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Biomedical subjects

T A Robb

Publications and source records attributed to T A Robb.

At least 19 recordsLinked to original sources

Bowel dysfunction in cystic fibrosis: importance of breath testing.

OBJECTIVE: To investigate the prevalence of carbohydrate malabsorption and bacterial overgrowth in children with cystic fibrosis (CF) and abnormal stool pattern referred for breath hydrogen testing. METHODS: Results from 89 tests using lactose, sucrose and lactulose in 54 children with CF were compared with 5430 tests on children with non-CF-related stool abnormalities. RESULTS: Children with CF were more frequently unable to ferment lactulose to hydrogen (39% vs. 20%, P<0.03); they had significantly longer oro-caecal transit times (mean 99 vs. 68 min, P<0.0003); they had a higher incidence of bacterial overgrowth (32% vs. 7%, P<0.003) and sucrose malabsorption (47% vs. 14.5%, P<0.004); but they had no increase in lactose malabsorption (40% vs. 31%). Children with bacterial overgrowth in both groups had longer transit times (CF 123 min, non-CF 108 min) compared to the non-CF children without overgrowth (68 min) and reference normal children (69 min). CONCLUSIONS: Bacterial overgrowth and carbohydrate malabsorption, particularly of sucrose, should be considered when assessing children with CF and abnormal stool patterns.

Breath Tests↗

Effect of high-dose chemotherapy on intestinal permeability in humans.

1. Mucositis is a common side-effect of chemotherapy which is difficult to assess except by invasive means such as upper gastrointestinal endoscopy. Differential absorption of mono- and di-saccharides, such as rhamnose and lactulose, is a non-invasive measure of intestinal damage. 2. The purpose of the study was to assess the duration and severity of intestinal damage in patients undergoing high-dose chemotherapy and autologous blood stem-cell transplantation for malignant disease. 3. Thirty-five patients were studied before treatment and at 7, 28, 60 and 90 days after treatment. 4. The median lactulose/rhamnose ratios before treatment and at 7 and 90 days post-treatment were 0.09, 0.62 and 0.06 respectively. Altered permeability was due to both increased lactulose permeation and decreased rhamnose absorption. These abnormalities suggest a defect in tight-junction integrity as well as a decrease in surface area of small bowel. 5. We conclude that chemotherapy given for malignant disease is associated with a transient abnormality in intestinal sugar permeability, which peaks at 7 days after treatment and is composed of both mono- and di-saccharide absorption abnormalities.

Adolescent↗

The nutritional management of acute diarrhea in young infants: effect of carbohydrate ingested.

To compare the efficacy of a low-lactose hydrolyzed milk formula, a lactose-free corn syrup-based milk formula, and a standard lactose-containing formula during refeeding after rehydration in infants with gastroenteritis, 135 patients older than 2 years were studied by randomized trial. Clearly demonstrated disadvantages in terms of early weight loss and longer duration of diarrhea were observed with the lactose-based formula compared with early weight gains on both the low-lactose formulae, and thus the lactose-containing formula was discontinued after 91 patients. The early weight loss with the lactose-containing formula was statistically significantly related to the degree of relative (rehydrated) underweight. The two low-lactose formulae were further compared in the remaining 44 patients. Early weight gain (48 h) was significantly greater with the lactose-hydrolyzed formula compared with the corn syrup-based formula, but no statistically significant differences were observed in duration of diarrhea, energy intake, treatment failures, or late weight gain. We conclude that the routine use of a low-lactose formula during refeeding after rehydration in infants with gastroenteritis may have some advantages in underweight infants and toddlers in whom it is important to prevent further weight loss.

Acute Disease↗

Development of hydrogen excretion between feeds in breast and artificially fed full-term normal neonates.

The breath hydrogen test for carbohydrate malabsorption has been proved to be sensitive, specific and noninvasive. This study was performed to determine its applicability in the newborn period. Postprandial hydrogen excretion in the first 5 days of life was measured in 105 full-term normal newborns, who were either artificially or breast fed. Samples of expired air were collected via a nasopharyngeal catheter at 30 min intervals between feeds. Some babies showed no hydrogen production after 5 days, while others produced high (200 parts/10(6] levels. The incidence of hydrogen production increased postnatally--more than 80% of babies produced hydrogen by 5 days of age. None of the babies was unwell or developed frequent or loose stools suggestive of clinical carbohydrate malabsorption. It is therefore postulated that these high hydrogen levels reflect biochemical evidence of clinically insignificant carbohydrate malabsorption in this age group. This study shows clearly that an interfeed interval of 4 h in these babies is insufficient to cause breath hydrogen levels to fall in a predictable way. The ethical and practical difficulties in fasting these infants for longer periods suggest that conventional carbohydrate challenges with breath hydrogen estimations will be difficult in the neonate.

Breast Feeding↗

Breath hydrogen response to milk containing lactose in colicky and noncolicky infants.

In 122 healthy newborn infants, we studied the relationship between breath hydrogen (H2) production after feedings containing lactose (human milk or commercial formula) in colicky and noncolicky infants at 6 weeks and 3 months. Eighty-three infants (68%) developed colic (mild, moderate, or severe) by 2.6 +/- 1.8 weeks of age (mean +/- SD). Zero time (baseline) breath H2 values were significantly higher in colicky compared with noncolicky infants at both 6 weeks (40.6 +/- 41.4 vs 14.8 +/- 32.9 ppm) and 3 months (27.7 +/- 38.1 vs 8.5 +/- 18.2 ppm). There were significantly more positive breath H2 tests in colicky compared with noncolicky infants at 6 weeks (78% vs 36%) and 3 months (89% vs 45%). Failure to produce H2 throughout the breath H2 test was significantly more frequent in noncolicky compared with colicky infants at 6 weeks (50% vs 18%) and 3 months (43% vs 4%). These findings remained significant even when infants with mild colic (at 6 weeks and 3 months) were included in the noncolicky group. We conclude that colicky infants produce more breath H2 in the fasting state and in response to feedings containing lactose than noncolicky infants produce. This may represent increased lactose malabsorption, differences in colonic bacterial fermentation conditions, or differences in the handling of colonic gas produced.

Breath Tests↗

Taurine supplementation, fat absorption, and growth in cystic fibrosis.

The effect of taurine supplementation (30 to 40 mg/kg/24 hr) on fat absorption and related measurements was examined in 21 preadolescent children with cystic fibrosis (CF) using a 12-month double-blind crossover technique. The mean coefficient of fat absorption was unchanged by taurine both in the unselected study group (without taurine, mean +/- SD 84.0% +/- 11.9%; with taurine, 84.4% +/- 11.8%, n = 20) and in a subgroup of seven children with moderately severe fat malabsorption (without taurine, 75.6% +/- 15.6%; with taurine, 74.8% +/- 14.6%). The mean fecal split fat/total fat ratio, which generally reflects bile acid-related fat malabsorption, was also unchanged. Linoleic and arachidonic acid deficiencies noted in plasma before supplementation showed no significant improvement with taurine supplementation. Likewise, plasma/serum vitamin A, E, and D levels were unchanged. Standard scores for height and weight were not affected significantly. This study does not support the use of taurine supplementation in the nutritional management of CF.

Body Height↗

Abnormal pancreatic electrolyte secretion in cystic fibrosis. Reliability as a diagnostic marker.

We performed pancreatic function tests on sixty-five cystic fibrosis (CF), and eleven control children. The technique used continuous IV infusion of cholecystokinin and secretin, with duodenal juice collection over a 90 min period, and was made quantitative by continuous duodenal infusion and distal collection of an unabsorbable marker (bromosulphthalein). Some CF patients had near normal pancreatic enzyme outputs, some had impaired but measurable levels, but most (79%) had almost absent trypsin secretion. CF children with better pancreatic function, were younger and more likely to be male. All controls showed a large increase in bicarbonate concentration and secretion rate per kilogram body weight during the test, but most children with CF (96.5%) did not. Because two of our CF patients had water and bicarbonate secretion within the control range, this finding does not exclude the diagnosis of CF. Sodium, potassium and chloride ion secretion in CF patients was lower than controls but overlap occurred. We found a linear correlation between acinar and tubular secretion in CF patients which indicates that there is probably not a primary genetic defect in pancreatic bicarbonate secretion in CF.

Adolescent↗

Value of breath hydrogen analysis in management of diarrheal illness in childhood: comparison with duodenal biopsy.

Breath hydrogen tests were carried out on 157 children either because they had chronic diarrhea or because they were on disaccharide-free diets. Lactose malabsorption was common in patients with postgastroenteritis syndrome (43%), and sucrose malabsorption was readily detected in patients with congenital sucrase-isomaltase deficiency. Secondary sucrose malabsorption and small bowel bacterial overgrowth were also detected. In predicting clinical response to dietary change, the breath hydrogen test, as we perform it, was clearly the most specific and sensitive and had a predictive accuracy of 96%. Duodenal biopsy results obtained from 48 of the children gave a 23% incidence of misleading disaccharidase results (16.7% falsely normal, 6.3% falsely abnormal), but biopsy remains vital in the diagnosis of congenital sucrase-isomaltase deficiency. False negative breath hydrogen results were obtained on occasions (4%) but in most instances were related to recent antimicrobial therapy or failure of the breath test mechanics (e.g., vomiting, length of sampling).

Biopsy↗

Faecal hydrogen production in vitro as an indicator for in vivo hydrogen producing capability in the breath hydrogen test.

In the assessment of carbohydrate malabsorption, it is important to determine if a flat breath hydrogen test is a false negative result. Currently, the only reliable way to do this is with a lactulose test. We determined the reliability of assessing faecal hydrogen production as an indicator of an adequate in vivo hydrogen producing colonic bacterial flora. Unfortunately, the results clearly show that the incidence of falsely positive and negative faecal hydrogen production, when compared with in vivo lactulose testing, is so high that the simple faeces screening test is unsuitable for routine use. Until a simpler alternative is found, centres using the breath hydrogen test to determine carbohydrate malabsorption must continue to rely on lactulose breath testing when it is necessary to exclude potential false negative results.

Breath Tests↗

Conjugated bile acids in serum and secretions in response to cholecystokinin/secretin stimulation in children with cystic fibrosis.

More than 80% of patients with cystic fibrosis have poor pancreatic function, and have large daily faecal bile acid losses. This has been postulated to lower luminal bile acid concentrations and adversely affect fat absorption. We studied, for the first time, quantitative individual conjugated duodenal bile acid secretion rates into the duodenum during cholecystokinin/secretin infusion in 55 cystic fibrosis patients and six controls, using a quantitative non-absorbable marker technique. We were able to show adequate duodenal total bile acid concentrations and normal secretion rates in these children. The bile acid secretion pattern in cystic fibrosis patients showed a marked increase in bile acid concentration during cholecystokinin/secretin infusion, to levels which were above the critical micellar concentration indicating that the gall bladder is a functional organ in this disease. The subsequent fall in secretion rate was similar to controls. We have documented a significantly raised glycine/taurine bile acid conjugation ration in duodenal juice from cystic fibrosis patients and suggest that the combined effects of lowered ileal pH and increased glycine conjugated proportion of bile acids may cause precipitation of bile acids leading to decreased fat absorption and large faecal bile acid losses. To further investigate bile acid secretion in children with cystic fibrosis, we modified the high performance thin layer chromatography/densitometry method to enable measurement of individual glycine and taurine conjugates in serum. In comparing cystic fibrosis patients and controls, we were able to determine a group of 18 (36%) with bile acid evidence of liver damage who also showed reduced bile acid secretion into the duodenum. We were unable to study changes in serum bile acids during cholecystokinin/secretin infusion because of the high level of bile acid contamination in Boots Secretin. Some patients showed raised fasting serum bile acid concentrations more than two years before changes in conventional liver function tests or clinically evident liver disease. We have shown fasting serum bile acids to be a sensitive measure of liver dysfunction in cystic fibrosis and postulate that raised proportions of glycine conjugated bile acids may be responsible for the high incidence of liver disease in cystic fibrosis.

Adolescent↗

Analysis of individual bile acids and their glycine/taurine conjugates by high-performance thin-layer chromatography and densitometry.

We have investigated a thin-layer chromatography method for the quantitative measurement of free and conjugated bile acids in duodenal juice. Evaluation of solvent systems and colour spray reagents has enabled us to select conditions which improve the resolution, sensitivity and colour stability of the method. The modified method, using high-performance thin-layer chromatography and densitometry, is rapid, accurate, reproducible and practicable. The technique deserves wider routine use.

Bile Acids and Salts↗

Bacterial contamination of the small intestine as an important cause of chronic diarrhea and abdominal pain: diagnosis by breath hydrogen test.

Unsuspected bacterial contamination of the small intestine was indicated by breath hydrogen testing in nine patients aged 2 to 34 months during physical examinations for chronic diarrhea and abdominal pain. Elevated bacterial counts of questionable significance were found in duodenal aspirates before and after antibiotic treatment. There was no evidence of bile salt deconjugation or structural changes in the small intestine by light or electron microscopy. This may indicate that the site of colonization is distal to the biopsy site. Breath testing indicated lactose malabsorption in all patients, and four of five patients tested also malabsorbed sucrose. Duodenal disaccharidase levels in all patients were within the normal ranges, but in eight patients the lactase-sucrase ratio was greatly elevated (0.80 +/- 0.36; normal less than 0.45). Dietary restriction alone did not cause complete cessation of symptoms, whereas all patients responded dramatically to oral antibiotic therapy. When patients were well, the lactase-sucrase ratio had returned to normal in those tested, and all nine had normal lactose and lactulose breath hydrogen tests. Unsuspected bacterial contamination of the small intestine, which is easily detected using the breath hydrogen test, may be more commonly associated with chronic diarrhea in children than has been previously realized. In such cases, therapy should be directed at removing the contamination.

Abdomen↗