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Biomedical subjects

H C Lou

Publications and source records attributed to H C Lou.

At least 19 recordsLinked to original sources
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↗
PubMed1992

An occipito-temporal syndrome in adolescents with optimally controlled hyperphenylalaninaemia.

The study included 16 adolescents with optimally controlled hyperphenylalaninaemia (McKusick 26160), of whom six did not require treatment according to conventional criteria. All except the two patients with lowest median serum phenylalanine level throughout childhood (most values at 200-300 mumol/L) had white matter abnormalities detectable with magnetic resonance imaging. The lesions were particularly prominent in the watershed regions between the posterior and middle cerebral arteries. In most patients with moderate or severe hyperphenylalaninaemia frontal white matter lesions were present as well. Normal proton magnetic resonance spectra indicated that the lesions were stable. Occipital EEG abnormalities were frequent, and deficient performance on a pattern-recognition test was a characteristic neuropsychological finding. Serum phenylalanine levels at about 300 mumol/L or below throughout childhood and early adolescence may be required to avoid lesions. The present study demonstrates the limitations of even an optimally controlled dietary regimen in hyperphenylalaninaemia.

Adolescent↗
PubMed1992

Low CSF HVA levels in the Rett syndrome: a reflection of restricted synapse formation?

The concentration of neurotransmitter metabolites in the CSF was determined in 10 girls with the Rett syndrome (RS) (age range 5.8-17.2) and in 14 control children (age range 4.5-16.7) treated for acute leukemia without signs of CNS involvement. Homovanillic acid concentration decreased with age in both groups. The decrease was less steep in RS compared to controls, with lower concentrations in young girls and normal concentrations at 15 years of age. 5-hydroxyindoleacetic acid decreased proportionally in both groups. It is suggested that the low concentration of HVA in young girls reflect deficient multiplication of catecholaminergic synapsis.

Adolescent↗
PubMed1990

Focal cerebral dysfunction in developmental learning disabilities.

In 24 children with developmental learning disabilities and 15 age-matched controls regional cerebral activity was studied with xenon-133 single photon emission tomography. In the 9 children with pure attention deficit and hyperactivity disorder (ADHD), the distribution of regional cerebral activity was abnormal--low in striatal and posterior periventricular regions and high in occipital regions. Low activity in striatal and posterior periventricular areas was also seen in the 8 children with ADHD in combination with phonologic-syntactic dysphasia. 7 children with dysphasia, but without hyperactive behaviour, had low cerebral activity in left temporofrontal regions.

Adolescent↗
PubMed1990

Biochemical and clinical effects of tyrosine and tryptophan in the Rett syndrome.

In the Rett syndrome (RS), a progressive encephalopathy affecting girls, deficient neurotransmitter synthesis has been suggested as a pathogenetic mechanism. Nine girls with RS were treated with 0.3 g of tyrosine and 0.1 g of tryptophan per kg body weight for 2 to 17 weeks. This resulted in a median rise in the spinal fluid concentration of the dopamine metabolite homovanillic acid by 31%, and of the serotonin metabolite 5-hydroxyindoleacetic acid by 40%. This finding supports the hypothesis of a compromised neurotransmitter synthesis and indicates that it can be stimulated by supply of amino acid precursors. A double-blind cross-over trial including 11 girls did not show clinical improvement during a treatment period of 8 to 10 weeks.

Adolescent↗
PubMed1989

Striatal dysfunction in attention deficit and hyperkinetic disorder.

We have previously reported that periventricular structures are hypoperfused in attention deficit and hyperactivity disorder (ADHD). This study has expanded the number of patients, who were divided into two groups: six patients with pure ADHD, and 13 patients with ADHD in combination with other neurologic symptoms. By using xenon 133 inhalation and emission tomography, the regional cerebral blood flow distribution was determined and compared with a control group. Striatal regions were found to be hypoperfused and, by inference, hypofunctional in both groups. This hypoperfusion was statistically significant in the right striatum in ADHD, and in both striatal regions in ADHD with other neuropsychologic and neurologic symptoms. The primary sensory and sensorimotor cortical regions were highly perfused. Methylphenidate increased flow to striatal and posterior periventricular regions, and tended to decrease flow to primary sensory regions. Low striatal activity, partially reversible with methylphenidate, appears to be a cardinal feature in ADHD.

Attention Deficit Disorder with Hyperactivity↗
PubMed1989

Intellectual impairment with regional cerebral dysfunction after low neonatal cerebral blood flow.

12 children, in whom neonatal CBF had been measured, were examined at the age of 9 to 10 years by means of clinical neurological examination, neuropsychologic tests and observations, and 133Xe single photon emission computed tomography (SPECT). Performance on most neuropsychologic tests or observations correlated with neonatal CBF but only rarely with other neonatal parameters (birthweight, gestational age, Apgar score at 5 min). Poor performance on each test or observation was in most instances correlated with a distinct pattern of regional cerebral dysfunction as assessed by SPECT. The dysfunctional region tended to be located periventricularly and in the watershed regions between major cerebral arteries. It is concluded that low neonatal cerebral perfusion may be an indicator, and possibly a determinant, of later intellectual dysfunction in stressed neonates, and that specific neuropsychologic deficits are associated with specific patterns of cerebral dysfunction in the present patient group.

Brain Diseases↗
PubMed1989

Endogenous opioids may protect the perinatal brain in hypoxia.

Endogenous opioids are released in great amounts in perinatal asphyxia. The role of this release has been unclear. In a study of cerebral blood flow and oxygen metabolism in 5 hypoxic newborn lambs, naloxone blocking of opioid receptors resulted in a proportional increase in telencephalic cerebral blood flow and oxygen metabolism. It is suggested that endogenous opioid release protects the neonatal brain in hypoxia by diminishing the cerebral metabolic rate of oxygen.

Animals↗