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Query: UMLS:C0032285 (pneumonia)
 54,520 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The pathophysiology of meconium aspiration syndrome(MAS) is related to mechanical obstruction of the airways and to chemical pneumonitis. Meconium is also suggested to cause functional deterioration of pulmonary surfactant. Recent studies have reported that meconium inhibits the physical surface properties of pulmonary surfactant, and that administration of exogenous surfactant may provide therapeutic benefits in animal models or infants with respiratory distress due to MAS. To assess the effects of meconium on physical surface properties, especially the changes on the air-liquid interface and hypophase of pulmonary surfactant in vitro, we studied the following findings; a) the surface spreading rate(SSR) and the surface adsorption rate(SAR), b) the viscosity, c) the electron microscopic changes, on a series of mixtures with various concentrations of lyophilized human meconium and Surfactant-TA(SurfactenTM). The human meconium has significantly increased the surface tension of SSR and the viscosity of pulmonary surfactant, but had decreased the surface pressure of SAR of surfactant, and changed the electron microscopic findings of surfactant. We have concluded that these findings support the concept that meconium-induced surfactant dysfunction may play a role in the pathophysiology of MAS.
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PMID:In vitro effect of meconium on the physical surface properties and morphology of exogenous pulmonary surfactant. 893 99

Aspiration of meconium produces an inflammatory reaction resulting in necrotic changes in lung tissue. To further investigate the mechanisms of the meconium-induced early pulmonary injury, twenty 10-12-d-old piglets were studied for lung tissue ultrastructural and apoptotic changes and phospholipase A2 activity. Twelve piglets received an intratracheal bolus (3 mL/kg) of a 20-mg/mL (thin, n = 6) or 65-mg/mL (thick, n = 6) mixture of human meconium, and control piglets (n = 5) received the same amount of intratracheal saline. Three ventilated piglets with no aspiration were also studied. Pulmonary hemodynamics and systemic oxygenation were followed for 6 h after meconium or saline insufflation. In the control groups, the pulmonary tissue showed open alveolar spaces and intact vascular walls, whereas meconium administration resulted in severe pneumonitis, with alveolar spaces filled with inflammatory exudate. Meconium instillation additionally resulted in edematous changes in the vascular walls and alveolar epithelium, whereas type II pneumocytes were intact. The amount of apoptotic cells was increased, especially in the respiratory epithelium, and the catalytic activity of phospholipase A2 in lung tissue samples was significantly elevated after thick meconium instillation. This activity rise proved to be mainly because of human group I phospholipase A2, introduced by meconium. Our data thus show that aspiration of meconium leads to severe lung tissue inflammation with early ultrastructural changes in the pulmonary alveolar walls and is associated with apoptotic cell death in the epithelium, already during the first hours after the insult. These results further suggest that high phospholipase A2 activity, mainly introduced into the lungs within the meconium, may have an important role in the initiation of these alterations in neonatal lungs.
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PMID:Human meconium has high phospholipase A2 activity and induces cellular injury and apoptosis in piglet lungs. 1054 29

Aspiration of meconium causes considerable perinatal morbidity and mortality. Meconium-stained amniotic fluid (MSAF) is present in 7-22% of all deliveries. Gastrointestinal secretions, bile, bile acids, mucus, pancreatic juice, cellular debris, amniotic fluid, swallowed vernix caseosa, lanuge, and blood comprise meconium. Passage of meconium occurs most often in deliveries after 42 weeks gestation (30%) because of high levels of the hormone motilin. This hormone is responsible for bowel peristalsis, defecation, and maturation of the innervation of the intestinal tract associated with vagal stimulation. It tends to be a marker of pre/intrapartum asphyxia. MSAF is also a sign of fetal hypoxia or acidosis. It appears that meconium aspiration is predominantly an intrauterine event. The definition of meconium aspiration syndrome (MAS) is respiratory distress in a meconium-stained newborn, compatible radiographic findings (e.g., coarse, irregular pattern of increased density throughout the lung), and symptoms that can not otherwise be explained. MAS occurs in 1-4% of infants with MSAF and up to 10% of those with thick meconium. Mortality ranges from 6% to 40%. Initially, meconium particles mechanically obstruct the small airways. Later, chemical pneumonitis and interstitial edema are responsible for small airway obstruction. As many as 66% of persistent pulmonary hypertension of the newborn cases are associated with MAS. Clinical signs and symptoms of MAS include frothy, yellow-green secretions from the mouth; very rapid breathing; intercostal retractions; cyanosis; overinflated chest due to air trapping; rales; and rattling in the throat. Transcervical amnio-infusion of warmed normal saline may be an obstetric intervention in cases of MSAF. Intrapartum oropharyngeal suctioning and postpartum intratracheal suctioning has reduced the incidence of MAS. Routine care of MAS infants includes monitoring and correcting of the thermal environment and blood glucose and calcium levels. Chest physiotherapy, saline lavage, management of hypoxemia, surfactant therapy, and systemic steroid treatment are MAS therapies.
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PMID:Meconium aspiration syndrome: current concepts. 1232 Mar 76

Inflammation plays an important role in the pathogenesis of meconium aspiration syndrome, and pneumonitis is one of the major characteristics. We have previously shown that meconium has chemotactic properties because of the presence of IL-8. We hypothesize that IL-8 and other proinflammatory substances in meconium may amplify inflammation in meconium aspiration syndrome, inducing endogenous cytokine production by lung epithelial cells. We measured proinflammatory substances in first-pass meconium from healthy newborns and evaluated the effect of sterile meconium on cytokine production in cultured A549 alveolar epithelial cells in vitro. IL-1beta, IL-6, IL-8, and tumor necrosis factor-alpha were measured by ELISA, and heme was measured spectrophotometrically. After incubation of meconium samples with A549 cells, cytokine concentrations in the supernatant were measured. Meconium samples contained variable amounts of IL-1beta, IL-6, IL-8, tumor necrosis factor-alpha, and heme. On stimulation of A549 cells with meconium, the IL-8 concentration in the culture supernatant significantly increased above baseline measurements, whereas tumor necrosis factor-alpha showed a variable pattern and IL-1beta or IL-6 remained unchanged. There was no quantitative relationship between the concentration of the measured cytokines and heme in meconium and cytokine release by the A549 cells after meconium exposure. Meconium contains proinflammatory substances. All samples induced IL-8 release and some induced tumor necrosis factor-alpha release in cultured A549 epithelial cells. We speculate that proinflammatory substances in meconium can induce lung inflammation in meconium aspiration syndrome in two ways: directly via cytokines and heme present in meconium and indirectly by inducing cytokine release by the epithelial lung cells.
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PMID:Meconium is a source of pro-inflammatory substances and can induce cytokine production in cultured A549 epithelial cells. 1284 Jan 56

Surfactant has led to a significant reduction in neonatal mortality for premature infants with lung immaturity and respiratory distress. However, surfactant therapy has been shown to be effective in the treatment of a number of other neonatal respiratory disorders and the evidence for surfactant use in such circumstances is presented. Meconium aspiration is characterised by severe atelectasis, the influx of neutrophils, edema, and hyaline membranes, with decreased levels of SP-A and SP-B and the large aggregate fraction of lung surfactant, and altered surfactant surface morphology. Meconium contains cholesterol, free fatty acids and bilirubin all of which can interfere with surfactant function in a dose-dependent fashion. Providing larger amounts of surfactant can overcome some of this inhibition. Animal models of meconium aspiration treated with surfactant have improved histology, lung mechanics and gas exchange. Studies in human infants with meconium aspiration have found elevated concentrations of total protein, albumin, and membrane-derived phospholipid in lung lavage fluid, and haemorrhagic pulmonary edema. Clinical studies in such neonates have reported improved gas exchange and clinical outcomes following surfactant treatment. More recently surfactant lavage has been shown to be a potentially efficacious therapy for such infants. The inflammatory exudate containing plasma proteins and cytokines which accompanies neonatal pneumonia may inactivate surfactant. Surfactant treatment given to animals following the tracheal instillation of group B Streptococcal resulted in significantly less bacterial growth and improved lung function. Small clinical experiences have demonstrated the benefit of surfactant to infants with pneumonia/sepsis. Pulmonary haemorrhage, which some consider a complication of surfactant therapy, has also been effectively managed using surfactant instillation. The hemoglobin and red blood cell lipids may act to inhibit natural surfactant and treatment with surfactant has been shown to improve outcome for infants with pulmonary haemorrhage. Animal models of congenital diaphragmatic hernia (CDH) have hypoplastic lungs with evidence of decreased lamellar bodies in their type II pneumocytes and resultant surfactant deficiency, and respond to surfactant replacement with improved gas exchange and lung mechanics. The lungs of human infants with CDH contain less phospholipids and phosphatidylcholine per milligram of DNA than control infants. Case reports have reported a benefit of surfactant for infants with CDH. In the near-term infants with severe respiratory distress, surfactant is one of the therapies along with inhaled nitric oxide and high frequency ventilations, that have resulted in improved outcomes. Surfactant treatment may be of significant benefit in newborn infants with respiratory compromise secondary to a number of insults, and further prospective evidence of its efficacy in such disorders is needed.
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PMID:Surfactant use for neonatal lung injury: beyond respiratory distress syndrome. 1498 Feb 86

Pulmonary surfactant is inactivated in meconium aspiration syndrome and neonatal pneumonia. Development of an exogenous surfactant less sensitive to inactivation might be useful for treating these diseases. We investigated in vitro whether addition of the cationic cyclic membrane cross-linking peptide polymyxin B (PxB) and/or calcium chloride (CaCl2) to modified porcine surfactant Curosurf increases resistance to meconium-induced inactivation of surface activity while antimicrobial activity of PxB is maintained. To study bacterial proliferation, Escherichia coli, group B streptococci (GBS), or Staphylococcus aureus were incubated 0-5 h in saline or in meconium in the presence or absence of Curosurf with or without PxB. PxB and CaCl2 improved spreading and adsorption of Curosurf. Curosurf plus CaCl2/PxB needed a 4-fold increase of meconium concentration to increase dynamic surface tension significantly compared with Curosurf plus CaCl2 alone, indicating that PxB further increases the resistance of Curosurf to meconium-induced inactivation. Meconium alone like meconium/Curosurf promoted growth of E. coli and GBS, but addition of Curosurf/PxB or PxB alone significantly reduced the growth of E. coli. Biophysical and antibacterial properties of Curosurf and PxB may be combined into a useful adjunct in the treatment of neonatal Gram-negative pneumonia and/or meconium aspiration syndrome.
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PMID:Polymyxin B/pulmonary surfactant mixtures have increased resistance to inactivation by meconium and reduce growth of gram-negative bacteria in vitro. 1649 80

The role of meconium in the respiratory system was studied in newborns, who died from various causes (250 up to 3000 g of weight). We monitored tracheal rings response to dopamine, serotonin and ethanol in different concentrations (dopamine: 0,05 mg/ml, 0,5 mg/ml, 5 mg/ml; serotonin (5-HT): 10-4, 10-3, 10-2, 10-1 mol/dm3; ethanol: 0,02 ml, 0,5 ml, 1,0 ml; 96%). Tracheal smooth musculature tonus (TSM) was examined in 48 tracheal preparations taken after the newborn exitus due to different reasons. Based on functional researche of isolated preparations of tracheas, it may be concluded that: aspiration of meconium has not changed the response of TSM to dopamine, serotonin and ethanol (p>0,1) in comparison with the control group, which have died due to different lung inflammatory processes (e.g. pneumonia, bronchopneumonia, atelectasis, cerebral hemorrhage). The results suggest that meconium does not potentiate the constricting action of dopamine, serotonin and ethanol in tracheobronchial system. Meconium causes mild relaxation of the TSM through a mechanism that is not intermediated by the products of cyclooxygenases (prostaglandins, prostacyclins) from the tracheal epithelium or proteins. Also, as it seems, the direct activity of many tested acids in the smooth musculature has no significant impact on increase of the airways tonus in MAS syndrome.
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PMID:Role of meconium in the reaction of airways smooth musculature in the newborn with meconium aspiration syndrome (MAS). 2000 2

Meconium is a common finding in amniotic fluid and placental specimens, particularly in the term or post-term pregnancy. The most important consequence of meconium-stained amniotic fluid (MSAF) is meconium aspiration syndrome (MAS), and at least 5% of infants born through MSAF develop MAS. MAS continues to be a threat to many newborns throughout the world, with a case fatality rate of 5% (as much as 40%), in addition to short- and long-term pulmonary and neurodevelopmental sequelae. The exact pathophysiology of meconium passage into the amniotic fluid and consequences of meconium aspiration are unknown. There are three prevailing and possibly compatible theories for mechanisms of meconium release. Firstly, meconium passage is probably related with the maturation of the gastrointestinal tract, because meconium passage in the preterm third trimester fetus has been reported to be a rare event, as typically it occurs near or post-term. Secondly, an alternate hypothesis for in utero meconium passage is that pathologic processes, such as stress via hypoxia or infection, can trigger meconium passage. However, the predictive values of MSAF for fetal distress and acidosis at birth are poor and controversial. Thirdly, an alternative route for the presence of MSAF in the presence of fetal hypoxia is reduced clearance of defecated meconium due to impaired fetal swallowing or unidentified placental dysfunction in addition to or instead of an increase in its passage. The pathophysiology of MAS is multifactorial and extremely complex. Meconium causes mechanical obstruction and pulmonary air leak, induces surfactant inactivation, causes pulmonary inflammation, and induces apoptosis. Preventing prolonged pregnancy by labor induction might reduce the risk of MSAF. Labor induction with prostaglandins appears to be associated with the occurrence of MSAF. Amnioinfusion for suspected umbilical cord compression has no clear effect on the occurrence of MSAF. Intrapartum suctioning of the naso- and oropharynx before delivery of the shoulders as well as postnatal endotracheal suctioning of vigorous infants with MSAF are no longer recommended. Currently, endotracheal suction is recommended only in neonates born through MSAF who are not vigorous at birth. Indications for mechanical ventilation in infants with MAS are arbitrary. Surfactant administration may reduce the severity of MAS. Bronchoalveolar lavage with surfactant in infants with MAS is risky and it cannot be recommended for routine use. At present, there is insufficient evidence to propose routine steroid therapy in the management of MAS. Although prophylactic antibiotics in infants with MAS are not justified, most of these patients receive antibiotics during the first days of life, before the diagnosis of pneumonia can be completely ruled out. Children surviving severe MAS are in fact reported to have higher prevalence of asthmatic symptoms and bronchiolar hyperreactivity than children in the general population. It remains undetermined how often and at what intensity systemic inflammation occurs in association with MAS and what its significance is for the outcome of infants with severe MAS.
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PMID:Meconium aspiration syndrome: do we know? 2185 47