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Biomedical subjects

D Leupold

Publications and source records attributed to D Leupold.

At least 37 records · Page 2Linked to original sources
PubMed1993

Contribution of odd-numbered fatty acid oxidation to propionate production in neonates with methylmalonic and propionic acidaemias.

Newborns with disturbed propionate metabolism (propionic and methylmalonic acidaemias) accumulate during fetal life large amounts of odd-numbered long-chain fatty acids in adipose tissue (8% to 10% of total fatty acids vs 1% in normal controls) and other body lipids. During periods of acute catabolism, such as in the early days of life, mobilization and oxidation of odd-chain fatty acids from adipose tissue yield extensive amounts of toxic propionyl-CoA in the mitochondria and thus might contribute to the severe illness of the patients. Our data suggest that not only catabolism of protein but also that of adipose tissue has to be avoided in order to alleviate the neonatal illness of patients with propionic and methylmalonic acidaemias. It seems prudent to avoid prolonged fasting during the 1st year of life.

Acyl Coenzyme A↗
PubMed1993

Spectroscopic properties of potential sensitizers for new photodynamic therapy start mechanisms via two-step excited electronic states.

Three substituted tetraazaporphyrins, octa-(4-tert-butylphenyl)-tetrapyrazinoporphyrazine, tetra-(4-tert-butyl)phthalocyanine and tetra-(4-tert-butyl)phthalocyanatomagnesium(t4-PcMg), were spectroscopically checked in solutions and liposomes with respect to suitability as potential sensitizers of a possible new start mechanism for photodynamic therapy (PDT) from a stepwise excited higher singlet state. This PDT start mechanism was recently proposed to overcome the problem of O2 (1delta2)-caused cutaneous phototoxicity in PDT. By means of absorption and fluorescence measurements as well as nonlinear absorption investigation, transient spectroscopy and lasing experiments, compound t4-PcMg was found to have the most appropriate properties: Based on a high fluorescence quantum yield (phiF1 = 0.84) and a very low crossing to the triplet (phiISC = 0.05), two higher excited states can be effectively populated both by two stepwise absorption transitions at 674nm consecutive absorption transitions at 684 and and 710 nm. Moreover, t4-PcMg incorporates into liposomes very well with spectroscopic properties similar to those in solution.

Indoles↗
PubMed1989

Peritoneal dialysis in the treatment of metabolic crises caused by inherited disorders of organic and amino acid metabolism.

Four neonates who presented with coma secondary to hyperammonaemia resulting in central respiratory failure were treated with peritoneal dialysis for between 16 and 120 hours. Underlying diseases were maple-syrup-urine disease, propionic acidaemia and citrullinaemia in two patients. Clinical improvement was observed in three patients within 16 to 72 hours after institution of peritoneal dialysis. Biochemical analysis revealed a rapid reduction in plasma concentration of leucine, isoleucine and valine as well as their alpha-keto-analogues in the infant suffering from maple-syrup-urine disease. Correction of ammonia, glycine, alanine and propionic acid concentrations was observed in the infant with propionic acidaemia 24-72 hours after institution of peritoneal dialysis. Severe hyperammonaemia (1,000-2,500mumol/l) in two infants with citrullinaemia before peritoneal dialysis was treated successfully in one infant; whereas the second infant showed no clinical improvement despite amelioration of biochemical parameters. Glucose-absorption from peritoneal dialysis solution was in the range of 216-441 mg/kg/h.

Amino Acid Metabolism, Inborn Errors↗
PubMed1989

[Incidence and symptoms of cow's milk protein intolerance following acute gastroenteritis in young infants. Effect of a hypoallergenic diet].

In a prospective randomized study we investigated in 28 mainly bottle-fed infants younger than 60 days whether in acute gastroenteritis a hypoallergenic formula could prevent the development of cow's milk protein intolerance. Group 1 (14 infants) was fed with a formula adapted to human milk, Group 2 (14 infants) got a semi-elementary formula (Alfaré). After 3 months group II was exposed to cow's milk protein with a standardized challenge and the incidence of CMPI in both groups was calculated. All cases with the acute form of CMPI occurred in group II (5/12) whereas in group I only one infant suffered from the protracted mild form of the disease. Inspite of the relatively small number of probands we conclude from our results that in infants who are not totally breast-fed in the post-enteritic period feeding with a formula adapted to human milk is preferable to hypoallergenic semi-elementary preparations. An allergen free period of 3 months seems to induce symptoms of cow's milk intolerance, probably as a booster-effect to early sensibilisation.

Animals↗
PubMed1988

Phenylketonuria: distribution of DNA diagnostic patterns in German families.

The distribution of DNA haplotype constellations within the phenylalanine hydroxylase (PAH) gene was investigated in 44 German families affected with phenylketonuria (PKU). The haplotype frequencies differed significantly from those observed in a Danish population. Furthermore, ten haplotypes were identified in addition to the 12 previously described. In one of ten PKU alleles linked to haplotype 3, the G to A transition at the 5' splice donor site of intron 12 could not be confirmed with the use of synthetic DNA probes. According to these data, which are still limited, carrier testing and prenatal diagnosis should be possible in 70% of individuals at risk in the German population.

Alleles↗
PubMed1988

[Treatment of Crohn disease with intravenous immunoglobulin].

In a 14.5 year old girl with Crohn's disease a complete remission was achieved with intravenous immunoglobulins. Earlier treatment with various therapeutical regimens had been unsuccessful. During the next two relapses the same prompt positive response was reproducible, whereas in the third the dose of immunoglobulin had to be doubled.

Adolescent↗
PubMed1986

Direct identification of propionylcarnitine in propionic acidaemia: biochemical and clinical results of oral carnitine supplementation.

Urinary short-chain acylcarnitine in a patient with propionic acidaemia and low levels of free carnitine was found to consist mainly of propionylcarnitine. The compound was isolated by sequential paper and thin layer chromatography and identified by ammonia desorption chemical ionization mass spectrometry. Treatment of the patient with oral carnitine supplements led to a near-normalization of the plasma free carnitine concentrations and an increase in his muscle tone. The propionylcarnitine excretion rose and there was a simultaneous decrease in the methylcitrate output. Carnitine treatment did not prevent the occurrence of an episode of metabolic decompensation.

Amino Acid Metabolism, Inborn Errors↗
PubMed1986

Skeletal growth in fetal rats. Effects of glucose and amino acids.

The modified hyperglycemia-hyperinsulinism hypothesis, which characterizes intrauterine growth of diabetic pregnancy, was studied in fetal rats. From day 19 to day 21 postconception, pregnant rats were constantly infused with saline, amino acids, or glucose. In the fetus, serum somatomedin activity was determined, with the porcine bioassay and the incorporation of 3H-thymidine into rib cartilage and isolated chondrocytes in vivo in response to serum from normal maternal or fetal rats. In comparison with control fetuses, body weights were decreased in glucose-exposed fetuses (4.66 +/- 0.25 versus 3.75 +/- 0.99, N = 121; P less than 0.001), and increased (4.87 +/- 0.57, N = 105; P less than 0.05) in amino acid-exposed fetuses. Serum somatomedin activity (U/ml) was higher in glucose-treated (0.79 +/- 0.40, N = 11; P less than 0.05) and amino acid-treated animals (0.90 +/- 0.16, N = 10; P less than 0.001) than in controls (0.55 +/- 0.04, N = 13). In vivo labeling with thymidine resulted in a higher radioactivity of cartilage in small fetuses compared with large fetuses when the dams had been infused with saline (r = -0.531, N = 56; P less than 0.001) or amino acids (r = -0.292, N = 52; P less than 0.01). Opposite results were obtained in hyperglycemic animals (r = 0.542, N = 54; P less than 0.001). When isolated chondrocytes were incubated with serum from normal fetal rats, the incorporation of thymidine was about 10 times higher into cells from small fetuses than from large fetuses, irrespective of the infusion regimen.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗
PubMed1985

Atypical phenylketonuria with "dihydrobiopterin synthetase" deficiency: absence of phosphate-eliminating enzyme activity demonstrated in liver.

An assay for the phosphate-eliminating enzyme (PEE) activity in liver was developed which required only 5-10 mg tissue. PEE catalyses the elimination of inorganic triphosphate from dihydroneopterin triphosphate, which is the second and irreversible step in the biosynthesis of tetrahydrobiopterin (BH4). In the presence of substrate, magnesium, NADPH, and a sepiapterin reductase fraction from human liver, PEE catalysed the formation of BH4 which was measured by HPLC and electrochemical detection. In adult human liver, a PEE activity of 1.02 +/- 0.134 microU/mg protein (mean +/- 1 SD; n = 5) was observed. In liver needle biopsy material from five patients with defective biopterin biosynthesis, no PEE activity was found (less than 2% and 6% of the control values, respectively). The presence of an endogenous inhibitor was excluded. In a patient who died without definite diagnosis and in a patient with beta-thalassaemia liver PEE activity was increased. Sepiapterin reductase activity was present in all cases. Results indicate that in "dihydrobiopterin synthetase" deficiency, the most frequent of the rare BH4-deficient variants of hyperphenylalaninaemia, the molecular defect consists in a defect of PEE.

Adult↗
PubMed1985

Immunoreactive calcitonin in brain regions and pituitary of sheep.

In this study we have investigated the presence of immunoreactive calcitonin in the central nervous system and pituitary of sheep. The calcitonin concentrations were determined radioimmunologically by two different antibodies. We have demonstrated calcitonin in extracts of areas of the central nervous system, whole pituitary, thyroid gland and plasma of 21 sheep. The concentrations were (ng/g wet weight, mean values +/- SE): thyroid 16.0 +/- 4.4, pituitary 2.03 +/- 0.34, reticular formation 1.64 +/- 0.25, substantia nigra 1.53 +/- 0.46, dentate nucleus 1.11 +/- 0.27, putamen 1.05 +/- 0.35, hippocampus 0.97 +/- 0.17, fornix 0.96 +/- 0.15, anterior thalamus 0.92 +/- 0.28, mammillary body 0.88 +/- 0.12, cerebellum 0.86 +/- 0.09, caudate nucleus 0.84 +/- 0.11, posterior hypothalamus 0.83 +/- 0.19, epiphysis 0.75 +/- 0.25, thalamus centralis 0.71 +/- 0.10, almond nucleus 0.69 +/- 0.16, medulla oblongata 0.67 +/- 0.15, anterior hypothalamus 0.66 +/- 0.20, precentral gyrus 0.66 +/- 0.16, globus pallidus 0.63 +/- 0.31, postcentral gyrus 0.36 +/- 0.08 and plasma (ng/ml) 0.058 +/- 0.013. Our results demonstrate that immunoreactive calcitonin is present in the central nervous system (CNS) of sheep, compatible with a neurotransmitter function for this hormone.

Animals↗
PubMed1983

Survival time in cystinosis. A collaborative study.

In a retrospective study the overall survival time of 205 cystinotic patients of six countries was determined. The median survival time was 8.5 years. The median time for 'renal death' (age at death due to uraemia or age at starting renal replacement therapy) was 9.2 years. The youngest patient dying of renal death was 5.2 years. No sex difference in survival time was noticed. Furthermore no difference in survival time was noted between the different countries. The analysis of the overall survival curve indicates no clear differences between the infantile and adolescent types of cystinosis.

Adolescent↗
PubMed1982

Atypical phenylketonuria with defective biopterin metabolism. Monotherapy with tetrahydrobiopterin or sepiapterin, screening and study of biosynthesis in man.

Administration of a single dose of tetrahydrobiopterin dihydrochloride, 10--20 mg/kg orally, to a patient with dihydrobiopterin deficiency led to disappearance of clinical symptoms for 4 days, normalization of urinary phenylalanine and serotonin and decrease of elevated neopterin for 2--3 days. A dose-dependent stimulation of serotonin production was observed. A similar effect was noted with even lower doses of L-sepiapterin. The patient is now under monotherapy with tetrahydrobiopterin . 2 HCl, 2.5 mg/kg daily. Other patients with this disease may not respond as well. Results of screening for tetrahydrobiopterin deficiency in 228 cases with hyperphenylalaninemia, including 140 newborns, are reported. There is evidence that biopterin biosynthesis in human kidney and liver proceeds via a dioxo compound and L-sepiapterin.

Biopterins↗
PubMed1982

3-hydroxy-3-methylglutaryl-CoA lyase deficiency in an infant with macrocephaly and mild metabolic acidosis.

A girl, now three years old, is reported, in whom at the age of 5 months the diagnosis of 3-HMG-CoA lyase deficiency was established. The characteristic excretion pattern consisted of 3-HMG, 3-CH3-glutaconic acid, 3-CH3-glutaric acid and 3-HIVA. Activity of 3-HMG-CoA lyase in leucocytes was very low. She had compensated metabolic acidosis and mild hypoglycemia. Therapy with a leucine restricted diet decreased excretion of metabolites moderately but did not influence the tendency to metabolic acidosis. Clinically the infant presented with macrocephaly. At the age of 3 years she is severely retarded. CAT scan revealed the picture of progressive demyelination of the white matter.

Acidosis↗
PubMed1982

Massive periosteal new bone formation in ulcerative colitis.

A case of periosteal new bone formation in a 14-year-old girl with recurrent ulcerative colitis is reported. There was exacerbation of the periosteal new bone formation during acute episodes of colitis, and incorporation of the periosteal appositions into the underlying bone during remission.

Adolescent↗