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Biomedical subjects

D Penn

Publications and source records attributed to D Penn.

At least 55 records · Page 3Linked to original sources

Transfer and metabolism of carnitine and carnitine esters in the in vitro perfused human placenta.

The transfer and metabolism of L-carnitine, L-acetylcarnitine, and L-palmitoylcarnitine were studied in the human placenta at term by means of in vitro dual perfusion of a placental lobe. L-Carnitine transfer was 20% that of the freely diffusing antipyrine and 40% that of L-lysine. The transfer of L-acetylcarnitine was similar to that of L-carnitine, but no placental transfer of L-palmitoylcarnitine was found. In contrast to L-lysine, L-carnitine, and L-acetylcarnitine were not actively transported from the maternal to the fetal circulation. No stereospecific transfer of carnitine across the placenta was found. However, there was stereospecific uptake of carnitine by placental tissue. The placenta exhibited an active carnitine metabolism by esterifying free carnitine and hydrolyzing carnitine esters taken up from the perfusion medium and releasing the metabolites into the fetal and maternal circulations.

Acetylcarnitine↗

Carnitine and carnitine esters in plasma and adipose tissue of chronic uremic patients undergoing hemodialysis.

Carnitine concentrations were measured in the plasma and adipose tissue of seven chronically uremic and hyperlipidemic patients undergoing hemodialysis. Plasma levels of carnitine had dropped by the end of dialysis. The clearance of free carnitine was greater than that of acylcarnitine. Fasting plasma free carnitine, long-chain acylcarnitine, D-beta-hydroxybutyrate and free fatty acid concentrations were normal but short-chain acylcarnitine values were elevated. In adipose tissue, total carnitine concentrations were normal but long-chain acylcarnitine concentrations were increased. These findings may indicate a hypermetabolic state in which the acute removal of carnitine during hemodialysis may lead to a critical shortage of this substance.

Acylation↗

Carnitine deficiency in premature infants receiving total parenteral nutrition: effect of L-carnitine supplementation.

To investigate whether L-carnitine supplementation may correct nutritional carnitine deficiency and associated metabolic disturbances in premature infants receiving total parenteral nutrition, an intravenous fat tolerance test (1 gm/kg Intralipid over four hours) was performed in 29 premature infants 6 to 10 days of age (15 receiving carnitine supplement 10 mg/kg . day L-carnitine IV, and 14 receiving no supplement). Total carnitine plasma values were normal or slightly elevated in supplemented but decreased in nonsupplemented infants. In both groups, fat infusion resulted in an increase in plasma concentrations of triglycerides, free fatty acids, D-beta-hydroxybutyrate, and short-chain and long-chain acylcarnitine, but total carnitine values did not change. After fat infusion, the free fatty acids/D-beta-hydroxybutyrate ratios were lower and the increase of acylcarnitine greater in supplemented infants of 29 to 33 weeks' gestation than in nonsupplemented infants of the same gestational age. This study provides evidence that premature infants of less than 34 weeks' gestation requiring total parenteral nutrition develop nutritional carnitine deficiency with impaired fatty acid oxidation and ketogenesis. Carnitine supplementation improves this metabolic disturbance.

Carnitine↗

Individualizing theophylline therapy: the impact of clinical pharmacokinetics on patient outcomes.

We have studied 19 male patients whose theophylline therapy was individualized by a clinical pharmacokinetics service and 34 male patients with empirically derived dosages. All patients were admitted to the medical intensive care unit. Patients in the pharmacokinetics group had fewer adverse reactions (15.7 vs. 50%), shorter intensive care unit stay (6.6 +/- 5.5 vs. 12.4 +/- 16.3 days), shorter hospital stay (15.4 +/- 10 vs. 22.3 +/- 14.1 days), and a shorter period of time to be placed on oral therapy (5.2 +/- 3.1 vs. 8.6 +/- 7.2 days) than the group with empirically derived regimens. The pharmacokinetic method used to individualize theophylline therapy offered an accurate and efficient method of achieving therapeutic concentrations. We conclude that the use of clinical pharmacokinetics to individualize theophylline therapy offers substantial benefits over empirical assessments.

Aged↗

A rapid qualitative method for detecting phosphatidylglycerol in amniotic fluid.

A fast, reliable and inexpensive procedure of the qualitative determination of phosphatidylglycerol (PG) in amniotic fluid, using one-dimensional thin layer chromatography and a phosphorus-specific spray, is described. The method detects amounts of PG exceeding 1 microgram or 1.7% of total phospholipids in amniotic fluid. Contamination with serum does not influence the results. Excessive amounts of meconium interfere with the chromatography. The presence of PG was always associated with a mature L/S ratio (greater than 2), whereas its absence did not necessarily exclude lung maturity.

Amniocentesis↗

Carnitine blood concentrations and fat utilization in parenterally alimented premature newborn infants.

To investigate the relationships among carnitine intake, carnitine blood concentrations, and the ability to utilize exogenous fat, total carnitine, free carnitine, acylcarnitine, beta-hydroxybutyrate, free fatty acid and triglyceride plasma concentrations were measured in 26 parenterally alimented appropriate-for-gestational-age premature infants before and at the end of a four-hour infusion of Intralipid, 1 gm/kg body weight. There was an increase in plasma levels of AC, BOB, FFA, and TG, but a decrease of FC, TC was unaffected by the infusion, but strongly correlated with calculated carnitine intake. At the end of the fat infusion, AC and BOB were positively correlated, and FFA negatively correlated with TC. The results demonstrate the proportion of AC to FC to be an additional indicator of fatty acid utilization and suggest that decreased carnitine intake in premature infants may impair fatty acid oxidation and ketogenesis.

3-Hydroxybutyric Acid↗

Renal calcifications: a complication of long-term furosemide therapy in preterm infants.

During the last four years ten premature infants developed renal calcifications while receiving long-term furosemide therapy. The drug was used in infants with present ductus arteriosus and later in the same infants with chronic lung disease. They had received furosemide in a dose of at least 2 mg/kg/day for at least 12 days before calcifications were noted on abdominal roentgenograms. Calcifications included small flecks, isolated stones, staghorn calculi, and nephrocalcinosis. Analysis of stones received from our infants showed calcium oxalate and calcium phosphate. Infants who were not receiving furosemide had no calcifications. The infants with renal calcifications had rates of calcium excretion ten to 20 times that of normal, age-matched premature infants in our nursery. When chlorothiazide was given to the infants, in addition to furosemide, a four- to 15-fold decrease in calcium excretion and a radiologic dissolution of the renal calcifications were documented. It is concluded that furosemide, in doses of at least 2 mg/kg/day for at least 12 days can be associated with renal calcifications. The probable mechanism of the stone formation is hypercalciuria, primarily caused by furosemide.

Ductus Arteriosus, Patent↗

The influence of maternal fat metabolism on fetal carnitine levels.

Carnitine facilitates fatty acid transport across mitochondrial membranes, playing a key role in fatty acid oxidation and ketogenesis. To investigate the mechanism by which carnitine and its esters are supplied to the fetus, we measured free carnitine (FC) and acyl carnitine (AC) in amniotic fluid during late pregnancy, and FC, AC and beta-hydroxybutyrate (beta-OHB) in maternal and fetal plasma at vaginal term delivery. Amniotic fluid AC levels were elevated in pregnancies complicated by toxemia and diabetes mellitus, possibly reflecting placental transfer during abnormal fat catabolism. Maternal plasma levels of beta-OHB and AC were elevated and positively correlated at vaginal delivery, indicating enhanced fatty acid utilization. The positive correlation between maternal and fetal FC, AC and beta-OHB plasma levels suggests placental transfer. The maternal-fetal concentration gradient was descending for beta-OHB and AC and ascending for FC. No umbilical venous-arterial gradient for AF and beta-OHB was found, suggesting that the fetus does not utilize substantial amounts of either substance. The results demonstrate that fetal FC and AC levels are influenced by changes in maternal fat metabolism.

3-Hydroxybutyric Acid↗

Carnitine deficiency in premature infants receiving total parenteral nutrition.

Carnitine plays a significant role in fatty acid utilization and ketone body production. Its availability is especially important during the immediate postnatal period. To determine whether low birth weight infants who cannot be orally fed are at risk of developing carnitine deficiency, we compared the carnitine blood levels and urinary excretion of 12 premature infants (Group A) receiving total parenteral nutrition (TPN) with those of 8 infants of similar gestational age and birth weight (Group B) who received carnitine-containing milk formulas. In Group A, serum levels of total and free carnitine fell after 5 days of carnitine-deficient parenteral nutrition, and urinary excretion was significantly reduced. Serum levels and urinary excretion increased after the onset of oral feedings. The control Group B exhibited no significant changes in carnitine blood levels between the first and fifth days of life, but did show a later increase. Children in Group A had lower carnitine blood levels compared to those in Group B on the fifth day of life. These findings suggest that premature infants are not able to synthesize enough carnitine to maintain blood levels, and that carnitine deficiency can occur following TPN. Further investigation of metabolic consequences secondary to deficient carnitine intake in premature infants is necessary before carnitine supplementation should be considered.

Carnitine↗

Comparison of hematocrit determinations by microhematocrit and electronic particle counter.

Hematocrit determinations by microhematocrit and electronic particle counter technics were obtained using newborn and adult blood samples. Coulter Model S hematocrit values greater than .47 were found to be significantly lower than those obtained by using the microhematocrit technic. These differences assume clinical importance when considering partial plasma exchange transfusion for the treatment of polycythemia and associated hyperviscosity.

Adult↗