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Biomedical subjects

P M Farrell

Publications and source records attributed to P M Farrell.

At least 109 records · Page 6Linked to original sources
PubMed1982

Essential fatty acid deficiency after hepatic portoenterostomy for biliary atresia.

Gas chromatography was used to determine the fatty acid composition of total lipids extracted from plasma and erythrocytes of five patients who had received an hepatic portoenterostomy for treatment of extrahepatic biliary atresia. Three patients, including one with successful surgery, demonstrated evidence of essential fatty acid deficiency, including decreased levels of linoleic and arachidonic acids with concomitant increases in palmitoleic and oleic acids. In two of these patients, the ratio of 5,8 11-eicosatrienoic acid to arachidonic acid ("triene/tetraene") exceeded 0.3, diagnostic of essential fatty acid deficiency. Even patients with successful hepatic portoenterostomy are at risk to develop essential fatty acid deficiency.

Bile Ducts↗
PubMed1982

Evaluation of vitamin E deficiency in children with lung disease.

The clinical assessment of vitamin E status has traditionally depended upon measurement of tocopherol concentrations in plasma or serum, with 0.5 mg/dl being used as the lower limit of normal. This approach can be supplemented by measurement of tocopherol in erythrocytes or by evaluating their susceptibility to hemolysis in the presence of hydrogen peroxide. Data obtained during the last decade indicate that tocopherol concentrations in blood samples may be misleading, and that tocopherol-lipid ratios are more reliable indicators of vitamin E status. In our studies, small populations of healthy children have been evaluated, along with infants and children with a variety of chronic diseases. Of interest is the observation that premature infants susceptible to lung disease, who often require high levels of inspired oxygen, and children with cystic fibrosis who have chronic obstructive pulmonary disease are almost invariably below 0.5 mg tocopherol per deciliter plasma. A substantial number, however, show no abnormality in peroxide-induced erythrocyte hemolysis. Expression of the tocopherol data per gram of total lipid indicates that many children with "low" tocopherol concentrations per unit volume of plasma are not deficient in vitamin E, but rather are above 0.8 mg/g, the ratio of tocopherol to lipid previously reported as the lower limit of normal.

Adolescent↗
PubMed1982

Biochemical and physiological development of fetal rhesus lung.

Study of 17 fetal rhesus monkeys (Macaca mulatta) revealed a sequential rise in lung phosphatidylcholine (PC) concentration due to elevations in both disaturated (DSPC) and unsaturated constituents. The % DSPC in lung tissue clinical abruptly at 145 days of gestation prior to significant increases in PC or DSPC concentration but in association with improved lung deflation stability (% V10). This suggests that the DSPC-to-PC ratio may be a sensitive biochemical indicator of surfactant phospholipid production in lung parenchyma. Phosphatidyl-glycerol content did not increase significantly until after 155 days gestation, which was coincident with maximizing pulmonary distensibility (V max). Declining levels of phosphatidylethanolamine and sphingomyelin in lung tissue at 162 days support the hypothesis that preferential synthesis of PC occurs during late gestation. A serial decline in lung glycogen content with advancing gestation may reflect glycogen utilization as a substrate for lung phospholipid production. Comparison of biochemical and physiological data confirms the impression that discordances occur among lung maturational events. Lastly, a relationship between rising fetal blood cortisol levels and indices of fetal lung development was not demonstrated.

Animals↗
PubMed1982

Granulocyte chemiluminescence in adolescent patients with cystic fibrosis.

The granulocyte chemiluminescence (CL) response is the result of activating its cellular "respiratory burst" and oxidative metabolism. The resulting light emission is an indication of intact metabolic events important in bactericidal activity. Patients with cystic fibrosis have recurrent pulmonary infections. To determine whether granulocytes from patients with CF have defective oxidative metabolism, CL was assayed in 8 patients and compared with that in normal control subjects. In CF, the peak CL response to opsonized zymosan is normal. If, however, the time required for peak light emission is compared with the NIH Clinical Score, a significant correlation is found. Granulocytes from patients with airway disease and more severe CF have a more rapid onset of the CL response. Although the clinical significance of this observation is not established, granulocytes from patients with CF appeared "primed" in their responses to a phagocytic stimulus.

Adolescent↗
PubMed1982

Complications of pregnancy and fetal development.

Although the outcome of pregnancy for women with diabetes mellitus has improved in recent years, the infant of the diabetic mother has an increased risk of major clinical problems, particularly in the early neonatal period. These include birth injury due to macrosomia, neonatal hypoglycemia, respiratory distress syndrome, and serious congenital anomalies. Because of the great difficulties encountered during attempts to investigate these problems in clinical research protocols, there is a continuing need to establish appropriate animal models of the diabetic pregnancy. Studies carried out over the past decade, primarily with chemically-induced diabetes have suggested techniques which might be useful. In general, the choice of the animal to be studied will depend on the hypotheses being addressed. For instance, small animals such as rabbits and rats made diabetic with streptozotocin have been successfully used for investigation of fetal lung development. Furthermore, the rat model has been helpful for evaluation of fetal anomalies associated with maldevelopment of the spine and central nervous system. Larger animals, such as the nonhuman primate, are more appropriate for studying placental function and amniotic fluid composition in diabetic pregnancies. The task group on pregnancy and fetal development recommends that animal models of diabetes mellitus be used for a more extensive hormonal and metabolic characterization of diabetic mothers during pregnancy, for investigation of placental physiology with respect to the transfer of substrates from mother to fetus, for systematic and comprehensive study of mechanisms controlling fetal lung development, and for delineation of the pathophysiology of neonatal hypoglycemia. It is further recommended that animal models of spontaneous diabetes such as the BB/W rat be used in future studies dealing with pregnancy and fetal development. Because females with spontaneous diabetes show reduced conception rates, there is a pressing need to enhance the fertility of these animals in order to intensify studies on fetal development.

Alloxan↗
PubMed1982

Analysis of causes of neonatal death in the United States with specific emphasis on fatal hyaline membrane disease.

National mortality statistics for hyaline membrane disease (HMD) and the respiratory distress syndrome (RDS) and other major causalities were examined in this study for the years 1968 to 1978. A progressive reduction in total neonatal deaths began in 1971 such that only 56% as many newborn deaths occurred in 1978 as in 1968 (31,618 vs 66,456). In each of the 11 years surveyed, the majority of deaths occurred during the first four days of life, with more than half of the infants dying before 48 hours of age. HMD/RDS was the leading cause of death during nine of the 11 years analyzed, accounting for an average 19.5% of neonatal fatalities. Deaths associated with HMD/RDS increased for 1968 to 1971 plateaved and progressively decreased in the ensuing years between 1974 and 1978. Thus, the percent of all neonatal deaths attributable to HMD/RDS increased from 14.7% in 1968 to a maximum of 21.3% in 1974, before declining to 17.5% in 1978. The average contribution of other major causes of death to overall neonatal mortality were: perinatal asphyxia, 13.4%; immaturity, 13.4%; and complications of pregnancy, 11.1%. These data indicate that: (1) despite the declining incidence of fatal HMD/RDS the disorder accounted for an increasing percent of total deaths through the later part of the 11-year period; (2) prevention and/or improved management of asphyxia made the most significant (29%) contribution to reduced neonatal mortality; (3) less change occurred in fatal complications of pregnancy, implying a continuing need for improved maternal/fetal care. Comparing national mortality statistics with those of Wisconsin suggests that further reduction in HMD/RDS death rates should be possible and could have a marked influence on national neonatal mortality statistics.

Asphyxia Neonatorum↗
PubMed1981

The stability of phospholipids in amniotic fluid.

A systematic study of amniotic fluid phospholipids including phosphatidylcholine (PC, lecithin), saturated phosphatidylcholine, and phosphatidylglycerol was undertaken to evaluate the stability of these surfactant indices as a function of temperature and time. The purpose of the study was to determine optimum conditions for storage and for transport of specimens to centralized laboratories performing comprehensive analyses of amniotic fluid phospholipids for improved assessment of fetal lung development. Remarkable stability was found for the above phospholipids, as well as for the more commonly employed ratio of lecithin to sphingomyelin. We determined that room temperature more commonly employed ratio of lecithin to sphingomyelin. We determined that room temperature storage is acceptable for periods up to 24 hours; however, when longer delays before lipid extraction are anticipated, it is essential that specimens be frozen or that refrigeration or wet-ice storage (4 degrees C) be employed. Results of this study indicate that when amniotic fluid samples are stored frozen and strict quality control is maintained in analytic procedures, only minimal changes occur in phospholipid concentrations over 12 months.

Amniotic Fluid↗
PubMed1981

Analysis of granulocyte beta-adrenergic response in cystic fibrosis: correlation of decreased responsiveness with disease severity.

Granulocytes from 21 nonasthmatic cystic fibrosis (CF) patients were isolated and the effects of isoproterenol, histamine, and prostaglandin E1 upon zymosan-induced beta-glucuronidase release was measured. Granulocytes from CF patients contained significantly less total beta-glucuronidase activity compared with those from control subjects, but response to zymosan stimulation was normal. Compared with those from control subjects, the granulocytes from CF patients with severe airway disease (% predicted FEV1 less than 60) had significantly reduced responsiveness to isoproterenol, which correlated with both the % predicted FEV1 values and the NIH clinical score. In this same population of CF patients, granulocyte responsiveness to PGE1 was also decreased compared with that of the control subjects, but the degree of impairment was not as severe as that observed with isoproterenol nor did it correlate with disease severity. Histamine responsiveness, however, was normal. Our findings suggest that abnormal beta-adrenergic responses may reflect the severity of airway disease and clinical score.

Adolescent↗
PubMed1979

Familial respiratory distress syndrome in three consecutive full-term infants. Case reports and documentation of lung enzyme activities.

Familial respiratory distress syndrome in full-term newborn infants is a rare occurrence. Our patient delivered three consecutive full-term infants who developed findings consistent with respiratory distress syndrome. All three died from autopsy-proven hyaline membrane disease. Analysis of the activities of four enzymes that play an important role in the biosynthesis of lecithin (choline kinase, choline phosphotransferase, phospholipase A and lysolecithin acyltransferase) failed to disclose an abnormality in lung samples in our patient with familial respiratory distress syndrome.

1-Acylglycerophosphocholine O-Acyltransferase↗
PubMed1978

Evidence for the existence of a single enzyme catalyzing the phosphorylation of choline and ethanolamine in primate lung.

Choline kinase (ATP:choline phosphotransferase, EC 2.7.1.32) has been isolated and purified 1000-fold from adult African Green monkey lung with a yield of 10%. The purified enzyme also phosphorylated ethanolamine (ratio of ethanolamine kinase to choline kinase = 0.30). This ratio remained constant throughout the purification procedure. The Km for choline (3.0 - 10(-5) M) was lower than that of ethanolamine (1.2 - 10(-3) M.) Choline was also found to inhibit ethanolamine kinase activity by 50% at a concentration of 0.005 mM, while ethanolamine inhibited choline only at very high concentrations (100--150 mM). When the enzyme was subjected to inactivation by heat, hemicholinium-3, trypsin digestion, and p-hydroxymercuribenzoate, both ethanolamine kinase and choline kinase activities were destroyed at the same rate. Freezing and thawing in the absence of glycerol also destroyed both activities at the same rate. Based on these findings, we conclude that in adult African Green monkey lung tissue, there is only one enzyme for the phosphorylation of ethanolamine and choline, and that choline phosphorylation predominates.

Animals↗
PubMed1978

Determination of disaturated lecithin in rhesus monkey amniotic fluid as an index of fetal lung maturity.

Although increased concentrations of total lecithin in amniotic fluid allow prenatal assessment of fetal lung maturation, it has become clear that routine use of the L/S index may lead to a substantial number of inaccurate predictions. Since disaturated lecithin (DL) is a more specific marker of pulmonary surfactant than total lecithin, we developed a convenient method for measuring this phospholipid in amniotic fluid, and then evaluated its level in pregnant rhesus monkeys of 120 to 163 days of gestation. The method involves osmic acid destruction of unsaturated lipids, chromatographic isolation of disaturated lecithin, and quantitation by phosphorus assay. It can be performed in approximately 5 hours on 4 ml. of amniotic fluid and yield 67 +/- 3 per cent average recovery of added 14C-dipalmitolyl lecithin. The results of analyzing 36 rhesus amniotic fluid specimens showed the disaturated lecithin and the disaturated lecithin/sphingomyelin ratio (DL/S) increase sharply after 150 days of gestation, consistent with the pattern of lung maturation in this species. We conclude that disaturated lecithin can be readily quantitated in primate amniotic fluid and that its concentration, the DL/S ratio, and percentage of disaturated lecithin are potentially useful indices of fetal lung maturity for the clinical laboratory.

Amniotic Fluid↗
PubMed1978

Lung lecithin synthesis in primates as related to respiratory distress syndrome.

Lecithin is synthesized de novo in the lung by two biochemical pathways, choline incorporation and phosphatidylethanolamine methylation. These studies in the Macaca mulatta fetus and neonate have demonstrated the relative contributions of the two pathways and the timing in monkey gestation of increased pulmonary lecithin production.

Amniotic Fluid↗