Search PubMed⌕ Search

Biomedical subjects

H Helge

Publications and source records attributed to H Helge.

At least 55 records · Page 3Linked to original sources
PubMed1985

[13C]Acetate oxidation in infants after oral versus rectal administration: a kinetic model.

To study the fate of volatile fatty acids (VFA) in the large bowel, we compared the rate of oxidation of 13C-labeled VFA administered rectally with that of the orally administered substrate. On two different days, 1-[13C]acetate was administered rectally or orally to five infants recovering from diarrhea. Breath samples were collected over 4 h and analyzed for 13C enrichment of breath CO2 by gas isotope ratio mass spectrometry. The percent dose recoveries of 13C in breath were fitted to multicompartmental models using the SAAM-27 program. Following model development procedures, the oral acetate breath test curves could be accounted for only by a compartmental model in which labeled acetate underwent absorption into and mixed with a systemic pool before oxidation took place. The rectal acetate breath test curves could be accounted for by a simpler model in which oxidation occurred directly in the compartment in which the rectal acetate was administered, and required no rate-limiting absorptive process. Our results indicate that the labeled acetate was oxidized more rapidly when the substrate was administered rectally than orally. This observation points to the direct utilization of volatile fatty acids within the colon.

Acetates↗
PubMed1985

[Fat utilization in newborn infants with and without heparin administration. Comparative study with the 13C-triolein breath test].

The elimination of parenterally administered lipids from the bloodstream of premature infants can be accelerated by activation of the lipoprotein-lipase using heparin. We have no evidence that the free fatty acids increasing under enhanced lipolytical activity are utilized for energy production. For this reason, the oxidation rates of intravenously administered lipids in premature infants are examined both with and without heparin. Triolein marked with 13C and processed in soybean oil is administered intravenously at a dosage of 10 mg/kg. 13CO2 results from fatty acid oxidation and is exhaled through the lungs, whereafter it is collected in separate breath samples over a period of 6 hours and determined by mass spectrometry. The examination was performed in 5 premature infants, first without heparin, then after heparin injection (10 U/kg). The extent of 13CO2 exhalation was not significantly influenced by heparin. Without heparin supply we measured a fatty acid oxidation of 32.0 +/- 2.57% which was the same (31.6 +/- 2.34%) after heparin injection. Single intravenous administration of 10 U heparin/kg does not cause increased fatty acid oxidation in premature infants.

Blood Glucose↗
PubMed1985

Neonatal behaviour disturbances in infants of epileptic women treated during pregnancy.

Infants exposed in utero to antiepileptic drugs showed significantly more behaviour disturbances such as sedation (p less than 0.05) and hyperexcitability (p less than 0.01) than infants of a control group. The presence of these clinical symptoms and the time of their appearance did not seem to be dependent on the type of maternal medication, nor on the drug serum concentration in cord blood nor on the rate of drug disappearance from the infant's plasma.

Akathisia, Drug-Induced↗
PubMed1984

Valproic acid in the perinatal period: decreased maternal serum protein binding results in fetal accumulation and neonatal displacement of the drug and some metabolites.

The total concentrations of valproic acid were higher in cord serum than in the serum of epileptic mothers given this drug (fetal/maternal total concentration ratios 1.7 +/- 0.5). The maternal free fractions of VPA correlated with the fetal accumulation of the drug. The fetal/maternal free fraction ratios (0.47 +/- 0.24) correlated inversely with the fetal/maternal total concentration ratios. The free concentrations of VPA in fetal blood were similar to those in maternal blood. These results obtained in vivo were confirmed by an in vitro study in which the drug had been added to drug-free serum samples. The free fractions (x100) of VPA in the maternal serum at birth (27.3 +/- 6.3) were significantly higher than in the serum of adult controls (8.0 +/- 2.4) and in cord serum (11.8 +/- 1.3). The pattern of VPA metabolite binding in the three groups was similar to that of VPA, although an unsaturated metabolite (2-en) was bound to a much higher degree than VPA (greater than 98%). The high total drug load in the fetus was partially displaced from binding sites during the first few postnatal days. The free fractions of the drug and metabolites in the neonates were almost twice as high as those in the fetus at birth. The decreased protein binding of VPA in the mothers at birth and in the neonates during the first postnatal week was related to increased free fatty acid levels. VPA concentrations in mother's milk were much lower than the free concentrations in plasma milk/plasma ratios 0.025 +/- 0.01). In neonates, half-lives for VPA were prolonged (43 +/- 14 hours). Our results indicate that increased free fatty acid concentrations in the maternal blood at the time of birth result in partial displacement of VPA from maternal binding sites, additional placental transfer, and thus fetal accumulation of the drug. The high drug load in the fetus is subsequently partially displaced after birth, resulting in increased free fractions and free concentrations of VPA in the neonate.

Blood Proteins↗
PubMed1984

Measurement of fatty acid oxidation in premature newborn infants with the 13C-triolein breath test.

The 13C-triolein breath test is a method giving evidence of extent and rate of fatty acid oxidation in newborn infants on parenteral nutrition. The test has the special advantage of being non-invasive. Triolein labeled with the stable carbon isotope 13C and emulsified in soybean-oil is used as a tracer. 10 mg of 13C triolein per kg body weight are administered intravenously. The 13CO2 resulting from the fatty acid oxidation is analysed in expired breath by ratio-mass-spectrometry. The calculated 13C elimination is representative of the rate of fatty acid oxidation during the examination period. First studies on 15 premature infants have shown that an average of 27.0 +/- 1.8% of the dose administered is oxidized within 4 h. The present results suggest that the oxidation rate may be related to the maturity of the prematurely born infants.

Journal Article↗
PubMed1984

Ethosuximide in epileptic women during pregnancy and lactation period. Placental transfer, serum concentrations in nursed infants and clinical status.

A total of 10 epileptic mothers treated with ethosuximide (ES) as well as their 13 newborns were included in this study. At birth foetal/maternal serum concentration ratios were 0.97 +/- 0.02 (n = 7) and ES half-lives in three neonates were 32, 37 and 38 h. The breast milk concentrations of ES were similar to those in maternal serum (milk/serum: 0.86 +/- 0.08, n = 12) and the nursed infants maintained serum levels between 15 and 40 micrograms/ml. Two major malformations (bilateral clefting, hare-lip) were observed in two neonates whose mothers received either ES/PB or ES/PMD comedication. The number of minor anomalies was higher in the ES group (6.2, n = 12) than in the pair-matched control group of infants born to non-epileptic mothers (2.1, n = 10). Neonatal behaviour complications occurred in seven infants, two of them were severely affected.

Abnormalities, Drug-Induced↗
PubMed1984

Rapid determination of whole-body bicarbonate kinetics by use of a digital infusion.

Accurate determination of substrate oxidation rates from breath 13CO2 levels often requires information on the bicarbonate status of the subject. We have developed a rapid method to obtain a complete set of bicarbonate kinetic parameters, prime bicarbonate pools with 13C, clamp breath 13CO2 levels rapidly and accurately with predetermined ranges, and provide a steady base-line enrichment of 13C for a subsequent substrate oxidation measurement. The method consists of administering NaH13CO3 intravenously as a combination of a bolus dose, an exponentially decreasing infusion, and a constant infusion. A Harvard model 2729 microprocessor-controlled syringe pump was modified for external control and coupled to a Hewlett-Packard HP-85 desk-top computer to deliver the complex infusion. An infusion algorithm that would rapidly attain and maintain an increase of 50% 13C enrichment of breath CO2 was derived by using the SAAM-27 program to interrogate a three-compartmental model of bicarbonate kinetics in normal, fasted, resting adult subjects. When the method was tested on five adult fasted subjects who had rested for 1.5 h, plateau enrichments were achieved within 10-20 min. The bicarbonate pool sizes and kinetic parameters obtained by compartmental analysis of their 13CO2 data were used to obtain a refined infusion protocol, which resulted in more rapid attainment of plateau enrichments. If carried out immediately before a substrate oxidation test, the method can provide a complete description of bicarbonate kinetics for use in the compartmental and noncompartmental analysis of substrate catabolism.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1983

[Anti-epileptic agents during pregnancy. A prospective study on the course of pregnancy, malformations and child development].

In a prospective controlled study 70 children of females with epilepsy and on anticonvulsant medication during pregnancy were investigated. It was shown that epileptic females had stillbirths more frequently than expected. After delivery particularly children on phenobarbitone are sedated. Due to weak suckling this may lead to inadequate food intake. Withdrawal symptoms manifest in affected children as hyperexcitability lasting for weeks. Children of epileptic women on medication are generally smaller, of lower weight and have smaller heads than children from all control groups. Ingestion of more than one anticonvulsant leads to an even more pronounced reduction of infantile body measurements below the expected mean value. Small malformations are observed more frequently after intrauterine exposition to anticonvulsants than in the control groups. Ingestion of more than one anticonvulsant leads to an increase of the number of small malformations in the child than after single drug therapy. Children of epileptic parents are affected more frequently by large malformations than children of nonepileptic parents.

Abnormalities, Drug-Induced↗
PubMed1983

Enzyme induction in neonates after fetal exposure to antiepileptic drugs.

The 13C-AP breath test is shown to be a convenient, noninvasive method to monitor velocity and capacity of P450-dependent AP N-demethylation in infancy and childhood. According to 13C-AP breath tests, neonates have a very low capacity to eliminate 13CO2, which is only 15 to 21% of the activity in adults. During the first year of life AP N-demethylation increases to reach its maximum at about 2 years; afterwards a slight decrease occurs. In 25 neonates exposed prenatally to different antiepileptic drugs 13C-AP breath test was efficiently used to prove that cytochrome AP N-demethylation was considerably stimulated. After primidone/phenobarbitone, especially in combination with phenytoin, 13C elimination reaches and even surpasses the range for older children. Valproate exposure during fetal life is not consistently followed by a significant increase in AP N-demethylation. The enzyme induction demonstrated by 13C-AP breath test was often accompanied by accelerated metabolic clearance and shortened half-life times of transplacentally acquired antiepileptic drugs. There was good agreement between 13C-AP breath tests and pharmacokinetic data for primidone/phenobarbitone but not for phenytoin. In contrast, in the case of phenytoin exposure during pregnancy the pharmacokinetic parameters and the 13C breath test data will transport very different informations about enzyme induction in these neonates.

Aminopyrine↗
PubMed1983

Carbamazepine and carbamazepine-10,11- epoxide during pregnancy and postnatal period in epileptic mother and their nursed infants: pharmacokinetics and clinical effects.

A total of 11 epileptic mothers treated with carbamazepine (CBZ) as well as their 12 newborns were included in this study. Maternal CBZ concentrations remained rather constant during pregnancy and slightly increased after parturition. Carbamazepine-10, 11-epoxide ( CBZE ) levels were less predictable and either increased or decreased during pregnancy. Fetal/maternal serum concentration ratios at birth were 0.78 +/- 0.14 (n = 5) for CBZ and 0.75 +/- 0.09 (n = 5) for CBZE . Neonatal half-lives were 28 +/- 11 hours (n = 4) for CBZ and 20 and 24 hours (n = 2) for CBZE . maternal milk/serum concentration ratios of CBZ and CBZE were 0.39 +/- 0.22 (N = 11) and 0.49 +/- 0.28 (n = 6), respectively. The steady-state CBZ serum levels of nursed infants were about 1.0 micrograms/ml in all cases but one, where a maximum concentration of 4.7 micrograms/ml was reached. One of the infants had major malformations. Minor anomalies were less frequent in the CBZ group, compared to the whole group of infants exposed to anticonvulsive drugs other than CBZ and as frequent as in a matched pair control group of unexposed neonates. Neonatal somatic data were found to be below the corresponding values of neonates exposed to antiepileptic drugs other than CBZ.

Abnormalities, Drug-Induced↗
PubMed1983

[Screening of newborn infants for hypothyroidism in Berlin (West) 1978-1982].

In July 1978 a neonatal screening program for congenital hypothyroidism was introduced in Berlin (West) covering more than 98% of the neonates born in the city area. Up to July 1982 TSH was determined on the fifth day of life in 74,350 newborns using a radioimmunoassay for TSH determination in dried blood spots. With a cut-off limit at 20 microU/ml, a control examination was necessary in 0.96% of the newborns. 32 infants with congenital hypothyroidism were detected and treated with 1-thyroxine, giving a total incidence of 1 in 2,323 newborns (permanent and transient cases). 63% of all newborns with elevated TSH levels (greater than 20 microU/ml) were born in the obstetric department of the Neukölln-Hospital, which uses PVP-Iodine for vaginal disinfection of the mothers during labor and delivery, especially after premature rupture of membranes. Those newborns had only transient TSH-elevations, which were normalized on the tenth day of life. The replacement therapy was started on the average on the ninth day of life. The symptoms present in the newborns with congenital hypothyroidism differed from patient to patient and from the "classical" signs of congenital hypothyroidism described in the literature. All infants detected by the screening program are followed in the outpatient department of the Children's Hospital of the Free University in Berlin and show a normal motor and mental development, except for two infants with other causes for retardation in psychomotor development.

Berlin↗
PubMed1982

Development of N-demethylase activity measured with the 13C-aminopyrine breath test.

The 13C-aminopyrine (AP) breath test was used to measure the normal development of N-demethylase activity in 25 children, aged 2 days to 14 years, with normal liver function. Five mg of 13C-AP per kg body weight were administered orally. After AP-demethylation by the hepatic mixed function oxidase system 13CO2 excess was analysed in expired breath by mass spectrometry. In the first days of life no 13C excretion could be detected in unstimulated newborns. N-demethylase activity then slowly increased and reached adult levels by two years of life. Though the range of normal values showed considerable scattering, patients with liver disease or with enzyme induction following anticonvulsant therapy could be well discriminated. This study of the 13C-aminopyrine breath test in children provides evidence for the assumption that hepatocellular function and development of specific enzymatic activities can be measured by such non-invasive methods. It may be expected that breath tests making use of a broader spectrum of 13C-labeled substrates will prove applicable to study prenatal inducibility and other aspects of developing hepatocellular and intestinal function of children in health and disease.

Adolescent↗
PubMed1982

Teratogenic and pharmacokinetic studies of primidone during pregnancy and in the offspring of epileptic women.

Fourteen epileptic women treated with primidone, either alone or in combination with other antiepileptic drugs, were studied prospectively during their pregnancy. Plasma levels of primidone and its metabolites were monitored and correlated to findings in the offspring. Maternal serum concentrations of primidone and metabolites were generally low during pregnancy. The levels of its main metabolites--phenobarbital and PEMA--were found to drop within the first month of pregnancy in two cases. The plasma concentrations remained low until birth and rose sharply thereafter. The phenobarbital/primidone ratio (mean 0.84) and PEMA/primidone ratio (mean 0.56) in pregnant patients were found to be lower than in non-pregnant patients, except when primidone was given in combination with phenytoin in which case the expected phenobarbital/primidone (mean 2.5) and PEMA/primidone (mean 1.5) ratios were found. A ventricular septal defect was found in one of the offspring of the fourteen mothers and five children had microcephaly. There was a high incidence of poor somatic development with dystrophy (n=3) and short stature (n=2). Head circumferences (n=8), lengths (n=4) and/or weights (n=8) were below the 10th percentile in a number of children. Four children showed marked facial dysmorphy. Our preliminary data suggest that primidone intake during pregnancy may be important in the pathogenesis of minor anomalies and in the induction of poor somatic development.

Abnormalities, Drug-Induced↗
PubMed1981

Valproic acid and several metabolites: quantitative determination in serum, urine, breast milk and tissues by gas chromatography-mass spectrometry using selected ion monitoring.

A method has been developed for the simultaneous quantitative determination of valproic acid (2-propylpentanoic acid) and its metabolites 2-propyl-2-pentenoic acid (trans), 2-propyl-3-pentenoic acid (trans), 2-propyl-4-pentenoic acid, 3-hydroxy-2-propylpentanoic acid, 4-hydroxy-2-propylpentanoic acid, 5-hydroxy-2-propylpentanoic acid, 3-oxo-2-propyl-pentanoic acid, and and 2-propylglutaric acid. All compounds were extracted at pH 5.0 with ethyl acetate. The concentrated extracts were trimethylsilylated and the resulting mixtures analyzed by a gas chromatography-mass spectrometry-computer system operated in the selected ion monitoring mode. Linear calibration curves were obtained in the concentration ranges studied (0.1-20 microgram/ml for metabolites, 0.1-150 microgram/ml for valproic acid. The recoveries of the drugs were between 92 and 97%. The relative standard deviations were between 3.9 and 8.1% (analysis of multiple 10-microliter samples of patient urine). The lower detection limits were found to be between 2.8 and 18 ng/ml using 200-microliter serum samples. The derivatized extracts were stable for at least one week. Applications of the method described include studies of placental transfer for valproic acid and metabolites in the human, the elimination of these substances by the neonate, their transfer via mother's milk, and their levels in mouse brain.

Adult↗
PubMed1981

Valproic acid and its metabolites: placental transfer, neonatal pharmacokinetics, transfer via mother's milk and clinical status in neonates of epileptic mothers.

The pharmacokinetics of valproic acid (VPA) and several metabolites were measured in 11 epileptic mothers and their 12 newborns. VPA was found in higher concentrations in cord serum than in maternal serum [(factor 1.7 +/- 0.6; (n = 6)]. VPA was excreted in the neonates with a mean half-life of 47 +/- 15 hr (n = 8) which is approximately 4 times the mean value found in adult epileptics. Maternal comedication (primidone and phenytoin) resulted in slightly reduced half-lives. The transplacental kinetics of the two main VPA metabolites in blood were similar to those of VPA. The very low levels of VPA in mother's milk (3% of maternal serum concentrations) suggest apparent safety of breast feeding. The [13C]aminopyrine breath test indicated neonatal hepatic enzyme activities which were slightly above those of unexposed neonates, but much below those of neonates which had been exposed to primidone and phenytoin in utero. Six of eight neonates exposed to VPA-monotherapy, but only one exposed to primidone or phenytoin comedication, developed an icterus neonatorum. A number of minor anomalies (four to eight per child) were observed, particularly hernias, diastasis of musculus rectus abdominis and weak abdominal walls. Two children were microcephalic and in another four children the head circumferences were below the 10th percentile. Significant withdrawal symptoms were not observed. Also hypoplasia of the nails and phalanges and facial dysmorphism associated with the "fetal hydantoin syndrome" did not occur in VPA-exposed children except in one case in which primidone had been administered as comedication.

Abnormalities, Drug-Induced↗