PubMed Health⌕ Search

Biomedical subjects

D Rating

Publications and source records attributed to D Rating.

At least 91 records · Page 5Linked to original sources
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

GABA in cerebrospinal fluid of children with febrile convulsions.

In 23 children with febrile convulsions the concentration of gamma-aminobutyric acid (GABA) in lumbar cerebrospinal fluid (CSF) was measured by a radioreceptor assay. The mean CSF GABA concentration of 134 (range, 73-294) pmoles/ml was significantly lower than that of 16 seizure-free children serving as controls, who had 210 (range, 117-475) pmoles/ml. The reduction in CSF GABA levels in patients with febrile convulsions was not reflected in plasma GABA concentrations. These data provide further evidence that impairment of GABA neurotransmission may contribute to an increased seizure propensity.

Child, Preschool↗
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↗
PubMed1980

Changes of CSF-protein pattern in children with acute lymphoblastic leukemia during prophylactic CNS therapy (Berlin protocol).

The cerebral spinal fluid (CSF)-protein profiles of ten children with previously untreated acute lymphoblastic leukemia (ALL) were investigated by agarose gel electrophoresis. The profiles were determined at diagnosis and during the fifth to eighth week of treatment when preventive therapy for central nervous system (CNS) leukemia (skull irradiation, intrathecal methotrexate (ithMTX) was administered. The profiles were compared with those obtained from a control group of 67 children and those from 42 patients with acute aseptic meningitis. The data from the latter group demonstrated the CSF-protein pattern of partial blood-CSF barrier (B-CSF-B) breakdown. The children with ALL showed no or only minor signs of a B-CSF-B impairment at diagnosis and after four weeks of systemic treatment. However, CSF changes indicative of a lesion of the B-CSF-B increased in all children continuously during CNS prophylaxis. The protein profile at the end of combined chemotherapy and radiotherapy was very similar to that in patients with acute aseptic meningitis. These observations point to neurotoxic side effects on the CNS barrier system with the combination of cranial radiation and ithMTX. A striking finding was restricted heterogeneity of gamma-globulin, observed in the CSF of nine out of the ten children with ALL before or during treatment. The significance of this abnormality is unknown.

Antineoplastic Agents↗
PubMed1979

[High doses of thiopental for therapy of post-ischaemic anoxia of the brain. A case report (author's transl)].

The case of a 7-year-old child is presented, who suffered circulatory arrest during induction of anaesthesia for surgery for a posterior fossa tumour. A brain ischaemia lasting 6 minutes duration had to be assumed. After restoration of circulation, 825 mg ethiopenta were administered in order to ameliorate a possible post-ischaemic anoxia of the brain according to a protocol by Safar [18]. 11 hours after circulatory arrest the child awoke. Except for a more pronounced left sided hemiparesis and paresis of the left n. abducens no additional neurological deficit was observed compared to the neurological status before induction of anaesthesia.

Anesthesia↗
PubMed1976

Protein patterns of the cerebrospinal fluid in children with cerebral palsy.

Cerebrospinal fluid in 69 children with cerebral palsy (CP) of different etiology was examined by an improved method of agarose-gel electrophoresis. The protein pattern was normal in 12 cases only. In children with CP caused by congenital and postnatal infections raised psi-globulin fractions and the appearance of oligoclonal phi-globulin bands were the most obvious finding. In patients with CP due to malformations or perinatal brain damage and in children with CP of unknown etiology decreased prealbumin and increased albumin values were combined with hydrocephalus e vacuo in about half of the cases. Less frequent changes of the beta-globulin fractions were found, an increase of the beta-fraction being more rare than a decrease of the tau-globulin.

Age Factors↗
PubMed1975

[The relationship between age and the cerebrospinal fluid protein profile profile of normal children. Cellulose acetate and agarose gel electrophoretic studies].

Neuropädiatrie 6: 383--397 (1975). CSF samples of 63 normal children 2 days to 14 years of age were concentrated (ultrafiltration in "Kollodiumhülsen") and examined by electrophoresis on cellulose acetate and agarose gel. In the CSF of all children 7 protein fractions were found by cellulose acetate electrophoresis. Analysing the pherograms by the means of an analog computer 15 fractions could be separated by agarose gel electrophoresis. Compared with the children of school age the newborn showed low prealbumin, beta1-globulin and tau-globulin fractions besides high albumin and gamma-globulin concentrations owing to an increased permeability of the blood-CSF barrier. During the following weeks a low prealbumin and a high albumin fraction still was found. Children from 3 month to 2 years of age showed a moderate increase of the relative prealbumin and beta1-globulin concentration in comparison with older children. The gamma-globulin fraction was lowest beyond the third month of life and increased again in the group of the 2--14 years old children. The variation of the protein profile with age could not only be demonstrated by the more difficult agarose gel electrophoresis but also by a simple technique of cellulose acetate electrophoresis.

Adolescent↗
PubMedDate not supplied

13C-ethanol and 13C-acetate breath tests in normal and aldehyde dehydrogenase deficient individuals.

Four normal and five aldehyde dehydrogenase (ALDH) isozyme I deficient individuals were subsequently loaded with (1-13C)ethanol and (1-13C)sodium acetate and the conversion of the label to 13CO2 was determined in expired air by isotope ratio mass spectrometry. In the 13C-acetate breath test, both groups showed virtually identical recovery of the label in expired air, namely 48.5 +/- 2.3% (mean +/- S.D.) for normal and 46.8 +/- 5.7% for deficient individuals. However, in the 13C-ethanol breath test, both the groups performed differently. On average, although a certain overlap of the single data was observed, the recovery of the label after four hours was 43.4 +/- 3.8% for the normal and 35.6 +/- 6.8% for the ALDH deficient subjects. These findings suggest a slower conversion of ethanol to carbon dioxide in aldehyde dehydrogenase deficient individuals, which may be another consequence of this deficiency besides the higher plasma acetaldehyde levels observed after ethanol loading in comparison to individuals with normal aldehyde dehydrogenase activity.

Acetates↗
PubMedDate not supplied

[Optimizing epilepsy therapy in children and adolescents with lamotrigine].

Lamotrigine is a broadly effective antiepileptic drug in mono- and add-on therapy for children and adolescents with focal and generalized epilepsies. Some epileptologists consider lamotrigine as the drug of primary choice in older school children and adolescents because of its good tolerability (no increase of body weight, no impairment of cognitive functions, due to new data probably no teratogenic properties). Lamotrigine can be used with good efficacy in numerable epilepsy diseases, such as tuberous sclerosis, juvenile neuronal lipofuscinosis and Rett syndrome. The first studies show that lamotrigine is also effective in children under 2 years of age. For therapy of difficult-to-treat epilepsies the combination of lamotrigine with valproate has proved as especially useful. This clinical observation is supported by new results of animal experiments. The dose-dependant and typical CNS side effects vertigo, ataxia, nausea, tremor and diplopia are found most frequently. The rate of allergic skin rashes which was very high before 1998 has decreased markedly by new dosage guidelines and is now as low as in older antiepileptic drugs. Lamotrigine does not impair cognitive functions, especially not memory and language. It has mood-stabilizing features and may improve quality of life. In animal experiments lamotrigine shows antiepileptogenic and neuroprotective effects.

Adolescent↗
PubMedDate not supplied

Preradiation chemotherapy of children and young adults with malignant brain tumors: results of the German pilot trial HIT'88/'89.

BACKGROUND: Preradiation chemotherapy could be beneficial in malignant brain tumors, because the blood-brain tumor-barrier is disrupted after surgery, bone marrow recovery--essential for intense chemotherapy--is still intact, and CNS toxicity and ototoxicity of active drugs are lower before irradiation of a child's brain. PATIENTS AND METHODS: A neoadjuvant phase 2 and a single arm pilot trial were initiated to investigate the efficacy and toxicity of an intense multidrug regimen before radiotherapy in 147 patients aged between 3 and 29; 9 years with medulloblastoma (94), malignant glioma (22), ependymoma (21), and stPNET (10). They were treated with one or two cycles consisting of procarbazine, ifosfamide/mesna with etoposide, high dose methotrexate/CF, and cisplatin with cytarabine. RESULTS: Radiation therapy was delayed for 17-30 weeks (median 23 weeks) in 112 patients who received two cycles. Chemotherapy was well tolerated. Serious infections were observed in 20 patients, with one fatal fungal septicemia. In 69 high risk patients with a residual tumor and/or solid CNS metastases an objective response (CR plus PR) was achieved in 67% medulloblastoma, 57% stPNET, 55% anaplastic ependymoma and 25% malignant glioma. Progression-free survival (PFS) at 5 years was 57% in 14 high risk patients with medulloblastoma, who achieved a complete response (CR). After a less than CR the PFS was 20% (p = 0.01). Overall survival at 5 years was 57% in medulloblastoma, 62% in ependymoma, 36% in malignant glioma and 30% in stPNET. CONCLUSION: The HIT'88/'89 regimen was well tolerated and efficacious in regard to response rates and early PSF particularly in medulloblastoma and anaplastic ependymoma. Based on these results the prospectively randomized trial HIT'91 was designed to investigate the optimal timing of chemotherapy. Preradiation chemotherapy according to the HIT'88/'89 regimen was compared with the standard regimen using CCNU, cisplatin, and vincristine after radiation therapy. Additionally, strict quality control of the three treatment modalities was instituted to help improve the survival rates in both trial arms.

Adolescent↗
PubMedDate not supplied

Treatment of infantile spasms with high-dosage vitamin B6.

High-dose vitamin B6 (pyridoxine-HCl, 300 mg/kg/day orally) was introduced as the initial treatment of recently manifested infantile spasms in 17 children (13 symptomatic cases with identified brain lesion and 4 cryptogenic cases). 5 of 17 children (2 cryptogenic, 2 with severe pre/perinatal brain damage and one with Sturge-Weber syndrome) were classified as responders to high-dose vitamin B6. In all 5 cases the response to vitamin B6 occurred within the first 2 weeks of treatment and within 4 weeks all patients were free of seizures. Two patients developed other seizures (partial seizures, etiologically unclear blinking attacks), but no relapse of infantile spasms was observed among the five responders to vitamin B6. No serious adverse reactions were noted. Side effects were mainly gastrointestinal symptoms, which were reversible after reduction of the dosage. Considering the life-threatening side effects of treatment with ACTH/corticosteroids or valproate, a controlled clinical trial with high-dose vitamin B6 would appear justified to either prove or disprove efficacy.

Administration, Oral↗