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Biomedical subjects

Ingemar Kjellmer

Publications and source records attributed to Ingemar Kjellmer.

15 recordsLinked to original sources

Sex differences in electrocortical activity in human neonates.

Cerebral cortical activity in healthy, full-term human neonates (10 boys and 10 girls) was evaluated using spectral estimation of electroencephalogram frequency content with new equipment and analysis technique allowing the assessment of the lowest frequencies (i.e. infraslow waves). The activity was analysed under quiet sleep and active wakefulness taking sex into consideration. During sleep, the mean amount of infraslow activity was 27% larger in boys, whereas during wakefulness the average amount of higher frequencies was 17% larger in girls. Both these differences indicate an earlier maturation of cortical function in girls than in boys.

Cerebral Cortex↗

Cytokines in the placenta of Pakistani newborns with and without intrauterine growth retardation.

Although intrauterine growth retardation (IUGR) is a major risk factor for increased neonatal mortality and morbidity, the mechanisms behind it are not clear. We analyzed cytokine gene expression and gene polymorphisms in infants with and without IUGR in Pakistan, where IUGR is very common. 45 IUGR and 55 control mother/infant pairs were studied. mRNA for IL-10, IL-8, TNF-alpha, TGF-beta, IL-6, IL-4, IL-1beta, IL-12, IFN-gamma and GAPDH was quantified with RT-PCR from placenta. Cytokine and cytokine receptor gene polymorphisms for -1087IL10, -308TNFA, -174IL6, +915TGFB1, intron 2 IL1RN, +36TNFR1, 150V IL4RA and -159CD14 were determined from genomic DNA. The serum levels of IL-1beta, IL-6, IL-8, IL-10, IL-12, TNF-alpha and TGF-beta were measured. There was a significant decrease of IL-10 and IL-12, but increase of TGF-beta in the decidua and similarly decrease of IL-10, but increase of TGF-beta in the trophoblasts of the IUGR placentas compared with the non-IUGR placentas. We found significantly lower levels of IL-1beta in serum from the mothers of the IUGR infants and of TGF-beta in serum of the infants with IUGR compared with the non-IUGR infants. We note that the IL-10 mRNA expression in the decidua was down-regulated, but the TGF-beta mRNA up-regulated in IUGR placentas of mothers from a population with multiple risk factors for IUGR. We propose that the low IL-10 in the placenta may be involved in the pathogenesis of IUGR and might possibly be treatable.

Base Sequence↗

Spectroscopy study of the dynamics of the transencephalic electrical impedance in the perinatal brain during hypoxia.

Hypoxia/ischaemia is the most common cause of brain damage in neonates. Thousands of newborn children suffer from perinatal asphyxia every year. The cells go through a response mechanism during hypoxia/ischaemia, to maintain the cellular viability and, as a response to the hypoxic/ischaemic insult, the composition and the structure of the cellular environment are altered. The alterations in the ionic concentration of the intra- and extracellular and the consequent cytotoxic oedema, cell swelling, modify the electrical properties of the constituted tissue. The changes produced can be easily measured using electrical impedance instrumentation. In this paper, we report the results from an impedance spectroscopy study on the effects of the hypoxia on the perinatal brain. The transencephalic impedance, both resistance and reactance, was measured in newborn piglets using the four-electrode method in the frequency range from 20 kHz to 750 kHz and the experimental results were compared with numerical results from a simulation of a suspension of cells during cell swelling. The experimental results make clear the frequency dependence of the bioelectrical impedance, confirm that the variation of resistance is more sensitive at low than at high frequencies and show that the reactance changes substantially during hypoxia. The resemblance between the experimental and numerical results proves the validity of modelling tissue as a suspension of cells and confirms the importance of the cellular oedema process in the alterations of the electrical properties of biological tissue. The study of the effects of hypoxia/ischaemia in the bioelectrical properties of tissue may lead to the development of useful clinical tools based on the application of bioelectrical impedance technology.

Animals↗

White matter injury following prolonged free radical formation in the 0.65 gestation fetal sheep brain.

Free radicals seem to be involved in the development of cerebral white matter damage after asphyxia in the premature infant. The immature brain may be at increased risk of free radical mediated injury, as particularly the preterm infant has a relative deficiency in brain antioxidants systems, such as superoxide dismutase and glutathione peroxidase. In vitro studies show that immature oligodendrocytes express an intrinsic vulnerability to reactive oxygen species and free radical scavengers are able to protect immature oligodendrocytes from injury. The aim of this study was to examine the formation of ascorbyl radicals as a marker of oxidative stress in the preterm brain in association with cerebral white matter injury after intrauterine asphyxia. Fetal sheep at 0.65 gestation were chronically instrumented with vascular catheters and an occluder cuff around the umbilical cord. A microdialysis probe was placed in the periventricular white matter. Fetal asphyxia was induced by occlusion of the umbilical cord for 25 min (n = 10). Microdialysis samples were collected for 72 h and analyzed for ascorbyl radicals using electron spin resonance. Five instrumented fetuses served as controls. Three days after the insult, fetal brains were examined for morphologic injury. Umbilical cord occlusion resulted in prolonged and marked increase in ascorbyl radical production in the brain in connection with white matter injury, with activation of microglia cells in periventricular white matter and axonal injury. These data suggest that reperfusion injury following asphyxia in the immature brain is associated with marked free radical production.

Animals↗

Electrocardiographic changes following umbilical cord occlusion in the midgestation fetal sheep.

BACKGROUND: Clinical studies show that analysis of the fetal electrocardiographic (FECG) ST waveform at term gives important information on the myocardial response to intrapartum asphyxia. However, it is not known whether the preterm fetus responds in a similar fashion. The objective of the present study was to evaluate the FECGST response to umbilical cord occlusion in the preterm fetal sheep. METHODS: Fetal sheep at midgestation were subjected to 25 min umbilical cord occlusion (n = 7) and compared to controls (n = 5). Changes in the FECGST waveform were recorded together with arterial blood pressure, heart rate, and acid base status during the occlusion and for 3 days afterward. RESULTS: Umbilical cord occlusion resulted in immediate bradycardia (control: 187 +/- 7 bpm versus occlusion: 102 +/- 7 bpm), hypertension (control: 43.2 +/- 1.1 mmHg versus occlusion: 59.8 +/- 2.2 mmHg), and an initial increase in the T/QRS ratio (control: 0.10 +/- 0.02 versus occlusion: 0.60 +/- 0.10, P < 0.001), followed by hypotension (21.7 +/- 1.2 mmHg), normalization of the T/QRS ratio, and in some cases the development of negative T waves toward the end of the occlusion. CONCLUSIONS: These studies show that the midgestation fetal sheep has the capacity to react to umbilical cord occlusion with a significant increase in the amplitude of the ST waveform together with an augmentation of blood pressure, which then subsides as the occlusion continues. The appearance of negative ST segment appears to signify significant cardiac dysfunction. The characteristic progression of ST-waveform changes in response to umbilical cord occlusion in midgestation fetal sheep, suggests that monitoring the ST waveform may contribute clinically important information also in the preterm individual.

Animals↗

Plasma 8-isoprostane is increased in preterm infants who develop bronchopulmonary dysplasia or periventricular leukomalacia.

Our aim was to assess the plasma free 8-epi-prostaglandin F(2alpha) (8-isoprostane) and ascorbyl radical as risk indicators for oxidative damage in extremely low birth weight infants (ELBWIs) and the effect of N-acetylcysteine (NAC) on these markers. Plasma samples were collected on days 3 and 7 of life from infants who were enrolled in a randomized, controlled trial in which i.v. NAC or placebo was administered to ELBWIs during the first week of life, with the aim of preventing bronchopulmonary dysplasia (BPD). Plasma 8-isoprostane was analyzed in 83 infants using an enzyme immunoassay kit. Ascorbyl radical concentration was measured in 61 infants with electron spin resonance spectroscopy. The 8-isoprostane concentrations were similar in the NAC and placebo groups. In infants who later developed BPD or died (n = 29), the median (range) 8-isoprostane concentration was significantly higher (p = 0.001) on day 3 and day 7 [50.0 pg/mL (19-360) and 57.0 pg/mL (14-460), respectively] than in survivors without BPD [n = 54; 34.5 pg/mL (5-240) and 39.5 pg/mL (7-400), respectively]. The 8-isoprostane levels increased significantly more (p < 0.05) in infants who later developed periventricular leukomalacia. NAC treatment or the later development of BPD was not related to the ascorbyl radical levels. The ascorbyl radical level decreased significantly in all groups from day 3 to day 7, but the difference between the groups was not significant. The mean (SD) ascorbyl radical level on day 3 was significantly higher (p < 0.01) in infants who later developed periventricular leukomalacia [287 (124) versus 194 (90)]. These data suggest that plasma 8-isoprostane could serve as a marker in assessing the risk for BPD development in ELBWIs.

Biomarkers↗

Visual evoked potentials in disproportionately growth-retarded human neonates.

To study brain function in the neonatal period, disproportionately growth-retarded (n = 33) and appropriately grown (n = 21) infants were examined using Doppler flow velocities prenatally and visual evoked potentials postnatally. Visual evoked potentials recordings were made at gestation of 40 and 46 weeks. The group of growth-retarded infants had significantly prolonged latencies to both of the two major peaks (designated P and N), most pronounced for the P peak. This result was observed at both ages investigated and corresponds to a developmental delay of 3 weeks. For individuals, the increase in P latency correlated to prenatal flow indices and to neonatal anthropometric parameters indicative of growth retardation. We conclude that in utero growth retardation affects brain development as assessed by visual evoked potentials in the neonatal period. This developmental delay may be produced by intracerebral factors during the process of growth retardation, and these alterations may have a prognostic value.

Anthropometry↗

Neuropsychological follow-up into young adulthood of term infants born small for gestational age.

BACKGROUND: The aim of the study was to investigate whether children born small for gestational age without other complications nor signs of neurological impairment or developmental delay before 18 months of age may display neuropsychological impairments later in life. MATERIAL/METHODS: Neuropsychological outcome, school achievement, and social adjustment in young adulthood (21-28 years of age) were investigated in a prospectively followed group of 17 children born small for gestational age (SGA) and compared with 30 controls born with appropriate weight. A questionnaire including items about highest education, present social situation, and self-estimation of health was conducted. A comprehensive neuropsychological assessment of the main aspects of cognitive function was performed in 12 young adults from the SGA group and compared with 18 subjects selected as normal controls. Intelligence, verbal functions, visuo-spatial and visuo-constructive functions, learning and memory of words and figures, attention, lateral preference, motor functions, and cognitive adaptive functions were investigated. RESULTS: The young adults born SGA displayed lower intelligence quotients, specifically reduced verbal comprehension and deficits in figurative learning and memory functions, compared with normal controls. No differences in educational achievement and social adjustment were found. Neither were any differences observed in maternal education levels. CONCLUSIONS: Infants born SGA display a reduced cognitive capacity at young adult age compared with controls. However, this lower capacity is not considered sufficiently severe to affect educational level or social adjustment.

Adult↗

White matter injury following systemic endotoxemia or asphyxia in the fetal sheep.

White matter injury is the most frequently observed brain lesion in preterm infants. The etiology remains unclear, however, both cerebral hypoperfusion and intrauterine infections have been suggested as risk factors. We compared the neuropathological outcome, including the effect on oligodendrocytes, astrocytes, and microglia, following either systemic asphyxia or endotoxemia in fetal sheep at midgestation. Fetal sheep were subjected to either 25 minutes of umbilical cord occlusion or systemic endotoxemia by administration of Escherichia coli lipopolysaccharide (LPS O111:B4, 100 ng/kg, IV). Periventricular white matter lesions were observed in 2 of 6 asphyxiated fetuses, whereas the remaining animals showed diffuse injury throughout the subcortical white matter and neuronal necrosis in subcortical regions, including the striatum and hippocampus. LPS-treatment resulted in focal inflammatory infiltrates and cystic lesions in periventricular white matter in 2 of 5 animals, but with no neuron specific injury. Both experimental paradigms resulted in microglia activation in the white matter, damaged astrocytes, and loss of oligodendrocytes. These results show that the white matter at midgestation is sensitive to injury following both systemic asphyxia and endotoxemia. Asphyxia induced lesions in both white and subcortical grey matter in association with microglia activation, and endotoxemia resulted in selective white matter damage and inflammation.

Animals↗

Fetal electrocardiography in labor and neonatal outcome: data from the Swedish randomized controlled trial on intrapartum fetal monitoring.

OBJECTIVE: Cardiotocography plus automatic ST analysis of the fetal electrocardiography has been shown recently to reduce both the operative delivery rate for fetal distress and the cord artery metabolic acidosis rate. The purpose of this study was to analyze findings that were related to cases with a complicated/adverse neonatal outcome in the Swedish randomized controlled trial. STUDY DESIGN: Of the 4966 term fetuses that were included in the trial, all 351 newborn infants who required special neonatal care were identified. Cases of perinatal death, neonatal encephalopathy, or metabolic acidosis at birth were reviewed. RESULTS: Of the 29 fetuses with adverse/complicated neonatal outcome, 22 fetuses had cardiotocography and ST patterns that indicated a need for intervention, according to the cardiotocography plus ST clinical guidelines. The number of live-born with moderate or severe neonatal encephalopathy showed a significant decrease from 0.33% (8/2447 fetuses) in the cardiotocography-only group to 0.04% (1/2519 fetuses) in the cardiotocography plus ST group. CONCLUSION: Cardiotocography plus ST analysis provides accurate information about intrapartum hypoxia and may prevent intrapartum asphyxia and neonatal encephalopathy by giving a clear alert to the staff members who are in charge.

Acidosis↗

Remote sessions and frequency analysis for improved insight into cerebral function during pediatric and neonatal intensive care.

A project involving recording and analysing EEG together with cardiovascular signals and temperature has been initiated. The aim of this project is to establish difficulties and possibilities involved with implementing a system for remote sessions and analysing EEG in correlation with other physiological signals. One objective is to find indicators of cerebral function during postasphyxia neonatal intensive care and pediatric cardiopulmonary bypass surgery with hypothermia. Remote sessions for joint interpretation have been carried out between pediatricians and clinical neurophysiologists, and EEG has been analyzed using frequency analyzing tools. One result is the discovery of reversible spectral changes coinciding with blood pressure falls, which may indicate loss of autoregulation function. This finding is one outcome from initial use of a system, developed during the project to facilitate communication about, and analysis of the recorded signals. Thus, already from a limited number of remote sessions and the use of basic signal processing techniques, important results have been achieved and better insight has been gained of how cerebral function is affected by cardiopulmonary bypass surgery. In this paper, we present our experiences from introducing a system for remote consultations, and evaluate the use for such a system in the current applications.

Algorithms↗

A simple and rapid method for the determination of "free" iron in biological fluids.

We present a convenient method for determining "free" or non-protein-bound iron in biological fluids. The new method is based on the bathophenantroline method for determination of total serum iron, and comprises binding of iron by a chromogenic chelator (bathophenantroline-disulphonate, BPS), which is specific for ferrous iron. The ferrous complex of BPS absorbs strongly at 535 nm, and the detection limit is less than 1 microM in a sample size of 50 microliters. The chelator does not liberate iron from either haemoglobin or transferrin. Interference from copper or zinc in concentrations up to 50 microM does not significantly disturb measurements. The main problem when measuring in blood plasma, the high and fluctuating background in the region around 535 nm, has been overcome through filtering techniques. Data from measurements of ferrous iron in microdialysate, cerebrospinal fluid, and blood plasma in different animal models and clinical conditions are presented as illustrative examples of the usefulness of the method. The method allows the determination of ferric, as well as ferrous, iron in the same sample.

Animals↗

Aberrations in placental cytokine mRNA related to intrauterine growth retardation.

During normal pregnancy, a predominance of Th2 type cytokines prevails and is considered to protect the fetus. Animal experiments suggest that an increase of Th1 type cytokines may instead have deleterious effects. We have studied with the reverse transcription PCR technique mRNA for IL-1alpha, IL-1beta, IL-6, IL-8, IL-10, transforming growth factor-beta, tumor necrosis factor-alpha, and interferon-gamma in placentas from full-term appropriately grown newborns, newborns with intrauterine growth retardation (IUGR) and newborns who were only small for gestational age. The mRNA for IL-10 was significantly reduced in the IUGR placentas (p < 0.05), whereas the mRNA for IL-8 was significantly higher (p < 0.05) for the IUGR cases compared with the full-term neonates. It might be that reduced IL-10 in the placenta is involved in the pathogenesis of IUGR.

Animals↗

Non-protein-bound iron in brain interstitium of newborn pigs after hypoxia.

Oxidative damage is implied in perinatal hypoxic-ischemic brain injury, most importantly in white matter. Nonprotein-bound iron (NPBI) catalyzes the formation of toxic hydroxyl radicals. We measured the extracellular level of NPBI through microdialysis in the cortex, striatum, and periventricular white matter before, during and after severe hypoxia in newborn pigs. NPBI was analyzed by a new spectrophotometric method in which ferrous iron is chelated by bathophenanthroline. NPBI was present in all brain areas under baseline conditions and increased in white matter from 0.97 (0.69) to 2.75 (1.85) micromol/l (not corrected for recovery rate) during early reoxygenation. NPBI may contribute to oxidative injury after perinatal hypoxic insults.

Animals↗