Malabsorption syndromes and celiac disease.
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Biomedical subjects
Publications and source records attributed to J A Perman.
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Recent studies have shown reduced breath hydrogen (H2) excretion in methane (CH4)-producing healthy individuals following ingestion of lactulose. This questions the reliability of the breath hydrogen test (BHT) in CH4 excretors, but the relationship between CH4 and H2 excretion in other clinical applications of the BHT is not known. We reviewed BHT results in two groups of subjects: (1) 385 children tested for lactose malabsorption in a hospital setting, and (2) 109 lactose-malabsorbing patients tested with a home kit. The percentage of lactose malabsorbers in group 1 (51%) was the same regardless of CH4-producing status (P = 0.97). The BHT data from group 2 showed a positive correlation (r = 0.6, P < 0.000001) between the magnitude of the rise in CH4 and H2 concentrations, and the H2 excretion curves were significantly higher in the CH4-producing individuals. We conclude that attention to CH4-producing status is not necessary in the interpretation of the lactose BHT.
Interest in possible microbiological causes of gastritis has significantly increased since the discovery of Helicobacter pylori. Recently a spiral bacterium named Gastrospirillum hominis was described in association with chronic gastritis in adult patients. Here, we present the finding of Gastrospirillum hominis in the gastric biopsies of two children who underwent upper endoscopy for gastrointestinal symptoms. The frequency of Gastrospirillum hominis (0.3%) in our pediatric population was similar to that reported in adults. We observed a chronic gastritis associated with the spiral bacteria which was milder than the gastritis noted in our pediatric patients with Helicobacter pylori infection. Further comparisons between these two organisms, as well as the literature on Gastrospirillum hominis, are also reviewed.
Increased intestinal permeability to lactulose has been reported in patients with cystic fibrosis (CF). To determine whether this finding is unique to CF or whether it is related to accompanying exocrine pancreatic dysfunction, we evaluated 31 patients with CF and 10 with Shwachman syndrome who had variable degrees of pancreatic dysfunction, together with 17 healthy control subjects. There was no significant difference in the mean urinary lactulose excretion, expressed as the percentage of dose recovered, between CF and non-CF patients with pancreatic insufficiency (2.1% +/- 1.2% and 1.9% +/- 0.8, respectively) or between CF and non-CF patients with pancreatic sufficiency (0.6% +/- 0.5% and 0.6% +/- 0.3%, respectively). However, there was a significant difference in mean lactulose excretion between the pancreatic-insufficient and the pancreatic-sufficient patients (both CF and non-CF groups; p less than 0.001 and p less than 0.013, respectively). We further analyzed the results from 26 of the 41 patients (16 patients with CF and 10 non-CF patients) with pancreatic dysfunction who had previously undergone quantitative pancreatic function testing. A nonlinear, inverse relationship was found between urinary lactulose excretion and exocrine pancreatic function determined by duodenal trypsin output. These data confirm a direct relationship between intestinal lactulose permeability and the degree of exocrine pancreatic dysfunction, unrelated to the cause of the pancreatic disease.
Breath hydrogen testing (BHT) is a simple and reliable method for identifying impaired carbohydrate absorption. We describe a laboratory exercise in physiology for medical students using BHT as the teaching tool. The students collect fasting samples of expired air from each other using a simple nasal prong technique. They then drink one of several different aqueous carbohydrate solutions. Additional samples of expired air are collected by the students at 90 and 120 min after substrate ingestion and are analyzed by gas chromatography. Between sampling periods, discussions of digestive physiology are provided by the faculty. Students tabulate their BHT results as well as recording any symptoms using a standard scoring system. A total of 460 students have participated. We found that the percentage of students who malabsorbed a given substrate was similar each year. The results obtained in these student exercises closely parallel those reported in the literature. We conclude that BHT is an excellent teaching tool for illustrating carbohydrate digestion and absorption, even when performed by minimally trained subjects.
Because gastrointestinal dysfunction is a major problem in children with human immunodeficiency virus (HIV) infection, we utilized breath hydrogen measurements to determine the relationship between disaccharide malabsorption and gastrointestinal dysfunction in HIV-infected children. We found a strong association between lactose intolerance and persistent diarrheal disease in this population (p less than 0.007, Mann-Whitney U test). We also found evidence of sucrose malabsorption and persistent diarrheal disease in three of the children. Extensive microbiologic evaluations failed to reveal an etiologic agent related to the occurrence of gastrointestinal symptoms. Our findings indicate that disaccharide intolerance is a common occurrence in HIV-infected children with persistent diarrheal disease. Careful attention to dietary intake may be required to ameliorate clinical symptoms and to maintain adequate nutrition.
Lactose intolerance is a common condition that can cause nonspecific gastrointestinal symptoms. A reliable diagnosis cannot be made on the basis of the patient's history. The breath hydrogen test is simple, noninvasive, accurate, and inexpensive and is the diagnostic method of choice. In addition to traditional dietary restriction of lactose, treatment may consist of alterations in dietary fat content or caloric density to reduce symptoms and use of dairy products or additives that provide lactase activity.
Breath hydrogen (H2) measurements are applied in clinical medicine for the detection of carbohydrate malabsorption. H2 in expired air results when dietary sugars escape absorption in the small intestine, thereby becoming available for bacterial fermentation. H2 produced by bacterial metabolism of the carbohydrate is absorbed into the portal circulation and excreted in breath. Relatively simple collection, storage, and analysis methodologies have been developed in recent years. They permit convenient and noninvasive testing of patients in most age groups for common clinical disorders of digestion and absorption, including lactase deficiency and other disorders of di- and mono-saccharide malabsorption, starch malabsorption, and small bowel bacterial overgrowth. Limitations of breath hydrogen testing are few. Developmental considerations constrain the ease of interpretation of breath H2 measurements in early infancy, and factors affecting intraluminal H2 production by the intestinal flora may occasionally affect the H2 signal. Despite these factors, breath H2 testing has repeatedly been demonstrated to be the most accurate indirect indicator of lactase deficiency, and breath H2 measurements have been widely applied in studying digestion of the entire spectrum of dietary carbohydrates.
The purpose of our study was to determine if the ethane content of expired air could be a useful index of vitamin E status in children. Eight children with vitamin E deficiency secondary to chronic severe liver disease were studied: six of these children were treated with parenteral vitamin E (2-5 mg/kg/dose every 4-7 d). Measures of vitamin E status pre- and posttherapy were: serum vitamin E, 2 +/- 1 versus 7 +/- 1 micrograms/mL (p less than 0.001); serum vitamin E:total lipids, 0.3 +/- 0.1 versus 1.0 +/- 0.1 mg/g (p less than 0.001); and erythrocyte peroxide hemolysis test, 80 +/- 10 versus 6 +/- 12% (p less than 0.001). Fasting breath ethane in the patients pre- and posttherapy was 78 +/- 10 versus 31 +/- 11 pmol/kg/min (p less than 0.001). Breath ethane correlated negatively with serum vitamin E (p less than 0.042) and serum E:total lipids (p less than 0.004) and positively with the erythrocyte peroxide hemolysis test (p less than 0.003). Values for treated patients did not differ from those for fasted sibling controls (34 +/- 12 pmol/kg/min), postprandial sibling controls (31 +/- 12 pmol/kg/min), and healthy children sampled randomly, in the nonfasted state (21 +/- 14 pmol/kg/min). Breath ethane production in one patient (up to 168 pmol/kg/min) did not normalize after treatment of vitamin E deficiency until her selenium deficiency was corrected as well. We conclude that this noninvasive test can be useful as a screen for vitamin E deficiency in children and for ascertaining response to therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
To examine the association between methane (CH4) excretion and experimental colonic carcinogenesis, we measured CH4 excretion in rats treated with the colonic carcinogen azoxymethane (AOM, 7 mg/kg weekly for 10 weeks) and paired controls. CH4 excretion was not initially detected in either experimental or control groups, but all animals acquired positive CH4 excretion status by time of sacrifice (week 26). There was no difference between groups or among AOM-treated animals with and without tumors in the median time to onset of detectable CH4 excretion or in the amount of CH4 excreted. Our results fail to provide support for a link between CH4 excretion and experimental colonic dysplasia or adenocarcinoma.
The most important of the genetically determined causes of carbohydrate malabsorption, lactase deficiency, affects the majority of the world's adults. Management of carbohydrate malabsorption consists of temporary or permanent removal of the offending sugar from the patient's diet or providing the sugar in a more digestible form.
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To assess for altered fat absorption in a group of 26 patients who underwent bladder replacement or augmentation between 1975 and 1988 serum samples were assayed for levels of B12 and carotene. Reconstruction was done with ileum and/or cecum in 22 patients, and 4 who had undergone sigmoid cystoplasty and were not expected to be at risk for fat malabsorption were included as controls. Followup ranged from 4 months to more than 8 years. No patient demonstrated low values of B12 or carotene regardless of postoperative duration, bowel segment location or length of segment. Use of ileal segments less than 45 cm. long even with associated incorporation of the ileocecal valve and adjacent cecum does not appear to compromise fat absorption or the enterohepatic circulation.
To determine whether the acidifying effect of malabsorbed carbohydrate on fecal pH differed between methane-excreting and nonexcreting individuals, we administered the poorly absorbed disaccharide lactulose to five CH4 excretors and six CH4 nonexcretors. Lactulose, 20 g twice daily for 1 wk, significantly lowered fecal pH among CH4 nonexcretors as compared with CH4-excreting individuals (5.38 +/- 0.66 vs 6.90 +/- 0.61, p less than 0.01). To determine whether this observation was due to differences in acid production from bacterial carbohydrate fermentation, feces from each subject were incubated with lactulose. There were no differences in in vitro acid or hydrogen production between groups. We conclude that malabsorbed carbohydrate fails to induce in vivo colonic acidification in CH4 excretors. In contrast, in vitro fecal carbohydrate fermentation is similar among CH4 excretors and nonexcretors. These results suggest differences between these two groups in the colonic absorption of fermentation products.
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Urinary excretion of orally administered lactulose is used as an index of intestinal permeability. We have developed a simple thin-layer chromatographic technique for measuring lactulose in urine, using silica gel 60 plates and a propanol-borate solvent system. Lactulose concentrations as low as 62.5 mg/L can be detected with high reproducibility and without interference by urinary chromogens. After oral administration, the urinary excretion of lactulose in 8 h equaled 2.33 (SD 1.86)% in 15 patients with cystic fibrosis, as compared with 0.13 (SD 0.12)% in 16 healthy subjects (P less than 0.001).
The diagnosis of inflammatory bowel disease rests on radiologic, endoscopic, and histologic criteria. Five patients, 2 to 17 years of age, sought medical attention because of chronic abdominal pain, diarrhea, and heme-positive stools. Rectal biopsies, visual inspection of colonic mucosa through the colonoscope, and contrast radiographs of the large and small intestine yielded nonspecific results. Serial endoscopic biopsies demonstrated a gradient of inflammatory changes diminishing in severity distally from the ileocecal valve and cecum. The disease process was most evident in specimens from the cecum, whereas biopsies distal to the transverse colon had a normal histologic appearance in all five patients. Biopsies from the proximal colon may provide evidence of inflammatory bowel disease not detectable using standard techniques. The combination of chronic abdominal pain, diarrhea, and heme-positive stools associated with inflammatory changes in biopsy specimens obtained from the proximal colon, but normal findings on radiologic, colonoscopic, and rectal biopsy examinations, may represent an early stage in the evolution of chronic nonspecific inflammatory bowel disease, including ulcerative colitis or regional enteritis (Crohn disease).