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)

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 adult llama (Lama glama) has several compensatory mechanisms that allow it to successfully survive at high altitude. Llama fetuses at 0.6-0.7 of gestation, and near-term llama fetuses studied close to surgery, did not increase cerebral blood flow and decreased cerebral oxygen delivery during acute hypoxemia. It is not known whether these responses were the result of immaturity or surgical stress. The aim of this study was to determine whether the lack of increase in cerebral blood flow and the decrease in cerebral oxygen delivery during hypoxemia in the fetal llama is characteristic of this high-altitude species near term, and under nonstressed conditions. We chronically catheterized 7 llamas and their fetuses near to term, at 0.7-0.9 of gestation. Fetal cardiac output, cerebral and regional blood flows, systemic blood pressure, heart rate, pH, and blood gases, organ vascular resistances and organ oxygen deliveries were determined at least 4 days after surgery, both during the basal state and after 1 hr of acute fetal hypoxemia. During hypoxemia the llama fetus did not increase cerebral blood flow and markedly decreased its cerebral oxygen delivery. There was also a marked decrease in kidney blood flow and oxygen delivery. These results indicate that, in contrast to fetuses of lowland species, the fetal llama does not increase the cerebral blood flow during hypoxemia, suggesting specific cellular mechanisms to preserve brain integrity during oxygen limitation.
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PMID:Cardiorespiratory responses to acute hypoxemia in the chronically catheterized fetal llama at 0.7-0.9 of gestation. 968 9

Newborns requiring intensive clinical care are susceptible to a wide range of excessive oxygen free radical production-related problems. In utero, fetal organs, particularly lungs, are exposed to relatively hypoxic tensions which rise abruptly after birth and this transition may cause oxidative injury in the neonate. The aims of this study were to determine oxygen free radical activity in neonates at the first 24 h, examine the role of immaturity and infection risk and compare the degree of oxidant stress in newborns treated with different oxygen concentrations. Plasma selenium levels in neonates with high infection risk (IR) were significantly lower than in healthy neonates. Comparative study of selenium in preterm, term and young infants showed age-related increases and differences were significant. Plasma selenium values were lower when oxygen therapy was administered. Vitamin E levels were significantly decreased in IR compared with healthy newborns. The results suggest that selenium and vitamin E deficiencies predispose to neonatal infection and that supplementary oxygen contributes significantly to decreasing the antioxidant defence system.
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PMID:Impact of oxygen therapy on antioxidant status in newborns. Relationship with infection risk. 969 23

To assess the influence of brain immaturity on the effects of oxygen deprivation and the participation of excitotoxicity, the consequences of a 6-h exposure to either hypoxia (95% N2/5% CO2) or 100 microM glutamate were studied in cultured fetal rat forebrain neurons taken at two maturational stages, i.e., 6 and 13 days in vitro. Cells were examined for their morphology, viability, energy metabolism reflected by 2-D-[3H]deoxyglucose uptake, and protein synthesis assessed by [3H]leucine incorporation. Apoptosis and necrosis were scored using the fluorescent dye 4,6-diamidino-2-phenylindole. Whereas 6-day-old neurons responded to a 6-h hypoxia by transient hypermetabolism, biphasic increase in protein synthesis, and cycloheximide-sensitive apoptotic death within 72 h postexposure, glutamate did not affect cell characteristics by the same time. In 13-day-old neurons, hypoxia induced both apoptosis (8.2%) and necrosis (22.3%). At this age, glutamate definitely reduced energy metabolism (26%) and protein synthesis (17%) by the end of exposure. The percentage of necrotic neurons reached 40.7%, but the rate of apoptosis was unchanged compared with controls. Therefore, excitotoxicity cannot account for hypoxia-induced injury in immature neurons, but its participation is suggested in older cells by the suppression of the necrotic component of hypoxia by glutamate receptor antagonists at 13 days.
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PMID:Lack of correlation between the effects of transient exposure to glutamate and those of hypoxia/reoxygenation in immature neurons in vitro. 972 43

We investigated colonization with Ureaplasma urealyticum (Uu) in infants <30 weeks gestation and assessed the relationship to other risk factors influencing respiratory morbidity, plus the effect of treatment with erythromycin. Ventilated preterm infants [n = 155; median GA 26 (23-29) weeks] were cultured for Uu in endotracheal aspirate and nasopharynx. Colonized infants were randomly assigned to treatment with erythromycin 40 mg/kg/d, intravenously or orally. The rate of colonization was 29/155 (19%) and the Uu-colonized infants had lower mean gestational ages than the culture-negative infants (25 vs 26 weeks). For the colonized infants PROM (48% vs 12%), chorioamnionitis in the mother (46% vs 17%) and vaginal delivery (71% vs 29%) were more common. More colonized infants needed supplemental oxygen at 36 weeks' postconceptual age (p < 0.05). Erythromycin treatment was effective in reducing colonization with negative control cultures in 12/14 (86%) of treated infants. No significant differences were found between the colonized treated infants (n = 14) and those not treated (n = 14) in time with supplemental oxygen. Oxygen requirement at 36 weeks was related to lower gestational age, late appearance of PDA, late onset sepsis and signs of chorioamnionitis in the mother. We conclude that the Uu colonization is related to increasing immaturity, the presence of prolonged rupture of membranes, signs of chorioamnionitis and vaginal delivery. Treatment with erythromycin reduced colonization but did not significantly alter length of time with supplemental oxygen.
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PMID:Ureaplasma urealyticum, erythromycin and respiratory morbidity in high-risk preterm neonates. 982 77

The immature brain is considered relatively resistant to anoxia and ischemia. Although hypoxia without ischemia has not been considered to produce brain damage in immature rats as well as in adult rats (S. Levine, Anoxic-ischemic encephalopathy in rats, Am. J. Pathol., 36 (1960) 1-17 [8]; D.E. Levy, J.B. Brieley, D.G. Silverman, F. Plum, Brief hypoxia-ischemia initially damages cerebral neurons, Arch. Neurol., 32 (1975) 450-456 [9]; J.E. Rice, R.C. Vannucci, J.B., Brieriey, The influence of immaturity on hypoxic-ischemic brain damage in rat, Ann. Neurol., 9 (1981) 131-141 [14]), hypoxia in postnatal period is possible to cause a functional brain damage (T. Hender, P. Lundborg, Regional changes in monoamine synthesis in the developing rat brain during hypoxia, Acta. Physiol. Scand., 106 (1979) 139-143 [3]; W. Ihle, J. Gross, R. Moller, Effect on chronic postnatal hypoxia on dopamine uptake by synaptosomes from striatum of adult rats, Biomed. Biochem. Acta., 44 (1985) 433-437 [7]; A. Lun, J. Gross, M. Beyer, H.D. Fischer, C. Wustmann, J. Schmidt, K. Hecht, The vulnerable period of perinatal hypoxia with regard to dopamine release and behavior in adult rats, Biomed. Biochem. Acta., 45 (1986) 619-627 [10]). Using microdialysis, we studied the anoxic or hypoxic effect on catecholamine metabolism in immature rat brain by measuring extracellular concentrations of norepinephrine (NE), dopamine (DA), and its metabolites and also 5-hydroxyindole-3-acetic acid (5-HIAA), the serotonin metabolite. DA is a well established excitatory neurotransmitter (R.C. Vannucci, Experimental biology of cerebral hypoxia-ischemia: relation to perinatal brain damage, Pediatr. Res., 27 (1990) 317-326 [16]), and in the previous report using hypoxic 7-day-old rat pups increase of DA was not detected without additional stimulations (K. Gordon, D. Johnston, M.V. Robinson, T.E. Statman, J.B. Becker, F. Silverstein, Transient hypoxia alters striatal catecholamine metabolism in immature brain: An in vivo microdialysis study, J. Neurochem., 54 (1990) 605-611 [2]). Whereas recently in newborn piglets, hypoxic hypoxia produced increase of extracellular DA (C.-C. Huang, N.S. Lajevardi, O. Tammela, A. Pastuszko, Relationship of extracellular dopamine in striatum of newborn piglets to cortical oxygen pressure, Neurochem. Res., 19 (1994) 649-655 [6]; Olano, M., Song, D., Murphy, S., Wilson, D. F. and Pastuszko, A., Relationships of dopamine, cortical oxygen pressure, and hydroxyl radicals in brain of newborn piglets during hypoxia and posthypoxic recovery, J. Neurochem., 65 (1995) 1205-1212 [13]). We consider that hypoxic ischemic brain damage of human newborns that we can treat is a damage, which does not show overt neuropathological changes. We therefore tried to show that transient anoxia and hypoxia caused biochemical alteration if the exposure did not produce marked morphological changes. This rodent model is adequate to study perinatal asphyxia and alteration of monoamine level could be useful for evaluation of brain damage, even if it is not detected histologically.
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PMID:Anoxic and hypoxic immature rat model for measurement of monoamine using in vivo microdialysis. 997 39

Newborn mammals exhibit a number of physiological reactions which differ from normal adult physiology and are often regarded as signs of immaturity. However, when looked upon from a comparative point of view, it becomes obvious that some of these 'physiological peculiarities' bear striking similarity to adaptation mechanisms known from hypoxia-tolerant animals and may thus contribute to the well-established, yet poorly understood, phenomenon of neonatal hypoxia tolerance. As the mammalian fetus lives at oxygen partial pressures corresponding to 8000 m altitude, the first line of perinatal hypoxia defense consists of long-term adaptations to limited intrauterine oxygen supply: (1) improved O2 transport by fetal acclimatization to high altitude, (2) reduced metabolic rate by hibernation-like deviation from metabolic size allometry, (3) diminished cerebral vulnerability by functional analogies to diving turtle brain, and (4) enhanced metabolic flexibility by optional repartitioning of energy supply from growth to maintenance metabolism. In the case of birth asphyxia, these background mechanisms are complemented by short-term responses to acute oxygen lack: (1) reduction of body temperature as in natural torpor, (2) reduction of heart rate and redistribution of circulation as in diving mammals, (3) reduction of respiration rate typical of 'hypoxic hypometabolism', and (4) reduction of blood pH according to the concept of 'acidotic torpidity'. Although anaerobic metabolism is improved in neonatal mammals by increased glycogen stores, reduced metabolic demands, and sustained wash-out of acid metabolites, neonatal hypoxia tolerance seems to be primarily based on the ability to maintain tissue aerobiosis as long as possible. This is even reflected by isoenzyme patterns which do not consistently favour anaerobic glycolysis and, thus, are reminiscent of the 'lactate paradox' found in high altitude adaptation. Altogether, from a biological point of view, the perinatal period appears as a source of adaptive mechanisms that can be refound, in varying combinations, in many survival strategies. From a clinical point of view, the interplay of long- and short-term mechanisms offers a novel approach to estimation of the newborn's ability to withstand temporary oxygen lack. However, most of these mechanisms are not unambiguous and, above all, not unlimited in their protective effect so that they do not release obstetricians or neonatologists from their obligation to counteract fetal or neonatal hypoxia without delay.
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PMID:Neonatal tolerance to hypoxia: a comparative-physiological approach. 1050 Oct 17

Administration of supplemental oxygen, despite being an important clinical therapy, can cause significant lung damage. Because they have underdeveloped lungs, prematurely born human infants frequently require supportive therapies that employ elevated oxygen concentrations, which put them at risk for developing pulmonary oxygen toxicity. This risk is made even greater by the immaturity of their cellular antioxidant defenses. Although the exact mechanisms of oxygen toxicity are still not fully defined, cellular damage is probably mediated by increased production of chemically reactive oxygen species (ROS) in the mitochondria. Cellular protection against ROS is provided by a variety of antioxidant molecules and enzymes, including the glutathione (GSH)-dependent antioxidant system. The GSH-dependent antioxidant enzyme system provides vital cellular protection against ROS, particularly hydrogen peroxide and certain organic hydroperoxides, under pathological and toxicological conditions, by using selenium-dependent and -independent peroxidases to reduce hydrogen peroxide or lipid peroxides to water or the respective alcohols, with the concurrent oxidation of GSH to glutathione disulfide (GSSG). In the mitochondria, limitations of GSH synthesis and transmembrane transport suggest that optimal functioning of the mitochondrial GSH system, and maintenance of adequate thiol-disulfide redox tone is essential to protect against the injurious effects of ROS. Manipulation of endogenous GSH concentrations can alter cellular responses to oxidant injury. Beneficial effects are evident when intracellular GSH concentrations are increased. In conditions that increase mitochondrial production of ROS, such as exposure to high concentrations of oxygen, therapies based on enhancing mitochondrial GSH concentrations could be highly beneficial.
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PMID:Mitochondrial glutathione and oxidative stress: implications for pulmonary oxygen toxicity in premature infants. 1100 27

The pathophysiology of bronchopulmonary dysplasia (BPD) as an inflammatory disorder secondary to neonatal respiratory distress syndrome (RDS) is not yet fully understood and still represents a major complication of prematurity. The main pathophysiologic feature of RDS is a primary surfactant deficiency in a structurally immature lung. Pulmonary surfactant contains 90 percent phospholipids and 10 percent proteins (surfactant proteins A, B, C, and D). As surfactant protein A (SP-A) has several major immunological and metabolic intrapulmonary functions, we aimed at investigating an association of polymorphisms of SP-A1 and SP-A2 encoding genes and the risk of BPD. We performed a case-control study exclusively including Caucasian preterm infants below 32 weeks of gestation matched for the degree of immaturity and the year of birth. Venous cord blood was taken prospectively and analyzed by polymerase chain reaction (PCR), single-strand conformation polymorphism (SSCP), cloning and sequencing. BPD was defined as oxygen dependency or need for mechanical ventilation at day 28. Twenty-three infants with BPD were enrolled (mean gestational age 26.2 weeks; mean birth weight 760.4 g) and compared with 23 infants matched on the basis of gestational age (mean gestational age 27.9 weeks; mean birthweight 1015 g). We observed a significantly increased frequency of the SP-A1 polymorphism 6A6 in infants with BPD compared with controls. In addition to previously established risk factors for BPD, 6A6 polymorphism for SP-A1 gene is an independent co-factor. We believe treatment of neonatal RDS should also include stratification according to genetic risk factors.
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PMID:Polymorphisms of surfactant protein A genes and the risk of bronchopulmonary dysplasia in preterm infants. 1110 14

The infant born with congenital diphragmatic hernia (CDH) remains one of the most complex patients to manage. Pulmonary hypoplasia and immaturity of the CDH lung are well recognized as the definitive limitation leading to the high mortality rates. Based on the knowledge that CDH is more a physiological disease than a surgical disease, we have shifted our management strategy from immediate repair to delayed repair and stabilization. The associated pulmonary hypertension and right-to-left shunt are common and rarely the cause of death and as such may be largely ignored. Extracorporeal membrane oxygen has been shown to salvage some of the most severely affected neonates. Other advanced and experimental respiratory therapies merit investigation in properly conducted prospective randomized multi-center trials. Survivors of CDH have predictable pulmonary, gastrointestinal and nutritional problems which, when identified and treated early, are correctable. CDH survival is close to 90% at most advanced centers. Uniform standards for CDH management do not exist however. Therefore a minimal set of practice standards should be developed from evidenced-based scientific review.
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PMID:Congenital diaphragmatic hernia: where are we and where do we go from here? 1115 3


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