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Biomedical subjects

T E Inder

Publications and source records attributed to T E Inder.

At least 19 recordsLinked to original sources
PubMed2005

Insights into the acute cerebral metabolic changes associated with childhood diabetes.

AIMS: Type 1 diabetes is a prevalent chronic disease in childhood with the commonest single cause of death being cerebral oedema in the context of diabetic ketoacidosis (DKA). The nature of the alterations in cerebral metabolism that may result in vulnerability to neuronal injury remains unknown. The aim of this study was to analyse the magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) brain data from eight children with diabetes following acute presentation with hyperglycaemia with or without ketoacidosis, to determine the nature and timing of any alterations in cerebral structure and metabolism. METHODS: This study used MRI and MRS to investigate regional cerebral abnormalities in a small series of diabetic patients with and without DKA. Changes were compared with the clinical and biochemical features of the patients studied. RESULTS: Our small series of patients all demonstrated abnormal signal changes in the frontal region on fluid attenuated inversion recovery (FLAIR) MR imaging, suggestive of oedema, and spectroscopic abnormalities of increased taurine, myoinositol and glucose levels. The MR abnormalities varied in severity but did not correlate with any clinical or biochemical parameters. CONCLUSIONS: These changes indicate that many diabetic children, particularly at presentation, may have alterations in cerebral metabolism with implications for the pathogenesis and treatment of the cerebral complications of DKA. In addition, our findings suggest that increased taurine may be one of the important differentiating factors in the response of the brain of diabetic children to DKA that may reflect an increase in their vulnerability to cerebral oedema compared with diabetic adults.

Adolescent↗
PubMed2003

Assessment of the impact of the removal of cerebrospinal fluid on cerebral tissue volumes by advanced volumetric 3D-MRI in posthaemorrhagic hydrocephalus in a premature infant.

Current clinical practice in the premature infant with posthaemorrhagic ventricular dilatation (PHVD) includes drainage of cerebrospinal fluid (CSF). This case study used advanced volumetric three dimensional magnetic resonance imaging to document the impact of CSF removal on the volume of regional brain tissues in a premature infant with PHVD. The removal of a large volume of CSF was associated with an identical reduction in CSF volume, but more dramatically with a significant increase in the regional volumes of cortical grey matter and myelinated white matter. The alterations in cerebral cortical grey matter and myelinated white matter volumes may provide insight into the established association of PHVD with deficits in cognitive and motor functions.

Brain↗
PubMed2002

Posthaemorrhagic ventricular dilatation in the premature infant: natural history and predictors of outcome.

OBJECTIVE: To investigate the natural history and predictors of outcome of posthaemorrhagic ventriculomegaly in the very low birthweight (VLBW) infant. METHODS: All VLBW infants admitted between September 1994 and September 1997 to the neonatal intensive care units of Brigham and Women's Hospital (Boston), Children's Hospital (Boston), and Christchurch Women's Hospital (New Zealand) with germinal matrix intraventricular haemorrhage (IVH) were identified. All charts and ultrasound scans were reviewed to define the natural history and perinatal and/or postnatal factors of value in prediction of the course of posthaemorrhagic ventriculomegaly. Progressive ventricular dilatation (PVD) was defined from the results of serial cranial ultrasound scans. RESULTS: A total of 248 VLBW infants had evidence of IVH (22% of all VLBW infants, mean (SD) gestational age 26.8 (2.6) weeks). A quarter of the infants exhibited PVD. Spontaneous arrest of PVD occurred without treatment in 38% of infants with PVD. Of the remaining 62% with persistent PVD, 48% received non-surgical treatment only (pharmacological and/or drainage of cerebrospinal fluid by serial lumbar punctures), 34% received surgical treatment with insertion of a ventriculoperitoneal reservoir and/or shunt, and 18% died. The development of PVD after IVH and adverse short term outcome, such as the requirement for surgery, were predicted most strongly by the severity of IVH. CONCLUSIONS: These data reflect the natural history of PVD in the 1990s and show that, despite a slight reduction in its overall incidence, there appears to be a more aggressive course, with appreciable mortality and morbidity in the extremely premature infant. The major predictor of adverse short term outcome, defined as death or need for surgical intervention, was the severity of IVH. These findings may be valuable for the management of very small premature infants.

Boston↗
PubMed2001

Magnetic resonance techniques in the evaluation of the perinatal brain: recent advances and future directions.

Magnetic resonance (MR) techniques are attractive for use in the developing brain because of their resolving power and their relative noninvasiveness. Their ability to provide detailed structural as well as metabolic and functional information without the use of ionizing radiation is unique. Conventional MR Imaging has widely proven its potential for identifying normal and pathologic brain morphology. Functional MR imaging such as diffusion-weighted imaging (DWI) and perfusion and blood-oxygenation-dependent BOLD imaging are newer imaging methods providing insights into brain physiology. This review will focus on the application of different MR techniques including the conventional structural MR imaging techniques and the more advanced MR techniques, such as the quantitative morphometric MR methods, the diffusion weighted MR techniques, the functional MR techniques and MR spectroscopy in the study of the fetal and newborn brain.

Brain↗
PubMed2001

Impaired cerebral cortical gray matter growth after treatment with dexamethasone for neonatal chronic lung disease.

OBJECTIVE: The specific aim of this study was to quantify at term the influence of postnatal systemic dexamethasone treatment for neonatal chronic lung disease on subsequent brain growth and development in premature infants without evidence of severe intraventricular hemorrhage or white matter injury. METHODS: Eighteen premature (23 to 31 weeks) infants, 7 treated with dexamethasone and 11 not treated, were studied at term, ie, 38 to 41 postconceptional weeks, by an advanced quantitative volumetric 3-dimensional magnetic resonance imaging (MRI) technique to quantify cerebral tissue volumes. Fourteen healthy term infants also were studied for comparison. A sequence of image processing algorithms was used to segment each of the MRI slices into the following separate tissue classes: cerebral cortical gray matter, basal ganglia/thalami, unmyelinated white matter, myelinated white matter, and cerebrospinal fluid, all classified based on magnetic resonance signal intensity and anatomic location. A final summing of voxels for each tissue class was performed to compute absolute volumes in milliliters. RESULTS: Cerebral cortical gray matter volume in premature infants treated with dexamethasone was reduced 35% when compared with gray matter volume in premature infants not treated with dexamethasone (mean +/- standard deviation, 130.3 +/- 54.0 vs 200.6 +/- 35.1 mL, respectively). Subcortical gray matter volumes (basal ganglia and thalami) and myelinated and unmyelinated white matter volumes were not significantly different among the treated and untreated groups. However, premature infants treated with dexamethasone exhibited a reduction (30%) in total cerebral tissue volume compared with total cerebral tissue volume in both the premature infants not treated with dexamethasone and the control term infants (312.7 +/- 43.7 vs 448.2 +/- 50.2 and 471.6 +/- 36.4 mL respectively). This latter finding relates primarily to the decrease in cerebral cortical gray matter volume. CONCLUSIONS: The data suggest an impairment in brain growth, principally affecting cerebral cortical gray matter, secondary to systemic dexamethasone therapy. Although the premature infants who received dexamethasone were smaller with more severe respiratory disease, these findings are consistent with growing evidence of a potential deleterious effect of dexamethasone on neonatal brain and subsequent neurodevelopmental outcome. This apparent deleterious effect should be taken into consideration by clinicians when weighing the potential risks and benefits of this therapy for low birth weight infants with neonatal chronic lung disease.

Case-Control Studies↗
PubMed2001

Microstructural brain development after perinatal cerebral white matter injury assessed by diffusion tensor magnetic resonance imaging.

OBJECTIVE: Brain injury in premature infants is characterized predominantly by perinatally acquired lesions in the cerebral white matter (WM). The impact of such injury on the subsequent development of cerebral WM is not clear. This study uses diffusion tensor magnetic resonance imaging (MRI) to evaluate the effects of cerebral WM injury on subsequent microstructural brain development in different WM areas of the brain. METHODS: Twenty premature infants (gestational age: 29.1 +/- 1.9 weeks) were studied by conventional MRI within the first 3 weeks of life and again at term, with the addition at the latter time of diffusion tensor MRI. Ten of the preterm infants had cerebral WM injury identified by the early MRI and were matched with 10 premature infants of similar gestational age and neonatal course but with normal neonatal MRI scans. Diffusion tensor MRI at term was acquired in coronal and axial planes and used to determine the apparent diffusion coefficient, a measure of overall restriction to water diffusion, and the relative anisotropy (RA), a measure of preferred directionality of diffusion, in central WM, anterior frontal WM, occipital WM, temporal WM, and the posterior limb of the internal capsule. Diffusion vector maps were generated from the diffusion tensor analysis to define the microstructural architecture of the cerebral WM regions. RESULTS: At term, the diffusion tensor MRI revealed no difference in apparent diffusion coefficient among preterm infants with or without perinatal WM lesions. By contrast, RA, the measure of preferred directionality of diffusion and thereby dependent on development of axonal fibers and oligodendroglia, was 25% lower in central WM, the principal site of the original WM injury. However, RA was unaffected in relatively uninjured WM areas, such as temporal, anterior frontal, and occipital regions. Notably, RA values in the internal capsule, which contains fibers that descend from the injured cerebral WM, were 20% lower in the infants with WM injury versus those without. Diffusion vector maps showed striking alterations in the size, orientation, and organization of fiber tracts in central WM and in those descending to the internal capsule. CONCLUSIONS: Perinatal cerebral WM injury seems to have major deleterious effects on subsequent development of fiber tracts both in the cerebral WM and more distally. The ultimate impact of brain injury in the newborn should be considered as a function not only of tissue destruction, but also of impaired subsequent brain development.

Humans↗
PubMed2000

In vivo studies of brain development by magnetic resonance techniques.

Understanding of the morphological development of the human brain has largely come from neuropathological studies obtained postmortem. Magnetic resonance (MR) techniques have recently allowed the provision of detailed structural, metabolic, and functional information in vivo on the human brain. These techniques have been utilized in studies from premature infants to adults and have provided invaluable data on the sequence of normal human brain development. This article will focus on MR techniques including conventional structural MR imaging techniques, quantitative morphometric MR techniques, diffusion weighted MR techniques, and MR spectroscopy. In order to understand the potential applications and limitations of MR techniques, relevant physical and biological principles for each of the MR techniques are first reviewed. This is followed by a review of the understanding of the sequence of normal brain development utilizing these techniques. MRDD Research Reviews 6:59-67, 2000.

Brain↗
PubMed2000

The effect of selenium supplementation on outcome in very low birth weight infants: a randomized controlled trial. The New Zealand Neonatal Study Group.

BACKGROUND: Low selenium (SE) status has been documented in preterm infants and has been suggested to be a risk factor for chronic lung disease. METHODS: A total of 534 infants with birth weight <1500 g were enrolled in 8 New Zealand centers in a double-blind placebo-controlled randomized trial of SE supplementation from week 1 of life until 36 weeks' postmenstrual age or discharge home. Supplemented infants received 7 microg/kg/d of SE when fed parenterally and 5 microg/kg/d when fed orally. Plasma SE and glutathione peroxidase concentrations were measured in mothers after delivery and in infants before randomization and at 28 days and 36 weeks' postmenstrual age. Primary outcome measures were oxygen dependency at 28 days and total days oxygen dependency. RESULTS: No significant differences were seen between the groups with respect to primary or secondary outcome measures, with the exception that fewer supplemented infants had an episode of sepsis after the first week of life (P <.038). Mean plasma SE concentrations were 0.33 micromol/L before randomization in both groups and at 28 days had risen in the supplemented group (0.56 micromol/L) but fallen in the control group (0.29 micromol/L) (P <.0001). There was no association between outcome measures and SE concentrations at 28 days or 36 weeks' postmenstrual age. However, lower maternal and infant prerandomization SE concentrations were associated with increased respiratory morbidity. CONCLUSIONS: Postnatal SE supplementation in very low birth weight infants did not improve neonatal outcome. Further investigation of SE supplementation of mothers from the second half of pregnancy is warranted.

Double-Blind Method↗
PubMed2000

Mechanisms of perinatal brain injury.

This article is focused on the mechanisms underlying primarily ischaemic/reperfusion brain injury in both the term and premature infant. Although the mechanisms involved include similar initiating events, principally ischaemia-reperfusion, and similar final common pathways to cell death, particularly free radical-mediated events, there are certain unique maturational factors influencing the type and pattern of cellular injury. We will therefore initially describe the physiological and cellular/molecular mechanisms of brain injury in the term infant, followed by the mechanisms in the premature infant.

Asphyxia Neonatorum↗
PubMed2000

Protein carbonyls and lipid peroxidation products as oxidation markers in preterm infant plasma: associations with chronic lung disease and retinopathy and effects of selenium supplementation.

The purpose of this study was to determine whether protein carbonyls and the lipid peroxidation product malondialdehyde (MDA) are elevated in plasma from very low birth weight (<1500 g) infants, whether they are affected by selenium supplementation, and whether they are associated with poor respiratory outcome or retinopathy. The study group comprised 173 infants enrolled in a randomized controlled trial of selenium supplementation. Plasma samples, collected before randomization, at 7 and 28 d after birth, and at 36 wk postmenstrual age, were analyzed for protein carbonyls and total MDA. Respiratory outcome was assessed as oxygen requirement at 28 d of age or 36 wk postmenstrual age and as number of days on oxygen. Protein carbonyl concentrations in very low birth weight infants were significantly higher than for adults but lower than for cord blood from term infants. Median values decreased significantly by 28 d, and there was no relationship with birth weight. MDA concentrations in very low birth weight infants overlapped the ranges for healthy adults and cord blood from term infants. They correlated positively with birth weight at 28 d but not at other times. Supplementation almost doubled plasma selenium concentrations, but carbonyls and MDA did not differ between the supplemented and unsupplemented groups. There were no significant differences in oxidant marker levels in infants who did or did not develop chronic lung disease or retinopathy. Protein carbonyls and MDA measurements in plasma do not show evidence of systemic oxidative stress in <1500-g infants and are not affected by selenium supplementation. Oxidative injury at sites such as the lung may be important in prematurity, but markers from such sites must be measured to relate to outcome and antioxidant supplementation.

Adult↗
PubMed1999

The postmigrational development of polymicrogyria documented by magnetic resonance imaging from 31 weeks' postconceptional age.

We report the case of a 27-week premature infant in whom magnetic resonance imaging (MRI) at 4 postnatal weeks (postconceptional age, 31 weeks), term, and 6 months of age documented the postnatal postmigrational evolution of bilateral perisylvian polymicrogyria. The polymicrogyria was readily detected by ultrafine 1.5-mm coronal slices on three-dimensional, Fourier-transformed, spoiled gradient-recalled and T2-weighted MRI sequences. These MRI sequences provide the first in vivo documentation of the postmigrational evolution of polymicrogyria. The likelihood that the polymicrogyria was related to an ischemic encephaloclastic mechanism is supported by the simultaneous occurrence of periventricular leukomalacia.

Brain Diseases↗
PubMed1999

Periventricular white matter injury in the premature infant is followed by reduced cerebral cortical gray matter volume at term.

Periventricular white matter injury, that is, periventricular leukomalacia (PVL), the dominant form of brain injury in the premature infant, is the major neuropathological substrate associated with the motor and cognitive deficits observed later in such infants. The nature of the relationship of this lesion to the subsequent cognitive deficits is unclear, but such deficits raise the possibility of cerebral cortical neuronal dysfunction. Although cortical neuronal necrosis is not a prominent feature of brain injury in premature infants, the possibility of a deleterious effect of PVL on subsequent cerebral cortical development has not been investigated. An advanced quantitative volumetric three-dimensional magnetic resonance imaging technique was used to measure brain tissue volumes at term in premature infants with earlier ultrasonographic and magnetic resonance imaging evidence of PVL (mean gestational age at birth, 28.7 +/- 2.0 weeks; n = 10), in premature infants with normal imaging studies (mean gestational age at birth, 29.0 +/- 2.1 weeks; n = 10), and in control term infants (n = 14). Premature infants with PVL had a marked reduction in cerebral cortical gray matter at term compared with either premature infants without PVL or normal term infants (mean +/- SD: PVL, 157.5 +/- 41.5 ml; no PVL, 211.7 +/- 25.4 ml; normal term, 218.8 +/- 21.3 ml). As expected, a reduction in the volume of total brain myelinated white matter was also noted (mean +/- SD: PVL, 14.5 +/- 4.6 ml; no PVL, 23.1 +/- 6.9 ml; normal term, 27.6 +/- 10.3 ml). An apparent compensatory increase in total cerebrospinal fluid volume also was found (mean +/- SD: PVL, 64.5 +/- 15.2 ml; no PVL, 52.0 +/- 24.1 ml; normal term, 32.9 +/- 13.5 ml). PVL in the premature infant is shown for the first time to be followed by impaired cerebral cortical development. These findings may provide insight into the anatomical correlate for the intellectual deficits associated with PVL in the premature infant.

Basal Ganglia↗
PubMed1998

Plasma vitamin A levels in the very low birthweight infant--relationship to respiratory outcome.

OBJECTIVE: To examine the association between plasma vitamin A levels and outcome measures in very low birthweight (VLBW) infants, including meta-analysis of all observational studies. DESIGN: A prospective observational longitudinal study of plasma vitamin A levels measured in the cord blood; maternal blood in the first 48 h after delivery; and the infants' blood at 48 h, 7 days and 28 days of age and correlated with antenatal and postnatal events. A meta-analysis of all published observational studies on the association of vitamin A with respiratory outcome in the VLBW infant was undertaken. PATIENTS: Fifty-seven infants (88% of all eligible) VLBW infants (< 1500 g) admitted from January through October 1993 to one of two regional neonatal intensive care units in the South Island of New Zealand. RESULTS: Exposure to antenatal steroids led to a significant increase in infant cord plasma vitamin A levels (P = 0.003), but no influence on infant plasma vitamin A levels at any other time. Exposure to postnatal steroids produced a significant rise in infant plasma vitamin A levels between 7 and 28 days (P = 0.008). After controlling for gestational age, antenatal and postnatal steroid exposure, low vitamin A levels at 48 h increased the risk of developing chronic lung disease (odds ratio for 50 microg/l decrease: 2.04, 95% CI 1.19-5.77) and bronchopulmonary dysplasia (odds ratio 1.96, 95% CI 1.14-6.87). On combining our results in meta-analysis with those of other published prospective observational studies, infants with chronic lung disease had lower plasma vitamin A levels at all times. CONCLUSIONS: Our results support an association between low plasma vitamin A levels and adverse outcome in the VLBW infant.

Chronic Disease↗
PubMed1998

Recovery of congenital isolated pharyngeal dysfunction: implications for early management.

The authors describe a case of severe congenital dysphagia caused by isolated pharyngeal dysfunction to highlight the clinical variability in the time to spontaneous recovery of this syndrome. The infant demonstrated recovery at 2 months of age, much earlier than previously reported examples. This case assists in the definition of this syndrome. This diagnosis should be considered in the evaluation of infants with congenital dysphagia.

Cisapride↗
PubMed1997

Endotracheal suctioning of the neonate: comparison of two methods as a source of mucus material for research.

Endotracheal suctioning in the neonatal intensive care setting is a routine procedure performed to maintain patency of the airway in ventilated infants. Harvested material can also be a source of mucus for research into neonatal respiratory disorders. We aimed to investigate whether the composition of material obtained by our clinically preferred technique of dry shallow suctioning differed significantly from that obtained with saline lavage and deep suctioning. Eleven pairs of dry and saline lavage aspiration samples were compared for neutrophil enzyme myeloperoxidase, total and active alpha(1)-antitrypsin, alpha(1)-antitrypsin complexed with elastase, and secretory leukoprotease inhibitor. Even though individual values of each analyte, expressed per gram of albumin, varied over at least a fivefold range, there was no difference between mean values of dry and lavage samples for any of the constituents. We conclude that the yield of material for research obtained by dry shallow suctioning is adequate and the quality at least as satisfactory as that provided by saline lavage.

Bronchoalveolar Lavage Fluid↗
PubMed1996

The correlation of elevated levels of an index of lipid peroxidation (MDA-TBA) with adverse outcome in the very low birthweight infant.

The objective of this study was to examine the relationship between malondialdehyde-thiobarbituric acid (MDA-TBA) levels, as a measure of lipid peroxidation, in very low birthweight (VLBW) infants and outcome measures. A prospective observational longitudinal study was carried out in two level III neonatal units in the South Island of New Zealand measuring MDA-TBA levels in 61 VLBW infants in 1993. MDA-TBA levels were measured in (i) maternal plasma within 48 h of parturition, (ii) cord plasma, and (iii) infants' plasma at 2, 7, 14 and 28 days of age and correlated with antenatal and postnatal factors. Elevated levels of plasma MDA-TBA at 7 days were associated with adverse respiratory and ophthalmological outcome in the VLBW infants. Elevated MDA-TBA levels were measured at sample times close to the time of death in the infants who died. These results substantiate previously reported preliminary observations and support the hypothesis that oxidative injury, particularly within the first 7 days of life, is associated with the development of the long-term complications of the pre-term infant. MDA-TBA levels appear to be a useful measure to continue to explore the role of free radical mediated disease in the VLBW infant.

Fat Emulsions, Intravenous↗
PubMed1995

Oxidation of parenteral lipid emulsion by ambient and phototherapy lights: potential toxicity of routine parenteral feeding.

Vitamin E can be a prooxidant in isolated lipoprotein suspensions. Because lipid emulsions used in parenteral nutrition are lipoprotein-like suspensions rich in polyunsaturated fatty acids and vitamin E, we hypothesized that vitamin E may act as a prooxidant in lipid emulsions, as it is in lipoprotein suspensions. We therefore exposed an intravenously administered lipid emulsion (Intralipid) to a single spotlight commonly used in the treatment of neonatal jaundice, and measured the formation of triglyceride hydroperoxides by using high-performance liquid chromatography with postcolumn chemiluminescence detection. Concentrations of these hydroperoxides in different batches of fresh intralipid were usually approximately 10 mumol/L but increased up to 60 times after exposure to phototherapy light for a period of 24 hours, even though significant amounts of vitamin E were present at the end of the exposure. Triglyceride hydroperoxides were formed during phototherapy light exposure whether the intralipid was in plastic tubing used routinely for infusion or in glass containers. Ambient light also caused significant peroxidation of the formula lipids, although to a much lesser extent than observed with phototherapy light. For infants in the neonatal intensive care unit who were receiving intralipid but not phototherapy, solutions being infused at the end of 24 hours contained a mean of 40 mumol/L hydroperoxides. For infants receiving phototherapy, the mean was 97 mumol/L. Phototherapy light-induced formation of triglyceride hydroperoxides was prevented by covering the intralipid with aluminum foil or supplementation with sodium ascorbate before light exposure. We conclude that intralipid is highly susceptible to oxidation and that elevated levels of oxidized lipids can be formed during its clinical use, especially when intralipid infusion is combined with phototherapy. Because lipid hydroperoxides are cytotoxic and can cause adverse effects, inadvertent infusion of rancid intralipid may add to the numerous problems encountered by premature neonates.

Aluminum↗