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Biomedical subjects

N Evans

Publications and source records attributed to N Evans.

At least 37 records · Page 2Linked to original sources
PubMed2003

Effect of early targeted indomethacin on the ductus arteriosus and blood flow to the upper body and brain in the preterm infant.

OBJECTIVE: To determine if indomethacin given to preterm infants with a large ductus arteriosus (DA) in the first hours of life results in maintained or improved brain and upper body blood (superior vena cava (SVC)) flow. STUDY DESIGN: A randomised, double blind trial of indomethacin v placebo. Echocardiography was performed on 111 infants born at < 30 weeks gestation at 3 and/or 10 hours after birth. Infants were eligible if the DA diameter was > 1.6 mm. Infants were randomised to receive indomethacin 0.2 mg/kg or placebo. Crossover occurred if the DA was still > 1.6 mm. Echocardiography was performed one hour after each treatment. RESULTS: Seventy (63%) infants had a DA > 1.6 mm, with 35 randomised to receive indomethacin and 35 to receive placebo. At one hour there was no difference in DA constriction (indomethacin -20% v placebo -15%), change in SVC flow (-1% v -9%), for right ventricular output (RVO). Two hours after indomethacin, 62 infants had uncontrolled observations, at which time significant ductal constriction had occurred. At this time, infants of > or = 27 weeks gestation had significantly greater increases in SVC flow and RVO than infants of < 27 weeks gestation. Infants with failed ductal constriction had significantly lower initial SVC flow and developed more late grade 3/4 peri/intraventricular haemorrhage (P/IVH). Initial SVC flow, but not ductal constriction, was a significant predictor of late grade 3/4 P/IVH in adjusted analysis. CONCLUSIONS: Indomethacin had minimal effect on ductal constriction and blood flow at one hour compared with placebo. Failure of ductal constriction is associated with low SVC flow and subsequent late severe P/IVH.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2003

Analysing differences in clinical outcomes between hospitals.

OBJECTIVE: To examine the variation between hospitals in rates of severe intraventricular haemorrhage (IVH) in preterm babies adjusting for case mix and sampling variability. DESIGN: Cross sectional study of pooled data from 1995 to 1997. SETTING: 24 neonatal intensive care units (NICUs) in the Australian and New Zealand Neonatal Network. PARTICIPANTS: 5413 infants of gestational age 24-30 weeks. MAIN OUTCOME MEASURES: Crude rates of severe (grades 3 and 4) IVH and rates adjusted for case mix using logistic regression, and for sampling variability using shrinkage estimators. RESULTS: The overall rate of severe IVH was 6.8%, but crude rates for individual units ranged from 2.9 to 21.4%, with interquartile range (IQR) 5.7-8.1%. Adjusting for the five significant predictor variables--gestational age at birth, 1 minute Apgar score, antenatal corticosteroids, transfer after birth, and sex--actually increased the variability in rates (IQR 5.9-9.7%). Shrinkage estimators, which adjust for differences in unit sizes and outcome rates, reduced the variation in rates (IQR 6.3-7.5%). Adjusting for case mix and using shrinkage estimators showed that one unit had a significantly higher adjusted rate than expected, while another was significantly lower. If all units could achieve an average rate equal to the 20th centile (5.74%), then 60 cases of severe IVH could be prevented in a 3 year period. CONCLUSIONS: The use of shrinkage estimators may have a greater impact on the variation in outcomes between hospitals than adjusting for case mix. Greater reductions in morbidity may be achieved by concentrating on the best rather than the worst performing hospitals.

Australia↗
PubMed2002

Immunohistochemical localisation of nicotinic acetylcholine receptor subunits in human cerebellum.

Neuronal nicotinic acetylcholine receptors are members of the ligand-gated ion channel superfamily composed of alpha and beta subunits with specific structural, functional and pharmacological properties. In this study we have used immunohistochemistry to investigate the presence of nicotinic acetylcholine receptor subunits in human cerebellum. Tissue was obtained at autopsy from eight adult individuals (aged 36-56 years). Histological sections were prepared from formalin-fixed paraffin-embedded material. alpha 3, alpha 4, alpha 6, alpha 7, beta 2, and beta 4 subunits were present in this brain area associated with both neuronal and non-neuronal cell types. Most Purkinje cells were immunoreactive for all the above subunits, but most strongly for alpha 4 and alpha 7. A proportion of granule cell somata were immunoreactive for all subunits except alpha 3. Punctate immunoreactivity in Purkinje cell and granule cell layers was evident with antibodies against alpha 3, alpha 4, alpha 6, and alpha 7 in parallel with synaptophysin immunoreactivity, suggesting the presence of these subunits on nerve terminals in the human cerebellum. All subunits were present in the dentate nucleus associated with neurones and cell processes. Strong immunoreactivity of neuropil in both the molecular and granule cell layers and within the dentate nucleus was noted with alpha 4, alpha 7 and beta 4 subunits. Astrocytes and astrocytic cell processes appeared to be immunoreactive for alpha 7 and cell processes observed in white matter, also possibly astrocytic, were immunoreactive for beta2. Immunoreactivity to all subunits was noted in association with blood vessels. We suggest that nicotinic acetylcholine receptor subunits may be involved in the modulation of cerebellar activity. Further investigations are warranted to evaluate the participation of nicotinic acetylcholine receptors in cerebellar pathology associated with both developmental and age-related disorders.

Adult↗
PubMed2002

Perinatal risk factors for major intraventricular haemorrhage in the Australian and New Zealand Neonatal Network, 1995-97.

BACKGROUND: In 1995, large differences were identified in rates of grade 3-4 intraventricular/periventricular haemorrhage (major IVH) among neonatal intensive care units (NICUs) in the Australian and New Zealand Neonatal Network. AIMS: To develop a predictive model for major IVH in order to allow risk adjustment for the variation in rates of major IVH among NICUs. METHODS: Rates of IVH were determined in 5712 infants of 24-30 weeks gestation born from 1995 to 1997. Significant antenatal and perinatal variables for major IVH in 1995 and 1996 were identified by univariate and multivariate analysis. A predictive model was developed and then validated on 1997 data. RESULTS: Rates of all grades of IVH fell from 1995 to 1997 (30.4 to 24.3%) but wide interunit variation remained. Seven antenatal and perinatal characteristics had significant association with major IVH: fetal distress, intrauterine growth restriction (protective), antenatal corticosteroids (protective), gestational age, 1 minute Apgar <4, male gender, and transfer after birth. A predictive model based on the last five of these variables was developed using data from 1995 and 1996 which gave an area under the receiver operator characteristic (ROC) curve of 0.76. This model was then validated on the 1997 dataset where an identical ROC curve resulted. CONCLUSIONS: Antenatal and perinatal factors are important in the pathogenesis of major IVH. The predictive model developed from these factors can be used to adjust for confounders in interunit outcome comparison.

Analysis of Variance↗
PubMed2002

Which to measure, systemic or organ blood flow? Middle cerebral artery and superior vena cava flow in very preterm infants.

AIM: To describe, in very preterm babies, postnatal changes in measures of middle cerebral artery (MCA) Doppler variables. To relate these peripheral measures to echocardiographic measures of systemic blood flow and ductal shunting, and to study their relation to subsequent intraventricular haemorrhage (IVH). METHODS: 126 babies born before 30 weeks were studied with serial echocardiography and cerebral and Doppler ultrasound of the MCA at 5, 12, 24, and 48 hours of age. Echocardiographic measures included superior vena cava (SVC) flow and colour Doppler diameter of the ductal shunt. MCA Doppler measures included mean velocity, pulsatility index (PI), and estimated colour Doppler diameter. RESULTS: MCA mean velocity increased whereas the PI decreased significantly over the first 48 hours. Babies with low SVC flow had significantly lower MCA mean velocity and estimated diameter than babies with normal SVC flow. There was no difference in PI. On multivariant analysis, the significant associations with MCA mean velocity were mean blood pressure (MBP), heart rate, SVC flow, and lower calculated vascular resistance. The significant associations with PI were larger ductal diameter and lower mean MBP. The significant associations with MCA diameter were higher SVC flow and lower calculated vascular resistance. After controlling for gestation, there was a highly significant association between lowest SVC flow and subsequent IVH but no association between IVH and lowest MCA mean velocity, estimated diameter, PI, or MBP. CONCLUSIONS: These data are consistent with the speculation that SVC flow is a reflection of cerebral blood flow. Low SVC flow is more strongly associated with subsequent IVH than cerebral artery Doppler measures or MBP.

Blood Flow Velocity↗
PubMed2001

Surface aneurysmal bone cysts: a pictorial review.

The aim of this article is to present the imaging features of surface aneurysmal bone cysts (ABCs). Twenty-three surface ABCs were identified from of a series of 144 histologically proven ABCs treated in our unit over the past 20 years. The surface ABCs showed a high female preponderance with a predilection for the forearm bones, tibia and femur. With the use of radiographs in all cases and CT and MR imaging in 18 cases it was possible to subdivide the series into subperiosteal (11 cases), cortical (8 cases) and mixed (4 cases) categories. The imaging features distinguishing the various categories are illustrated and the differential diagnosis is discussed.

Adolescent↗
PubMed2001

Early volume expansion for prevention of morbidity and mortality in very preterm infants.

BACKGROUND: Reduced perfusion of organs such as the brain, heart, kidneys and the gastrointestinal tract may lead to acute dysfunction and be associated with permanent injury. Various strategies have been used to provide cardiovascular support to preterm infants including inotropes, corticosteroids and volume expansion. OBJECTIVES: In very preterm infants, does early volume expansion reduce morbidity and mortality. If volume expansion is effective, what type of volume expansion is most effective. SEARCH STRATEGY: The standard search strategy of the Neonatal Review Group was used. Searches were conducted of the Oxford Database of Perinatal Trials, Cochrane Controlled Trials Register, MEDLINE, previous reviews including cross references, abstracts and conference proceedings. SELECTION CRITERIA: Randomised trials of early volume expansion with normal saline, fresh frozen plasma, albumin, plasma substitutes or blood compared to no treatment or another form of volume expansion in preterm infants < 32 weeks gestation or < 1500g were included. Volume expansion was defined as at least 10 mls/kg given in the first 72 hours of life. DATA COLLECTION AND ANALYSIS: Standard methods of the Neonatal Review Group with use of relative risk (RR), risk difference (RD) and weighted mean difference (WMD). The fixed effects model using RevMan 4.1 was used for meta-analysis. Data from individual studies were only eligible for inclusion if a least 80% of infants were reported for that outcome. MAIN RESULTS: Seven studies were included. Five studies, four with data for mortality, compared volume to no treatment. Most studies enrolled very preterm infants on the basis of gestation or birthweight. Two studies comparing different types of volume expansion enrolled very preterm infants with hypotension. No study enrolled infants on the basis of low blood flow. One study examined the effect of volume expansion on blood flow but in normotensive very preterm infants. Comparing volume and no treatment, 4 studies with a total of 940 very preterm infants reported no significant difference in mortality (RR 1.11, 95% CI 0.88, 1.40). The large NNNI 1996 study reported no significant difference in severe disability (RR 0.80, 95% CI 0.52, 1.23), cerebral palsy (RR 0.76, 95% CI 0.48, 1.20) and combined death or severe disability (RR 1.00, 95% CI 0.80, 1.24). Although one small study (Beverley 1985) reported reduced P/IVH with volume expansion, this was not supported by any other study. No significant difference was reported in grade 3-4 P/IVH and combined death or grade 3-4 P/IVH. One study (NNNI 1996) reported no significant difference in the incidence of hypotension. The finding of decreased necrotising enterocolitis and increased sepsis in infants who received fresh frozen plasma compared to a gelatin-based plasma substitute or no treatment in one study should be treated with caution. No significant differences in mortality or disability were found in this study. In one small study, there were no significant differences in outcomes between hypotensive infants who received colloid (albumin) or crystalloid (saline). REVIEWER'S CONCLUSIONS: There is no evidence from randomised trials to support the routine use of early volume expansion in very preterm infants without cardiovascular compromise. There is insufficient evidence to determine whether infants with cardiovascular compromise would benefit from volume expansion. There is insufficient evidence to determine what type of volume expansion should be used in preterm infants (if at all) or for the use of early red cell transfusions. The trial comparing colloid (albumin) and crystalloid (saline) in hypotensive preterm infants found no benefit in using a more expensive blood product compared to saline, but is insufficiently powered to detect an important clinical difference.

Blood Volume↗
PubMed2001

Early volume expansion versus inotrope for prevention of morbidity and mortality in very preterm infants.

BACKGROUND: Reduced perfusion of organs such as the brain, heart, kidneys and the gastrointestinal tract may lead to acute dysfunction and be associated with permanent injury. Various strategies have been used to provide cardiovascular support to preterm infants including inotropes, corticosteroids and volume expansion. OBJECTIVES: In very preterm infants, to determine the effect of early volume expansion compared to inotrope in reducing morbidity and mortality. Subgroup analysis was planned according to method of diagnosis of poor perfusion, postnatal age of treatment and type of volume expansion and inotrope used. SEARCH STRATEGY: The standard search strategy of the Cochrane Neonatal Review Group was used. SELECTION CRITERIA: All randomised trials that compared volume expansion to an inotrope in preterm infants in the first days of life were included. DATA COLLECTION AND ANALYSIS: Data were extracted independently by each author and analysed using the standard methods of the Cochrane Collaboration and its Neonatal Review Group using relative risk (RR), risk difference (RD) and weighted mean difference (WMD). MAIN RESULTS: Two small studies comparing volume expansion, using albumin, with dopamine were included. Both studies were adequately randomised, unblinded studies of albumin versus dopamine with no losses to follow up and analysed by intention to treat. Data for clinical outcomes were available from one study in hypotensive preterm infants in the first day of life. In this study, albumin had a higher failure rate for correcting hypotension (RR 5.2, 95% CI 1.3, 20.6). As 49% of these infants had already been given volume, the question of which treatment should be given first was not answered. A second study compared albumin with dopamine in preterm infants with a normal mean blood pressure at a mean age of 32 hours. Dopamine produced a significant increase in mean blood pressure when compared to infants who received albumin or no treatment, although the difference between the dopamine and albumin groups did not reach significance. Albumin and dopamine produced similar increases in left ventricular output but no significant change in cerebral blood flow. No difference was found in mortality (RR 1.5, 95% CI 0.5, 4.0) or morbidity including any P/IVH, chronic lung disease or retinopathy. There was a higher rate of grade 2-4 P/IVH of borderline statistical significance in infants who received albumin in one study (RR 1.47; 95% CI 0.96 to 2.25: RD 0.27, 95% CI 0.00 to 0.54). No data were available for neurodevelopmental outcomes. REVIEWER'S CONCLUSIONS: Dopamine was more successful than albumin at correcting low blood pressure in hypotensive preterm infants, many of whom had already received volume. Neither intervention has been shown to be superior at improving blood flow, or in improving mortality and morbidity in preterm infants. The trials do not allow any firm conclusions to be made as to whether or when volume or dopamine should be used in preterm infants.

Albumins↗
PubMed2001

Imaging recurrent parosteal osteosarcoma.

The aim of this study was to document the imaging features of recurrent parosteal osteosarcoma. The clinical and imaging records of 33 patients with a parosteal osteosarcoma referred to an orthopaedic oncology service over a 17-year period were retrospectively reviewed. The mode of identification of locally recurrent tumour was noted, together with the management and clinical outcome. Five patients developed a local recurrence of their parosteal osteosarcoma ranging from 6 months to 10 years after initial surgery. In 4 patients the recurrence was first suspected clinically due to the development of a mass. In the fifth patient recurrence was first detected on routine follow-up radiography. In 4 patients the recurrence could be identified on radiography as a mineralized mass. All the recurrences were readily identified on MR imaging, despite artefacts from prostheses. The recurrences were also evident in the 3 cases in which bone scintigraphy was performed. Local recurrence of parosteal osteosarcoma is adequately detected with a combination of clinical examination and conventional radiography. MR imaging is required to stage local recurrence or where radiography has failed to confirm clinically suspected recurrence. The routine use of MR imaging to follow-up patients is of doubtful value because of the frequently long time between initial surgery and relapse.

Adolescent↗
PubMed2001

MR imaging of brown tumour with fluid-fluid levels: a report of three cases.

Fluid-fluid levels on CT and MR imaging are a typical feature of aneurysmal bone cysts but have also been reported in many other osseous lesions containing haemorrhage. We report fluid-fluid levels in four brown tumour in three patients with primary hyperparathyroidism in which the initial radiological diagnosis was thought to be a bone tumour. To the authors' knowledge, this is the first time that association has been reported in the international literature.

Adult↗
PubMed2001

Gain- and loss-of-function Lyn mutant mice define a critical inhibitory role for Lyn in the myeloid lineage.

To investigate the role of the Lyn kinase in establishing signaling thresholds in hematopoietic cells, a gain-of-function mutation analogous to the Src Y527F-activating mutation was introduced into the Lyn gene. Intriguingly, although Lyn is widely expressed within the hematopoietic system, these mice displayed no propensity toward hematological malignancy. By contrast, analysis of aging cohorts of both loss- and gain-of-function Lyn mutant mice revealed that Lyn(-/-) mice develop splenomegaly, increased numbers of myeloid progenitors, and monocyte/macrophage (M phi) tumors. Biochemical analysis of cells from these mutants revealed that Lyn is essential in establishing ITIM-dependent inhibitory signaling and for activation of specific protein tyrosine phosphatases within myeloid cells. Loss of such inhibitory signaling may predispose mice lacking this putative protooncogene to tumorigenesis.

Aging↗
PubMed2001

Low systemic blood flow in the preterm infant.

Low systemic blood flow in the first hours after birth of a preterm infant is an often unrecognized complication. Traditional measures of cardiovascular adequacy used in the neonatal intensive care unit such as capillary refill time and blood pressure may not identify this problem. Longitudinal measurement of systemic blood flow demonstrates a falling off of blood flow in the first 6-12 h after birth, often to less than half of normal, before a gradual return to normal values by 24-48 h of age. Identification and appropriate treatment of this reduction in flow may assist in preventing some of the complications of prematurity.

Cardiac Output, Low↗
PubMed2001

Low systemic blood flow and hyperkalemia in preterm infants.

OBJECTIVE: Early low systemic blood flow is common in preterm infants. This study examines the relationship among low flow, renal function, and early changes in blood potassium (K(+)). METHODS: Preterm infants (n = 119) born before 30 weeks' gestational age underwent serial Doppler echocardiographic studies. Superior vena cava flow (SVC flow) was assessed as a measure of upper body systemic blood flow uncorrupted by systemic to pulmonary shunts. Serial whole blood K(+) concentrations on each arterial blood gas sample and urinary output in the first 48 hours were recorded. RESULTS: Most infants had a variable degree of rise in K(+) during the first 24 hours of life. The mean rate of rise was 0.17 mmol/L/h, the mean peak K(+) was 5.54 mmol/L, and the mean time of peak K(+) was 20 hours. The peak K(+) occurred after the lowest measured SVC flow in 84% of infants. A significant positive relationship was found between the lowest measured SVC flow and the mean (r = 0.31, P =.001) and peak (r = 0.31, P =.001) K(+) in the first 24 hours. Low SVC flow at 5 hours best predicted the rate of K(+) rise (r = 0.28, P =.002) and at 12 hours best predicted the peak K(+) concentration (r = 0.47, P <.001). The mean minimum SVC flow in the 17 babies who became hyperkalemic was 29.5 mL/kg/min versus 46.2 mL/kg/min in the 102 infants with normokalemia. Urine output in the first 24 hours was significantly lower in the hyperkalemic infants. A K(+) rate rise exceeding 0.12 mmol/L/h in the first 12 hours predicted low SVC flow with 93% accuracy. CONCLUSIONS: The data are consistent with a role for low systemic blood flow leading to reduced urinary output and subsequent hyperkalemia in preterm infants.

Blood Flow Velocity↗