Changing concepts of nutrient requirements in disease: implications for artificial nutritional support.
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Biomedical subjects
Publications and source records attributed to M Elia.
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Systemic endotoxaemia is a well recognized feature of inflammatory bowel disease but its pathogenic role remains uncertain. This study examined plasma endotoxin and cytokine concentrations and the acute-phase protein response in a hapten-induced model of experimental colitis. On days 2, 8 and 14 after induction of colitis with trinitrobenzenesulphonic acid in ethanol (TNBS-E), plasma endotoxin, immunoglobulin (Ig) G and IgM endotoxin-core antibody (EndoCAb), tumour necrosis factor (TNF), interleukin (IL) 6 and alpha 2-macroglobulin (alpha 2M) concentrations and colon macroscopic inflammation score were determined. At all time points there was significant colonic inflammation when compared with control values (P < 0.0001). Animals treated with TNBS-E had raised concentrations of endotoxin at all time points (P < 0.04). In TNBS-E-treated animals EndoCAb concentrations were reduced on day 2 (P < 0.0001) and later increased. There were increases in IL-6 and alpha 2M concentrations in TNBS-E-treated animals but no significant change in TNF concentrations. Endotoxin concentrations correlated with macroscopic inflammation score, IL-6 and alpha 2M concentrations. There was a less consistent correlation between EndoCAb concentrations and these parameters. These results suggest that endotoxin is a mediator of the systemic response in this model of experimental colitis.
Brainstem auditory evoked potentials (BAEPs) were recorded in 51 Down's syndrome (DS) subjects and compared with those of 38 normal controls; the correlations between the BAEP measures and age, sex, and degree of mental retardation were then evaluated. The DS patients showed a significant reduction in wave V latency and amplitude and in I-III, III-V, and I-V interpeak intervals. An age-related shortening of the I-V interpeak interval found in DS patients was interpreted as being a result of changes in central inhibitory/excitatory mechanisms. In both groups, female subjects presented an I-V interval shorter than that of males but this difference was greater in the DS subjects than in the normal population. The DS patients with severe mental retardation showed significantly longer I-V interpeak intervals than those with moderate retardation; this could be due to the presence of additional central nervous system abnormalities.
In this study, we report the cases of five unrelated patients with Klinefelter's syndrome and seizures or EEG epileptiform abnormalities; the karyotype was 47,XXY in four, and 47,XXY/46,XX in one. They were aged 13-25 years and followed up both clinically and by means of EEG. Two of the patients had epilepsy, one had only one isolated generalized tonic-clonic seizure, one had febrile convulsions and one presented focal epileptiform EEG abnormalities without seizures. In two of the patients, it was possible to classify the epilepsy (childhood epilepsy with occipital paroxysms and cryptogenic or symptomatic generalized epilepsy). Although the electroclinical patterns appeared to be rather heterogeneous in our patients, it is possible to infer the relative good evolution of seizures in Klinefelter's syndrome.
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Data from animal studies suggests that glutamine supplementation may reduce the incidence or severity of cytotoxic-induced mucositis. This study examined the effect of glutamine supplements on mucositis in patients receiving bone marrow transplants. 24 patients were randomly assigned to receive an oral supplement of either glutamine or placebo (16 g/day) from the time of transplantation until discharge from hospital. There was no significant difference in the incidence of oral mucositis, assessed either by the patient (mucositis score: glutamine 17 vs. placebo 26.6) or an independent observer (glutamine 31.1 vs. placebo 32.3), or the number of days of diarrhoea (glutamine 3.1 vs. placebo 3.3 days). Similarly there were no significant differences in haematological indices (haemoglobin, WBC, platelets), the requirement for parenteral nutrition or hospital stay. Possible reasons for this negative result, which contrasts with those obtained in recent studies of patients receiving intravenous glutamine after bone marrow transplants, are discussed.
This study investigated the effects of glutamine and steroid enemas on disease activity in an animal model of colitis. Colitis was induced in male Wistar rats by intracolonic instillation of 30 mg trinitrobenzenesulphonic acid in 50% ethanol (TNBS/E). Controls were given an isovolumetric bolus of normal saline. After 24 h, animals were randomised to receive enemas (1 mL twice daily) of prednisolone (200 mg/L), or L-glutamine (500 g/L) or the suspending agent (placebo). On day 8, the colon was weighed and the degree of inflammation assessed using a colon macroscopic score (CMS). Thymic weight, splenic weight, percentage gain in body weight (%GBW), food intake, plasma interleukin-6 (IL6) and plasma alpha(2)-macroglobulin (alpha(2)M) were also determined. There was a significant increase in CMS, colon weight, splenic weight, IL6 and alpha(2)M in TNBS/E animals compared to controls (P< 0.01). There was also a significant decrease in %GBW, food intake and thymic weight in TNBS/E animals (P< 0.01). The therapeutic enema of prednisolone reduced colonic inflammation (CMS, colon weight), improved thymic weight, %GBW and food intake, and reduced plasma IL6 concentrations (P< 0.05). In contrast administration of glutamine enemas was associated with an exaggerated acute phase protein (alpha(2)M) response (P< 0.05) and failed to improve the colonic and systemic inflammatory response in this experimental model of colitis.
1. There are few data regarding the accuracy of Hologic QDR-1000W dual-energy X-ray absorptiometry for the measurement of body composition. In two studies, one in an in vitro experimental system using oil and water mixtures and the other in samples of pork meat, the effect of depth and tissue thickness on the measured composition was assessed. In the latter study the measured fat mass was compared with that measured by direct analysis. 2. All data indicated a trend in the measured fat mass with depth, such that more fat was measured at extremes of depth (< 10 cm and > 25 cm) than at intermediate depths. 3. In samples of meat weighing approximately 55 kg, dual X-ray absorptiometry significantly under-estimated the absolute fat mass compared with direct analysis (mean 20.4 +/- 1.65%) by 5-8% or 1-4 kg of fat. 4. These findings are of direct relevance to both clinical and research work using this technique to measure body composition, in particular in circumstances in which changes in body composition and/or tissue thickness are anticipated.
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It has been suggested that incomplete digestion of cereal starch explains the low energy values of certain cereals of large particle size. We used human subjects with ileostomies to investigate the digestion of barley and to determine whether the physical form of barley affects stomal excretion of starch, glucooligosaccharides, nitrogen, fat, and calculated energy. Only 2 +/- 1% of starch remained undigested after finely milled barley was eaten, but after flaked barley was eaten 17 +/- 1% resisted digestion, partly as oligosaccharides (G1-G10) but largely as intact unpitted starch granules bound by intact cell walls. The calculated energy excretion from the stoma was three times higher after flaked than after milled barley [51.5 decreasing to 15.3 kJ/g nonstarch polysaccharide (NSP, P < 0.001]. NSP, starch, and fat made almost equal contributions to the higher energy excretion. It is concluded that possibly the botanical source of cereals and certainly processing, other than retrogradation of the starch, are important determinants of starch digestibility and energy value. Possible clinical implications are introduced.
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Five healthy male subjects were continuously infused subcutaneously with [14C]bicarbonate (12.3 microCi/day) using a mini pump for 5 days while in a whole body calorimeter. Energy expenditure was varied over a range of 1.35-1.75 times basal metabolic rate. Urine collections were obtained throughout the study and used to measure the specific activity of urea, from which CO2 production was estimated. It was assumed that the recovery of label in gaseous CO2 was 95% of that infused and that the specific activity of urea was 85% that of expired CO2. Continuous daily collections of calorimeter air revealed that 95.6 +/- 1.3% (SD) of infused label was recovered as gaseous CO2, with little daily variation. Another 1.5 +/- 0.4% was recovered as urinary urea. The estimated CO2 production, calculated from the specific activity of urea in 24-h urine samples corrected for the small effects due to changes in the size and specific activity of the urea pool, was found to be 100 +/- 5% of the calorimeter estimate for 1-day periods (20.80 +/- 1.44 mol CO2/day) and 100 +/- 2% for 4-day periods. This study suggests that, in healthy subjects, the labeled [14C]bicarbonate-urea method can provide reasonable estimates of net CO2 production over the range examined.
Clinical and neurophysiological findings for 28 patients with mental retardation, autism, and epilepsy were described. Correct classification of seizure type and epileptic syndrome (when possible), etiology, severity of autism and epilepsy, EEG findings, and neuroimaging findings were given. No particular epileptic syndrome was found to be more frequently correlated to autism, severity of autism was not correlated with a more pronounced tendency to develop seizures, and females with autism were more frequently affected by seizures than were males. In conclusion, the risk for epilepsy does not seem to be correlated to autism itself, but the same noxious event induces autism and epilepsy. The severity of epilepsy is strictly correlated with its etiopathogenetic mechanisms.
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A model of prolonged systemic injury was generated in the rat by three sequential injections of turpentine, delivered at 2-day intervals. The model was then used to identify the subsequent changes in the distribution of tissue protein and the effects of the changes in skin protein on the tensile strength of healing skin wounds. The model produced a sustained acute phase response during the 6 days of the study, including a significant (26%) reduction in the plasma glutamine concentration (P < 0.01), which was not achieved with a single injection of turpentine. When compared with pair-fed controls, the animals injected with turpentine had 18% more nitrogen in the liver (P < 0.05), 25% less in the gastrocnemius muscle (P < 0.01), and a similar amount in the upper small intestine. There was also a 30% loss of nitrogen from dorsal skin (P < 0.001) and a 15% loss from ventral skin (P < 0.01), with a parallel loss of collagen (measured as hydroxyproline). Ten days after the first injection of turpentine, the dorsal skin was still 18% thinner than that of the pair-fed controls (P < 0.01): this was associated with an 18% reduction in the bursting strength of linear skin wounds (P < 0.05). Such changes were not observed in pair-fed controls. These studies demonstrate that systemic injury (independent of dietary intake) causes a preferential loss of protein from peripheral tissues (skin, muscle) and preservation of protein in splanchnic tissue (liver, intestine). They also suggest that the loss of skin protein including collagen is quantitatively important, with functional consequences in reducing the bursting strength of surgical skin wounds.
We report the case of a 7 year old boy with fragile-X syndrome and epilepsy. In this patient, the detection of rolandic epileptiform potentials during sleep and hand tapping-evoked rolandic EEG spikes, together with giant somatosensory evoked potentials, further support the already suggested neurophysiological similarities between fragile-X syndrome and benign childhood epilepsy with centrotemporal spikes.