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)

Numerous subsequent controlled trials and recent meta-analysis have confirmed the efficiency of antenatal glucocorticoid therapy in reducing both the incidence of respiratory distress syndrome (RDS) and perinatal mortality. Moreover, antenatal glucocorticoid administration reduces the odds of several severe complications relating to immaturity: intraventricular hemorrhage (IVH), ductus arteriosus patency, necrotising enterocolitis, and hemodynamic failure. Exogenous surfactant therapy has not ruled out the benefits of corticosteroids: on the contrary, a synergic effect is obtained when both antenatal and postnatal therapeutic approaches are combined. Very premature infants may also take advantage of the hormonal treatment: in this population, RDS occurrence, IVH incidence and perinatal mortality are also reduced. Unfortunately, despite convincing evidence, the incidence of antenatal steroids therapy has not yet achieved the optimal and desirable level. Obstetricians and pediatricians must be encouraged to ensure high maternal exposure to steroids when preterm delivery is likely to occur.
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PMID:[Prenatal corticotherapy and acceleration of fetal maturation. II. Results of clinical applications]. 895 78

Antibiotics are the leading cause of drug-induced kidney disease, and among them the aminoglycosides (AMG) are the main nephrotoxic agents, bringing about kidney damage via a direct dose-dependent mechanism. The combination of an aminoglycoside and a penicillin derivative is still the most commonly recommended and used first-line treatment modality in the empirical therapy of neonatal sepsis, despite the low therapeutic index of AMG. The immaturity of neonatal kidney function, particularly in preterm neonates, makes newborn infants particularly susceptible to AMG-induced kidney damage. Numerous factors intervene in bringing about AMG-induced kidney damage, such as factors related to the antibiotic itself (intrinsic toxicity, administration route, type of monitoring of blood concentrations), those related to the subject treated (neonatal age, constitutional sensitivity), and others related to associated pathology (neonatal anoxia, renal hypoperfusion, respiratory distress/mechanical ventilation, hyperbilirubinaemia/phototherapy, electrolyte disorders, and even the acute sepsis calling for antibiotic therapy), as well as pharmacological factors (concomitant therapies such as diuretics, indomethacin and other antibiotics, particularly glycopeptides and cephalosporins).
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PMID:[Aminoglycosides, risk factors and neonatal kidney]. 905 89

The mammalian lung develops through branching morphogenesis which is controlled by growth factors, hormones, and extracellular matrix proteins. We have evaluated the role of EGF-receptor signaling in lung morphogenesis by analyzing the developmental phenotype of lungs in mice with an inactivated the EGF-receptor gene both in vivo and in organ culture. Neonatal EGF-receptor-deficient mice often show evidence of lung immaturity which can result in visible respiratory distress. The lungs of these mutant mice had impaired branching and deficient alveolization and septation, resulting in a 50% reduction in alveolar volume and, thus, a markedly reduced surface for gas exchange. The EGF-receptor inactivation also resulted in type II pneumocyte immaturity, which was apparent from their increased glycogen content and a reduced number of lamellar bodies. The defective branching was already evident at Day 12 of embryonic development. When explants of embryonic lungs from Day 12 embryos were cultured under defined conditions, the branching defect in EGF-receptor-deficient lungs was even more pronounced, with only half as many terminal buds as normal lungs. EGF treatment stimulated the expression of surfactant protein C and thyroid transcription factor-1 in cultured normal lungs, but not in EGF-receptor-deficient lungs, suggesting that EGF-receptor signaling regulates the expression of these marker genes during type II pneumocyte maturation. Taken together, our data indicate that signal transduction through the EGF receptor plays a major role in lung development and that its inactivation leads to a respiratory distress-like syndrome.
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PMID:Impaired lung branching morphogenesis in the absence of functional EGF receptor. 920 41

Our aim was to evaluate long-term effects of exogenous surfactant therapy on pulmonary functional outcome in children born very preterm. We examined 40 children aged 7-12 years who were born before 30 weeks of gestation with an immature surfactant system, and were randomized to one of three treatment groups: human surfactant given at birth (prophylactic), human surfactant given after development of neonatal respiratory distress syndrome (rescue), and placebo (air) treatment. Spirometric parameters of preterm born children were compared with those of 20 children born at term. In addition, spirometric parameters were monitored twice daily for 4 weeks using a home spirometer. All spirometric parameters were significantly lower in the preterm groups than in the controls, except for the forced vital capacity (FVC) in the prophylactically treated group. Bronchial obstruction was found in 53% of the prophylactically treated group, in 36% of the rescue group, in 67% of the placebo group, and in 0% of the control group. Peak expiratory flow (PEF) and FVC values were higher in those children who received surfactant compared with the placebo group (P < 0.05). In 16 children (40%) born preterm, a beta2-agonist induced an increase in PEF > or = 15% at least three times during 2 weeks of home monitoring; eight children (20%) had abnormal diurnal PEF variation. Multiple regression analysis indicated that the independent variables associated with favorable outcomes in spirometric parameters were surfactant therapy (P = 0.012-0.045) and short intubation time after birth (P = 0.0009-0.0044). Bronchial obstruction, responsiveness to a beta2-agonist, and high diurnal PEF variation are common in children born before 30 gestational weeks. Surfactant supplementation reducing the need for mechanical ventilation or supplementary oxygen after birth may decrease the severity of immaturity related bronchial obstruction in childhood.
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PMID:Effect of neonatal surfactant therapy on lung function at school age in children born very preterm. 955 10

The epidermal growth factor receptor (EGF-R) is perhaps the best studied member of tyrosine kinase receptors. Its inactivation by homologous recombination results in three different phenotypes ranging from peri-implantation lethality to postnatal lethality. The mildest form of EGF-R inactivation leads to epithelial immaturity and postnatal death due to respiratory failure and necrotizing enterocolitis-like lesions in the intestine. The defects seen in this 'postnatal lethality phenotype' manifest in the classical EGF-responsive organs (skin, intestine) and organs undergoing branching morphogenesis during development (lung, kidney, mammary gland, pancreas and prostate), and thus accord with the concept of EGF family members being important epithelial mitogens. The respiratory failure of the EGF-R (-/-) mice results from impaired branching of the alveolar tree and leads to decreased surface for gas exchange. Overall, the lung phenotype bears similarity to respiratory distress syndrome and bronchopulmonary dysplasia--the most common complications of prematurity in humans. Intestinal changes seen in the EGF-R (-/-) mice vary in severity, the end-point being severe mucosal lesions and necroses. These findings resemble those seen in necrotizing enterocolitis of premature babies, a serious intestinal problem in the neonate. Although deficient EGF-R function is not the reason for these prematurity-associated diseases it may nevertheless exacerbate them. Potential usage of EGF transforming growth factor-alpha in clinical work is discussed.
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PMID:Epidermal growth factor receptor in mice and men--any applications to clinical practice? 956 19

Transforming growth factor-beta (TGF-beta), a potent inhibitor of epithelial cell proliferation, and epidermal growth factor (EGF), a mitogenic polypeptide that binds to cell surface receptors, are important regulators of cell differentiation; however, their distinct role(s) in lung development and their mechanisms of action are not well understood. We evaluated the effects of these factors on lung morphogenesis in murine fetal lungs at gestational day 14 (time:zero) and again after 7 days in culture. Baseline controls were cultured after tracheal transection in supplemented BGJb medium, and other tracheally transected lungs were cultured following addition of EGF (10 ng/ml BGJb), TGF-beta1 (2 ng/ml BFJb), or with both in combination added to the medium. The control lungs in culture had poorly developed airways and an absence of defined acinar structures. The addition of EGF resulted in hyperplasia of primary airways with stunted outgrowths, monopodial branching, and absence of distinct acinar structures. Addition of TGF-beta1 alone, led to significant elongation of primary airways, without normal airway branching; however, terminal dipodial branching was seen and the prospective pulmonary acini were well defined. Combination of these growth factors (GF) resulted in a more normal branching pattern and differentiation, suggesting their epigenetic role in lung morphogenesis and mutual interactive mechanisms that regulate lung development. These lungs had more abundant and larger lamellar bodies than those after other treatments. Control lungs remained immature with prominent glycogen aggregates with occasional dense lamellar bodies. The total protein and DNA contents were highest with EGF treatment, followed by combination treatment; these observations were supported by immunohistochemical localization of proliferating cell nuclear antigen, an indication of the proliferative state of tissues. All the surfactant proteins were relatively unaltered and their messages were up-regulated for SP-A, but down-regulated for SP-B and SP-C in the lungs treated with growth factors. In conclusion, we have demonstrated enhanced biochemical and structural development of lungs treated in vitro with GF, and propose that further research in this area may lead to therapeutic uses of GF alone or in combination with other agents for the treatment of newborn respiratory distress due to lung immaturity or hypoplastic lung development.
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PMID:Influence of epidermal growth factor and transforming growth factor beta-1 on patterns of fetal mouse lung branching morphogenesis in organ culture. 959 Apr 85

In Japan, chronic lung disease (CLD) is defined as an oxygen requirement greater than that obtainable in room air at 28 days of age, with symptoms of persistent respirator distress and a hazy or emphysematous and fibrous appearance upon chest x-ray. A total of 4964 infants weighing less than 1500 g at birth and born in 1990 were admitted to and cared for at level II and III neonatal care centers in Japan. A total of 4293 infants (86.3%) survived at 28 days after birth. Analyses of infants who developed CLD through their preceding illnesses and chest x-ray findings resulted in the classification of CLD into six types. Types I and II are defined as CLD following the acute stage respiratory distress syndrome (RDS). Type I is the typical case of bronchopulmonary dysplasia (BPD) as described previously, whereas Type II shows atypical radiological findings, namely only diffuse haziness without typical emphysema and fibrosis. Type III has a history of intrauterine inflammation. Chest x-ray shows the typical bubbling and cystic appearance described in the original report of Wilson-Mikity syndrome or neonatal pulmonary emphysema in the very low birth weight infant. Type III also has atypical radiological findings in cases with intrauterine infection. Type IV does not have a history of either intrauterine inflammation or RDS but shows typical emphysematous and fibrous appearance upon chest x-ray. Type V includes those with atypical chest x-ray appearance similar to Type II but without history of RDS and intrauterine inflammation. CLD is a heterogeneous condition which shows different spectra. However, the cardinal event is common to all types--the excessive inflammatory response caused by various insults to the immature airways and alveoli, such as oxygen, barotrauma, infection and so on. The excessive inflammatory response leads to lung tissue damage and the abnormal healing process due to immaturity, (such as vitamin A deficiency and insufficient oxygen radical scavenging system) and results in dysplasia and metaplasia of the respiratory system. The treatment of respiratory distress due to CLD also acts as an insult to the lungs and thus forms a vicious cycle. The different spectra of the disease are most possibly attributed to the difference in the timing and the kind of insults to the lungs. In Type I and II CLD, the insults are given in the first hours of life when the infants with surfactant deficiency receive high concentrations of oxygen for stabilization before the surfactant replacement. In Type III and III' CLD the insults are most likely given before birth. Excessive and sustained inflammatory response in the lungs with different onset times may result in the development of Type IV and V CLD. The strategy for the prevention of CLD should be different according to the origins and causes. The prevention of Type I and II CLD, or CLD following RDS, should be accomplished by successful prophylactic surfactant replacement therapy. Another procedure may be the application of high frequency oscillatory ventilation (HFOV) in the acute stage of RDS or at the time of stabilization right after birth. Types III and III' CLD present the most difficult challenge for prevention strategy because the disease process already started before birth. At the moment there are no effective measures for prevention. The strategy for the prevention of Type IV and V CLD may reside in the early detection and treatment of patent ductus arteriosus, sepsis and airway infection including pneumonia.
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PMID:Chronic lung disease of the very low birth weight infant--is it preventable? 967 27

The Diabetes Mellitus is the pathology that frequently is associated to the pregnancy and it is responsible for perinatal mobility specially by the respiratory distress syndrome since exists delay in the conversion of myoinositol-phosphatidyl inositol-phosphatidyl glycerol. To demonstrate the reliability of the DO tho 650 nm with standard of 20 in the determination of fetal lung maturity of the infant of diabetic mother. There were included 143 patient with pregnancy > or = 37 weeks with amenorrhea reliable and gestational age confirmed by ultrasound, of those 94 corresponded to gestational Diabetes Mellitus, 49 to pregestational (46 non insulin-dependent and 3 insulin-dependent). In all of them amniotic fluid studies was perform at 37 week and the resolution of the pregnancy was when DO to 650 nm showed fetal lung maturity. It was found a correlation among the DO to 650 nm of 20 and absence of RDS in 130 cases (true positive); there were seven cases with immaturity results by DO that they did not express RDS (false negative) and six cases with results that showed immaturity by DO and there were manifestations of RDS (true negative). We did not find results of false positive. The frequency of RDS was of 4.9% with a positive predictive value of the 100% an negative predictive value of 46%, a specificity of 100% and a sensitivity of 94%. An interesting finding was the fact that six cases true negative cases had poor maternal metabolic control of different degrees. For our results can be deduced that DO to 650 nm with standard of .20 it is reliable for the diagnosis of fetal lung maturity in the pregnancies complicated with Diabetes Mellitus, in addition to be an easy elaboration test and low cost.
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PMID:[Reliability of optic density at 650 nm in determining lung maturity in children of diabetic mothers]. 982 5

Thyroid gland function develops and matures during fetal life, with production of serum thyroxine (T4) concentrations beginning around 12 weeks gestation and increasing to term. Infants born prior to term have lower cord serum T4 concentrations that correlate with gestational age or birth weight. This is partially the result of lower thyroxine-binding globulin (TBG) concentrations. The cord serum free thyroxine (FT4) concentrations also correlate with gestational age, but they are not proportionately as low as the cord T4 concentration. Preterm infants have a postnatal thyrotropin (TSH) surge and rise in serum T4 and triiodothyronine (T3), which is qualitatively similar to, but quantitatively smaller than, term infants. In contrast to term infants, preterm infants often experience a fall in serum T4 and T3 in the first week of life to below birth levels. This drop appears to be the result of many factors, including nutritional problems and decreased hepatic TBG production, immaturity of hypothalamic-pituitary control of the thyroid gland, immaturity of the thyroid gland itself, and increased tissue utilization of T4. These changes are impacted by complications of prematurity, such as respiratory distress syndrome (RDS), which result in nonthyroidal illness-like changes. Again, serum FT4 seems less affected, and when measured by equilibrium dialysis may be in the normal range for age. Several studies have correlated different measures of morbidity and mortality in the preterm infant with lower serum T4 concentrations. However, as with adults, it may be that low serum T4 concentrations are a marker of the sickest preemies. Also, as with adults, this has led to speculation that T4 treatment might be beneficial in improving these complications of prematurity, in particular the neurological outcome. While some studies appear to show improvement in some facet of medical complications with T4 treatment, most show no effect. Regarding neurological outcome, the 2 best controlled trials do not show improvement in neuropsychiatric testing outcome assessed up to 2 years of age. One study, however, showed an IQ that was 18 points higher in the T4-treated subgroup less than 27 weeks gestational age. It may be that the most preterm infants, eg, those less than 27 weeks of age, are at a disadvantage compared with their intrauterine counterparts, in that they lack the maternal thyroid hormone contribution and are forced to adapt to extrauterine life before their hypothalamic-pituitary-thyroid axis is mature enough to deal with tissue thyroxine demands. Further controlled studies are needed to determine if this subgroup of infants indeed may benefit from transient thyroid hormone supplementation.
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PMID:Thyroid function in the preterm infant. 1003 80

Babies of 37-41 wk gestation are, by international convention, said to be born at 'term', but some still develop respiratory distress. It is not clear how mature a baby has to be to be free of risk of primary surfactant deficiency. An area-based retrospective study of all the 179,701 babies of 34 or more weeks' gestation born alive in a defined area of the north of England in 1988-92 identified 149 babies with features of respiratory distress typical of surfactant deficiency severe enough to be managed with ventilatory support and with no evidence of aspiration or intrapartum infection. Gestation was carefully cross-validated against antenatal information, including at least one ultrasound assessment in the first half of pregnancy. Thirty-six of these babies were born at or after 37 wk gestation. Only 4 of the 35 delivered at 37-38 wk went into spontaneous labour. Seven became ill enough to be candidates for ECMO and two died. A review of all neonatal deaths in the study area between 1981 and 1995 identified four similar deaths in 1981-87 and two in 1993-95. Babies who are not premature, using the internationally agreed definition, can show signs of potentially lethal pulmonary immaturity at birth, especially if subjected to pre-labour Caesarean delivery. Those born at 37-38 wk are 120 times more likely to receive ventilatory support for surfactant deficiency than those born at 39-41 wk. Elective delivery should only be undertaken before 39 wk gestation for good medical reasons.
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PMID:Surfactant-deficient respiratory distress after elective delivery at 'term'. 1059 16


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