KO and P2Y2KO mice than in WT mice. Conversely, initial leukocyte counts in the peripheral blood were higher in KO mice than in WT mice. Neutrophil sequestration to the lungs reached a maximum 2 h after CLP and remained significantly higher in WT mice compared with A3KO and P2Y2KO mice (P < 0.001). Survival after 24 h was significantly lower in WT mice (37.5%) than in A3KO or P2Y2KO mice (82.5%; P < 0.05). These data suggest that A3 and P2Y2 receptors are involved in the influx of neutrophils into the lungs after sepsis. Thus, pharmaceutical approaches that target these receptors might be useful to control acute lung tissue injury in sepsis. PMID:18091570

Inoue, Yoshiaki; Chen, Yu; Hirsh, Mark I.; Yip, Linda; Junger, Wolfgang G.

2014-01-01

301

The clinical utility of fibrin-related biomarkers in sepsis.  

PubMed

Sepsis is associated with systemic inflammatory responses and induction of intravascular fibrin formation. Our aim is to investigate whether three fibrin-related markers (FRM) reflect the extent of coagulation activation in vivo and evaluate their clinical usefulness in identifying as well as monitoring patients with sepsis. Fibrin-degradation products (FDP), D-dimer and soluble fibrin monomer assays were measured on plasma samples from patients in the ICU with sepsis (n?=?37), systemic inflammatory response syndrome (SIRS) (n?=?35) and healthy individuals (n?=?15). The levels were correlated with each other and also with fibrinogen, prothrombin time, platelets and antithrombin III. Clinical correlation was also performed for the diagnosis of sepsis and longitudinal monitoring for survival or death.There was strong correlation between the three FRM (r?=?0.38-0.93, P?sepsis, SIRS and healthy individuals with FDP, and D-dimer showing statistical significance (P?sepsis from those without. In addition, FDP would be preferable for monitoring with its statistically significant time-dependent prediction of survival or death from sepsis. PMID:24030119

Toh, Julien M H; Ken-Dror, Gie; Downey, Colin; Abrams, Simon T

2013-12-01

302

Cefotaxime for treatment of neonatal sepsis and meningitis.  

PubMed

Neonatal sepsis is a clinical syndrome characterized by systemic signs and symptoms, and bacteremia during the first month of life. The incidence is relatively low (one to eight cases/1000 live births), yet the risk of mortality is approximately 25%. Meningitis in the neonate is usually a sequela of bacteremia; however, it is discussed with neonatal sepsis, because they commonly share etiology and pathogenesis. The incidence of meningitis is usually a fraction of the number of infants with sepsis, varying in different settings from one-fourth to one-third. The mortality rate is high, varying in some series from 15%-50%. There are two major forms of presentation of neonatal sepsis. Early-onset disease presents as a fulminant, multisystemic illness during the first 5-7 days of life; late-onset disease is more commonly recognized after the first weeks of life. Because different microorganisms are responsible for the two forms of disease, the choice of antimicrobial agents also differs. Some organisms such as Escherichia coli, group B streptococci, and Listeria monocytogenes may be responsible, whereas other pathogens such as Staphylococcus aureus and S. epidermidis, and Pseudomonas aeruginosa are usually associated with late-onset disease. Classic initial (empiric) treatment of neonatal sepsis and meningitis consists of ampicillin and an aminoglycoside. With the advent of the third-generation cephalosporins, however, the empiric antimicrobial approach for neonatal sepsis and meningitis has changed in most centers. Third-generation cephalosporins cover more of the pathogens implicated in neonatal sepsis and meningitis, except for the enterococci and L. monocytogenes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7587023

Odio, C M

1995-01-01

303

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

304

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

305

Novel therapeutic targets for sepsis: regulation of exaggerated inflammatory responses.  

PubMed

Sepsis is a devastating and complex syndrome and continues to be a major cause of morbidity and mortality among critically ill patients at the surgical intensive care unit setting in the United States. The occurrence of sepsis and septic shock has increased significantly over the past two decades. Despite of highly dedicated basic research and numerous clinical trials, remarkable progress has not been made in the development of novel and effective therapeutics. The sepsis-induced physiologic derangements are due largely to the host responses to the invading microorganism in contrast to the direct effects of the microorganism itself. Sepsis, the systemic inflammatory response to infection, is marked by dysregulated production of pro-inflammatory cytokines. Although pro-inflammatory cytokine production is normally indispensable to protect against pathogens and promote tissue repair, the dysregulated and prolonged production of these cytokines can trigger a systemic inflammatory cascade mediated by chemokines, vasoactive amines, the complement and coagulation system, and reactive oxygen species (ROS), amongst others. These mediators collectively lead to multiple organ failure, and ultimately to death. In this regard, the role of inflammation in the pathophysiology of sepsis, although still incompletely understood, is clearly critical. Recent findings resulting from vigorous investigations have contributed to delineate various novel directions of sepsis therapeutics. Among these, this review article is focused on new promising mechanisms and concepts that could have a key role in anti-inflammatory strategies against sepsis, including 1) "inflammasome": a multiprotein complex that activates caspase-1; 2) "the cholinergic anti-inflammatory pathway": the efferent arm of the vagus nerve-mediated, brain-to-immune reflex; 3) "stem cells": unspecialized and undifferentiated precursor cells with the capacity for self-renewal and potential to change into cells of multiple lineages; 4) "milk fat globule-EGF factor VIII (MFG-E8)": a bridging molecule between apoptotic cells and phagocytes, which promotes phagocytosis of apoptotic cells. PMID:22398786

Matsuda, Akihisa; Jacob, Asha; Wu, Rongqian; Aziz, Monowar; Yang, Weng-Lang; Matsutani, Takeshi; Suzuki, Hideyuki; Furukawa, Kiyonori; Uchida, Eiji; Wang, Ping

2012-01-01

306

Presymptomatic Prediction of Sepsis in Intensive Care Unit Patients?  

PubMed Central

Postoperative or posttraumatic sepsis remains one of the leading causes of morbidity and mortality in hospital populations, especially in populations in intensive care units (ICUs). Central to the successful control of sepsis-associated infections is the ability to rapidly diagnose and treat disease. The ability to identify sepsis patients before they show any symptoms would have major benefits for the health care of ICU patients. For this study, 92 ICU patients who had undergone procedures that increased the risk of developing sepsis were recruited upon admission. Blood samples were taken daily until either a clinical diagnosis of sepsis was made or until the patient was discharged from the ICU. In addition to standard clinical and laboratory parameter testing, the levels of expression of interleukin-1? (IL-1?), IL-6, IL-8, and IL-10, tumor necrosis factor-?, FasL, and CCL2 mRNA were also measured by real-time reverse transcriptase PCR. The results of the analysis of the data using a nonlinear technique (neural network analysis) demonstrated discernible differences prior to the onset of overt sepsis. Neural networks using cytokine and chemokine data were able to correctly predict patient outcomes in an average of 83.09% of patient cases between 4 and 1 days before clinical diagnosis with high sensitivity and selectivity (91.43% and 80.20%, respectively). The neural network also had a predictive accuracy of 94.55% when data from 22 healthy volunteers was analyzed in conjunction with the ICU patient data. Our observations from this pilot study indicate that it may be possible to predict the onset of sepsis in a mixed patient population by using a panel of just seven biomarkers. PMID:18480235

Lukaszewski, R. A.; Yates, A. M.; Jackson, M. C.; Swingler, K.; Scherer, J. M.; Simpson, A. J.; Sadler, P.; McQuillan, P.; Titball, R. W.; Brooks, T. J. G.; Pearce, M. J.

2008-01-01

307

Should Israel screen all mothers-to-be to prevent early-onset of neonatal group B streptococcal disease? A cost-utility analysis  

PubMed Central

Background In Israel, an average of 37 children are born each year with sepsis and another four with meningitis as a result of Group B Streptococcal (GBS) disease. Israel currently only screens mothers with defined risk factors (around 15% of all pregnancies) in order to identify candidates for Intrapartum Antiobiotic Prophyhlaxis (IAP) of GBS. This paper presents a cost-utility analysis of implementing an alternative strategy, which would expand the current protocol to one aiming to screen all pregnant women at 35–37 weeks gestation based on taking a vaginal culture for GBS. Methods A spreadsheet model was built incorporating technical, epidemiological, health service costs, demographic and economic data based primarily on Israeli sources. Results The intervention of universal screening (compared with the current scenario) would increase screening costs from 580,000 NIS to 3,278,000 million NIS. In addition, the intervention would also increase penicillin costs from 39,000 NIS to 221,000 NIS. Current culture screening of approximately 15% of mothers-to-be with high risk factors resulted in 42 GBS births in 2008-9 (0.253/1000 births). Expanding culture screening to 85% of mothers-to-be, will decrease the number of GBS births to 17.3 (0.104/1000 births). The initial 2.9 million NIS incremental intervention costs are offset by decreased treatment costs of 1.9 million NIS and work productivity gains of 811,000 NIS as a result of a decrease in neurological sequelae from GBS caused meningitis. Thus the resultant net cost of the intervention is only around 134,000 NIS. Culture based screening will reduce the burden of disease by 12.6 discounted Quality Adjusted Life Years (QALYS), giving a very cost effective baseline incremental cost per QALY (cf. risk factor screening) of 10,641 NIS per QALY. The data was very sensitive to rates of anaphylactic shock and changes in the percentage of meningitis cases that had associated long term-sequelae. Conclusion It is recommended that Israel adopt universal culture-based GBS screening. PMID:23425020

2013-01-01

308

Population-based Surveillance for Group A Streptococcal Necrotizing Fasciitis: Clinical Features, Prognostic Indicators, and Microbiologic Analysis of Seventy-Seven  

Microsoft Academic Search

acquired in a nursing home. Forty-seven percent of cases were associated with the presence of streptococcal toxic shock syndrome (Strep TSS) and 46% were bacteremic. Thirty-four percent of cases died and mortality was correlated with increasing age (P Å 0.006), presence of hypotension (P Å 0.01), and bacteremia (P Å 0.03). The most common streptococcal serotypes were M1 (35%) and

Cases Rupert Kaul; Allison McGeer; Donald E. Low; Karen Green; Benjamin Schwartz; Andrew E. Simor

309

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

310

Complete genome sequencing and analysis of a Lancefield group G Streptococcus dysgalactiae subsp. equisimilis strain causing streptococcal toxic shock syndrome (STSS)  

Microsoft Academic Search

BACKGROUND: Streptococcus dysgalactiae subsp. equisimilis (SDSE) causes invasive streptococcal infections, including streptococcal toxic shock syndrome (STSS), as does Lancefield group A Streptococcus pyogenes (GAS). We sequenced the entire genome of SDSE strain GGS_124 isolated from a patient with STSS. RESULTS: We found that GGS_124 consisted of a circular genome of 2,106,340 bp. Comparative analyses among bacterial genomes indicated that GGS_124

Yumi Shimomura; Kayo Okumura; Somay Yamagata Murayama; Junji Yagi; Kimiko Ubukata; Teruo Kirikae; Tohru Miyoshi-Akiyama

2011-01-01

311

Improving the care of sepsis: Between system redesign and professional responsibility: A roundtable discussion in the world sepsis day, September 25, 2013, Riyadh, Saudi Arabia  

PubMed Central

This paper summarizes the roundtable discussion in September 25, 2013, Riyadh, Saudi Arabia as part of the World Sepsis Day held in King Abdulaziz Medical City, Riyadh. The objectives of the roundtable discussion were to (1) review the chasm between the current management of sepsis and best practice, (2) discuss system redesign and role of the microsystem in sepsis management, (3) emphasize the multidisciplinary nature of the care of sepsis and that improvement of the care of sepsis is the responsibility of all, (4) discuss the bundle concept in sepsis management, and (5) reflect on the individual responsibility of the health care team toward sepsis with a focus on accountability and the moral agent. PMID:24987470

Arabi, Yaseen; Alamry, Ahmed; Levy, Mitchell M.; Taher, Saadi; Marini, Abdellatif M.

2014-01-01

312

Pharmacologic Targeting of Sphingosine-1-Phosphate Receptor 1 Improves the Renal Microcirculation during Sepsis in the Mouse.  

PubMed

Microvascular failure is hallmark of sepsis in humans and is recognized as a strong predictor of mortality. In the mouse subjected to cecal ligation and puncture (CLP) to induce a clinically relevant sepsis, renal microvascular permeability increases and peritubular capillary perfusion declines rapidly in the kidney leading to acute kidney injury (AKI). Sphingosine-1-phosphate (S1P) is a key regulator of microvascular endothelial function. To investigate the role of S1P in the development of microvascular permeability and peritubular capillary hypoperfusion in the kidney during CLP-induced AKI, we used a pharmacologic approach and a clinically relevant delayed dosing paradigm. Evans blue dye was used to measure renal microvascular permeability and intravital video microscopy was used to quantitate renal cortical capillary perfusion. The S1P receptor 1 (S1P1) agonist SEW2871 [5-[4-phenyl-5-(trifluoromethyl)-2-thienyl]-3-[3-(trifluoromethyl)phenyl]-1,2,4-oxadiazole] and S1P2 antagonist JTE-013 [N-(2,6-dichloro-4-pyridinyl)-2-[1,3-dimethyl-4-(1-methylethyl)-1H-pyrazolo[3,4-b]pyridin-6-yl]-hydrazinecarboxamide] were administered at the time of CLP and produced a dose-dependent but partial reduction in renal microvascular permeability at 6 hours after CLP. However, neither agent improved capillary perfusion at 6 hours. With delayed administration at 6 hours after CLP, only SEW2871 reversed microvascular permeability when measured at 18 hours. Importantly, SEW2871 also restored capillary perfusion and improved renal function. These data suggest that S1P1 and S1P2 do not regulate the early decline in renal capillary perfusion. However, later in the course of sepsis, pharmacologic stimulation of S1P1, even when delaying therapy until after injury has occurred, improves capillary and renal function, suggesting this approach should be evaluated as an adjunct therapy during sepsis. PMID:25355645

Wang, Zhen; Sims, Clark R; Patil, Naeem K; Gokden, Neriman; Mayeux, Philip R

2015-01-01

313

Propensity-based study of aminoglycoside nephrotoxicity in patients with severe sepsis or septic shock.  

PubMed

To assess the risk of acute kidney injury (AKI) attributable to aminoglycosides (AGs) in patients with severe sepsis or septic shock, we performed a retrospective cohort study in one medical intensive care unit (ICU) in France. Patients admitted for severe sepsis/septic shock between November 2008 and January 2010 were eligible. A propensity score for AG administration was built using day 1 demographic and clinical characteristics. Patients still on the ICU on day 3 were included. Patients with renal failure before day 3 or endocarditis were excluded. The time window for assessment of renal risk was day 3 to day 15, defined according to the RIFLE (risk, injury, failure, loss, and end-stage renal disease) classification. The AKI risk was assessed by means of a propensity-adjusted Cox proportional hazards regression analysis. Of 317 consecutive patients, 198 received AGs. The SAPS II (simplified acute physiology score II) score and nosocomial origin of infection favored the use of AGs, whereas a preexisting renal insufficiency and the neurological site of infection decreased the propensity for AG treatment. One hundred three patients with renal failure before day 3 were excluded. AGs were given once daily over 2.6 ± 1.1 days. AKI occurred in 16.3% of patients in a median time of 6 (interquartile range, 5 to 10) days. After adjustment to the clinical course and exposure to other nephrotoxic agents between day 1 and day 3, a propensity-adjusted Cox proportional hazards regression analysis showed no increased risk of AKI in patients receiving AGs (adjusted relative risk = 0.75 [0.32 to 1.76]). In conclusion, in critically septic patients presenting without early renal failure, aminoglycoside therapy for less than 3 days was not associated with an increased risk of AKI. PMID:25288085

Picard, W; Bazin, F; Clouzeau, B; Bui, H-N; Soulat, M; Guilhon, E; Vargas, F; Hilbert, G; Bouchet, S; Gruson, D; Moore, N; Boyer, A

2014-12-01

314

Proteome changes in mesenteric lymph induced by sepsis.  

PubMed

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

2014-12-01

315

Gram-negative sepsis: a dilemma of modern medicine.  

PubMed Central

Gram-negative sepsis is an increasingly common problem, with up to 300,000 cases occurring each year in the United States alone. Despite the ongoing development of new antibiotics, mortality from gram-negative sepsis remains unacceptably high. To stimulate earlier therapeutic intervention by physicians, a new set of broad definitions has been proposed to define the systemic inflammatory response characteristic of sepsis. In this review, the signs and symptoms of this progressive, injurious process are reviewed and its management is discussed, as are the mechanisms by which bacterial endotoxin triggers the biochemical events that lead to such serious complications as shock, adult respiratory distress syndrome, and disseminated intravascular coagulation. These events often occur even when appropriate antimicrobial therapy has been instituted. An increased understanding of the structure of endotoxin and its role in the development of sepsis, together with advances in hybridoma technology, has led to the development of monoclonal antibodies that bind to endotoxin and significantly attenuate its adverse effects. These agents promise to substantially reduce the morbidity and mortality associated with gram-negative sepsis. PMID:8457980

Bone, R C

1993-01-01

316

Sepsis in transit: from clinical to molecular classification  

PubMed Central

In the previous issue of Critical Care, Maslove and colleagues studied circulating neutrophil transcriptional expression to discover and validate a molecular subclassification of adult patients with sepsis. The authors divided patients into small derivation (n = 55) and validation (n = 71) cohorts. Their complex methodology included partitioning around medoid and hierarchical clustering methods to define two transcriptionally distinct subtypes of sepsis. Pathway analysis found that chemokine and cytokine pathways as well as Toll-like receptor signaling were enhanced. Investigation of specific drug target genes relevant to sepsis found significantly different expression levels between the two molecular subtypes. Interestingly, most patient characteristics did not differ between groups, except for an increase in the proportion of severe sepsis in molecular subtype 1. Possible confounders of this study were the small sample size, population stratification, and lack of information regarding drug interventions, all of which support the need for more studies with larger cohorts that include transcriptional profiles. This thought-provoking hypothesis-generating study could lead to a new neutrophil expression-based molecular classification of adult sepsis. PMID:23151274

2012-01-01

317

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

318

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

319

Penicillin-susceptible group B streptococcal clinical isolates with reduced cephalosporin susceptibility.  

PubMed

We characterized penicillin-susceptible group B streptococcal (PSGBS) clinical isolates exhibiting no growth inhibition zone around a ceftibuten disk (CTB(r) PSGBS). The CTB(r) PSGBS isolates, for which augmented MICs of cefaclor and ceftizoxime were found, shared a T394A substitution in penicillin-binding protein 2X (PBP 2X) and a T567I substitution in PBP 2B, together with an additional G429S substitution in PBP 2X or a T145A substitution in PBP 1A, although the T145A substitution in the transglycosidase domain of PBP 1A would have no effect on the level of resistance to ceftibuten. PMID:24920773

Nagano, Noriyuki; Nagano, Yukiko; Toyama, Masami; Kimura, Kouji; Shibayama, Keigo; Arakawa, Yoshichika

2014-09-01

320

Relatedness of Streptococcus canis from canine streptococcal toxic shock syndrome and necrotizing fasciitis.  

PubMed Central

The emergence of streptococcal toxic shock syndrome (STSS) and necrotizing fasciitis (NF) in dogs caused by Streptococcus canis has been reported by our laboratory. Since clonal expansion is thought to be partially responsible for the spread of invasive strains of Streptococcus pyogenes in humans, the relatedness of 15 isolates of S. canis from canine STSS and/or NF was examined using pulsed field gel electrophoresis and biotyping; production of proteases and of a CAMP-like reaction were also examined. Only 2 of the 15 STSS and/or NF isolates were clonally related, suggesting that the emergence of canine STSS/NF is not the result of clonal expansion of one or more highly virulent strains of S. canis. All of the isolates produced proteases and demonstrated a CAMP-like reaction, which appear to be additional characteristics of S. canis. PMID:10369564

DeWinter, L M; Prescott, J F

1999-01-01

321

Effect of penicillin on the humoral and cellular immune response following group A streptococcal pharyngitis.  

PubMed Central

The effect of oral and parenteral penicillin on the development of cellular and humoral immune responses in chimpanzees infected with group A streptococcal M-types 1, 5 and 12 was investigated. The interrelationship between type-specific antibody response and enhancement of phagocytic competence of polymorphonuclear neutrophils was documented. Penicillin depressed or suppressed type-specific antibody response depending on the mode and dose of administration, probably because of its effect on the streptococci responsible for antibody stimulation. Penicillin was not demonstrated to have a direct effect on phagocytic ability in vitro. Therefore the primary effect of antibiotic therapy is the indirect relationship to suppression or inhibition of type-specific antibody response to M-protein which results in a diminution of phagocytic competence. PMID:804981

Zimmerman, R A; Klesius, P H; Krushak, D H; Mathews, J H

1975-01-01

322

Novel Polymorphisms in the Myosin Light Chain Kinase Gene Confer Risk for Acute Lung Injury  

PubMed Central

The genetic basis of acute lung injury (ALI) is poorly understood. The myosin light chain kinase (MYLK) gene encodes the nonmuscle myosin light chain kinase isoform, a multifunctional protein involved in the inflammatory response (apoptosis, vascular permeability, leukocyte diapedesis). To examine MYLK as a novel candidate gene in sepsis-associated ALI, we sequenced exons, exon–intron boundaries, and 2 kb of 5? UTR of the MYLK, which revealed 51 single-nucleotide polymorphisms (SNPs). Potential association of 28 MYLK SNPs with sepsis-associated ALI were evaluated in a case-control sample of 288 European American subjects (EAs) with sepsis alone, subjects with sepsis-associated ALI, or healthy control subjects, and a sample population of 158 African American subjects (AAs) with sepsis and ALI. Significant single locus associations in EAs were observed between four MYLK SNPs and the sepsis phenotype (P < 0.001), with an additional SNP associated with the ALI phenotype (P = 0.03). A significant association of a single SNP (identical to the SNP identified in EAs) was observed in AAs with sepsis (P = 0.002) and with ALI (P = 0.01). Three sepsis risk-conferring haplotypes in EAs were defined downstream of start codon of smooth muscle MYLK isoform, a region containing putative regulatory elements (P < 0.001). In contrast, multiple haplotypic analyses revealed an ALI-specific, risk-conferring haplotype at 5? of the MYLK gene in both European and African Americans and an additional 3? region haplotype only in African Americans. These data strongly implicate MYLK genetic variants to confer increased risk of sepsis and sepsis-associated ALI. PMID:16399953

Gao, Li; Grant, Audrey; Halder, Indrani; Brower, Roy; Sevransky, Jonathan; Maloney, James P.; Moss, Marc; Shanholtz, Carl; Yates, Charles R.; Meduri, Gianfranco Umberto; Shriver, Mark D.; Ingersoll, Roxann; Scott, Alan F.; Beaty, Terri H.; Moitra, Jaideep; Ma, Shwu Fan; Ye, Shui Q.; Barnes, Kathleen C.; Garcia, Joe G. N.

2006-01-01

323

Prognostic Value of Venoarterial Carbon Dioxide Gradient in Patients with Severe Sepsis and Septic Shock  

PubMed Central

Aim To investigate the changes in the venoarterial carbon-dioxide gradient (V-a Pco2) and its prognostic value for survival of patients with severe sepsis and septic shock. Methods The study was conducted in General Hospital Holy Spirit from January 2004 to December 2007 and included 71 conveniently sampled adult patients (25 women and 46 men), who fulfilled the severe sepsis and septic shock criteria and were followed for a median of 8 days (interquartile range, 12 days). The patients were divided in two groups depending on whether or not they had been mechanically ventilated. Both groups of patients underwent interventions with an aim to achieve hemodynamic stability. Mechanical ventilation was applied in respiratory failure. Venoarterial carbon dioxide gradient was calculated from the difference between the partial pressure of arterial CO2 and the partial pressure of mixed venous CO2, which was measured with a pulmonary arterial Swan-Ganz catheter. The data were analyzed using Kaplan-Meier survival analysis, along with a calculation of the hazard ratios. Results There was a significant difference between non-ventilated and ventilated patients, with almost 4-fold greater hazard ratio for lethal outcome in ventilated patients (3.85; 95% confidence interval, 1.64-9.03). Furthermore, the pattern of changes of many other variables was also different in these two groups (carbon dioxide-related variables, variables related to acid-base status, mean arterial pressure, systemic vascular resistance, lactate, body mass index, Acute Physiology and Chronic Health Evaluation II, Simplified Acute Physiology II Score, and Sepsis-related Organ Failure Assessment score). Pco2 values (with a cut-off of 0.8 kPa) were a significant predictor of lethal outcome in non-ventilated patients (P?=?0.015) but not in ventilated ones (P?=?0.270). Conclusion V-a Pco2 was a significant predictor of fatal outcome only in the non-ventilated group of patients. Ventilated patients are more likely to be admitted with a less favorable clinical status, and other variables seem to have a more important role in their outcome. PMID:21162162

Troskot, Rosana; Simurina, Tatjana; Zizak, Mirza; Majstorovic, Karolina; Marinac, Ivana; Sutic, Ines Mrakovcic

2010-01-01

324

Microbial Analysis of Bite Marks by Sequence Comparison of Streptococcal DNA  

PubMed Central

Bite mark injuries often feature in violent crimes. Conventional morphometric methods for the forensic analysis of bite marks involve elements of subjective interpretation that threaten the credibility of this field. Human DNA recovered from bite marks has the highest evidentiary value, however recovery can be compromised by salivary components. This study assessed the feasibility of matching bacterial DNA sequences amplified from experimental bite marks to those obtained from the teeth responsible, with the aim of evaluating the capability of three genomic regions of streptococcal DNA to discriminate between participant samples. Bite mark and teeth swabs were collected from 16 participants. Bacterial DNA was extracted to provide the template for PCR primers specific for streptococcal 16S ribosomal RNA (16S rRNA) gene, 16S–23S intergenic spacer (ITS) and RNA polymerase beta subunit (rpoB). High throughput sequencing (GS FLX 454), followed by stringent quality filtering, generated reads from bite marks for comparison to those generated from teeth samples. For all three regions, the greatest overlaps of identical reads were between bite mark samples and the corresponding teeth samples. The average proportions of reads identical between bite mark and corresponding teeth samples were 0.31, 0.41 and 0.31, and for non-corresponding samples were 0.11, 0.20 and 0.016, for 16S rRNA, ITS and rpoB, respectively. The probabilities of correctly distinguishing matching and non-matching teeth samples were 0.92 for ITS, 0.99 for 16S rRNA and 1.0 for rpoB. These findings strongly support the tenet that bacterial DNA amplified from bite marks and teeth can provide corroborating information in the identification of assailants. PMID:23284761

Kennedy, Darnell M.; Stanton, Jo-Ann L.; Garcia, Jose A.; Mason, Chris; Rand, Christy J.; Kieser, Jules A.; Tompkins, Geoffrey R.

2012-01-01

325

Current recommendations for diagnosis and management of sepsis and septic shock.  

PubMed

Early recognition of sepsis and early goal-directed therapy following evidence-based bundles can reduce patient mortality from sepsis and septic shock. This article reviews current recommendations for diagnosis and management. PMID:24201922

Smith, Jami S

2013-10-01

326

Sepsis caused by food-borne infection with Escherichia coli.  

PubMed

We report a case of sepsis caused by Escherichia coli (E. coli) of serotype O-143. A 78-year-old man developed symptoms of gastroenteritis after ingesting raw meat on noodles. He rapidly developed respiratory failure. Blood culture grew E. coli. The sepsis seemed to have directly spread from a food-borne infection. The development of primary sepsis after ingesting E. coli is very rare. We suspect that bacterial translocation played a major role. Serotype O-143 is recognized in enteroinvasive E. coli (EIEC) as well as in Shigella dysenteriae. The pathogen in the present case is suspected of being EIEC although the isolated E. coli strain was negative for the inv and ipa genes. PMID:16415557

Wachi, Keiko; Tateda, Kazuhiro; Yamashiro, Yoshihiro; Takahashi, Miki; Matsumoto, Tetsuya; Furuya, Nobuhiko; Ishii, Yoshikazu; Akasaka, Yoshikiyo; Yamaguchi, Keizo; Uchida, Kou

2005-12-01

327

The microbiology and outcome of sepsis in Victoria, Australia.  

PubMed

We analysed data from 33741 patients with ICD-10-AM-defined sepsis from an Australian hospital morbidity dataset to investigate the relationships between specific types of organisms, potential risk factors for infection, organ dysfunction, ICU utilization and hospital mortality. A total of 24% of patients received some of their care in an intensive care unit, and the overall hospital mortality rate was 18%. Gram-positive bacteria were isolated in 27% of cases and Gram-negative bacteria in 20%. Sepsis due to Staphylococcus aureus was associated with vascular and joint devices whereas Pseudomonas aeruginosa and Gram-negative rods were more common with genitourinary devices and lymphoproliferative disease. Sepsis-associated organ dysfunction most commonly involved the respiratory system, followed by the renal and circulatory systems. These patterns may provide useful clues to the pathogenesis and therapy of this often fatal syndrome which is a major ongoing problem for hospitalized patients. PMID:16490135

Sundararajan, V; Korman, T; Macisaac, C; Presneill, J J; Cade, J F; Visvanathan, K

2006-04-01

328

[A case of Fasciola hepatica mimicking sepsis without eosinophilia].  

PubMed

Fasciolosis is a rare cause of hepatobiliary system infections and caused by the trematode Fasciola hepatica. It primarily infects sheeps or goats, and humans are accidental hosts. On laboratory findings, marked eosinophilia is present in most of the cases. Here, we report a case of fasciolosis without eosinophilia who was presented as sepsis and responded to therapy in second dose of triclabendazole. Sepsis like clinical presentation has been reported in few cases. Forty-eight year old female patient presented with high fever, abdominal pain, hypotension and tachycardia. The patient was considered as sepsis secondary to liver abscess, which was demonstrated on the initial abdominal ultrasonography (USG) findings. Therefore, empirical antibiotic therapy was started. Due to failure of the treatment, the image was found to be compatible with fasciolosis on control magnetic resonance imaging (MRI) and USG. On detailed anamnesis, history of eating watercress was learned and the diagnosis of fasciolosis was confirmed by serological tests. PMID:25016123

Oner Vatan, Asl?; Mete, Bilgül; Yemi?en, Mücahit; Kaya, Abdurrahman; Kantarc?, Fatih; Salto?lu, Ne?e

2014-06-01

329

Dynamic changes in thrombin generation in abdominal sepsis in mice.  

PubMed

Systemic inflammatory response syndrome and severe infections are associated with major derangements in the coagulation system. The purpose of this study was to examine the dynamic alterations in thrombin generation in abdominal sepsis. Abdominal sepsis was induced by cecal ligation and puncture (CLP) in C57/Bl6 mice. Cecal ligation and puncture caused a systemic inflammatory response, with neutrophil recruitment and tissue damage in the lung as well as thrombocytopenia and leukocytopenia. Thrombin generation, coagulation factors, lung histology, and myeloperoxidase activity was determined 1, 3, 6, and 24 h after induction of CLP. It was found that thrombin generation was increased 1 h after CLP and that thrombin generation started to decrease at 3 h and was markedly reduced 6 and 24 h after CLP induction. Platelet-poor plasma from healthy mice could completely reverse the inhibitory effect of CLP on thrombin generation, suggesting that sepsis caused a decrease in the levels of plasma factors regulating thrombin generation in septic animals. Indeed, it was found that CLP markedly decreased plasma levels of prothrombin, factor V, and factor X at 6 and 24 h. Moreover, we observed that CLP increased plasma levels of activated protein C at 6 h, which returned to baseline levels 24 h after CLP induction. Finally, pretreatment with imipenem/cilastatin attenuated the CLP-evoked decrease in thrombin generation and consumption of prothrombin 24 h after CLP induction. Our novel findings suggest that thrombin generation is initially increased and later decreased in abdominal sepsis. Sepsis-induced reduction in thrombin generation is correlated to changes in the plasma levels of coagulation factors and activated protein C. These findings help explain the dynamic changes in global hemostasis in abdominal sepsis. PMID:24978891

Wang, Yongzhi; O Braun, Oscar; Zhang, Su; Luo, Lingtao; Norström, Eva; Thorlacius, Henrik

2014-10-01

330

Ghrelin maintains the cardiovascular stability in severe sepsis  

PubMed Central

Background Cardiovascular dysfunction, characterized by reduced cardiac contractility and depressed endothelium-dependent vascular relaxation, is common in severe sepsis. Although it is known that ghrelin produces beneficial effects following various adverse circulatory conditions, it remains unknown whether ghrelin increases cardiac contractility and improves vascular responsiveness to vasoactive agents in severe sepsis. Methods Male adult rats were subjected to sepsis by cecal ligation and puncture (CLP). At 5 h after CLP, a bolus intravenous injection of 2 nmol ghrelin was followed by a continuous infusion of 12 nmol ghrelin via a primed mini-pump over 15 h. At 20 h after CLP (i.e., severe sepsis), the maximal rates of ventricular pressure increase (+dP/dtmax) and decrease (?dP/dtmax) were determined in vivo. In additional groups of animals, the thoracic aortae were isolated at 20 h after CLP. The aortae were cut into rings, and placed in organ chambers. Norepinephrine (NE) was used to induce vascular contraction. Dose responses for an endothelium-dependent vasodilator, acetylcholine (ACh), and an endothelium-independent vasodilator, nitroglycerine (NTG) were carried out. Results +dP/dtmax and ?dP/dtmax decreased significantly at 20 h after CLP. Treatment with ghrelin significantly increased +dP/dtmax and ?dP/dtmax by 36% (P<0.05) and 35% (P<0.05), respectively. Moreover, NE-induced vascular contraction and endothelium-dependent (ACh-induced) vascular relaxation decreased significantly at 20 h after CLP. Administration of ghrelin, however, increased NE-induced vascular contraction and ACh-induced vascular relaxation. In contrast, no significant reduction in NTG-induced vascular relaxation was seen in rats with severe sepsis irrespective of ghrelin treatment. Conclusions Ghrelin may be further developed as a useful agent for maintaining cardiovascular stability in severe sepsis. PMID:22459289

Wu, Rongqian; Chaung, Wayne W.; Dong, Weifeng; Ji, Youxin; Barrera, Rafael; Nicastro, Jeffrey; Molmenti, Ernesto P.; Coppa, Gene F.; Wang, Ping

2011-01-01

331

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

332

Optical detection of sepsis markers using liquid crystal based biosensors  

NASA Astrophysics Data System (ADS)

A liquid crystal based biosensor for the detection and diagnosis of sepsis is currently in development. Sepsis, a major clinical syndrome with a significant public health burden in the US due to a large elderly population, is the systemic response of the body to a localized infection and is defined as the combination of pathologic infection and physiological changes. Bacterial infections are responsible for 90% of cases of sepsis in the US. Currently there is no bedside diagnostic available to positively identify sepsis. The basic detection scheme employed in a liquid crystal biosensor contains attributes that would find value in a clinical setting, especially for the early detection of sepsis. Utilizing the unique properties of liquid crystals, such as birefringence, a bedside diagnostic is in development which will optically report the presence of biomolecules. In a septic patient, an endotoxin known as lipopolysaccharide (LPS) is released from the outer membrane of Gram-negative bacteria and can be found in the blood stream. It is hypothesized that this long chained molecule will cause local disruptions to the open surface of a sensor containing aligned liquid crystal. The bulk liquid crystal ampli.es these local changes at the surface due to the presence of the sepsis marker, providing an optical readout through polarizing microscopy images. Liquid crystal sensors consisting of both square and circular grids, 100-200 ?m in size, have been fabricated and filled with a common liquid crystal material, 5CB. Homeotropic alignment was confirmed using polarizing microscopy. The grids were then contacted with either saline only (control), or saline with varying concentrations of LPS. Changes in the con.guration of the nematic director of the liquid crystal were observed through the range of concentrations tested (5mg/mL - 1pg/mL) which have been confirmed by a consulting physician as clinically relevant levels.

McCamley, Maureen K.; Artenstein, Andrew W.; Opal, Steven M.; Crawford, Gregory P.

2007-02-01

333

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

PubMed

Abstract 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; Asenblad, Nils; Wallentin, Lars

2014-01-01

334

Acute lung injury review.  

PubMed

The first report of acute respiratory distress syndrome (ARDS) was published in 1967, and even now acute lung injury (ALI) and ARDS are severe forms of diffuse lung disease that impose a substantial health burden all over the world. Recent estimates indicate approximately 190,000 cases per year of ALI in the United States each year, with an associated 74,500 deaths per year. Common causes of ALI/ARDS are sepsis, pneumonia, trauma, aspiration pneumonia, pancreatitis, and so on. Several pathologic stages of ALI/ARDS have been described: acute inflammation with neutrophil infiltration, fibroproliferative phase with hyaline membranes, with varying degrees of interstitial fibrosis, and resolution phase. There has been intense investigation into the pathophysiologic events relevant to each stage of ALI/ARDS, and much has been learned in the alveolar epithelial, endobronchial homeostasis, and alveolar cell immune responses, especially neutrophils and alveolar macrophages in an animal model. However, these effective results in the animal models are not equally adoptive to those in randomized, controlled trials. The clinical course of ALI/ARDS is variable with the likely pathophysiologic complexity of human ALI/ARDS. In 1994, the definition was recommended by the American-European Consensus Conference Committee, which facilitated easy nomination of patients with ALI/ARDS for a randomized, clinical trial. Here, we review the recent randomized, clinical trials of ALI/ARDS. PMID:19420806

Tsushima, Kenji; King, Landon S; Aggarwal, Neil R; De Gorordo, Antonio; D'Alessio, Franco R; Kubo, Keishi

2009-01-01

335

Prolonged Lymphopenia, Lymphoid Depletion, and Hypoprolactinemia in Children with Nosocomial Sepsis and Multiple Organ Failure1  

Microsoft Academic Search

Lymphopenia and lymphoid depletion occur in adults dying of sepsis. Prolactin increases Bcl-2 expression, suppresses stress- induced lymphocyte apoptosis, and improves survival from experimental sepsis. We hypothesized that prolonged lymphopenia, lymphoid depletion, and hypoprolactinemia occur in children dying with sepsis and multiple organ failure (MOF). Fifty-eight critically ill children with and 55 without MOF admitted to a university hospital pediatric

Kate A. Felmet; Mark W. Hall; Robert S. B. Clark; Ronald Jaffe; Joseph A. Carcillo

336

Steroid responses in sepsis: some novel thinking that may provide new insight.  

PubMed

Glucocorticoid use in sepsis is controversial. In contrast to other extracellular signaling molecules, glucocorticoid receptors (GRs) are intra-cytoplasmic. Several GR isoforms have been identified. A study in Critical Care Forum suggests that sepsis alters the abundance of the dominant negative GR?. Here we discuss GR isoforms and how they may affect cellular responses to glucocorticoids in sepsis. PMID:23826670

Deutschman, Clifford S

2013-01-01

337

Steroid responses in sepsis: some novel thinking that may provide new insight  

PubMed Central

Glucocorticoid use in sepsis is controversial. In contrast to other extracellular signaling molecules, glucocorticoid receptors (GRs) are intra-cytoplasmic. Several GR isoforms have been identified. A study in Critical Care Forum suggests that sepsis alters the abundance of the dominant negative GR?. Here we discuss GR isoforms and how they may affect cellular responses to glucocorticoids in sepsis. PMID:23826670

2013-01-01

338

Preventing Staphylococcus aureus Sepsis through the Inhibition of Its Agglutination in Blood  

E-print Network

Preventing Staphylococcus aureus Sepsis through the Inhibition of Its Agglutination in Blood Molly Abstract Staphylococcus aureus infection is a frequent cause of sepsis in humans, a disease associated Staphylococcus aureus Sepsis through the Inhibition of Its Agglutination in Blood. PLoS Pathog 7(10): e1002307

339

Nucleotide sequence of the type A streptococcal exotoxin (erythrogenic toxin) gene from Streptococcus pyogenes bacteriophage T12.  

PubMed Central

The gene specifying type A streptococcal exotoxin (speA), also known as erythrogenic toxin, was cloned from the Streptococcus pyogenes bacteriophage T12 genome and analyzed by nucleotide sequencing. The speA gene consists of 753 base pairs and codes for a 29,244-molecular-weight protein. The speA gene product contains a putative 30-amino acid signal peptide, resulting in a molecular weight of 25,787 for the secreted protein. A possible promoter and ribosome-binding site are present in the region upstream from the speA gene, and a transcriptional terminator is located 69 bases downstream from the translational termination codon. The amino acid sequence of the carboxy-terminal portion of the type A streptococcal exotoxin exhibits extensive homology with the carboxy terminus of Staphylococcus aureus enterotoxins B and C1. PMID:3514452

Weeks, C R; Ferretti, J J

1986-01-01

340

Translocation of antibiotic resistance markers of a plasmid-free Streptococcus pyogenes (group A) strain into different streptococcal hemolysin plasmids  

Microsoft Academic Search

Wild-type strain A454 (Streptococcus pyogenes) transferred en bloc its erythromycin (Em) and tetracycline (Tc) resistance markers into several plasmid-free streptococcal recipients. No plasmid DNA was detected in either the wild-type or the transconjugant strains. Crosses were performed between A454 and S. faecalis Rec+ or Rec- recipients carrying hemolysin-bacteriocin plasmids, pIP964 or pAD1. The Em Tc-resistant transconjugants obtained harbored either the

Chantal Le Bouguenec; Thea Horaud; Gilda Bieth; R. Colimon; C. Dauguet

1984-01-01

341

Streptococcal upper respiratory tract infections and exacerbations of tic and obsessive-compulsive symptoms: A prospective longitudinal study  

PubMed Central

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 Associated with Streptococcal infections (PANDAS). A group of children with Tourette syndrome and/or obsessive-compulsive disorder without a PANDAS history served as the (non-PANDAS) comparison group. Method Consecutive clinical ratings of tic and OC symptom severity were obtained for 31 PANDAS subjects and 53 non-PANDAS subjects. Clinical symptoms and laboratory values (throat cultures and streptococcal antibody titers) were evaluated at regular intervals during a 25 month period. Additional testing occurred at the time of any tic or OC symptom exacerbation. New GABHS infections were established by throat swab cultures and/or recent significant rise in streptococcal antibodies. Laboratory personnel were blinded to case or control status, clinical (exacerbation or not) condition, and clinical evaluators were blinded to the laboratory results. Results No group differences were observed in either the number of clinical exacerbations or the number of newly diagnosed GABHS infections. On only six occasions out of a total of 51 (12%) a newly diagnosed GABHS infection was followed, within two months, by an exacerbation of tic and/or OC symptoms. In every instance, this association occurred in the non-PANDAS group. Conclusions This study provides no evidence for a temporal association between GABHS infections and tic/OC symptom exacerbations in children who meet the published PANDAS diagnostic criteria. PMID:21241948

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

2010-01-01

342

Locoregional immunotherapy of malignant effusion from colorectal cancer using the streptococcal preparation OK432 plus Interleukin2  

Microsoft Academic Search

In total, 16 patients with cytologically proven malignant effusion from colorectal cancer were treated by locoregional administration of the streptococcal preparation OK-432 alone or OK-432 plus the T-cell growth factor interleukin (IL)-2, and the action mechanism of the treatment was studied. A positive clinical response, showing a cytologic disappearance of cancer cells and decrease of effusion, was observed in nine

Y Yamaguchi; E Miyahara; A Ohshita; Y Kawabuchi; K Ohta; K Shimizu; K Minami; J Hihara; A Sawamura; T Toge

2003-01-01

343

Streptococcal Inhibitor of Complement Promotes Innate Immune Resistance Phenotypes of Invasive M1T1 Group A Streptococcus  

Microsoft Academic Search

Streptococcal inhibitor of complement (SIC) is a highly polymorphic extracellular protein and putative virulence factor secreted by M1 and M57 strains of group A Streptococcus (GAS). The sic gene is highly upregulated in invasive M1T1 GAS isolates following selection of mutations in the covR\\/S regulatory locus in vivo. Previous work has shown that SIC (allelic form 1.01) binds to and

Morgan A. Pence; Suzan H. M. Rooijakkers; Anna L. Cogen; Jason N. Cole; Andrew Hollands; Richard L. Gallo; Victor Nizet

2010-01-01

344

Group B Streptococcal ?-Hemolysin\\/Cytolysin Directly Impairs Cardiomyocyte Viability and Function  

Microsoft Academic Search

Background: Group B Streptococcus (GBS) is a leading cause of neonatal sepsis where myocardial dysfunction is an important contributor to poor outcome. Here we study the effects of the GBS pore-forming b-hemolysin\\/cytolysin (Bh\\/c) exotoxin on cardiomyocyte viability, contractility, and calcium transients. Methodology\\/Principal Findings: HL-1 cardiomyocytes exposed to intact wild-type (WT) or isogenic Dbh\\/c mutant GBS, or to cell-free extracts from

Mary E. Hensler; Shigeki Miyamoto; Victor Nizet

2008-01-01

345

Bench-to-bedside review: Understanding genetic predisposition to sepsis  

Microsoft Academic Search

Sepsis is a complex syndrome that develops when the initial, appropriate host response to an infection becomes amplified, and is then dysregulated. Among other factors, the innate immune system is of central importance to the early containment of infection. Death from infection is strongly heritable in human populations. Hence, genetic variations that disrupt innate immune sensing of infectious organisms could

Jesús Villar; Nicole Maca-Meyer; Lina Pérez-Méndez; Carlos Flores

2004-01-01

346

Lactate Clearance for Assessing Response to Resuscitation in Severe Sepsis  

PubMed Central

Severe sepsis remains a major public health problem both with a high hospital mortality rate and with staggering associated health care expenditures. The past decade has seen new insights into the early resuscitation of severe sepsis and this is an important, controversial, and constantly changing topic to emergency physicians. In this article, the recent support for lactate clearance as a measure of early sepsis resuscitation effectiveness is summarized, lactate-derived to oxygen-derived resuscitation variables are compared, and the shortcomings of lactate-derived variables are described. As summarized in this article, the best available experimental evidence suggests that lactate clearance of at least 10% at a minimum of 2 hours after resuscitation initiation is a valid way to assess initial response to resuscitation in severe sepsis. Associative data suggest that lactate normalization during resuscitation is a more powerful indicator of resuscitative adequacy; however, further research on the optimal lactate clearance parameters to use during resuscitation is needed, and many other important questions have yet to be answered. PMID:23879729

Jones, Alan E.

2013-01-01

347

Early Diagnosis and Its Benefits in Sepsis Blood Purification Treatment  

E-print Network

hour sepsis would be fully manifested). The onset of therapy was the same for all animal models appropriate therapeutic strategies at early stages, when therapies are usually the most effective for extracting patterns from such data and show that these patterns can be used to assist physicians in providing

Obradovic, Zoran

348

Down but not out: myocardial depression in sepsis  

PubMed Central

Myocardial depression in septic patients is well recognized yet still poorly understood. The prognostic significance in terms of overall mortality when it is identified, remains in dispute. Parameters of left ventricular function measured by tissue Doppler imaging may assist in resolving whether dysfunction identified early in the course of sepsis is a good prognostic sign. PMID:22748042

2012-01-01

349

Bench to bedside: A role for erythropoietin in sepsis  

PubMed Central

Sepsis is the systemic inflammatory response to infection and can result in multiple organ dysfunction syndrome with associated high mortality, morbidity and health costs. Erythropoietin is a well-established treatment for the anaemia of renal failure due to its anti-apoptotic effects on red blood cells and their precursors. The extra-haemopoietic actions of erythropoietin include vasopressor, anti-apoptotic, cytoprotective and immunomodulating actions, all of which could prove beneficial in sepsis. Attenuation of organ dysfunction has been shown in several animal models and its vasopressor effects have been well characterised in laboratory and clinical settings. Clinical trials of erythropoietin in single organ disorders have suggested promising cytoprotective effects, and while no randomised trials have been performed in patients with sepsis, good quality data exist from studies on anaemia in critically ill patients, giving useful information of its pharmacokinetics and potential for harm. An observational cohort study examining the microvascular effects of erythropoietin is underway and the evidence would support further phase II and III clinical trials examining this molecule as an adjunctive treatment in sepsis. PMID:20727227

2010-01-01

350

REVIEW Open Access Understanding brain dysfunction in sepsis  

E-print Network

and noninflammatory processes, which may induce significant alterations in vulnerable areas of the brain. Important. 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

Paris-Sud XI, Université de

351

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

352

First Case of Fulminant Sepsis Due to Wohlfahrtiimonas chitiniclastica?  

PubMed Central

We report the first case of fulminant sepsis due to Wohlfahrtiimonas chitiniclastica. This case is also the first one reported in South America. We emphasize the importance of recognizing bacteria that live in the larvae of a parasitic fly as the causative agent of severe infections in homeless patients. PMID:21471333

Almuzara, Marisa N.; Palombarani, Susana; Tuduri, Alicia; Figueroa, Silvia; Gianecini, Ariel; Sabater, Laura; Ramirez, Maria S.; Vay, Carlos A.

2011-01-01

353

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

354

Hypothermia predicts mortality in critically ill elderly patients with sepsis  

Microsoft Academic Search

BACKGROUND: Advanced age is one of the factors that increase mortality in intensive care. Sepsis and multi-organ failure are likely to further increase mortality in elderly patients. We compared the characteristics and outcomes of septic elderly patients (> 65 years) with younger patients (? 65 years) and identified factors during the first 24 hours of presentation that could predict mortality

Ravindranath Tiruvoipati; Kevin Ong; Himangsu Gangopadhyay; Subhash Arora; Ian Carney; John Botha

2010-01-01

355

Extracellular histones are major mediators of death in sepsis.  

PubMed

Hyperinflammatory responses can lead to a variety of diseases, including sepsis. We now report that extracellular histones released in response to inflammatory challenge contribute to endothelial dysfunction, organ failure and death during sepsis. They can be targeted pharmacologically by antibody to histone or by activated protein C (APC). Antibody to histone reduced the mortality of mice in lipopolysaccharide (LPS), tumor necrosis factor (TNF) or cecal ligation and puncture models of sepsis. Extracellular histones are cytotoxic toward endothelium in vitro and are lethal in mice. In vivo, histone administration resulted in neutrophil margination, vacuolated endothelium, intra-alveolar hemorrhage and macro- and microvascular thrombosis. We detected histone in the circulation of baboons challenged with Escherichia coli, and the increase in histone levels was accompanied by the onset of renal dysfunction. APC cleaves histones and reduces their cytotoxicity. Co-infusion of APC with E. coli in baboons or histones in mice prevented lethality. Blockade of protein C activation exacerbated sublethal LPS challenge into lethality, which was reversed by treatment with antibody to histone. We conclude that extracellular histones are potential molecular targets for therapeutics for sepsis and other inflammatory diseases. PMID:19855397

Xu, Jun; Zhang, Xiaomei; Pelayo, Rosana; Monestier, Marc; Ammollo, Concetta T; Semeraro, Fabrizio; Taylor, Fletcher B; Esmon, Naomi L; Lupu, Florea; Esmon, Charles T

2009-11-01

356

Yersinia enterocolitica sepsis in a 3-week-old child.  

PubMed Central

Yersinia enterocolitica has been described with increasing frequency in the United States. Commonly, Y enterocolitica is a self-limiting gastrointestinal disorder, but occasionally it can lead to fulminant infection. This case report describes a 3-week-old male who succumbed to Y enterocolitica sepsis and reviews the literature. PMID:7807564

Thompson, E. C.

1994-01-01

357

NHS England issues alert and resource packs for managing sepsis.  

PubMed

THE GOVERNMENT has been criticised by MPs for its lack of urgency in preventing deaths from sepsis. An estimated 37,000 patients in England die of the condition every year because of failings such as delayed examination and inadequate record taking. PMID:25270802

2014-10-01

358

Reactivation of Multiple Viruses in Patients with Sepsis  

PubMed Central

A current controversy is whether patients with sepsis progress to an immunosuppressed state. We hypothesized that reactivation of latent viruses occurred with prolonged sepsis thereby providing evidence of clinically-relevant immunosuppression and potentially providing a means to serially-monitor patients' immune status. Secondly, if viral loads are markedly elevated, they may contribute to morbidity and mortality. This study determined if reactivation of herpesviruses, polyomaviruses, and the anellovirus TTV occurred in sepsis and correlated with severity. Serial whole blood and plasma samples from 560 critically-ill septic, 161 critically-ill non-septic, and 164 healthy age-matched patients were analyzed by quantitative-polymerase-chain-reaction for cytomegalovirus (CMV), Epstein-Barr (EBV), herpes-simplex (HSV), human herpes virus-6 (HHV-6), and TTV. Polyomaviruses BK and JC were quantitated in urine. Detectable virus was analyzed with respect to secondary fungal and opportunistic bacterial infections, ICU duration, severity of illness, and survival. Patients with protracted sepsis had markedly increased frequency of detectable virus. Cumulative viral DNA detection rates in blood were: CMV (24.2%), EBV (53.2%), HSV (14.1%), HHV-6 (10.4%), and TTV (77.5%). 42.7% of septic patients had presence of two or more viruses. The 50% detection rate for herpesviruses was 5–8 days after sepsis onset. A small subgroup of septic patients had markedly elevated viral loads (>104–106 DNA copies/ml blood) for CMV, EBV, and HSV. Excluding TTV, DNAemia was uncommon in critically-ill non-septic patients and in age-matched healthy controls. Compared to septic patients without DNAemia, septic patients with viremia had increased fungal and opportunistic bacterial infections. Patients with detectable CMV in plasma had higher 90-day mortality compared to CMV-negative patients; p<0.05. Reactivation of latent viruses is common with prolonged sepsis, with frequencies similar to those occurring in transplant patients on immunosuppressive therapy and consistent with development of an immunosuppressive state. Whether reactivated latent viruses contribute to morbidity and mortality in sepsis remains unknown. PMID:24919177

Walton, Andrew H.; Muenzer, Jared T.; Rasche, David; Boomer, Jonathan S.; Sato, Bryan; Brownstein, Bernard H.; Pachot, Alexandre; Brooks, Terrence L.; Deych, Elena; Shannon, William D.; Green, Jonathan M.; Storch, Gregory A.; Hotchkiss, Richard S.

2014-01-01

359

Serum procalcitonin as a diagnostic marker of neonatal sepsis  

PubMed Central

Purpose We evaluated serum procalcitonin (PCT) as a diagnostic marker of neonatal sepsis, and compared PCT levels with C-reactive protein (CRP) levels. Methods We retrospectively reviewed the medical records of 269 neonates with a suspected infection, admitted to Wonkwang University School of Medicine & Hospital between January 2011 and December 2012, for whom PCT and CRP values had been obtained. Neonates were categorized into 4 groups according to infection severity. CRP and PCT values were analyzed and compared, and their effectiveness as diagnostic markers was determined by using receiver operating characteristic (ROC) curve analysis. We also calculated the sensitivity, specificity, and positive, and negative predictive values. Results The mean PCT and CRP concentrations were respectively 56.27±81.89 and 71.14±37.17 mg/L in the "confirmed sepsis" group; 15.64±32.64 and 39.23±41.41 mg/L in the "suspected sepsis" group; 9.49±4.30 and 0.97±1.16 mg/L in the "mild infection" group; and 0.21±0.12 and 0.72±0.7 mg/L in the control group. High concentrations indicated greater severity of infection (P<0.001). Five of 18 patients with confirmed sepsis had low PCT levels (<1.0 mg/L) despite high CRP levels. In the ROC analysis, the area under the curve was 0.951 for CRP and 0.803 for PCT. The cutoff concentrations of 0.5 mg/L for PCT and 1.0 mg/L for CRP were optimal for diagnosing neonatal sepsis (sensitivity, 88.29% vs. 100%; specificity, 58.17% vs. 85.66%; positive predictive value, 13.2% vs. 33.3%; negative predictive value, 98.6% vs. 100%, respectively). Conclusion PCT is a highly effective early diagnostic marker of neonatal infection. However, it may not be as reliable as CRP. PMID:25379046

Park, In Ho; Lee, Seung Hyun; Yu, Seung Taek

2014-01-01

360

Modeling Sepsis in the Laboratory: Merging Sound Science with Animal Well-Being  

PubMed Central

Despite impressive advances in biomedical research, few noteworthy breakthroughs have been made in the treatment of sepsis during the past several decades. This stalemate is primarily due to the intricate and heterogenic nature of the systemic immune responses characterized as the sepsis syndrome. In general, such complexity must be approached with in vivo models. Several animal models have been described, suggesting that none adequately address all of the pressing needs in sepsis research. The most clinically applicable models involve a localized infection, such as surgically induced polymicrobial sepsis, that gradually propagates a systemic immune response. Because relevant models must mimic a severe and chronic syndrome, animal well-being is often a concern in sepsis research. A balance between the needs of sepsis research and animal welfare can only be achieved through knowledge of the strengths and weaknesses of and alternatives to in vivo sepsis models. PMID:18524169

Nemzek, Jean A; Hugunin, Kelly MS; Opp, Mark R

2008-01-01

361

Protein kinase G oxidation is a major cause of injury during sepsis  

PubMed Central

Sepsis is a common life-threatening clinical syndrome involving complications as a result of severe infection. A cardinal feature of sepsis is inflammation that results in oxidative stress. Sepsis in wild-type mice induced oxidative activation of cGMP-dependent protein kinase 1 alpha (PKG I?), which increased blood vessel dilation and permeability, and also lowered cardiac output. These responses are typical features of sepsis and their combined effect is a lowering of blood pressure. This hypotension, a hallmark of sepsis, resulted in underperfusion of end organs, resulting in their damage. A central role for PKG I? oxidative activation in injury is supported by oxidation-resistant Cys42Ser PKG I? knock-in mice being markedly protected from these clinical indices of injury during sepsis. We conclude that oxidative activation of PKG I? is a key mediator of hypotension and consequential organ injury during sepsis. PMID:23716652

Rudyk, Olena; Phinikaridou, Alkystis; Prysyazhna, Oleksandra; Burgoyne, Joseph R.; Botnar, Rene M.; Eaton, Philip

2013-01-01

362

Protein kinase G oxidation is a major cause of injury during sepsis.  

PubMed

Sepsis is a common life-threatening clinical syndrome involving complications as a result of severe infection. A cardinal feature of sepsis is inflammation that results in oxidative stress. Sepsis in wild-type mice induced oxidative activation of cGMP-dependent protein kinase 1 alpha (PKG I?), which increased blood vessel dilation and permeability, and also lowered cardiac output. These responses are typical features of sepsis and their combined effect is a lowering of blood pressure. This hypotension, a hallmark of sepsis, resulted in underperfusion of end organs, resulting in their damage. A central role for PKG I? oxidative activation in injury is supported by oxidation-resistant Cys42Ser PKG I? knock-in mice being markedly protected from these clinical indices of injury during sepsis. We conclude that oxidative activation of PKG I? is a key mediator of hypotension and consequential organ injury during sepsis. PMID:23716652

Rudyk, Olena; Phinikaridou, Alkystis; Prysyazhna, Oleksandra; Burgoyne, Joseph R; Botnar, René M; Eaton, Philip

2013-06-11

363

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

364

Efficacy and Safety of Intravenous Colistin in Preterm Infants with Nosocomial Sepsis Caused by Acinetobacter baumannii.  

PubMed

Objectives?To describe the efficacy of intravenous colistin on clinical and microbiological outcomes in preterm infants with nosocomial sepsis in neonatal intensive care unit (NICU) and define adverse events observed with this treatment. Methods?The records of preterm infants who received colistin with or without positive cultures in the NICU were retrospectively reviewed. Patients were evaluated for response to therapy and side effects. Results?A total of 21 preterm infants with medians of 28 weeks (23-36) gestational age and 870?g (620-2,650) birth weight were included. The median duration and dose of colistin therapy were 9 days (3-26) and 3 mg/kg/d (2-5). Recovery rate in patients including all with/without positive culture was 81% (17/21). Microbiological clearance by colistin was 69% (9/13). The major side effect observed was acute kidney injury (19%). At least 24% of infants required electrolyte supplementation during the colistin therapy. Magnesium levels were significantly lower at the end of the colistin therapy (p?Acute kidney injury and electrolyte disturbances including hypomagnesemia were reversible in all surviving patients. Conclusion?We suggest that renal function tests and serum electrolytes should be monitored closely and replaced in case of any need during the colistin therapy in preterm infants. PMID:24584997

Alan, Serdar; Yildiz, Duran; Erdeve, Omer; Cakir, Ufuk; Kahvecioglu, Dilek; Okulu, Emel; Ates, Can; Atasay, Begum; Arsan, Saadet

2014-12-01

365

The role of streptococcal hypersensitivity in the pathogenesis of Behçet's Disease.  

PubMed

Behçet's disease (BD) is still considered as a mysterious multisystemic disorder characterized by recurrent involvement of muco-cutaneous, ocular, intestinal, vascular and/or nervous system organs. In this review, we would like to highlight and discuss several important advances in our understanding of the pathogenesis of BD based on the intrinsic genetic factors including HLA-B51 and MICA expression and extrinsic triggering factors. As one of the extrinsic triggering factors, we focused on the hypersensitivity against oral streptococci which might be acquired through the innate immune mechanism. It was found that HLA-B51 restricted CD8 T cell response was clearly correlated with the target tissues expressing MICA*009 by stress in active BD patients with HLA-B51 as the intrinsic factors. Bes-1 gene and HSP-65 derived from oral S. sanguinis, which is the uncommon serotype (KTH-1, strain BD113-20), are supposed to play important roles as an extrinsic factor in BD pathogenesis. The peptides of the Bes-1 gene are highly homologous with the retinal protein Brn3b and moreover, the Bes-1 peptides were homologous with HSP-65 derived from microorganisms in association with the counterpart human HSP-60, which appeared reactively in the patients. HSP-65/60 also has high homologies with the respective T cell epitope of BD patients. Although HSP-65/60 and the peptides of Bes-1 gene were found to stimulate PBMCs from BD patients in the production of pro-inflammatory Th1 type cytokines, some homologous peptides of HSP-65 with T cell epitopes were found to reduce IL-8, IL-12 and TNF-alpha produced from PBMCs of active BD patients. The findings might be correlated with the clinically therapeutic effects for BD patients with severe uveitis, who were led to immunotolerance by the peptide of human HSP-60 (336-351), as previously reported. Then, the pathogenesis of BD was discussed referring to intrinsic genetic factors and extrinsic triggering factors in aspects of streptococcal hypersensitivity, which might be acquired through the innate immune mechanisms. The BD symptoms were thought to be due to vascular reactions as immune responses in correlation with monocyte expressed streptococcal agents. PMID:18693149

Kaneko, Fumio; Oyama, Noritaka; Yanagihori, Hirokatsu; Isogai, Emiko; Yokota, Kenji; Oguma, Keiji

2008-01-01

366

Treatment of sepsis-induced acquired protein C deficiency reverses Angiotensin-converting enzyme-2 inhibition and decreases pulmonary inflammatory response.  

PubMed

The protein C (PC) pathway plays an important role in vascular and immune function, and acquired deficiency during sepsis is associated with increased mortality in both animal models and in clinical studies. However, the association of acquired PC deficiency with the pathophysiology of lung injury is unclear. We hypothesized that low PC induced by sepsis would associate with increased pulmonary injury and that replacement with activated protein C (APC) would reverse the activation of pathways associated with injury. Using a cecal ligation and puncture (CLP) model of polymicrobial sepsis, we examined the role of acquired PC deficiency on acute lung injury assessed by analyzing changes in pulmonary pathology, chemokine response, inducible nitric-oxide synthase (iNOS), and the angiotensin pathway. Acquired PC deficiency was strongly associated with an increase in lung inflammation and drivers of pulmonary injury, including angiotensin (Ang) II, thymus and activation-regulated chemokine, plasminogen activator inhibitor (PAI)-1, and iNOS. In contrast, the protective factor angiotensin-converting enzyme (ACE)-2 was significantly suppressed in animals with acquired PC deficiency. The endothelial protein C receptor, required for the cytoprotective signaling of APC, was significantly increased post-CLP, suggesting a compensatory up-regulation of the signaling receptor. Treatment of septic animals with APC reduced pulmonary pathology, suppressed the macrophage inflammatory protein family chemokine response, iNOS expression, and PAI-1 activity and up-regulated ACE-2 expression with concomitant reduction in AngII peptide. These data demonstrate a clear link between acquired PC deficiency and pulmonary inflammatory response in the rat sepsis model and provide support for the concept of APC as a replacement therapy in acute lung injury associated with acquired PC deficiency. PMID:18182560

Richardson, Mark A; Gupta, Akanksha; O'Brien, Lee A; Berg, David T; Gerlitz, Bruce; Syed, Samreen; Sharma, Ganesh R; Cramer, Martin S; Heuer, Josef G; Galbreath, Elizabeth J; Grinnell, Brian W

2008-04-01

367

Guillain-Barre syndrome complicated by acute fatal rhabdomyolysis  

PubMed Central

Guillain-Barre syndrome (GBS) is a heterogenous group of peripheral-nerve disorders with similar clinical presentation characterized by acute, self-limited, progressive, bilateral and relatively symmetric ascending flaccid paralysis, which peaks in 2-4 weeks and then subsides. The usual complications, which occur in a patient of GBS are pneumonia, sepsis, pulmonary embolism, respiratory insufficiency and cardiac arrest. The clinical course of GBS complicated by acute rhabdomyolysis is extremely rare. We present the case of GBS with marked elevation in serum creatine kinase, serum myoglobin levels and persistent hyperkalemia as a result of associated acute rhabdomyolysis. PMID:24872655

Saxena, Amrish; Singh, Vineeta; Verma, Nitin

2014-01-01

368

Acute cholecystitis  

MedlinePLUS

Cholecystitis - acute ... uses to digest fats in the small intestine. Acute cholecystitis occurs when bile becomes trapped in the ... Siddiqui T. Early versus delayed laparoscopic cholecystectomy for acute cholecystitis: a meta-analysis of randomized clinical trials. ...

369

Purification of Staphylococcal ?-Hemolysin and Its Action on Staphylococcal and Streptococcal Cell Walls  

PubMed Central

Chesbro, William R. (University of New Hampshire, Durham), Fred P. Heydrick, Roland Martineau, and Gail N. Perkins. Purification of staphylococcal ?-hemolysin and its action on staphylococcal and streptococcal cell walls. J. Bacteriol. 89:378–389. 1965.—After growth of bovine-derived strains of Staphylococcus aureus in a completely dialyzable medium, the ?-hemolysin in the culture supernatant fluids was purified by gradient-elution chromatography on cellulose phosphate. The purified hemolysin contained two components, demonstrable by immunodiffusion or electrophoresis, but was free from ?-hemolysin, coagulase, ?-hemolysin, enterotoxins A and B, glucuronidase, hyaluronidase, lipase, muramidase, Panton-Valentine leukocidin, phosphatase, and protease. The hemolysin was heat-labile and sulfhydryl-dependent, and the preparation was leukocidal for guinea pig macrophages. When rabbit red blood cell (RBC) stroma and staphylococcal or enterococcal cell walls were treated with the purified hemolysin, it liberated mucopolysaccharides from the rabbit RBC stroma, polysaccharides and mucopolysaccharides (or mucopeptides) from the staphyloccoal cell walls, and rhamnose, glucose, an unidentified monosaccharide, N-acetylglucosamine, and at least two polysaccharides from the enterococcal cell walls. The hemolytic and cell-wall degradative activities had similar thermal inactivation kinetics, pH optima, sedimentation coefficients, and chromatographic and electrophoretic mobilities; both required Mg and were inhibited by thiol-inactivating agents. Consequently, it seems likely that both activities are expressions of the same enzyme. PMID:14255704

Chesbro, William R.; Heydrick, Fred P.; Martineau, Roland; Perkins, Gail N.

1965-01-01

370

Identification of streptococcal m-protein cardiopathogenic epitopes in experimental autoimmune valvulitis.  

PubMed

The M protein of rheumatogenic group A streptococci induces carditis and valvulitis in Lewis rats and may play a role in pathogenesis of rheumatic heart disease. To identify the epitopes of M5 protein that produce valvulitis, synthetic peptides spanning A, B, and C repeat regions contained within the extracellular domain of the streptococcal M5 protein were investigated. A repeat region peptides NT4, NT5/6, and NT7 induced valvulitis similar to the intact pepsin fragment of M5 protein. T cell lines from rats with valvulitis recognized M5 peptides NT5/6 and NT6. Passive transfer of an NT5/6-specific T cell line into naïve rats produced valvulitis characterized by infiltration of CD4+ cells and upregulation of VCAM-1, while an NT6-specific T cell line did not target the valve. Our new data suggests that M protein-specific T cells may be important mediators of valvulitis in the Lewis rat model of rheumatic carditis. PMID:24346820

Kirvan, Christine A; Galvin, Jeffrey E; Hilt, Silvia; Kosanke, Stanley; Cunningham, Madeleine W

2014-03-01

371

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

372

X-ray crystal structure of the streptococcal specific phage lysin PlyC  

PubMed Central

Bacteriophages deploy lysins that degrade the bacterial cell wall and facilitate virus egress from the host. When applied exogenously, these enzymes destroy susceptible microbes and, accordingly, have potential as therapeutic agents. The most potent lysin identified to date is PlyC, an enzyme assembled from two components (PlyCA and PlyCB) that is specific for streptococcal species. Here the structure of the PlyC holoenzyme reveals that a single PlyCA moiety is tethered to a ring-shaped assembly of eight PlyCB molecules. Structure-guided mutagenesis reveals that the bacterial cell wall binding is achieved through a cleft on PlyCB. Unexpectedly, our structural data reveal that PlyCA contains a glycoside hydrolase domain in addition to the previously recognized cysteine, histidine-dependent amidohydrolases/peptidases catalytic domain. The presence of eight cell wall-binding domains together with two catalytic domains may explain the extraordinary potency of the PlyC holoenyzme toward target bacteria. PMID:22807482

McGowan, Sheena; Buckle, Ashley M.; Mitchell, Michael S.; Hoopes, James T.; Gallagher, D. Travis; Heselpoth, Ryan D.; Shen, Yang; Reboul, Cyril F.; Law, Ruby H. P.; Fischetti, Vincent A.; Whisstock, James C.; Nelson, Daniel C.

2012-01-01

373

Immunochemical analysis of streptococcal group A, B, and C carbohydrates, with emphasis on group A.  

PubMed Central

Streptococcal group A, B, and C carbohydrates were analyzed by counterimmunoelectrophoresis, immunoelectrophoresis, and inhibition of immunoprecipitation. Extracts of streptococci group A or C were shown by counterimmunoelectrophoresis to contain both anodic and cathodic migrating components. In immunoelectrophoresis, group A and C substances formed a continuous precipitation line stretching from the anode to the cathode, suggesting a heterogeneous population of molecules with immunochemical identity. This identity was confirmed by inhibition of immunoprecipitation, in which both anodic and cathodic immunoprecipitates were inhibited by the same constituent sugars: group A-anti-A was inhibited by N-acetylglucosamine, and group C-anti-C was inhibited by N-acetylgalactosamine. Extracts of group B showed only anodic migration in counterimmunoelectrophoresis and a narrow, anodic arc in immunoelectrophoresis. The group B-anti-B reaction was inhibited by rhamnose. Carbohydrates of variant strains of group A streptococci were also analyzed by the same methods. The results suggest that the heterogeneity of group A carbohydrate may have resulted from attachment of various amounts of N-acetylglucosamine to the polyrhamnose backbone. Images PMID:7049950

Fung, J C; Wicher, K; McCarty, M

1982-01-01

374

Properties and type antigen patterns of group B streptococcal isolates from pigs and nutrias.  

PubMed Central

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; Lammler, C; Smola, J

1993-01-01

375

Inflammatory and Endothelial Activation Biomarkers and Risk of Sepsis: A Nested Case-Control Study  

PubMed Central

PURPOSE Elevated biomarkers of inflammation and endothelial cell activation have been associated with severity of sepsis. We sought to determine the association between these baseline markers and subsequent episodes of sepsis. MATERIALS AND METHODS We performed a nested case-control analysis using subjects from the REasons for Geographic and Racial Differences in Stroke (REGARDS) cohort. We compared 162 sepsis cases (hospitalized for a serious infection with two or more systemic inflammatory response syndrome criteria) with 162 non-sepsis controls (hospitalized for a serious infection but not sepsis) matched by age, sex and observation time epoch. Using conditional logistic regression, we evaluated the associations between sepsis and baseline levels of interleukin-6 (IL-6), tumor necrosis factor (TNF-?), E-selectin, inter-cellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1), adjusting for smoking status, hypertension and chronic kidney disease. RESULTS Compared with controls, individuals with higher baseline IL-6, E-Selectin and ICAM-1 were more likely to develop sepsis (p-trend 0.02, 0.02, 0.04). Baseline TNF-? and ICAM-1 were not associated with future sepsis (p-trend 0.29, 0.33). CONCLUSIONS Individuals with higher baseline IL-6, E-Selectin and ICAM-1 were more likely to develop future sepsis episodes. These biomarkers may play a role in the early characterization, mitigation or prevention of sepsis. PMID:23414982

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

2013-01-01

376

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

377

Diagnostic value of serum leptin and a promising novel diagnostic model for sepsis  

PubMed Central

Diagnosis of sepsis in critically ill patients is important to reduce morbidity and mortality. The present study was conducted to determine the role of serum leptin in the early diagnosis of sepsis and to establish a diagnostic model for sepsis. A retrospective study was conducted of 331 patients from an intensive care unit. All patients underwent consistent blood collection at 6:00 a.m. every morning after fasting. Serum leptin concentrations and additional markers of sepsis were compared between the sepsis group (n=128) and the non-sepsis group (n=203). Septic patients displayed significantly higher leptin serum concentrations compared with those of the non-sepsis group (mean concentration, 11.67 versus 4.824 mg/dl; P<0.001). The leptin levels in male patients were higher than those in female patients, particularly in the sepsis group. The accuracy of serum leptin levels in distinguishing septic patients from non-septic patients was 76%, and the area under the receiver operating characteristic (ROC) curve of serum leptin was ?0.8. Additional markers of inflammation in the sepsis group were also significantly higher than those in the non-sepsis group. Positive correlations were identified between leptin and body temperature, heart rate and creatinine levels. Therefore, a prognostic model comprising a combination of leptin with temperature, platelet count, white blood cell count and heart rate was evaluated as an effective logistic regression model for the diagnosis of sepsis. The logistic regression output cut-off value was 0.46 and the area under the ROC curve was 0.953 (P<0.0001). It may be concluded that leptin is a valuable marker in the diagnosis of sepsis and the proposed prognostic model is an effective logistic regression model for the diagnosis of sepsis. The prognostic model is able to aid the differentiation of septic patients from non-septic patients. PMID:24669245

CHEN, MINGYI; WANG, BIN; XU, YAPING; DENG, ZIHUI; XUE, HUI; WANG, LUHUAN; HE, LEI

2014-01-01

378

Selective downregulation of neutrophils by a phosphatidic acid generation inhibitor in a porcine sepsis model.  

PubMed

Effects of lisofylline (1-(5-R-hydroxyhexyl)-3,7-dimethylxanthine), a functional inhibitor of phosphatidic acid (PA) generation derived from de novo synthesis, on neutrophil function were examined in a porcine sepsis model. Hanford minipigs (18-25 kg) were randomly separated into six groups of six animals each: (1) saline control group; (2) sepsis control group, infused with Pseudomonas aeruginosa (1 x 10(6) colony-forming units/kg/min) for 2 h; (3) lisofylline control group, given a 25 mg/kg bolus of lisofylline 30 min prior to time zero, followed by a continuous infusion of 10 mg/kg/h throughout the study; (4) lisofylline pretreatment sepsis group, given lisofylline 30 min prior to sepsis, (5) lisofylline 1-h post-treatment sepsis group, and (6) lisofylline 2-h post-treatment sepsis group. All animals were studied for 6 h. Neutrophils were isolated at -0.5, 2, and 6 h. In the pretreatment and 1-h post-treatment groups, sepsis-induced neutrophil attachment to fibronectin was significantly attenuated. Sepsis-enhanced phagocytic activity was significantly reduced in the lisofylline pretreatment sepsis group, but not in the post-treatment groups. No treatment affected phorbol 12-myristate 13-acetate-induced chemiluminescence and basal filamentous actin content, which increased in sepsis, and cap formation, which declined in sepsis. Sepsis caused neutropenia, pretreatment produced neutrophilia, and 1-h post-treatment caused the neutropenia to recover to control levels. Interestingly, toward the end of the 6-h period, the neutrophil count was higher in the lisofylline control group than in the saline control groups. Thus, the inhibition of PA generation from de novo synthesis during sepsis not only can selectively downregulate some neutrophil functions but can also reverse neutropenia. PMID:9927533

Oka, Y; Hasegawa, N; Nakayama, M; Murphy, G A; Sussman, H H; Raffin, T A

1999-02-01

379

Early increase in intestinal permeability in patients with severe acute pancreatitis: Correlation with endotoxemia, organ failure, and mortality  

Microsoft Academic Search

Sepsis accounts for 80% of deaths from acute pancreatitis. This study aimed to investigate early changes in intestinal permeability\\u000a in patients with acute pancreatitis, and to correlate these changes with subsequent disease severity and endotoxemia. The\\u000a renal excretion of enterally administered polyethylene glycol (PEG) 3350 and PEG 400 was measured within 72 hours of onset\\u000a of acute pancreatitis to determine

Basil J. Ammori; Paul C. Leeder; Roderick F. G. J. King; G. Robin Barclay; Iain G. Martin; Mike Larvin; Michael J. McMahon

1999-01-01

380

Atypical presentation of purpura fulminans following sepsis in an adult  

PubMed Central

A 67-year-old morbidly obese female with a background of stage 4 chronic renal failure, ischaemic heart disease, congestive cardiac failure, atrial fibrillation and type 2 diabetes mellitus presented with sepsis and necrotic lesions of the proximal lower limbs. Initial histological findings were consistent with the clinical diagnosis of calciphylaxis and supportive treatment was commenced with addition of a phosphate binder and dietary restriction. Due to high anaesthetic risk, her wounds were managed with larva therapy in the first instance, however, ultimately surgical debridement was the required. Repeat histology from a further biopsy revealed necrosis secondary to numerous thrombi in the cutaneous vessels and a new diagnosis of purpura fulminans was made, likely secondary to her sepsis. Unfortunately, despite aggressive medical and surgical treatment measures, this patient died of multiple organ dysfunction following a prolonged admission. PMID:22675087

Lyon, Paul; Nambi, Rabi; Faruqi, Faisal

2011-01-01

381

Clavanin bacterial sepsis control using a novel methacrylate nanocarrier  

PubMed Central

Controlling human pathogenic bacteria is a worldwide problem due to increasing bacterial resistance. This has prompted a number of studies investigating peptides isolated from marine animals as a possible alternative for control of human pathogen infections. Clavanins are antimicrobial peptides isolated from the marine tunicate Styela clava, showing 23 amino acid residues in length, cationic properties, and also high bactericidal activity. In spite of clear benefits from the use of peptides, currently 95% of peptide properties have limited pharmaceutical applicability, such as low solubility and short half-life in the circulatory system. Here, nanobiotechnology was used to encapsulate clavanin A in order to develop nanoantibiotics against bacterial sepsis. Clavanin was nanostructured using EUDRAGIT® L 100-55 and RS 30 D solution (3:1 w:w). Atomic force, scanning electron microscopy and dynamic light scattering showed nanoparticles ranging from 120 to 372 nm in diameter, with a zeta potential of -7.16 mV and a polydispersity index of 0.123. Encapsulation rate of 98% was assessed by reversed-phase chromatography. In vitro bioassays showed that the nanostructured clavanin was partially able to control development of Staphylococcus aureus, Klebsiella pneumoniae, and Pseudomonas aeruginosa. Furthermore, nanostructures did not show hemolytic activity. In vivo sepsis bioassays were performed using C57BL6 mice strain inoculated with a polymicrobial suspension. Assays led to 100% survival rate under sub-lethal sepsis assays and 40% under lethal sepsis assays in the presence of nanoformulated clavanin A until the seventh day of the experiment. Data here reported indicated that nanostructured clavanin A form shows improved antimicrobial activity and has the potential to be used to treat polymicrobial infections. PMID:25382976

Saude, Amanda CM; Ombredane, Alicia S; Silva, Osmar N; Barbosa, Joao ARG; Moreno, Susana E; Guerra Araujo, Ana Claudia; Falcao, Rosana; Silva, Luciano P; Dias, Simoni C; Franco, Octavio L

2014-01-01

382

Bench to bedside: A role for erythropoietin in sepsis  

Microsoft Academic Search

ABSTRACT: Sepsis is the systemic inflammatory response to infection and can result in multiple organ dysfunction syndrome with associated high mortality, morbidity and health costs. Erythropoietin is a well-established treatment for the anaemia of renal failure due to its anti-apoptotic effects on red blood cells and their precursors. The extra-haemopoietic actions of erythropoietin include vasopressor, anti-apoptotic, cytoprotective and immunomodulating actions,

Andrew P Walden; J Duncan Young; Edward Sharples

2010-01-01

383

Sophorolipids Improve Sepsis Survival: Effects of Dosing and Derivatives  

Microsoft Academic Search

Introduction. Sophorolipids, a family of natural and easily chemo-enzymatically modified microbial glyco- lipids, are promising modulators of the immune re- sponse. We have previously demonstrated that sopho- rolipids mediate anti-inflammatory effects, including decreasing sepsis-related mortality at 36 h in vivo in a rat model of septic peritonitis and in vitro by decreas- ing nitric oxide and inflammatory cytokine produc- tion.

Rosemarie Hardin; Joelle Pierre; Robert Schulze; Cathy M. Mueller; Sophia L. Fu; Sabine R. Wallner; Albert Stanek; Vishal Shah; Richard A. Gross; Jeremy Weedon; Maja Nowakowski; Michael E. Zenilman; Martin H. Bluth

384

Intra-abdominal sepsis: newer interventional and antimicrobial therapies.  

PubMed

Complicated intra-abdominal infections are the second most common cause of septic death in the intensive care unit. Although there have been improvements in the outcome of sepsis regardless of etiology, this is even more striking for intra-abdominal infections. From observation, recent advances in interventional techniques, including more aggressive use of percutaneous drainage of abscesses and use of "open abdomen" techniques for peritonitis, have significantly affected the morbidity and mortality of physiologically severe complicated intra-abdominal infection. PMID:19665085

Solomkin, Joseph S; Mazuski, John

2009-09-01

385

Evaluating the Near-Term Infant for Early Onset Sepsis  

PubMed Central

Although the rate of early onset sepsis in the near-term neonate is low (one to eight of 1000 cases), the rate of mortality and morbidity is high. As a result, infants receive multiple, broad-spectrum antibiotic therapy, many for up to 7 days despite blood cultures showing no growth. Maternal intrapartum antibiotic prophylaxis and small blood volume collections from infants are cited as reasons for the lack of confidence in negative culture results. Incorporating an additional, more rapid test could facilitate a more timely diagnosis in these infants. To this end, a 16S rDNA polymerase chain reaction (PCR) assay was compared to blood culturing for use as a tool in evaluating early onset sepsis. Of 1751 neonatal intensive care unit admissions that were screened, 1233 near-term infants met inclusion criteria. Compared to culture, PCR demonstrated excellent analytical specificity (1186 of 1216, 97.5%) and negative predictive value (1186 of 1196, 99.2%); however, PCR failed to detect a significant number of culture-proven cases. These findings underscore the cautionary stance that should be taken at this time when considering the use of a molecular amplification test for diagnosing neonatal sepsis. The experience gained from this study illustrates the need for changes in sample collection and preparation techniques so as to improve analytical sensitivity of the assay. PMID:16825509

Jordan, Jeanne A.; Durso, Mary Beth; Butchko, Allyson R.; Jones, Judith G.; Brozanski, Beverly S.

2006-01-01

386

Nanomechanics of the Endothelial Glycocalyx in Experimental Sepsis  

PubMed Central

The endothelial glycocalyx (eGC), a carbohydrate-rich layer lining the luminal side of the endothelium, regulates vascular adhesiveness and permeability. Although central to the pathophysiology of vascular barrier dysfunction in sepsis, glycocalyx damage has been generally understudied, in part because of the aberrancy of in vitro preparations and its degradation during tissue handling. The aim of this study was to analyze inflammation-induced damage of the eGC on living endothelial cells by atomic-force microscopy (AFM) nanoindentation technique. AFM revealed the existence of a mature eGC on the luminal endothelial surface of freshly isolated rodent aorta preparations ex vivo, as well as on cultured human pulmonary microvascular endothelial cells (HPMEC) in vitro. AFM detected a marked reduction in glycocalyx thickness (266 ± 12 vs. 137 ± 17 nm, P<0.0001) and stiffness (0.34 ± 0.03 vs. 0.21 ± 0.01 pN/mn, P<0.0001) in septic mice (1 mg E. coli lipopolysaccharides (LPS)/kg BW i.p.) compared to controls. Corresponding in vitro experiments revealed that sepsis-associated mediators, such as thrombin, LPS or Tumor Necrosis Factor-? alone were sufficient to rapidly decrease eGC thickness (-50%, all P<0.0001) and stiffness (-20% P<0.0001) on HPMEC. In summary, AFM nanoindentation is a promising novel approach to uncover mechanisms involved in deterioration and refurbishment of the eGC in sepsis. PMID:24278345

Wiesinger, Anne; Peters, Wladimir; Chappell, Daniel; Kentrup, Dominik; Reuter, Stefan; Pavenstadt, Hermann; Oberleithner, Hans; Kumpers, Philipp

2013-01-01

387

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

388

Sepsis: Something Old, Something New, and a Systems View  

PubMed Central

Sepsisis a clinical syndrome characterized by a multi-system response to a microbial pathogenic insult consisting of a mosaic of interconnected biochemical, cellular, and organ-organ interaction networks. A central thread that connects these responses is inflammation, which, while attempting to defend the body and prevent further harm, causes further damage through the feed-forward, pro-inflammatory effects of damage-associated molecular pattern molecules. In this review, we address the epidemiology and current definitions of sepsis, and focus specifically on the biological cascades that comprise the inflammatory response to sepsis. We suggest that attempts to improve clinical outcomes by targeting specific components of this network have been unsuccessful due to the lack of an integrative, predictive, and individualized systems-based approach to define the time-varying, multi-dimensional state of the patient. We highlight the translational impact of computational modeling and other complex systems approaches as applied to sepsis, including in silico clinical trials, patient-specific models, and complexity-based assessments of physiology. PMID:21798705

Namas, Rami; Zamora, Ruben; Namas, Rajaie; An, Gary; Doyle, John; Dick, Thomas E.; Jacono, Frank J.; Androulakis, Ioannis P.; Nieman, Gary F.; Chang, Steve; Billiar, Timothy R.; Kellum, John A.; Angus, Derek C.; Vodovotz, Yoram

2011-01-01

389

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

2014-11-01

390

Treatment of acute kidney injury in children: from conservative management to renal replacement therapy  

Microsoft Academic Search

Over the past two decades, the etiology and therapy of acute kidney injury (AKI) in children has changed. Historically, hemolytic uremic syndrome was the major cause of pediatric AKI, but advances in technology have meant that sepsis and deterioration of often unrecognized long-term organ dysfunction are now more common causes of pediatric AKI in the developed world. At the same

Timothy E Bunchman

2008-01-01

391

Macrophage migration inhibitory factor is a critical mediator of severe acute pancreatitis  

Microsoft Academic Search

Background & Aims: Macrophage migration inhibitory factor (MIF), originally described as an inhibitor of the random migration of macrophages, has been shown recently to be involved in the pathogenesis of several inflammatory diseases such as sepsis. The aim of this study was to clarify the role of MIF in acute pancreatitis (AP). Methods: Hemorrhagic necrotizing pancreatitis and edematous pancreatitis were

Yoshitaka Sakai; Atsushi Masamune; Akihiko Satoh; Jun Nishihira; Tetsuya Yamagiwa; Tooru Shimosegawa

2003-01-01

392

Evolving a Successful Acute Care Surgical\\/Surgical Critical Care Group at a Nontrauma Hospital  

Microsoft Academic Search

A large acute care but nontrauma teaching hospital in Manhattan, New York performing 24 000 operations\\/year has evolved a Surgical Intensive Care Unit (SICU) Service with 3 attendings and 5 physician assistants over 9 years. The division follows nationally recognized, published best practices in shock, sepsis, ventilator management, nutrition, and antibiotic use and has maintained a total mortality of 1.9%

Marvin A. McMillen

2011-01-01

393

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

394

Local IGF-I Prevents Sepsis-Induced Muscle Atrophy  

PubMed Central

The present study tests the hypothesis that local bioavailability of IGF-I is capable of regulating muscle protein balance and that muscle-directed IGF-I can selectively maintain muscle mass during bacterial infection. Initial studies in C57BL/6 mice demonstrated that increasing or decreasing bioavailable IGF-I within muscle by local administration of either Leu24 Ala31 IGF-I or IGF binding protein (IGFBP)-1, respectively, produced proportional changes in surrogate markers (e.g., phosphorylation of 4E–BP1 and S6K1) of protein synthesis. We next examined the ability of a sustained local administration of IGF-I to prevent sepsis-induced muscle atrophy over a 5-day period. At the time of cecal ligation and puncture or sham surgery, mice had a time-release pellet containing IGF-I implanted next to the gastrocnemius and a placebo pellet placed in the contralateral limb. Data indicated IGF-I released locally only affected the adjacent muscle and was not released into the circulation. Gastrocnemius from septic mice containing the placebo pellet was atrophied and had a reduced IGF-I protein content. In contrast, locally-directed IGF-I increased IGF-I protein within adjacent muscle to basal control levels. This change was associated with a proportional increase in muscle weight and protein, as well as increased phosphorylation of 4E–BP1 and the redistribution of eIF4E from the inactive eIF4E· 4EBP1 complex to the active eIF4E· eIF4G complex. Local IGF-I also prevented the