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)

Surfactant proteins A (SP-A) and D (SP-D) are important in the innate host defense against pathogenic microorganisms. A deficit in these proteins in premature infants, either because of immaturity or as a consequence of superimposed chronic lung disease (CLD), could increase their susceptibility to infection. The study reported here examined infection in CLD in the premature newborn baboon, and correlated it with the amounts of SP-A and SP-D in lung tissue and lavage fluid. Two groups of baboons were delivered prematurely, at 125 d gestational age (g.a.), and differed principally in whether they developed naturally acquired pulmonary infections and sepsis. Group I animals were ventilated with clinically appropriate oxygen for 6 d and 14 d without clinical incident. Group II animals were ventilated for 5 to 71 d, but differed from those in Group I in that most developed pulmonary infection and/or sepsis. In Group I animals, tissue pools of both SP-A and SP-D were equal to or exceeded those in adults, and lavage pools of SP-A increased progressively with the time of ventilation to about 35% of adult levels after 14 d. In contrast, most Group II animals had concentrations of lavage SP-A that were less than 20% of that in adult animals. A low concentration of lavage SP-A correlated with the release of interleukin-8, and with a high "infection index" based on histopathology, microbiologic cultures, and clinical indications of sepsis. Our data suggest that the amounts of SP-A and SP-D in lavage fluid are indicators of the risk of infection in the evolution of neonatal CLD. Deficits in the amount of lavage SP-A, even after 60 d of ventilation, may have inhibited the resolution of infection and thereby contributed to the developing injury among our Group II animals.
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PMID:Deficiencies in lung surfactant proteins A and D are associated with lung infection in very premature neonatal baboons. 1117 12

The mortality of very preterm infants has significantly improved after introducing into clinical practice the antenatal use of glucocorticoid steroids prior to premature births and postnatal treatment with pulmonary surfactant which effectively decreases the tendency of the alveoli to collapse. The period of necessary mechanical ventilation was shortened. Reducing the concentration of inspired oxygen and inflation pressures became possible. In spite of this, long-term damage of lung tissue in immature infants is still a major clinical problem. However, its origin seems to be slightly different. A new form of bronchopulmonary dysplasia (BPD) has been recently evaluated. The most important factors in the pathogenesis of the "new" BPD are: lung tissue immaturity, infections initiating a cascade of events caused by formation of free oxygen radicals and cytokines and the presence of persistent patent ductus arteriosus. Primary prevention of BPD is possible by reducing the rates of prematurity and intrauterine infections. Secondary prevention includes antenatal steroids administration and postnatal surfactant treatment according to the accepted known standards. When protracted mechanical ventilation is necessary, low and subsequently reduced doses of i.v. glucocorticoid steroids in the second and third week of life are administrated, together with diuretics, bronchodilators and suitably high calorie feeding.
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PMID:[Changes in the clinical picture of bronchopulmonary dysplasia]. 1132 69

Bronchopulmonary dysplasia is the most common cause of chronic pulmonary disease in premature infants. Airway inflammation appears to play a major pathogenetic role together with barotrauma and oxygen toxicity. The aim of the present study was to determine the effect of a 15-d exposure to moderate hyperoxia (FiO2, 50%) on airway reactivity and inflammatory response in neonatal and adult rats. We studied in isolated tracheal rings the 1) isometric contraction to cumulative concentrations of carbachol (10(-8) to 10(-3) M); 2) epithelial, submucosal, smooth muscle, and connective tissue surface area; and 3) distribution of inflammatory cells (mastocytes, granulocytes, macrophages) by using MAb. Reactivity to carbachol was significantly increased in the hyperoxic pups, in which a 13% increase in tracheal smooth muscle surface area was observed. Type-I mast cells and macrophages (submucosa and connective tissue) and granulocytes (connective tissue) were increased in the neonatal hyperoxic group. Hyperoxia did not influence functional, morphometric, or cellular data in adult rats. In conclusion, exposure of newborn rats to moderate hyperoxia induces airway hyperresponsiveness and histologic changes similar to those reported in bronchopulmonary dysplasia. Hyperresponsiveness may be ascribed to an increase in smooth muscle related to the release of yet undetermined mediators by inflammatory cells infiltrating the airways. Lung immaturity definitely plays a role because similar alterations are not observed in adult rats.
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PMID:Prolonged moderate hyperoxia induces hyperresponsiveness and airway inflammation in newborn rats. 1156 96

The neonatal brain appears to be selectively vulnerable to oxidative stress. Several potential mechanisms associated with altered reactive oxygen species metabolism would explain the increased susceptibility. They include increased accumulation of hydrogen peroxide with subsequent neurotoxicity. This enhanced neurotoxicity from H2O2 accumulation may be related to inadequate scavenging abilities of the immature nervous system, such as lower glutathione peroxidase activity. Contributing to the immaturity of the scavenging enzymes is the inability of the developing nervous system to maintain glutathione stores. The immature nervous system is rich in iron, and has more free iron than the mature nervous system. As H2O2 accumulates because of these improper defense mechanisms, it is exposed to this free iron. This exposure results in the generation of OH radical (Fenton reaction), a more potent free radical that can cause severe damage. The rapid conversion of H2O2 to OH in the setting of free iron sets up the immature nervous system for increased cytotoxicity. Understanding the molecular mechanisms of oxidative stress will lead to better therapies for neonatal hypoxia-ischemia.
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PMID:Oxidant mechanisms in neonatal hypoxia-ischemia. 1159 20

Apnea, defined as cessation of breathing resulting in pathological changes in heart rate and oxygen saturation, is a common occurrence in sick neonates. Apnea is a common manifestation of various etiologies in sick neonates. In preterm children it may be related to the immaturity of the central nervous system. Secondary causes of apnea should be excluded before a diagnosis of apnea of prematurity is made. Methylaxanthines and Continuous Positive Airway Pressure form the mainstay of treatment of apnea in neonates. Mechanical ventilation is reserved for apnea resistant to above therapy. An approach to the management of apnea in neonates has been described.
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PMID:Apnea in the newborn. 1175 33

There is increasing evidence that oxidative stress is implicated in the development of bronchopulmonary dysplasia. Several important factors contribute to augmented oxidative stress in the newborn and especially the preterm infant: first, because of its immaturity, the lung of preterm infants is frequently exposed to oxygen therapy and hyperoxia. Second, the antioxidant defense and its ability to be induced during an hyperoxic challenge are impaired. Third, the preterm infant has an increased susceptibility to infection and inflammation, which increases oxidative stress. Fourth, free iron, which catalyzes the production of toxic reactive oxygen species, can be detected in preterm infants. The molecular and cellular mechanisms for free radical-induced injury are now understood in more detail, and it is clear that oxidative stress plays an important role in triggering apoptosis, in serving as second messenger and in signal transduction. This new insight might lead to novel and efficient therapies. So far, there has been no significant breakthrough regarding antioxidant therapies. Care should, however, be exercised in supplementing the preterm infant with antioxidants since this may affect growth and development.
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PMID:Bronchopulmonary dysplasia-oxidative stress and antioxidants. 1266 29

Bronchopulmonary dysplasia (BPD) continues to be one of the most common long-term complications associated with preterm birth. Its incidence is increasing as the survival of extreme premature infants improves, but its clinical presentation is milder than the original description of Northway and collaborators. In contrast to the classic BPD that was strongly related to mechanical injury and oxygen toxicity, current forms of the condition are more related to immaturity, perinatal infection and inflammation, persistent ductus arteriosus and disrupted alveolar and capillary development. Many different definitions of BPD have been proposed, most of which are based on the duration of supplemental oxygen requirement. The different definitions can produce strikingly different incidence figures, which may account for the wide variations in the condition reported in the literature. Some of the limitations of the criteria most commonly used to diagnose BPD are discussed in this article.
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PMID:Bronchopulmonary dysplasia: changes in pathogenesis, epidemiology and definition. 1266 31

Doppler parameters enable noninvasive and direct detection of placental insufficiency and brain sparing effect, which occurs as an adaptive mechanism to chronic hypoxemia. It is of great interest if further changes of Doppler parameters, which occur after the detection of the first pathologic value, can anticipate a moment of fetal distress. We investigated growth-restricted fetuses with the brain sparing effect in the time interval between the detection of blood flow redistribution until the distress. The aim of our study was to evaluate longitudinally Doppler parameters in umbilical (Aum), medial cerebral (MCA), renal (AR) and femoral (AF) artery, and find: 1) if there are significant changes in their value; 2) the character and time interval of these changes; and 3) if they differ from changes in biophysical profile (BFP). Prospective clinical study evaluated 35 pregnancies with fetal growth restriction. Fetuses were selected for the study if: 1) there were pathologic cerebral/umbilical (C/U) ratio, 2) at least four Doppler examinations in 3-4 days interval were performed and 3) prepartal fetal distress, defined as silent fetal heart rate pattern with spontaneous and late decelerations, was present. In 28 neonates after delivery umbilical artery gas and acid-base status was determined. Blood flow velocity waveforms were evaluated in Aum, MCA, AR, and AF. Arterial blood flow was estimated by pulsatility index (Pi), while in Aum we also used: present end-diastolic velocity (PEDV), absent end-diastolic velocity (AEDV) and reverse end-diastolic velocity (REDV). All of the fetuses were monitored by cardiotocogram (CTG) once to twice a day and by BFP twice a week. Elective Cesarean section was done in the presence of distress, except if severe immaturity or extreme malnutrition occurred. Etiological factors of placental insufficiency were: 1) hypertensive syndrome (n = 26), 2) chronic renal disease (n = 3), 3) primary antiphospholipid syndrome (n = 2), 4) diabetes mellitus (n = 1), 5) cardiac disease (n = 1) and 6) unknown (n = 2). Initial Doppler examination, with the detection of pathological C/U, was done in time interval between 26. to 32. weeks of gestation (wg) (29.4 +/- 2.5); delivery was between 29. to 34. wg (32.2 +/- 1.9); and average body weight was 1327 +/- 245 g. Pathological BFP was registered in 91.4% of fetuses. Cesarian section has not been done, in spite of distress, in two fetuses (5.7%) due to their extreme immaturity and/or malnutrition, so they died "in utero". Hypoxemia was registered in 96.4% (27/28) neonates, while acidosis in 71.4% (20/28). Neonatal morbidity was 93.9% (31/33), neonatal mortality 8.6%, while perinatal mortality was 14.3%. We found high significant difference (P < 0.001) in Pi Aum, Pi ACM and Pi AR in the time interval between the detection of pathological C/U ratio and fetal distress, while the difference was insignificant for the values of Pi AF (table). The value changes are characterized by: continuing increase of Pi Aum, with a maximum in the last week before the distress; biphasic character of PI MCA--tendency to decrease in the first two and significant increase in the last week; and significant increase of Pi AR one and a half week before the distress (table, graphic). Three weeks before the distress in 7 (53.8%) cases we registered PEDV, in 6 (46.2%) AEDV, while we didn't register REDV in any case. In the last week there were 3 (8.6%) PEDV, 23 (65.7%) AEDV and 9 (25.7%) REDV. Significant changes in Doppler parameters suggest that even after the blood redistribution in growth restricted hypoxemic fetuses further haemodynamic changes occur. Preterminal increase in Pi Aum can be due to: 1) release of leucotrien, tromboxan and free oxygen radicals and consecutive vasoconstriction in villous arteries; 2) increase of diastolic arterial pressure as a result of hypoxic-ischemic central nervous system (CNS) insult; 3) decreased combined heart minute volume in preterminal phase of hypoxemia. The increase of Pi MCA values is a result of hypoxic-ischemic CNS insult. As a consequence of hypoxia ischemia occurs by two mechanisms: local vasodilatatory agents production decrease, or due to the brain edema. The increase of Pi AR values can be explained by severe hypoxemia with the failure of local autoregulation of renal blood flow. The greatest changes in BFP values were registered in the first half, while in Doppler parameters in the second half of the studied interval suggesting that Doppler parameters more accurately announce fetal distress. We can conclude the following: 1) fetal distress appears after the presence hypoxic-ischemic CNS insult, and therefore late when sequels are concerned; 2) if the fetus is mature, elective delivery should be planed after the appearance of pathological C/U ratio, or with the pathological BFP at the latest, in order to avoid post-hypoxic sequels; 3) if the fetus is immature, pregnancy can be prolonged safely, in spite of pathological C/U ratio and BFP, with intensive monitoring of Doppler parameters until the detection of their increased values.
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PMID:[Longitudinal analysis of arterial Doppler parameters in growth retarded fetuses]. 1460 57

The final proof of principle that cancer patients can be effectively treated with angiogenesis inhibitors is eagerly awaited. Various preclinical in vivo experiments have proven that most tumours need new vessel formation in order to grow and to form metastases. First of all, tumours do not grow in avascular corneas until new blood vessels reach the implant. Secondly, the introduction of only one angiogenic gene can cause a switch from tumour dormancy to progressive tumour growth. Thirdly, tumour growth can be inhibited and sometimes tumour regression can be obtained just by attacking the vascular compartment with specific angiogenesis inhibitors. These three examples of preclinical experiments and many others have led to the conclusion that, in general, tumours are angiogenesis-dependent. Supported by disappointing clinical results, the angiogenesis dependency of tumours has been questioned, mainly because of the immaturity and the presumed lack of a functional blood supply (oxygen delivery and discarding of waste products) from a newly formed tumour vasculature. However, human tumours are highly heterogeneous in vascular architecture, differentiation, and functional blood supply. Vascular immaturity is a natural consequence of a genetically based unlimited expansion of tumour cells, compared to the well-regulated growth of different organs during embryonic development, for example. Unlimited tumour expansion and therefore the continuous stimulation of vessel outgrowth prevent endothelial cells from generating a mature vasculature, but instead continuously stimulate them to expand the vascular compartment of the growing tumour. In this review, the translation of angiogenesis inhibitors as a treatment for cancer from preclinical experiments to the clinic is evaluated. The preclinical evidence that tumours are angiogenesis-dependent is summarized and explanations are put forward for why the clinical results so far are not as exciting as was expected from preclinical studies. Reviewing the translation, one may conclude that human tumours are heterogeneous in their vascular architecture and function and that tumour-induced angiogenesis in humans is a more complex (multifactorially regulated) process compared with angiogenesis in preclinical cancer models.
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PMID:Are tumours angiogenesis-dependent? 1469 16

Following metabolic size allometry, the specific metabolic rate of mammals increases with decreasing body mass, resulting in a steeper metabolic fall-off and a faster exhaustion of energy reserves under hypoxic conditions. However, both mammalian hibernators and fetuses are able to temporarily "switch-off" Kleiber's rule as an adaptation to limited food or oxygen supply. Further exceptions to the usual metabolic size relationship are observed in newborn mammals. For instance, neonatal mouse hearts exhibit slower calorimetric "dying curves" under conditions of ischemia, although their aerobic tissue metabolic rates are higher than in adult samples. This is apparently due to a transient reduction of metabolic rate back to the former feto-maternal level. A continuing deviation from metabolic size allometry is found in newborn marsupials (Monodelphis domestica) where the "inappropriately" low specific metabolic rate is a precondition of efficient growth and tissue aerobiosis in spite of extreme immaturity. Obviously, adaptive suppression of elevated metabolism in organisms of small size results in a dramatic improvement of oxygen supply. Vice-versa, the overall increase in specific metabolic rate with decreasing body size might be regarded as one of several phylogenetic adaptations to protect tissues from hyperoxygenation.
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PMID:Metabolic adaptation to hypoxia: cost and benefit of being small. 1528 95


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