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A Whitelaw

Publications and source records attributed to A Whitelaw.

At least 19 recordsLinked to original sources
PubMed2006

Cognitive outcome and cyclo-oxygenase-2 gene (-765 G/C) variation in the preterm infant.

BACKGROUND: Cyclo-oxygenase (COX) inhibition by indomethacin does not result in an improvement in long-term neurocognitive outcome, despite reducing the incidence of both severe intraventricular haemorrhage and white matter injury visible on ultrasound. Diffuse brain injury after preterm birth may have inflammatory origins. These two points suggest that, in the preterm brain, COX inhibition may have a dominant proinflammatory or neuropathological role. The inducible form of the COX2 gene is polymorphic: the -765 C (rather than G) variant of the gene is associated with reduced COX2 activity. OBJECTIVE: To test the hypothesis that the C allele of COX2 is associated with worse neurodevelopmental outcomes after premature birth. OUTCOMES: Cerebral palsy, disability, Griffith's developmental quotient at 2 years and British Ability Scales-11 general cognitive ability and motor performance (movement assessment battery for children) at 5(1/2) years were compared with COX2 genotype. RESULTS: The C allele (GC 65 (31%), CC 3 (1%)) was independently associated with worse cognitive performance at 2 and 5(1/2) years: C allele mean (SEM) developmental quotient 92.7 (1.7), v GG 97.6 (1.5), p = 0.039; C allele mean (SEM) general cognitive ability, 94.3 (2.2) v GG 100.9 (1.7), p = 0.028. CONCLUSION: An antineuropathological role for COX2 in the preterm brain may help account for the lack of effect of indomethacin treatment in improving neurocognitive outcomes in children born preterm, despite reported reduction in apparent brain injury.

Alleles↗
PubMed2004

Transforming growth factor-betas in a rat model of neonatal posthaemorrhagic hydrocephalus.

Posthaemorrhagic ventricular dilatation (PHVD) is a common complication of intraventricular haemorrhage in premature infants. The aim of this study was to investigate the role of transforming growth factor-betas (TGF-betas), a family of polypeptides with potent desmoplastic properties, in the aetiology of PHVD in a newly developed neonatal rat model of this disorder. Pups were injected with citrated rat blood or artificial cerebrospinal fluid (ACSF) into alternate lateral ventricles on postnatal days 7 and 8. The brains were perfusion-fixed 14 days later and immunohistochemistry was performed for TGF-beta1, -beta2 and -beta3, p44/42 mitogen-activated protein (MAP) kinases, and the extracellular matrix proteins laminin, vitronectin and fibronectin. Ventricular dilatation occurred in 58.3% of animals injected with blood and 36.7% of those injected with ACSF. Periventricular immunoreactivity for TGF-beta1 and -beta2 increased in injected animals irrespective of the presence or absence of ventricular dilatation, although the levels of both isoforms tended to be higher in animals with hydrocephalus. TGF-beta3 immunoreactivity was elevated in hydrocephalic rats only. The immunolabelling for phosphorylated p44/42 MAP kinases rose in a pattern similar to that for TGF-beta1 and -beta2. Expression of TGF-betas was accompanied by deposition of the extracellular matrix proteins fibronectin, laminin and vitronectin. The changes caused by injection of ACSF were the same as those caused by injection of blood. Our results raise the possibility that expression of TGF-betas, together with extracellular matrix protein deposition, may be involved in the development and/or maintenance of hydrocephalus after ventricular distension due to haemorrhage in the neonate.

Animals↗
PubMed2004

Posthaemorrhagic ventricular dilatation: new mechanisms and new treatment.

Post haemorrhagic ventricular dilatation is associated with a high rate of disability, multiple impairments and adverse effects of shunt surgery for hydrocephalus. Post haemorrhagic ventricular dilatation results initially from multiple small blood clots throughout the cerebrospinal fluid channels impeding circulation and re-absorption. Transforming growth factor beta is released into the cerebrospinal fluid and there is evidence that this cytokine stimulates the laying down of extracellular matrix proteins which produce permanent obstruction to the cerebrospinal fluid pathways. Prolonged raised pressure, pro-inflammatory cytokines and free radical damage from iron may contribute to periventricular white matter damage and subsequent disability. Interventions such as early lumbar punctures, diuretic drugs to reduce cerebrospinal fluid production and intraventricular fibrinolytic therapy have been tested and, not only fail to prevent shunt dependence, death or disability, but have significant adverse effects. Surgical interventions such as subcutaneous reservoir, external drain, choroid plexus coagulation and third ventriculostomy have not been subject to controlled trial. Ventriculoperitoneal shunt is not feasible in the early phase after intraventricular haemorrhage but, despite the problems with blockages and infections, remains the only option for infants with excessive head expansion over periods of weeks. We have piloted drainage, irrigation and fibrinolytic therapy as a way of removing blood early enough to stop the progressive deposition of matrix proteins, permanent hydrocephalus and shunt dependence.

Cerebral Hemorrhage↗
PubMed2004

Iron status in a group of Norwegian children aged 6-24 months.

UNLABELLED: An adequate iron status is of vital importance for health and development in infancy and early childhood. Iron status was evaluated in a group of full-term Norwegian children followed longitudinally, at the ages of 6 mo (n = 278), 12 mo (n = 249) and 24 mo (n = 231) by measuring haemoglobin (Hb), mean cell volume (MCV) and serum ferritin. At 6, 12 and 24 mo of age, 3, 10 and 12%, respectively, had iron deficiency anaemia (IDA) defined as Hb <110 g/l in combination with ferritin <15 microg/l. With more restrictive criteria for defining IDA (Hb <110 g/l or <105 g/l in combination with ferritin <12 microg/l), the prevalence decreased to 1-2% at 6 mo and 2-5% at 12 and 24 mo of age. If children with a history of fever in the previous month were excluded, the proportion of children with depleted iron stores (ferritin <10 microg/l) increased from 2 to 3% at 6 mo, from 5 to 7% at 12 mo and from 9 to 13% at 24 mo. CONCLUSION: Mild iron deficiency anaemia exists among otherwise healthy Norwegian infants and toddlers. The prevention and early treatment of iron deficiency should be a priority for the child health services.

Age Factors↗
PubMed2003

Effect of global hypoxia-ischaemia followed by 24 h of mild hypothermia on organ pathology and biochemistry in a newborn pig survival model.

BACKGROUND: Perinatal asphyxia may lead to multiorgan damage as well as brain injury. Posthypoxic hypothermia (HT) may protect other organs in addition to the brain. The aim of this study was to assess the systemic effects of our global hypoxic-ischaemic (HI) insult and compare the effect of mild 24-hour HT with normothermia (NT) during unsedated recovery. METHOD: Thirty-eight newborn pigs were subjected to 45 min of global HI by ventilating them with approximately 6% O2. On reoxygenation, pigs were randomised to NT or HT. The 18 NT piglets were maintained at rectal temperature 39.0 degrees C for 72 h. Twenty-three HT pigs (20 experimental HT and 3 sham controls) were cooled to rectal temperature 35 degrees C for 24 h before NT was resumed and the animals then survived a further 48 h. RESULTS: All lesions were small with no apparent clinical effect. The incidence of any damage to the heart (6 HT vs. 9 NT), liver (9 HT vs. 7 NT), kidney (6 HT vs. 9 NT) or intestinal injury (8 HT vs. 2 NT, p = 0.07) was not different in the two groups. More HT piglets developed lung injury, 10 HT and 3 NT. Plasma [Na], [K], [Ca] and [Mg] increased significantly after the HI insult as compared to baseline values. For the 24-hour period plasma [K] and [Ca] were significantly higher in the HT group, the mean area under the curve (AUC) being for [K] AUC(HT) 4.4 mmol/l vs. AUC(NT) 3.9 mmol/l, p = 0.04 and for [Ca] AUC(HT) 2.7 mmol/l vs. AUC(NT) 2.5 mmol/l, p = 0.01, respectively. Aspartate aminotransferase peaked at 48 h in the HT group and at 24 h in the NT group. Creatinine peaked at >72 h in the HT pigs and at 48 h in the NT pigs. White blood cells (WBC) peaked at 12 h for the HT pigs and at 6 h for the NT animals. AUC of the WBC during the cooling was significantly lower in the HT pig (AUC(HT) 11.1 vs. AUC(NT) 15.3 10(3)/mm3, p = 0.04). The HT pigs needed more glucose to maintain normal glucose during the last 12 h of HT. Also HT animals needed more oxygen during cooling to maintain PaO2. CONCLUSION: Twenty-four hours of mild HT did not reduce damage in any organ. There was a slight increase in lung damage in the HT group. None of the biochemical or pathological changes were of clinical significance. We conclude that mild HT for 24 h does not affect the organ systems adversely when compared to NT. Additional glucose and oxygen is needed during cooling to maintain normal values.

Adrenal Glands↗
PubMed2002

Furosemide for transient tachypnea of the newborn.

BACKGROUND: Transient tachypnea of the newborn results from delayed clearance of lung liquid and is a common cause of admission of full term infants to neonatal intensive care units. The condition is particularly common after elective Caesarean section. Conventional treatment involves appropriate oxygen administration and continuous positive airway pressure in some cases. Most infants receive antibiotic therapy. Hastening the clearance of lung liquid should shorten the duration of the symptoms and reduce complications. OBJECTIVES: To determine whether furosemide reduces the duration of oxygen therapy and respiratory symptoms and shortens hospital stay in term infants with transient tachypnea of the newborn. SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register, PubMed and EMBASE. The primary author and experts in the field were contacted. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials. Infants of less than 7 days of age, born after 37 or more weeks of gestation with the clinical picture of transient tachypnea of the newborn. Intravenous, oral or nebulized furosemide compared to placebo or no diuretic in the first 7 days. DATA COLLECTION AND ANALYSIS: Two reviewers assessed trial quality in each potentially eligible manuscript and two reviewers extracted data. MAIN RESULTS: Searching revealed only one randomised trial which was methodologically sound. This recruited 50 infants with transient tachypnea. Infants were randomised to receive oral furosemide 2 mg/kg followed by 1 mg/kg 12 hours later, or placebo. Weight loss in the first 24 hours was greater in the furosemide treated group but there was no evidence of a difference between the groups in duration of tachypnea or severity of symptoms or length of hospitalization. The study was methodologically satisfactory. REVIEWER'S CONCLUSIONS: Oral furosemide cannot be recommended as treatment for transient tachypnea of the newborn and it should not be used unless additional data become available. The question remains as to whether intravenous furosemide given to the infant (or even to the mother before Caesarean section) might shorten the duration of the illness. As elective Caesarean section continues at a high level, these two interventions might be worthy of trials.

Administration, Oral↗
PubMed2002

Cytokine response in cerebrospinal fluid from preterm infants with posthaemorrhagic ventricular dilatation.

AIM: Posthaemorrhagic ventricular dilatation (PHVD) is closely associated with white matter damage and neurological disability in the preterm infant. Proinflammatory cytokines have been implicated in the pathogenesis of white matter injury and subsequent cerebral palsy. The aim of this study was to determine the levels of proinflammatory cytokines in cerebrospinal fluid (CSF) from preterm infants with PHVD and to correlate the levels to white matter damage and neurodevelopmental outcome. METHODS: CSF samples were obtained from 24 preterm infants with expanding PHVD and 19 preterm infants with normal ultrasound. Tumour necrosis factor-alphaa (TNF-alpha ), interleukin-1beta (IL-1beta), interleukin-8 (IL-8) and interferon-gamma (IFN-gamma) in CSF were measured by enzyme-linked immunosorbent assay, and IL-6 was measured by bioassay. RESULTS: The concentrations of TNF-alpha, IL-1beta, IL-6 and IL-8 were significantly elevated in CSF from infants with PHVD. TNF-alpha was detected in 43% of PHVD infants and 11% of controls (p = 0.04). IL-1beta was detected in 67% of PHVD infants and 0% of controls (p < 0.0001). The concentrations of IL-6 were 368 (145-460) pg ml(-1) in the PHVD group and 30 (25-41) pg ml(-1) in the control group (p < 0.0001), and those of IL-8 were 3000 (1620-3400) pg ml(-1) in the PHVD group and 35 (0-230) pg ml(-1) in the control group (p < 0.0001). Cytokine concentrations did not correlate with white matter lesions on ultrasound, shunt dependence or neurological outcome within the PHVD group. CONCLUSION: There was an intense and prolonged inflammatory reaction in CSF from preterm infants with PHVD and a high risk for subsequent white matter injury and permanent neurological impairment.

Cerebral Hemorrhage↗
PubMed2002

Posthaemorrhagic ventricular dilatation.

Posthaemorrhagic ventricular dilatation is the most serious direct complication of intraventricular haemorrhage after preterm birth. It results initially from multiple small blood clots throughout the cerebrospinal fluid channels impeding circulation and reabsorption. Management is difficult and new treatment approaches are needed.

Cerebral Hemorrhage↗
PubMed2002

"Walk in to Work Out": a randomised controlled trial of a self help intervention to promote active commuting.

STUDY OBJECTIVE: To determine if a self help intervention, delivered via written interactive materials (the "Walk in to Work Out" pack), could increase active commuting behaviour (walking and cycling). DESIGN: Randomised controlled trial. The intervention group received the "Walk in to Work Out" pack, which contained written interactive materials based on the transtheoretical model of behaviour change, local information about distances and routes, and safety information. The control group received the pack six months later. Focus groups were also conducted after six months. SETTING: Three workplaces in the city of Glasgow, Scotland, UK. PARTICIPANTS: 295 employees who had been identified as thinking about, or doing some irregular, walking or cycling to work. MAIN RESULTS: The intervention group was almost twice as likely to increase walking to work as the control group at six months (odds ratio of 1.93, 95% confidence intervals 1.06 to 3.52). The intervention was not successful at increasing cycling. There were no distance travelled to work, gender, or age influences on the results. Twenty five per cent (95% confidence intervals 17% to 32%) of the intervention group, who received the pack at baseline, were regularly actively commuting at the 12 month follow up. CONCLUSION: The "Walk in to Work Out" pack was successful in increasing walking but not cycling. The environment for cycling must be improved before cycling will become a popular option.

Adult↗
PubMed2001

Emergency treatment of neonatal hyperammonaemic coma with mild systemic hypothermia.

An infant aged 3 days presented with hyperammonaemic coma and seizures, which were found to be a result of a urea-cycle defect. Haemofiltration, alternative pathway metabolites, and glucose and insulin failed to lower the plasma ammonia concentration below 2000 micromol/L. The infant was then cooled to a rectal temperature of 34 degrees C for 48 h and put on haemofiltration for 12 h. Plasma ammonia fell to around 100 micromol/L and remained at this concentration after haemofiltration. He roused from his coma, breathed spontaneously, and resumed bottle feeding. Hypothermia may be therapeutic in such instances of metabolic coma because it lowers the enzymatic rate of production of the toxin while non-enzymatic methods remove the toxin.

Ammonia↗
PubMed2001

Diuretic therapy for newborn infants with posthemorrhagic ventricular dilatation.

BACKGROUND: Intraventricular hemorrhage remains a serious complication of premature birth and post hemorrhagic hydrocephalus still has no satisfactory treatment. Acetazolamide and furosemide, which both reduce the production of cerebrospinal fluid, have been suggested as non-invasive therapies to reduce hydrocephalus and the need for ventriculo-peritoneal (V-P) shunting. OBJECTIVES: The aim of this review was to determine whether the use of acetazolamide and furosemide improves outcome, especially shunt dependence, in infants developing post-hemorrhagic ventricular dilatation. SEARCH STRATEGY: The standard search strategy of the Cochrane Collaboration was used. SELECTION CRITERIA: Randomised, or quasi-randomised trials, of acetazolamide and/or furosemide compared with standard therapy in infants with IVH or post-hemorrhagic ventricular dilatation DATA COLLECTION AND ANALYSIS: Data were extracted independently by each author and were analysed by the standard methods of the Cochrane Collaboration using relative risk (RR) and risk difference (RD), a fixed effect model and sensitivity analyses where appropriate. MAIN RESULTS: There were two eligible trials: one randomized 16 infants and the other, 177. Neither showed a decreased risk for V-P shunt or for V-P shunt or death associated with acetazolamide and furosemide therapy. The larger trial showed that acetazolamide and furosemide treatment resulted in a borderline increase in the risk for motor impairment at one year (RR 1.27, CI 1.02 to 1.58; RD 0.16, CI 0.02 to 0.31), but did not significantly affect the risk for the combined outcome of delay, disability or motor impairment among survivors, or the risk of the combined outcome of death, delay, disability or impairment at one year. The larger trial showed that diuretic treatment increased the risk for nephrocalcinosis (RR 5.31, CI 1.90 to 14.84; RD 0.19, CI 0.09 to 0.29); meta-analysis confirmed this result. REVIEWER'S CONCLUSIONS: Acetazolamide and furosemide therapy is neither effective nor safe in treating post hemorrhagic ventricular dilatation. Acetazolamide and furosemide cannot be recommended as therapy for post hemorrhagic hydrocephalus.

Acetazolamide↗
PubMed2001

Intraventricular haemorrhage and posthaemorrhagic hydrocephalus: pathogenesis, prevention and future interventions.

Intraventricular haemorrhage (IVH) is still a major complication of preterm birth with serious disability resulting. The fragile blood vessels in the germinal matrix below the ventricular lining and the instability of blood flow to this highly vascular area are the main mechanisms behind IVH. There is good evidence that corticosteroid therapy before preterm delivery reduces mortality and IVH substantially with a trend towards a reduction in disability. There is good evidence that postnatal indomethacin reduces IVH but no evidence that mortality or disability is reduced. There is evidence that stabilizing cerebral blood flow with pancuronium in infants with respiratory distress reduces IVH in the minority of infants with marked fluctuations. There is limited evidence that postnatal vitamin E and ethamsylate reduce IVH but insufficient evidence of reduced mortality or disability. Hydrocephalus following IVH results initially from multiple small blood clots throughout the CSF channels impeding circulation and re-absorption. Transforming growth factor beta is released into the CSF and there is mounting evidence that this cytokine stimulates the laying down of extracellular matrix proteins such as laminin and fibronectin which produce permanent obstruction to the CSF pathways. Interventions such as early lumbar punctures, diuretic drugs to reduce CSF production and intraventricular fibrinolytic therapy have been tested and, not only fail to prevent shunt dependence, death or disability, but have significant adverse effects. Surgical interventions such as subcutaneous reservoir and external drain have not been subject to controlled trial. Ventriculoperitoneal shunt is not feasible in the early phase after IVH but, despite the problems with blockages and infections, remains the only option for infants with excessive head expansion over periods of weeks. New treatment approaches aimed at preventing hydrocephalus are needed.

Cerebral Hemorrhage↗
PubMed2001

Brain specific proteins in posthaemorrhagic ventricular dilatation.

Median neurofilament and glial fibrillary acidic protein concentrations in the cerebrospinal fluid of 18 infants with posthaemorrhagic ventricular dilatation were 20-200 times higher than control values. S-100 protein in cerebrospinal fluid was four times higher than control values. Glial fibrillary acidic protein concentrations correlated with death or disability and with parenchymal lesions but not with shunt dependence.

Case-Control Studies↗
PubMed2001

Non-protein-bound iron is elevated in cerebrospinal fluid from preterm infants with posthemorrhagic ventricular dilatation.

Posthemorrhagic ventricular dilatation (PHVD) is closely associated with white matter injury and neurologic disability in the preterm infant. An important factor in periventricular white matter damage may be the specific vulnerability of iron-rich immature oligodendroglia to reactive oxygen species toxicity. Non-protein-bound iron (NPBI) is a potent catalyst in the generation of hydroxyl radicals (Fenton reaction). Our objective was to determine whether NPBI is increased in cerebrospinal fluid (CSF) from preterm infants with PHVD compared with preterm control infants. Samples of CSF were obtained from 20 infants with PHVD and 10 control subjects. The level of NPBI was determined by a new spectrophotometric method using bathophenanthroline as a chelator. To evaluate the effect of hemolysis, CSF and blood were mixed in different proportions, spun, frozen and thawed, and then analyzed for NPBI. NPBI was found in 75% (15 of 20) of infants with PHVD and in 0% (0 of 10) of control infants (p = 0.0002). Hemolysis induced in vitro did not result in any significant levels of NPBI. Within the group with PHVD, NPBI concentrations in CSF did not correlate with disability, parenchymal brain lesions, or the need for shunt surgery. NPBI was increased in CSF from preterm infants with PHVD, and the increase could not be explained by hemolysis alone. Free iron may help to explain the association between intraventricular hemorrhage and white matter damage.

Cerebral Hemorrhage↗