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Biomedical subjects

H C Lou

Publications and source records attributed to H C Lou.

At least 37 records · Page 2Linked to original sources
PubMed1997

Metabolic changes in the striatum after germinal matrix hemorrhage in the preterm infant.

To investigate the metabolic consequences of germinal matrix hemorrhage (GMH) we used volume-selective 1H magnetic resonance spectroscopy in the striatal region in 12 preterm infants with predominantly small GMH. Both sides of the brain were investigated twice. Metabolite indices were calculated as the metabolite signal, recorded with TR = 1.6 s and TE = 272 ms, divided by the fully relaxed water signal corrected for transverse relaxation time constant (T2) decay. At the first investigation, when the infants were 32.5 +/- 2.0 (mean +/- SD) wk postmenstrual age, the hemorrhage was unilateral or markedly asymmetrical in size in 10 of 12 infants. The lactate index was higher (p < 0.01) and the phosphocreatine + creatine (Cr) (p < 0.05) and N-acetyl-L-aspartate (NAA) (p < 0.05) indices lower in the side with the larger hemorrhage. At the second investigation, 54.1 +/- 2.7 wk postmenstrual age, no sign of a previous GMH could be seen on magnetic resonance imaging in three of 10 infants. Lactate could be detected in two of 10 infants only, and the Cr and NAA indices did not differ between sides. However, the choline index was significantly higher in the side with the larger hemorrhage (p < 0.01). We conclude that GMH is initially followed by lactate accumulation and possibly a delay in maturation as indicated by the transiently low Cr and NAA indices. Moreover, an increased choline index at the corrected age of 3 mo indicates a more persistent metabolic change after small GMH.

Cell Count↗
PubMed1996

[The significance of psychosocial stress for pregnancy course and fetal development].

In a population-based study, 3021 women in a central Copenhagen district received a questionnaire on environmental and psychological factors during mid-gestation. Of these, 70 women were selected consecutively on the basis of moderate to severe stressful life-events (DSM-III-R categories 3 to 5), in combination with an inadequate social network. They were compared with 50 non-stressed women with an intact social network. Stress and smoking significantly affected birthweight and head circumference. When birthweight was corrected, stress remained a significant determinant of small head circumference, indicating a specific effect on brain development. Stress also led to a suboptimal Prechtl neonatal neurological score. These findings suggest the existence of a fetal stress syndrome with adverse effects on fetal development, including deficient brain development.

Birth Weight↗
PubMed1996

Etiology and pathogenesis of attention-deficit hyperactivity disorder (ADHD): significance of prematurity and perinatal hypoxic-haemodynamic encephalopathy.

Attention-deficit Hyperactivity Disorder (ADHD), defined as a disorder of awareness with impulsivity, has lately been characterized as a dysfunction of the striatum (neostriatum = globus pallidus + putamen). This structure is in a unique position of contextual analysis and samples information samples information from almost the entire cortex through its spiny neurons. The etiology is heterogeneous, with genetic as well as lesional factors. Among the latter, pre- and perinatal events are prominent. Advances in the understanding of the role of fetal circulatory insufficiency with loss of autoregulation and systemic hypotension have drawn attention to the vulnerability of watershed regions, including the striatum. Not only circulatory facts are important for this selectivity, however. The anatomical characteristics, with convergent glutaminergic afferent synaptic transmission from almost the entire cortex contribute to the vulnerability in ischemia-induced liberation of glutamate: The striatum becomes the victim of its virtue. Repeated hypoxic-ischemic events are particularly common in prematurity, a fact which seems to explain the high incidence of ADHD in this patient group. The magnitude, of the problem is increasing with the increased survival rate among premature infants.

Animals↗
PubMed1996

Use of brain lactate levels to predict outcome after perinatal asphyxia.

Perinatal asphyxia is an important cause of neurological disability, but early prediction of outcome can be difficult. We performed proton magnetic resonance spectroscopy (MRS) and global cerebral blood flow measurements by xenon-133 clearance in 16 infants with evidence of perinatal asphyxia. Cerebral blood flow was determined daily in the first 3 days after birth in seven cases. Proton MRS was performed in 11 infants within the first week (mean 3.7 days), the rest within the first month (mean 22.2 days), and all had a scan around 3 months of age. Four infants died neonatally, three showed neurological deficits and the rest seemed to be progressing normally at neurodevelopmental follow-up at 1 year of age. A significant correlation was found between initial brain lactate levels and severe outcome (p = 0.0003) just as between cerebral hyperperfusion (mean cerebral blood flow (CBF) 86 ml(100 g)-1 min-1), (p = 0.02) and outcome. The diagnostic and prognostic implications of early MRS and CBF are predictive of poor outcome in severely asphyxiated infants.

Asphyxia Neonatorum↗
PubMed1996

Cerebral glucose metabolism is decreased in white matter changes in patients with phenylketonuria.

Cerebral magnetic resonance imaging (MRI) has revealed white matter changes in patients with phenylketonuria (PKU), an inborn error of metabolism with increased plasma phenylalanine level. Because the significance of these lesions is unknown, this study was undertaken to determine whether glucose metabolism was depressed in cerebral white matter MRI changes in patients with PKU. Four patients with PKU and nine healthy volunteers with an average age of 23 y (range 19-26 y) and 23 y (range 20-27 y), respectively, were studied. The IQ of patients with PKU was between 58 and 97. Cerebral MRI and positron emission tomography images with 18F-deoxyglucose were obtained, and arteriovenous differences for oxygen and glucose as well as cerebral blood flow was measured simultaneously to determine global cerebral oxygen and glucose metabolism. Cerebral MRI revealed that all patients with PKU had white matter changes with characteristic localization. In patients with PKU, regional glucose metabolism was 36% lower in the anterior periventricular areas, 0.14 +/- 0.06 compared with 0.22 +/- 0.04 mumol.g-1.min-1 in controls (mean +/- SD, p < 0.05, Mann-Whitney). Further, the ratio between glucose metabolism in the affected white matter and the cortex was 14% lower in the patients, decreasing from 0.57 +/- 0.05 to 0.48 +/- 0.06 (p < 0.05). Global cerebral blood flow, oxygen and glucose consumption were similar in the two groups. In conclusion, regional glucose metabolism is lower in MRI-demonstrated white matter changes. In mildly intellectually impaired patients with PKU, global cerebral glucose and oxygen metabolism remain intact.

Adult↗
PubMed1996

Intrauterine growth retardation and premature delivery: the influence of maternal smoking and psychosocial factors.

OBJECTIVES: This study investigated the influence of psychosocial stress, maternal schooling, social support, psychological well-being, alcohol, and smoking on intrauterine growth retardation and premature delivery. METHODS: At a Copenhagen university hospital, 2432 pregnant women completed a questionnaire on general health, psychosocial stressors, and sociodemographic characteristics. RESULTS: In 212 cases (8.7%) the women delivered prematurely. Preterm delivery as associated with psychosocial stress (adjusted odds ratio [OR]=1.14 for each 1-point increase on the psychosocial stressor 5-point scale and 1.92 for the whole scale) and poor school education (adjusted OR=2.62 for 7-9 years of schooling, 1.91 for 10 years, and 1.0 for 11-13 years). In 152 cases (6.3%), infants had a birthweight below the 10th percentile. Intrauterine growth retardation was associated with smoking, daily drinking, school education, and social network variables. In a multiple logistic regression model, intrauterine growth retardation was associated with smoking habits (adjusted OR=2.40 for 0-9 cigarettes daily, 2.68 for 10-15 daily, and 2.88 for more than 15 daily). CONCLUSIONS: Psychosocial stressors and limited duration of schooling appeared to influence preterm delivery. Smoking habits influenced intrauterine growth retardation.

Adult↗
PubMed1995

Volumetric analysis of the normal infant brain and in intrauterine growth retardation.

Twenty-eight infants with postmenstrual ages (PMA) in the range of 32-80 weeks were investigated. Twenty were newborn; among these the observed birth weight divided by the expected weight ranged from 0.31 to 1.1. Axial magnetic resonance images were recorded with a triple spin-echo sequence and the volumes were determined by encircling each structure of interest on every slice. Segmentation into grey matter, white matter and CSF was done by semi-automatic discriminant analysis. Growth charts for the cerebrum, cerebellum, corpora striata, thalami, ventricles, and grey and white matter are provided for infants with appropriate birth weight. The striatal (P = 0.02) and thalamic (P < 0.001) percentage of the hemispheric volume decreased with age, whereas the ratio of grey matter to white matter (G/W-ratio) increased (P = 0.01). In the neonatal patients, brain volumes were independently associated with both PMA and the degree of growth retardation. It was calculated that the hemispheric volume was reduced by from 16% to 23% if the total bodyweight was reduced by 40%. The G/W-ratio was found to be independently associated with the PMA (P < 0.05) and the degree of IUGR (P < 0.1) suggesting that fetal growth retardation reduces grey matter volume more than white matter.

Birth Weight↗
PubMed1995

Local vascular CO2 reactivity in the infant brain assessed by functional MRI.

The local cerebral vascular response to hyperventilation was investigated in five distressed, intubated infants by means of a T2 sensitive gradient-echo MRI technique at 1.5 T. In one preterm infant, the MR signal change during hyperventilation was sparse. In four term infants, the mean MR signal of the brain slice investigated decreased by 1.2-2.6% per kPa change in PCO2 as a reflection of decreased cerebral blood flow during hyperventilation. Pixel-wise analysis revealed absence of vascular response in the basal ganglia, the thalamus or in the occipital region. In two adult controls, who hyperventilated voluntarily, the vascular reactivity was homogeneously distributed predominantly over the grey matter. The experiments demonstrate that local impairment of vascular CO2 reactivity in the distressed infant brain can be detected by T2 sensitive gradient-echo MRI, which is also known as functional MRI.

Adult↗
PubMed1995

In vivo assessment of mutations in the phenylalanine hydroxylase gene by phenylalanine loading: characterization of seven common mutations.

UNLABELLED: Mutations in the gene encoding phenylalanine hydroxylase (PAH) cause persistent hyperphenylalaninaemia. To date, more than 200 point mutations and microdeletions have been characterized. Each mutation has a particular quantitative effect on enzyme activity and recessive expression of different mutant alleles results in a marked interindividual heterogeneity of metabolic and clinical phenotypes. In this paper we demonstrate how a simple clinical test can be used to evaluate the correlation between mutation genotype and phenylalanine metabolism. In hyperphenylalaninaemic patients with known PAH mutation genotype, we have investigated phenylalanine turnover in vivo by measuring the ability to eliminate a test dose of L-phenylalanine. All patients could be considered functionally hemizygous for one of their mutant alleles by carrying on the other allele a mutation that is known to completely abolish PAH activity and encode a peptide with no immunoreactivity. Seven mutations (R408W, IVS-12nt1, R261Q, G46S, Y414C, A104D, and D415N) were characterized by oral phenylalanine loading, each mutation being represented by at least three patients. The elimination profile determined for a 3-day period provides a measure to compare residual activity of the mutant proteins and to assign each mutation to a particular metabolic phenotype. The established relation between genotype and phenotype may enable prediction of the severity of the disease by genotype determination in the newborn period. This will aid in the management of hyperphenylalaninaemia and may improve prognosis. CONCLUSION: The possibility of predicting the residual enzyme activity by DNA analysis performed already in the newborn period allows the prompt implementation of a diet that is adjusted to the degree of PAH deficiency. This may improve management and prognosis of hyperphenylalaninaemia.

Alleles↗
PubMed1995

Brain lactate in preterm and growth-retarded neonates.

Glucose is the predominant cerebral energy source under physiological conditions, although other substrates may support cerebral metabolism. The present study was undertaken to determine if lactate is present in the immature human brain, and if so, whether or not concentrations of lactate differ between small-for-gestational-age and appropriate-for-gestational-age infants. Thirty stable, healthy infants with normal brains were investigated. As the only nutrient, all received milk enterally prior to the investigation, which was carried out without sedation. Mean gestational age was 35 completed weeks (range 28-41 weeks) and mean birth weight was 2170 g (range 855-4100 g). Proton nuclear magnetic resonance spectra from the striatal region were obtained while the infants were sleeping quietly. Lactate was present in all 10 preterm small-for-gestational-age and 10 of 13 preterm appropriate-for-gestational-age infants, and the concentration was inversely related to postmenstrual age (p < 0.002). In addition, lactate increased with the degree of growth retardation (p < 0.01). At present the significance of lactate is unclear. Lactate may be produced locally or in peripheral tissues, and may support brain metabolism.

Brain↗
PubMed1994

Brain magnetic resonance imaging in children with optimally controlled hyperphenylalaninaemia.

This study was undertaken to investigate whether the white-matter changes on MRI and the EEG abnormalities detectable in treated adolescents and adults with hyperphenylalaninaemia (HPA) can be detected in younger children on an optimally controlled diet. The study included 17 children, 7-12 years of age, with HPA. The MRI of five healthy children were included in the blind evaluation of the MR images. According to mutation genotype and dietary tolerance of phenylalanine, 9 patients have severe HPA and 8 have moderate HPA, all requiring dietary treatment. Mild white-matter hyperintensity was detected in 1 of the 5 healthy children and in 10 of 17 patients. EEG was abnormal in 2 patients. This group of children was compared with a previously reported group of adolescents with HPA who had been treated according to the same dietary regimen. MRI changes and EEG abnormalities were significantly less frequent in the group of children than in the group of adolescents. It is suggested that the more frequent MRI changes and EEG abnormalities seen in adolescents are related to the fact that a relaxation of the dietary treatment after the age of 8 years is often accepted.

Adolescent↗
PubMed1994

Prenatal stressors of human life affect fetal brain development.

In a population-based study, 3021 women in a central Copenhagen district received a questionnaire on environmental and psychological factors during mid-gestation. Of these, 70 women were selected consecutively on the basis of moderate to severe stressful life-events (DSM-III-R categories 3 to 5), in combination with an inadequate social network. They were compared with 50 non-stressed women with an intact social network. Stress and smoking significantly affected birthweight and head circumference. When birthweight was corrected, stress remained a significant determinant of small head circumference, indicating a specific effect on brain development. Stress also led to a suboptimal Prechtl neonatal neurological score. These findings suggest the existence of a fetal stress syndrome with adverse effects on fetal development, including deficient brain development.

Brain↗
PubMed1994

Dopamine precursors and brain function in phenylalanine hydroxylase deficiency.

Phenylalanine and tyrosine constitute the two initial steps in the biosynthesis of dopamine, which, in its turn, is the metabolic precursor of noradrenaline and adrenaline. The extracellular phenylalanine concentration influences brain function in phenylalanine deficiency (PHD) by decreased dopamine synthesis. It has been shown to induce EEG slowing, and prolonged the performance time on neuropsychological tests. The tyrosine concentration in the CNS is reduced in PHD, possibly implying insufficient substrate (= tyrosine) for catecholamine synthesis due to competition inhibition, for instance across the blood brain barrier. In experimental studies it has been shown that the synthesis and release of dopamine can be influenced by an increase in the availability of tyrosine. In PHD an extra dietary intake of three doses of tyrosine (160 mg/kg/24h) induced a shortening of reaction time and decreased variability, and in a double-blind crossover study a similar dose has been reported to induce an improvement on psychological tests. In a study with lower doses of tyrosine (110 mg/kg/24 h) no effect was found on reaction time tests. These findings need to be substantiated, and more detailed information should be obtained.

Brain Chemistry↗
PubMed1993

Magnetic resonance imaging in juvenile Canavan disease.

We present a 2-year-old boy and a 6-year-old girl with mild Canavan disease (CD). Aspartoacylase activity in skin fibroblasts was deficient. Magnetic resonance imaging (MRI) of the brain did not show the prominent leucodystrophy previously reported in CD, but there was a hyperintense signal from the lentiform nuclei and the heads of the caudate nuclei on the T2-weighted MR images. This suggests a specific vulnerability of the corpus striatum in these patients. In the older patient, the white matter became affected at the age of 6 years. Proton magnetic resonance spectroscopy (1H-MRS) of white matter revealed a normal concentration of N-acetyl-L-aspartate (NAA) and a markedly decreased concentration of choline containing compounds (Cho) in the boy but a normal ratio of NAA to Cho in the girl. We conclude that deficient NAA catabolism affects myelin metabolism. This may present as changes in the striatum and/or as a low concentration of Cho before leucodystrophy appears on MRI.

Amidohydrolases↗
PubMed1993

Nitric oxide does not act as a mediator coupling cerebral blood flow to neural activity following somatosensory stimuli in rats.

The possible role of nitric oxide (NO) on vibrissa-stimulated increase of regional cerebral cerebral blood flow (rCBF) and cerebral metabolic rate of glucose (rCMRglu) was investigated in conscious Wistar rats by using an inhibitor of NO synthase, NG-nitro-L-arginine (NOLAG) at a concentration of 30 mg/kg. In vivo autoradiography distribution with 14C-iodoantipyrine and 14C-deoxyglucose in two separate series showed CBF of 174% of control and CMRglu of 196% of control in the primary sensory cortex opposite the stimulated side in saline treated control animals. Similar increases were found in NOLAG-treated animals. Furthermore, NOLAG did not change either basal CMRglu or CMRO2. The findings suggest, that NO is not involved in coupling flow to the increased metabolism accompanying physiological sensory stimuli.

Animals↗