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Biomedical subjects

E J Elliott

Publications and source records attributed to E J Elliott.

At least 55 records · Page 3Linked to original sources

Acetate absorption in the normal and secreting rat jejunum.

Acetate absorption was studied in rat jejunum using steady state perfusion in vivo. Absorption conformed to apparent saturation kinetics and was similar in magnitude to glucose absorption. When compared with normal saline, acetate perfusion was associated with luminal alkalinisation. There was no difference in total CO2 secretion when similar rates of acetate and glucose absorption were compared, suggesting that total CO2 secretion was the result of mucosal metabolism. Absorption of acetate and propionate were mutually inhibitory. Acetate absorption was also inhibited by Tris-Hepes pH 7.0. When the gut was pretreated with cholera toxin to induce a secretory state, acetate absorption was reduced by 41.9%. This effect could be reproduced if similar water secretion was osmotically induced by the addition of mannitol. These data suggest that acetate is absorbed, at least, partially by non-ionic diffusion in the rat jejunum and that its absorption is reduced in the secreting intestine by solvent drag.

Acetates↗

Clinical experience with a hypotonic oral rehydration solution for treatment of pediatric gastroenteritis in the United Kingdom.

Animal and human perfusion studies suggest that water absorption can be optimized by glucose-electrolyte solutions with low total osmolality. A new oral rehydration solution (ORS), reformulated Dioralyte (RD), containing 60 mmol/L of sodium and 90 mmol/L of glucose with an osmolality of 240 mosm/kg, was tested for safety and efficacy in children in the United Kingdom with acute gastroenteritis. In a double-blind, controlled trial, RD was compared with standard Dioralyte (SD), a widely used low-sodium, high-glucose solution containing 35 mmol/L of sodium and 200 mmol/L of glucose, with an osmolality of 310 mosm/kg. Infants and children aged 2 weeks to 3 years admitted with acute gastroenteritis of less than five days' duration and mild to moderate dehydration were randomized to receive either RD or SD. Clinical and laboratory assessments were made on admission and 12, 24, and 48 hours after treatment. Thirty-two children were enrolled in the study; 14 received RD and 18 SD. No adverse effects from either ORS were reported. Efficacy was evaluated in 24 patients, of whom eight received RD and 16 SD. Total ORS intake and intake in milliliters per kilogram were similar in both treatment groups. Mean fluid balance, mean percentage weight change, and median stool frequency did not differ between the groups at 12, 24, and 48 hours after onset of treatment. Three (12.5%) patients had greater than or equal to 0.05% reducing substances in the stool during treatment, and the incidence was similar in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Child, Preschool↗

Evaluation of three oral rehydration solutions designed for use in developed communities.

One hundred and sixteen children (less than 2 years old) admitted to a London hospital with acute gastroenteritis were randomized to receive either an oral rehydration solution (ORS) with low sodium and high glucose concentration (Na+ 35, glucose 200 mmol/L), an ORS with a high sodium but low glucose concentration (Na+ 60, glucose 111 mmol/L), or an ORS containing glycine and a glucose polymer (Na+ 50, glucose 50, glycine 50 mmol/L). Clinical, biochemical and haematological features of the three groups were similar on admission. Rotavirus was common (31%); the majority of children had minimal dehydration or acid-base disturbance. The clinical outcome, including ORS intake, prevention of dehydration, rehydration, and duration of hospital stay was similar in the three treatment groups. All initial electrolyte abnormalities were corrected; no child developed hypernatraemia or hyponatraemia. At 24 h, the mean serum urea was higher in those who received the ORS containing glycine than in other groups, and it had not fallen significantly since admission. Eighteen per cent of children had carbohydrate intolerance: four children with greater than or equal to 2% reducing substances in their stool had all received ORS with a high glucose content and had numerous watery green stools containing rotavirus. All ORS solutions were safe and effective for rehydration and correction of biochemical abnormalities, however carbohydrate intolerance was more prevalent in children who received the ORS with a high glucose content.

Acid-Base Equilibrium↗

Efficacy of a standard United Kingdom oral rehydration solution (ORS) and a hypotonic ORS assessed by human intestinal perfusion.

Human triple-lumen intestinal perfusion was used to compare water and solute absorption from the oral rehydration solution (ORS) most widely used in the United Kingdom and a new experimental hypotonic ORS (HYPO-ORS). HYPO-ORS (osmolality 210 mOsm/kg) promoted significantly greater water absorption than UK-ORS (7.03 +/- 1.1 vs 2.73 +/- 1.0 ml cm-1 h-1; P less than 0.01). HYPO-ORS produced net sodium and chloride absorption whereas the low sodium UK-ORS produced a net secretion of these ions. Bicarbonate absorption was also greater from HYPO-ORS although potassium and glucose absorption were similar from both solutions. This study suggests that UK-ORS may not promote optimal water and solute absorption and that clinical studies with HYPO-ORS are indicated.

Adult↗

The role of human perfusion techniques in the assessment of oral rehydration solutions.

Early human intestinal perfusion studies provided valuable information on gut transport procession in vivo. Subsequently, similar models have proved a useful means of assessing the efficacy of glucose-electrolyte oral rehydration solutions. In contrast to clinical trials they enable quantification of water and solute movement across the small intestine and, unlike animal studies, results are directly applicable to man. However, limitations exist, including the fact that a short, usually normal, segment of intestine is studied. Recent studies confirm the relationship between oral rehydration solution sodium concentration and sodium movement; the stimulatory effect of glucose on sodium and water movement; and the detrimental effect of high glucose content. Glycine, bicarbonate, citrate and acetate provide little additional benefit for water absorption when added to solutions containing glucose. Preliminary comparative studies of results obtained in the rat and in man show parallels between these models suggesting they may be complimentary methods of assessing new oral rehydration solutions.

Humans↗

Rise and fall of coeliac disease 1960-85.

A total of 192 children who presented with coeliac disease to Queen Elizabeth Hospital for Children from 1960-85 were reviewed in order to investigate the frequency and the age of presentation. There was a clear peak in the number of children presenting from 1971-5, and although the numbers declined subsequently they have remained at a level similar to numbers found before 1971. There was no difference in the mode of presentation but there was a definite increase in the age of presentation over the time period reviewed. Breast fed babies presented later than bottle fed babies (14 compared with 9 months) despite a similar age of gluten introduction. Similarly bottle fed babies and breast fed babies presented later after 1975 (10.5 compared with 7 months, and 18 compared with 9.5 months, respectively). Before 1975 the median age of gluten introduction was significantly less than that after 1975 (2 compared with 4 months) and the age of gluten introduction correlated with the age of presentation. It is concluded that breast feeding and the age of gluten introduction may influence the age of presentation of childhood coeliac disease but no clear reasons for the rise in incidence in the 1970s have been determined. It does not appear that the disease is declining, however, in recent years children have tended to present later in life.

Acute Disease↗

Oral rehydration therapy without bicarbonate for prevention and treatment of dehydration: a double-blind controlled trial.

Forty children (less than or equal to 2 years of age) were admitted to hospital with acute gastroenteritis and were randomly assigned to receive either an oral rehydration solution (ORS) containing bicarbonate (Na 35, K 20, Cl 37, HCO3 18, glucose 202 mmol litre-1) or an identical solution in which bicarbonate was replaced by chloride ions. Groups were matched for age, sex, ethnic origin, duration of diarrhoea and nutritional status. On admission, degree of dehydration, biochemical and haematological parameters were similar. The majority had minimal or no dehydration and only 30% had moderate to severe dehydration. All children were treated successfully with no complications. Oral rehydration solution intake by each group was similar. Clinical outcome, as judged by speed of rehydration or maintenance of hydration, duration of diarrhoea, stool frequency and length of hospital stay, was the same in both groups. After 24 h of ORS there was no difference between groups in venous pH, serum bicarbonate, urea and electrolytes. In hospitalized children with acute gastroenteritis in the United Kingdom an ORS without bicarbonate is a safe, effective means to prevent dehydration and maintain hydration and acid-base status where dehydration is not severe. Exclusion of bicarbonate would simplify production, increase stability and reduce the cost of ORS without apparent impairment of efficacy.

Acidosis↗

Effect of bicarbonate on efficacy of oral rehydration therapy: studies in an experimental model of secretory diarrhoea.

In situ perfusion of rat intestine was used to evaluate the effect of bicarbonate on the efficacy of a low sodium (35 mmol/l) glucose-electrolyte oral rehydration solution in normal and cholera toxin-treated rat small intestine. In normal intestine, absorption of water was greater (108 (8.1) microliters/min/g; p less than 0.01) and sodium secretion less (-4.3 (0.3) mumol/min/g; p less than 0.01) from the oral rehydration solution containing bicarbonate than from the solution in which bicarbonate was replaced by chloride ions (59.5 (7.2) microliters/min/g and -7.8 (0.8) mumol/min/g, respectively). Glucose absorption in normal intestine was similar with both solutions. In the secreting intestine, both oral rehydration solutions reversed net water secretion to absorption, but inclusion of bicarbonate resulted in significantly less net absorption of both water (2.18 (6.9) microliters/min/g; p less than 0.05) and glucose (18.7 (2.1) mumol/min/g; p less than 0.001) compared with bicarbonate free oral rehydration solution (19.4 (3.9) microliters/min/g and 35.8 (3.7) mumol/min/g, respectively). Net sodium secretion occurred in normal and secreting intestine but was significantly less with the bicarbonate containing oral rehydration solution. These findings suggest that the demonstrable advantage of bicarbonate in promoting water absorption from this oral rehydration solution in normal rat intestine does not apply to cholera toxin treated secreting intestine.

Animals↗

Morphology of chemosensory organs required for feeding in the leech Hirudo medicinalis.

Sensilla that line the upper edge of the lip in the leech Hirudo medicinalis and that contain chemoreceptors required for feeding were examined in the scanning and transmission electron microscopes. The sensilla include two size-classes of ciliated button-like mounds--one about 35 microns in diameter and another about 10 microns in diameter. The larger sensilla are at the center of unpigmented patches of skin which are visible in the light microscope, while the smaller sensilla have not been previously described as distinct structures. Electron microscopy, though not light microscopy, shows that the lip sensilla differ markedly from the segmental sensilla of the leech, which have been shown to mediate mechanoreception and photoreception. In particular, the chemosensory lip sensilla contain multiciliated cells with cilia of a uniform length, whereas the segmental sensilla contain uniciliated cells with long, whip-like cilia, as well as multiciliated cells with short, stiff cilia. Thus, the two types of sensilla differ morphologically as well as functionally. In addition to the ciliated sensilla along the upper lip, structures consisting of a short, club-like process surrounded by granular material were observed inside the mouth. These structures may also be chemosensory organs.

Animals↗

Patient use of a paediatric hospital casualty department in the east end of London.

This paper describes two surveys carried out at the accident and emergency department of Queen Elizabeth Hospital, a specialist children's hospital situated in the east end of London. Both studies explored factors influencing attendance at the accident and emergency department. One was based on an analysis of recorded information (hospital notes) for a random sample of attenders, spread over a 12-month period. The second was based on personal interviews with a sample of children's parents. Both studies found problems with access to general practitioner care to be the main factors influencing attendance.

Child↗

The parD- mutant of Escherichia coli also carries a gyrAam mutation. The complete sequence of gyrA.

The phenotype of a recently-described mutant (OV6), conditionally defective in chromosome partitioning and septal positioning, was originally thought to be due to a new gene (parD) mapping at 88.4 min. We have now shown that, in addition to the parD mutation, OV6 carries a gyrAam mutation and that this mutation is probably responsible for the gross phenotype of the mutant. We have cloned the gyrA gene, identified the GyrA protein, sequenced the gyrA gene and flanking genes, cloned and sequenced the gyrAam mutation, and identified its truncated product. In addition, we have identified the transcriptional start point of the gyrA gene. The E. coli GyrA protein has extensive homologies with Gyrase proteins of other organisms and weak sequence homologies with some eukaryotic cytoskeletal proteins.

Amino Acid Sequence↗

Chemosensory stimuli in feeding behavior of the leech Hirudo medicinalis.

The involvement of chemotherapy stimuli in the feeding behavior of the blood-sucking leech Hirudo medicinalis was investigated using a behavioral feeding test in which test solutions were encased in a highly permeable membrane and presented to the leech. Whole human blood or plasma at ambient temperature elicited the complete sequence of feeding behavior: probing, attachment, biting and ingestion. Spring water, 300 mM sucrose, or dialyzed plasma did not elicit any of these responses. Spring water warmed to 38 degrees C elicited probing and transient attachment but not ingestion. Thus, appropriate chemical stimuli were necessary for complete feeding behavior. A chemically defined artificial blood mix, containing the major components of low molecular weight found in blood, elicited all aspects of leech feeding behavior. Eliminating either NaCl or arginine from the mix resulted in complete loss of effectiveness. Moreover, a solution containing only NaCl (150 mM) and arginine (90 microM) was also an effective feeding stimulus. Thus, appropriate chemical stimuli are sufficient for complete feeding behavior. Neither NaCl nor arginine alone induced feeding although NaCl alone elicited probing. Sensory detection of blood was localized to a region of the dorsal lip that contains structures composed of ciliated, bipolar neurons, which are likely candidates as chemoreceptors. Surgical ablation of this region of the skin resulted in complete loss of ability to alert to, orient toward and ingest blood, while sham-operated controls fed normally. Substitution with other ions revealed specificity, with respect to both the cation and the anion, in the response to NaCl. Of the inorganic and organic cations tested, only Li+ substituted effectively for Na+. Of the inorganic and organic anions tested, only Br- was as effective as Cl-. Thus, the requirement for NaCl in leech feeding represents more than simply an ionic strength requirement or a requirement for Na+ ions and bears similarities to the chemosensory detection of NaCl in other species. Substitution with other amino acids and analogues for arginine revealed marked specificity in the feeding response to this compound as well. D-arginine at concentrations of up to 1000-fold greater than the effective threshold for L-arginine did not elicit ingestion, nor did other common L-amino acids, including the other basic amino acids histidine and lysine. Of the arginine analogues tested, only homoarginine and canavanine (in which all three functional groups of arginine are unchanged) were effective feeding stimulants.

Animals↗

Morphological evidence that regenerating axons can fuse with severed axon segments.

Regenerating axons of sensory neurons in the leech nerve cord usually reconnect with their normal targets by growing the entire distance from the site of lesion to the target. However, in less than 1% to nearly 10% of cases a rapid restoration of the normal arborization occurs when the regenerating axon connects with the severed distal segment of the same cell or another cell of the same modality. The passage of horseradish peroxidase (mol. wt approximately 40,000 daltons) from the regenerating axon selectively into the axon or cell with which it has connected indicates that the two have joined or fused, rather than become linked by an electrical synapse, as sometimes occurs for other neurons in the leech. These results support the conclusions, based largely on physiological data from regenerating motor axons in crayfish, that unusually rapid and complete regeneration can occur when a growing axon fuses with its severed distal segment.

Animals↗

Microglial movement to sites of nerve lesion in the leech CNS.

The small glial cells in the central nervous system of the leech, Hirudo medicinalis, have been studied using two histological stains. Weak silver carbonate, a classic stain for vertebrate microglia, can selectively stain these small glial cells and shows that they are morphologically similar to vertebrate microglia. Feulgen's DNA-specific stain is useful for counting the compact and distinctive microglial nuclei. In uninjured connectives, which link segmental ganglia, there are 134 +/- 28 microglia per 210 micron of connective length. Within 24 h after the nerve cord is crushed leech microglia aggregate at the site of injury. This increase in cells, seen both in vivo and in culture, is approximately 5-fold. Although cells do not continue to accumulate at the injury site after the first day, their numbers continue to vary with time in the regions immediately adjacent to the crush for at least one week. A second crush made 24 h after the first shows that leech microglia are capable of responding to repeated injury.

Animals↗

Accurate regeneration of an electrical synapse between two leech neurones after destruction of the ensheathing glial cell.

An interneurone, the S cell in the central nervous system of the leech, regenerates its severed axon and forms an electrical synapse with its target, another S cell, entirely within the ensheathment of two glial cells. After the two glial cells were killed selectively by intracellular injection of protease, axonal regeneration and synapse formation occurred in a normal fashion during the month following nerve injury. Soon after reconnexion of S cells, the conduction of impulses across the non-rectifying electrical junction between the cells was more reliable from the target than into it from the thinner regenerating axon. The distal segments of severed S-cell axons survived for weeks or months after destruction of their glial cells, indicating that the ensheathing glia is not required for long-term survival of axon segments. The distal axon segment of the S cell remained connected to the target axon at the normal region of synapse midway between ganglia within the nerve cord. In about half the cases in which reconnexion between injured S cell and target S cell occurred between 10 and 25 days following nerve crush, the regenerating neurone had formed an electrical synapse with its severed distal axon and had thereby become reconnected, indirectly, with its target. In the other cases, reconnexion was by direct contact. By 4 weeks, the proportion of injured S cells that were coupled and making direct contact with their targets rose to more than 80% of the total population, indicating that regeneration continued until the two S cells contacted one another directly. This is similar to the course of S-cell regeneration in the presence of the ensheathing glia. Microscopy of the regenerating neurone and both its distal axon segment and its target showed that the site of synapse formation in the absence of the usual glial sheath was normal. Fluorescence microscopy following intracellular injection of Lucifer Yellow dye, which crosses between S cells at the electrical synapse, showed that the regenerated synapse formed specifically between S cells. Moreover, the target did not form alternative synapses when regeneration failed.

Animals↗