PubMed HealthSearch

Biomedical subjects

J M Kennaugh

Publications and source records attributed to J M Kennaugh.

10 recordsLinked to original sources

Adaptation of an ECMO team in the era of successful alternative therapies for neonatal pulmonary failure.

Neonates with persistent pulmonary hypertension show severe hypoxemia that requires a variety of therapeutic modalities. When patients do not respond to conventional medical management that includes hyperventilation, inotropic support, and vasodilating agents, treatment with extracorporeal membrane oxygenation (ECMO) may be used. More recently, high-frequency oscillatory ventilation and nitric oxide inhalation have been used in these infants and have impacted the need for ECMO. In light of these changes in therapy, the authors reviewed the 6-year clinical experience of an ECMO team to assess trends in patient population and outcome and document adaptation of the medical professionals to a new treatment era. Between 1988 and 1993, 88 neonates who met the institutional criteria were placed on venoarterial ECMO. Oscillatory ventilation was locally introduced in 1991 and nitric oxide treatment in 1992. Patient outcomes for the 1988 to 1990 period were compared with those for 1991 to 1993. Analyses included indication for ECMO therapy, length and complexity of the run, length of hospital stay, and cost of patient care. During the first 3 years, 65 patients were placed on ECMO, compared with 23 patients during the 3 years after introduction of oscillatory ventilation and nitric oxide therapy (P < .001). The length of ECMO therapy increased from a mean of 128 hours to 190 hours (P = .005), and the average hospital stay, likewise, increased from 27 days to 42 days. The total cost of care increased by approximately $40,000 per patient.(ABSTRACT TRUNCATED AT 250 WORDS)

Costs and Cost Analysis

Eicosanoids decrease with successful extracorporeal membrane oxygenation therapy in neonatal pulmonary hypertension.

Elevated concentrations of eicosanoids have been reported in bronchoalveolar lavage fluid (BALF) and blood of infants with persistent pulmonary hypertension (PPHN), thereby indicating their potential role in its pathophysiology. Extracorporeal membrane oxygenation (ECMO) has improved the outcome in selected infants with PPHN. We hypothesized that ECMO, by alleviating lung injury, would be associated with decreased eicosanoid production and clinical improvement. Twenty-two newborns with PPHN treated with either ECMO or conventional means were studied. Concentrations of TxB2, 6-keto-PGF1 alpha, PGD2, PGE2, LTB4, and LTE4 were serially measured in BALF. Elevated concentrations of all eicosanoids measured were observed in all infants with PPHN at the initiation of ECMO. Eicosanoid concentrations decreased in all infants with a good clinical outcome after ECMO, but they remained elevated in those with a poor outcome. In patients with less severe PPHN, not requiring ECMO, lower concentrations of eicosanoids were observed at initiation of therapy. Eicosanoid levels increased or did not change over the course of conventional treatment. We conclude that eicosanoids are present in high concentrations in infants with PPHN. Iatrogenic factors, including oxygen and barotrauma, appear to correlate with their concentrations. Removal of these factors is associated with decreased production of mediators and clinical improvement.

Acute Disease

Uptake of amino acids and ammonia at mid-gestation by the fetal lamb.

Fetal uptakes of amino acids and ammonia via the umbilical circulation were measured in single pregnant ewes at mid-gestation (range 66-81 days). There were significant net fluxes from placenta to fetus of ammonia and twelve amino acids (in decreasing order: glutamine, glycine, alanine, proline, lysine, arginine, threonine, valine, leucine, tyrosine, asparagine, isoleucine) and net fluxes from fetus to placenta of glutamate and serine. The estimated serine flux was 139 mumol day-1 (g fetal dry wt)-1. Comparison with late gestation data indicated a similar pattern of amino acid exchange. However, the relatively large placental uptake of fetal serine was a distinctive feature of mid-gestation. The net fetal uptake of amino acid nitrogen was 2.83 +/- 0.66 micrograms N (mumol O2 uptake)-1, or 18 mg N day-1 (g dry wt)-1. This uptake was similar in magnitude to the combined fetal requirements for nitrogen accretion and urea synthesis and represented approximately 32 and 43% of fetal carbon and energy requirements, respectively.

Amino Acids

Ontogenetic changes in the rates of protein synthesis and leucine oxidation during fetal life.

Studies of fetal leucine metabolism and protein synthetic rate, using L-(1-14)leucine as tracer, were carried out in 12 pregnant ewes at midgestation and compared with similar studies in late gestation. The disposal rate of fetal plasma leucine ranged between 3.07 and 9.06 mumol/min and was correlated (r = 0.89) to fetal dry weight. The fluxes to CO2 excretion and to protein synthesis were 18.6 +/- 2.6 and 37.2 +/- 2.6% of disposal rate, respectively. The flux of leucine molecules into the placenta was relatively large and correlated to the placental/fetal dry weight ratio (r = 0.84). The mean fractional protein synthetic rate was 0.216 +/- 0.01 day-1. Comparison with late gestation data showed that fractional protein synthetic rate is inversely correlated (r = 0.87) to gestational age and that fetal protein synthetic rate (PRs, g/day) is related to fetal dry weight (DW,g) by the allometric equation: log PRs = -0.503 + 0.754 log DW The 0.754 exponent is similar to the exponent relating fetal oxygen consumption to dry weight (0.729). This indicates that protein synthesis and energy metabolism per g dry weight decrease during fetal growth at approximately the same rate so that the protein synthesis/oxygen consumption ratio tends to remain constant.

Animals

Nutrition of the fetus and newborn.

Both the successful development of healthy, long-term animal models to study fetal nutrition and metabolism and the improved survival of low-birth-weight, preterm infants have focused interest and research on fetal and neonatal nutrition and metabolism. Such a focus is important, given the recent emphasis on promoting neonatal growth in preterm infants at "normal" in utero growth rates. Estimates of nutrient requirements for growth in a human fetus remain ill defined, however. Body composition data appear biased toward thin infants. Animal data suggest that fetal nutrition proceeds according to species-specific growth rates, with variations in fat content largely dependent on placental fat permeability and on maternal nutrient supply as regulated by the placenta. After birth, neonatal nutrition is affected primarily by food intake and the functional integrity and capacity of the gastrointestinal tract. Additionally, muscle activity, thermoregulation and stresses of various kinds and degrees modify a neonate's nutritional requirements. Functional deficits of the gastrointestinal tract have been circumvented by a more aggressive use of intravenous nutrition. Both intravenous and enteral nutrient mixtures have been substantially improved in the quantity of all nutrients and have been modified qualitatively toward compositions that are closer to those of human milk. These nutrient mixtures now produce plasma nutrient concentrations that approximate those of a healthy, breast-fed infant. Although such efforts to improve the nutritional balance and growth of preterm infants have been successful, much remains to be learned about the nutritional requirements of sick infants.

Animals

Metabolic and circulatory studies of fetal lamb at midgestation.

Uterine and umbilical blood flows, the placental clearance of 3H2O, uterine and umbilical uptakes of oxygen, glucose, and lactate were measured in conscious, pregnant sheep at 71-81 days gestation. Fetal weight was 210 +/- 20 g and less than half placental weight. In relation to fetal weight, umbilical flow was 468 +/- 57 ml X min-1 X kg-1, more than double normal values for the mature fetus. Clearance of 3H2O was approximately 12% of the late pregnancy value but high in relation to fetal weight (280 +/- 23 ml X min-1 X kg-1). Fetal oxygen uptake was 10.9 +/- 0.6 ml X min-1 X kg-1, approximately 40% greater than in late gestation. Umbilical uptake of glucose was also relatively high, whereas lactate uptake was low. Uteroplacental tissues consumed more than 80% of the oxygen and glucose taken up by the pregnant uterus. However, uteroplacental utilization rates of oxygen and glucose as well as net lactate production were lower (approximately 50, 30, and 25%, respectively) than in late pregnancy, despite a larger placental mass (486 +/- 22 vs. 302 +/- 12 g).

Animals

Agenesis of the corpus callosum in two brothers.

Two brothers with developmental delay and unusual cranial configurations were found to have agenesis of the corpus callosum (ACC) by CT scan. Six published families in which ACC occurred in the absence of extracranial malformations are reviewed. No single mode of inheritance can account for all of these familial cases. This family illustrates the value of CT scanning in evaluating children with developmental delay.

Abnormalities, Multiple

Reciprocal translocation 14q;21q in a patient with the Brachmann-de Lange syndrome.

A patient with the Brachmann-de Lange syndrome was found to have an apparently balanced de novo translocation 14q; 21q. The relationship between this uncommon translocation and the patient's phenotype is unclear. Although most patients with the Brachmann-de Lange syndrome have normal chromosomes, the possibility of aetiological heterogeneity, including some rare chromosomal abnormalities, cannot be dismissed.

Chromosomes, Human, 13-15