Application of a stable isotope (13C)-labeled glycocholate breath test to diagnosis of bacterial overgrowth and ileal dysfunction.
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Biomedical subjects
Publications and source records attributed to N W Solomons.
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A simple gas chromatographic technique for analyzing H2 in expired air with a compact, relatively inexpensive gas chromatography specifically adapted for H2 analysis is described. Modifications in the basic chromatograph included increasing the capacity of the sample loop, lengthening the column, and using argon as the carrier gas to increase the sensitivity of the system. Methods for collecting and storing respiratory gas samples and for quantifying the results are described for clinical studies of carbohydrate malabsorption. Small errors in collection and quantitation are introduced by the method, but they are minor in relation to the changes in H2 concentration which are seen with significant malabsorption. This simplification of chromatograph technology could increase the general availability of this convenient, noninvasive and well-tolerated test of intestinal absorption of carbohydrates such as lactose.
The methodology for measuring in vivo oxidation of substrates labeled with the nonradioactive carbon isotope 13C has been developed with isotope ratio mass spectrometry. The use of 13C offers the possibility of utilizing CO2 breath tests in infants, children, pregnant women, and all subjects in whom 14CO2 breath tests cannot be used. The excretion of 140 nmol/kg-hr of 13CO2 produced from the oxidation of the labeled substrate could be detected with 95% confidence during a total CO2 excretion of 9 mM/kg-hr. The precision of CO2 breath tests using 13C is limited by the natural fluctuations of the ratio of 13C/12C in expired CO2, which occur with a standard deviation of 0.72%, or approximately 7 parts 13CO2 per 10(6) parts expired CO2. Larger excursions in the ratio were observed if the subjects ate shortly before or during the breath test. Clinically significant diagnostic tests can reasonably be expected to require the excretion of 2 to 20 times as much labeled CO2, or 0.28 to 1.4 micronM/kg-hr.
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Zinc nutritional status was examined in 10 adult patients with biopsy-proven celiac disease; five of these patients were clinically well on gluten-free diets at the time of study. Plasma zinc and taste acuity were used as indices of zinc nutrition. Depression of plasma zinc and lowered taste discrimination were observed among the untreated patients, and some patients who were otherwise in clinical remission also had impaired zinc nutrition. With confirmation of plasma copper depression in patients with celiac sprue, these observations indicate that trace metal deficiency is another common nutritional complication of adult celiac disease.
Based on a previous report of a zinc deficiency syndrome in children characterized by low hair zinc, anorexia, poor growth, and hypogeusia, 12 children attending a pediatric endocrinology clinic for growth retardation and judged as having short stature as a variant of normal (SVN) were evaluated as to their zinc nutriture to learn whether zinc deficiency was a contributory factor. None was found to have the above syndrome, although one child did have a hair zinc concentration below 70 mug/g. The mean hair zinc of the SVN subjects was lower than the hair zinc of 40 apparently normal adolescents, 131+/-37 mug/g vs. 168+/-44 mug/g (P less than 0.02), but there was no difference found in plasma levels of zinc or in taste acuity. In contrast, five patients with total growth arrest secondary to juvenile Crohn's disease (CD) were found to have multiple findings consistent with zinc deficiency including low plasma zinc, low hair zinc, or hypogeusia.
The plasma concentrations of the trace metals zinc and copper were studied prospectively in 13 patients with gastrointestinal diseases treated with parenteral alimentation (TPA) for periods of from 8 days to 7 1/2 weeks. Plasma copper levels fell rapidly and consistently in all patients, with an overall rate of - 11 mug per 100 ml per week. Zinc concentrations declined in 10 of 13 patients at a more gradual rate. Analysis of the standard parenteral alimentation fluids revealed zinc content equivalent to 50% of the daily requirement and a negligible content of copper. From combined analysis of plasma zinc, hair zinc, and taste acuity, there is evidence that increased utilization or redistribution within the body may effect plasma concentrations in some patients. Neither an increase in urinary excretion nor a primary decrease in plasma binding proteins appeared to be a major factor in lowering plasma trace metal concentrations. These findings indicate that a marked decrease in plasma copper is regular and a decline in plasma zinc is common during TPA using fluids unsupplemented with trace metals. Supplementation of parenteral alimentation fluids with the trace metals zinc and copper is recommended.
An unusual incidence of a duodenal leiomyosarcoma in a 10-year-old boy is presented. The corrected diagnosis was made after a 27-month course of occult gastrointestinal bleeding, vague abdominal complaints, and anemia. Gastrointestinal radiography and upper gastrointestinal endoscopy were useful in localizing the lesion. The tumor was removed at exploratory surgery by simple excision. On frozen section, the tumor was thought to be benign, but fixed microscopic histological sections revealed a well-differentiated, malignant smooth muscle tumor. The presentation of this tumor in a child is compared to previously reported cases in adults, and the biological and clinical characteristics of malignant smooth muscle tumors of the gastrointestinal tract are reviewed.
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This study aimed to evaluate the feasibility and reliability of bioelectrical impedance spectroscopy in young children suffering of acute hydrational disorders. Whole body and segmental measurements were carried out in a group of 42 of children aged 4 to 147 months, using a BIS analyzer (Xitron 4000B). This phase of the study involved several hundred of BIS measurement, which showed the feasibility of using this technique in young children. Using the sweep mode and the modeling software provided for the manufacturer of the instrument, the resistance of the extracellular (RECW) and intracellular (RICW) compartment was calculated. Correlation coefficient (r) and technical error of measurement (TEM) were obtained from paired BIS measurements. RECW showed to be highly reproducible (r = 0.99), with a relatively low TEM (from 1 to 3.5%), across all segments. The reliability was markedly lower respect to RICW, which shows the potential application of BIS technique even in critically ill young child populations.
The debate about the pathogenicity of Giardia lamblia in man has ended, and th issues regarding the prevalence of clinical and subclinical infections and their nutritonal impact have become the foremost considerations. Giardiasis can produce steatorrhea, maldigestion, and malabsorption of carbohydrates and of vitamins A and B12. The mechanisms of the absorptive dysfunction are not clear, but morphological abnormalities of the intestinal mucosa and/or bacterial overgrowth might play a role. Severe clinical giardiasis can cause "failure to thrive" in young children, but the impact, if any, of subclinical giardiasis on growth in general populations is not well defined. Protein-energy malnutrition appears to predispose to giardial infection, perhaps because of the accompanying hypochlorhydria, immunosuppression, and altered gastrointestinal flora. The lack of a sensitive and noninvasive diagnostic test for human giardial infection limits the investigation of the nutritional correlates of giardiasis.
Twenty preschool children with severe edematous protein-energy malnutrition (PEM) were studied during the first 45 days of recovery. All children received 4 g/kg/day of protein and 150 kcal/kg/day of energy from a milk-based recovery formula, providing 130-140 mg/kg/day of calcium (Ca). Children were randomized to two treatment groups, one receiving intact milk formula and the other a lactose-free preparation. Both groups showed a high efficiency of intestinal calcium absorption, sustained even after the normalization of weight for height and lean body mass. The presence or absence of lactose in the diet did not affect intestinal calcium absorption, and increased stool volume in the early period of recovery in the children receiving intact milk was not associated with higher fecal Ca losses. Urinary Ca excretion was within the range reported for healthy children under a normal diet. These results suggest that therapeutic amounts of calcium should be delivered to children with PEM well beyond the normalization of body weight and lean body mass.
Seventy-three preschool children with adequate nutritional status underwent interval-sampling, 3-hour breath-hydrogen carbohydrate absorption tests after consuming either 240 ml of intact milk (containing 12 g of lactose) or the same volume of milk with 90-95% of its lactose prehydrolyzed in vitro (containing less than 1 g lactose, with the remaining sugar as glucose and galactose). Results were examined in a reappraisal of the cut-off criterion for the rise of breath H2 concentration signifying biologically incomplete absorption. If the greater than or equal to 10-ppm criterion advocated by some investigators is used, 83% of our subjects would have been classified as incomplete lactose digesters and 30% would have their tests with the monosaccharide-rich milk classified as positive. With the greater than or equal to 20 ppm criterion used in our laboratory and others, the prevalence of lactose maldigestion in the sample becomes 60% and only 4% of subjects have apparent monosaccharide absorption, 96% having a rise below the cut-off level with prehydrolyzed milk. At least in Guatemalan preschoolers, the 20-ppm criterion for a positive breath H2 test provides a superior specificity-sensitivity balance and more reasonable diagnostic conclusions.
The concentration of hydrogen (H2) in expired air after an overnight fast is receiving interest as a diagnostic indicator in itself. We analyzed 319 fasting samples collected from 90 healthy, well-nourished preschool children aged 29-72 months in two institutional settings in Guatemala City. The overall range of fasting H2 concentration was 0-40 ppm, with an arithmetic mean of 4.4 +/- 5.4 ppm (+/- SD) and a geometric mean of 3.2 ppm. No differences between boys and girls was found, but there was a progressive increase in the mean levels and an increase in the number of samples with H2 concentrations greater than 10 ppm with decreasing chronological age. One child with three of six samples having H2 concentrations greater than 40 ppm was found to have intestinal multiple parasitism and hence was excluded from the sample. As compared with a previous report from the United States of fasting breath H2 concentrations in older children, the mean and distribution of values for Guatemalan preschoolers is identical. Intraindividual coefficients of variation in 48 children studied on four occasions had a mean of 62 +/- 31% (range 0-143%).
The test-retest reproducibility of the H2 breath test within the same individual has not been rigorously evaluated in preschool children. In the present study, 10 children--5 of whom were diagnosed as lactose-digesters on their first testing, and 5 of whom were diagnosed as lactose-maldigesters at first screening--were retested under identical conditions of a second opportunity. In each case, the same diagnostic classification was provided, for a reproducibility of 100%. Regression of the area under the curve of the change in breath H2 concentration during the 3 h of the test had a Pearson's correlation coefficient of 0.59 (p = 0.05). The time-course of 3-h H2 breath tests in 43 children with lactose maldigestion revealed a peaking of the concentration of H2 most commonly 120 min following the oral dose of 240 ml whole milk. Seventy-seven percent of the children who eventually proved to be lactose maldigesters were so diagnosed by the end of the second hour of the breath test. Thus, even the abbreviated breath sampling schedule used in children is sensitive, and few maldigesters would go undetected because of a late rise in breath H2 concentration.