Search PubMed⌕ Search

Biomedical subjects

P M Farrell

Publications and source records attributed to P M Farrell.

At least 73 records · Page 4Linked to original sources
PubMed1989

Long-term mechanical ventilation in pediatric respiratory failure: medical and ethical considerations.

The outlook for survival of mechanically ventilated children with a variety of chronic respiratory disorders has improved to an extent that forces reexamination of traditional views of what is in these children's best interest with respect to medical care. In the ICU setting, this kind of situation represents a major dilemma in current pediatric medical practice since both alternatives (prolonged mechanical ventilation versus withholding/withdrawing) imply an unfavorable outcome. Because the survival and quality of life for children receiving long-term assisted ventilation are not highly discouraging, increasing numbers of pediatric patients are not being managed at home with life-support technology. This article reviews medical data on the survival of children managed with mechanical ventilation and discusses some of the key ethical issues pertaining to decisions about withholding/withdrawing assisted ventilation in infants and children. In addition, we suggest the following guidelines and procedures that might be useful in dealing with the prolonged mechanical ventilation dilemma in pediatric medical practice: (1) obtain the correct facts on prognosis (good ethics start with good facts); (2) avoid irreversible decisions under uncertainty; (3) remember that withdrawing treatment is ethically preferable to withholding; (4) resolve disagreements with the use of outside consultation; (5) include the entire family in the decision-making process; (6) remember that consent is a process, not an event, and requires regular discussions with the family; (7) one physician must be identified as the primary provider and communicator.

Bronchopulmonary Dysplasia↗
PubMed1988

Oxygen toxicity in the infant rhesus monkey: effects on regulatory peptides in lung and blood.

A total of ten 6-month-old male rhesus monkey (Macaca mulatta) infants, born full-term, were positive-pressure ventilated with greater than 95% oxygen or room air (controls). A protocol was used which closely simulated pediatric intensive care. To test if regulatory peptides were affected by the oxygen treatment, and to search for an early marker of oxygen toxicity, lung tissue samples and systemic mixed venous blood were collected at 6, 12 and 24 hours after onset of treatment. The peptides, gastrin releasing peptide (GRP), calcitonin gene-related peptide (CGRP), peptide YY (PYY), vasoactive intestinal peptide (VIP) and somatostatin (SOM), were quantitated in lung tissue extracts and plasma using radioimmunoassay. Lung tissue GRP, CGRP, and PYY levels appeared to decrease gradually with time, perhaps as a result of the positive pressure ventilation procedure. GRP and CGRP levels decreased less among monkey infants ventilated with oxygen, thus they were significantly higher at 24 hours than in air ventilated controls. VIP levels were significantly lower among tests compared to controls at that time. Blood peptide levels did not change with oxygen treatment. These results suggest that tissue concentrations of certain pulmonary regulatory peptides can become altered by ventilation with greater than 95% oxygen. A blood borne peptide marker was not identified.

Animals↗
PubMed1988

Essential fatty acid deficiency in premature infants.

To better characterize essential fatty acid (EFA) deficiency in neonates, we assessed 63 premature infants by serial determinations of plasma fatty acids for the level of linoleic acid, the presence of an abnormal trienoic acid (5,8,11-eicosatrienoic acid [20:3 omega 9]), and the ratio of this compound to arachidonic acid, ie, the triene-tetraene ratio. The data indicated that at age 7 d, 67% of these infants had low plasma linoleic acid levels, 62% showed readily detectable 20:3 omega 9, and 44% had a high triene-tetraene ratio. Infants fed by age 2 d had a normal mean linoleate level at 7 d and none showed detectable 20:3 omega 9 by 10 d. In contrast, infants who were not fed until 7 d showed a very high incidence of abnormal fatty acid status. By maintaining a daily record of linoleate intake, we calculated from regression models that the average amount required to achieve normal fatty acid nutrition was 1.19 g.kg-1.d-1.

8,11,14-Eicosatrienoic Acid↗
PubMed1988

Rapid methylprednisolone clearance in a patient with cystic fibrosis.

A pharmacokinetic investigation of administered corticosteroids was conducted in a 16-year-old girl with cystic fibrosis (CF). Equivalent doses of methylprednisolone were given orally and intravenously on consecutive days. Oral bioavailability was essentially 100 percent, ruling out impaired absorption. Drug half-life was shorter and both clearance and volume of distribution were greater in this patient than in normal young adults. From one patient it is impossible to conclude that this unusual disposition of corticosteroids is characteristic of CF. Given the interest in use of corticosteroids in this population, and the examples of other drugs with altered pharmacokinetics in patients with CF, further investigation is warranted.

Adolescent↗
PubMed1987

Biochemical maturation of fetal rat lung: a comprehensive study including surfactant determination.

The paper describes a comprehensive assessment of lung growth and biochemical maturation in the fetal and early postnatal rat. Fetal lung grew faster than whole body between gestational day 16.5 and term. Cell number increased quasi-exponentially, except for a slowing of cell growth between days 19.5 and 20.5 of gestation. By contrast, growth was limited during the two first postnatal days. Percentage of dry tissue and protein concentration increased in parallel during the whole period. Increases in whole lung tissue phosphatidylcholine were greatest between 20.5 and 21.5 days of gestation, whereas in isolated surfactant fraction, changes were most marked between 19.5 and 20.5 days. The most striking changes were a 19-fold increase in phosphatidylcholine and a 12.5-fold increase in the total phospholipid concentrations in the surfactant fraction between gestational day 19.5 and 1 day postpartum. Similar changes occurred in disaturated phosphatidylcholine (DSPC) concentration. During the same period, phospholipids of the residual (nonsurfactant) fraction increased only about 2-fold. These data indicate that analysis of an isolated surfactant fraction is advantageous in providing a very sensitive index of augmented phospholipid production during the process of fetal lung maturation. Evidence of biochemical maturation was detected earlier in females than in males, as indicated by a significantly larger surfactant fraction DSPC concentration in 19.5-day-old females; however, this difference was modest in degree and very transient, since it was no longer demonstrable in later stages.

Animals↗
PubMed1987

Predigested formula for infants with cystic fibrosis.

The object of this study was to assess the growth rates of patients with cystic fibrosis fed various diets and test the hypothesis that the weight of infants could be normalized by 1 year of age if they were placed on predigested formula before age 6 months. A group of 19 newly diagnosed patients placed on Pregestimil were compared with a group who were fed standard formula. At 1 year of age, the Pregestimil group showed significantly greater length and weight and a twofold higher average weight percentile. Growth velocity determined for the period between diagnosis and 12 months of age was better (p less than .001) for babies raised on Pregestimil (556 compared with 423 gm/month). Using weight percentile as the major growth index and values less than the fifth percentile as abnormal at age 12 months, we found that all 19 babies were normal in the group fed Pregestimil, whereas nine were below the fifth percentile in the group fed regular formula (p = .0006).

Birth Weight↗
PubMed1986

Fetal lung surfactant lipid synthesis from glycogen during organ culture.

The role of fetal lung glycogen as a precursor for lipids during late gestational development was explored by a combination of in vivo labeling with [U-14C]glucose, administered directly to rat fetuses at 18.5 days, and in vitro assessment using an organ explant culture system. Our major objectives were to demonstrate that radioactivity was transferred specifically and preferentially to surfactant lipids, as glycogenolysis occurred, and to determine the molecular distribution of 14C labeling in newly synthesized phosphatidylcholine (PC). Surfactant and residual (non-surfactant) lipids were separated by sucrose density gradient centrifugation, and other subcellular fractions such as microsomes were isolated by subsequent centrifugations. After 72 h of culture, there was a 5.7-fold increase in the concentration of PC in the surfactant fraction, which contributed 8.8% of total PC at the beginning and 29.6% (P less than 0.001) at the end of the 72 h period. The labeling of PC in the surfactant fraction increased markedly during culture, but there was no significant change in the residual fraction or microsomal PC. Hydrolysis of surfactant PC indicated that the radioactivity was predominantly located in the fatty acyl portion of the molecule, both before and after culture; however, PC glycerol labeling also increased significantly during culture. The distribution of PC radioactivity was similar in the residual fraction and microsomes, with the majority of 14C in the fatty acids. Neutral lipid radioactivity also increased significantly in both the surfactant (240%) and residual (136%) fractions. Quantitation of the changes in radioactivity among subcellular components during lung explant culture indicated that the greatest decrease occurred in glycogen, whereas only lipids, particularly those of the surfactant fraction, were found to show significant increases. These results support the hypothesis that glycogen, which accumulates in fetal lung prior to augmented surfactant production, can supply precursors for synthesis of functionally essential pulmonary phospholipids.

Animals↗
PubMed1986

Familial lung disease associated with proliferation and desquamation of type II pneumonocytes.

A family is described in which certain infants presented with a diffuse parenchymal pulmonary disorder characterized by proliferation and desquamation of alveolar epithelial cells that progressed to severe pulmonary fibrosis and cystic dysplasia, resulting in "honeycomb" lung typical of chronic pulmonary interstitial disease (idiopathic pulmonary fibrosis) at death. Electron microscopic examination of a lung biopsy specimen from one infant revealed that the proliferating/desquamating cells were ultrastructurally normal-appearing type II pneumonocytes with osmiophilic lamellar bodies. This patient did not respond to prednisone therapy, but she showed great improvement with chloroquine therapy, which was confirmed by a repeated lung biopsy. Possible mechanisms that might account for the effect of chloroquine, such as inhibition of DNA synthesis, as well as the cellular pathobiology of type II pneumonocyte proliferation in this disease, are discussed.

Cell Division↗
PubMed1986

A case report and literature review of "primary" pulmonary histiocytosis X of childhood.

"Primary" pulmonary histiocytosis X, a well-described entity in young adult males in which pulmonary disease is the overriding site of involvement, is exceedingly rare in children younger than 15 years old. We report a new case in a 2-year-old male and review other reported prepubertal cases. The diagnosis of pulmonary histiocytosis X is based on examination of lung tissue. Langerhans cells containing Birbeck granules, seen by electron microscopy, are virtually pathognomonic of histiocytosis X. These Langerhans cells also react with a monoclonal antibody (OKT6) as well as with antibody to S-100 protein. Based on the lack of consensus for the appropriate treatment of pulmonary histiocytosis X and on our patient's favorable response, we recommend initial therapy with corticosteroids alone, reserving more toxic agents for patients who fail to respond to this initial therapy.

Bone Diseases↗
PubMed1986

Changes in erythrocyte and plasma carnitine concentrations in preterm neonates.

Erythrocyte and plasma total, free, and acyl carnitine concentrations in 13 low birthweight, preterm infants were determined between birth and 21 days of age. Although erythrocytes contributed 73.6 +/- 4% (mean +/- SD) of total blood carnitine at birth, the contribution by day 14 declined to 42.2 +/- 14.1. Linear regression analysis showed no significant correlation between plasma and erythrocyte concentrations. At 3 wk erythrocyte total carnitine concentrations were similar to adult values, but erythrocyte acyl carnitine concentrations were markedly lower. Although a significant (p less than 0.05) positive correlation between plasma carnitine concentrations and mean daily intake from birth was found at 7, 14, and 21 days of age (r = 0.66, 0.87, and 0.88, respectively), no significant relationships between erythrocyte carnitine concentrations and carnitine intake could be demonstrated by linear regression analysis. It appears that the carnitine present in plasma and erythrocytes represents two separate pools which are influenced by different factors in preterm infants.

Adult↗
PubMed1986

Effect of choline deficiency on lung phospholipid concentrations in the rat.

Lung surfactant and nonsurfactant phospholipid concentrations were analyzed in relation to choline status in male rats fed a choline-deficient (CD) or choline-supplemented (CS) diet over an 8-d period. On the first day plasma choline concentrations were significantly lower (11.5 +/- 0.9 micron) in rats fed the CD diet than in those fed the CS diet (16.1 +/- 1.2 microM). This relationship continued for the duration of the study. Hepatic phosphatidylcholine/phosphatidylethanolamine (PC/PE) ratios were significantly lower after d 1 of the CD diet, further decreased on d 2 (1.09 +/- 0.04) and remained low through d 8. Only on d 4 were lung surfactant PC and total phospholipid concentrations lower in rats fed the CD diet than in those fed the CS diet. The composition of surfactant, determined by the ratio of PC to total phospholipids, did not change. On both d 4 and d 8 the PC/PE ratios in the nonsurfactant fraction were lower in rats fed the CD diet than in those fed the CS diet. This shift in PC/PE ratio in the lung is similar to the PC/PE shift in the liver associated with dietary choline deficiency. The altered lung phospholipid concentrations in the nonsurfactant (residual) fraction on d 4 and d 8 suggest an adaptation in the lung's phospholipid metabolism to replenish the physiologically essential surfactant PC.

Animals↗
PubMed1986

Correction of linoleic acid deficiency in cystic fibrosis.

To identify evidence of essential fatty acid deficiency, we screened 64 patients with cystic fibrosis by analyzing total lipid extracts from plasma. Forty-three had an abnormal linoleate (18:2) level (less than 26%). Thirteen deficient patients (aged 10-24 yr) ingested for 1 yr 7% of their total calories as linoleate derived from a daily supplement of Microlipid. Five deficient patients (aged 10-37 yr) served as controls. Plasma and erythrocyte fatty acid composition were monitored by gas chromatography of total lipid extracts seven times during the twelve month period. Prostaglandins E2 and F2 alpha and their 15 keto 13, 14 dihydrometabolite, 6-keto F1 alpha, and thromboxane B2 were measured by radioimmunoassay. Sweat tests, oxygen saturation, growth indices, clinical severity scores, compliance, and possible side effects from taking Microlipid were followed. Results showed that oral supplementation with Microlipid can significantly increase plasma and erythrocytes % 18:2. One compliant patient died during the study and had normal tissue 18:2 levels. Nine of 13 patients gained more weight while taking Microlipid than in the previous year. No significant changes in sweat electrolytes, clinical scores, or oxygen saturation were found during the study year. Prostaglandin metabolites prostaglandin E2 showed an upward trend in supplemented patients, compared to controls. Prostaglandin F2 alpha remained unchanged over 1 yr but showed a trend significantly downward over the final 6 months in supplemented patients. We conclude that linoleate deficiency can be corrected with daily Microlipid supplements and that correction may alter prostaglandin metabolism.

6-Ketoprostaglandin F1 alpha↗
PubMed1986

Changes in surfactant phospholipids in fetal rat lungs from normal and diabetic pregnancies.

The purposes of this study were to adapt and evaluate further a pulmonary surfactant isolation method applicable to unperfused fetal rat lung, to quantitate key phospholipids phosphatidylcholine (disaturated phosphatidylcholine, and phosphatidylglycerol) of the isolated material during the last 3 days of gestation, and to determine if abnormalities in surfactant phospholipids were present in fetuses of diabetic pregnancies. A simplified scheme of sucrose gradient centrifugation proved useful for small scale preparations of material enriched in the phospholipids most characteristic of pulmonary surfactant. It was shown that fetal blood phospholipids did not contaminate the surfactant fraction and therefore would not produce artifacts in assessment of lung maturational changes. Analyses of subcellular fractions isolated at 19.5, 20.5, and 21.5 days revealed that the percentages of disaturated phosphatidylcholine relative to total phospholipids were 23-44% in the surfactant preparations and 14-21% in the residual (nonsurfactant) fractions, while the disaturated phosphatidylcholine/phosphatidylcholine ratios were 0.62 +/- 0.06 and 0.41 +/- 0.03, respectively. Summation of the amounts of individual phospholipids in the two fractions yielded data that were nearly identical to the concentrations of these compounds in whole fetal lung samples analyzed independently, implying that losses during the surfactant isolation technique were negligible. The concentrations of phosphatidylcholine, disaturated phosphatidylcholine, phosphatidylglycerol, and total phospholipids increase markedly (more than 10-fold) and progressively in surfactant fractions prepared from normal fetal rat lung at 19.5, 20.5, and 21.5 days of gestation. In contrast, the residual fractions showed no changes from 19.5 to 20.5 days and then relatively modest increases from 20.5 to 21.5 days, except for phosphatidylglycerol, which increased markedly.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Fetal lung development in male and female nonhuman primates.

Indices of lung maturation were assessed in 58 rhesus fetuses at five gestational ages during the last trimester of nonhuman primate pregnancy to determine whether fetal sex influences lung maturation. In addition to analysis of whole lung phospholipids, glycogen, protein, DNA, and pressure-volume curves surfactant fraction phosphatidylcholine (PC) was quantitated following isolation by sucrose gradient centrifugation and a combination of predictors were assessed by all possible subsets regression to attain a composite "maturity index." For the total population, there was a uniform progression in physical growth characteristics, lung destensibility and stability and phospholipids with advancing gestation. The quantitative change in surfactant fraction PC concentration for both sexes was considerably greater than that observed for whole lung PC between 135 days gestation and term. Further, the increase in surfactant PC occurred in association with improving lung destensibility and deflation stability prior to maximum changes in the whole lung PC or disaturated PC concentration. There were no statistically discernible differences in biochemical or physiological assessment between sexes at any gestational age. These data in nonhuman primates suggest that documented differences in survival from the respiratory distress syndrome between males and females do not result from a discordance in lung maturation as a function of time throughout the last trimester of gestation.

Animals↗
PubMed1986

Oxygen toxicity in the infant rhesus monkey lung. Light microscopic and ultrastructural studies.

Eight monkeys were anesthetized with ketamine hydrochloride and positive pressure ventilated with greater than 95% oxygen (tests) or room air (controls) for 24 hours. Two test monkeys and one control were treated with E. coli endotoxin (500 micrograms/kg) IV at the start of the study and after 12 hours. Histopathological changes in the lung parenchyma were evaluated using light and electron microscopy. Interstitial edema was detected as early as 24 hours after the onset of hyperoxia but there was no significant increase in the alveolar-capillary distance (blood-air barrier). Morphologic signs of oxygen toxicity further included swelling and disruption of vascular endothelium, and swelling of alveolar Type II pneumocytes. There was no difference in the number of macrophages per high power field between the four groups but significant differences were observed in the number of neuroepithelial bodies (NEBs) per cm2 and mast cells per high power field at the light microscopic level. Treatment with endotoxin did not protect against oxygen toxicity and was associated with an exacerbation of the morphological alterations in the lung parenchyma and swelling of alveolar Type I pneumocytes.

Air↗
PubMed1986

Discordance between male and female deaths due to the respiratory distress syndrome.

General neonatal mortality statistics and those for the respiratory distress syndrome (RDS) were examined for the State of Wisconsin from 1979 through 1982. The objectives were to ascertain whether there are differences in total neonatal mortality related to sex and birth weight, to determine the veracity of reported gender differences in deaths due to RDS, and to assess the contribution of other risk factors for neonatal mortality to overall and sex-specific deaths occurring secondary to RDS. Additionally, a prospective analysis was performed at one perinatal center during a 5-year period in attempts to determine whether gender remained a significant factor in deaths due to RDS after adjusting for incidence. Overall, the most frequent diagnoses in those who died were RDS (15.6%), deaths due to complications of pregnancy (8%), immaturity (4.2%), and asphyxia (3.4%). The majority of fatalities for both sexes occur in neonates weighing less than 1 kg and the percentage of deaths attributable to RDS is greatest between 1 and 1.5 kg. The difference between sexes is also maximal in the latter weight group. Deaths secondary to RDS are greater for males regardless of Apgar score at one and five minutes, mode of delivery, maternal age, or ancillary diagnosis. These data suggest that deaths secondary to RDS are consistently greater in male neonates and that delivery within a limited "window" of time during gestation increases male susceptibility to fatal RDS.

Apgar Score↗
PubMed1985

Measurement of free choline concentrations in maternal and neonatal blood by micropyrolysis gas chromatography.

The development of a micropyrolysis gas chromatographic technique for the determination of free choline in plasma and erythrocytes is reported as a means to clinically assess choline status. A micropyrolyzer syringe unit was fabricated and the method was standardized through repeated trials with a single plasma specimen. The interassay coefficient of variance was 1.3% for the standardized trials on plasma and erythrocytes. Choline status was assessed in control women, mothers and premature infants at birth and up to 14 days of life. At birth, plasma choline levels in the infants (32.2 +/- 5.5 mumol/l) were significantly higher than those in the mothers (12.9 +/- 2.6 mumol/l) and the control women (16.9 +/- 1.6 mumol/l). The infant's plasma choline concentrations had decreased significantly by 7 days of life and remained at the lower level at day 14, independent of the nutritional intervention administered.

Choline↗