Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0728731 (prematurity)
 7,134 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Intestinal failure-associated liver disease develops in 40% to 60% of infants who require long-term total parenteral nutrition (TPN) for intestinal failure and 15% to 40% of adults on home parenteral nutrition. The clinical spectrum includes hepatic steatosis, cholestasis, cholelithiasis, and hepatic fibrosis. Progression to biliary cirrhosis and the development of portal hypertension and liver failure occurs in a minority but is more common in infants and neonates than in adults. The pathogenesis is multifactorial. In infants it is related to prematurity, low birth weight, duration of PN, short bowel syndrome requiring multiple laparotomies, and recurrent sepsis. Other important mechanisms include lack of enteral feeding, which leads to reduced gut hormone secretion; reduction of bile flow and biliary stasis, which leads to the development of cholestasis; and biliary sludge and gallstones, which exacerbate hepatic dysfunction. In adults, IFALD is less common and related to age, length of time on PN, total caloric intake, and lipid or glucose overload. In preterm infants, a deficiency of taurine or cysteine may play a role, whereas in both adults and children, choline deficiency may exacerbate IFALD. Lipid emulsions, choline deficiency, and manganese toxicity are associated with both hepatic steatosis and cholestasis in adults and children. Management strategies for the prevention of intestinal failure-induced liver disease include early enteral feeding, a multidisciplinary approach to the management of parenteral nutrition, and aseptic catheter techniques to reduce sepsis. The addition of choline, taurine, and cysteine to PN solutions may also play a role. Oral administration of ursodeoxycholic acid may improve bile flow and reduce gallbladder stasis. Survival after either isolated small bowel or combined liver and small bowel transplantation is approximately 50% at 5 years, making this an acceptable therapeutic option in adults and children with irreversible liver and intestinal failure.
 ...
PMID:Intestinal failure-associated liver disease: what do we know today? 1647 75

Studies in the last few years have shown a remarkably high activity of fatty acid oxidation (FAO) enzymes in human placenta. We have recently shown mRNA expression as well as enzymatic activity of long-chain FAO enzymes in the human embryo and fetus. In this study we show activity of the FAO enzymes carnitine palmitoyltranferase 1, medium-chain acyl-CoA dehydrogenase and short-chain hydroxyacyl-CoA dehydrogenase in embryonic and fetal tissues. In addition, we show the presence of different acylcarnitines in fetal liver and kidney, which substantiates the notion that the mitochondrial FAO enzymes are not only present in human fetal tissues but also metabolically active. In a glucose-rich environment FAO might be necessary for additional ATP production from fatty acids, but also for the breakdown of fatty acids that are products of the turnover of membranes in the growing fetus. The importance of FAO in the human embryo and fetus is further stressed by the fact that a higher frequency of prematurity, intrauterine growth retardation, fetal morbidity and intrauterine death is noted in long-chain FAO defects. Furthermore, in animal studies, gestational loss during early embryonic development has been observed as a consequence of disturbed FAO. Finally, there are indications that regulation of activity of FAO during fetal development might not only be important for fetal life but may also have implications for health and disease in adulthood.
 ...
PMID:Fatty acid oxidation in the human fetus: implications for fetal and adult disease. 1660 71

It is a common experience that during intravenous feeding (IVF) in neonates the administered amounts do not always meet the recommendations. In an attempt to quantify these deficits and to determine the causes we studied the data of 2 comparable groups of neonates admitted to a neonatal intensive care unit (NICU). In Group 1 (N = 107; gestational age 25-42 weeks; birth weight 690-5920 g) the minimum recommended intake of energy (70 kCal/kg/d) and of aminoacids (2.5g/kg/d) was not met in 17% and in 71% respectively. The main causes of inadequate intake were believed to be the nearly exclusive use of peripheral venous access, and the restriction in glucose and/or lipid administration because of extreme prematurity and/or severe illness. In Group 2 (N = 99; gestational age 24-42 weeks; birth weight 670-4300 g), where these causes were corrected, 11% and 54% of the patients still received an insufficient amount of energy and amino acids respectively. It can be concluded that in the daily practice in a NICU, even in optimal conditions and following the recent recommendations for IVF, a considerable proportion of preterm neonates do not receive the minimal recommended amount of energy and aminoacids.
 ...
PMID:Inadequate intravenous feeding in sick neonates: a retrospective study. 1684 76

Prematurity and low birth weight are important determinants of neonatal morbidity and mortality. A rising trend of preterm births is caused by an increase in the birth rate of near-term infants. Near-term infants are defined as infants of 34 to 36 6/7 weeks gestation. It is dangerous to assume that the incidence of hypoglycemia in the later preterm infant is similar to the infant born at full term. Although current methods for assessing effects of hypoglycemia are imperfect, the injury to central nervous system depends on the degree of prematurity, presence of intrauterine growth restriction (IUGR), intrauterine compromise, genotype, blood flow, metabolic rate, and availability of other substrates. Therefore, early recognition of glucose metabolic abnormalities pertaining to late preterm infants is essential to provide appropriate and timely interventions in the newborn nursery. Although many of the investigations have targeted full-term infants, premature infants inclusive of the extremely low birth weight infants and the intrauterine growth-restricted infants, adequately powered studies restricted to only the late preterm infants are required and need future consideration.
 ...
PMID:Glucose metabolism in the late preterm infant. 1714 9

IR is hypothesized to be the important pathophysiologic link between adiposity and future development of type 2 diabetes and cardiovascular disease. A variety of methods for measuring IR have been validated in children, from the gold-standard hyperinsulinemic euglycemic clamp, to simple fasting measures based on fasting insulin and glucose levels. Studies have shown that there are a number of important risk factors for IR in children, including adiposity and visceral adiposity, race/ethnicity, puberty, a family history of type 2 diabetes, sex, and being small for gestational age or prematurity. However, obesity represents the critical risk factor for IR in children. Greater than 50% of obese adolescents in the US have IR. Formal assessment of IR in obese children may represent an important strategy for improving the efficacy of pharmacologic therapy for weight loss and chronic disease prevention.
 ...
PMID:Insulin resistance in children and adolescents. 1716 45

A concept of balanced analgesia using nonsteroidal anti-inflammatory drugs (NSAIDs), paracetamol (acetaminophen), opioids, and corticosteroids can also be used in patients with pre-existing illnesses. NSAIDs are the most effective treatment for acute pain of moderate intensity in children; however, these drugs should be avoided in patients at increased risk for serious side effects, e.g. patients with renal impairment, bleeding tendency, or extreme prematurity. NSAIDs can be given with minimal risks to the younger child with mild to moderate asthma, and, in these patients, the use of steroids can be encouraged; in addition to their antiemetic and analgesic action, a beneficial effect on asthma symptoms can be expected. In the non-intubated child with cerebral trauma, exaggerated sedation caused by opioids and increased bleeding tendency caused by NSAIDs must be avoided. In neonates and small infants, the oral administration of sucrose or glucose is helpful to minimize pain reaction during short uncomfortable interventions.
 ...
PMID:[Systemic analgesia adapted to the children's condition]. 1753 98

The role of the pancreas and insulin secretion in utero is to support fetal growth and preparation of the fetus with the nutritional reserves to maintain glucose homeostasis after birth. Adaptation at birth includes dramatic endocrine changes, up-regulation of enzymes critical for gluconeogenesis and preparation for the infant to regulate glucose control in the setting of an intermittent enteral supply of nutrition. Disorders of glucose homeostasis are not uncommon at this time, particularly in the setting of prematurity and very low birth weight (VLBW<1,500 g). Although historically hypoglycaemia has been the clinical concern, hyperglycaemia is also a well-documented problem, particularly during the first week in VLBW infants. This hyperglycaemia is a marker of insulin resistance and relative insulin deficiency and may reflect the prolonged catabolism observed in VLBW infants. Reduced insulin levels may also contribute to reduced insulin-like growth factor 1 (IGF-1) generation, and an increased risk of retinopathy of prematurity. Pilot studies of insulin replacement in VLBW infants demonstrate improved glucose control, and increased circulating IGF-1 bioactivity. This suggests that, along with nutritional support, restoration of the normal hormonal balance may be important in promoting anabolism in the VLBW infant.
 ...
PMID:The physiology and clinical management of glucose metabolism in the newborn. 1792 75

Glucose homeostasis during fetal life depends entirely on continuous placental glucose transfer. Fetal endocrine milieu is characterized by high insulin which has mainly anabolic action. During third trimester, insulin promotes energetic stores as glycogen and fat deposition. At birth, constant maternal supply is interrupted and this is accompanied by a surge in glucagon and catecholamine levels and a decrease in insulin level. These hormonal changes induce hepatic glucose production provided by glycogenolysis during the first hours of life and then by gluconeogenesis. They also promote lipolysis which generates glycerol, a gluconeogenic substrate and free fatty acids. Free fatty acids provide gluconeogenesis activating factors and ketone bodies which represent alternative fuels for brain metabolism. Equilibrium between tissue consumption of glucose, hepatic glucose production and exogenous glucose supply maintains blood glucose level. If one of these mechanisms fails, hypoglycaemia may occur. Hypoglycaemia is predictable in three situations: depletion of energetic stores (prematurity and intra-uterine growth restriction), increase tissue energetic consumption and fetal hyperinsulinism. Blood glucose levels at which clinical interventions should be considered depend on operational thresholds. Therapeutic goal in case of hypoglycaemia is to increase blood glucose enhancing gluconeogenesis and providing continuous brain supply with glucose and ketone bodies. Paradoxically, many preterm infants less than 30 gestational weeks develop hyperglycaemia. There is evidence that processing of proinsulin in beta-cells is deficient and that preterm infants are partially resistant to insulin. Exogenous insulin infusion is efficient and may be used with caution.
 ...
PMID:[Ontogenesis of glucose regulation in neonate and consequences in neonatal management]. 1816 3

Peri-operative surgical stress (SS) is characterized by increased secretion of pituitary hormones and sympathetic activation and is correlated with changed blood levels of stress hormones and metabolites. Adverse effects of perioperative stress include mortality and morbidity and a negative nitrogen balance. Although peri-operative analgesia and stress response-free period are commonly considered as synonyms, pain seems not to be the only factor determining the hormonal-metabolic response to surgery. Other factors playing a role in the creation of SS in newborns include blood loss, site of surgery, superficial and visceral trauma, surgery duration, hypothermia, infection, prematurity and factors related to cardiac surgery. Potent semi-synthetic opioids attenuate the SS better than morphine. However, supplementation of general anesthesia (GA) with local anesthetics either by way of regional or local anesthesia seems to decrease SS more effectively than GA with IV opioids. Hemodynamic monitoring may not suffice for SS or analgesia quality estimation. The most accessible laboratory measure for the monitoring of the stress response for non-cardiac surgery and pre-bypass phase of cardiac surgery may be blood glucose. Blood glucose increases with stress and when analgesia is inadequate; it is easily measured and treated almost immediately once an excessive response is identified. This individualized approach and real-time feedback may be far better than using either excessive opioid doses (hoping to ablate stress response) or minimal opioid dosages.
 ...
PMID:[Peri-operative stress response and peri-operative analgesia in children]. 1869 33

To identify antecedent clinical and health services events in infants (>/=35 weeks gestational age (GA)) who were discharged as healthy from their place of birth and subsequently sustained kernicterus. We conducted a root-cause analysis of a convenience sample of 125 infants >/=35 weeks GA cared for in US healthcare facilities (including off-shore US military bases). These cases were voluntarily reported to the Pilot USA Kernicterus Registry (1992 to 2004) and met the eligibility criteria of acute bilirubin encephalopathy (ABE) and/or post-icteric sequelae. Multiple providers at multiple sites managed this cohort of infants for their newborn jaundice and progressive hyperbilirubinemia. Clinical signs of ABE, verbalized by parents, were often inadequately elicited or recorded and often not recognized as an emergency. Clinical signs of ABE were reported in 7 of 125 infants with a subsequent diagnosis of kernicterus who were not re-evaluated or treated for hyperbilirubinemia, although jaundice was noted at outpatient visits. The remaining infants (n=118) had total serum bilirubin (TSB) levels >20 mg per 100 ml (342 micromol l(-1); range: 20.7 to 59.9 mg per 100 ml). No specific TSB threshold coincided with onset of ABE. Of infants <37 weeks GA with kernicterus, 34.9% were LGA (large for gestational age) as compared with 24.7% of term infants (>37 weeks GA). Although >90% mothers initiated breast-feeding, assessment of milk transfer and lactation support was suboptimal in most. Mortality was 4% (5 of 125) in infants readmitted at age </=1 week. Along with a rapid rise of TSB (>0.2 mg per 100 ml per hour), contributing factors, alone or in combination, included undiagnosed hemolytic disease, excessive bilirubin production related to extra-vascular hemolysis and delayed bilirubin elimination (including increased enterohepatic circulation, diagnosed and undiagnosed genetic disorders) in the context of known late prematurity (<37 weeks), glucose 6-phosphate-dehydrogenase deficiency, infection and dehydration. Readmission was at age </=5 days in 81 of 118 (69%) infants and <10 days in 101 of 118 (86%) infants. TSB levels were </=35 mg per 100 ml (598 micromol l(-1)) in 46 (39%) infants, of whom one died before exchange transfusion, one was untreated and one was lost to follow-up. Timely and efficacious bilirubin reduction interventions defined by 'crash-cart' initiation of immediate intensive phototherapy and urgent exchange transfusion were accomplished in 11 of 43 infants, which were compared with 12 of 43 infants in whom a timely exchange sometimes could not be accomplished. No overt sequelae were found in 8 of 11 infants (73%) treated with a 'crash-cart' approach compared with none without sequelae when exchange was delayed by pre-admission delays, technical factors or need to transfer to a tertiary facility. None of the remaining 20 of 43 infants treated only with phototherapy escaped sequelae. Regardless of age at readmission and intervention, infants with peak measured TSB >35 mg per 100 ml had post-icteric sequelae (n=73). There was a narrow margin of safety between birthing hospital discharge or home birth and readmission to a tertiary neonatal/pediatric facility. Progression of hyperbilirubinemia to hazardous levels and onset of neurological signs were often not identified as infant's care and medical supervision transitioned during the first week after birth. The major underlying root cause for kernicterus was systems failure of services by multiple providers at multiple sites and inability to identify the at-risk infant and manage severe hyperbilirubinemia in a timely manner.
 ...
PMID:Clinical report from the pilot USA Kernicterus Registry (1992 to 2004). 1917 57


<< Previous 1 2 3 4 5 6 7 8 9 Next >>