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Biomedical subjects

G Hug

Publications and source records attributed to G Hug.

At least 19 recordsLinked to original sources
PubMed1991

Reduction of serum carnitine concentrations during anticonvulsant therapy with phenobarbital, valproic acid, phenytoin, and carbamazepine in children.

We determined four carnitine constituents (total and free carnitine and short- and long-chain fatty acid carnitine esters) in serum from 471 patients treated for convulsions with phenobarbital, valproic acid, phenytoin, and/or carbamazepine. The 471 patients were in eight treatment groups; four were treated with monotherapy and four with polytherapy. The means of all four carnitine constituents were significantly reduced in all treatment groups (except for free carnitine in four groups). Total carnitine was reduced by 23% to 48%, free carnitine by 9% to 45%, short-chain fatty acid carnitine by 46% to 64%, and long-chain fatty acid carnitine by 6% to 29%. Patient frequency of reduction for total carnitine was 20% of all patients (10% for free carnitine), 23% of patients receiving valproate (9% for free carnitine), 36% of those receiving phenobarbital (21% for free carnitine), 12% of those receiving phenytoin (8% for free carnitine), and 8% of those receiving carbamazepine (1% for free carnitine). Only for phenobarbital was there an inverse correlation between the serum concentration of the drug and that of carnitine concentration. One patient receiving carbamazepine had a 59% reduction in the total and a 65% reduction in the free carnitine concentration and a fivefold increase in long-chain fatty acid carnitine, values similar to those seen in neonatal lethal carnitine palmitoyl transferase II deficiency. It remains to be determined whether a reduction in serum carnitine values in patients receiving anticonvulsant therapy is of clinical consequence, whether the reduction is present in some patients before the start of therapy, when and by what mechanism carnitine levels may become reduced during therapy, and whether the reduction exists in the solid tissues of these patients.

Analysis of Variance↗
PubMed1990

Simultaneous measurement of 25-hydroxy, 24,25-dihydroxy-, and 1,25-dihydroxyvitamin D without use of HPLC.

A procedure is described for measuring the concentration of three major vitamin D metabolites: 25(OH)D, 24,25(OH)2D and 1,25(OH)2D, in 0.5 ml serum. The analytes are extracted using C18, and separated using aminopropyl solid phase extraction cartridges. 25(OH)D is separated completely; less than or equal to 10% overlap is observed between the 24,25(OH)2D and the 1,25(OH)2D fractions, and this overlap did not interfere in subsequent competitive radioligand assay. Coefficient of variation (SEM/mean x 100%) is intra-assay (n = 10) 5.8, 3.1, 5.2%, and inter-assay (n = 5) 10.1, 8.7 and 6.4%, respectively. Recoveries of the three analytes added to a single specimen are 103, 95 and 111%, respectively. One technician can extract and fractionate up to 24 specimens in one day, ready for HPLC or direct estimation.

24,25-Dihydroxyvitamin D 3↗
PubMed1989

Hypercalciuria with Bartter syndrome: evidence for an abnormality of vitamin D metabolism.

Some children with Bartter syndrome have hypercalciuria. To determine the mechanism for this phenomenon, we studied tubular function and calcium metabolism in six such children. All patients had hypokalemic alkalosis, normotension, hyperreninemia, growth retardation, low fractional distal chloride reabsorption (4/5), and elevated urinary prostaglandin E2 excretion (5/6). In addition, all had hypercalciuria (urinary calcium 6.5 to 25.0 mg/kg/day), with evidence of nephrocalcinosis in five. None, however, had evidence of rickets or hyperparathyroidism. There was a marked elevation in the serum concentration of 1,25-dihydroxyvitamin D in all, and four patients had a response to oral calcium loading suggestive of absorptive hypercalciuria. Five children have had long-term therapy with indomethacin. They have had improvement in hypokalemia and reduced urinary prostaglandin E2 excretion as well as reductions in the serum concentration of 1,25-dihydroxyvitamin D and in urinary calcium excretion. These data suggest that hypercalciuria in some children with Bartter syndrome is associated with an excess of 1,25-dihydroxyvitamin D. The improvement in hypercalciuria with prostaglandin synthesis inhibition may result in part from correction of this vitamin D abnormality.

Bartter Syndrome↗
PubMed1986

Fetal mucolipidosis II (I-cell disease): radiologic and pathologic correlation.

A pregnant woman whose previous child had a diagnosis of I-cell disease was referred for evaluation of the fetus. Fluid obtained by amniocentesis and maternal serum showed abnormally increased levels of lysosomal enzymes suggesting that the fetus had I-cell disease. Sonography at 18 weeks showed abnormally short femurs and intrauterine growth retardation. The pregnancy was electively terminated at 19 weeks' gestation and the diagnosis was confirmed. Radiographs of the fetus demonstrated that the bony dysplasia is present early in fetal life with diffuse decrease in bone mineralization, a coarse, lacy, trabecular pattern, overall shortening and under-modelling of the long bones, subperiosteal bone deficiency in the diaphysis giving the appearance of periosteal new bone, hypoplasia of the anterior superior aspect of the upper lumbar vertebral bodies, broad ribs, abnormal pelvis with squared iliac wings and flattened acetabular roofs, and a small irregular calcaneal ossification center. There was good correlation between the radiographic findings and the microscopic findings in the bones. We observed deficient endosteal bone formation, small epiphyses, and poorly developed intervertebral discs. We speculate that this indicates impaired production of extra-cellular matrix by several different types of specialized mesenchymal cells. Abnormalities of transport of glycoproteins other than lysosomal enzymes or excess of extracellular acid hydrolases may be involved in the pathogenesis.

Bone and Bones↗
PubMed1986

Glycogen accumulation in the pars recta of the proximal tubule in Fanconi syndrome.

We reviewed the renal pathology in 10 cases of renal Fanconi syndrome. Five cases showed the Armanni-Ebstein lesion, i.e., clear glycogen-filled cells limited to the pars recta of the proximal tubules. The 5 cases included 2 siblings with a unique syndrome characterized by death in infancy, severe Fanconi syndrome, severe rickets, carnitine deficiency, and atrophy of the exocrine pancreas. Two other siblings had glycogen storage disease type XI. One of 4 cases of putative tyrosinemia had the lesion. The ultrastructure was studied in 2 cases. The Armanni-Ebstein lesion in these cases was morphologically indistinguishable from that seen in diabetic patients dying after prolonged hyperglycemia. Glycosuria is the only common factor in both diabetic hyperglycemia and the varied proximal tubular diseases studied. The mechanism of the glycogen accumulation in this short parts recta segment of the proximal renal tubule was further investigated by reviewing the renal histology in cases of glycogen storage disease types I, II, III, and VIII. None showed the Armanni-Ebstein lesion, but type I showed glycogen deposition throughout the proximal tubule. Thus, the Armanni-Ebstein lesion is not the result of an enzymatic deficiency for glycogen synthesis in the convoluted tubules.

Adolescent↗
PubMed1985

Morphologic characteristics of the placenta in glycogen storage disease type II (alpha-1,4-glucosidase deficiency).

Five placentas from infants with enzymatically diagnosed glycogen storage disease type II (three from midtrimester abortions, two from term deliveries) were studied by light and electron microscopy. On routine histologic examination with hematoxylin and eosin staining, storage cells were identifiable in the connective tissue of the amnion. These cells provide the means to diagnose this glycogen storage disease prior to the development of clinical symptoms. Electron microscopy, even in the midtrimester placenta, shows typical membrane-bound, glycogen-filled vacuoles in the villous endothelium and stromal cells. These vacuoles can provide confirmation of glycogen storage in cases of prenatal enzymatic diagnosis and therapeutic abortion.

Amnion↗
PubMed1984

Rapid prenatal diagnosis of glycogen-storage disease type II by electron microscopy of uncultured amniotic-fluid cells.

Glycogen-storage disease Type IIa is a fatal, genetically determined disease of infancy or early childhood that is characterized by deficient activity of acid alpha-glucosidase and by the presence of intracellular vacuoles full of glycogen, which are found in most tissues, including skin and liver. On electron microscopy these specific vacuoles are tightly packed accumulations of glycogen particles surrounded by a single membrane. We did electron-microscopical examinations on uncultured amniotic-fluid cells from 26 women whose fetuses were at risk for glycogen-storage disease Type IIa and from 8 normal control pregnant women. We found specific vacuoles in cells from 6 of the 26 high-risk patients. At delivery, glycogen-storage disease Type IIa was present in the infants of these 6 women and absent in those of the other 20 according to results of clinical, biochemical, and electron-microscopical studies of gestational products. After amniocentesis at 15 to 18 weeks of gestation, the prenatal diagnosis made by electron microscopy of uncultured amniotic-fluid cells was available in three to six days, whereas it took from three to six weeks to make the diagnosis by enzymatic analysis of the cultured amniotic-fluid cells. We conclude that the electron-microscopical prenatal diagnosis of glycogen-storage disease Type IIa is rapid, safe, and reliable. It should facilitate earlier diagnosis and thereby help to preserve parental options.

Amniocentesis↗
PubMed1984

Antenatal diagnosis of mucopolysaccharidosis type I (Hurler's disease) is not possible by electron microscopy of uncultured amniotic fluid cells.

Mucopolysaccharidosis type I (MPS I) is a lysosomal storage disorder characterised by the deficient activity of iduronidase and by the presence of MPS vacuoles in many tissues of affected patients. We studied whether these characteristics could be used for the antenatal diagnosis of the disease. We obtained amniotic fluid cells from two pregnancies at risk for MPS I, one pregnancy at risk for GSD II (another lysosomal disease), and eight normal control pregnancies. Measurements of iduronidase activity in cultured amniotic fluid cells indicated the presence of a MPS I fetus in one high risk pregnancy and an unaffected fetus in the other. This diagnosis was confirmed at delivery. On electron microscopy the uncultured amniotic fluid cells exhibited MPS-like vacuoles in the pregnancy with a GSD II fetus, in three of eight normal pregnancies, and in the pregnancy at risk for MPS I that had a normal fetus. No such vacuoles were seen in the pregnancy with the MPS I fetus. These false positive and false negative findings indicate that antenatal diagnosis of MPS I cannot be based on the electron microscopic presence or absence of MPS I vacuoles in uncultured amniotic fluid cells.

Amniotic Fluid↗
PubMed1982

Alpha 1-antitrypsin phenotype: transient cathodal shift in serum of infant girl with urinary cytomegalovirus and fatty liver.

A 2-month-old white girl had severe liver disease (but without signs of hepatic necrosis, infection or cirrhosis), urinary cytomegalovirus, transient reduction of alpha 1-antitrypsin concentration and transient abnormal alpha 1-antitrypsin phenotype that were not present in her parents. Five serum specimens that were obtained during the 11/2 months of acute phase liver disease indicated, by polyacrylamide gel isoelectric focusing (PAG-IEF), acid starch gel and agarose electrophoresis as well as immunofixation, an unusual alpha 1-antitrypsin phenotype that we labeled delta (delta). It migrated adjacent to Z, i.e., cathodal of Z and Zpratt on PAG-IEF; anodal of Z but cathodal of X, S, Zpratt on starch gel. We labeled the girl's complete phenotype M delta. After clinical recovery, her phenotype was MM and identical to that of her parents. Hepatic electronmicroscopy of the acute phase specimen showed dilated bile canaliculi. We observed the following in hepatocytes: clusters of globular inclusions surrounded by myelin sheets that, to a lesser extent, also appeared in the liver of CMV-infected children with phenotype MM; dilated endoplasmic reticulum cisternae that contained floccular material; and marked steatosis. These changes were less severe in the convalescent liver specimen.

Cytomegalovirus↗
PubMed1981

Elevated serum 1,25 dihydroxyvitamin D concentrations in rickets of very low-birth-weight infants.

Elevated 1,25 dihydroxyvitamin D concentrations were found in five VLBW infants who developed rickets at two to three months postnatal age or term postconceptual age; 25 hydroxyvitamin D concentrations were low. Bone mineralization was found to be extremely low as measured by infant-adapted direct photon absorptiometry. After treatment with a formula supplemented with additional Ca and P, there was a rapid improvement in bone mineralization with a concomitant decrease of 1,25(OH)2D to normal adult values, whereas 250HD values increased and parathyroid hormone values decreased. In the VLBW infants studied, we suggest that rickets may be caused by Ca and P deficiency rather than by a deficiency of vitamin D metabolism.

Calcitriol↗
PubMed1981

Reye's syndrome simulacra in liver of mice after treatment with chemical agents and encephalomyocarditis virus.

In children with Reye's syndrome, liver specimens exhibit the following characteristics: mitochondrial dysfiguration, fatty infiltration, decreased activity of carbamyl phosphate synthetase and of ornithine transcarbamylase, histochemically reduced activity of succinic dehydrogenase and cytochrome oxidase, and depletion of glycogen. We intended to create an animal model for Reye's syndrome by treating mice with encephalomyocarditis virus, and/or salicylate, fructose, Atlox, butylated hydroxytoluene, pentachlorophenol, and an equal mixture of butylated hydroxytoluene and monosodium stearate. Liver specimens were then examined for the listed characteristics as well as for the activity of argininosuccinic lyase, arginase, phosphorylase, and glucose-6-phosphatase. Results of interest in regard to the experimental intention were obtained in livers of mice treated with virus and Atlox (A) or virus and butylated hydroxytoluene (B). In these specimens, we found a significant reduction (p less than 0.05)--except for ornithine transcarbamylase (A)--to the following levels (in percentage of normal mean): carbamyl phosphate synthetase (A, 79 per cent; B, 57 per cent); ornithine transcarbamylase (A, 91 per cent; B, 75 per cent); glycogen (A, 26 per cent; B, 37 per cent). Simultaneous morphologic analysis of these liver specimens indicated mitochondrial dysfiguration, absence of dense granules, fatty infiltration, and normal activity of succinic dehydrogenase and cytochrome oxidase. The induction of Reye's syndrome-like features in mouse liver may be useful for the study of disease mechanisms and therapy.

Animals↗