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1.
Neurogastroenterol Motil ; 14(2): 123-31, 2002 Apr.
Article in English | MEDLINE | ID: mdl-11975712

ABSTRACT

Pramlintide delays gastric emptying, possibly by a centrally mediated mechanism. Our aim was to determine whether the effects of pramlintide on gastric emptying differ in people with type 1 or type 2 diabetes who had no history of complications. Using a randomized, three-period, two-dose, crossover design, we studied the effects of 0, 30, or 60 microg t.i.d. pramlintide subcutaneously for 5 days each in six type 1 and six type 2 diabetic subjects. Gastric emptying of solids was measured by 13C-Spirulina breath test. Plasma pancreatic polypeptide (HPP) response to the test meal was also measured. Relative to placebo [t 50% 91 +/- 6 min (means +/- SEM)], pramlintide equally delayed gastric emptying following 30 or 60 microg t.i.d. (268 +/- 37 min, 329 +/- 49 min, respectively; P < 0.01]. Postprandial HPP levels were lower in response to 30 and 60 microg pramlintide compared to placebo. There were no significant differences in the effects on gastric emptying or HPP levels between type 1 and type 2 diabetic subjects. Pramlintide delays gastric emptying in diabetes unassociated with clinically detected complications. Further studies are needed in diabetic patients with impaired gastric motor function.


Subject(s)
Amyloid/pharmacology , Amyloid/therapeutic use , Diabetes Mellitus, Type 1 , Diabetes Mellitus, Type 2 , Gastric Emptying/drug effects , Hypoglycemic Agents/pharmacology , Aged , Anti-Ulcer Agents/pharmacology , Anti-Ulcer Agents/therapeutic use , Cross-Over Studies , Diabetes Mellitus, Type 1/drug therapy , Diabetes Mellitus, Type 1/physiopathology , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/physiopathology , Dose-Response Relationship, Drug , Female , Gastric Emptying/physiology , Humans , Hypoglycemic Agents/therapeutic use , Islet Amyloid Polypeptide , Linear Models , Male , Middle Aged , Statistics, Nonparametric
2.
Aliment Pharmacol Ther ; 15(11): 1763-7, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11683690

ABSTRACT

BACKGROUND: In a previous study, the use of a citric acid test meal produced a rapid dose-dependent increase in urease activity that was significantly greater than that resulting from a pudding meal, ascorbic acid or sodium citrate. The mechanism was hypothesized to be related to the ability of citric acid to delay gastric emptying and possibly to enhance intragastric distribution of the urea. OBJECTIVE: To compare the effects of sodium citrate, two doses of citric acid and a pudding meal on gastric motor function. METHOD: Eleven normal healthy volunteers were investigated using non-invasive techniques to measure gastric emptying and gastric motility. We evaluated gastric emptying using the Meretek 13Ceebiscuit solid phase gastric emptying breath test, which employs a 340-calorie biscuit containing 200 mg of the edible 13C-blue-green alga Spirulina platensis, after the administration of test meals of pudding, 2 g and 4 g of citric acid and 2 g of sodium citrate. Electrogastrograms (Digitrapper EGG) were also recorded for 30 min before and 180 min after the test meal. RESULTS: Gastric emptying, as assessed by the half-time (T1/2), was delayed similarly with the pudding (136.8 +/- 9 min) and with 4 g of citric acid (144.5 +/- 7 min) (P > 0.7). Sodium citrate (108.7 +/- 6 min) and 2 g of citric acid (110.1 +/- 6 min) had similar effects on gastric emptying (P=0.986), and were significantly less effective in delaying gastric emptying (P < 0.01) compared to pudding or 4 g of citric acid. The electrogastrograms remained normal and there were no differences among meals and no relation with the gastric emptying results. CONCLUSIONS: The increased intragastric urea hydrolysis associated with citric acid test meals cannot be attributed to delayed gastric emptying. Changes in the intragastric distribution of urea or a direct effect of citric acid on the bacteria (e.g. via the cytoplasmic protein, UreI) are more likely to be responsible.


Subject(s)
Citrates/pharmacology , Citric Acid/pharmacology , Gastric Emptying/drug effects , Helicobacter Infections/pathology , Helicobacter pylori/enzymology , Urea/metabolism , Adolescent , Adult , Aged , Breath Tests , Citrates/administration & dosage , Citric Acid/administration & dosage , Dairy Products , Female , Helicobacter pylori/pathogenicity , Humans , Hydrolysis , Male , Middle Aged , Sodium Citrate
3.
Am J Gastroenterol ; 96(6): 1741-5, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11419823

ABSTRACT

OBJECTIVE: The U.S. standard 13C-urea breath test (13C-UBT) has proven to be extremely reliable but entails several complicated performance requirements and a test period of approximately 1 h. The aim of this study was to compare the standard 13C-UBT with a simplified version embodying modifications of test meal, duration of fasting, amount of 13C-urea, method of breath collection, and duration of test. METHODS: This was a randomized, three-way, crossover study of the standard U.S. 13C-UBT, which contains 125 mg of 13C-urea and a pudding test meal. The final breath sample is taken 30 min after urea ingestion. This test was compared with a formulation containing 75 mg of 13C-urea, a 2.5-g citric acid test meal (UBT-Lite), and a final breath sample taken by direct exhalation into tubes 15 min after urea ingestion. We also compared the effect of prior meals versus fasting on the test outcome with the UBT-Lite. RESULTS: A total of 259 subjects were enrolled in the trial, and 249 completed all three urea breath tests. There was excellent agreement between the three versions of the UBT with >98% of subjects having concordant results. Using predetermined criteria, there was substantial equivalence between the tests. Neither solid and/or liquid food up to 1 h before performing the UBT-Lite affected outcome. CONCLUSION: The UBT-Lite formulation of the 13C-UBT proved to be an improved version of the U.S. standard 13C-UBT offering less expensive ingredients, shorter test duration, and a simplified breath test collection method, without sacrificing accuracy.


Subject(s)
Breath Tests/methods , Helicobacter Infections/diagnosis , Helicobacter pylori , Urea , Adolescent , Adult , Aged , Carbon Radioisotopes , Citric Acid/administration & dosage , Cross-Over Studies , Fasting , Female , Humans , Male , Middle Aged , Reference Standards , Sensitivity and Specificity , Time Factors
4.
J Nutr ; 131(5): 1637S-42S, 2001 May.
Article in English | MEDLINE | ID: mdl-11340131

ABSTRACT

Breath tests have been used in research laboratories for over 25 y. Originally, the tests were based on the use of (14)C, rather than on the nonradioactive isotope, (13)C. When (13)C became widely available at a reasonable cost, research groups in the United States and Europe developed methodologies to measure (13)C abundance in samples of CO(2). The tests used a variety of substrates and measured pancreatic function, fat absorption, bacterial overgrowth and P(450) mixed-function oxidase. Thus far, the only test to be approved by the Food and Drug Administration is the (13)C-urea breath test. This manuscript describes the process by which approval is gained, and indicates the steps necessary for other tests to receive Food and Drug Administration approval.


Subject(s)
Breath Tests/methods , United States Food and Drug Administration , Carbon Isotopes , Diagnostic Tests, Routine/methods , Humans , Intestinal Mucosa/metabolism , Liver/metabolism , Reproducibility of Results , United States
5.
Can J Vet Res ; 65(1): 45-9, 2001 Jan.
Article in English | MEDLINE | ID: mdl-11227194

ABSTRACT

The objectives of this study were to determine whether a 13C-aminopyrine demethylation blood test is technically feasible in clinically healthy dogs, whether oral administration of 13C-aminopyrine causes a detectable increase in percent dose/min (PCD) of 13C administered as 13C-aminopyrine and recovered in gas extracted from blood, and whether gas extraction efficiency has an impact on PCD. A dose of 2 mg/kg body weight of 13C-aminopyrine dissolved in deionized water was administered orally to 6 clinically healthy dogs. Blood samples were taken from each dog 0, 30, 60, and 120 min after administration of the 13C-aminopyrine. Carbon dioxide was extracted from blood samples by addition of acid and analyzed by fractional mass spectrometry. None of the 6 dogs showed any side effects after 13C-aminopyrine administration. All 6 dogs showed a measurable increase of the PCD in gas samples extracted from blood samples at 30 min, 60 min, and 120 min after 13C-aminopyrine administration. Coefficients of variation between the triplicate samples were statistically significantly higher for the %CO2, a measure of extraction efficiency, than for PCD values (P < 0.0001). The 13C-aminopyrine demethylation blood test described here is technically feasible. Oral administration of 13C-aminopyrine did not lead to gross side effects in the 6 dogs. Clinically healthy dogs show a measurable increase of PCD in gas extracted from blood samples after oral administration of 13C-aminopyrine. Efficiency of CO2 extraction from blood samples does not have an impact on PCD determined from these blood samples. This test may prove useful to evaluate hepatic function in dogs.


Subject(s)
Aminopyrine/blood , Dog Diseases/diagnosis , Liver Diseases/veterinary , Liver/metabolism , Aminopyrine/administration & dosage , Aminopyrine/metabolism , Animals , Carbon Isotopes , Dogs , Dose-Response Relationship, Drug , Female , Kinetics , Liver Diseases/diagnosis , Male
6.
Neurogastroenterol Motil ; 13(6): 567-74, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11903917

ABSTRACT

To validate a 13C-Spirulina platensis breath test for measurement of accelerated or delayed gastric emptying, we measured gastric emptying of egg containing 13C-S. platensis and 99mTc-sulphur colloid by breath 13 CO2 every 15 min over 3 h and scintigraphy every 15-30 min over 5 h in 57 healthy volunteers. Thirty-three received no treatment, 10 received erythromycin, and 14 atropine. A generalized linear regression model predicted half-emptying time by scintigraphy (t1/2S) from breath 13CO2 (t1/2B) data. Accuracy was assessed by standard deviation (SD) of differences between t1/2S and t1/2B and by receiver operating characteristic (ROC) curves. Regression models using breath samples at baseline, and 45, 90, 105 and 120 min, predicted t1/2B (mean +/- SD) at 118 +/- 59 min, similar to t1/2S (118 +/- 67 min). Correlation between t1/2B and t1/2S was significant (r=0.88; P < 0.0001). Differences between t1/2S and t1/2B were: 18-19.2 min for t1/2 < 70-150 min, and 68.3 min for t1/2 > 150 min. Breath test detected abnormal emptying with a sensitivity of 86% and specificity of 80%. Thus, the 13C-S. platensis test measures gastric emptying t1/2 for solids, which is accelerated or delayed to mimic a range of conditions from dumping syndrome to severe gastroparesis, with high sensitivity and specificity. Additional breath samples are needed to increase sensitivity in detecting accelerated gastric emptying.


Subject(s)
Breath Tests , Gastric Emptying/drug effects , Adolescent , Adult , Aging/physiology , Algorithms , Anti-Bacterial Agents/adverse effects , Atropine/adverse effects , Bacterial Proteins/chemistry , Carbon Dioxide/analysis , Carbon Isotopes , Erythromycin/adverse effects , Female , Humans , Linear Models , Male , Middle Aged , Models, Statistical , Parasympatholytics/adverse effects , Sex Characteristics , Spirulina
7.
Eur J Surg ; 167(12): 903-8, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11841080

ABSTRACT

OBJECTIVE: To audit the early and late results of repairs of incisional hernias before and after the introduction of peroperative tensiometry. DESIGN: Retrospective study. SETTING: University hospital, Germany. PATIENTS: 675 operations on 553 patients in 18 years. INTERVENTIONS: Before we introduced tensiometry we closed 560 incisional hernias by direct suture and 63 by the inlay-onlay technique. Since we took up tensiometry the numbers were 9 and 43, respectively. MAIN OUTCOME MEASURES: Postoperative complications including recurrences. RESULTS: Recurrences developed in 246/560 (44%) after direct suture in the early series, compared with 2/9 (22%) after adoption of tensiometry. After inlay-onlay operations there were 4/63 (6%) recurrences before, and 1/43 (2%) after adoption of tensiometry. CONCLUSIONS: Tensiometry allows the surgeon to tailor his operation to the conditions that he finds during the operation.


Subject(s)
Abdominal Muscles/surgery , Hernia, Ventral/surgery , Suture Techniques , Hernia, Ventral/physiopathology , Humans , Polypropylenes , Recurrence , Retrospective Studies , Surgical Mesh , Treatment Outcome , Wound Healing/physiology
8.
Pediatr Res ; 48(3): 323-8, 2000 Sep.
Article in English | MEDLINE | ID: mdl-10960497

ABSTRACT

A galactose breath test that quantitates [1-(13)C]galactose conversion to 13CO2 provides information on the whole body galactose oxidative capacity. As there is little information on the relationship between whole body oxidation and the genotype in patients with galactosemia, we measured the 13CO2 excretion for 2 h after administration of [1-(13)C]galactose in 37 patients (3-48 y old) with galactose-1-phosphate uridyltransferase (GALT) deficiency and 20 control subjects (3-37 y old). Eleven patients with the common Q188R/Q188R genotype and no detectable erythrocyte GALT activity eliminated <2% of a bolus of [1-(13)C]galactose as 13CO2 compared with 8.47 to 28.23% in controls. This defines a severe metabolic phenotype. Seven patients with one Q188R allele and a second mutant allele such as L195P, E308K, V151A, M142K, or Q344K and one patient with a K285N/unknown genotype also released <2% as 13CO2 in 2 h. The presence of N314D or S135L as the second mutant allele does not impair total body galactose oxidation, as individuals with the GALT genotype of Q188R/N314D, K285N/N314D, and Q188R/S135L had normal 2-h galactose breath tests. Subjects with S135L/S135L, N314D/N314D, S135L/deltaT2359 as well as other rarer genotypes such as R258C/Y209C, E203K/IVSC-N314D, K285N/T138M, Q188R/D113N, S135L/F171S, R148W/N314D, and IVSC-N314D/N314D oxidized galactose comparable to controls. The dissociation of residual erythrocyte GALT activity and whole body galactose oxidative capacity is exemplified by blacks with a S135L/S135L genotype and absent erythrocyte GALT activity. An oral 2-h [1-(13)C]galactose breath test distinguishes severe and variant GALT genotypes and enables delineation of the extent of impaired galactose metabolism in an array of patients who possess diverse GALT mutations. It may prove to be useful in establishing whether a patient is capable of manifesting disease similar to patients with a Q188R/Q188R genotype.


Subject(s)
Galactose/metabolism , UTP-Hexose-1-Phosphate Uridylyltransferase/genetics , UTP-Hexose-1-Phosphate Uridylyltransferase/metabolism , Adolescent , Adult , Breath Tests , Child , Child, Preschool , Female , Genetic Variation , Humans , Male , Middle Aged , Mutation , Predictive Value of Tests
9.
Gut ; 46(6): 768-73, 2000 Jun.
Article in English | MEDLINE | ID: mdl-10807886

ABSTRACT

BACKGROUND: Current breath tests for measurement of gastric emptying of solids are expensive, possibly inaccurate, and require cumbersome calculations. AIMS: We wished to validate a simplified solid gastric emptying test using a [(13)C]Spirulina platensis breath test for accurate results relative to scintigraphy. SUBJECTS: Thirty healthy volunteers. METHODS: We measured gastric emptying of egg containing [(13)C]S platensis and (99m)Tc sulphur colloid by breath (13)CO(2) and scintigraphy over six hours. A generalised linear regression model was used to predict t(1/2) and t(LAG) by scintigraphy from breath (13)CO(2) data. The model was cross validated and normative data calculated for a prepacked [(13)C]meal. RESULTS: Regression models using all breath data over six hours, for the first three hours, and for samples at 75, 90, and 180 minutes ("reduced model") predicted t(1/2) and t(LAG) values similar to scintigraphy (t(LAG) 43 (SD 12) min; t(1/2) 100 (20) min). Standard deviations of differences in t(1/2) and t(LAG) between scintigraphy and the "reduced model" were both 10 minutes. Gastric t(1/2) for the prepacked [(13)C]meal was 91 (15) min (10-90% range: 74-118). CONCLUSION: The [(13)C]S platensis breath test and a simple formula using breath (13)CO(2) at baseline, 90, and 180 minutes measured gastric emptying t(1/2) for solids with results that were comparable with scintigraphy.


Subject(s)
Breath Tests/methods , Eggs , Gastric Emptying/physiology , Adolescent , Adult , Carbon Isotopes , Female , Humans , Male , Radionuclide Imaging/methods , Sensitivity and Specificity
10.
Gastroenterol Clin North Am ; 29(4): 885-93, x, 2000 Dec.
Article in English | MEDLINE | ID: mdl-11190073

ABSTRACT

The preferred schema for management of Helicobacter pylori infection is diagnosis, treatment, and confirmation of cure. The 13C-urea breath test is ideal for active H. pylori infection for those in whom endoscopy is not required (e.g., those in whom cancer is not suspected) because it offers the combination of simplicity, accuracy, reliability, and absence of exposure to radioactivity. New versions of the test also offer increasing simplicity and lower costs.


Subject(s)
Breath Tests/methods , Carbon Isotopes , Helicobacter Infections/diagnosis , Helicobacter pylori , Urea/analysis , Carbon Dioxide/analysis , Humans , Reproducibility of Results
11.
J Pediatr Gastroenterol Nutr ; 29(3): 297-301, 1999 Sep.
Article in English | MEDLINE | ID: mdl-10467995

ABSTRACT

BACKGROUND: The 13C-urea breath test detects the presence of Helicobacter pylori from an enrichment of breath 13CO2, which, in turn, is critically dependent on the amount of dilution by endogenous CO2 production. The production of CO2 differs according to age (adults > children), sex (male > female) weight, and height. The cutoff value of 2.4 delta%(delta over baseline, DOB) for the 13C-urea breath test, defined in adults, does not take into account actual CO2 production. Therefore, this cutoff value (2.4 delta%) may or may not be appropriate for children. The purpose of this study was to determine a cutoff value that would provide accurate results in pediatric patients, independent of their differences in anthropometric parameters. METHODS: Estimates of CO2 production were combined with DOB values to calculate the host-dependent urea hydrolysis rate. RESULTS: Calculated as urea hydrolysis rate, the cutoff range for adults was 10.4 to 10.9 microg/min. Individual ranges were concentric (men, 9.6-10.9 microg/min; women, 8.5-12.2 microg/min). Results in studies of 312 children show that a urea hydrolysis rate of more than 10 m microg/min may also be appropriate to predict H. pylori infection. CONCLUSION: Calculating 13C-urea breath test values as urea hydrolysis rate removes the effect of individual anthropometric differences on test outcome and provides a single cutoff value for pediatric patients of all ages.


Subject(s)
Breath Tests , Carbon Dioxide/analysis , Urea/metabolism , Adolescent , Adult , Aged , Carbon Isotopes , Child , Child, Preschool , Female , Helicobacter Infections/diagnosis , Helicobacter pylori , Humans , Hydrolysis , Male , Middle Aged , Reference Values , Sex Characteristics
12.
Am J Gastroenterol ; 94(5): 1214-7, 1999 May.
Article in English | MEDLINE | ID: mdl-10235196

ABSTRACT

OBJECTIVE: Test meals are used in the urea breath test to slow gastric emptying and to increase the area of contact with the substrate. Recently, citric acid has been suggested as an improved liquid test meal. The mechanism is unknown and could act by delaying gastric emptying, decreasing the pH at the site of the bacteria, or both. Our aim was to evaluate the effects of citric acid test meals on urea hydrolysis in vivo, to identify the possible mechanism for enhanced urea hydrolysis, and to identify the minimum effective dose. METHODS: We compared the U.S. commercial 13C-urea breath test with four liquid test meals (200 ml of water) consisting of citric acid, ascorbic acid, sodium citrate, and glucose polymer and also after the subcutaneous administration of pentagastrin. We studied healthy volunteers with and without proven H. pylori infection (by serology and histology). 13C-urea was administered orally simultaneously with the liquid test meals or immediately after the pudding had been ingested. Breath samples were taken before and after oral administration of the 13C-urea. RESULTS: A dose response in urease activity was evident as the amount of citric acid was increased from 1 to 4 g. Citric acid at 1, 2, or 4 g produced significant increases in breath 13CO2 activity, compared with the commercial pudding (p < 0.05). Ascorbic acid (p = 0.053), subcutaneous pentagastrin (to lower pH) (p = 0.199), and glucose polymer (p = 0.03) (to delay gastric emptying) all approximately doubled breath 13CO2, compared with the commercial kit. Nevertheless, the increases were all significantly less than with the 4 g citric acid test meal. CONCLUSIONS: The data are consistent with the marked effect of citric acid on gastric emptying and, possibly, distribution of the urea within the stomach being largely responsible for the enhanced urease activity with citric acid test meals. It should be possible to use a low dose of citric acid (e.g., 1 g per 200 ml) to enhance the simplicity and palatability of the test.


Subject(s)
Breath Tests/methods , Citric Acid/administration & dosage , Urea , Ascorbic Acid/administration & dosage , Carbon Dioxide/analysis , Carbon Isotopes , Citrates/administration & dosage , Dose-Response Relationship, Drug , Gastric Acidity Determination , Gastric Emptying/drug effects , Glucans/administration & dosage , Helicobacter Infections/diagnosis , Helicobacter pylori , Humans , Pentagastrin/pharmacology , Sodium Citrate , Urease/metabolism
13.
Eur J Pediatr ; 156 Suppl 1: S43-9, 1997 Aug.
Article in English | MEDLINE | ID: mdl-9266215

ABSTRACT

We employed [1-13C] galactose in isotope kinetic studies to delineate whole body galactose metabolism in vivo in patients with galactose-1-phosphate uridyltransferase (GALT) deficiency. The data in three control and three adult galactosemic subjects, homozygous for the most common GALT gene defect, the Q188R mutation, and with absent RBC GALT activity, revealed an apparent endogenous galactose synthesis rate of 0.53-1.05 mg/kg per hour. Unlike normal children and adults who eliminated 3%-6% and 21%-47% of an intravenous bolus of [1-13C] galactose as 13CO, in expired air in 1 and 5 h respectively, classic galactosemic patients, either Q188R/Q188R or Q188R/unknown, released almost none in 1 h and 3%-6% in 5 h. In contrast, an African-American galactosemic variant patient with a S135L/S135L mutation and no residual RBC GALT activity oxidized [1-13C]galactose to 13CO2 at a rate comparable to control subjects. Individuals homozygous for the Duarte mutation, N314D/N314D and Q188R/ N314D. Q188R/+ and S135L/+ subjects also had normal breath test results. Not surprisingly, the Q188R/Q188R classic galactosemic patient cannot handle an acute galactose load, failing to match a control subject in the rapid conversion of [1-13C]galactose to [13C]glucose and 13CO2. However, classic patients synthesize substantial quantities of galactose de novo and on a lactose-free diet must oxidize comparable amounts of galactose to maintain steady-state levels of galactose and galactose metabolites such as galactose-1-phosphate, galactitol and galactonate. In vivo isotope kinetic analyses may allow us to understand better these aspects of galactose metabolism and, through the use of studies in variant galactosemics, perhaps allow us to begin to unravel the pathophysiology of galactosemia.


Subject(s)
Galactose/analysis , Galactose/biosynthesis , Galactosemias/metabolism , Adolescent , Adult , Breath Tests/methods , Carbon Isotopes , Case-Control Studies , Child , Female , Galactosemias/genetics , Humans , Male , Oxidation-Reduction , UTP-Hexose-1-Phosphate Uridylyltransferase
14.
Eur J Pediatr ; 156 Suppl 1: S50-8, 1997 Aug.
Article in English | MEDLINE | ID: mdl-9266216

ABSTRACT

The central pathways of metabolism include glycolysis and gluconeogenesis, fatty acid synthesis and beta-oxidation, the citric acid cycle and ureagenesis. Because these pathways intersect, changes in one pathway, due to inborn error or disease, affect pathways that may seem remote from the initial metabolic defect. These metabolic interrelationships also present difficulties for isotopic studies, because once carbon derived from isotopic tracers is introduced into metabolism it is extensively recycled. The use of multiple labeled (especially uniformly 13C-labeled ([U-13C]), metabolic tracers, in conjunction with mass isotopomer distribution analysis of mass and nuclear magnetic spectra, has enabled the development of methods that resolve some of these difficulties. Suitable choices of tracers and analytes allow the simultaneous measurement of multiple pathways and, importantly, their kinetic interrelationships. We illustrate three uses of the technique: (1) the unequivocal determination of trace fluxes; (2) the quantification of biosynthetic pathways: and (3) the dissection, in vivo, of the citric acid (Krebs) cycle. In each case, different combinations of [U-13C]tracer and metabolic end product have revealed metabolic phenomena that otherwise would remain unidentified. A particularly striking, and unexpected, observation that has emerged from recent studies using the technique, suggests that the key dehydrogenase reactions in the Krebs cycle may be reversible. Although this approach is of relatively recent development, it has already given a number of novel insights into the organization of the central metabolic pathways. It should provide a powerful method of investigating the metabolic impact of genetic disease and provide invaluable support of the assessment of new therapeutic interventions.


Subject(s)
Amino Acids/metabolism , Carbon/metabolism , Isotope Labeling/methods , Animals , Carbon Isotopes , Citric Acid Cycle , Gluconeogenesis/physiology , Humans , Infant , Isotope Labeling/instrumentation , Mammals/metabolism
15.
Am J Physiol ; 272(6 Pt 1): E1099-107, 1997 Jun.
Article in English | MEDLINE | ID: mdl-9227457

ABSTRACT

To investigate whether protein, carbohydrate, and fat metabolism was normalized in insulin-treated gestational diabetes mellitus (GDM), eight Hispanic women with GDM and eight healthy controls were studied at 32-36 wk of gestation and 6 wk postpartum. Net substrate utilization was measured using room respiration calorimetry. Exogenous substrate oxidation was determined by 13C recovered in breath CO2 from 13C-labeled leucine, glucose, and Hiolein. Women with GDM had higher 24-h oxygen consumption, carbon dioxide production, total energy expenditure, and basal metabolic rates than controls due to larger body mass. Adjusted for weight or fat-free mass, total energy expenditure, basal metabolic rate, and basal and 24-h whole body net protein, carbohydrate, and fat utilization did not differ between insulin-treated GDM subjects and controls in pregnancy or postpartum. Oxidation of [13C]leucine and [13C]glucose did not differ by group or pregnancy status. Recovery of exogenously administered [13C]Hiolein, a biosynthetic triglyceride, as breath 13CO2 was significantly lower in the GDM group antepartum and postpartum (P = 0.02), indicating lower oxidation of exogenous triglycerides in GDM.


Subject(s)
Diabetes, Gestational/metabolism , Energy Metabolism , Hypoglycemic Agents/therapeutic use , Insulin/therapeutic use , Oxygen Consumption , Postpartum Period/metabolism , Pregnancy/metabolism , Adipose Tissue/anatomy & histology , Adolescent , Adult , Basal Metabolism , Blood Glucose/metabolism , Body Weight , Carbon Dioxide/analysis , Carbon Isotopes , Diabetes, Gestational/drug therapy , Fatty Acids, Nonesterified/blood , Female , Glucagon/blood , Glucose/metabolism , Glycated Hemoglobin/analysis , Humans , Hydrocortisone/blood , Insulin/blood , Leucine/metabolism , Oxidation-Reduction , Triglycerides/blood , Triglycerides/metabolism
17.
Helicobacter ; 1(3): 165-7, 1996 Sep.
Article in English | MEDLINE | ID: mdl-9398899

ABSTRACT

BACKGROUND: In large-scale multi-center clinical trials, the US 13C-urea breath test (UBT) has proven to have a sensitivity and specificity of approximately 95%. Ingestion of a meal to delay gastric emptying has advantages of increasing the level of signal as well as prolonging the duration of significantly increased 13C excretion, at the expense of requiring 40 to 60 minutes to complete the test. Our aim was to explore the utility of the 13C-UBT with a total duration of 30 minutes or less. METHODS: After a baseline breath sample was obtained, 125 mg of 13C-urea was given in 100 ml of water, and additional breath samples were taken after 20 and 30 minutes. The results of the UBT were compared to histological assessment, culture, and the rapid urease test. 13C-UBTs were carried out on normal volunteers who underwent gastroscopy during which six mucosal biopsies were taken. Three biopsies were for histological evaluation (Genta stain), two for culture, and one was for agar gel rapid urease testing. The UBT was conducted 2 to 3 days either before or after the endoscopic procedure. RESULTS: The cutoff value for a positive UBT was enrichment of 2.4 delta/1000 (delta over baseline). Of the 66 tests, 51/1000 were Helicobacter pylori-positive. There were no false positive UBTs and only two false negative UBTs at 20 minutes (sensitivity, 96%; specificity, 100%). At 30 minutes, one other UBT was false negative (gray zone of 2.36/1000) (sensitivity, 94%; specificity, 100%). CONCLUSION: These results suggest that omission of the meal and shortening the duration of the US 13C-UBT to 20 minutes still may maintain excellent specificity and sensitivity of the test.


Subject(s)
Bacterial Proteins/metabolism , Breath Tests/methods , Fasting , Gastritis/diagnosis , Helicobacter Infections/diagnosis , Helicobacter pylori/enzymology , Urea , Urease/metabolism , Adult , Aged , Anti-Bacterial Agents/therapeutic use , Bacterial Proteins/analysis , Biopsy , Carbon Dioxide/analysis , Carbon Isotopes , Evaluation Studies as Topic , False Negative Reactions , False Positive Reactions , Female , Gastritis/drug therapy , Gastritis/metabolism , Gastritis/microbiology , Helicobacter Infections/drug therapy , Helicobacter Infections/metabolism , Helicobacter Infections/microbiology , Helicobacter pylori/isolation & purification , Humans , Male , Middle Aged , Sensitivity and Specificity , Time Factors , Urea/pharmacokinetics , Urease/analysis
18.
Am J Clin Nutr ; 64(1): 32-9, 1996 Jul.
Article in English | MEDLINE | ID: mdl-8669411

ABSTRACT

We examined the adaptive responses of body protein metabolism in the fed state to dietary protein restriction in lactating women to determine whether rates of body protein degradation and synthesis were lower than those of nonlactating women. Thirteen healthy women (five lactating, four nonlactating postpartum, four nulliparous) aged 28-32 y were given protein intakes of 1.5, 0.4, and 1.0 g.kg-1.d-1 over three consecutive 3-d periods, respectively. At the end of each period, while in the fed state, subjects received orally a single bolus dose of [1-13C]leucine. A 24-h urine collection was obtained simultaneously. Whole-body protein metabolism was characterized by using the end product model based on nitrogen excretion and leucine catabolism. Nitrogen flux and rates of protein degradation and synthesis in the fed state were significantly lower at a dietary protein intake of 1.0 g.kg-1.d-1 in lactating women than in their nonlactating postpartum counterparts. Net protein retention in the fed state was significantly higher at a dietary protein intake of 1.0 g.kg-1.d-1 in lactating than in nonlactatating postpartum and nulliparous women because of the relatively greater reduction in protein degradation than in protein synthesis. These studies suggest that lactating women rapidly adapt to dietary protein restriction by down-regulating protein metabolism, and that 13C-labeled amino acid tracers in combination with urinary nitrogen excretion serve as useful metabolic markers for the adequacy of the dietary protein content of lactating women.


Subject(s)
Dietary Proteins/administration & dosage , Food , Lactation/physiology , Proteins/metabolism , Adult , Carbon Isotopes , Female , Humans , Leucine/metabolism , Nitrogen/metabolism , Nitrogen/urine
19.
Am J Gastroenterol ; 91(6): 1112-5, 1996 Jun.
Article in English | MEDLINE | ID: mdl-8651154

ABSTRACT

OBJECTIVE: A recent study from Italy reported a high prevalence of ulcer disease in asymptomatic Helicobacter pylori infection. Such results are at variance with previous endoscopy screening studies. Our study was performed to obtain data on ulcer prevalence in normal H. pylori-infected subjects in the United States. METHODS: One hundred and ninety healthy individuals of either gender, over the age of 18, were studied. After completion of a detailed questionnaire and a urea breath test for H. pylori status, endoscopy was performed. Ulcer was defined as a mucosal ulceration > 5 mm in diameter and with apparent depth. RESULTS: There were 108 (57%) women and 82 (43%) men. The mean (+/-SD) age was 38.9 (+/-10.7) yr, range 21-79 yr. Careful history obtained after enrollment revealed presence of dyspeptic symptoms in 35 subjects (18%); the remaining 155 individuals were completely symptom-free. Infection with H. pylori was present in 102 subjects (54%). The infection rate was highest in Hispanics (70%), followed by African-Americans (58%), Caucasians (38%), and Asians (17%). The prevalence increased with age. Only two (1%) of 190 subjects, both with H.pylori infection, had peptic ulcer. In the H. pylori-infected group, the prevalence of peptic ulcer was 2%. CONCLUSION: In the United States, significant unrecognized and asymptomatic gastroduodenal disease is uncommon in H. pylori-infected individuals. These findings do not support the need for a mass screening program for H. pylori infection or for the use of antimicrobial treatment of asymptomatic subjects with this infection.


Subject(s)
Helicobacter Infections/epidemiology , Helicobacter pylori , Peptic Ulcer/epidemiology , Adult , Age Distribution , Aged , Dyspepsia/diagnosis , Dyspepsia/epidemiology , Female , Helicobacter Infections/diagnosis , Humans , Male , Middle Aged , Peptic Ulcer/diagnosis , Prevalence , Surveys and Questionnaires , United States/epidemiology
20.
Gastroenterology ; 110(4): 1031-5, 1996 Apr.
Article in English | MEDLINE | ID: mdl-8612990

ABSTRACT

BACKGROUND & AIMS: An association between water sources and the prevalence of Helicobacter pylori infection in Peruvian children was shown previously. The aim of this study was to confirm the presence of H. pylori in drinking water in the same community. METHODS: Forty-eight drinking water samples from different locations in pueblo jovenes (new towns) near Lima were collected. Samples were frozen until technology advanced to the point to the point at which H. pylori might be reliably detected. Immunomagnetic beads coated with anti-H. pylori immunoglobulin Gs were used to concentrate H. pylori, and two polymerase chain reaction assays based on different H. pylori genes were used. One was a polymerase chain reaction for the detection of the H. pylori adhesin subunit encoding gene, and the second was a previously validated H. pylori 16S ribosomal RNA reverse transcriptase-polymerase chain reaction. RESULTS: The expected 375-base pair fragment from the adhesin gene was amplified from 24 water samples. The expected 500-base pair fragment of the 16S ribosomal RNA and the 375-base pair fragment of the adhesin gene were amplified from 11 of the samples. CONCLUSIONS: These results confirm the presence of H. pylori in drinking water in Peru and are consistent with conclusions from a previous epidemiological study of the same population. This provides additional evidence for waterborne transmission of H. pylori in some environments.


Subject(s)
Helicobacter pylori/isolation & purification , Water Microbiology , Water Supply , Adhesins, Bacterial/genetics , Base Sequence , Genes, Bacterial , Helicobacter pylori/genetics , Helicobacter pylori/metabolism , Immunomagnetic Separation , Molecular Sequence Data , Nucleic Acid Hybridization , Peru , Polymerase Chain Reaction , RNA, Bacterial/analysis , RNA, Ribosomal, 16S/analysis , Sensitivity and Specificity
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