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Medical & Clinical

Understanding of the biological processes that control human and animal physiology can be difficult considering the moral implications that are involved in performing such studies. The use of stable isotope analysis provides a non-invasive approach with no adverse reactions which may be observed through using radioisotopes. The use of enriched isotope tracers with artificially high abundances of minor isotopes provides a relatively simple way of probing subtle biological processes.

Breath Analysis

After your subject has ingested an isotopically labelled meal (e.g. 13C-labelled glucose), exhaled CO2 from the patient will show enrichment in 13C levels relative to 12C. The time taken for the 13C isotope to appear in the exhaled breath gives some indication of the metabolic rate of the subject. Up to 220 breath samples can be analysed using our iso FLOW sample handling system for rapid analysis of large numbers of samples.

Body Fluid Analysis

Dosing a subject (human or animal) with doubly labelled water (e.g. water enriched in both deuterium and 18O) allows the total energy expenditure (TEE) of the subject to be determined. High performance deuterium and 18O isotope analysis of up to 180 saliva, blood and urine samples can be performed via headspace equilibration using the iso FLOW sample handling system.

Biochemical Analysis

To understand more about the complex physiological chemical processes that occur within the body, it is necessary to go beyond coarse breath and body fluid analysis. Our gas and liquid chromatography (GC-IRMS and LC-IRMS) systems are able to perform individual compound stable isotope analysis allowing you to find out more about these complex processes. 

Medical publications using our instruments

Our customers use our instruments to do some amazing research in the medical application field. To show you how they perform their research and how they use our IRMS instruments, we have collected a range of peer-reviewed publications which cite our products. You can find the citations below and then follow the links to the publishing journal should you wish to download the publication.

If you would like to investigate our available citations in more detail, or email the citation list to yourself or your colleagues then take a look at our full citation database.

37 results:

Science and Justice Provenancing of unidentified corpses by stable isotope techniques – presentation of case studies
Science & Justice (2014)
Christine Lehn, Andreas Rossmann, Matthias Graw

Stable isotopemethods can be used to determine the provenance of unidentified corpses. Body tissue materials such as teeth, bone, hair and nail taken frommortal remains provide information of different time periods of an individuals' life from childhood to death. Tissues of newborns contain provenance information of different time periods during pregnancy of the child's mother. The results of stable isotope analyses of body residues of two adults and a newborn found in Germany between 2010 and 2012 are presented. To determine the geographic origin and movements of unknown individuals, stable isotopes of hydrogen, carbon, nitrogen and sulphur were analysed in hair and bone collagen samples. Amino acid composition and, as a consequence, δ2H, δ13C, δ15N, and δ34S values in human keratin and bone collagen are different. Consequently correction factorswere determined to compare isotopic data of bone colla- gen with those of an extensive worldwide reference hair collection. The isotopic signatures in hair and in bone collagen samples were compared to geographical groups of reference hair samples by canonical discriminant analysis. The results served as the basis for providing provenance constraints for the unidentified persons as requested by the police and prosecution. Ultimately the individuals were identified; hence the isotopic prove- nance interpretations can be critically evaluated and are shown to be successful
Tags: carbon , hydrogen , nitrogen , sulfur , medi , crim , elem

Isotopes in Environmental and Health Studies Change of geographical location from Germany ( Bavaria ) to USA ( Arizona ) and its effect on H – C – N – S stable isotopes in human hair
(2014)
Christine Lehn, Christina Lihl, Andreas Roßmann

To receive information about the duration of a person’s stay abroad related to those questions in forensics, stable isotopes of H–C–N–S were analysed in beard hair samples from four young soldiers, who went from Fürstenfeldbruck (Bavaria, Germany) to Phoenix (Arizona, USA) on the same date for their pilot training over a time period of 3 months. All study subjects were almost of the same age, had similar physical constitutions and stayed at the same military bases for the whole study period. However, the results showed considerable individual variabilities. In Arizona, hair δ13C increased by 2.3‰(±0.6) and δ34S decreased by 1.8‰(±1.2). No remarkable shifts of hair δ15Nand δ2H were observed. Significant shifts of δ13Cor δ34S in the shaved beard hair samples occurred 8 or 9 days after arrival in Arizona, respectively. The time lag to receive the isotope signals in hair due to US diet correspond to the growth period that hair needs to cover the distance of 2–3 mmfrom its root to the surface of the skin. This implies that isotopic changes due to the consumption of food and drinks were incorporated almost immediately into the hair protein. Consequently, if connected with an isotopic change of the diet, short-term stays for only a few days might be clearly recognizable within the first millimetres of a scalp hair strand which includes the hair roots.
Tags: carbon , hydrogen , nitrogen , sulfur , medi , crim , elem

A Bedside Measure of Body Composition in Duchenne Muscular Dystrophy.
Pediatric neurology (2014)
Sarah a Elliott, Zoe E Davidson, Peter S W Davies, Helen Truby

BACKGROUND: In clinical practice, monitoring body composition is a critical component of nutritional assessment and weight management in boys with Duchenne muscular dystrophy. We aimed to evaluate the accuracy of a simple bedside measurement tool for body composition, namely bioelectrical impedance analysis, in boys with Duchenne muscular dystrophy. METHODS: Measures of fat-free mass were determined using a bioelectrical impedance analysis machine and compared against estimations obtained from a reference body composition model. Additionally, the use of raw impedance values was analyzed using three existing predictive equations for the estimation of fat-free mass. Accuracy of bioelectrical impedance analysis was assessed by comparison against the reference model by calculation of biases and limits of agreement. RESULTS: Body composition was measured in 10 boys with Duchenne muscular dystrophy, mean age 9.01 ± 2.34 years. The bioelectrical impedance analysis machine values of fat-free mass were on average 2.3 ± 14.1 kg higher than reference values. Limits of agreement (based on 95% confidence interval of the mean) were -7.4 to 2.9 kg. There was a significant correlation between the mean fat-free mass and difference in fat-free mass between the bioelectrical impedance analysis machine and the reference model (r = -0.86; P = 0.02) suggesting that the bias was not consistent across the range of measurements. The most accurate predictive equation for the estimation of fat-free mass using raw impedance values was the equation by Pietrobelli et al. (mean difference, -0.7 kg; 95% limits of agreement, -3.5 to 2.0 kg). CONCLUSIONS: In a clinical setting, where a rapid assessment of body composition is advantageous, the use of raw impedance values, combined with the equation by Pietrobelli et al., is recommended for the accurate estimation of fat-free mass, in boys with Duchenne muscular dystrophy.
Tags: hydrogen , oxygen , medi , gashead

Validation and reliability of two activity monitor for energy expenditure assessment
Journal of Science and Medicine in Sport (2014)
Anne-Sophie Brazeau, Nadia Beaudoin, Virginie Bélisle, Virginie Messier, Antony D. Karelis, Rémi Rabasa-Lhoret

Objectives This study explores the reliability and validity of the SenseWear Armband (SWA) and Actical (ACT) for free-living total energy expenditure, and energy expenditure during rest and light-to-moderate exercises (walking, ergocycling). Design Participants wore the 2 devices during 7 days (free-living) and then participated to 3 days of testing in our laboratory. Methods SWA and ACT estimates of total energy expenditure was compared to the doubly labeled water technique (7 days), and energy expenditure during rest (60 min), treadmill (45 min; intensities ∼22% to ∼41% VO2peak) and ergocycling (45 min; ∼50% VO2peak) were compared to indirect calorimetry over the following 3 days. Paired T-tests and intra-class correlation coefficient (ICC) with 95% confidence interval (CI95) were computed. Results Twenty adults were recruited (BMI 23.1 ± 2.3 kg/m2). Compared to doubly labelled water, SWA overestimated energy expenditure by 94 kcal/d (±319; P = 0.2) and ACT underestimated by −244 kcal/d (±258; P = 0.001). Energy expenditure during rest (SWA 210 ± 116, ACT 124 ± 133 kcal/d; p < 0.05) and treadmill (according on intensity: SWA 54 ± 46 to 67 ± 38, ACT 68 ± 25 to 84 ± 40 kcal; p < 0.05) were overestimated and underestimated during ergocycling (SWA −93 ± 65, ACT −269 ± 111 kcal; p < 0.05) compared to indirect calorimetry. High ICC were observed at rest (SWA 0.994 CI95 0.987–0.997; ACT 0.998 CI95 0.996–0.999) and during ergocycling (SWA 0.941 CI95 0.873–0.975; ACT 0.854 CI95 0.687–0.939). Conclusion Acceptable estimation of total energy expenditure was observed with the SWA. Both devices were reliable but not accurate for energy expenditure's estimations during rest and for specific exercises.
Tags: hydrogen , oxygen , medi , gashead

The sedentary time and activity reporting questionnaire (STAR-Q): Reliability and validity against doubly labeled water and 7-day activity diaries
American Journal of Epidemiology (2014)
Ilona Csizmadi, Heather K. Neilson, Karen A. Kopciuk, Farah Khandwala, Andrew Liu, Christine M. Friedenreich, Yutaka Yasui, Rémi Rabasa-Lhoret, Heather E. Bryant, David C W Lau, Paula J. Robson

We determined measurement properties of the Sedentary Time and Activity Reporting Questionnaire (STAR-Q), which was designed to estimate past-month activity energy expenditure (AEE). STAR-Q validity and reliability were assessed in 102 adults in Alberta, Canada (2009-2011), who completed 14-day doubly labeled water (DLW) protocols, 7-day activity diaries on day 15, and the STAR-Q on day 14 and again at 3 and 6 months. Three-month reliability was substantial for total energy expenditure (TEE) and AEE (intraclass correlation coefficients of 0.84 and 0.73, respectively), while 6-month reliability was moderate. STAR-Q-derived TEE and AEE were moderately correlated with DLW estimates (Spearman's ρs of 0.53 and 0.40, respectively; P < 0.001), and on average, the STAR-Q overestimated TEE and AEE (median differences were 367 kcal/day and 293 kcal/day, respectively). Body mass index-, age-, sex-, and season-adjusted concordance correlation coefficients (CCCs) were 0.24 (95% confidence interval (CI): 0.07, 0.36) and 0.21 (95% CI: 0.11, 0.32) for STAR-Q-derived versus DLW-derived TEE and AEE, respectively. Agreement between the diaries and STAR-Q (metabolic equivalent-hours/day) was strongest for occupational sedentary time (adjusted CCC = 0.76, 95% CI: 0.64, 0.85) and overall strenuous activity (adjusted CCC = 0.64, 95% CI: 0.49, 0.76). The STAR-Q demonstrated substantial validity for estimating occupational sedentary time and strenuous activity and fair validity for ranking individuals by AEE.
Tags: hydrogen , oxygen , medi , gashead

Human metabolism and elimination of the anthocyanin , cyanidin-3-glucoside : a 13 C-tracer study 1 – 3
American Journal of Clinical Nutrition (2013)
Charles Czank, Aedı Cassidy, Qingzhi Zhang, Douglas J Morrison, Tom Preston, Paul A Kroon, Nigel P Botting, Colin D Kay

Background: Evidence suggests that the consumption of anthocyanin- rich foods beneficially affects cardiovascular health; however, the absorption, distribution, metabolism, and elimination (ADME) of anthocyanin-rich foods are relatively unknown. Objective: We investigated the ADME of a 13C5-labeled anthocy- anin in humans. Design: Eight male participants consumed 500 mg isotopically labeled cyanidin-3-glucoside (6,8,10,3#,5#-13C5-C3G). Biological samples were collected over 48 h, and 13Cand 13C-labeled metabolite concentrations were measured by using isotope-ratio mass spectrometry and liquid chromatography–tandem mass spectrometry. Results: The mean 6 SE percentage of 13C recovered in urine, breath, and feces was 43.9 6 25.9% (range: 15.1–99.3% across participants). The relative bioavailability was 12.38 6 1.38% (5.37 6 0.67% excreted in urine and 6.91 6 1.59% in breath). Maximum rates of 13C elimination were achieved 30 min after in- gestion (32.53 6 14.24 mg13C/h), whereas 13C-labeled metabolites peaked (maximum serum concentration: 5.97 6 2.14 mmol/L) at 10.25 6 4.14 h. The half-life for 13C-labeled metabolites ranged between 12.44 6 4.22 and 51.62 6 22.55 h. 13C elimination was greatest between 0 and 1 h for urine (90.30615.28 mg/h), at 6 h for breath (132.87 6 32.23 mg/h), and between 6 and 24 h for feces (557.28 6 247.88 mg/h), whereas the highest concentrations of 13C- labeled metabolites were identified in urine (10.77 6 4.52 mmol/L) and fecal samples (43.16 6 18.00 mmol/L) collected between 6 and 24 h. Metabolites were identified as degradation products, phenolic, hippuric, phenylacetic, and phenylpropenoic acids. Conclusion: Anthocyanins are more bioavailable than previously perceived, and their metabolites are present in the circulation for #48 h after ingestion
Tags: carbon , medi , liqfac

The TaqIA RFLP is associated with attenuated intervention-induced body weight loss and increased carbohydrate intake in post-menopausal obese women
Appetite (2013)
Jameason D. Cameron, Marie Ève Riou, Frédérique Tesson, Gary S. Goldfield, Rémi Rabasa-Lhoret, Martin Brochu, Éric Doucet

Introduction: Polymorphisms of the dopamine receptor D2 (DRD2) gene have been associated with obesity phenotypes. Our aim was to examine if the genotype of TaqIA Restriction Fragment Length Polymorphism (RFPL) was related to an attenuated weight loss response or to changes in energy expenditure (EE) and food preference before and after weight loss. Methods: Obese post-menopausal women (age=57.1±4.6yr, weight=85.4±15.4kg and BMI=32.8±4.5kg/m2) were genotyped for TaqIA (n=127) by using PCR-RFLP analysis and categorized as possessing at least one copy of the A1 allele (A1+) or no copy (A1-). Women were randomized into two groups, caloric restriction (CR) and caloric restriction+resistance training (CRRT) and in this study were further classified as follows: A1+CR, A1+CRRT, A1--CR and -A1-CRRT. Body composition, total daily EE, physical activity EE, Resting EE (REE), and energy intake were obtained at baseline and post-intervention using DXA, doubly-labeled water, indirect calorimetry, and 3-day dietary records, respectively. Results: Overall, all of the anthropometric variables and REE significantly decreased post-intervention (p<0.001). Women in the CRRT group lost significantly more fat mass (FM) than the CR women (p<0.05). There were significant time by group by allele interactions for attenuated body weight (BW), BMI, and FM loss for A1+ (vs. A1-) in CRRT (p<0.05) and for increased % carbohydrate intake (p<0.01). Conclusion: TaqIA genotype was associated with body weight loss post-intervention; more specifically, carriers of the A1 allele lost significantly less BW and FM than the A1- and had increased carbohydrate intake in the CRRT group. © 2012 Elsevier Ltd. All rights reserved.
Tags: hydrogen , oxygen , medi , gashead

Energy restriction only slightly influences protein metabolism in obese rats, whatever the level of protein and its source in the diet.
International journal of obesity (2005) (2013)
L Chevalier, C Bos, D Azzout-Marniche, G Fromentin, L Mosoni, N Hafnaoui, J Piedcoq, D Tomé, C Gaudichon

BACKGROUND: High protein (HP) diets during energy restriction have been studied extensively regarding their ability to reduce body fat and preserve lean body mass, but little is known about their effects on protein metabolism in lean tissues. OBJECTIVE: To determine the effects of energy restriction and protein intake on protein anabolism and catabolism in rats. METHODS: For 5 weeks, 56 male Wistar rats were fed an obesity induction (OI) diet . They were then subjected to a 40% energy restriction using the OI diet or a balanced HP diet for 3 weeks, whereas a control group was fed the OI diet ad libitum (n=8 per group). HP-restricted rats were divided into five groups differing only in terms of their protein source: total milk proteins, casein (C), whey (W), a mix of 50% C and W, and soy (n=8). The animals were then killed in the postprandial state and their body composition was determined. Protein synthesis rates were determined in the liver, gastrocnemius and kidney using a subcutaneous (13)C valine flooding dose. mRNA levels were measured for key enzymes involved in the three proteolysis pathways. RESULTS: Energy restriction, but not diet composition, impacted weight loss and adiposity, whereas lean tissue mass (except in the kidney) was not influenced by diet composition. Levels of neoglucogenic amino acids tended to fall under energy restriction (P<0.06) but this was reversed by a high level of protein. The postprandial protein synthesis rates in different organs were similar in all groups. By contrast, mRNA levels encoding proteolytic enzymes rose under energy restriction in the muscle and kidney, but this was counteracted by a HP level. CONCLUSIONS: In adult obese rats, energy restriction but not diet composition affected fat pads and had little impact on protein metabolism, despite marked effects on proteolysis in the kidney and muscle.
Tags: carbon , medi , gaschrom

Dietary proteins contribute little to glucose production, even under optimal gluconeogenic conditions in healthy humans.
Diabetes (2013)
Claire Fromentin, Daniel Tomé, Françoise Nau, Laurent Flet, Catherine Luengo, Dalila Azzout-Marniche, Pascal Sanders, Gilles Fromentin, Claire Gaudichon

Dietary proteins are believed to participate significantly in maintaining blood glucose levels, but their contribution to endogenous glucose production (EGP) remains unclear. We investigated this question using multiple stable isotopes. After overnight fasting, eight healthy volunteers received an intravenous infusion of [6,6-²H₂]-glucose. Two hours later, they ingested four eggs containing 23 g of intrinsically, uniformly, and doubly [¹⁵N]-[¹³C]-labeled proteins. Gas exchanges, expired CO₂, blood, and urine were collected over the 8 h following egg ingestion. The cumulative amount of dietary amino acids (AAs) deaminated over this 8-h period was 18.1 ± 3.5%, 17.5% of them being oxidized. The EGP remained stable for 6 h but fell thereafter, concomitantly with blood glucose levels. During the 8 h after egg ingestion, 50.4 ± 7.7 g of glucose was produced, but only 3.9 ± 0.7 g originated from dietary AA. Our results show that the total postprandial contribution of dietary AA to EGP was small in humans habituated to a diet medium-rich in proteins, even after an overnight fast and in the absence of carbohydrates from the meal. These findings question the respective roles of dietary proteins and endogenous sources in generating significant amounts of glucose in order to maintain blood glucose levels in healthy subjects.

Modulating absorption and postprandial handling of dietary fatty acids by structuring fat in the meal: A randomized crossover clinical trial
American Journal of Clinical Nutrition (2013)
Cécile Vors, Gaëlle Pineau, Laure Gabert, Jocelyne Drai, Corinne Louche-Peĺissier, Catherine Defoort, Denis Lairon, Michel Deśage, Sabine Danthine, Stéphanie Lambert-Porcheron, Hubert Vidal, Martine Laville, Marie Caroline Michalski

BACKGROUND: Prolonged postprandial hypertriglyceridemia is a potential risk factor for cardiovascular diseases. In the context of obesity, this is associated with a chronic imbalance of lipid partitioning oriented toward storage and not toward beta-oxidation., OBJECTIVE: We tested the hypothesis that the physical structure of fat in a meal can modify the absorption, chylomicron transport, and further metabolic handling of dietary fatty acids., DESIGN: Nine normal-weight and 9 obese subjects were fed 40 g milk fat (+[(13)C]triacylglycerols), either emulsified or nonemulsified, in breakfasts of identical composition. We measured the postprandial triacylglycerol content and size of the chylomicron-rich fraction, plasma kinetics of [(13)C]fatty acids, exogenous lipid oxidation with breath-test/indirect calorimetry, and fecal excretion., RESULTS: The emulsified fat resulted in earlier (>1 h) and sharper chylomicron and [(13)C]fatty acid peaks in plasma than in spread fat in both groups (P < 0.0001). After 2 h, the emulsified fat resulted in greater apolipoprotein B-48 concentrations (9.7 + 0.7 compared with 7.1 + 0.9 mg/L; P < 0.05) in the normal-weight subjects than did the spread fat. In the obese subjects, emulsified fat resulted in a 3-fold greater chylomicron size (218 + 24 nm) compared with the spread fat (P < 0.05). The emulsified fat induced higher dietary fatty acid spillover in plasma and a sharper (13)CO(2) appearance, which provoked increased exogenous lipid oxidation in each group: from 45% to 52% in normal-weight subjects (P < 0.05) and from 40% to 57% in obese subjects (P < 0.01)., CONCLUSION: This study supports a new concept of "slow vs fast fat," whereby intestinal absorption can be modulated by structuring dietary fat to modulate postprandial lipemia and lipid beta-oxidation in humans with different BMIs. This trial was registered at clinicaltrials.gov as NCT01249378.
Tags: carbon , medi , gaschrom