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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    European journal of pediatrics 139 (1982), S. 129-134 
    ISSN: 1432-1076
    Keywords: Breath test ; Enzyme induction ; Stable isotopes ; Anticonvulsants
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract 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.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    European journal of pediatrics 153 (1994), S. S94 
    ISSN: 1432-1076
    Keywords: Organic acid disorders ; Neurological symptoms ; Central nervous system ; Cerebrospinal fluid
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Neurological manifestations are very common and can be the leading and/or presenting feature in organic acid disorders, sometimes in the absence of metabolic derangement. Review of the time course and presentation of neurological disease in organic acid disorders reveals characteristic clinical findings of ataxia, myoclonus, extrapyramidal symptoms, metabolic stroke and megalencephaly. A group of organic acid disorders presents exclusively with neurological symptoms. These include glutaryl-CoA dehydrogenase deficiency (glutaric aciduria type I), succinic semialdehyde dehydrogenase deficiency (4-hydroxybutyric aciduria), mevalonic aciduria,n-acetylaspartic aciduria (Canavan disease) andl-2-hydroxyglutaric aciduria. As a group these “cerebral” orgamic acid disorders appear to remain often undiagnosed and their true incidence is much less wellknown than that of the “classical” organic acid disorders. Unfortunately, stringent guidelines for a clinical preselection of neuropaediatric patients to be investigated for organic acid disorders cannot be provided. Today, screening for neurometabolic disorders should be as comprehensive as possible and include determinations of amino acids, purines and pyrimidines and markers of peroxisomal function in addition to organic acid analysis.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-1076
    Keywords: Key words Metabolic decompensation ; Double-labelled water ; Resting energy expenditure ; Preterm ; infant ; Methylmalonic acidaemia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The assessment of energy expenditure is valuable for the management of children with various conditions such as obesity and failure to thrive. Total daily energy expenditure (TDEE) includes resting energy expenditure (REE), energy expenditure during physical activity, dietary thermogenesis and growth. TDEE can be assessed by using the double-labelled water technique, but it has complex pitfalls and potential sources of errors and is impractical for everyday use. As REE is a substantial part of TDEE (65%–70%) and computerised indirect calorimeters have become recently available, this non-invasive, relatively cheap and easy to use technique is valuable for the assessment of short-term changes in energy metabolism. This can be used to assess REE of children with inborn errors of metabolism, whilst well and during episodes of metabolic decompensation and therefore to accurately determine energy intake.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    European journal of pediatrics 156 (1997), S. S18 
    ISSN: 1432-1076
    Keywords: Key words13C breath test ; Stable isotopes ; Liver ; function ; Carbohydrate absorption ; Aminopyrine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Breath tests (BT) using stable isotopically labelled substrates seem to fullfil all the demands and desires for a non-invasive investigation. There are no radiation hazards, substrates are given in tracer amounts perorally, breath and urine samples can be collected easily, and tests can be done repeatedly, thus easily allowing the monitoring of function with time. There are, however, some disadvantages. Any BT has the same assumption: after intake of the 13C tracer the substrate is metabolized to 13CO2. An increase of 13CO2 above baseline levels is said to reflect the function investigated – in 13C sucrose studies, the amount of carbohydrate absorbed; in 13C aminopyrine BT, the liver function; in 13C glucose BT in a diabetic child, the impaired handling of glucose. However, as only the end product 13CO2 is measured, there is no information on all the pools and fluxes the labelled substrate and its metabolites have to pass. At least in inborn errors of metabolism, probably in any disease, one has to assume that these fluxes and pools are substantially changed. Therefore all calculations are weak and finally one has to resort to invasive methods, i.e. drawing blood to measure pools and fluxes to allow a correct interpretation of the BT data. Furthermore, changes in the basal exhalation of 13CO2 during the test will have an impact on the BT calculation. Another problem is that for an exact calculation, the basal metabolic rate (BMR) and the actual endogenous CO2 production in the patient is needed, which in most instances is unknown. It is not easy to maintain a stable endogenous CO2 production, particularly in younger children who will not rest or in neonates and toddlers who may fight against taking breath samples. Taking together these limitations are the reason why BT have not been able to reach the level of routine clinical methods, especially in the diagnostic work up of impaired liver function or inborn errors of metabolism.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    European journal of pediatrics 157 (1998), S. 824-830 
    ISSN: 1432-1076
    Keywords: Key words Intelligence ; Neurology ; Neuropsychology ; Phenylketonuria
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Due to the observation of severe neurological symptoms in single patients as well as brain imaging, neuropsychological and neurophysiological abnormalities, the long-term prognosis of treated phenylketonuria is still under discussion. We investigated the neurological outcome of 57 (24 male, 33 female) patients with phenylketonuria (diet onset 〈3 months) at a mean age of 23.6 (17–33) years in comparison to control subjects. Methods used were a clinical-neurological examination, tests for fine motor abilities, IQ test (WAIS-R), a neuropsychological attention task and MRI (30 patients only). Tremor was increased in the patients (28%) compared to controls (15%). Fine motor abilities were significantly reduced in three areas: hand-wrist steadiness, finger-hand dexterity and hand-wrist speed. Tremor as well as reduced fine motor skills were not associated with treatment-related variables, e.g. diet onset, strictness of biochemical control or amount of MRI white matter change. IQ was lower in patients (mean 97.6) compared to matched control subjects (mean 105.5). IQ at 12 years was correlated with biochemical control from birth up to the age of 12 and remained stable up to adult age, independent of biochemical control after 12 years of age. In contrast to the other outcome parameters, the performance in a neuropsychological attention task was influenced by the concurrent plasma phenylalanine concentration. Specific late-onset neurological impairment was not identified in this sample of early-treated adults with phenylketonuria. Conclusion Careful neurological investigation revealed subtle symptoms of brain damage even after early-initiated treatment in adult patients with phenylketonuria. At present it cannot be excluded that further neurological deterioration could emerge later in life. Thus, patients with phenylketonuria – either on or off diet – should be monitored throughout life.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    European journal of pediatrics 157 (1998), S. 606-607 
    ISSN: 1432-1076
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-1041
    Keywords: primidone ; phenobarbital ; placental transfer ; PEMA ; neonatal metabolism ; aminopyrine demethylation ; renal clearance ; breast milk ; withdrawal symptoms ; GC-MS analysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The placental transfer of primidone and its metabolites phenobarbital, phenylethylmalondiamide (PEMA) and p-hydroxyphenobarbital (free and conjugated) has been investigated at birth in 14 epileptic women who had been treated with primidone throughout pregnancy. All drugs studied were found in similar concentrations in maternal and cord blood. In seven of the newborns the pharmacokinetics of these drugs were studied during the first postnatal weeks. Primidone and phenobarbital were eliminated with mean half-lives of 23±10 h and 113±40 h, respectively, PEMA with 35±6 h. In some neonates the serum concentrations of phenobarbital and PEMA increased during the first few days due to their formation by neonatal primidone metabolism. Some babies showed a biphasic elimination pattern with elimination rates increasing after a few days. Although half-lives varied greatly, they corresponded well with renal clearance values and aminopyrine demethylase activities as measured by13CO2-exhalation from13C-labelled aminopyrine. Two newborns whose mothers had been treated with phenytoin in addition to primidone, showed half-lives, renal clearance values and aminopyrine demethylase activities well within the corresponding ranges for adults, thus demonstrating prenatal induction. Newborns whose mothers had been treated with valproate as comedication, did not exhibit elevated excretion rates as compared to newborns of mothers who were treated with primidone alone. Withdrawal symptoms developed in two newborns at times when primidone had been essentially excreted, and in spite of the presence of elevated phenobarbital and PEMA levels. All drugs studied were also present in mothers' milk. During breast feeding, drugs ingested with the milk contributed to the neonate's blood levels, particularly in the case of phenobarbital.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 0009-8981
    Keywords: Bile acid ; Chenodeoxycholic acid ; Cholesterol ; Cholic acid ; Gas-chromatography-mass spectrometry ; Mevalonate kinase deficiency ; Stable-isotope
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 0009-8981
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 0009-8981
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Medicine
    Type of Medium: Electronic Resource
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