Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0029713 (immaturity)
 4,335 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glucocorticoids (GC) are known to inhibit the proliferative response of leukocytes after mitogenic activation. Until now, the effects of GC on the immune system have been studied predominantly in adults. However, GC are frequently administered to human fetuses and newborns for the prevention and treatment of respiratory distress syndrome. The immune system of human newborns is still a functionally immature system. Therefore, we wondered whether the immaturity is also reflected by altered responses to hormonal signals such as glucocorticoids. We studied the effects of the GC dexamethasone (DEX) on the proliferation of peripheral blood mononuclear cells and T cells in vitro after stimulation with phytohemagglutinin, anti-CD3, anti-CD3/anti-CD28 or anti-CD2/anti-CD28. Our data demonstrate that neonatal cells are much more sensitive to inhibition of the proliferative response by DEX than adult cells (ED50 1 +/- 0.8 nM vs. 221 +/- 135 nM). This difference in sensitivity is not related to differences in affinity and capacity of binding of [3H] DEX. Moreover, we show that the mechanisms of GC inhibition differ between adult and neonatal cells. In adult cells, addition of interleukin (IL)-2 does not restore DEX inhibition of the proliferative response. In contrast, the proliferative response of neonatal cells can be restored completely by the addition of IL-2. These data suggest that the primary target of GC in neonatal cells is inhibition of IL-2 production. In adult cells, other mechanisms are responsible for inhibition of T cell proliferation.
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PMID:Increased dexamethasone sensitivity of neonatal leukocytes: different mechanisms of glucocorticoid inhibition of T cell proliferation in adult and neonatal cells. 777 38

This study examined the trends in early neonatal mortality by birthweight during 1981-90 at Ramathibodi Hospital in Thailand. Deaths were analyzed by causes of death within the first 7 days of life. Causes included congenital malformation, immaturity, asphyxia, respiratory distress syndrome (RDS), infection, and other causes. The results showed that 71,153 births occurred during the 10 year period, an increase of 22% over the period. Low birthweight increased from 6.3% in the first five years to 7.1% in the last five years. Very low birthweight (less than 1500 g) increased from 0.47% in the first five years to 0.57% in the last five years. Early neonatal mortality decreased from 0.53% in 1981 to 0.23% in 1990, which was over a reduction of over 50%. The reduction was 60% when congenital malformations were excluded. Early neonatal mortality declined for all birthweight groups by 40-75%, with the exception of birthweights under 1000 g. 90% of early neonatal deaths were due to congenital malformation, immaturity, RDS, asphyxia, and infection. Mortality due to congenital malformation remained at a rate of about 1.3:1000 live births. Causes of death varied with birthweight group. Neonates less than 1000 g died of RDS and immaturity in both 5-year periods. Neonates between 1000-1499 g and 1500-1999 g died of congenital malformation in the most recent period; for the first period, neonatal mortality was caused by RDS and infection respectively. Congenital malformation was the primary cause over the 10-year period for births weighing 2000 and higher grams. Hospital management for delivering and postpartum women changed over the ten year period. Although there was no specific intensive care unit, equipment for intensive neonatal care management was available. The improvement in neonatal mortality occurred during a period of increased numbers of births and low birthweight babies. Neonates under 1000 g were not managed as aggressively by medical staff because of the poor chances of survival and the high cost of care. In 1990, there was a change for more aggressive management of neonates with a birthweight between 750-999 g. The incidence of infection, asphyxia, and RDS decreased or remained stable due to better management of RDS and early detection and treatment with antibiotics of infection.
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PMID:Early neonatal mortality and causes of death in Ramathibodi Hospital: 1981-1990. 782 80

Neonatal mink kits infected with Aleutian mink disease parvovirus (ADV) develop an acute interstitial pneumonia with clinical symptoms and pathological lesions that resemble those seen in preterm human infants with respiratory distress syndrome and in human adults with adult respiratory distress syndrome. We have previously suggested that ADV replicates in the alveolar type II epithelial cells of the lung. By using double in situ hybridization, with the simultaneous use of a probe to detect ADV replication and a probe to demonstrate alveolar type II cells, we now confirm this hypothesis. Furthermore, Northern (RNA) blot hybridization showed that the infection caused a significant decrease of surfactant-associated protein C mRNA produced by the alveolar type II cells. We therefore suggest that the severe clinical symptoms and pathological changes characterized by hyaline membrane formation observed in ADV-infected mink kits are caused by a dysfunction of alveolar surfactant similar to that observed in respiratory distress syndrome in preterm infants. However, in the infected mink kits the dysfunction is due to the replication of ADV in the lungs, whereas the dysfunction of surfactant in preterm infants is due to lung immaturity.
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PMID:Role of alveolar type II cells and of surfactant-associated protein C mRNA levels in the pathogenesis of respiratory distress in mink kits infected with Aleutian mink disease parvovirus. 813 47

The lungs of patients born with severe congenital diaphragmatic hernia (CDH) are biochemically and morphologically immature. Because antenatal glucocorticoid therapy can accelerate pulmonary maturation in premature neonates who have respiratory distress syndrome, we hypothesized that it may correct the pulmonary biochemical and morphological immaturity associated with CDH. We showed in previous experimental studies that antenatal low-dose dexamethasone improved the biochemical and morphological parameters of pulmonary immaturity in rats that had severe CDH. Somatic and pulmonary growth were inhibited with high doses of dexamethasone. In the present study, we examined the effects of antenatal low-dose dexamethasone and thyrotropin-releasing hormone (TRH), alone or in combination, on the pulmonary maturation in CDH. Combined antenatal low-dose dexamethasone and TRH significantly reduced mean lung glycogen concentration (P = .001), and increased mean disaturated phosphatidylcholine content (P < .005) to better than that observed with either therapy alone, without changing mean body or lung weight. Combined TRH and low-dose glucocorticoid as an antenatal therapy may reduce the morbidity and mortality of CDH.
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PMID:Combined antenatal thyrotropin-releasing hormone and low-dose glucocorticoid therapy improves the pulmonary biochemical immaturity in congenital diaphragmatic hernia. 817 20

Approximately 20% to 30% of infants with respiratory distress syndrome (RDS) do not respond to surfactant replacement therapy. Unfortunately there is no uniform definition of 'response' or 'non-response' to surfactant therapy. Response was based on improvement in a/A PO2 and/or mean airway pressure (MAP) by some and on improvement in FIO2 and/or MAP by others. Even the point of time at which evaluation of response was done is different in various reports. There is an urgent need to adopt an uniform definition. Most premature babies are surfactant deficient which is the aetiological factor of RDS. Generally good antenatal care and perinatal management are essential in avoidance of premature birth. Babies with lung hypoplasia and who are extremely premature (less than 24 weeks of gestation) do not respond well to exogenous surfactant replacement because of structural immaturity. Prompt management of asphyxiated birth and shock are necessary as there may be negative response to surfactant replacement. Foetal exposure to glucocorticoids improves responsiveness to postnatal administration of surfactant. Antenatal steroid therapy has become an important part of management of RDS with surfactant replacement. The premature lungs with high alveolar permeability tend to develop pulmonary oedema. With the presence of plasma-derived surfactant inhibitors, the response to exogenous surfactant may be affected. These inhibitors may also be released following ventilator barotrauma. The standard of neonatal intensive care such as ventilatory techniques has an important bearing on the outcome of the RDS babies.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Factors affecting responses of infants with respiratory distress syndrome to exogenous surfactant therapy. 826 36

Bronchopulmonary dysplasia (BPD), a respiratory disorder first described in prematurely born infants with respiratory distress syndrome (RDS) treated with mechanical ventilation and oxygen supplementation, is the most common cause of chronic lung disease in infants. It is defined as the need for increased inspired oxygen at 28 days of age, and is observed with the highest frequency following premature delivery of very low birth weight infants. Indeed, an incidence of 48% has been recently reported in a population with a mean gestational age of 27 weeks. The etiology of BPD is multifactorial including lung immaturity, respiratory distress, oxygen therapy, and mechanical ventilation. Based on the current understanding of the pathogenesis of the disease, several therapeutical strategies are used. One of them is focused on the prevention of BPD by correcting surfactant deficiency in premature infants with RDS using exogenous surfactant, and also by improving the techniques of mechanical ventilation used for the management of RDS. Another approach which is being developed is focused on the factors involved in the processes of repair of the injured immature lung. These factors include the use of inhibitors of the inflammatory cascade, antioxidants, and inhibitors of fibrosis.
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PMID:[Bronchopulmonary dysplasia]. 876 16

A negative finding of amniotic fluid (AF) phosphatidyl glycerol (PG) does not eliminate the need for determining the lecithin/sphingomyelin ratio (LSR). We use a novel approach to classify fetal lung maturity (FLM) data, and to validate the fluorescence polarization (FP) surfactant assay (Abbott), which replaces the PG assay and reduces the frequency of repeat LSR. This method finds the values (decision points) of these tests that allow for classifying the data with least errors. These tests best identify the risk of respiratory distress syndrome (RDS) from fetal lung immaturity. We find the decision values for tests by exploring the data for information content and optimize their selection using group-based reference. We previously defined normal reference as the maximum entropy set with no information. The uncertainty resolved by information provided in the data allows formation of syndromic classes. This is greatest at the values for the variables (decision-points) associated with the greatest decrease in entropy. Decision-values found for PF, EGA, PG, LSR that classify amniotic fluids into the mature and not-mature classes are in agreement with the results of ROC analysis. We validate the replacement of PG by the PF method. We also find a level of FP below which LSR might be required to resolve uncertainty and above which the FP indicates maturity. We confirm the ability to evaluate fetal maturity methods using information analysis.
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PMID:Amniotic fluid polarization of fluorescence and lecithin/sphingomyelin ratio decision criteria assessed. 879 2

Although surfactant replacement therapy has dramatically improved the outcome of premature infants with respiratory distress syndrome, approximately 30% of treated infants show a transient or no response. Nonresponse to surfactant replacement therapy may be due to extreme lung immaturity and possibly surfactant inactivation. Surfactant inactivation involves aspecific biophysical events, such as interference with the formation or activity of an alveolar monolayer, and specific interactions with serum proteins, including antibodies, leaking into the alveolar space. As formulations containing surfactant proteins appear to better tolerate serum inactivation, we used an excised rat lung model to compare the susceptibility to serum inactivation of a mixture of synthetic phospholipids selected from surfactant lipid constituents, Exosurf (a protein-free synthetic surfactant), Survanta [containing surfactant proteins B and C (SP-B and -C)], and a porcine surfactant (containing SP-A, -B, and -C). For each of these preparations, we used pressure/volume determinations as an in situ measure of surfactant activity and retested the same preparations after mixing with human serum, a nonspecific surfactant inactivator. Human serum inactivated porcine surfactant to a lesser extent than Survanta, Exosurf, or synthetic phospholipids. Temperature exerted a significant effect on deflation stability, as shown by a greater lung compliance in untreated, normal lungs and a larger improvement in compliance after treating lavaged lungs with synthetic phospholipids at 37 degrees C than at 22 degrees C. We conclude that surfactant containing SP-A, -B, and -C is only moderately susceptible to inactivation with whole serum and may therefore exert a greater clinical response than protein-free surfactants or those containing only SP-B and -C.
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PMID:Inactivation of surfactant in rat lungs. 882 93

A 480 g, 38-day-old female infant underwent ventriculo-peritoneal shunt surgery for hydrocephalus after intra-ventricular hemorrhage. The patient was born at a gestational age of 25 weeks and 5 days, weighing 600 g, as one of twins by a cesarean section. Although respiratory distress syndrome developed, it was relieved with surfactant. The esophagus was easily perforated by a gastric tube. At the age of 7 days, PDA was closed conservatively with indomethacin. Anesthesia was induced and maintained with fentanyl (induction dose 4 micrograms.kg-1, total dose 6 micrograms.kg-1) and vecuronium. Ventilation was controlled with oxygen and air (FIO2 0.21-0.25). The main problems encountered by anesthetists in the perioperative period were; fluid management (hyperkalemia, hyponatremia, infusion volume), bradycardia due to increased intracranial pressure, body temperature control (hypothermia), and transport to the operating room. In anesthesia for extremely low birth weight (extremely premature) infants, utmost care and proficient procedure are required because of their immaturity, fragility and smallness.
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PMID:[Anesthetic problems in a 480 g infant for ventriculo-peritoneal shunt surgery]. 886 31

Noninfective acute respiratory disease develops in approximately 1% of all newborn infants and results in their admission to a critical care unit. Transient tachypnea of the newborn occurs as a result of a delay in the clearance of fetal lung liquid; however, respiratory distress syndrome, typically thought to be exclusively a problem of relative surfactant deficiency, is now suspected to be characterized by an even greater air space fluid burden from the inability to absorb fetal lung liquid. In vivo experiments have demonstrated that the lung epithelium secretes Cl and fluid throughout gestation and develops the ability to actively reabsorb Na+ only during late gestation. At birth, the mature lung switches from active Cl- (fluid) secretion to active Na+ (fluid) absorption in response to circulating catecholamines. Changes in oxygen tension augment the Na(+)-transporting capacity of the epithelium and increase gene expression for the epithelial Na+ channel (ENaC). The inability of the immature fetal lung to switch from fluid secretion to fluid absorption results, at least in large part, from an immaturity in the expression of ENaC, which can be upregulated by glucocorticosteroids. Both pharmacological blockade of the lung's epithelial Na+ channel and genetic knockout experiments using mice deficient in the ENaC pore-forming subunit have demonstrated the critical physiological importance of lung Na+ transport at birth. When Na+ transport is ineffective, newborn animals develop respiratory distress and hypoxemia, retain their fetal lung liquid and, in the case of the ENaC knockout mice, die. Bioelectrical studies of human infants' nasal epithelia demonstrate that both transient tachypnea of the newborn and respiratory distress syndrome have defective amiloride-sensitive Na+ transport. These results suggest that neonatal respiratory distress syndrome has, in addition to a relative deficiency in surfactant, defective Na+ transport, which plays a mechanistic role in the development of the disease.
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PMID:Immature epithelial Na+ channel expression is one of the pathogenetic mechanisms leading to human neonatal respiratory distress syndrome. 890 78


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