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Biomedical subjects

T Preston

Publications and source records attributed to T Preston.

At least 19 recordsLinked to original sources

Improving the specificity of the [13C]mixed triacylglycerol breath test by estimating carbon dioxide production from heart rate.

BACKGROUND: The [13C]mixed triacylglycerol (MTG) breath test is a non-invasive measure of fat digestion and can be used to assess the need for enzyme replacement therapy in children with cystic fibrosis (CF). However, it lacks specificity. Quantitation of cumulative percent dose recovered (cPDR) requires knowledge of carbon dioxide production rate (VCO2). A resting value is assumed, but children are unlikely to remain at rest during the test. OBJECTIVE: To improve the specificity and therefore the positive predictive value (PPV) of the MTG breath test using calibrated heart rate monitors to estimate non-resting VCO2. DESIGN: Proof of concept study. SUBJECTS: Six children with CF, 10 healthy children and eight healthy adults performed [13C]MTG breath tests. METHODS: Heart rate monitors were worn throughout the test. Non-resting VCO2 was estimated continuously from heart rate. Percentage dose recovered was calculated using predicted resting VCO2, measured resting VCO2 and non-resting VCO2 estimated from heart rate. Physical activity level (PAL) was taken as cPDR calculated using non-resting VCO2 divided by cPDR calculated using measured resting VCO2. The cutoff point was determined using two graph-receiver operator characteristics. RESULTS: Use of calibrated heart rate monitors to estimate non-resting VCO2 improved the specificity of the test. The PPV increased from 0.67 to 0.99. PAL was 1.3 in adults and children who performed the test in hospital, and 1.7 in children who performed the test at home. CONCLUSION: Individually calibrated heart rate monitors are useful tools to estimate non-resting VCO2 during the [13C]MTG breath test.

Adolescent↗

The relationship between an inflammation-based prognostic score (Glasgow Prognostic Score) and changes in serum biochemical variables in patients with advanced lung and gastrointestinal cancer.

BACKGROUND: The Glasgow Prognostic Score (GPS), an inflammation-based prognostic score formed from standard thresholds of C reactive protein (CRP) and albumin, has prognostic value in patients with advanced cancer. Little is known about the general biochemical disturbance associated with the systemic inflammatory response in cancer. AIM: To examine the relationship between the GPS and blood biochemistry in patients with advanced lung and gastrointestinal cancer. METHODS: The GPS (albumin <35 g/l = 1 and CRP >10 mg/l = 1 combined to form a prognostic score of 0 (normal) and 1 or 2 (abnormal)) and a variety of biochemical variables were examined in patients (n = 50) with advanced lung or gastrointestinal cancer and in a healthy control group (n = 13). RESULTS: The GPS was normal in all the controls, but abnormal in 78% of the cancer group. Serum levels of sodium, chloride, creatine kinase, zinc and vitamin D were lower in the cancer group (all p<0.01), whereas levels of calcium, copper (both p<0.05), alkaline phosphatase, gamma-glutamyl transferase (both p<0.001) and lactate dehydrogenase (p<0.10) were raised. In the patient group, with increasing GPS, there was a median reduction in Karnofsky Performance Status (25%), haemoglobin (22%), sodium (3%), zinc (15%) and survival (93%, all p<0.05) and a median increase in white cell count (129%), alkaline phosphatase (217%), gamma-glutamyl transferase (371%) and lactate dehydrogenase (130%, all p<0.05). CRP levels were strongly and similarly correlated with alkaline phosphatase and gamma-glutamyl transferase, accounting for more than 25% of the variation in their activities. CONCLUSION: Several correlations were seen between biochemical variables and increasing GPS. In particular, chronic activation of the systemic inflammatory response in cancer was associated with increase in gamma-glutamyl transferase and alkaline phosphatase activity in patients with advanced lung and gastrointestinal cancer.

Adult↗

Effects of GI and content of indigestible carbohydrates of cereal-based evening meals on glucose tolerance at a subsequent standardised breakfast.

OBJECTIVE: To evaluate the impact of four low-glycaemic index (GI) and one high-GI cereal-based evening meals on glucose tolerance at a subsequent standardised breakfast. DESIGN: Wheat kernels, barley kernels, spaghetti, spaghetti with added wheat bran and white wheat bread (WWB) were consumed in the evening in a random order at five different occasions. At the subsequent breakfast, blood glucose, serum insulin, plasma short chain fatty acid, plasma free fatty acid (FFA) and breath hydrogen were measured. SETTING: The study was performed at Applied Nutrition and Food Chemistry, Lund University, Sweden. SUBJECTS: Fifteen healthy volunteers were recruited. One subject was later excluded owing to abnormal blood glucose values. RESULTS: The blood glucose response (0-120 min) to the standardised breakfast was significantly lower after consuming barley kernels in the evening compared with evening meals with WWB (P=0.019) or spaghetti+wheat bran (P=0.046). There were no significant differences in insulin concentrations at breakfast. Breath hydrogen excretion at breakfast was significantly higher after an evening meal with barley kernels compared with WWB, wheat kernels or spaghetti (P=0.026, 0.026 and 0.015, respectively), and the concentration of plasma propionate at breakfast was significantly higher following an evening meal with barley kernels compared with an evening meal with WWB (P=0.041). In parallel, FFA concentrations were significantly lower after barley kernels compared with WWB (P=0.042) or spaghetti evening meals (P=0.019). CONCLUSIONS: The improved glucose tolerance at breakfast, following an evening meal with barley kernels appeared to emanate from suppression of FFA levels, mediated by colonic fermentation of the specific indigestible carbohydrates present in this product, or, to the combination of the low-GI features and colonic fermentation.

Adult↗

Comparison of accuracy and precision of heart rate calibration methods to estimate total carbon dioxide production during 13C-breath tests.

BACKGROUND: 13C-breath tests are noninvasive tools to measure gastrointestinal function and nutritional interventions. Calculation of percentage dose recovered of 13C in exhaled breath requires knowledge of CO2 production rate (VC02). A resting value is usually assumed, but this can underestimate VC02 because subjects are unlikely to remain at rest during tests that last for many hours. There is a need for a method to estimate nonresting VC02 during 13C-breath tests. OBJECTIVE: To calibrate a heart rate monitor to continually estimate VC02 during 13C-breath tests. DESIGN: Proof of concept study. SUBJECTS: Eight healthy adults, 10 healthy children and six children with cystic fibrosis. METHODS: Heart rate and VC02 were measured simultaneously at resting and nonresting levels. A new calibration method (smoothing heart rate and fitting a sigmoid function) was compared with published methods. A [ 3C]acetate breath test was used to demonstrate the range of physical activity during breath tests. RESULTS: The new calibration method was more accurate than existing methods (mean bias -0.0002%, 95% confidence interval (CI) -0.0007, 0.0003% of the mean measured VC02). Smoothing heart rate gave a more precise estimate of VC02 and a more accurate estimate of resting energy expenditure (mean bias -0.09, 95% Cl -0.22, 0.05 mmol CO2 min-' m-2 body surface area) than using raw data (mean bias -0.21, 95% Cl -0.38, -0.04 mmol CO2 min' m-2 body surface area). Physical activity level ranged from 1.0 to 2.5 in children, and 1.0 to 1.5 in adults. CONCLUSION: Use of smoothed HR with a sigmoid function provides an accurate method of estimating nonresting VC02 during 13C-breath tests.

Adolescent↗

Ultrasonographic assessment of the rate of solid-phase gastric emptying in dogs.

Twelve healthy dogs were used in an ultrasonographic assessment of the effect of the composition of a solid meal on the rate of gastric emptying. The dogs were fasted for nine hours before they were fed either a standard or a high energy density test meal, in a cross-over study design. The gastric antrum was visualised with a 6.5 MHz microconvex transducer, and the area inside the elliptical shape defined by the craniocaudal and ventrodorsal diameters of the stomach was measured. Antral images were acquired at regular intervals for six hours after the ingestion of the test meal. Three indices to describe the rate of gastric emptying were computed: the gastric half-emptying time (t1/2), the time to 50 per cent maximal antral area (t50%), and the time of maximal antral area (tmax). The values of t50% and t1/2 calculated for the high energy density meals were significantly longer than for the standard meals, but there was no significant difference between the tmax values.

Animal Feed↗

Effects of changes to the stable environment on the exhalation of ethane, carbon monoxide and hydrogen peroxide by horses with respiratory inflammation.

The aim of this study was to assess the effects of changes to the stable environment on exhaled markers of respiratory inflammation in six horses with clinical histories of recurrent airway obstruction. The horses were maintained for two weeks under conventional stable management (straw bedding and hay) and for two weeks on a reduced-dust regimen (paper bedding and ensiled grass), in a crossover study design. Exhaled ethane and carbon monoxide (CO) and exhaled breath condensate hydrogen peroxide (H(2)O(2)) were measured every three days under each regimen. The presence of clinical signs of airway inflammation (nasal discharge and cough) was monitored daily. The reduced-dust regimen was associated with fewer clinical signs of airway inflammation than the conventional regimen. Exhaled ethane and CO were significantly lower on the reduced-dust regimen and these markers were correlated with clinical signs of respiratory inflammation, but exhaled H(2)O(2) was not affected by the management regimen.

Airway Obstruction↗

The response of leptin, interleukin-6 and fat oxidation to feeding in weight-losing patients with pancreatic cancer.

At baseline, weight-losing pancreatic cancer patients (n=7) had lower leptin (P<0.05) but higher cortisol, interleukin-6, resting energy expenditure and fat oxidation than healthy subjects (n=6, P<0.05). Over a 4 h feeding period, the areas under the curve for glucose, cortisol and interleukin-6 were greater (P<0.05), but less for leptin in the cancer group (P<0.05). Therefore, it would appear that low leptin concentrations, increased fat oxidation and insulin resistance are associated with increased concentrations of cortisol and interleukin-6 in weight-losing patients with pancreatic cancer.

Blood Glucose↗

Current and future uses of breath analysis as a diagnostic tool.

The analysis of exhaled breath is a potentially useful method for application in veterinary diagnostics. Breath samples can be easily collected from animals by means of a face mask or collection chamber with minimal disturbance to the animal. After the administration of a 13C-labelled compound the recovery of 13C in breath can be used to investigate gastrointestinal and digestive functions. Exhaled hydrogen can be used to assess orocaecal transit time and malabsorption, and exhaled nitric oxide, carbon monoxide and pentane can be used to assess oxidative stress and inflammation. The analysis of compounds dissolved in the aqueous phase of breath (the exhaled breath condensate) can be used to assess airway inflammation. This review summarises the current status of breath analysis in veterinary medicine, and analyses its potential for assessing animal health and disease.

Animals↗

Reduced total energy expenditure and physical activity in cachectic patients with pancreatic cancer can be modulated by an energy and protein dense oral supplement enriched with n-3 fatty acids.

The aim of the study was to assess the total energy expenditure (TEE), resting energy expenditure (REE) and physical activity level (PAL) in home-living cachectic patients with advanced pancreatic cancer. The influence of an energy and protein dense oral supplement either enriched with or without the n-3 fatty acid eicosapentaenoic acid (EPA) and administered over an 8-week period was also determined. In total, 24 patients were studied at baseline. The total energy expenditure was measured using doubly labelled water and REE determined by indirect calorimetry. Patients were studied at baseline and then randomised to either oral nutritional supplement. Measurements were repeated at 8 weeks. At baseline, REE was increased compared with predicted values for healthy individuals (1387(42) vs 1268(32) kcal day(-1), P=0.001), but TEE (1732(82) vs 1903(48) kcal day(-1), P=0.023) and PAL (1.24(0.04) vs 1.50) were reduced. After 8 weeks, the REE, TEE and PAL of patients who received the control supplement did not change significantly. In contrast, although REE did not change, TEE and PAL increased significantly in those who received the n-3 (EPA) enriched supplement. In summary, patients with advanced pancreatic cancer were hypermetabolic. However, TEE was reduced and this was secondary to a reduction in physical activity. The control energy and protein dense oral supplement did not influence the physical activity component of TEE. In contrast, administration of the supplement enriched with EPA was associated with an increase in physical activity, which may reflect improved quality of life.

Administration, Oral↗

Validation of a method for collection and assay of pentane in the exhaled breath of the horse.

Oxidative stress refers to an imbalance between the production of oxidising free radicals and the antioxidant defenses of the cell, and is associated with many pathogenic processes. Oxidative damage to cellular lipids results in the evolution of pentane and ethane gas, and detection of these hydrocarbons in the exhaled breath can be used to monitor in vivo oxidative stress. The aim of this study was to validate a gas chromatography (GC) method for measurement of breath pentane in the horse. The GC-system developed showed good specificity for discrimination of pentane from other breath hydrocarbons, and was sensitive to 0.5 ppb pentane. Pentane was detected in the exhaled breath of five horses investigated on two occasions. The results of this preliminary study demonstrate that breath pentane can be measured in the horse, and further work is now justified to investigate the feasibility of applying this method for monitoring in vivo oxidative stress in the horse.

Animals↗

Effect of body size on gastric emptying using the 13C-octanoic acid breath test.

The 13C-octanoic acid breath test (OABT) may be a useful non-invasive method for assessing the rate of gastric emptying in dogs. The aim of this study was to determine whether an association exists between body size and rate of gastric emptying in dogs. Fifty-five dogs ranging from 6 to 39 kg were recruited and rate of gastric emptying was assessed using the OABT. The time to peak 13CO2 excretion (tmax) and half-dose recovery time (t1/2) were calculated. The OABT was simple to perform and well tolerated by the dogs. Mean (sd) tmax was 2.67 hours (0.6) and mean t1/2 was 3.38 hours (0.79). Inter-individual variation in the rate of gastric emptying was 23.3 per cent for t1/2 and 22.5 per cent for tmax. No association was detected between the rate of gastric emptying and body surface area, mass, age, sex or test operator. The OABT may be a useful non-invasive and non-radioactive test for assessment of the rate of gastric emptying in dogs in clinical practice.

Animals↗

The usefulness of stable isotopes in nutrition and human health: the application of mass spectrometry and 13C-breath tests to detect helicobacter pylori infection.

The interest in Helicobacter pylori has escalated in recent years. H. pylori may produce a chronic gastric infection which is usually life-long and many epidemiological studies have shown that this is the most common bacterial infection throughout the world involving 50% of the world population. Thus, it is clear that the diagnosis of H. pylori infection represents at least a key step in the management of many of the patients referred to the gastroenterologist. Additionally, due to the wide range and relevance of pathologies possibly related to this infection, from micronutrient malnutrition and co-infections to malignancies, there is the potential for H. pylori to be a major health problem. Improved methods for the diagnosis and follow up treatment of the infection have been developed. Use of stable isotopes as non-invasive and safe diagnostic methods, namely (13C) breath tests, has been the key to a new era of research in H. pylori epidemiology and diagnosis as well as the establishment of eradication therapies. This non-invasive nuclear technique, that is considered the gold standard for the diagnosis of this bacterial infection, has successfully been standardized and implemented along Latin America. Taking into account the high prevalence of this bacterial infection, the impact of this technique in the whole region is very high. In this article we discuss several aspects of this methodology in order to harmonize the application of this method in developing regions.

Breath Tests↗

A comparison of the rate of recovery of 13CO2 in exhaled breath with 2H in body water following ingestion of [2H/13C]octanoic acid in a dog.

The objective of this study was to assess post-gastric processing of octanoic acid (OA) by comparing the rate of recovery of 13C in breath with the rate of recovery of 2H in saliva following ingestion of [2H/13C]OA. A test meal with 100mg [13C]OA and 750 mg [2H]OA was ingested on two separate occasions by one dog. Exhaled breath and saliva samples were collected at set time points for 6h following ingestion of the test meal. Two indices were computed, half recovery time (t(1/2)) and the time of peak excretion (t(max)). Recovery of 2H in saliva was quicker than recovery of 13C in breath as determined by the difference in the indices for each isotope; 1.33 and 1.59 h for t(1/2) and t(max), respectively. These findings suggest that the post-gastric processing of OA imposes a delay on the recovery of 13C in breath in the dog, as occurs in man and in the horse.

Animals↗

Gastrointestinal handling of glycosyl [13C]ureides.

OBJECTIVES: Lactose [(13)C]ureide has been proposed as a noninvasive marker for oro-caecal transit time in adults and children. The present study investigates the handling of lactose [(13)C]ureide ((13)C LU) and glucose [(13)C]ureide ((13)C GU) by the gastrointestinal tract and describes the metabolic fates of these substrates and describes the extent of tracer excretion by different routes. STUDY DESIGN AND SUBJECTS: Four subjects underwent five studies in which they ingested a test meal plus (1) no substrate, (2) (13)C LU, (3) (13)C GU, (4) (13)C LU after predosing with unlabelled lactose ureide and (5) (13)C LU after predosing with glucose ureide. Subjects were studied at home with at least 1 week between tests and they all completed the study. Breath was analysed for (13)CO(2) recovery and urine was analysed for total (13)C recovery, (13)C urea recovery and (13)C GU recovery. RESULTS: The profiles and extent of tracer recovery in breath and urine were similar when either (13)C GU or (13)C LU was used, suggesting similar handling of these substrates by the gut. (13)C GU was the major (13)C-enriched species recovered in the urine even when (13)C LU was consumed. Predosing with either lactose ureide or glucose ureide increased the rate of appearance of tracer, but did not alter transit times. CONCLUSIONS: (13)C LU is hydrolysed to (13)C GU in the small intestine with the fraction of (13)C GU appearing in the urine probably limited by small intestinal permeability. Either (13)C LU or (13)C GU can be used to measure oro-caecal transit time.

Adult↗

Starch fermentation by faecal bacteria of infants, toddlers and adults: importance for energy salvage.

OBJECTIVE: Little is known of the degree to which the colon salvages energy through starch fermentation in young children. Using a simulated colonic environment, we aimed to account for the fate of fermented raw and cooked starch in two groups of young children and in adults. DESIGN: A slurry was prepared from faecal samples from six infants (7-10 months), six toddlers (16-21 months) and seven adults (24-56 y). Each slurry was anaerobically incubated with raw or cooked maize starch in MacCartney bottles in a shaking water bath. Parallel incubations were stopped at 4 and 24 h. The headspace gas volume was analysed for CO(2) and methane. The culture supernatant was analysed for short-chain fatty acids (SCFA), lactate and residual starch. RESULTS: Different patterns of fermentation were seen at 4 and 24 h. For raw starch, the production of SCFA decreased with subject age at 4 h but not at 24 h. With both substrates at 4 h, toddler stools produced significantly more CO(2) than infants or adults, but there were no statistical differences at 24 h. Methane was detected in three adults only. Lactate was detected mainly at 4 h in children. CONCLUSIONS: The results suggest that fermentation, particularly of raw starch, is a more rapid process in young children than in adults. A highly efficient energy salvage process may occur in the colon of young children.

Adult↗

Validation of the 13C-octanoic acid breath test for measurement of equine gastric emptying rate of solids using radioscintigraphy.

REASONS FOR PERFORMING STUDY: Disordered gastric motility may be a significant factor in the pathogenesis of many equine conditions. Although tests for liquid phase emptying rate have been validated in the horse, there are no effective tests for solid phase emptying measurement that can be performed routinely in the field. OBJECTIVES: The objective of this study was the assessment of a novel stable isotope technique, the 13C-octane acid breath test (13C-OABT), for the measurement of gastric emptying of solid ingesta, by direct comparison with the optimum method of gastric scintigraphy. METHODS: To facilitate dual measurement of gastric emptying, a test meal was used containing baked egg yolk labelled with both 13C-octanoic acid and 99mtechnetium sulphur colloid. Simultaneous, serial lateral gastric scintigraphs and expiratory breath samples were obtained in 12 healthy horses after voluntary ingestion of the test meal. Analysis of breath 13CO2:12CO2 ratio was performed by continuous flow isotope ratio mass spectrometry. Power regression was used to determine the gastric emptying coefficient, the gastric half-emptying time (t 1/2) and duration of the lag phase (tlag). RESULTS: Significant correlations (P < 0.001) were found between the 2 techniques for measurement of both t 1/2 and tlag. In addition, scintigraphic left t 1/2 was correlated significantly to breath test gastric emptying coefficient (P < 0.001). CONCLUSIONS: It was concluded that the 13C-octanoic acid breath test is a reliable diagnostic procedure to measure gastric emptying rate of solids in the horse. POTENTIAL RELEVANCE: Being safe, noninvasive and easy to perform, this test has potential value as both sensitive diagnostic modality and humane research tool for motility studies.

Animals↗

In vitro studies indicate that acid catalysed generation of N-nitrosocompounds from dietary nitrate will be maximal at the gastro-oesophageal junction and cardia.

BACKGROUND: Dietary nitrate increases saliva nitrite levels and swallowed saliva is the main source of nitrite entering the acidic stomach. In acidic gastric juice, this nitrite can generate potentially carcinogenic N-nitrosocompounds. However, ascorbic acid secreted by the gastric mucosa can prevent nitrosation by converting the nitrite to nitric oxide. METHODS: To study the potential for N-nitrosocompound formation in a model simulating salivary nitrite entering the acidic stomach and the ability of ascorbic acid to inhibit the process. Concentrations of ascorbic acid, total vitamin C, nitrite, nitrosomorpholine, oxygen and nitric oxide were monitored during the experiments. RESULTS: The delivery of nitrite into HCl containing thiocyanate resulted in nitrosation of morpholine, with the rate of nitrosation being greatest at pH 2.5. Under anaerobic conditions, ascorbic acid converted the nitrite to nitric oxide and prevented nitrosation. However, in the presence of dissolved air, the ascorbic acid was ineffective at preventing nitrosation. This was due to the nitric oxide combining with oxygen to reform nitrite and this recycling of nitrite depleting the available ascorbic acid. Further studies indicated that the rate of consumption of ascorbic acid by nitrite added to natural human gastric juice (pH 1.5) was extremely rapid with 200 micromol/l nitrite consumed 500 micromol/l ascorbic acid within 10 s. CONCLUSIONS: The rapid consumption of ascorbic acid in acidic gastric juice by nitrite in swallowed saliva indicates that the potential for acid nitrosation will be maximal at the GO junction and cardia where nitrite first encounters acidic gastric juice. The high incidence of mutagenesis and neoplasia at this anatomical location may be due to acid nitrosation arising from dietary nitrate.

Ascorbic Acid↗