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Biomedical subjects

G Neale

Publications and source records attributed to G Neale.

At least 19 recordsLinked to original sources

Persistent diarrhea and malnutrition--the impact of treatment on small bowel structure and permeability.

Previous studies using dual sugar permeability tests suggested that damage to the small intestinal mucosa plays an important part in the development of persistent diarrhea in The Gambia. The present study has extended these findings by examining the effect of nutritional rehabilitation on intestinal permeability and mucosal morphology. Intestinal permeability, measured by lactulose:mannitol (L:M) absorption, and mucosal structure, measured by a quantitative, computerised morphologic technique, were evaluated in 20 children before and after such treatment. L:M ratios were high on admission, (0.66 +/- 0.36) and, despite some temporary improvement, did not significantly improve (0.49 +/- 0.30) following rehabilitation for one month. The changes in L:M ratio were largely due to an increase in lactulose absorption, showing that the small intestinal mucosa becomes more "leaky" as a result of nutritional rehabilitation. Although no correlation was found between measures of intestinal permeability and mucosal morphology, nutritional restitution was associated with a significant increase in size of the mucosal crypt cell compartment, but not in villous epithelial volumes during the same period. It is necessary to establish, by further prospective studies, the interval required for full restitution of small intestinal structure and function during treatment for persistent diarrhea.

Anti-Bacterial Agents

para-amino benzoic acid in the assessment of completeness of 24-hour urine collections from hospital outpatients and the effect of impaired renal function.

Eighteen (29%) of 24-h urine collections made by 63 hospital outpatients attending a gastroenterology clinic were incomplete, as judged by 24 h urine recovery of an oral marker, para-amino benzoic acid (PABA), despite more than the usual efforts to obtain complete collections. Incomplete collections contained significantly less sodium, urea and total nitrogen than full collections. Average outputs were 134 mmol and 103 mmol per day for sodium (P less than 0.02); 301 mmol and 223 mmol for urea (P less than 0.001); and 10.1 g and 8.3 g nitrogen (P less than 0.01) in the complete and incomplete collections respectively. In renal outpatients with a plasma creatinine in excess of 125 mumol per litre, urine recoveries of PABA were reduced, but within the expected range in renal patients whose plasma creatinine was normal.

4-Aminobenzoic Acid

Chronic diarrhea and malnutrition--histology of the small intestinal lesion.

The purpose of this study was to quantitate the jejunal lesion in Gambian children with chronic diarrhea-malnutrition syndrome. There were 40 subjects (20 male, 20 female) with a mean age of 19.7 months. All were severely malnourished, with marasmus in 30, marasmic kwashiorkor in 9, and kwashiorkor in 1. Of subjects tested, 70% were anergic to intradermal challenge with either purified protein derivative or candidin. Jejunal biopsies, performed on every subject after admission to hospital, were studied by computerised image analysis and immunocytochemistry. A spectrum of mucosal changes that varied from "normal" to "flat" was seen. Mucosae with "normal" architecture revealed infiltration of villous epithelium by small lymphocytes, while crypt hypertrophy was invariably present. At the other extreme, the surface epithelium of flat mucosae was less severely infiltrated, although heavy lymphoid infiltrates persisted within crypt epithelium. Immunohistochemical studies revealed that most intraepithelial lymphocytes were of the CD8 + phenotype. Mucosal morphology did not relate to clinical, biochemical, or anthropometric data for each child. These findings are consistent with an intestinal reaction to some environmental antigen (dietary, microbial, or both) of the cell-mediated type. This interpretation is strengthened by the expression of major histocompatibility class 2D locus alloantigens on crypt epithelial cells in the absence of gut-reactive autoantibodies.

Biopsy

The treatment of persistent diarrhoea and malnutrition: long-term effects of in-patient rehabilitation.

This study aimed to characterise the clinical condition of Gambian children presenting with persistent diarrhoea and severe protein energy malnutrition and to evaluate the effects of short term in-patient treatment in terms of long-term outcome. Twenty-two children (aged 6 to 36 months) with persistent diarrhoea (greater than or equal to four loose stools/day for more than two weeks) and severe malnutrition (weight-for-height less than 75% of the National Center for Health Statistics median value) were assessed prior to in-patient treatment for three weeks with antibiotics and high nutrient-density milk. Initial assessment included biochemical and immunological status together with stool microbiology. Criteria for discharge--cessation of diarrhoea for five consecutive days and steady weight gain--were met in all subjects within four weeks. Progress was assessed clinically and anthropometrically at weekly intervals and 6 and 12 months following discharge. Results showed a steady improvement in growth during the period of in-patient treatment. Continuing improvement in weight-for-age and mid-upper arm circumference was observed after 6 and 12 months and weight-for-height continued to improve up to 6 months but fell back by 12 months. This study has demonstrated that, in the treatment of persistent diarrhoea in the tropics, relatively short periods of in-patient rehabilitation, whilst leading to a resolution of diarrhoeal symptoms and weight gain in the short term, do not lead to complete recovery. Persistent diarrhoea and malnutrition are likely to recur when the child returns to his village.(ABSTRACT TRUNCATED AT 250 WORDS)

Anthropometry

Prevalence and treatment of giardiasis in chronic diarrhoea and malnutrition.

To determine the prevalence of giardiasis in Gambian children with chronic diarrhoea and to assess their response to treatment, 31 children with chronic diarrhoea and malnutrition were investigated for giardiasis using a combination of serology (specific antigiardia IgM antibody) and microscopy of faeces and jejunal biopsy specimens. Fourteen of 31 children with chronic diarrhoea had giardiasis compared with only four of 33 healthy age and sex matched control children. Four of 15 malnourished children without diarrhoea were giardia positive. Twenty-three children with chronic diarrhoea were reinvestigated after treatment with metronidazole; giardia was found in 11 of them. These results show that giardia is highly prevalent in children with chronic diarrhoea and malnutrition and that the infection does not respond to standard therapeutic measures.

Animals

Metabolism of dietary sulphate: absorption and excretion in humans.

Dietary sulphate may affect colonic pathophysiology because sulphate availability determines in part the activity of sulphate reducing bacteria in the bowel. The main product of sulphate reducing bacterial oxidative metabolism, hydrogen sulphide, is potentially toxic. Although it is generally believed that the sulphate ion is poorly absorbed, there are no available data on how much sulphate reaches the colon nor on the relative contributions from diet and endogenous sources. To resolve these questions, balance studies were performed on six healthy ileostomists and three normal subjects chosen because they did not have detectable sulphate reducing bacteria in their faeces. The subjects were fed diets which varied in sulphate content from 1.6-16.6 mmol/day. Sulphate was measured in diets, faeces (ileal effluent in ileostomists), and urine by anion exchange chromatography with conductivity detection. Overall there was net absorption of dietary sulphate, with the absorptive capacity of the gastrointestinal tract plateauing at 5 mmol/day in the ileostomists and exceeding 16 mmol/day in the normal subjects. Endogenous secretion of sulphate in the upper gastrointestinal tract was from 0.96-2.6 mmol/day. The dietary contribution to the colonic sulphate pool ranged up to 9 mmol/day, there being linear identity between diet and upper gastrointestinal losses for intakes above 7 mmol/day. Faecal losses of sulphate were trivial (less than 0.5 mmol/day) in the normal subjects at all doses. It is concluded that diet and intestinal absorption are the principal factors affecting the amounts of sulphate reaching the colon. Endogenous secretion of sulphate by colonic mucosa may also be important in determining amounts of sulphate in the colon.

Aged

The effect of dietary nitrate on nitrate and nitrite excretion in man.

Dietary nitrate and nitrite may affect colonic pathophysiology. These anions influence fermentation, and nitrite has been shown to augment sodium absorption by the colon and participate in the formation of N-nitroso compounds. There is, however, no general agreement as to how much dietary nitrate and nitrite reaches the colon. To help resolve this question, balance studies were performed on six healthy ileostomy subjects who were given diets that varied in nitrate content from 0.83 to 5.20 mmol/d. Nitrate and nitrite excretion in ileal effluent and urine were measured by anion-exchange chromatography with conductivity detection. There was no significant nitrite in the diets, urine or ileal effluent. Dietary nitrate was largely excreted in urine (1.31-4.25 mmol/d). The urinary excretion findings indicated net synthesis of nitrate at low dietary intakes and net catabolism of nitrate at high intakes. Nitrate losses in ileal effluent were very low (0.03-0.05 mmol/d, 0.03-0.06 mmol/kg) and unrelated to intake for all the diets. It is concluded that dietary nitrate and nitrite do not enter the colon from the small intestine in amounts that would affect fermentation and mucosal metabolism in man. The possibility of significant amounts of nitrate reaching the colon via blood in normal subjects has not been excluded.

Aged

Helicobacter pylori in Gambian children with chronic diarrhoea and malnutrition.

Infection with Helicobacter pylori (formerly Campylobacter pylori) was studied by measuring antibody titres to H pylori in Gambian children. Serological evidence of infection was found in 12 of 82 (15%) infants aged less than 20 months; this increased to 62 of 135 (46%) in those aged 40-60 months. Positive serology was found in 41 of 77 (53%) infants with chronic diarrhoea and malnutrition (mean age 19 months, range 5-36) compared with 18 of 70 (26%) of age matched healthy controls and nearly a quarter (12/49, 24%) of age matched undernourished (marasmic) subjects. These data show that infection with H pylori is common in the Gambia and that in infancy this infection is associated with chronic diarrhoea and malnutrition.

Adult

The relative merits of acute phase proteins in the recognition of inflammatory conditions.

A study has been undertaken on the relative merits of a variety of acute phase proteins in the assessment of patients with inflammatory conditions. Five acute phase proteins (alpha 1-antitrypsin, alpha 1-antichymotrypsin, orosomucoid, haptoglobin and C-reactive protein) and the ESR were measured in 171 patients presenting to the gastroenterologists (gastrointestinal disease: 130, other disease: 41). Assessment of the sensitivity and specificity of the proteins and the ESR showed alpha 1-antichymotrypsin to be the most sensitive test (95%) with specificity (81%) similar to the other acute phase proteins measured. Factors such as oestrogens, renal failure and genetic variants affected the value of alpha 1-antitrypsin, orosomucoid and haptoglobin. In the routine protein laboratory the combination of a 'short' half-life and 'long' half-life protein is likely to offer the most useful screen for inflammation in samples obtained from a wide range of patients. The two acute phase proteins C-reactive protein and alpha 1-antichymotrypsin fulfil these criteria.

Acute-Phase Proteins

51Cr-EDTA/14C-mannitol intestinal permeability test. Clinical use in screening for coeliac disease.

An intestinal permeability test with a combination of 51Cr-EDTA and 14C-mannitol was performed under routine conditions on 176 occasions in 161 adult patients. Of these patients, 116 were under investigation for possible coeliac disease, 33 were known to have coeliac disease, and 12 had inflammatory bowel disease. Small-bowel biopsies were performed in 61 patients. Expressing the results as the ratio of the 6-h urinary recoveries of the two probes was as sensitive as (95%) but more specific for histologic mucosal abnormality (62% versus 46%) than measuring the urinary recovery of 51Cr-EDTA alone. All but two of the patients with active inflammatory bowel disease, whether Crohn's disease or ulcerative colitis, had an abnormal ratio. The 51Cr-EDTA/14C-mannitol intestinal permeability test with a 6-h urine collection is a rapid and simple test of small-intestinal function suitable for routine use.

Carbon Radioisotopes

The energy cost of triglyceride-fatty acid recycling in nonobese subjects after an overnight fast and four days of starvation.

The basal blood glycerol concentration was determined and the rate of glycerol turnover was assessed by a nonradioactive infusion technique in six healthy nonobese adults after an overnight fast and again after four days of total starvation. Simultaneously, estimates of total energy expenditure and net fat oxidation were made from measurements of oxygen consumption, carbon dioxide production, and urinary nitrogen excretion. The data were combined to provide quantitative estimates of the activity of the triglyceride/fatty acid cycle. The basal concentration of glycerol in venous blood rose from a mean value of 54 +/- 8 mumol/L (SEM) before starvation to 154 +/- 5 mumol/L on day 4 of starvation. Glycerol turnover rates correlated well with the basal blood glycerol concentration (r = .95) and increased from a mean value of 115 +/- 17 mumol/min before starvation (equivalent to mobilization of about 3.95 kJ triglyceride/min) to 304 +/- 20 mumol/min (equivalent to mobilization of about 18.41 kJ/min). The estimated rate of net fat oxidation was 3.00 +/- 0.47 kJ/min before starvation and 4.00 +/- 0.14 kJ/min on day +4 of starvation. The rate of triglyceride energy recycling or rate of deposition of triglyceride energy into fat stores was calculated from the difference in the rate of fat energy mobilization and the rate of energy released during net fat oxidation. The values were found to be 0.94 +/- 0.26 kJ/min before starvation and 6.29 +/- 0.54 kJ/min on day +4 of starvation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Evaluation of mannitol, lactulose and 51Cr-labelled ethylenediaminetetra-acetate as markers of intestinal permeability in man.

1. Factors affecting the intestinal uptake and urinary excretion of mannitol, lactulose and 51Cr-labelled ethylenediaminetetra-acetate (51Cr-EDTA), have been investigated in normal subjects and three patients with ileostomy. 2. The distribution volume of markers within the body, the rate of disappearance from plasma and renal clearance were assessed after an intravenous injection of a mixture of mannitol (2 g), [14C]mannitol (10 microCi), lactulose (0.1 g) and 51Cr-EDTA (5 microCi). 3. The urinary recovery of all the intravenously administered markers was close to 100%. Distribution volumes and patterns of excretion were virtually identical. Oxidation of intravenously administered mannitol accounted for only about 1% of the dose. 4. The passage of an orally administered mixture of markers was traced through the intestine and into urine. Transit time through the gastrointestinal tract was measured by the breath hydrogen method and by radionuclide scanning. 5. The passage of markers from mouth to the large bowel was essentially complete by 3.5 h. In some subjects the marker appeared in the large bowel as early as 30-40 min but in others it took three times as long. 6. After an oral dose the urinary excretion of mannitol fell progressively from 2 to 6 h, whereas the excretion of lactulose and 51Cr-EDTA increased slightly. As a consequence the lactulose/mannitol and 51Cr-EDTA/mannitol ratios in urine collected between 0 and 2 h were more than twofold higher than in urine collected between 4 and 6 h (P less than 0.001). After 6 h, the urinary excretion

Chromium Radioisotopes