Partially anomalous pulmonary venous connection: demonstration of dual drainage allowing nonsurgical correction

The 13C-urea breath test (13C-UBT) is a non-invasive method for detecting Helicobacter pylori. This study was performed to determine the cutoff value and evaluate the sensitivity and specificity of 13C-UBT in Taiwan. 13C-Urea (100 mg of 99% 13C-labeled urea) was dissolved in 50 ml sterile water for the test. The test meal for delaying gastric emptying was 100 ml fresh milk. Patients fasted for at least 6h. A baseline breath sample was collected 5 min after they had the test meal. Two other samples were collected at 15 and 30 min after the patients ingested the 13C-urea. The test was evaluated in 352 patients after routine upper gastrointestinal endoscopy, and the urease test, culture, and histopathology were taken as the gold standards for detecting H. pylori. According to the receiver operating characteristic (ROC) curves, we chose values of 2.8 and 4.2 excess delta 13CO2 per mil as the cut-off values for 15 and 30 min, respectively, post 13C-urea. The sensitivity and specificity of 13C-UBT were 99% and 93% at 15 min, and 98% and 93% at 30 min post 13C-urea, respectively. The 13C-UBT breath test is an efficient non-invasive method of high sensitivity and high specificity for detecting H. pylori infection. We suggest that the use of fresh milk as the test meal and the detection of excess delta 13CO2 15 min after the ingestion of 13C-urea are suitable for the clinical use of 13C-UBT. This test is simple and rapid.     

Analysis of the 13C-urea breath test for detection of Helicobacter pylori infection based on the kinetics of delta-13CO2 using laser spectroscopy

We have previously reported on laser spectroscopy as a simple alternative to mass spectrometry. To validate a simplified 13C-urea breath test (UBT) with laser spectroscopy for the detection of Helicobacter pylori in clinical use, we evaluated the optimal time of breath sample collection. The 13C-UBT was carried out on each of 102 infected and 70 non-infected subjects (32 without eradication and 38 after eradication therapy). Breath samples were taken at five time points within 60 min followed by 100 mg of 13C-urea administration. The ratio of 13CO2 to 12CO2 was measured using laser spectroscopy and the recovery of tracer in the exhaled breath was calculated. Results were compared with histological and culture examinations of gastric biopsies to establish the infection status. For statistical evaluation of 13C-UBT, the optimal timing of breath sample collection was examined on the basis of the kinetics of delta-13CO2. In 32 H. pylori-negative patients (without therapy), the mean +/- 2SD of delta-13CO2 was at its minimum 20 min after urea ingestion whereas in H. pylori-positive patients, the mean +/- SD delta-13CO2 was maximum at 20 min. In addition, receiver operating characteristic (ROC) curve analysis showed that the cut-off value was estimated between 2.5-3.0 per mil (%0) at 20 min before therapy. Based on the histology and culture results, the sensitivity, specificity and positive and negative predictive values were 98.0%, 100%, and 94.1%, respectively. In conclusion, 13C-UBT with laser spectroscopy is a non-invasive, simple, sensitive and specific test to determine H. pylori status. Our findings suggest that in clinical use, measurements made at 20 min after substrate administration could be recommended for most sensitive and specific 13C-UBT results.     

Qualitative and semi-quantitative value of a modified 13C-urea breath test for identification of Helicobacter pylori infection

OBJECTIVE: The 13C-urea breath test (13C-UBT) is the method of choice in evaluating the success of therapy for eradication of Helicobacter pylori infection. For reasons of cost efficiency and practicability, urea dose and measurement duration have been reduced and the DOB (delta over baseline) cutoff level with the highest predictive value determined. Further, the efficacy of the modified 13C-UBT as a semi-quantitative test method was evaluated by comparison with histologically determined bacterial infiltration. METHODS: In a prospective study, a modified 13C-UBT with reduced urea dose (75 mg) and shortened measurement duration (30 min) was administered to 145 patients. The DOB cutoff with the highest predictive value was determined using relative operating characteristic analysis. Reference methods included histology, bacterial culture and the rapid urease test. The DOB value was compared with the histologically determined grade of bacterial infiltration and the correlation evaluated using the Spearman ranking method. RESULTS: Reduction of the DOB cutoff level from 5.0 per thousand to 3.5 per thousand led to significant improvement in sensitivity (78.9% vs. 91.2%) and accuracy (88.6% vs. 90.2%) of the 13C-UBT. Only five of 57 infected patients were incorrectly reported as non-infected after modification of the DOB level. In two of three patients in whom histological findings were negative but the 13C-urease test positive, bacterial growth was observed at culture. The DOB level correlated significantly with histological grade of bacterial infection. CONCLUSION: The modified 13C-UBT proved to be a sensitive, practicable and cost-effective method for detecting H. pylori infection and permits a semi-quantitative estimation of bacterial infiltration.     

Detection of Helicobacter pylori by culture and the 13C-urea breath test using an automated breath 13C analyzer

Up to now, the diagnosis of H. pylori infection has been made by the breath test using 13C-urea. In this study, 13C-urea breath samples were tested in 34 patients (peptic ulcer scar 17, chronic gastritis 17 cases) with an automated breath 13C analyzer (ABCA. Europa Scientific, Crewe, UK) and compared with the results of endoscopical diagnosis for H. pylori infection. Endoscopic and 13C-urea breath test (13C-UBT) were performed before eradicative medication. We described a modified protocol for the growth grade of H. pylori colonies in microbiology (H. pylori score), and for the delta 13C area under curve (AUC; permil*hr) obtained from each sample of expired breath. There was a significant correlation between delta 13C-AUC and the delta 13C level of each sample, but the correlation coefficient obtained at 10min (R2 = 0.582) was lower than that obtained at the other four time points (20min; 0.891, 30min; 0.949, 40min; 0.946, 50min; 0.946, 60min; 0.820). The delta 13C-AUC well correlated with H. pylori score (p < 0.01), none of 26 H. pylori positive patients detected by culture was 13C-UBT negative (delta 13C-AUC < 8.2 permil*hr in mean + 2SD of H. pylori negative group). In conclusion, 13C-UBT using ABCA has high sensitivity and specificity, and it provides a non-invasive method for the detection of H. pylori urease activity.     

Clinically feasible stable isotope technique at a reasonable price: analysis of 13CO2/12CO2-abundance in breath samples with a new isotope selective-nondispersive infrared spectrometer

Up to now, stable isotope analysis of carbon dioxide in breath samples is carried out with sensitive but very expensive and complex isotope ratio mass spectrometry (IRMS). Aiming at a more widespread application of breath tests in gastroenterological diagnostic routine, we tested a newly developed isotope selective non-dispersive infrared spectrometer (NDIRS) in comparison to IRMS. 13C-urea breath tests were performed in 63 patients as the routine screening method for Helicobacter pylori infection. Breath samples at baseline and (15) 30 min after administration of the test solution containing 13C-urea were analysed both by NDIRS and conventional IRMS. The correlation between the delta values of both devices was linear and in good agreement (r = 0.96; p < 0.0001; Y = 1.01 X -0.94). Comparing the delta over baseline-values, the correlation was Y = 1.11 X -0.36 (r = 0.98; p < 0.0001). Referring to the diagnosis of Helicobacter pylori infection with IRMS we calculated a sensitivity of 95.0% and an unchanged specificity (100%) for NDIR analysis. In conclusion, NDIRS appears a promising, easy to operate, and low cost potential alternative to conventional IRMS thus encouraging further detailed investigation and more widespread application of the noninvasive stable isotope technique in breath tests for gastrointestinal function testing.     

Positive result by serology indicates active Helicobacter pylori infection in patients with atrophic gastritis

Patients with atrophic corpus gastritis and elevated Helicobacter pylori antibody titers but 13C-urea breath test (13C-UBT) and histology results negative for H. pylori were randomized into eradication therapy or follow-up only. Antibody levels decreased significantly in six out of seven patients in the eradication group, while in the follow-up group, the titers declined in only one out of eight patients. In patients with atrophic corpus gastritis, positive serology results may indicate an ongoing infection in spite of negative 13C-UBT and histology results.     

Methodological study of 13C-urea breath test for detection of Helicobacter pylori infection

In this study, we investigate simple breath test for detection of Helicobacter pylori (HP) infection using 13C-urea. Thirty-nine patients (30 were HP positive, 9 were HP negative) were given three different doses (50, 100 and 150 mg) of 13C-urea at fasting, and keep sitting after mouth washing with water. Breath samples were taken before and 10, 20, 30, 45, and 60 minutes after urea administration. More than 100mg of 13C-urea was necessary for correct diagnosis of HP infection, because 2 HP positive cases were not detected by 50mg 13C-urea administration. In cases with patchy distribution of HP in the stomach, it may be necessary to change the posture to distribute urea within the whole stomach. In most of HP positive cases, peak delta 13CO2 were obtained within 30 minutes, but one HP negative case showed high delta 13CO2 at 10 minutes, which was probably caused by urease activity in the mouth. So it is appropriate to take breath sample at 20 minutes after urea administration. In this study, cut-off value for a positive test can be setted between 4 to 7 delta/1000, it is necessary to investigate much more cases to set exact cut-off value.     

Safety and efficacy of rabeprazole in combination with four antibiotic regimens for the eradication of Helicobacter pylori in patients with chronic gastritis with or without peptic ulceration

OBJECTIVES: Rabeprazole is a new fast acting proton pump inhibitor that has recently been proven to be effective in the treatment of peptic ulceration and reflux esophagitis. The aim of this study was to evaluate rabeprazole in combination with antibiotics for the eradication of Helicobacter pylori (H. pylori) in patients with chronic active gastritis with or without peptic ulcer disease. METHODS: Seventy-five H. pylori-infected patients were randomized in a double-blind fashion to receive a 7-day treatment regimen consisting of: RAC, RAM, RCM, or RC (R=rabeprazole 20 mg b.d., A=amoxycillin 1 g b.d., C=clarithromycin 500 mg b.d., M=metronidazole 400 mg b.d.). Randomized patients were H. pylori-positive by gastric biopsy urease test, histology and 13C urea breath test (13C-UBT). H. pylori eradication was assessed by 13C-UBT, 4 and 8 wk after finishing treatment. Endoscopy with histology and culture for antibiotic sensitivity testing was performed pretreatment and if treatment failed. RESULTS: On an intention-to-treat analysis, treatment success was: RCM 100%, RAC 95%, RAM 90%, and RC 63%. The most common side effects were loose stools, headache, and taste disturbance, but there were no serious adverse events related to the study medication. The two patients failing RAM treatment had metronidazole-resistant strains before and after treatment. None of the pretreatment H. pylori isolates from six patients failing RC were clarithromycin resistant, but three of five successfully cultured posttreatment had developed clarithromycin resistance. CONCLUSION: Rabeprazole-based triple therapy with two antibiotics for 1 wk is safe and effective in eradicating H. pylori. Dual therapy with clarithromycin is less successful, and the majority of treatment failures develop clarithromycin resistance.     

Quantitative noninvasive testing for Helicobacter pylori does not predict gastroduodenal ulcer disease

BACKGROUND: Helicobacter pylori is strongly associated with gastric and duodenal ulcer disease. However, the diagnosis of gastroduodenal ulcers requires an endoscopic or radiographic examination. In this study, we attempted to establish a relationship between the magnitude of [13C]urea breath test results or serum H. pylori IgG levels and endoscopic findings in H. pylori-infected individuals. METHODS: Patients who had undergone endoscopy and had a positive [13C]urea breath test and/or positive H. pylori IgG serology were identified. Endoscopic diagnoses included duodenal ulcer, gastric ulcer, nonulcer dyspepsia, and others. Results of 6% or greater on the [13C]urea breath test was defined as positive for H. pylori infection. H. pylori IgG serology was determined by an enzyme linked immunosorbent assay with values of greater than or equal to 1.0 being seropositive. RESULTS: One hundred seventy-five patients were seropositive (mean = 3.01 +/- 1.58). One hundred sixty-eight patients had a positive [13C]urea breath test (mean = 25.43 +/- 16.90). One hundred fifty-five patients were common to both the groups. Statistical analysis did not reveal any relationship between quantitative [13C]urea breath test results or H. pylori IgG values and endoscopic diagnoses. CONCLUSION: The magnitude of [13C]urea breath test or H. pylori IgG serology cannot be used to predict the presence or absence of gastroduodenal ulcer disease.     

Expression of two morphologic parameters concerning tumor-stroma interaction in benign and malignant melanocytic skin lesions

BACKGROUND: The 13C-urea breath (13C-UBT) test value is (semi-)quantitatively related to Helicobacter pylori density in the gastric antrum, and the value correlates with the grade of gastritis. The aim of this study was to assess variation of the 13C-urea breath test value by sociodemographic factors in H. pylori-positive children. METHODS: The analysis was performed on 127 asymptomatic children (aged 5-7 years) who were identified as H. pylori-positive with the 13C-UBT test in a large population-based epidemiologic study in the city of Ulm (southern Germany). The parents of the children were asked to fill out a standardized questionnaire about sociodemographic data. RESULTS: Forty-two infected children (33.1%) were of German nationality, 47 children (37.0%) were of Turkish and 38 children (29.9%) were of another nationality. Turkish children had a significantly higher 13C-UBT value (geometric mean = 27.2%) than German children (16.7%) or children with another nationality (19.3%) (P < 0.001). Girls had a trend towards higher values than boys (P = 0.058 after adjustment for nationality). Body mass index, education of the parents, and prior use of antibiotics were unrelated to the extent of the 13C-UBT. CONCLUSIONS: This study identified significant variation in the extent of the 13C value by nationality among H. pylori-infected children. Further studies are needed to elucidate the causes and potential consequences of these variations.     

A comprehensive analysis of complex traits in problem 2A

Helicobacter pylori infection is mainly acquired in childhood, and studies on the epidemiology of this infection depend on the availability of a noninvasive diagnostic test for use in children. The aim of this study was to determine whether the carbon 13-labeled urea breath test (UBT) can be used in children by evaluating: (1) its sensitivity and specificity compared with either culture or both rapid urease test and histologic examination, (2) whether a test meal or a prolonged fast is required, (3) the usefulness after treatment for H. pylori. Eighty-eight children (mean age, 10.6 +/- 4.19 years) who were undergoing upper endoscopy were studied while fasting, not fasting, and after treatment. Children were given 50 mg of 13C-urea if they weighed less than 50 kg or 75 mg of 13C-urea if they weighed more than 50 kg with 50 mg of a glucose polymer solution in 7.5 ml of water. Breath samples were collected at baseline and at 15, 30, 45, and 60 minutes. In 63 fasting children the UBT was 100% sensitive and 97.6% specific at 30 minutes with a cutoff value of 3.5 delta 13CO2 per mil. Nonfasting tests in 23 children, performed between 1 and 2 hours after their usual meal, were 100% sensitive and 91.6% specific. In 13 children fed directly before the UBT, the sensitivity of the test was reduced to 50%. Thirty minutes was the optimal sampling time. There was a significant decrease in specificity when samples were obtained at 15 minutes, possibly caused by the interference of oral urease-producing organisms. The test was 100% sensitive and specific in 20 children after treatment for H. pylori infection. The UBT is a highly sensitive and specific test for the diagnosis of H. pylori infection in children. Neither a prolonged fast nor a test meal is required.     

Evaluation of clinical and home performance of the 13C-urea breath test for the detection of Helicobacter pylori

OBJECTIVE: This study analyses the 13C-urea breath test with the aim of determining the optimal time interval between dosing and breath sampling and examines the feasibility of having patients perform the test without supervision at home. DESIGN: Prospective study comparing the 13C-urea breath test with four antral biopsy-based tests in a random population undergoing upper gastrointestinal endoscopy. SETTING: One university hospital and one general hospital. PATIENTS: One hundred and four patients were included; 61 were Helicobacter pylori-positive and 43 H. pylori-negative according to biopsy-based tests. INTERVENTIONS: The 13C-urea breath test was performed at home by collecting a baseline and two post-dosing samples; the next day it was performed clinically by collecting a baseline and six post-dosing samples. A 100 mg dose of 13C-urea and a test meal were used. OUTCOME MEASURES: The breath samples collected were analysed. Excess delta 13CO2/12CO2 values above five per million were considered positive. RESULTS: The specificity of the clinical test was 100% whereas that of the home-based test was 95.1%. The sensitivity of the clinical test depended on the time interval between dosing and collection of the evaluated sample. Sensitivity was 100% if the sample was taken 50 min or more after dosing. The home-based test had a sensitivity of 94.8%. CONCLUSION: To obtain maximum sensitivity (100%) using the single-sample technique the sample has to be collected at least 50 min after dosing. It is feasible to have the test performed at home. Patient selection and thorough instruction are necessary.     

13C-urea breath test for diagnosis of experimental Helicobacter pylori infection in barrier born pigs

Previous studies with Helicobacter pylori infected barrier born pigs indicate that the infection has a patchy distribution, resulting in false negative culture results on endoscopic biopsy specimens. This study aimed to adapt the 13C-urea breath test as used in humans to diagnose H pylori infection in barrier born pigs. The breath test was also performed after bismuth as a single treatment and after triple therapy (bismuth, ampicillin, metronidazole). In control pigs the median excess of 13CO2 in expired air was 2.2 (range 0-12 n = 22) ppm. The infected pigs (n = 4) showed consistently high values (median 23 range 14-43) when examined on four occasions (n = 16) four to 10 weeks after inoculation. Biopsy specimens for culture had lower sensitivity than the breath test. No reduction in excess 13CO2 was seen after three days' single bismuth treatment, but after two weeks' triple therapy the breath test results had returned to normal. This suppression was temporary only, however, as the breath test was positive again four weeks after stopping treatment. In conclusion, the 13C-urea breath test is a simple and reliable test for determining H pylori infection and monitoring treatment effects in barrier born pigs. Because the test can be performed in awake pigs anaesthesia and gastroscopy are unnecessary.     

Comparison of two rapid whole-blood tests for Helicobacter pylori infection in Chinese patients

Consecutive Chinese patients undergoing endoscopy for dyspepsia were tested for Helicobacter pylori infection by two rapid whole-blood tests: FlexPack HP (Abbott Laboratories) and Helisal One-Step (Cortecs Diagnostics). Biopsy-based tests (rapid urease test and histology) and the [13C]urea breath test were used as the "gold standard." One hundred sixty-one consecutive patients were studied, and 88 (54.7%) were confirmed to have H. pylori infection. The sensitivities, specificities, and positive and negative predictive values were 81.8%, 83.6% (P = 0.008), 85.7% (P = 0.04), and 79.2% for FlexPack HP and 84.1%, 63.0% (P = 0.008), 73.3% (P = 0.047), and 76.7% for Helisal One-Step, respectively.     

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.     

Usefulness of the [13C]-urea breath test for detection of Helicobacter pylori infection in fasting patients

Most of the reported [13C]-urea breath test procedures use a test meal, which is believed to assist in the spread of the [13C]-urea solution into the entire stomach, as results without a test meal may mainly reflect urease activity in the antrum.Yet, procedures for the [13C]-urea breath test and interpretation of the obtained 13C excess value have not been well established. We carried out the present study to validate the usefulness of the [13C]-urea breath test in fasting subjects and to establish cut-off values. [13C]-Urea breath tests were performed on 258 Helicobacter pylori-positive and 151 -negative subjects (247 H. pylori positive and 26 negative prior to any H. pylori cure treatment and 125 H. pylori negative and 11 positive after undergoing H. pylori cure treatment). The breath test procedure was performed under the following conditions: an 8 h fast, mouth washing before and after dosing, administration of 100 mg [13C]-urea, collection of breath sample in a plastic bag, a baseline and a 20 min sampling point and subject in a sitting position. Delta-13C at the 20 min sampling point in H. pylori-positive and -negative subjects was 31.0+/-1.25 and 1.6+/-0.11%, respectively. Although the mean delta13C value was greatest in duodenal ulcer or ulcer scar patients, there were no significant differences among mean delta13C values in the various diseases. From Receiver Operator Characteristic curves and calculation of accuracy of the test, a cut-off value of 5.0% is considered to be appropriate for diagnosis of H. pylori infection, which provides 96.7% specificity and 96.5% sensitivity, suggesting that the [13C]-urea breath test in the fasting state is as effective in detecting the presence of H. pylori as other reported methods.     

Effect of standard and high dose ranitidine on [13C]urea breath test results

OBJECTIVE: It has been suggested that standard dose H2 blockers will affect the [14-C]urea breath test. The aim of this study was to evaluate the effect of standard and high dose ranitidine on the [13C]urea breath test in a prospective cross-over study. METHODS: Volunteers found to be positive for H. pylori by IgG serology and [13C]urea breath test were given either ranitidine 150 mg b.i.d. or 300 mg b.i.d. for 14 days. Repeat breath tests were completed on the last day of antisecretory dosing and study patients were immediately crossed over to the other ranitidine dose. The third breath test was performed at 14 days after initiation of the new dose. RESULTS: A total of 20 volunteers were enrolled. Using the established cut-off of 2.4% for the commercial breath test, only one patient developed negative results on H2 blockers. This patient had negative breath tests on both ranitidine doses and remained test-negative off all medications 6 wk after study completion, suggesting either a false positive baseline test or an unexpected bacterial eradication. No specific trend in breath test results was observed for the group (p=NS). On ranitidine 300 mg, six of 19 patients elevated their breath results from 23% to 112% (mean 76%) above baseline. CONCLUSION: Ranitidine at standard or high doses did not generate a reproducible decline in breath test results. Histamine 2 blockers do not need to be discontinued before urea breath testing.     

p53 expression is of independent predictive value in lymph node-negative breast carcinoma

OBJECTIVES: To compare the diagnostic accuracy of the most widely available tests for diagnosis of Helicobacter pylori infection after antibiotic treatment. METHODS: A total of 59 H. pylori-positive, duodenal ulcer patients (mean age, 40.7 +/- 11.7 yr; 40 male and 19 female) were treated for 2 wk with either amoxicillin-metronidazole (n = 36) or omeprazole-amoxicillin-tinidazole (n = 23), and after 4 wk, were tested for H. pylori infection by [14C]urea breath test (UBT), serum IgG antibody level, and multiple antral biopsies for rapid urease testing, histology, Warthin-Starry stain, and polymerase chain reaction to detect H. pylori DNA. Infection status was established by a concordance of test results. RESULTS: H. pylori was eradicated in 47 patients (80%). UBT and rapid urease testing had the best sensitivity and specificity, although not statistically different to Warthin-Starry stain and polymerase chain reaction. Serology and histology had little diagnostic value in this setting due to high proportion of false-positive results. CONCLUSIONS: Noninvasive UBT is as accurate in predicting H. pylori status after antibiotic treatment as rapid urease testing and Warthin-Starry stain. Especially for duodenal ulcer patients, UBT could be considered the gold standard to confirm eradication of H. pylori.     

Measurement of very low stable isotope enrichments by gas chromatography/mass spectrometry: application to measurement of muscle protein synthesis

Measurement of muscle protein synthesis using stable isotopically labeled tracers usually requires isotope ratio mass spectrometry (IRMS) because of the need to measure very low enrichments of stable isotopically labeled tracers (tracer to tracee ratio [TTR], 0.005% to 0.10%). This approach is laborious, requiring purification of the metabolite of interest and combustion to a gas for IRMS analysis, and is best suited for use with 13C tracers. We have developed an approach whereby low enrichments can be conveniently measured by a conventional gas chromatography/mass spectrometry (GC/MS) instrument. The approach includes three critical elements: (1) use of a highly substituted tracer containing three or more labeled atoms, to measure enrichment above a very low natural abundance of highly substituted isotopomers; (2) use of a highly substituted natural abundance isotopomer as a base ion for comparison rather than the most abundant m + 0 isotopomer, to reduce the dynamic range of the isotopomer ratio measurement; and (3) a sensitive mass spectrometric analysis that measures the natural abundance of the isotopomer used as a tracer with a high signal to noise ratio (> 100:1). This approach was used to measure the rate of synthesis of muscle protein following a primed continuous infusion of L-[13C6]-phenylalanine (PHE) in eight fasted dogs and L-[2H3]-leucine in five fasted human subjects. Values for [13C6]-PHE enrichment by GC/MS rates were virtually identical to those obtained by a conventional approach using high-performance liquid chromatography (HPLC) to isolate PHE, combustion to CO2, and measurement of 13CO2 enrichment by IRMS (IRMS enrichment = 0.9988 x GC/MS enrichment, R2 = .891), resulting in identical values for muscle fractional synthesis rates ([FSRs] mean +/- SEM: 2.7 +/- 0.2 and 2.5 +/- 0.2%/d for GC/MS and IRMS, respectively). Human muscle synthesis rates measured by GC/MS analysis of [2H3]-leucine enrichment (1.90 +/- 0.17%/d) were similar to published values based on IRMS analysis using a 1- 13C-leucine tracer. We conclude that compared with the IRMS approach, the GC/MS approach offers faster throughput, has a lower sample requirement, and is suitable for a wider variety of tracers such as 2H. The principles outlined here should be applicable to the measurement of low enrichments by GC/MS in a wide variety of stable isotope tracer applications.     

Breath tests in intestinal diseases and functional gastrointestinal diagnosis

Among the numerous breath tests described for gastroenterological applications, breath hydrogen (H2) tests have emerged during the past two decades as a most sensitive, reliable and feasible method for detecting carbohydrate malabsorption and maldigestion (e. g. lactose maldigestion). Hence they are regarded time honored standards of contemporary gastroenterological function tests. For the diagnosis of the small bowel bacterial overgrowth syndrome the glucose H2 breath test is a feasible tool with moderate sensitivity (approximately 65%), which, however, is not higher with alternative breath test (e. g. the 1 g 14C-D-xylose breath test). Measuring mouth-to-caecum-transit time by the breath H2 response after lactulose is more of scientific interest than clinically informative. Breath tests making use of 14C labeled substrates (usually 5 to 10 microCi) bear a rather low calculated radiation hazard and are thus in routine use in some countries, e. g. in Scandinavia, but they are abandoned in others. At least, however, radioactive 14C breath tests are (partially) dispensible, as these restrictions do not apply for the stable isotope 13C breath tests which are nonradioactive and thus devoid of any radiation hazard. For the purpose of gastroenterological function testing the 13C urea breath test for the detection of Helicobacter pylori infection, quantitative studies of gastric emptying with 13C-acetate or 13C-octanoate and quantitative liver function tests have gained diagnostic use while 13C-breath tests assessing intestinal absorption or exocrine pancreatic function have been found less effective than the respective alternatives, or too expensive. Both, H2-breath tests and 13CO2-breath tests are clinically important, diagnostic methods with well delineated indications in gastroenterology.