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

Recombinant human granulocyte colony-stimulating factor (rHuG-CSF) has been shown to stimulate the production and function of neutrophils in vitro and in vivo. Clinical studies in patients receiving myelosuppressive chemotherapy showed earlier neutrophil recovery, a reduction in infectious complications of neutropenia, and the use of fewer antibiotics. Its use has also been established for mitigating the infectious complications associated with severe chronic neutropenia (SCN). Data are emerging that neutropenia also contributes to the risk of infections in patients with acquired immunodeficiency syndrome (AIDS) and in neonates with presumed sepsis, and that rHuG-CSF may be a useful adjunct therapy in these patients. More recent studies have focused on enhancing neutrophil number and function in patients with infections not associated with neutropenia. These studies were approached cautiously because of the suggestion that neutrophils might non-selectively amplify the body's inflammatory response in the immunocompetent host and lead to inadvertent tissue injury. Preclinical models have provided a strong rationale for clinical studies to determine whether rHuG-CSF lessens the severity or duration of serious infections or their complications in patients with suboptimal outcome from antibiotics. These studies suggest that elevation of neutrophil levels in these settings is not only safe but has clinical benefit.
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PMID:Clinical benefits of improving host defences with rHuG-CSF. 910 12

The surveillance of pneumococcal resistance in nasopharyngeal isolates is a practical way to determine the prevalence of resistant strains and is a reasonable predictor of resistance in systemic isolates. The increasing prevalence of resistance is shifting the distribution of invasive pneumococcal serotypes toward those included in conjugate vaccines. If these vaccines reduce carriage, they may eliminate or greatly reduce the prevalence of resistant strains. Meningitis is the most important infection caused by PRP for which penicillin or ampicillin therapy is inappropriate. Although the extended spectrum cephalosporins will be effective for most cases of PRP meningitis, it is clear that such therapy is not foolproof. It is important for the laboratory to test CSF isolates not only for penicillin resistance but also for resistance to the cephalosporins. beta-Lactam antibiotics can still be considered appropriate empiric therapy for otitis media, pneumonia, or sepsis. However, occasional treatment failures with these agents may necessitate use of alternative therapeutic strategies.
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PMID:Antibiotic-resistant pneumococci in pediatric disease. 915 79

Streptococcus pneumoniae (SPN) is the most common cause of invasive infections in children, with high levels of mortality in developing countries. An increase in frequency of penicillin-resistant strains is reported in most parts of the world. A study was undertaken in Argentina and 5 other countries of the region, to determine the type distribution and penicillin resistance rate of SPN isolated from invasive infections in children less than 5 years old. Between June 1994 and March 1996, a total of 505 SPN isolated from sterile sites were collected from 15 hospitals located in 9 cities of different geographic areas. Clinical and epidemiological data from 443 children were analyzed. Sixty five percent SPN were isolated from children less than 2 years old. Pneumonia was the clinical diagnosis in 58% of the cases, meningitis in 22%, and sepsis in 10.6%. Isolates were recovered from blood (51.2%), pleural fluid (22.7%), CSF (20.7%), and other sterile sites (5.4%). Thirty different pneumococcal capsular types were identified and the 10 most frequent in descending order were: 14, 5, 1, 6A/6B, 7F, 9V, 19F, 19A, 16F y 23F, representing 89.3% of the total. Overall, 13.1% of isolates showed intermediate resistance to penicillin while 11.3% showed high resistance. Lethality was 8.8%, without correlation with penicillin-resistance and/or type. These result should be used in selecting the optimal combination of specific types for a conjugate vaccine, useful in children less than 2 years old and for considering therapeutic strategies for invasive pneumococcal infections.
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PMID:Distribution of capsular types and penicillin-resistance of strains of Streptococcus pneumoniae causing systemic infections in Argentinian children under 5 years of age. Streptococcus pneumoniae Working Group. 918 40

The effects of recombinant granulocyte-colony stimulating factor (rhG-CSF) in neonatal neutropenia with presumed sepsis, which has a poor prognosis, were investigated. The study involved 14 neonates with presumed sepsis and neutropenia. Findings were compared with those from 24 historical controls. rhG-CSF (5 micrograms/ kg/day i.v. for 5 days) was administered immediately following diagnosis. Complete blood counts were obtained before and 24, 48, 72, 96 and 120 h after initiation of treatment. Neutrophil storage pool (NSP) was assessed (in 4 patients) before and after treatment. Statistical analysis was performed using one way analysis of variance. Treatment led to an increase in absolute neutrophil count (ANC) levels in 13/14 patients. At the end of treatment, the mean ANC was higher than that of controls (P = 0.007). There was a marked increase in the NSP of between 32% and 65% (P = 0.005). There were two clinical failures, one of whom was considered to have died from his underlying condition. There were no reports of clinical or haematological toxicity during treatment or follow up.
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PMID:The in vivo effect of recombinant human granulocyte-colony stimulating factor in neutropenic neonates with sepsis. 926 99

Septic encephalopathy (SE) is present in up to 70% of all patients with sepsis. In some cases, SE may proceed other parameters of sepsis. Loss of consciousness to a various extent is the leading symptom. CSF findings and CCT are usually unremarkable. EEG is a sensitive parameter to monitor SE. EEG-changes deteriorate in correspondence to the degree of SE. If sepsis can be treated successfully, clinical and electrophysiological signs are completely reversible. SE has a complex etiology. Bacterial endotoxins and other microbial products trigger the release of a multitude of mediators of sepsis. Due to liver dysfunction in sepsis, the brain neurotransmitter profile may be deranged. Other etiological factors include bacteriemia, liver or renal dysfunction, fluid and electrolyte imbalance, hypoglycemia and drug effects. Due to the prognostic significance of early adequate treatment, recognition of SE as a possible initial sign may be crucial for patients with sepsis.
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PMID:[Infection: impaired consciousness as the initial symptom. Clinical and pathophysiologic aspects of septic encephalopathy]. 946 47

Neutrophils play a key role in the pathophysiology of septic multiple organ dysfunction syndrome (MODS) through excessive release of toxic granule components and reactive oxygen metabolites with consequent tissue destruction. The increase of senescent neutrophils during sepsis indicates a potential breakdown of autoregulatory mechanisms including apoptotic processes to remove activated neutrophils from inflammatory sites. Therefore, neutrophil apoptosis of patients with severe sepsis and its regulatory mechanisms were investigated. Spontaneous neutrophil apoptosis from patients with severe sepsis was significantly reduced in comparison to healthy individuals. Cytokines detected in the circulation during sepsis (tumor necrosis factor-alpha [TNF-alpha], interferon-gamma [IFN-gamma], granulocyte colony-stimulating factor [G-CSF], granulocyte-macrophage colony-stimulating factor [GM-CSF]) inhibited neutrophil apoptosis in both groups, though the effect was more distinct in neutrophils from healthy humans. Addition of lipopolysaccharide (LPS) to neutrophils from healthy humans markedly (P < .05) reduced apoptosis which was partially restored through addition of anti-TNF-antibody. Interleukin-10 (IL-10) counteracted (P < .05) inhibition of neutrophil apoptosis induced by LPS, recombinant human (rh) TNF-alpha, rhIFN-gamma, rhG-CSF, and rhGM-CSF, whereas rhIL-4 or rhIL-13 were ineffective. Reduced neutrophil apoptosis during sepsis was concomitant with increased tyrosine phosphorylation, while IL-10 markedly inhibited tyrosine phosphorylation in LPS-stimulated neutrophils. These results identify proinflammatory cytokines and IL-10 as strong regulators of spontaneous neutrophil apoptosis during sepsis. Inhibition as well as acceleration of neutrophil apoptosis seems to be associated with alterations of signal transduction pathways.
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PMID:Interleukin-10 counterregulates proinflammatory cytokine-induced inhibition of neutrophil apoptosis during severe sepsis. 934 17

We investigated the effects of recombinant granulocyte colony-stimulating factor (rG-CSF) during canine bacterial pneumonia. Beagles with chronic tracheostomies received daily subcutaneous rG-CSF (5 micrograms/kg body wt) or placebo for 14 days, beginning 9 days before intrabronchial inoculation with E. coli. Animals received antibiotics and fluid support; a subset received humidified oxygen (fractional inspired O2 0.40). Compared with controls, rG-CSF increased circulating neutrophil counts (57.4 vs. 11.0 x 10(3)/mm3, day 1 after infection; P = 0.0001), decreased plasma endotoxin (7.5 vs. 1.1 EU/ml at 8 h; P < 0.01) and serum tumor necrosis factor-alpha (3,402 vs. 729 pg/ml at 2 h; P = 0.01) levels, and prolonged survival (relative risk of death = 0.45, 95% confidence interval 0.21-0.97; P = 0.038). Also, rG-CSF attenuated sepsis-associated myocardial dysfunction (P < 0.001). rG-CSF had no effect on pulmonary function or on blood and lung bacteria counts (all P = not significant). Other animals challenged with endotoxin (4 mg/kg i.v.) after similar treatment with rG-CSF had lower serum endotoxin levels (7.62 vs. 5.81 log EU/ml at 6 h; P < 0.01) and less cardiovascular dysfunction (P < 0.05 to < 0.002) but similar tumor necrosis factor-alpha levels (P = not significant) compared with controls. Thus prophylactic rG-CSF sufficient to increase circulating neutrophils during bacterial pneumonia may improve cardiovascular function and survival by mechanisms that in part enhance the clearance of bacterial toxins but do not improve lung function.
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PMID:rG-CSF reduces endotoxemia and improves survival during E. coli pneumonia. 937 7

Neonatal sepsis is a major cause of morbidity and mortality in newborn infants. Hematopoiesis and host defense in the neonate is developmentally immature compared with the adult. Defects in both the quantitative and qualitative aspects of the phagocytic system contribute significantly to a relative state of immunodeficiency in the neonate. Dysregulation of neonatal hematopoiesis and the immune response is a significant contributing factor to the increased susceptibility of the neonate to infection. A relatively small set of pluripotent stem cells gives rise to large numbers of functionally diverse mature effector cells. Cell proliferation and differentiation are regulated and controlled by highly specific protein factors, affecting single and multiple lineage hematopoiesis. Reduced neonatal rat myeloid progenitor pools, accelerated myeloid progenitor proliferative rates and decreased total body neutrophil storage pools predispose the newborn rat to depletion of mature effector neutrophils and a tendency to develop neutropenia during states of increased demand such as overwhelming bacterial infection. We review here the multifactorial complex biological process involved in the regulation of hematopoietic growth factors. We also review the biological effects of various non-lineage-committed and lineage-committed growth factors as reported in in vitro investigations and in vivo neonatal animal experiments. We also review our results of phase I/II clinical studies utilizing rhuG-CSF in neonates with presumed sepsis, and of rhuGM-CSF in very low birth weight neonates.
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PMID:The role of cytokines in modulating neonatal myelopoiesis and host defense. 938 73

In contrast to the anticipation that in sepsis granulocyte colony-stimulating factor (G-CSF) would overactivate the nonspecific immune system by recruiting and priming leukocytes with consequent aggravation of inflammatory tissue lesions, recombinant (r) G-CSF pretreatment was protective in various experimental non-neutropenic models of inflammation. The mechanisms of protection, however, are not fully understood. Using intravital fluorescence microscopy, we show that rG-CSF enhances leukocyte endothelial cell interaction within the microvasculature of normal rat livers, whereas rG-CSF pretreatment of animals exposed to lipopolysaccharide (LPS) attenuates the LPS-induced leukocytic response, including stasis in sinusoids as well as rolling and adherence in postsinusoidal venules with subsequent tissue infiltration. Moreover, rG-CSF, which did not affect Kupffer cell activity in normal rat livers, reduced the immediate activation of Kupffer cells on LPS exposure, as indicated in vivo by the delayed adherence/phagocytosis of intra-arterially administered latex particles associated with attenuation of proinflammatory cytokine release (tumor necrosis factor alpha and interleukin-6). Finally, rG-CSF reduced LPS-induced nutritive perfusion failure and hepatocellular excretory dysfunction. This study provides evidence for a distinct, possibly tumor necrosis factor alpha-dependent modulation of LPS-induced cellular response within the liver by rG-CSF, thereby achieving protection against microcirculatory perfusion failure and hepatic dysfunction.
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PMID:Immunomodulatory action of G-CSF in a rat model of endotoxin-induced liver injury: an intravital microscopic analysis of Kupffer cell and leukocyte response. 940 Aug 11

Recent advances in the diagnosis and therapy of infections in patients with hematological diseases are reviewed. In general, 40-60% of febrile episodes lack clinical or microbiological evidence of infection and are thus treated empirically. Among the cases of microbiologically documented bacteremia treated in our department, the incidence of Gram-negative bacteria was high (47.1%) and the incidence of Gram-positive bacteremia is increasing. To improve the diagnostic rate of Gram-negative sepsis, the measurement of plasma endotoxin was performed. Of 147 febrile neutropenic episodes, endotoxemia was observed in 58 (39.5%) and the causative microorganisms of these infections were deemed Gram-negative bacteria. The measurement of plasma (1-->3)-beta-D-glucan, a ubiquitous component of fungi, was also performed for making early diagnosis of deep mycosis; the sensitivity of this assay was 90% and the specificity was 100%. The detection of (1-->3)-beta-D-glucan appears to be useful as a screening test of deep mycosis. The effects of the concomitant use of granulocyte-colony stimulating factor (G-CSF) and empiric antibiotic therapy for febrile neutropenia were studied in a randomized fashion. G-CSF did not affect the rate of the response to the empiric antibiotic therapy, although a significant effect of G-CSF on neutrophil recovery was observed. Guidelines for empiric antibiotic and antifungal therapy combined with serological diagnosis are proposed.
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PMID:Infections in patients with hematological diseases: recent advances in serological diagnosis and empiric therapy. 940 Dec 73


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