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Biomedical subjects

D H Hunneman

Publications and source records attributed to D H Hunneman.

At least 37 records · Page 2Linked to original sources
PubMed1995

Glyceroltrioleate/glyceroltrierucate therapy in 16 patients with X-chromosomal adrenoleukodystrophy/adrenomyeloneuropathy: effect on clinical, biochemical and neurophysiological parameters.

UNLABELLED: We have investigated the effect of glyceroltrioleate/glyceroltrierucate (GTO/GTE) therapy on X-chromosomal adrenoleukodystrophy in 16 patients with adrenoleukodystrophy (n = 6), adrenomyeloneuropathy (n = 3), Addison disease without neurological involvement (n = 2), and neurologically and endocrinologically asymptomatic patients (n = 5). Therapy was carried out for 19.4 +/- 10 months. All patients showed a normalization of C 26:0 plasma fatty acid concentrations. None of the seven neurologically asymptomatic patients developed neurological symptoms. Somatosensory evoked potentials of the tibialis nerve was the most sensitive electrophysiological parameter, showing a slight improvement in neurologically asymptomatic patients during therapy. In none of the patients with normal cranial MRI at start of therapy (n = 6) has MRI deterioration been observed whilst on therapy. Follow up of the neurologically asymptomatic children supports the hypothesis that GTO/GTE therapy might prevent the development of neurological symptoms. Six of the nine neurologically symptomatic patients deteriorated to varying degrees whilst on therapy. MRI alterations have worsened in all patients with clinical deterioration. CONCLUSION: GTO/GTE treatment should be initiated in all neurological asymptomatic boys before first neurological symptoms develop. To discover these patients very long-chain fatty acid determination should be performed in all family members at risk when adrenoleukodystrophy or adrenomyeloneuropathy is diagnosed.

Adolescent↗
PubMed1994

[Adrenomyeloneuropathy. A frequent cause of Addison's disease].

Adrenomyeloneuropathy (AMN) is a "milder form" of adrenoleukodystrophy with a X-linked inheritance. Abnormal catabolism of the very long-chain fatty acids (VLCFA) results in Addison's disease and spastic paraparesis. The VLCFA concentration was measured in 23 of 26 patients with Addison's disease (mean age 48.5 [20-75] years) being treated at the University Hospital Marburg during May, 1991. The concentration was elevated in four of the 12 men with the disease, while it was within normal limits in the 11 women. Only two patients had paraparesis-like neurological deficits. This finding suggests that AMN is not as rare as has been supposed. It is recommended that the concentration of VLCFA be measured in all patients with Addison's disease, because an increase could have important consequences.

Addison Disease↗
PubMed1993

Serial measurements of neuropeptide Y in plasma for monitoring neuroblastoma in children.

Neuropeptide Y (NPY) was studied as a marker for neuroblastoma in 12 children. All but one patient with neuroblastoma had elevated plasma NPY concentrations at diagnosis. During treatment NPY values returned to normal in 9 of 12 children. All three children without normalization of plasma NPY values died; two of them had a relapse and the third died of toxic effects. Plasma NPY appears to be a sensitive marker of neuroblastoma.

Adolescent↗
PubMed1992

Serum vanillylmandelic acid/homovanillic acid contributes to prognosis estimation in patients with localised but not with metastatic neuroblastoma.

In 211 patients with neuroblastoma, serum vanillylmandelic acid (VMA) and homovanillic acid (HVA) levels were determined and correlated to stage, histological differentiation, ferritin, neuron-specific enolase, lactate dehydrogenase (LDH) and outcome. Elevated serum VMA and/or HVA levels were found 16% less frequently than elevated urine levels. The incidence of the elevated serum levels increased with stage (stages I-III 58%, IV 78%, IVS 100%). Increased VMA/HVA ratios were not associated with a higher grade of tumour differentiation. Serum ferritin and neuron-specific enolase showed no correlation, and LDH a borderline non-random correlation with the serum catecholamine metabolites. Using age-related reference values a quotient of serum VMA/HVA (P = 0.061) < 0.7 indicated a poorer event-free survival (48 +/- 10%) than ratios > or = 0.7 (event-free survival 81 +/- 6%) for children with localised neuroblastoma (P = 0.0004). No correlation with prognosis was detected for patients with stage IV and stage IVS disease. We conclude that serum VMA and HVA determinations may be useful as tumour markers for 71% of neuroblastoma patients, and aid in estimating the prognosis in children with localised disease.

Biomarkers, Tumor↗
PubMed1991

Facts and artefacts in mevalonic aciduria: development of a stable isotope dilution GCMS assay for mevalonic acid and its application to physiological fluids, tissue samples, prenatal diagnosis and carrier detection.

A stable isotope dilution assay using D3-mevalonic acid was developed and applied to the study of mevalonic aciduria. The method also appears to be suitable for the evaluation of different therapeutic regimens in patients with hypercholesterolemia. Mevalonic acid was isolated by liquid partition chromatography and quantified as the underivatized lactone by means of ammonia chemical ionization selected ion monitoring capillary gas chromatography-mass spectrometry. In heterozygotes there was significantly greater urinary excretion of mevalonic acid, while the range of enzymatic activity of mevalonate kinase showed an overlap with that of controls. The analysis of amniotic fluids of two pregnancies at risk for mevalonic aciduria showed a 3277-fold elevation as compared to controls in the first case, diagnostic of an affected fetus, and a normal value in the second one. Mevalonic acid concentration was much increased in tissues of the affected and aborted fetus. Concentrations ranged from 840 to 1120 mumol/kg in various tissues and were as high as 1810 mumol/kg in brain. Concentrations in control fetal tissues were approximately 1 mumol/kg.

Adult↗
PubMed1991

Neuroblastoma screening: arguments from retrospective analysis of three German neuroblastoma trials.

The justification for a neuroblastoma screening program has been discussed controversially. The analysis of 701 patients of the German neuroblastoma trials NB 79, 82, and 85 provides additional information on this subject. The basis of our investigation was the good prognosis of stage I and II patients (92% survival 5-10 years after diagnosis) compared with 66% in stage III and 11% in metastatic disease. The correlation of age and stage (p less than 0.0001), a median progression time of 14.6 months (range 3.4-33.5 mo) from localized to metastatic disease as observed in 18 patients, the high incidence of asymptomatic diseases in stages I (49%) and II (30%) patients and the cost-benefit estimation arguments in favor of a screening program. The key problem for the lab part is the lower incidence of abnormal catecholamine metabolite excretion in stage I and II patients. The origin of 89% of metastatic disease from intraabdominal sites suggests that ultrasonography may be of additional value.

Abdomen↗
PubMed1991

Glutaryl-coenzyme A dehydrogenase deficiency: a distinct encephalopathy.

Clinical course, diagnostic and therapeutic management, and neurodevelopmental outcome were evaluated in 11 patients with glutaryl-coenzyme A dehydrogenase deficiency. In 9 patients macrocephalus was present at or shortly after birth and preceded the neurological disease. In 7 children an acute illness resembling encephalitis appeared after a period of normal development; 2 had developmental delay and progressive "dystonic cerebral palsy." Later, all 9 displayed typical signs of a disorder of the basal ganglia. In 1 patient with macrocephalus the disorder was diagnosed before the onset of neurological disease; in another it was diagnosed prenatally. Computed tomography and magnetic resonance imaging scans revealed severe generalized cerebral atrophy, most striking in the frontal and temporal lobes in 10 patients. Further deterioration was halted after initiation of treatment consisting of low-protein diets, special formulas low in lysine and tryptophan, and supplements of riboflavin and L-carnitine. Only 1 patient showed a slight clinical improvement. Later, dietary therapy was discontinued in 2 older patients and relaxed in a third without observed adverse effects. Two patients in whom treatment could be initiated before the onset of neurological symptoms have developed normally. However, duration of follow-up (6 and 29 months) does not yet allow classification of glutaryl-coenzyme A dehydrogenase deficiency as a treatable disorder. Total body production of glutaric acid, reflected in the daily urinary output, was efficiently reduced by therapeutic measures. Levels of glutaric acid in plasma and cerebrospinal fluid remained unchanged, which may in part explain the overall unsatisfactory outcome. All patients presented with a severe secondary deficiency of carnitine.(ABSTRACT TRUNCATED AT 250 WORDS)

Child, Preschool↗
PubMed1990

The surface to volume ratio of mitochondria, a suitable parameter for evaluating mitochondrial swelling. Correlations during the course of myocardial global ischaemia.

Cellular changes occurring in the left ventricular myocardium during ischaemia after different methods of cardiac arrest have been evaluated by morphological and morphometric parameters: volume densities of mitochondria (VVMi), sarcoplasm (VVSp), myofibrils (VVMf), surface densities of mitochondria (SVMi). The surface to volume ratio of mitochondria (SVratioMi) has been used as an independent parameter of mitochondrial swelling. Since ischaemic swelling of myocardial cells increases the volume of the reference space and ischaemic swelling of mitochondria decreases the free sarcoplasm, VVMi and VVSp cannot be considered as reliable indicators of the degree of oedema. SVMi/VVMf remains nearly constant after different forms of cardiac arrest, demonstrating the integrity of mitochondrial outer membranes. The inverse linear ratio between SVratioMi and the mean mitochondrial volume indicates that the increase in mitochondrial volume is achieved by surface smoothing. Loss of matrix structure and fragmentation of cristae occur at an SVratioMi of about 5.8, cristolysis at 5.5 to 5.6 and amorphous matrix densities at an SVratioMi of less than 5.5 micron2/micron3. The SVratioMi is a suitable parameter for evaluating mitochondrial swelling both at the onset and during global myocardial ischaemia, independent of the method of cardiac arrest used. It serves as an indicator of the state of structural preservation of mitochondria during ischaemia.

Animals↗
PubMed1989

Neonatal pyruvate dehydrogenase deficiency with lipoate responsive lactic acidaemia and hyperammonaemia.

A 2-day-old girl developed a severe lactic acidosis with a normal lactate/pyruvate ratio and hyperammonaemia. Plasma arginine and citrulline levels were below the limit of detection. In muscle total pyruvate dehydrogenase complex (PDHC) and pyruvate decarboxylase (E1) activities were reduced to a fraction of lower control values. The acute neonatal period was bridged with peritoneal dialysis, dichloroacetate therapy, supplements of arginine and branched chain amino acids, a complete vitamin B complex and lipoic acid. Lactate homeostasis responded to pharmacological supplements of lipoic acid. At age 1 year the child was hypotonic, showed severe developmental retardation, optic atrophy and cranial dysmorphism. She died aged 1 year 8 months with signs of respiratory paralysis but with normal lactate levels under assisted breathing. Pathological findings at autopsy were suggestive of Leigh syndrome, interstitial pneumonia and extensive fatty infiltration of hepatocytes. Regression analysis of data from 187 plasma amino acid determinations from the patient over a period of 1 year 8 months revealed a persistent-imbalance involving alanine, glutamic acid, glutamine, proline, citrulline and branched chain amino acids. Aspects of acute and long-term therapy in this patient and some implications of the imbalances in plasma amino acids are discussed.

Acidosis, Lactic↗
PubMed1987

The value of determination of homovanillic and vanillylmandelic acids in plasma for the diagnosis and follow-up of neuroblastoma in children.

The plasma levels of homovanillic and vanillylmandelic acids were determined in 84 children with neuroblastoma prior to treatment to evaluate the usefulness of these parameters for the diagnosis of this disease. Elevated levels of one or both of these metabolites were observed in 50% of children with Stage I or II disease, in 88% of those with Stage III, in 93% of those with Stage IV and in 100% of children with Stage IV-S for a total of 88% of all patients. The clinical course of the disease can be followed readily by determination of these metabolites, successful therapy or surgery being accompanied by a corresponding decrease in the plasma levels and relapse by a corresponding increase. Determination of homovanillic and vanillylmandelic acids in plasma can obviate many of the problems associated with the collection of urine, especially in young children or ambulant patients, and thus facilitates a more frequent control with consequent advantages for the management of this disease.

Child↗
PubMed1986

Importance of endogenous substrates for cultured adult rat cardiac myocytes.

In Ca-tolerant adult cardiomyocytes the contribution of endogenous substrates (glycogen, tri- and diacylglycerol) to oxidative substrate metabolism was investigated. After 4 h in culture medium (M 199 plus 4% fetal calf serum) the cellular triacylglycerol content is 3.6-fold higher than in fresh myocardium and reflects the free fatty acid composition of the medium. When triacylglycerol is degraded, all long-chain fatty acids are hydrolysed at equal rates. In these quiescent cells, the activity of pyruvate dehydrogenase is low (10% of full activity, in Tyrode solution with 5 mM glucose). Up to 30% of full pyruvate dehydrogenase activity, the contribution of non-lipid substrates (glycogen, glucose, lactate and pyruvate) to oxidative energy production is correlated to pyruvate dehydrogenase activity. At 5 mM medium concentration, glucose, lactate and pyruvate share in energy production the proportions of 15, 36 and 50%, whereas endogenous lipolysis accounts for 78, 61 and 46%. It is concluded that these quiescent cardiomyocytes represent cardiac metabolism in a basal state in which the preference for fatty acids, especially from endogenous lipids, is very pronounced. The utilization of endogenous substrates therefore has to be considered in all studies investigating the oxidative metabolism of these isolated cells.

Animals↗
PubMed1986

Effect of age on homovanillic and 4-hydroxy-3-methoxymandelic acid levels in plasma.

The plasma levels of homovanillic and 4-hydroxy-3-methoxymandelic acids have been determined in 524 normal subjects ranging from birth to 49 years of age using a mass fragmentographic method. The mean concentration of homovanillic acid in plasma declines exponentially from the age of 1 day (X = 2342.0 nmol/l, 426.6 ng/ml) to adulthood (X = 60 nmol/l, 10.9 ng/ml). 4-Hydroxy-3-methoxymandelic acid behaves in a similar although not so extreme manner (392 nmol/l, 77.6 ng/ml-50 nmol/l, 10 ng/ml).

Adolescent↗
PubMed1986

Carbohydrate and fatty acid metabolism of cultured adult cardiac myocytes.

The energy metabolism of exogenous and endogenous substrates was investigated in Ca-tolerant adult ventricular myocytes in short-term culture. CO2 production from exogenous glucose (5 mM), lactate (5 mM), and palmitate (100 microM) were 8, 20, and 29 mumol X h-1 X g wet wt-1. Endogenous lipolysis shared in energy production by 78, 61, and 31%, respectively. Fatty acids represented the main respiratory fuel even when 10(-7) M insulin, 5 mM lactate, or 5 mM dichloroacetate were supplied in addition to glucose. With palmitate, triglyceride contents were doubled within 3 h of cell incubation. With 5 mM glucose as sole exogenous substrate the energy turnover in these resting cells resembled that of arrested hearts, corresponding to 2 ml O2 X min-1 X 100 g wet wt-1. It is concluded that the basic features of substrate metabolism resemble those of the intact myocardium in that fatty acids represent the major fuel, but the contribution of endogenous lipolysis is greater than in the beating heart.

Animals↗
PubMed1985

Effectiveness of nicorandil in the preservation of myocardium stressed by transient ischemia and its influence on cardiac metabolism during coronary artery occlusion with subsequent reperfusion: a comparison with isosorbide dinitrate.

This study was designed to investigate the effects of nicorandil in comparison to isosorbide dinitrate (ISDN) on hemodynamics, on myocardial metabolism and on effectiveness in the preservation of ischemically stressed myocardium. Repeated ischemia (3 min) was produced in anaesthetized open-chest mongrel dogs by proximal, intermittent left anterior descending artery occlusion with subsequent reperfusion. In each experiment 2--3 control occlusions were compared to 2--3 occlusions under nicorandil or ISDN. Application of both nicorandil (0.64 mumol X kg-1 body weight, i.v.) and ISDN (1.27 mumol X kg-1 body weight, i.v.) led to a significant afterload reduction and to a decrease of the coronary vascular resistance. The efficiency of the compounds in the protection of ischemic myocardium was examined by quantification of oxygen-debt and oxygen-repayment in the occlusion and reperfusion periods. Compared to control, premedication with nicorandil led to a significant increase of oxygen-debt, whereas ISDN reduced it significantly. Oxygen-repayment remained unchanged. The influence of the drugs on the metabolism of glucose, lactate and free fatty acids (FFA) was examined under basic conditions, in ischemia and during reperfusion. For all substrates, extraction, extraction ratio and oxygen extraction ratio were calculated. Under basic conditions, glucose metabolism was significantly enhanced in both groups but FFA metabolism was inhibited only by ISDN. In ischemia, FFA metabolism was enhanced by nicorandil and depressed by ISDN.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Ornithine-containing lipids in Thiobacillus A2 and Achromobacter sp.

20 bacterial strains (corresponding to 16 species) were screened for ornithine lipids. Only two species (Thiobacillus A2 and Achromobacter sp.) turned out to contain ornithine lipids (2.71 mmol/100 g and 0.38 mmol/100 g bacterial dry weight, respectively). In both ornithine lipids, a 3-hydroxy fatty acid was amide-linked to the alpha-amino group of ornithine, a normal fatty acid was ester-linked to the 3-hydroxy group of the former. The predominant fatty acids were 18:1(11) and 3-hydroxy-20:1(13) in Thiobacillus A2, 16:0 and 3-hydroxy-18:1(11) in Achromobacter sp. All monounsaturated fatty acids (with one exception) belonged to the (n-7) family. 11, 12-Epoxy octadecanoic acid was identified among the ester-linked fatty acids of Thiobacillus A2. Phosphatidylcholine was the principal phospholipid in both bacterial species.

Alcaligenes↗