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Biomedical subjects

P M Farrell

Publications and source records attributed to P M Farrell.

At least 91 records · Page 5Linked to original sources
PubMed1985

Vitamin E, vitamin A and essential fatty acid status of patients hospitalized for anorexia nervosa.

A group of 17 patients hospitalized for anorexia nervosa was assessed for nutritional status with respect to the essential fatty acids and vitamins E and A. Plasma aliquots available from blood drawn upon hospital admission were frozen and later extracted for total lipids. The total lipids were then fractionated by thin layer chromatography to isolate the phospholipids (PL). The fatty acid profile of both total plasma and PLs was determined by gas chromatography. High pressure liquid chromatography was used to quantitate the tocopherol isomers and retinol (vitamins E and A, respectively). The anorexic patients showed below normal weight-for-height, decreased percent body fat, and a high incidence of secondary amenorrhea. Of the four tocopherol isomers measured, only the beta + gamma fraction was significantly lower than the normal value (0.16 +/- .06 mg/dl vs 0.25 +/- 0.51 mg/dl, p less than .001). The essential fatty acids, linoleate and linolenate, were lower in the PL fraction of the anorexic group (linoleate, 19.35 +/- 5.65 vs 24.96 +/- 2.24, p less than .01); linolenate, none detected vs 0.16 +/- 0.13, p less than .05). Other indicators of essential fatty acid status differed from the normal group in the direction of deficiency (total omega 6, 31.44 +/- 7.41 vs 37.42 +/- 3.40, p less than .05; 20:4 omega 6/18:2 omega 6, 0.49 +/- 0.14 vs 40 +/- 0.02, mean +/- standard deviation, p less than .01). Eicosatrienoic acid, however, was not detected in either group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗
PubMed1985

Lung surfactant phospholipids as related to hydration and choline status of fasted rats.

Hydration status and choline nutrition were evaluated relative to the concentration of lung surfactant phosphatidylcholine (PC) in fasted rats. Rats deprived of food for 72 h showed lower voluntary water consumption and consistently lower levels of both PC and total phospholipid (TPL) present in isolated pulmonary surfactant than ad libitum-fed controls, although the ratio of surfactant PC to TPL and the residual PC and TPL concentrations were not different. Higher hematocrit values observed in the fasted animals were not altered by the administration of water or saline by orogastric tube nor was the low surfactant PC level corrected by fluid therapy. Evidence of choline deficiency was demonstrated in the fasted rats as there was a significant shift in hepatic PC:phosphatidylethanolamine; however, plasma choline levels did not change. The administration to fasted animals of up to 2.4 mmol of choline chloride via the drinking water (containing 60 mM choline) or an orogastric tube did not affect the plasma choline concentrations or the production of lung surfactant PC.

Animals↗
PubMed1985

Early intravenous correction of vitamin E deficiency in premature infants.

We undertook to determine the efficacy of intravenous alpha-tocopheryl acetate in rapidly correcting the vitamin E deficiency of the premature infant. Twenty-nine infants were assigned to either a control or treatment group. The latter group received a median intravenous dose of 3 IU/kg/day alpha-tocopheryl acetate as MVI-12 (USV Pharmaceuticals, Inc.). On days 1, 2, 3, 7, 14, and 21, plasma tocopherol isomers and peroxide-induced hemolysis were analyzed. While all but one control infant with initial tocopherol deficiency were still deficient on day 3, all but two of the treatment infants were normal. Rapid, safe correction is possible with an intravenous multivitamin preparation.

Birth Weight↗
PubMed1985

Developmental aspects of lung lipids.

From this review, it is evident that multiple maternal/fetal endogenous or completely exogenous factors have been associated with the complex process regulating fetal lung development. Recent in vitro experiments with human fetal lung explants are especially noteworthy and may establish a perspective for future research. Snyder et al (108) and Medelson et al (74) have found that lung explants from 16-22-week abortuses show differentiated type II cells and augmented PC synthesis within 4 days of culture, rather than the minimum 10- to 15-week period expected in utero. Such a phenomenon is reminiscent of the usual time for clinical recovery from uncomplicated RDS (34). Thus, although expression of the genes influencing lung surfactant phospholipid synthesis and related biochemical processes normally occurs relatively late in gestation, the potential for biochemical differentiation is clearly present in earlier stages. It appears then that the "programming" of the fetal lung for maturation is not absolute but may be altered under certain influences. Whether the advent of lung biochemical maturation occurs as a result of release from inhibition, as the human lung explant data imply, or occurs in response to stimuli, as suggested by exogenous corticosteroid effects, remains to be clarified and is a very challenging scientific problem. It will also be of great interest to define further other biochemical regulators, such as fibroblast pneumocyte factor, that may play an important role in fetal lung maturation.

Androgens↗
PubMed1985

Fatty acid abnormalities in cystic fibrosis.

Fatty acids were measured by gas chromatography in lipid extracts of plasma and tissues obtained from three categories of 46 patients with cystic fibrosis. Low levels of the major essential fatty acid linoleate were found in plasma total lipids of patients who had malabsorption but not in those without evidence of steatorrhea. Circulating arachidonic acid was only slightly decreased, and the unusual triene reflecting pathologically altered fatty acid metabolism (20:3 omega 9) was generally not detected, nor was the triene/tetraene ratio abnormal except for in two patients. There was no correlation between plasma linoleate and age, clinical severity score, or vitamin E status. Decreased linoleate did correlate with two indices of malabsorption, namely plasma carotene (r = 0.64) and fecal fat excretion (r = 0.76). Our data therefore indicate that the abnormality in linoleate is associated with (secondary to) malabsorption of dietary fat despite pancreatic enzyme replacement therapy and consumption of a regular diet. The frequency of this alteration was determined to be quite high in 40 patients with steatorrhea, 85% of whom showed values below the lower limit of normal for plasma linoleate. It was of interest to find markedly decreased levels of linoleate in adipose tissue, cardiac muscle, and lung and lesser reductions in liver and psoas muscle taken at autopsies. Tissue arachidonic acid percentage was normal, however, and 20:3 omega 9 was rarely present. Thus, the physiological significance of this common abnormality in CF patients with malabsorption remains to be determined.

Adipose Tissue↗
PubMed1985

Fetal lung development in the diabetic pregnancy.

It seems quite likely that the normal process of fetal lung biochemical maturation is delayed by maternal diabetes and that abnormalities in the pulmonary surfactant system are involved. The appearance of PG in amniotic fluid and possibly in fetal lung is impaired or at least delayed. The same is possibly true for DSPC, the main constituent of surfactant, but recent discrepant data call for further clarification of this specific point. Careful determination of the fetal lung phospholipid profile by amniotic fluid analysis helps predict and prevent RDS in IDM, along with a careful control of the maternal diabetic condition. A study of alveolar surfactant at birth, if it could be performed in addition to amniotic fluid analysis, would help to better characterize surfactant deficiency in IDM. On the basis of both in vivo and in vitro experimental approaches, it seems clear that hyperglycemia and fetal reactional hyperinsulinism are both involved in the processes delaying fetal lung maturation. Further advances in the understanding of cellular and molecular mechanisms leading to this delay will be conditional on the availability of animal models reproducing the features of the metabolic and hormonal environment of human fetuses in diabetic pregnancies. The appropriateness of in vivo models needs to be defined by two kinds of criteria: 1) presence of simultaneous hyperglycemia and hyperinsulinemia in the fetus; 2) the presence of delayed fetal lung maturation as judged by morphology and morphometry of epithelial lung cells, by physiological assessment of surfactant, and by the phospholipid composition of the lung (and including lung tissue per se, bronchoalveolar lavage fluid, lamellar bodies, and/or isolated surfactant fractions). Therefore, future studies must necessarily be comprehensive in scope and include information indicating that fetal growth, blood glucose, and circulating insulin are all increased. Such models already exist in rats and rabbits. Rat models are possibly not the best because of the high basal level of fetal blood insulin in this species and the relatively rapid rate of lung maturation that is not analogous to the human. Monkey models are of interest, because of their close relationship with the human pregnancy, and need to be studied further. They are particularly attractive also because primary fetal hyperinsulinism can be studied (268), as well as the combination of hyperglycemia and hyperinsulinemia in pregnancies of STZ-treated monkeys (152). An appropriate model of the diabetic pregnancy could provide answers to the following questions. Are the biosynthetic pathways of surfactant phospholipids directly impaired?(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1984

Clinical and roentgenographic scoring systems for assessing bronchopulmonary dysplasia.

Because investigation of bronchopulmonary dysplasia (BPD) has been hampered by imprecise methods for diagnosis and grading of severity, we evaluated new clinical and roentgenographic scoring systems in neonates with severe respiratory distress. The study population included 110 premature neonates who were admitted consecutively over a two-year period and who required mechanical ventilation. The clinical scoring system used measures of gas exchange, respiratory distress, and growth rate; roentgenographic scoring involved numerical assessment of features characteristic of BPD. A significant correlation was noted at 21 days of age between clinical and roentgenographic scores. In a linear stepwise multiple regression, we found that the best predictors of clinical score were birth weight (ie, degree of prematurity) and roentgenographic score. With further development and validation, BPD scoring should be helpful by improving our understanding of the epidemiology of this disease, providing a means for evaluation of treatment, and facilitating multicenter investigations.

Bronchopulmonary Dysplasia↗
PubMed1984

Changes in food intake during menstrual cycles and pregnancy of normal and diabetic rhesus monkeys.

Food intake of control and streptozotocin-diabetic rhesus monkeys was measured during menstrual cycles and pregnancy. Intake of control monkeys was lower at the time of ovulation than during other phases of the menstrual cycle. Intake of control monkeys was also low during most of pregnancy, but this was accompanied by normal fetal growth and net maternal weight gain. Diabetic monkeys ate more than controls in all conditions and their intake did not vary reliably according to reproductive status. It is suggested that (1) oestrogen normally inhibits food intake during menstrual cycles and pregnancy, (2) food energy is utilized more efficiently during pregnancy than during non-pregnant states, and (3) the influence of oestrogen on food intake is either attenuated by insulinopenia or is obscured by the hyperphagia typically exhibited by the diabetic monkeys.

Animals↗
PubMed1984

Advances in the diagnosis and management of cystic fibrosis.

Cystic fibrosis (CF), the most common lethal genetic disease affecting Caucasians, is a multi-system illness, most frequently characterized by childhood chronic obstructive pulmonary disease, pancreatic exocrine insufficiency, and abnormal sweat electrolyte concentrations. The diagnosis of CF is based on a combination of the above clinical findings and/or a positive family history of the illness in conjunction with an abnormal sweat test. The quantitative pilocarpine iontophoresis test is the sole acceptable method for diagnostic confirmation of the clinical suspicion of CF. A recent advance in the diagnosis of CF has been in the development of methods for neonatal detection. The immunoreactive trypsinogen (IRT) detection test is practical, adaptable to large scale screening of dried neonatal blood spots, relatively inexpensive, and promising for the detection of newborns with CF who have pancreatic insufficiency. However, the reliability and validity of this method have not yet been adequately established. Major advances in the treatment of patients with CF have emerged in the last decades, particularly in supportive pulmonary and nutritional care.

Adolescent↗
PubMed1984

Vitamin A losses to plastic intravenous infusion devices and an improved method of delivery.

This study was designed to reevaluate the kinetics of vitamin A losses in the plastic intravenous infusion system used clinically in premature infants and to attempt to establish an improved method of delivery that would avoid significant and unpredictable losses. The losses of retinol, retinyl acetate, and retinyl palmitate were assessed in the presence of various concentrations of the emulsifier Tween 20. For a period of more than 24 h and at a concentration of 0.0085% Tween 20, retinol and retinyl acetate were delivered at 17.4 and 33.9% of the originally intended dose, respectively, while retinyl palmitate was at 100%. At 1% Tween 20, retinyl acetate was completely delivered but even at 2% Tween 20 only 51% of the retinol was delivered. The data suggest that predictable infusions of vitamin A may be attained by using retinyl palmitate rather than retinol in multivitamin preparations.

Adsorption↗
PubMed1984

An evaluation of vitamin E status in premature infants.

Prematurely born, low birth weight infants are abnormal by their very existence ex utero. Thus, the well-documented finding in such infants of low plasma vitamin E concentrations when compared to the adult poses philosophical and pragmatic difficulties as to whether or not a true deficiency state exists: do these low levels represent age-adjusted reference values or do they in fact represent a deficiency state, warranting treatment? We examined multiple measures of vitamin E status in 62 prematurely born, low birth weight infants in order to address this issue. Mathematical and statistical modeling of these measures during the first 21 days of life lead us to conclude that the ex utero antioxidant protective role of vitamin E is best achieved at plasma concentrations of tocopherol very close to those observed in the adult; specifically, when total tocopherol is greater than 0.64 mg/dl and alpha-tocopherol is greater than 0.50 mg/dl. Thus, at birth, a true deficiency in vitamin E exists for most preterm, low birth weight infants and early treatment is warranted.

Aging↗
PubMed1984

Relationship between the severity of experimental diabetes and altered lung phospholipid metabolism.

Glucose intolerance was induced in rats by iv infusion of streptozotocin (STZ) in doses of 30, 40, 50, and 100 mg/kg. Serum glucose concentrations were elevated versus controls and weight gains were reduced in a dose-dependent fashion up to 50 mg/kg. Urine outputs and blood urea nitrogen (BUN) values were higher than control values in the animals treated with 40 and 50 mg/kg and serum albumin concentrations were decreased after infusion with 50 mg STZ/kg. Lung phosphatidylcholine (PC) concentrations and dry-to-wet weight ratios were unchanged by STZ treatment, while lung protein and disaturated phosphatidylcholine (DSPC) concentrations were depressed in the 50-mg/kg group. Animals surviving treatment with 100 mg/kg demonstrated increased fasting blood glucose levels, BUN values, and 48-hr urine outputs, and decreased lung protein levels. However, these alterations were less than those found in the 50-mg/kg animals. Pulmonary concentrations of PC, DSPC, and lung dry-to-wet weight ratios were unchanged. It was found advantageous to express the results relative to fasting blood glucose levels. This demonstrated that urine output and BUN values increased and weight gain decreased with rising glucose concentrations, but serum albumin decreased only in moderate and severe hyperglycemia. Fasting glucose concentrations greater than 400 mg/dl were associated with reduced lung DSPC and protein levels, while pulmonary PC and dry-to-wet weight ratios demonstrated no change with increasing hyperglycemia.

Animals↗
PubMed1984

Saturated phospholipids in amniotic fluid of normal and diabetic pregnancies.

To assess fetal lung maturation in normal and diabetic pregnancies, the authors studied two phospholipids that are more specific for pulmonary surfactant than total phosphatidylcholine (lecithin), namely saturated phosphatidylcholine and phosphatidylglycerol. Results indicated that saturated phosphatidylcholine concentrations normally increase from 10 to 20 nmol/mL before 34 weeks to as high as 150 nmol/mL at term. Although the absolute concentration of saturated phosphatidylcholine could not be used to reliably identify pregnancies leading to respiratory distress syndrome, a saturated phosphatidylcholine level greater than 50% of total phosphatidylcholine was associated with satisfactory neonatal pulmonary function, whereas RDS often occurred in premature infants when less than half the phosphatidylcholine was saturated. Carefully regulated diabetic pregnancies at 36 to 42 weeks of gestation were not different from matched control subjects with respect to total phosphatidylcholine, its ratio to sphingomyelin, saturated phosphatidylcholine, or phosphatidylglycerol. Respiratory distress syndrome did not occur in any infant of the 40 diabetic mothers studied, nor were there any congenital anomalies or cases of symptomatic hypoglycemia.

Amniotic Fluid↗
PubMed1983

Amniotic fluid phospholipids after maternal administration of dexamethasone.

The administration of corticosteroids to pregnant women in premature labor can accelerate fetal lung development and potentially prevent neonatal respiratory distress syndrome (RDS). Controversy exists, however, as to whether amniotic fluid phospholipid indices of lung maturation are influenced by such treatment. Without a suitable test for evaluating the fetal response to corticosteroids, there is no method of recognizing whether and when lung development has been stimulated. In an attempt to resolve this issue, we carried out a study of amniotic fluid phospholipids as part of the National Institutes of Health multicenter trial of prenatal corticosteroids. Amniocenteses were performed before the administration of either steroid hormone or placebo and approximately 1 week after a series of four injections was initiated. Analysis of the ratio of lecithin (phosphatidylcholine) to sphingomyelin (L/S ratio) revealed nearly identical values initially and no significant difference in the posttreatment means when 25 steroid-treated pregnancies were compared to 20 control pregnancies. Although there were significant increases in both groups during the interval between amniocenteses, no statistical difference was found in the extent of change in L/S ratios between the two groups, when pretreatment values were compared with those obtained an average of 1 week later. In addition to evaluating L/S ratios, we performed an assessment of phospholipid concentrations in 17 pregnancies before and after administration of dexamethasone. This revealed no detectable phosphatidylglycerol. There were increases in the absolute concentrations of phosphatidylcholine and disaturated phosphatidylcholine, but these changes were relatively modest in magnitude and could be attributable to either advanced gestational age or dexamethasone. Our results demonstrate that current tests of fetal lung maturity do not provide a routine means for prenatal detection of pulmonary maturational responses to corticosteroids.

Amniotic Fluid↗
PubMed1982

Comparison of effectiveness of pancreatic enzyme preparations in cystic fibrosis.

To evaluate claims that enteric-coated pancreatic enzyme preparations are more effective than conventional digestants in managing malabsorption in cystic fibrosis (CF), we conducted a trial comparing the efficacy of pancrealipase (enzyme supplement containing lipase, amylase, and protease) in the form of pH-sensitive microspheres (Pancrease) with that in the form of encapsulated enzyme powder (Cotazym). Ten boys with CF received equivalent dosages in a controlled, double-blind fashion using a random sequence of capsule administration with crossover and "washout" periods. Patients experienced significantly enhanced nitrogen and fat absorption while receiving either enzyme when compared with placebo. The enteric-coated product promoted significantly improved fat absorption as compared with the conventional enzyme capsule. Both enzyme preparations caused significantly improved protein absorption as compared with placebo, but there as no significant difference between the two products in the degree of effect on azotorrhea.

Adolescent↗