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Biomedical subjects

E J Elliott

Publications and source records attributed to E J Elliott.

At least 37 records · Page 2Linked to original sources

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↗

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↗

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↗

Dominant role for osmolality in the efficacy of glucose and glycine-containing oral rehydration solutions: studies in a rat model of secretory diarrhoea.

The effect of osmolality on the efficacy of oral rehydration solutions (ORS) and the contribution of the amino acid glycine to water absorption from ORS have been studied in an animal model of secretory diarrhoea. After exposure to pure cholera toxin, rat small intestine (excluding the duodenum) was perfused in situ with seven different ORS. All ORS were derived from a "basic" solution containing Na 50, K 25, Cl 75 and glucose 50 mmol/l to which 25 or 50 mmol/l of glycine, glucose, or mannitol was added. All ORS reversed water secretion to absorption, but maximum water absorption was obtained with the "basic" solution with an osmolality of 200 mOsm/kg. When the osmolality of the "basic" solution was raised to 225 and 250 mOsm/kg by adding mannitol, water absorption decreased. At each of these osmolalities, substitution of mannitol by glycine or glucose resulted in similar increases in water absorption, but all modifications compared unfavourably with the "basic" solution. Net sodium secretion occurred with all ORS tested, despite net water absorption. These findings in a perfusion model of rat small intestine suggest that osmolality is a key factor influencing the efficacy of ORS and that addition of a second substrate, such as glycine, has no beneficial effects. Our results suggest that there is a maximal rate for water absorption from the small intestine which is inversely related to the osmolality of the perfusate.

Animals↗

Water and solute absorption from a new hypotonic oral rehydration solution: evaluation in human and animal perfusion models.

Controversy continues regarding the optimal composition of glucose electrolyte oral rehydration solutions for the treatment of acute diarrhoea. Four perfusion models (normal human jejunum, normal rat small intestine, cholera toxin treated secreting rat small intestine and rotavirus infected rat small intestine) have been developed and used to compare the efficacy of a hypotonic oral rehydration solution with standard United Kingdom British National formulary and developing world oral rehydration solutions (WHO). Despite obvious physiological and pathophysiological differences between these models there was general congruence in the water and solute absorption profiles of the different oral rehydration solutions. Hypotonic oral rehydration solution promoted significantly greater water absorption than other oral rehydration solutions in all rat models (p < 0.001) but apparently increased water absorption failed to achieve significance in human jejunum. British National Formulary-oral rehydration solution was unable to reverse net water secretion in both rotavirus and cholera toxin models. Net sodium absorption from hypotonic and WHO-oral rehydration solutions was significantly greater than from the low sodium British National Formulary-oral rehydration solutions (p < 0.001) except in the rotavirus model when absorption was similar to hypotonic-oral rehydration solutions. These findings show that there is agreement in the apparent efficacy of oral rehydration solutions in these animal and human perfusion models, and that improved water absorption with adequate sodium absorption may be achieved by reducing oral rehydration solution osmolality.

Adolescent↗

Water and solute absorption from hypotonic glucose-electrolyte solutions in human jejunum.

While oral rehydration therapy with glucose-electrolyte solutions is highly effective, the optimal formulation has not yet been defined. Recent clinical studies suggest that stool volume, and thus water losses, may be reduced if glucose is replaced by a polymeric substrate which reduces osmolality. It is possible that the efficacy of glucose monomer based oral rehydration solutions (ORS) will also improve if osmolality is decreased. Using jejunal triple lumen perfusion in healthy adult volunteers net water and solute absorption were studied from three hypotonic solutions with different sodium concentrations (46, 60, 75 mmol/l) but identical glucose concentrations (90 mmol/l), thus allowing osmolality to rise (210, 240, and 270 mOsm/kg, respectively). Results from these solutions (ORS 45:210, ORS 60:240, and ORS 75:270) were compared with the World Health Organisation oral rehydration solution (WHO-ORS). Greatest water absorption was seen with ORS 60:240 (p less than 0.01). Sodium absorption from ORS 60:240 and WHO-ORS was similar and greater than sodium absorption from ORS 45:210 (p less than 0.05). Potassium and glucose absorption were greater from ORS 60:240 than from any of the other hypotonic solutions (p less than 0.05) and were equal to absorption from WHO-ORS). These results in a short segment of healthy human jejunum suggest that hypotonic ORS containing monomeric glucose may increase water absorption.

Adolescent↗

Comparison of rat and human intestinal perfusion models for assessing efficacy of oral rehydration solutions.

The optimal composition for oral rehydration solutions remains controversial. Animal models have been used to assess the efficacy of new formulations but the relevance of these studies to the handling of oral rehydration solutions in human intestine during diarrhoeal disease states remains uncertain. Using steady state perfusion techniques we have compared water and solute transport from a variety of oral rehydration solutions in both the entire rat small intestine and in the human jejunum. Overall the pattern of water, sodium and glucose absorption was similar from the three oral rehydration solutions tested, indicating close parallelism between the two models despite the species and methodological differences. Although the relationship between the findings of these studies to the handling of oral rehydration solution in diarrhoeal disease states remains uncertain, we believe they do support the view that animal models may have a part to play in the preliminary screening of oral rehydration solutions before clinical trial.

Adult↗

Search for the ideal oral rehydration solution: studies in a model of secretory diarrhoea.

In situ perfusion of whole rat small intestine was used to compare the efficacy of five oral rehydration solutions in promoting water and sodium absorption in normal intestine and secreting intestine after exposure to cholera toxin. Solutions varied in their sodium (35-90 mmol/l) and glucose (111-200 mmol/l) concentrations, molar ratio of glucose:sodium (1.2-5.8), and osmolality (281-331 mOsmol/kg), and contained either bicarbonate (18-30 mmol/l) or citrate (10 mmol/l). In normal intestine all solutions promoted net water absorption. Cholera toxin induced reproducible water secretion but all solutions reversed this to absorption. Water absorption was greatest with solutions containing sodium 60 mmol/l and glucose 111 or 140 mmol/l, and with a glucose:sodium ratio approximately 2, in both normal and secreting intestine. All solutions promoted net glucose absorption in both normal and secreting intestine. Net sodium absorption occurred with solutions containing greater than or equal to 60 mmol/l sodium in normal intestine but sodium secretion occurred from all solutions in secreting intestine. Sodium movement was directly related to the sodium concentration of the solution and sodium secretion occurred despite net water and glucose absorption. We consider that these studies may guide future development of oral rehydration solutions.

Animals↗

The anion in salt taste: a possible role for paracellular pathways.

It is well established from psychophysical and electrophysiological measurements that both Na and Cl contribute to the taste response to NaCl. The contribution of Na to the NaCl response can be studied using amiloride, a drug that inhibits Na transport in taste and other epithelial cells. The pathways involved in response to Cl are less well understood. We undertook a series of experiments in the rat to determine whether tonic chorda tympani responses to NaCl are inhibited by specific inhibitors of anion transport. Whole nerve responses to NaCl were unchanged by bathing the tongue in SITS, DIDS, bumetanide, furosemide, 9-anthracene carboxylic acid, or an antibody that blocks Cl conductance pathways in many epithelia. Thus, Cl co-transporters, exchangers, and channels (at least in the apical membrane of taste cells) are probably not involved in NaCl taste responses. When other anions (acetate, isethionate, methane sulfonate, gluconate, tartrate), which are generally impermeant in other Cl-selective pathways, were substituted for Cl, the dose-response curves for the chorda tympani response were shifted toward higher concentrations than the response to NaCl, but achieved the same maximum value at sufficiently high concentrations (1.0 M Na). For all the organic Na salts, the amiloride-insensitive portion of the response was substantially less than for NaCl. Experiments with Na acetate at different pHs showed that intracellular acidification is not responsible for the differences between NaCl and organic salts of Na. One possibility which remains is that apical stimulation with these other Na salts results in a taste cell membrane potential that is hyperpolarized with respect to the membrane potential in NaCl.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetates↗