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ABSTRACT: AIM: The aim of this study was to investigate the direct relationship of sleep schedule and sleep quality variables between healthy preschool children and their parents, focusing on the influence of the difference in bedtime between each other. METHODS: Forty-seven Japanese 5-year-old children and their primary parent were studied. The parents completed questionnaires including the Epworth Sleepiness Scale and Pittsburgh Sleep Quality Index. The children wore an actigraph for one week. RESULTS: Although sleep patterns of children were generally independent of their parents, late sleep end time and bedtime of children were associated with parents' late sleep end time on weekends. For 87% of children and parents who shared a bedroom, sleep quality was negatively affected by a shorter difference in bedtimes between child and parent, but not by co-sleeping. CONCLUSION: Sleep behaviours of parents can influence those of their children. For parents and children who share a bedroom, the timing of bedtime rather than co-sleeping may be a key factor in modulating sleep patterns. Trying to get children asleep and subsequently falling asleep at a similar time may disturb parents' sleep quality, which may subsequently affect that of their children.
Acta Paediatrica 02/2013; · 2.07 Impact Factor
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Nicola J Robertson,
Takenori Kato,
Alan Bainbridge,
Manigandan Chandrasekaran,
Osuke Iwata,
Andrew Kapetanakis,
Stuart Faulkner,
Jeanie Cheong, Sachiko Iwata,
Mariya Hristova,
Ernest Cady,
Gennadij Raivich
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ABSTRACT: Na(+) /H(+) exchanger (NHE) blockade attenuates the detrimental consequences of ischemia and reperfusion in myocardium and brain in adult and neonatal animal studies. Our aim was to use magnetic resonance spectroscopy (MRS) biomarkers and immunohistochemistry to investigate the cerebral effects of the NHE inhibitor, methyl isobutyl amiloride (MIA) given after severe perinatal asphyxia in the piglet. Eighteen male piglets (aged <24h) underwent transient global cerebral hypoxia-ischemia and were randomized to (i) saline placebo; or (ii) 3mg/kg intravenous MIA administered 10 mins post-insult and 8 hourly thereafter. Serial phosphorus-31 ((31) P) and proton ((1) H) MRS data were acquired before, during and up to 48h after hypoxia-ischemia and metabolite-ratio time-series Area under the Curve (AUC) calculated. At 48h, histological and immunohistochemical assessments quantified regional tissue injury. MIA decreased thalamic lactate/N-acetylaspartate and lactate/creatine AUCs (both p<0.05) compared to placebo. Correlating with improved cerebral energy metabolism, TUNEL positive cell density was reduced in the MIA group in cerebral cortex, thalamus and white matter (all p<0.05) and caspase 3 immunoreactive cells were reduced in pyriform cortex and caudate nucleus (both p<0.05). Microglial activation was reduced in pyriform and midtemporal cortex (both p<0.05). Treatment with MIA starting 10 minutes after hypoxia-ischemia was neuroprotective in this perinatal asphyxia model. © 2012 International Society for Neurochemistry, J. Neurochem. (2012) 10.1111/jnc.12097.
Journal of Neurochemistry 11/2012; · 4.06 Impact Factor
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ABSTRACT: Background:In the rodent and human fetus, a diurnal cortisol rhythm is observed that is entrained in antiphase to the maternal rhythm. However, after birth, the adrenal circadian rhythm becomes unsynchronized with the clock time, and an adult-type, 24-h rhythm is observed only after a few months. Little is known about when and how the fetal adrenal circadian rhythm is synchronized with the day-night cycle.Methods:To investigate the function of adrenal circadian clock in the newborn infant, eight serial saliva samples were collected every 3 h over 24 h (starting at 0900 h) in 27 newborn infants.Results:Cortisol levels were higher during the period 1500 to earlier than 2100 h than during 0900 to earlier than 1500 h and 0300 to earlier than 0900 h (both P < 0.05). Salivary cortisol levels collected during 0 to <6, 6 to <12, and 12 to <18 hours after the clock time at birth (birth time) were higher than those collected during 18 to <24 hours after the birth time (P < 0.005, 0.05, and 0.05, respectively). The acrophase of salivary cortisol was linearly correlated with the birth time within the first 5 d of life (P < 0.005) but not thereafter.Conclusion:In the newborn infant, diurnal increase in cortisol was observed in the late afternoon and in correspondence with the birth time. The adrenal circadian rhythm acquired in utero may be reentrained by endocrinological events at birth. Such complex regulation of the adrenal circadian clock may inhibit a swift synchronization of the circadian clock to the day-night rhythm.
The Journal of clinical endocrinology and metabolism 11/2012; · 6.50 Impact Factor
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ABSTRACT: A prospective study was performed to assess the relationship between the appearance of cerebral MRI at term and the cognitive functioning at 9 years old in very preterm born infants.
Seventy-six very preterm born infants (birth weight <1500 g or gestational age ≤32 weeks) obtained cerebral MRI at term-equivalent period, which was assessed by using established composite scores for the white and gray matter; cognitive outcomes at 9 years old were assessed in 60 subjects by using Wechsler Intelligence Scale for Children, Third Edition.
Mildly low scores on the different IQ indices (<85) were observed in 23.3% (verbal IQ), 41.7% (performance IQ), and 30.0% (full-scale IQ) of the cohort, whereas moderately low scores (<70) were noted in 3.3% (verbal IQ), 11.7% (performance IQ), and 11.7% (full-scale IQ); cerebral palsy was diagnosed in 10.0%, whereas special assistance at school was required in 56.7%. Abnormal white matter appearances predicted mildly low verbal, performance, and full-scale IQs; moderately low performance and full-scale IQs; cerebral palsy; and the requirement for special assistance at school. Abnormal white matter appearances predicted mild cognitive impairment even after the adjustment for known clinical risk factors. In contrast, abnormal gray matter appearances did not predict any of the outcome measures.
In a cohort of very preterm born infants, abnormal white matter appearance on term MRI showed consistent associations with cognitive impairments at 9 years old, further supporting the benefit of obtaining term MRI for very preterm born infants.
PEDIATRICS 04/2012; 129(5):e1138-47. · 4.47 Impact Factor
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ABSTRACT: Therapeutic hypothermia is now recommended as a standard of care for neonatal encephalopathy. Although adherence to standard cooling protocols used in the phase-III trials is essential, empiric approaches have prevailed in Japan.
To elucidate the gap between the standard cooling methods and the current practice in Japan.
In July 2010, a questionnaire regarding the practice of neonatal encephalopathy was mailed to clinical leads of registered neonatal intensive care units.
56.2% of the units were incapable of offering therapeutic hypothermia because of the reasons such as the shortage of human/medical resources (85.1%) and limited number of cases (21.1%). Eighty-nine centres provided therapeutic hypothermia using either selective-head cooling (88.8%) or whole-body cooling (11.2%). Various target temperatures and cooling durations were used; 20.2% of the units cooled infants without using purpose-built equipments, whereas 14.6% did not continuously monitor the body temperature.
Only 43.8% of the units provided therapeutic hypothermia. Even in centres where hypothermia was offered, adherence to the standard protocols was extremely poor. To secure the safety and efficacy, further promotion of the standard cooling protocols is required; an efficient cooling centre network has to be established by optimizing the work forth distribution and transportation system.
Acta Paediatrica 12/2011; 101(5):e197-202. · 2.07 Impact Factor
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ABSTRACT: Although disturbed sleep quality such as night awakenings and difficulties in falling asleep are common symptoms during sleep in preschool children, relationships between sleep quality and sleep schedule are mostly unknown. This study aimed to evaluate the relationships between sleep schedule and quality variables in preschool children.
Sleep-wake patterns of 48 healthy 5-year-old children were assessed over 7 consecutive days using actigraphy.
Children with longer sleep latency had a lower sleep quality, a later bedtime, a later sleep onset time, a shorter nocturnal sleep period and a longer daytime nap. Children with a longer nocturnal sleep period on weekends compared with weekdays had longer sleep latency and a later sleep onset time on weekdays, resulting in a lower sleep quality on weekends. An irregular bedtime on weekdays was associated with a later sleep onset time and a shorter sleep period on weekends.
Sleep quality and schedule were linked with each other, which may explain why sleep problems tend to aggregate and form a wider syndrome of disturbed sleep even in young children. Strategies solely targeting the improvement of sleep quantity may not promote ideal sleep; simultaneous considerations for the sleep rhythm and quality may be required.
Acta Paediatrica 11/2011; 101(3):e110-4. · 2.07 Impact Factor
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ABSTRACT: Neonatal encephalopathy associated with perinatal hypoxia-ischaemia is one of the most common causes of death and permanent disability worldwide. However, of a wide range of "experimentally neuroprotective treatments" invented so far, only therapeutic hypothermia has been promoted into a standard clinical practice. Such a wide gap in the efficacy of neuroprotective treatments between the experimental setting and clinical practice may be attributed to the strategic flaw in translating basic knowledge into clinical care. When previous clinical studies are carefully reviewed, one may notice that few therapeutic options were chosen based on their track records in experimental studies; protective effects of some drugs had been assumed only based on their pharmacokinetics in adult species; several therapies were chosen merely because clinicians were familiar to these treatments for other purpose; some other therapies were imported too preliminarily from laboratory to clinical practice, potentially ignoring the difference in physiological and pathological backgrounds between rodent models and human patients. When further clinical trials are planned, it is important to ask whether (i) the treatment is supported by pharmacokinetics specific to immature brain, and (ii) the neuroprotective effect of the treatment has consistently been demonstrated using clinically relevant models and study designs. The use of translational large animal models allows the practical simulation and fine-tuning of clinical protocols, which may further assist successful translation of basic knowledge. In addition to the effort to develop alternative therapeutic options, it is important to maximise the effect of the current only neuroprotective option, or therapeutic hypothermia. Independent variables which influence the efficacy of hypothermia have to be elucidated to improve its therapeutic protocol, and to increase the number of patients who will benefit from this treatment.
Brain & development 03/2011; 33(3):221-8. · 1.74 Impact Factor
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ABSTRACT: Background Recent studies suggest that refractory hypotension from causes other than septicaemia or cardiac failure is common in extremely preterm infants even out of the transitional period. Marked response to low-dose cortisol suggests underlying adrenal insufficiency, although the exact mechanism remains unknown.Methods To investigate potential triggers for and related short-term outcomes of early-onset (<Day 7) and late-onset (≥Day 7) refractory hypotension, clinical data for 70 infants <30 weeks gestation were assessed.Results The incidence of early-onset refractory hypotension (n = 7) was correlated with younger gestational ages <26 weeks (P < 0·05), whereas the incidence of late-onset refractory hypotension (n = 14) was correlated with younger gestational ages and levothyroxine supplementation (P < 0·05 and 0·01, respectively). The incidence of both early- and late-onset refractory hypotension was correlated with risks of short-term adverse outcomes such as prolonged mechanical ventilation and hospital stay.Conclusions Levothyroxine supplementation was identified as an independent variable correlated with an increased incidence of refractory hypotension out of the transitional period; as seen in hypothyroidism with Addison’s disease, the immature hypothalamic-pituitary-adrenal axis may not respond properly to the increased demand for cortisol, which may precipitate premature infants into refractory hypotension. Following the administration of levothyroxine, preterm infants may have to be carefully monitored for early signs of refractory hypotension.
Clinical Endocrinology 02/2011; 74(3):354 - 364. · 3.17 Impact Factor
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ABSTRACT: Perinatal hypoxia-ischaemia affects cognitive outcomes of infants even when clinical symptoms were latent and intensive care was not required. We performed a retrospective analysis in a cohort of term infants who required intensive care (i) to investigate the incidence of abnormal white matter appearances on the magnetic resonance imaging obtained before 2 months corrected age, and (ii) to examine its relationships with other cerebral lesions, clinical backgrounds, and short-term outcome at 12 months.
White matter appearances on T2-weighted imaging (T2WI) and fluid-attenuated inversion recovery imaging (FLAIR) were assessed in relationship with other cerebral lesions, clinical backgrounds, established white matter lesions on follow-up scans, and abbreviated developmental outcomes at 12 months in 150 term-born infants who were cared for at a tertiary neonatal intensive care unit with mixed indications for admission (positive pressure ventilation and intravenous inotropes required in 38% and 49% of infants respectively).
On T2WI and FLAIR, 14.0% and 41.3% of infants showed abnormal white matter intensities respectively, which were both related with lesions in the internal capsule and deep grey matter. Abnormal T2WI appearances were correlated with low Apgar scores and low blood base-excess whereas abnormal FLAIR appearances were associated with younger corrected age at scan. Follow-up studies in a cohort of infants revealed that abnormal white matter intensities further correlated with chronic long-T2 lesions after 8 months corrected age (n=40) and severe neuro-developmental disability at 12 months (n=104).
Abnormal white matter intensities were associated with pathological clinical variables. White matter injury may not be a specific form of cerebral damage in preterm infants. For the precise evaluation of newborn brain imaging, it may be beneficial to account for corrected age even in term infants.
International journal of developmental neuroscience: the official journal of the International Society for Developmental Neuroscience 11/2010; 28(7):573-80. · 2.03 Impact Factor
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ABSTRACT: Early childhood is an important period for the development of sleep patterns; studies of sleep patterns in young preschool children may help elucidate the mechanism of associated mental/physical conditions and later sleep problems.
The aim of this study was to investigate intrinsic and extrinsic independent variables associated with sleep patterns in preschool children using actigraphy. Forty-eight 5-year-old children from two types of nurseries, which accommodate children with (Type A) or without (Type B) in-home caregivers, were invited to undergo a 7-day actigraphic sleep study.
Compared with weekdays, both sleep onset time and sleep end time were later on weekends (28 and 17 min later in average, respectively). On weekdays, cultural lessons were associated with a later sleep onset time (22 min later); female gender, sports lessons and fixed bathing times were related with an earlier sleep end time (17, 21 and 17 min earlier, respectively); sports lessons were also associated with higher sleep efficiency (3.7% higher). During weekends, unfixed bedtimes and daytime naps were related with a later sleep onset time (73 and 54 min later, respectively); male gender, Type A nursery and daytime naps were associated with a later sleep end time (33, 37 and 34 min later, respectively); sports lessons were associated with higher sleep efficiency (3.6% higher).
Our current findings suggested that both intrinsic and extrinsic factors, such as gender, child care, lifestyle and after-nursery lessons, influence the establishment of sleep patterns in young preschool children. Further investigation of these independent variables may help establish a strategy for predicting and preventing sleep disorders later in life.
International journal of developmental neuroscience: the official journal of the International Society for Developmental Neuroscience 09/2010; 29(1):57-62. · 2.03 Impact Factor
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ABSTRACT: Sleep pattern is an important factor in a child's mental, behavioural and physical status. To evaluate the sleep patterns of children, subjective tools such as sleep logs and questionnaires are still widely used in addition to objective methods of sleep assessment. Despite the established correlation between subjective and objective sleep variables, the characteristic features of subjective assessment have not been elucidated.
To investigate the characteristics of parental sleep assessment (daily sleep log and brief questionnaire) in preschool children, a 7-day actigraphic sleep study was conducted in 48 healthy 5-year-old children.
Sleep schedule variables in the parental reports generally correlated well with actigraphic assessment of sleep patterns; however, sleep periods were longer in parental reports than in actigraphic recordings. Although the daily sleep log was better correlated with actigraphy, the brief questionnaire showed a good correlation with sleep pattern on weekday actigraphic assessments. Parental reports recorded fewer than 10% of the night wakings recorded by actigraphy.
Subjective sleep assessments remain useful, although their utility depends on the purpose and size of the study in question. However, knowledge of the potential biases and characteristics of such assessments is essential for correct interpretation of the data.
Journal of Epidemiology 02/2010; 20(2):143-9. · 1.86 Impact Factor
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ABSTRACT: Antenatal stress, maturation and other foetal conditions affect the postnatal cardiovascular function. Atrial- (ANP) and brain-type natriuretic peptide (BNP) play important roles in regulating extracellular fluid volume and blood pressure, which may surrogate the foetal cardiovascular condition. The aim of this study was to investigate the dependence of serum ANP and BNP at birth on antenatal variables in high-risk infants.
Plasma ANP and BNP levels in the umbilical cord blood were compared with antenatal clinical information in 280 infants.
High levels of ANP and BNP were associated with multiple pregnancy, antenatal magnesium sulphate and foetal distress. Caesarean section (CS) was paradoxically associated with low ANP and high BNP; low ANP was related with CS before labour whereas high BNP was related with CS after the commencement of labour. High BNP levels further correlated with younger gestational age and intrauteral growth restriction. With regard to short-term postnatal variables, high BNP levels were associated with low Apgar scores and respiratory failure whereas high ANP only correlated with the latter.
High natriuretic peptide levels were associated with prematurity at birth, uteral contraction and antenatal stress: cord blood ANP and BNP may be a useful surrogate marker for hidden antenatal stress.
Acta Paediatrica 10/2009; 98(9):1421-5. · 2.07 Impact Factor
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ABSTRACT: The seroprevalence of Human T-cell Leukemia Virus Type 1 (HTLV-1) is female predominant despite the higher incidence of Adult T-cell Leukemia (ATL) in males. If the mother-to-child transmission of HTLV-1 is more common for male infants than in female infants, longer exposure to the virus for males may explain the paradoxically higher incidence of ATL.
To test the hypothesis that the seroprevalence of HTLV-1 is male predominant during adolescence.
The presence of HTLV-1 antibody in 272,043 blood samples donated to a regional blood bank in an HTLV-1 high-endemic region was assessed.
The entire population of female donors had a significantly higher seroprevalence compared to males (2.05% and 1.80%, respectively, p<0.0001). However, compared with male donors, the carrier rate for female donors was lower for the youngest subgroup (16-19 years, p=0.0011); was similar for the next two age subgroups (20-29 years and 30-39 years); and was significantly higher for the last two age subgroups (40-49 years and over 50-64 years, both p<0.0001). In general, older age subgroups led to higher seroprevalence in both genders.
HTLV-1 infection is more common for males until after age 20, when male to female sexual transmission becomes likely. This suggests that mother-to-child transmission is more common for males.
Journal of clinical virology: the official publication of the Pan American Society for Clinical Virology 05/2009; 45(2):135-8. · 3.12 Impact Factor
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S Iwata,
O Iwata,
L Olson,
A Kapetanakis,
T Kato,
S Evans,
Y Araki,
T Kakuma,
T Matsuishi,
F Setterwall,
H Lagercrantz,
N J Robertson
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ABSTRACT: Therapeutic hypothermia, a safe and effective treatment for neonatal encephalopathy in an intensive care setting, is not available in low-resource settings. Aims/
To assess two low-tech, low-cost cooling devices for use in low-resource settings: (i) commercially available water bottles filled with tepid water (25 degrees C); (ii) a mattress made of phase changing material (PCM) with a melting point of 32 degrees C (PCM works as a heat buffer at this temperature). Eleven anaesthetised newborn piglets were studied following transient hypoxia-ischaemia. The cooling device was applied 2-26 h after hypoxia-ischaemia with a target rectal temperature (T(rectal)) of 33-34 degrees C. T(rectal) undershoot was adjusted using cotton blankets; the cooling device was renewed when T(rectal) rose above 35 degrees C. T(rectal) data during cooling were dichotomised (within or without target) to assess: (a) the total period within the target T(rectal) range; (b) the stability and fluctuation of T(rectal) during cooling.
Therapeutic hypothermia was achieved with both water bottles (n = 5) and the PCM mattress (n = 6). The mean (SD) time to reach target T(rectal) was 1.8 (0.5) h with water bottles and 1.9 (0.3) h with PCM. PCM cooling led to a longer period within the target T(rectal) range (p<0.01) and more stable cooling (p<0.05). Water bottle cooling required device renewal (in four out of five piglets).
Simple, low-tech cooling devices can induce and maintain therapeutic hypothermia effectively in a porcine model of neonatal encephalopathy, although frequent fine tuning by adjusting the number of blankets insulating the piglet was required to maintain a stable temperature. PCM may induce more stable cooling compared with water bottles.
Archives of Disease in Childhood 01/2009; 94(5):387-91. · 2.88 Impact Factor
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ABSTRACT: Following hypoxia-ischaemia (HI), an early biomarker of insult severity is desirable to target neuroprotective therapies to patients most likely to benefit; currently there are no biomarkers within the 'latent phase' period before the establishment of secondary energy failure. Brief transient phosphocreatine (PCr) recovery overshoot (measured absolutely or relative to nucleotide triphosphate, NTP) following HI has been observed in cardiac and skeletal muscle; its significance however is unclear. To investigate cerebral PCr recovery levels after HI in relation to (i) baseline metabolism, (ii) insult severity, (iii) energy metabolism at recovery and (iv) subsequent metabolic derangement, cerebral NTP, PCr and inorganic phosphate (relative to the exchangeable high-energy phosphate pool) were measured serially in an in vivo model of perinatal asphyxial encephalopathy using phosphorus-31 magnetic resonance spectroscopy. Measures were compared either in all piglets or between 3 subgroups with no (n = 5, favourable outcome), moderate (n = 8, intermediate outcome) or severe (n = 5, unfavourable outcome) secondary energy failure at 24 h after HI. Maximum NTP, PCr and inorganic phosphate recoveries were observed 2-8 h after HI. Following resuscitation, in subjects with favourable outcome PCr recovered to higher than its baseline level (overshoot); in subjects with unfavourable outcome maximum PCr recovery was lower than baseline and lower than in subjects with favourable and intermediate outcomes. Recovery PCr correlated linearly and negatively with both acute insult severity and baseline PCr/NTP. These results suggest that recovery metabolism 2-8 h after HI may provide an early biomarker of injury severity. PCr recovery overshoot in the developing brain may indicate a protective response to HI leading to cell recovery, survival and protection against subsequent stress. In addition, baseline cerebral metabolism (PCr/NTP) may identify vulnerable infants prior to invasive surgery.
Brain 09/2008; 131(Pt 8):2220-6. · 9.46 Impact Factor
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ABSTRACT: Preterm infants are at significant risk of neuro-developmental disorders at school-age. MRI is a potentially useful screening tool of such disorders. Using FLAIR imaging in the preterm infants at term, here we demonstrate that abnormal low-intensity signal in the white matter predicts the neuro-developmental outcome at 6 years.
Clinical factors associated with white matter appearance on MRI obtained at term were investigated in 210 preterm infants.
Low-intensity signal on FLAIR imaging was commonly observed (69%) at <2 months corrected-age. Its incidence correlated with corrected-age at scan, maternal pyrexia and cystic periventricular leukomalacia. Low-intensity signal on FLAIR significantly correlated with performance and full-scale developmental quotients, whereas diffuse high-intensity signal on T2-weighted imaging correlated only with the full-scale developmental quotient at 6 years (n = 75, WISC-R). FLAIR imaging, but not T2-weighted imaging, predicted mild neuro-developmental delay.
FLAIR appeared to detect subtle white matter injury related with neuro-developmental disorders at school-age, whereas T2-weighted imaging seemed to identify relatively more severe injury. FLAIR is a potentially sensitive screening tool that is readily available and easily interpretable.
International Journal of Developmental Neuroscience 12/2007; 25(8):523-30. · 2.42 Impact Factor
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Osuke Iwata, Sachiko Iwata,
John S Thornton,
Enrico De Vita,
Alan Bainbridge,
Linda Herbert,
Francesco Scaravilli,
Donald Peebles,
John S Wyatt,
Ernest B Cady,
Nicola J Robertson
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ABSTRACT: For optimal neuroprotection following transient perinatal hypoxia-ischaemia (HI), therapy should start before overt secondary energy failure and its irreversible neurotoxic cascade. Hypothermia is a promising neuroprotective intervention that also prolongs the therapeutic time window ("latent-phase"; the period between re-establishment of apparently normal cerebral metabolism after HI, and the start of secondary energy failure). The influences of HI severity on latent-phase duration and regional neuroprotection are unclear. Under normothermia and delayed whole-body cooling to 35 and 33 degrees C we aimed to assess relationships between HI severity and: (i) latent-phase duration; (ii) secondary-energy-failure severity; and (iii) neuronal injury 48 h following HI.
Newborn piglets were randomized to: (i) HI-normothermia (n=12), (ii) HI-35 degrees C (n=7), and (iii) HI-33 degrees C (n=10). HI-35 degrees C and HI-33 degrees C piglets were cooled between 2 and 26 h after HI. Insult and secondary-energy-failure severity and latent-phase duration were evaluated using phosphorus magnetic resonance spectroscopy and compared with neuronal death in cortical-grey and deep-grey matter.
More severe HI was associated with shorter latent-phase (p=0.002), worse secondary energy failure (p=0.023) and more cortical-grey-matter neuronal death (p=0.016).
Latent-phase duration is inversely related to insult severity; latent-phase brevity may explain the apparently less effective neuroprotection following severe cerebral HI.
Brain Research 07/2007; 1154:173-80. · 2.73 Impact Factor
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ABSTRACT: Hypothermia was not neuroprotective in low body weight (BW) infants on subgroup analysis in a recent clinical trial of selective head cooling (SHC) in neonatal encephalopathy (CoolCap Trial).
The BW dependence of regional cerebral temperature was investigated in 14 newborn piglets under normothermia (38.5 degrees C), whole-body cooling (WBC; 36.5, 34.5, 32.5, and 30.5 degrees C), or SHC (20, 15, and 10 degrees C).
Normothermia: Lower BW led to lower superficial brain temperature (p < 0.01). Deep to superficial brain and rectal to superficial brain temperature gradients increased with decreasing BW (both p < 0.05). WBC: Lower BW led to lower superficial brain temperature and higher rectal to superficial brain temperature gradient (p < 0.05 and p < 0.01, respectively). SHC: For lower BW, superficial and deep brain temperatures decreased (p < 0.01 and p < 0.05, respectively), whereas rectal to deep, rectal to superficial, and deep to superficial brain temperature gradients increased (p < 0.05, p < 0.01, and p < 0.05, respectively). Compared with SHC alone, superimposition of WBC (34.5 degrees C) reduced all regional temperatures (all p < 0.001); gradients were unaffected.
Brain cooling (under normothermia, WBC, or SHC) was more efficient with lower BW due to greater head surface area-to-volume ratios. In the CoolCap Trial, low BW infants might have been excessively cooled. WBC and SHC may require BW adjustment to accomplish consistent regional temperatures and optimal neuroprotection.
Annals of Neurology 12/2006; 60(5):578-85. · 11.09 Impact Factor
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Frances E O'Brien,
Osuke Iwata,
John S Thornton,
Enrico De Vita,
Mark W Sellwood, Sachiko Iwata,
Yasuko S Sakata,
Susan Charman,
Roger Ordidge,
Ernest B Cady,
John S Wyatt,
Nicola J Robertson
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ABSTRACT: Fundamental questions remain about the precise temperature providing optimal neuroprotection after perinatal hypoxia-ischemia (HI). Furthermore, if hypothermia delays the onset of the neurotoxic cascade and the secondary impairment in cerebral energy generation, the "latent phase" may be prolonged, thus extending the period when additional treatments may be effective. The aims of this study were to investigate the effects of delayed systemic cooling at either 33 degrees C or 35 degrees C on the following: (1) latent-phase duration, and (2) cerebral metabolism during secondary energy failure itself, in the 48-hour period after transient HI.
Piglets were randomly assigned to the following: (1) HI-normothermic (HI-n) rectal temperature (Trectal; n = 12), (2) HI-Trectal 35 degrees C (HI-35; n = 7), and (3) HI-Trectal 33 degrees C (HI-33; n = 10). Groups were cooled to the target Trectal between 2 and 26 hours after HI. Serial magnetic resonance spectroscopy was performed over 48 hours. The effect of cooling on secondary energy failure severity (indexed by the nucleotide triphosphate/exchangeable phosphate pool [NTP/EPP] and phosphocreatine/inorganic phosphate [PCr/Pi] ratios) was assessed.
Compared with HI-n, HI-35 and HI-33 had a longer NTP/EPP latent phase and during the entire study duration had higher mean NTP/EPP and PCr/Pi. The latent phase (both PCr/Pi and NTP/EPP) and the whole-brain cerebral energetics were similar for HI-35 and HI-33. During the hypothermic period, compared with HI-n, PCr/Pi was preserved in the cooled groups, but this advantage was not maintained after rewarming. Compared with HI-n, HI-35 and HI-33 had higher NTP/EPP after rewarming.
Whole-body hypothermia for 24 hours at either 35 or 33 degrees C, commenced 2 hours after resuscitation, prolonged the NTP/EPP latent phase and reduced the overall secondary falls in mean PCr/Pi and NTP/EPP during 48 hours after HI. Reducing the temperature from 35 to 33 degrees C neither increased mean PCr/Pi and NTP/EPP nor further lengthened the latent phase.
PEDIATRICS 06/2006; 117(5):1549-59. · 4.47 Impact Factor
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Osuke Iwata,
John S Thornton,
Mark W Sellwood, Sachiko Iwata,
Yasuko Sakata,
Martina A Noone,
Frances E O'Brien,
Alan Bainbridge,
Enrico De Vita,
Gennadij Raivich,
Donald Peebles,
Francesco Scaravilli,
Ernest B Cady,
Roger Ordidge,
John S Wyatt,
Nicola J Robertson
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ABSTRACT: Hypothermia after perinatal hypoxia-ischemia (HI) is neuroprotective; the precise brain temperature that provides optimal protection is unknown. To assess the pattern of brain injury with 3 different rectal temperatures, we randomized 42 newborn piglets: (Group i) sham-normothermia (38.5-39 degrees C); (Group ii) sham-33 degrees C; (Group iii) HI-normothermia; (Group iv) HI-35 degrees C; and (Group v) HI-33 degrees C. Groups iii through v were subjected to transient HI insult. Groups ii, iv, and v were cooled to their target rectal temperatures between 2 and 26 hours after resuscitation. Experiments were terminated at 48 hours. Compared with normothermia, hypothermia at 35 degrees C led to 25 and 39% increases in neuronal viability in cortical gray matter (GM) and deep GM, respectively (both p < 0.05); hypothermia at 33 degrees C resulted in a 55% increase in neuronal viability in cortical GM (p < 0.01) but no significant increase in neuronal viability in deep GM. Comparing hypothermia at 35 and 33 degrees C, 35 degrees C resulted in more viable neurons in deep GM, whereas 33 degrees C resulted in more viable neurons in cortical GM (both p < 0.05). These results suggest that optimal neuroprotection by delayed hypothermia may occur at different temperatures in the cortical and deep GM. To obtain maximum benefit, you may need to design patient-specific hypothermia protocols by combining systemic and selective cooling.
Annals of Neurology 07/2005; 58(1):75-87. · 11.09 Impact Factor
