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A comparison of the structure and function of the terminal ileum in Crohn's disease using radiology, the "Dicopac" Schilling test and [14C] G.C.A. breath test.

Twenty patients with Crohn's disease were studied. Thirteen had radiological evidence of involvement of the terminal ileum. None had significant bacterial overgrowth of the small bowel contents and none had had resection of the terminal ileum. In all patients a [14C] glycocholic acid ([14C] G.C.A.) breath test and a "Dicopac" Schilling test were performed to assess terminal ileal function. The data showed poor correlation between the radiological appearance of the terminal ileum and the results of the functional tests. There was also poor correlation between the results of the [14C] G.C.A. breath test and the "Dicopac" Schilling test. Without terminal ileal histology, any assessment of the extent of Crohn's disease of the terminal ileum and of its effect on terminal ileal function, must include the [14C] G.C.A. breath test as well as radiology and the "Dicopac" Schilling test. The limitations of the [14C] G.C.A. breath test as a test of terminal ileal function in Crohn's disease are discussed.

Breath Tests

Alterations of the colonic flora and their effect on the hydrogen breath test.

The hydrogen breath test was performed by ingestion of 20 g lactulose and analysis of end-expiratory air. Eighteen patients undergoing colonoscopy, 17 receiving antibiotics, 12 prepared for colon surgery, and 15 controls were examined. The test was repeated under control conditions in the treated patients. Eleven of 55 subjects failed to produce significant amounts of hydrogen under control conditions. This 20% proportion of non-hydrogen producers is much higher than that reported by other investigators. The hydrogen production was very markedly depressed after preparation for colonscopy and antibiotic therapy. The effect of neomycin and enemata as used in preparation for colon surgery was less marked. Hydrogen production by the colonic flora is thus subject to individual variations and may be affected by various therapeutic regimens. All these may cause false negative results when using the hydrogen breath test to evaluate carbohydrate absorption. The test should therefore not be performed for a considerable time after therapeutic manipulation of the colonic flora.

Adolescent

The lactulose hydrogen breath test as a diagnostic test for small-bowel bacterial overgrowth.

The lactulose hydrogen breath test has been evaluated as a diagnostic test for small-bowel bacterial overgrowth using the 14C-glycocholate breath test for comparison. Twenty-seven patients with suspected bacterial overgrowth and 37 control patients were studied. The lactulose test was positive in 8 out of 9 patients with Subsequently proven bacterial overgrowth, all of whom had positive 14C-glycocholate tests. However, 6 patients with ileal disease or resection had positive 14C-glycocholate tests but negative lactulose tests. subsequent bacteriological study of duodenal juice from these patients was negative. Negative results were obtained by both tests in the remaining 12 patients, none of whom were subsequently shown to have bacterial overgrowth. All 37 control subjects had negative lactulose tests. The lactulose breath test is a simple and promising diagnostic test for the detection of small-bowel bacterial overgrowth and, unlike the 14C-glycocholate test, has the advantage of being able to distinguish bacterial overgrowth from ileal disease.

Breath Tests

[Performance and clinical usefulness of the 14CO2-glycocholate-breath-test].

14C-glycocholate breath-tests were performed in 22 clinical patients without gastointestinal disorders, in 11 cases with M. Crohn of the ileum and in 8 patients, in whom an intestinal overgrowth with bacteria was suspected. Additional to the usual discontinuous measurement of the specific activity of 14CO2 the exhaled amount of CO2 and 14CO2 and 14C-serum activity were determined. No advantage was found in the determination of the latter; for 1. discontinuous measurement of the specific activity of 14CO2 was sufficient for detecting disturbed enterohepatic bile-salt circulation; and 2. measurement of 14C-serum-activity or 14C-activity in cholic acids or protein were of no help in differentiating between bacterial overgrowth and diseases of the ileum. There remained doubts regarding the clinical usefulness of the test. Low specificity and many positive tests in patients without corresponding symptoms require that therapeutical procedures in such patients are initiated with some reserve.

Adult

Assessment of the (14C) aminopyrine breath test in liver disease.

Different methods of performing the (14C) aminopyrine breath test have been assessed. A tracer dose of 2 muCi without a loading dose and with a single breath collection at two hours was the method selected, since it gave the best discrimination between patients with hepatocellular diseases and normal subjects (5.2 +/- 0.2%, mean +/- SEM). Reduced values occurred in patients with chronic active hepatitis (with and without cirrhosis) (1.5 +/- 0.2%), alcoholic cirrhosis (1.7 +/- 0.4%) and hepatitis (2.5 +/- 0.3%), and late primary biliary cirrhosis suggesting defective microsomal function with respect to demethylation. Normal results were common in early primary biliary cirrhosis. Two weeks of prednisolone therapy caused some improvement in the breath test in nine of 10 patients with chronic active hepatitis. It is concluded that the (14C) aminopyrine breath test is a simple test for detecting hepatocellular dysfunction, but has no obvious diagnostic advantage over the determination of serum aspartate transaminase and two hour post-prandial bile-acids.

Adolescent

Triolein breath test: a sensitive and specific test for fat malabsorption.

In order to develop a simple and accurate screening test for steatorrhea, the authors compared quantitative stool fat excretion with breath excretion of 14CO2 after the ingestion of 14C-labeled trioctanoin, tripalmitin, or triolein. The study group included 24 nonobese subjects without steatorrhea but with diarrhea secondary to irritable bowel syndrome and 40 subjects with steatorrhea. The triolein breath test provided the most reliable discrimination, with 100% sensitivity and 96% specificity. The trioctanoin and tripalmitin breath tests were sensitive, but lacked specificity (69% and 58% false-positive results, respectively). Three of the 12 obese patients with irritable bowel syndrome had false-positive triolein breath results. In detecting steatorrhea, the triolein breath test was moderately superior to the measurement of serum carotene and to qualitative stool fat. Thus, the triolein breath test appears to be a sensitive, specific, noninvasive, and relatively simple screening test for the detection of steatorrhea.

Adult

Clinical value of the bile acid breath test. Evaluation of the Mayo Clinic experience.

The Mayo Clinic experience with more than 200 bile acid breath tests was analyzed retrospectively to assess its clinical value. In patients with suspected bacterial overgrowth, the result of the bile acid breath test was compared with that of culture of aspirates of small bowel, and the test was found to have a sensitivity of 0.70 and a specificity of 0.90 (1.0 highest possible value). Although in one-third of the patients with a positive small-bowel culture the bile acid breath test failed to demonstrate the presence of bacterial overgrowth, analysis of the data according to the Bayes theorem showed that, compared with a routine evaluation without a small-bowel culture, the availability of breath test results will double the probability with which the clinician can be certain about the presence or absence of bacterial overgrowth. The test result appeared to influence the diagnosis in 83% and the management in 74% of the 163 patients in whom it was performed because of suspected bacterial overgrowth. In patients with suspected malabsorption of bile acids, on the other hand, the test that was performed without determination of fecal bile acid excretion appeared to be rather insensitive, and only rarely was information gained that was not already known from a routine workup of the patient.

Bacterial Infections

Sensitivity of bile acid breath test in the diagnosis of bacterial overgrowth in the small intestine with and without the stagnant (blind) loop syndrome.

The bile acid breath test was studied to examine its sensitivity for establishing the diagnosis of bacterial overgrowth in comparison to that of the Schilling test and small-intestinal cultures in 12 patients with a stagnant (blind) loop syndrome, as well as in 38 patients who had other conditions with suspected bacterial contamination of the small intestine. The presence of bile acid malabsorption was excluded in all 50 patients by studies of fecal excretion of radioactively labeled bile acids. The bile acid breath test was positive in 100% (12/12) of the patients with a stagnant (blind) loop syndrome, whereas 92% (11/12) had a positive Schilling test and 75% (9/12) a positive small-intestinal culture. The abnormal tests improved only in 2 of 4 patients treated with tetracycline. In the group of 38 patients without demonstrable dilated or blind loops of small bowel who were suspected of having bacterial contamination of small bowel, the bile acid breath test was positive in 53% (20/38), the Schilling test in 39% (15/38), and the small-intestinal culture in 45% (17/38). The difference in the incidence of positive results between the tests in the two patient groups was statistically not significant. The findings of these studies have the following diagnostic implications: (1) Bile acid breath test, Schilling test, and cultures of aspirates from the upper small bowel are of comparable sensitivity in the detection of bacterial overgrowth in the small intestine. (2) A negative bile acid breath test makes the diagnosis of a stagnant (blind) loop syndrome very unlikely.

Bacteria

Hydrogen and methane breath tests for evaluation of resistant carbohydrates.

This review considers in detail the background, principles, techniques, limitations and advantages of the hydrogen and methane breath tests. Resistant food carbohydrates, defined as dietary carbohydrates partly or totally escaping small intestinal assimilation, are fermented in the human colon. This results in production of H2, CH4 and volatile fatty acids. Increased colonic H2 production is a sensitive index of increased carbohydrate fermentation, and a rather constant fraction of the colonic H2 production is excreted by the lungs. It is therefore possible to assess mouth-to-caecum transit times as well as to estimate absorption capacities for several types of resistant carbohydrates by means of H2 breath tests. A prerequisite for correct interpretation is that procedures for determination of H2 concentrations and for breath sampling and storage are carefully validated and standardized. Due to the large interindividual variations of hydrogen excretion, unabsorbable standards should be used. The intraindividual variations of H2 production/excretion and differences in fermentability of different carbohydrate substrates only allow for semiquantitative estimates of malabsorbed amounts of some carbohydrates. Methane breath tests may supplement the information gained from hydrogen measurements, but further evaluations are needed. The hydrogen breath technique is rapid, simple and non-invasive as well as non-radioactive. It may be carried out in a large number of intact individuals under physiological circumstances, and it may be used for studies in children and for field studies. Compared to classical tolerance tests the hydrogen breath test is more sensitive. It is concluded that the hydrogen breath test is a useful tool for investigations of dietary carbohydrates.

Breath Tests

The [14C]-aminopyrine breath test. A comparison of different forms of analysis.

1 Following ingestion of [14C]-aminopyrine, breath 14CO2 data were analysed from normal individuals, patients with hepatic disease, epileptics receiving anticonvulsant therapy and volunteers before and after treatment with glutethimide. 2 The 'standard' 2 h [14C]-aminopyrine breath test discriminated successfully between the main groups but failed to detect the change in microsomal enzyme function produced by glutethimide. 3 A 'modified' form of the 2 h breath test calculated from the area under the breath specific activity curve detected the increase in demethylation following glutethimide. 4 The breath elimination constant (Kb) derived from the breath 14CO2 disappearance curve was as sensitive as the 'modified' 2 h breath test and was simpler to compute. 5 Glutethimide 500 mg/day for 14 days resulted in a 42% increase in the metabolic clearance of antipyrine and a 26% increase in demethylation of [14C]-aminopyrine.

Aminopyrine

Is the fat breath test effective in the diagnosis of fat malabsorption and pancreatic disease?

An attempt was made to evaluate the diagnostic effectiveness of the 14CO2-tripalmitin breath test in the screening or diagnosis of fat malabsorption. The differential absorption of 14C-tripalmitin and palmitic acid was evaluated in the diagnosis of pancreatic insufficiency. 24 controls, 13 patients with steatorrhea and 6 with pancreatic disease (4 of them with sufficiency) were studied. 81 breath tests were performed using 75 ml sour cream as a carrier. In 11 cases the 14C-tripalmitin test was repeated using 27 g corn oil as carrier. Both the 14C-tripalmitin and 14C-palmitic acid breath tests failed to provide any discrimination between normals and patients with fat malabsorption. Variation in type and amount of the carrier fat did not alter these results. 14C-tripalmitin absorption was distinctly abnormal in the patients with pancreatic insufficiency. The differential absorption of 14C-tripalmitin and 14C-palmitic acid provided an even better separation between patients with and without pancreatic disease. In contrast to some other investigators we did not find the 14C-tripalmitin and/or palmitic acid breath tests useful in the diagnosis or screening of fat malabsorption. These tests appear promising in the diagnosis of pancreatic disease.

Adolescent

Clinical diagnosis with the stable isotope 13C in CO2 breath tests: methodology and fundamental considerations.

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.

Adult

Aminopyrine breath test in alcoholic liver disease and in patients on enzyme-inducing drugs.

The 14C-aminopyrine breath test was used to measure liver function in 14 normal subjects, 16 patients with alcoholic cirrhosis, 14 alcoholics without cirrhosis, and 29 patients taking a variety of drugs. The normal value for the breath test was 8.6 +/- 1.5%, whereas it was significantly lower (5.1 +/- 3.8%) in patients with alcoholic cirrhosis. Higher than normal values were found in some alcoholic patients without cirrhosis and in patients receiving enzyme-inducing drugs, such as phenobarbitone. There was a significant correlation between serum gamma-glutamyltransferase and breath test in these groups. Some patients with alcoholic cirrhosis may also be capable of enzyme induction.

Adrenal Cortex Hormones

The cholyl glycine-1-14C breath test in various gastrointestinal disorders.

The cholyl glycine-1-14C breath test was evaluated in a variety of gastrointestinal disorders. 138 tests were performed in 106 patients. Methods of data expression were evaluated and the cumulative 8-hour value was used. In 27 control patients the upper limit of the normal was found to be 78. A good correlation was found between the peak values and the cumulative 8-hour values (r = 0.95, p less than 0.01). The reproducibility of the test was good (r = 0.985, p less than 0.05). Abnormal results were found in 12 out of 13 cases with resection of the ileum and 11 out of 14 cases with Crohn's disease of the distal small bowel. The test was normal in cases with diseases of the proximal small bowel (celiac, Whipple's and Chron's diseases). The test was also normal in patients with colitis. It was abnormal in some of the cases after cholecystectomy and in most cases with carcinoma of the pancreas. The breath test was useful in monitoring the results of treatment in bacterial overgrowth of the small bowel. False negative results were observed after antibiotic treatment. The method seems to be more sensitive than the Schilling test in diagnosing disease of the distal small bowel.

Adolescent

An evaluation of the 'breath test' in Crohn's disease.

The 1-(14C)-glycine-glycocholic-acid breath test was evaluated in 10 normal subjects and in 38 patients with Crohn's disease. Twelve patients were non-operated and 26 had been subjected to ileal resection (10-180 cm). In addition, coecal resection or right-sided hemicolectomy was performed on 20 patients and subtotal colectomy on six. The 14C-excretion in breath was abnormally elevated in only 16 of the 38 patients with Crohn's disease. Combining 14C-excretion in both breath and faeces, the test was found to be correlated with the activity of the disease in non-operated cases, whereas all resected patients were found to have bile acid malabsorption. It is concluded that the breath test is useless in Crohn's disease without concomitant measurement of the radioactivity in stools. The faecal 14C-excretion was correlated with the extent of ileal resection and with the extent of colonic resection, whereas the 14C-excretion in breath was independent of the type of operation performed. The breath test was found to be a more sensitive assay for ileal dysfunction than the duodenal bile acid concentration and the vitamin B12 absorption. No correlation with an elevated G/T-ratio and an abnormal bacterial growth was found.

Bile Acids and Salts

H2 breath tests during diarrhea.

The peak rise in breath hydrogen and the volume of excess pulmonary excretion of hydrogen in response to a 10 g dose of the non-abosorbable disaccharide, lactulose, was significantly lower in children with active gastroenteritis and diarrhea than in nondiarrheal controls. Thus, despite the fact that the H2 breath test is a convenient, noninvasive technology for use in children, it cannot be recommended for measuring carbohydrate malabsorption in individuals with active, on-going episodes of diarrhea.

Breath Tests

Abnormal aminopyrine metabolism in patients with hepatic neoplasm. Detection by breath test.

Aminopyrine metabolism was assessed by the aminopyrine breath test (ABT) in 153 patients with malignant disease, of whom 75 had hepatic neoplasm and 78 had none. Radioactive carbon dioxide (14CO2) exhalation was measured two hours after oral administration of a trace dose of carbon-14 labeled aminopyrine. The ABT was correct in 62 of 75 (83%) patients with hepatic neoplasm and in 73 of 78 (94%) patients without. It was correct in 16 of 22 (73%) patients who had hepatic neoplasm without abnormal serum biochemistry. Aminopyrine metabolic clearance rate (AMCR) was 32.4 ml/min in patients with hepatic neoplasm and 103.4 +/- 18.8 ml/min in the patients without. There was a highly significant correlation between ABT and AMCR (r =.76, P less than .01). We conclude that aminopyrine metabolism is depressed in most patients with hepatic neoplasm and that the ABT affords a useful method for detecting malignant tumors of the liver.

Administration, Oral