Evidence-based pediatrics: the future is now.
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Child↗
Biomedical subjects
E J Elliott
Publications and source records attributed to E J Elliott.
Do eicosanoids cause colonic dysfunction in experimental E coli O157:H7 (EHEC) infection?
BACKGROUND: The pathophysiology of enterohaemorrhagic Escherichia coli (EHEC) infection remains unclear. Eicosanoids have been implicated as pathophysiological mediators in other colitides. AIMS: To determine if prostaglandin E(2) (PGE(2)) and leukotriene B(4) (LTB(4)) contribute to mucosal inflammation and dysfunction in EHEC colitis. METHODS: Ten day old rabbits were infected with EHEC. For five days after infection, mucosal synthesis of PGE(2) and LTB(4) was measured in distal colonic tissue from control and infected animals and (51)Cr-EDTA permeability was assessed in vivo. Myeloperoxidase activity was measured and histological inflammation and damage were assessed at five days in control and infected animals and after treatment of infected animals with the LTB(4) synthesis inhibitor MK-886. In separate experiments, ion transport was measured in Ussing chambers, before and after in vitro addition of the cyclooxygenase inhibitor indomethacin. RESULTS: LTB(4) synthesis was increased from day 2 after infection onwards and PGE(2) synthesis was increased on day 3. Mucosal permeability did not increase until day 5 after infection. MK-886 inhibited colonic LTB(4) production but did not reduce diarrhoea, inflammation, or mucosal damage. Electrolyte transport was not significantly altered on day 3 after infection. However, both Cl secretion and reduced Na absorption found on day 5 were partially reversed by indomethacin. CONCLUSIONS: Tissue synthesis of PGE(2) and LTB(4) did not correlate temporally with EHEC induced inflammation or changes in mucosal permeability and ion transport. Cyclooxygenase inhibition partially reversed ion transport abnormalities but lipoxygenase inhibition did not affect mucosal inflammation or histological damage. We conclude that the contribution of eicosanoids to mucosal injury and dysfunction is more complex than previously suggested.
Animals↗
alpha 1-tubulin expression in proximally axotomized mouse cortical neurons.
This paper further characterizes the response to axotomy of mouse transcallosal cortical neurons, a population of neurons that seems to be particularly refractory to regeneration. Mouse transcallosal cortical neurons did not upregulate mRNA for the growth-associated protein alpha 1-tubulin following axotomy, even when the axonal distance from injury to cell body was only 100-300 microns. Previous experiments had found no upregulation of another growth-associated protein, GAP-43, by transcallosal neurons following axotomy 1-2 mm from the cell body. These latest results establish that this population of neurons fails to respond to axotomy even when it is extremely proximal and that this failure is not a peculiarity specific to one growth-associated protein but is indicative of a generally poor regenerative response.
Animals↗
Yellow nails following brown snake bite.
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Adolescent↗
Evidence-based paediatrics.
Evidence-based medicine is practised widely in some specialties and is now part of many undergraduate and graduate medical curricula. However, the extent to which it is used in clinical paediatric practice is not known and its expansion remains a major challenge. Access to technology which facilitates literature searching, and development of journals addressing specific paediatric problems, will encourage the use of evidence-based medicine by the busy paediatrician. Informed practice of evidence-based medicine will ensure that clinical expertise is complemented by a thorough search, evaluation and judicious application of relevant information from the medical literature.
Evidence-Based Medicine↗
Effect of proximal axotomy on GAP-43 expression in cortical neurons in the mouse.
As an approach to understanding why central neurons fail to regenerate, we have studied the response to proximal axotomy of transcallosal neurons of the cerebral cortex of the mouse. Anatomical studies have indicated only very slight regenerative responses by this population of cortical neurons. To further examine the regenerative response of these cells, we have looked by in situ hybridization at the expression of GAP-43 mRNA following axotomy caused by a stab wound delivered within about 200 microm to 1.25 mm of the cell body. Axotomized transcallosal neurons were compared with near-by unaxotomized transcallosal neurons, as well as with distant unaxotomized cortical neurons in the contralateral hemisphere. All three populations of neurons had been pre-labeled with Fluoro-Gold to allow identification. No up-regulation of GAP-43 mRNA above background levels was detected for axotomized cortical neurons at 1, 3 or 7 days after injury. In contrast, increases in mean silver grain density of up to 8-fold were measured in axotomized spinal cord motor neurons used as positive controls. Thus, as a population, the transcallosal cortical pyramidal neurons did not show a significant regenerative response, as monitored by GAP-43 upregulation, even with very close axotomy. These results identify this population of neurons as among the least regenerative studied, and suggest that, on a molecular level, inherent neuronal properties play a role in the limited regenerative response to brain injury.
Animals↗
Communicable diseases and the Australian Paediatric Surveillance Unit.
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Australia↗
Colonic structural and ion transport abnormalities in suckling rabbits infected with Escherichia coli K12.
BACKGROUND: Escherichia coli K12 is a laboratory strain considered nonpathogenic. The purpose of this study was to examine the effect of E. coli K12 infection on colonic structure and function. METHODS: Suckling rabbits were infected at 10 days of age with 6 x 10(9) CFU E. coli by intragastric inoculation and were examined 4 to 5 days later. Segments of ileum and proximal and distal colon were removed for light and electron microscopy, and NaCl transport was examined in vitro under short-circuited conditions in Ussing chambers. RESULTS: Infection did not cause weight loss or diarrhea. Colonic mucosa was inflamed with infiltration by polymorphonuclear neutrophils mainly in the lamina propria. The proximal and distal colon exhibited reduced Na+ absorption. The proximal colon also showed increased Cl- secretion; the ileum was unaffected. CONCLUSIONS: Infection with E. coli K12 disrupts the epithelium and alters ion transport in the colon, probably as a result of mucosal inflammation. The changes indicate that nonpathogenic E. coli have the potential to cause intestinal disease.
Animals↗
Progressive myoclonic epilepsies: recent genetic advances.
The progressive myoclonic epilepsies are a rare group of debilitating epileptic encephalopathies characterized by myoclonic seizures, progressive neurological dysfunction and dementia. In the past year advances in gene mapping have isolated gene loci for the majority of progressive myoclonic disorders, paving the way for specific diagnosis, more accurate prognosis and risk calculation, as well as opening the potential for prenatal and pre-symptomatic diagnosis in at risk families.
Adolescent↗
Pre-admission management of acute gastroenteritis.
OBJECTIVE: Acute gastroenteritis contributes to significant morbidity and need for hospital admission. The current literature suggests outpatient management is often inappropriate. This study examines the pre-admission management of children admitted with acute gastroenteritis to a major children's hospital. METHODOLOGY: Information was obtained from parental questionnaires and the medical notes for 164 children. RESULTS: Parents were poorly informed regarding appropriate home management. Over 70% sought professional advice prior to admission, usually from their general practitioner. Although 58% received advice on fluid therapy, an oral rehydration solution was recommended for only 32%, and only 9% actually used one before admission. Advice regarding fluid requirements was usually inadequate. Inappropriate medications were prescribed for 22% of children, including antibiotics (15.4%), antidiarrhoeals (1.2%) and anti-emetics (5.5%). Hospitalized children were generally well nourished with minimal dehydration and electrolyte disturbance. CONCLUSIONS: Oral rehydration therapy is utilized rarely and medications are over-utilized in home management of gastroenteritis. Education of parents, general practitioners and hospital doctors is essential to optimize outpatient management. The impact of optimal outpatient management on hospital admission rates and morbidity requires formal assessment.
Adolescent↗
Rare disease surveillance.
Rare diseases in children account for disproportionate morbidity and mortality and are particularly demanding of both families and health resources. Surveillance may provide data on their epidemiology, aetiology, management and outcome and on the support requirements of affected children. Existing methods for rare disease surveillance include mandatory and voluntary notification schemes, which may be active or passive, hospital discharge databases and death certification data. The recent establishment of the Australian Paediatric Surveillance Unit has facilitated active, prospective, national case ascertainment by voluntary notification of selected rare conditions. Information obtained should enable estimation of incidence rates, evaluation of prevention and management strategies, extend data collected by existing methods and help estimate future health needs.
Australia↗
Predictive value of umbilical artery pH in preterm infants.
Compared with term infants, little information is available about the usefulness of the umbilical artery pH in relation to outcome in extremely preterm infants. This prospective study evaluates the relation between umbilical artery pH (UapH), Apgar scores, perinatal events, and outcome in infants born at less than 32 weeks' gestation. Six hundred and twenty three infants of < 32 weeks' gestation were studied. The median UapH was 7.25, with a range of 6.78-7.49. A low UapH was significantly associated with male sex, hyaline membrane disease, grade 3 or 4 intraventricular haemorrhage, and neonatal death. It was also associated with lower birth weight and lower birthweight centile. The relations between the UapH and outcomes of neonatal death, cerebral palsy, and developmental quotient at 1 year, and other perinatal risk factors were then examined using multiple logistic regression. After adjusting for other risk factors, UapH was not significantly associated with any outcome. In contrast, a low one minute Apgar (< 4) remained a significant risk factor, with odds ratios of 2.7 (95% confidence interval (CI) 1.5 to 5.2) for neonatal death and 3.8 (95% CI 1.4 to 10.4) for cerebral palsy.
Apgar Score↗
Rare disease surveillance in children.
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Australia↗
Ion transport across lingual epithelium is modulated by chorda tympani nerve fibers.
Each chorda tympani (CT) nerve innervates taste cells in fungiform papillae on one side of the anterior two-thirds of mammalian tongues. In this study, three effects of unilateral CT transection were investigated: (1) the persistence of taste cells on the ipsilateral and contralateral sides; (2) the ability of the CT to modulate ion transport across the ipsilateral and contralateral sides of canine lingual lingual epithelia; and (3) the effect on contralateral CT responses. Unilateral transection of dog CT caused the mean number of taste buds/fungiform papilla on the ipsilateral side to decrease from five to zero by 29-30 days after surgery. Taste buds reappeared after 44 days but in reduced numbers (two taste buds/papilla). This reappearance of taste buds after 44 days is consistent with the time predicted for the CT to regenerate and reach the anterior portion of the tongue. The number of taste buds/papilla remained unchanged on the contralateral side. Measurements of the short-circuit current (Isc) across both ipsilateral and contralateral sections of isolated canine lingual epithelia were performed at various times after unilateral CT transection. Both sides responded similarly. The Isc began to decline after 3 days, reached a minimum after approximately 18 days (approximately 40% of control Isc) and increased to control values after approximately 40 days. This includes experiments performed 30 days after surgery, when no taste buds were present on the ipsilateral side and the Isc was 80% of control values. For all times after CT transection, amiloride, an epithelial Na+ channel blocker, inhibited Isc. Thus, epithelial cells in dog tongue have amiloride-inhibitable pathways. These results show that proteins involved in active Na+ transport across lingual epithelial can be modulated by CT nerve fibers.
Animals↗
Bicarbonate and citrate in oral rehydration therapy: studies in a model of secretory diarrhea.
In situ perfusion of the rat jejunum and ileum was used to study the effect of inclusion of bicarbonate or citrate on the ability of four oral rehydration solutions to promote small-intestinal absorption of water and sodium. Solutions varied in their sodium (60-90 mM) and glucose (111-140 mM) content and osmolality (281-331 mosmol/kg). They were studied before and after exclusion of base both in normal intestine and in secreting intestine after exposure to cholera toxin. All solutions promoted net water absorption in the normal intestine and reversed net water secretion to absorption in the cholera toxin-treated intestine to varying degrees. Net sodium movement was directly related to the sodium content of oral rehydration solutions. Inclusion of bicarbonate or citrate did not promote significantly greater absorption of water or sodium than did solutions without base, in normal or secreting intestine. In the secreting intestine, inclusion of bicarbonate in two solutions actually resulted in greater sodium secretion than did identical solutions from which bicarbonate was omitted. These studies suggest that the inclusion of base or base precursors in oral rehydration solutions to enhance water and sodium absorption is unjustified in both normal and secreting small intestine.
Animals↗
Lafora disease: a progressive myoclonus epilepsy.
Lafora disease is a rare inborn error of metabolism resulting in storage of a polyglucosan in tissues including the brain, skin and liver. Four children are described with progressive myoclonus epilepsy and intellectual deterioration in whom this diagnosis was made. In two the diagnosis was confirmed by the presence of periodic acid schiff (PAS) positive, diastase resistant, colloidal iron staining inclusion material in the liver when they were referred to a paediatric gastroenterologist with abnormal liver function tests. In one, the diagnosis was made from cerebellar biopsy, although on retrospective review the liver biopsy performed at this time was abnormal. In a fourth child, whose sibling was affected, histological diagnosis was confirmed by skin biopsy, although clinical and EEG findings had been highly suggestive for several years. The disease has autosomal recessive inheritance, is progressive and the prognosis is poor. Paediatricians should be aware of this diagnosis, which is often delayed, as early histological diagnosis allows prognostic and genetic counselling and optimal treatment. Although the diagnosis was made by liver or brain biopsy in three cases, skin biopsy offers a reliable, less invasive means of diagnosis.
Adolescent↗