Trevor A. Robb

Effect of pelvic irradiation on gastrointestinal function: A prospective longitudinal study

PURPOSE Although radiation enteritis is a well-recognized sequel of therapeutic irradiation, the effects of abdominal and/or pelvic irradiation on gastrointestinal function are poorly defined and treatment is often unsuccessful. To determine both the short- and long-term effects of therapeutic irradiation on gastrointestinal function, we performed a prospective study. PATIENTS AND METHODS Various aspects of gastrointestinal function were evaluated in 27 patients with potentially curable malignant disease (23 female, 4 male) before the commencement of, during, and 6 to 8 weeks, 12 to 16 weeks, and 1 to 2 years following completion of radiation therapy. Seventeen patients received pelvic irradiation alone and 10 patients received both abdominal and pelvic irradiation. Gastrointestinal symptoms, absorption of bile acid, vitamin B12, lactose, and fat, gastric emptying, small-intestinal and whole-gut transit, stool weight, and intestinal permeability were measured. Results were compared with those obtained in 18 normal volunteers. RESULTS All 27 patients completed at least 2 series of measurements and 18 patients completed all 5 series of experiments. During radiation treatment, increased stool frequency (p < 0.001) was associated with decreased bile acid and vitamin B12 absorption (p < 0.001 for both), increased fecal fat excretion (p < 0.05), an increased prevalence of lactose malabsorption (p < 0.01), and more rapid small-intestinal (p < 0.01) and whole-gut (p < 0.05) transit. Although there was improvement in most of these changes with time, at 1 to 2 years after the completion of irradiation, the frequency of bowel actions was greater (p < 0.001), bile acid absorption was less (p < 0.05), and small-intestinal transit was more rapid (p < 0.01) when compared with that of baseline and the normal subjects. At this time, at least 1 parameter of gastrointestinal function was abnormal in 16 of the 18 patients. Stool weight was greater (p < 0.05) and whole-gut transit faster (p < 0.01) in patients who received both pelvic and abdominal irradiation, when compared with those who received pelvic irradiation alone. Stool frequency (p < 0.001) and fecal fat excretion (p < 0.05) were greater in those patients who had surgery before radiation therapy. CONCLUSION Pelvic irradiation is usually associated with widespread, persistent effects on gastrointestinal function.

Gastrointestinal function in chronic radiation enteritis--effects of loperamide-N-oxide.

The effects of loperamide-N-oxide, a new peripheral opiate agonist precursor, on gastrointestinal function were evaluated in 18 patients with diarrhoea caused by chronic radiation enteritis. Each patient was given, in double-blind randomised order, loperamide-N-oxide (3 mg orally twice daily) and placebo for 14 days, separated by a washout period of 14 days. Gastrointestinal symptoms; absorption of bile acid, vitamin B12, lactose, and fat; gastric emptying; small intestinal and whole gut transit; and intestinal permeability were measured during placebo and loperamide-N-oxide phases. Data were compared with those obtained in 18 normal subjects. In the patients, in addition to an increased frequency of bowel actions (p < 0.001), there was reduced bile acid absorption, (p < 0.001) a higher prevalence of lactose malabsorption (p < 0.05) associated with a reduced dietary intake of dairy products (p < 0.02), and faster small intestinal (p < 0.001) and whole gut transit (p < 0.05) when compared with the normal subjects. There was no significant difference in gastric emptying between the two groups. Treatment with loperamide-N-oxide was associated with a reduced frequency of bowel actions (p < 0.001), slower small intestinal (p < 0.001), and total gut transit (p < 0.01), more rapid gastric emptying (p < 0.01), improved absorption of bile acid (p < 0.01), and increased permeability to 51Cr EDTA (p < 0.01). These observations indicate that: (1) diarrhoea caused by chronic radiation enteritis is associated with more rapid intestinal transit and a high prevalence of bile acid and lactose malabsorption, and (2) loperamide-N-oxide slows small intestinal transit, increases bile acid absorption, and is effective in the treatment of diarrhoea associated with chronic radiation enteritis.

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.

Incidence and duration of lactose malabsorption in children hospitalized with acute enteritis: Study in a well-nourished urban population

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A retrospective study of the effects of pelvic irradiation for carcinoma of the cervix on gastrointestinal function

PURPOSE To evaluate the prevalence of disordered gastrointestinal function following therapeutic irradiation. METHODS AND MATERIALS Gastrointestinal function was evaluated in 30 randomly selected patients who had received pelvic irradiation for treatment of carcinoma of the cervix between 1 and 6 years previously. Each patient underwent evaluations of (a) gastrointestinal symptoms (b) absorption of bile acid, vitamin B12, lactose and fat (c) gastrointestinal transit: gastric emptying, small intestinal transit and whole gut transit and (d) intestinal permeability. Results were compared with those obtained in 18 normal volunteers. RESULTS Stool frequency was above the control range in five patients and had increased (p < 0.001) since radiotherapy treatment. Bile acid (p < 0.001) vitamin B12 (p < 0.01) and lactose (p < 0.01) absorption were less in the patients when compared with the control subjects. Bile acid absorption was below the control range in 14 of the 30 patients. Dietary calcium intake was lower (p < 0.05) in those patients with lactose malabsorption. Gastric emptying (p < 0.01) and small intestinal transit (p < 0.01) were more rapid in the patients. Both small intestinal (r = -0.39, p < 0.05) and whole gut (r = -0.45) transit were inversely related to stool frequency. Either bowel frequency, bile acid absorption, vitamin B12 absorption was outside the control range in 19 of the 30 patients. CONCLUSION Abnormal gastrointestinal function is essentially an inevitable long-term sequel of pelvic irradiation.

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).

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.

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.

The effects of abdominal irradiation for seminoma of the testis on gastrointestinal function

Abstract To evaluate the long‐term effects of abdominal irradiation for the treatment of seminoma of the testis on gastrointestinal function, 15 randomly selected patients who had been treated for stage I seminoma of the testis 2‐10 years previously had the following parameters of gastrointestinal function evaluated: gastrointestinal symptoms; absorption of bile acid; vitamin B12; lactose and fat; gastric emptying; small intestinal and total gut transit; and intestinal permeability. Results were compared to those obtained in 18 normal volunteers.

Abnormal pancreatic electrolyte secretion in cystic fibrosis: reliability as a diagnostic marker

ABSTRACT. 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.