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

During the final prenatal period of fetal lung development in humans, important maturational processes occur, including the production of surfactant necessary to decrease surface tension at the air-liquid interface of the alveoli. During early gestation, the glucocorticoid receptor is expressed in the fetal lung, and glucocorticoids stimulate the production of surfactant-associated proteins and increase phospholipid synthesis by enhancing the activity of phosphatidylcholine. Other glucocorticoid-induced effects may include stimulation of cell maturation and differentiation, inhibition of DNA synthesis, changes in interstitial tissue components, stimulation of antioxidant enzymes, and regulation of pulmonary fluid metabolism. Recently, it was suggested that glucocorticoids are also important in postnatal pulmonary development, and may be related to the development of neonatal lung disease in preterm infants. Surfactant deficiency that can be prevented by antenatal corticosteroid treatment causes infant respiratory distress syndrome and requires mechanical ventilation. Ventilation by itself or in combination with high levels of oxygen, fluid overload, pulmonary infections, sepsis, and air leak syndrome causes an acute pulmonary inflammatory reaction that may result in chronic lung disease or bronchopulmonary dysplasia. Glucocorticoids are effective in the treatment of chronic lung disease of prematurity and regulate the inflammatory response by the interaction with transcription factors such as nuclear factor kappaB and activated protein 1. Indeed, inflammatory cells and the levels of chemokines and cytokines in bronchoalveolar fluid decrease after dexamethasone treatment. However, treatment of fetuses and preterm infants with repeated and/or high doses of corticosteroids may have considerable long-term side effects on somatic, brain, and lung growth. The difficult balance between short-term gain and the possible long-term side effects of glucocorticoids in preterms remains a difficult issue.
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PMID:Glucocorticoids and lung development in the fetus and preterm infant. 1141 80

Respiratory muscle dysfunction associated with ventilatory loading may be partially attributed to respiratory muscle injury. Exertion-induced muscle injury can be defined as structural alterations of the muscle, however, a better understanding of the biochemical, morphologic, and functional correlates of injured respiratory muscles will facilitate discrimination of how injury, fatigue, and weakness contribute to respiratory muscle dysfunction. In addition to the increased loads associated with lung disease, many factors such as poor arterial blood gases, immobilization, sepsis, decreased nutrition, and corticosteroids may increase susceptibility to exertion-induced respiratory muscle injury. Respiratory muscle injury in humans is not well-described, however, more extensive evidence has been shown in animal models of increased ventilatory loading. Potential mechanisms of respiratory muscle injury are mechanical stress, metabolic stress, and inflammation. In order to optimize therapeutic interventions, a better understanding of these mechanisms and the patients that are most susceptible to respiratory muscle injury needs to be determined.
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PMID:Respiratory muscle injury: evidence to date and potential mechanisms. 1148 9

The authors carried out an experiment on mice infected with dark-pigmented micromicetes Aspergillus clavitus and Exophiala dermatitidis, preplanted from lung operational material of patients with chronic non-specific lung disease and destructive tuberculosis. The infection was produced by the peroral method in the first group of animals and by the intranasal method in the second group. By day 30 the test animals developed mycotic sepsis, fifty percent of the animals had malignant lung growths (adenocarcinoma, squamous cell carcinoma and angiopericytoma). Established in the experiment was toxicity and cancerogenity of dark-pigmented micromicetes Aspergillus clavitus and Exophiala dermatitidis. A model of mycotic sepsis and micromicete-induced lung cancer has been created.
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PMID:[Deep mycosis and lung tumor induced by dark-pigmented micromycetes]. 1169 96

Over the past year, human studies have confirmed and expanded the involvement of macrophage migration inhibitory factor (MIF) in a number of diseases that had originally been studied in animals. In addition to sepsis, rheumatoid arthritis, glomerulonephritis and inflammatory lung disease, elevated MIF levels have been described in patients suffering from ulcerative colitis, inflammatory neurological diseases and cancer. Cellular studies indicate that in addition to macrophages, MIF affects the activities of CD4+ and CD8+ T cells, natural killer cells, fibroblasts and endothelial cells, actions that may explain the contribution of MIF to inflammatory diseases and cancer. Molecular studies have identified direct interactions between MIF and several intracellular regulatory proteins (Jab1, PAG and p53) that control cellular growth and proliferation; however, how interactions with these proteins fit into a general scheme to explain MIF's biological activity has not been elucidated. The three-dimensional structure of MIF has offered some surprising clues and if the potential enzymatic sites identified are involved with MIF-associated diseases, they may provide good targets for therapeutic intervention.
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PMID:Glucocorticoid counter regulation: macrophage migration inhibitory factor as a target for drug discovery. 1175 24

There is growing evidence that sepsis-related complications in neonates are crucially mediated by the action of proinflammatory cytokines. It has previously been demonstrated that elevated IL-6 and IL-8 levels can predict brain damage and chronic lung disease in preterm infants. However, it is the current view that neonates have a reduced capability to produce proinflammatory cytokines. To clarify this issue, we analyzed the inflammatory response in term and preterm infants directly at the single cell level by flow cytometry. Endotoxin challenge was performed under defined conditions on monocytes obtained from 50 healthy adults and 119 neonates, which consist of 45 term infants, 63 preterm infants (26.1-36.7 wk of gestational age), and 11 preterm infants with proven infection (24.6-29.9 wk). Our results challenge the existing view of an immature inflammatory response by demonstrating that term infants and preterm infants display a higher percentage of IL-6- and IL-8-positive cells than adults. After preincubation with dexamethasone the number of cytokine-positive cells decreased in all groups, but the number of IL-8-positive cells remained higher in term and preterm infants >32 wk compared with adults. These observations demonstrate not only a well-developed but also an enhanced inflammatory response in term and preterm infants. Under consideration of several detrimental effects of IL-6 and IL-8, our data may have major implications on the pathophysiology of inflammatory-triggered neonatal diseases.
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PMID:Enhanced interleukin-6 and interleukin-8 synthesis in term and preterm infants. 1271 93

Persistent pulmonary hypertension is seen in association with a number of diseases and conditions in the newborn including perinatal asphyxia, meconium aspiration syndrome, Group B strep sepsis, and certain surgical conditions such as congenital diaphragmatic hernia. The conventional therapy of persistent pulmonary hypertension is discussed as well as the adjunctive role of surfactant replacement therapy and high frequency ventilation. The mechanism of action of inhaled nitric oxide as a selective pulmonary vasodilator is explained. Human neonatal clinical experience is chronicled from the original studies of Roberts in 1992 and Kinsella in 1993. A review of three large prospective randomized trials of nitric oxide is presented as well as a summary of new areas of investigation including the use of nitric oxide in pre-term infants and the use of nitric oxide in the prevention of chronic lung disease. Current dosing recommendations are presented as well as guidelines recently published from the American Academy of Pediatrics. A review of follow up literature in relationship to patients receiving inhaled nitric oxide is also summarized.
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PMID:Status report: inhaled nitric oxide in persistent pulmonary hypertension/hypoxic respiratory failure of neonate. 1210 54

The survival rate for extremely preterm or extremely low-birth-weight (LBW) newborns born at the threshold of viability (25 or fewer completed weeks of gestation) improved in the early 1990s, largely as the result of a greater use of assisted ventilation in the delivery room and surfactant therapy. Increased use of antenatal and neonatal corticosteroids also may have influenced survival rates. However, this improvement in survival has not been associated with an equal improvement in morbidity. The incidence of chronic lung disease, sepsis, and poor growth remains high and may even have increased. There is concern that the treatment of extremely preterm and extremely LBW newborns may result in unforeseen effects into adulthood, and that the neurodevelopmental outcome and cognitive function of extremely preterm and extremely LBW infants may be suboptimal. The purpose of this document is to describe the potential consequences of extremely preterm birth and to provide clinical management guidelines based on the best available data.
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PMID:ACOG Practice Bulletin: Clinical Management Guidelines for Obstetrcian-Gynecologists: Number 38, September 2002. Perinatal care at the threshold of viability. 1222 Jul 92

Eosinophilia is common in the neonatal period. However, its causes, pathomechanism and clinical significance are still unknown. Previous reports have described that eosinophilia may be associated with numerous conditions (establishment of an anabolic state, drug reactions, response to foreign antigens, chronic lung disease, erythropoietin treatment and infections). The aim of this study was to evaluate the possible association of various conditions, especially infection, with eosinophilia and to clarify whether recognition of increase in eosinophil count is of any clinical significance in the management of a sick neonate. Fifty-six neonates with eosinophilia (absolute eosinophil count > 700/mm3) and 55 control neonates matched for gestational age, birth weight and hospitalization days were included in the study. A significant difference between the two groups was found only in blood transfusions, immuno-globulin treatment, specific antibiotic treatment and infectious disease. However, neonates who develop sepsis and are treated with antibiotics and immuno-globulin are more often transfused. It can thus be concluded that the main relationship observed is between eosinophilia and infection whereas the other associations are secondary. The relative risk factor for infection when the absolute eosinophil count is > 700/mm3, is 1.58, with a confidence interval 1.30-1.91. Eosinophilia seems to be a reliable indicator of sepsis while normal absolute eosinophil count does not exclude infection. Infection should be strongly considered in the evaluation of a sick neonate with eosinophilia.
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PMID:Eosinophilia in sick neonates. 1224 53

The seminar on maternal morbidity and mortality in the Philippines held in 1991 is described. The objective of the meeting was to define the status of women's health in the country and to prepare for a more comprehensive and developed implementation of local reproductive health services. The seminar honored the International Day of Action for Women's Health. Maternal mortality statistics show a rate of 1.1.1000 live births since 1988 vs. 2.1/1000 live births in 1980. Maternal mortality is greater among young 1st time mothers, among those with 5 children, and among those 40 years regardless of the number of children. Obstetric deaths account for 85% of all maternal deaths. The common causes in 1985-89 were hemorrhage, infection, and hypertensive disorders. Pulmonary disease and acute hepatitis account for indirect obstetric mortality. The prior period from 1984 to 1985 in Manila showed the leading causes to be puerpural sepsis, septic induced abortion, postpartum hemorrhage, and eclampsia. In Manila 33% deliver at home. 65% of hospital emergency cases involve women without prenatal care, and 1 out of 4 are dying upon admission and 1 out of 5 die within 5-6 hours. 58% died within 2 days after admission. 80% of these deaths were preventable. Lack of health education and inadequate diet due to poverty account for a major predisposing role. Confounding factors are anemia, tuberculosis, and parasitism. Broad risk factors are the inadequacy of health services and socioeconomic conditions. Proposals to reduce maternal mortality by 50% include focusing health programs on both mother and child, improving knowledge about prenatal care, improving the quality of prenatal care, and improving the quality of family planning (FP) services. Medical institutions need to maintain adequate supplies of equipment and supplies. Statistics and research are needed. Contraception for the health of the child was proposed as the appropriate tool for acceptance of FP. Competition for funds was a problem. Problems were also identified as the power imbalance between the sexes. High risk screening was recommended at the local level by the health worker. Workshops were formed and issues were identified, recommendations made, activities described, and the government and nongovernmental responses given.
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PMID:The perils of motherhood. 1228 38

The fetus and the neonate are particularly vulnerable to injury caused directly by immunologic mechanisms or inflicted by infectious agents that take advantage of their relatively immature and inexperienced immune system. With increasing survival of high-risk neonates in the surfactant era, prevention/treatment of sepsis and chronic lung disease (CLD) has emerged as an area of priority in neonatal research. Considering the role of inflammatory mediators in the pathogenesis of sepsis and CLD, the clinical application of immunomodulator therapy to neonatology is perhaps more important at present than ever. Advances in molecular biology and immunology have led to development of newer immune modulator therapies that are directed towards specific cells or cytokines rather than resulting in a general suppression of the immune response. Failure of promising, newer immunomodulator therapies in sepsis trials in adults has, however, clearly documented the difficulties in diagnosing/correcting the imbalance between pro- and anti-inflammatory responses. As in the case of sepsis, development of a single magic bullet for prevention/management of a multi-factorial illness like CLD may be difficult, as prevention of prematurity - the single most important high-risk factor for CLD - is an unachievable goal at present. As new frontiers are being explored, older, well-established therapies like antenatal anti-D immunoglobulin prophylaxis continue to emphasize the tremendous potential of immunomodulator therapy in neonatology/perinatology. The current immunomodulators/immunotherapeutic agents with established/potential clinical applications in the perinatal period are reviewed.
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PMID:Perinatal immunomodulation. 1238 69


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