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See detailImpact of strenuous exercise on the release of cardiac biomarkers
LE GOFF, Caroline ULg; MELON, Pierre ULg; Kaux, Jean-François ULg et al

in Biochimica Clinica (2013, May), 37(SS), 545

Background: Cardiac troponins (cTn) are considered as the best biomarkers for detection of myocardial cell injury and NT-proBNP as the best for the cardiac insufficiency. In this study, cTnT was measured ... [more ▼]

Background: Cardiac troponins (cTn) are considered as the best biomarkers for detection of myocardial cell injury and NT-proBNP as the best for the cardiac insufficiency. In this study, cTnT was measured by new commercially available high-sensitive methods in subjects un-dergoing the Maasmarathon. Our aim was to compare cTnT and NT-proBNP levels before and after the stress tests, in sportive subjects. Methods: Twenty eight subjects (26 ♂, 42.5±11yo) underwent a race of 42.195 kilometers be-tween Visé (Belgium) and Maastricht (The Netherlands). We drowned blood sample before (T0), just after (T1) and three hours after the race (T3). In all patients, cTnT concentrations were measured by high sensitive methods (hsTnT, Roche Diagnostics) on heparin plasma. The NT-proBNP was also determined with the kit Roche on heparin plasma. The protocol was approved by the ethics committee of the University of Liège (Belgium). All subjects gave their informed consent. All statistical analyses were performed using Medcalc version 8.1 for Windows. p-value <0.01 was regarded as statistically significant. Results: There was a significant difference between hsTnT concentrations at T0 and T1 (p<0.0001), and between T0 and T3 (p<0.001) for NT-proBNP, but not between T1 and T3. This observation appeared only after a strenuous exercise but today this type of exercise is not reproduce easier in a laboratory of sport. Moreover, at this moment, nobody knows if these observations would have cardiac consequences at long terms. Conclusions: Measurement of cardiac troponins by high sensitive methods allows detecting significant release of biomarkers from the heart during exercise. The value of NT-proBNP are also significant but less than TnThs. We think that the TnThs could be an interesting tool in the future to help sport medicine to detect risk of developing a cardiac problem in the future or a sudden death. [less ▲]

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See detailComparison of the Heart-type fatty acid-binding protein (H-FABP) with the high sensitive cardiac troponin T in healthy runners
LE GOFF, Caroline ULg; Kaux, Jean-François ULg; BREVERS, Eric ULg et al

in Biochimica Clinica (2013, May), 37(SS), 544

Background: Heart-type fatty acid-binding protein (H-FABP) is a low molecular weight protein involved in the intracellular uptake and buffering of long chain fatty in the myocardium. It is an early marker ... [more ▼]

Background: Heart-type fatty acid-binding protein (H-FABP) is a low molecular weight protein involved in the intracellular uptake and buffering of long chain fatty in the myocardium. It is an early marker for acute coronary syndrome. Troponin T (TnT) is a component of the contractile apparatus of the striated musculature. Cardiac TnT is a cardio-specific, highly sensitive marker for myocardial damage. The aim of our study was to compare the results obtained with the H-FABP and the highly sensitive cardiac troponins (hsTnT) and to test their cardiospecificity in healthy runners. Methods: Twenty three runners (marathon) were enrolled. We drowned samples at three times: just before (T0), just after (T1), and three hours after the end of the race (T3). H-FABP was determined with a Randox immunoturbidimetric assay and hs-TnT with a Roche electrochemiluminescence immunoassay, both on Cobas 6000. A linear regression was calculated to observe if there is any correlation between the two biomarkers. Values above the 95th percentile for H-FABP (2.5ng/mL) and the 99th percentile for hsTnT (14ng/L) were considered as positive. Results: At T0, none of the subjects were positive for hsTnT but 35% were positive for H-FABP; at T1, 83% for hsTnT and 100% for H-FABP; at T3, 83% for hsTnT and 96% for H-FABP. At T0, the regression equation was H-FABP T0 = 3.9454 – 0.1001 x hsTnT T0; at T1: H-FABP T1 = 51.838 – 1.7026 x hsTnT T1; at T3: H-FABP T3 = 47.977 – 1.6193 x hsTnT T3. No correlation was observed between the two biomarkers at the different time. Conclusions: We observed a significant increase of H-FABP and hsTnT in runners. These markers are independent to each other. These values could biologically correspond to a heart ischemia. However, we suggested that exercise-induced cardiac hsTnT and H-FABP release is not a marker of exercise-induced pathology but likely a physiologic response to effort or an exercise-induced cardiac remodelling. [less ▲]

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See detailRace Cycling: biological evolution
LE GOFF, Caroline ULg; Kaux, Jean-François ULg; MELON, Pierre ULg et al

in Biochimica Clinica (2013, May), 37(SS), 544

Background: The metabolic and cardiac impact of a cycling effort on blood biology is not very well described in the literature. We aimed to measure the concentration of different biomarkers (cardiac and ... [more ▼]

Background: The metabolic and cardiac impact of a cycling effort on blood biology is not very well described in the literature. We aimed to measure the concentration of different biomarkers (cardiac and metabolic) released during an international cycling race. Methods: Venous blood samples of 15 young men (25.1 ± 6.4 y.o.) were collected just before (T1), just after (T2), 3 hours (T3) after an international cycling race of 179.6 kilometers in Belgium for the determination of cardiac and metabolic biomarkers: red blood cell (RBC), haemoglobin (HgB), creatinin (Cr), highly sensitive troponin T (hsTnT), myoglobin (MYO) and NT-proBNP. All automated assays were performed according to the manufacter’s specifications. For the statistical analysis, an Anova calculated with the Statistica Software version 9.1 was used. Results: RBC and HgB levels varied significantly between T0 and T3 (respectively p=0.0026, and p=0.002). Cr concentration also varied significantly between all times (T0-T1:p<0.0001, T1-T3:p=0.0326 and T0-T3 p=0.0001). These changes might be related to renal flow depletion during exercice. MYO increased significantly between T0 and T1 (p<0.0001), but quickly decreased between T1 and T3, however the T3 level stay higher than T0 (p=0.014). The stress delivered from the physical activity performed during the race induced a significant variation of hsTnT which increased significantly between T0 and T1 (p<0.0001) and stayed higher 3 hours after the end of the exercise (T0-T3: p<0.0001) .The intense exercise delivery by the race induced a significant variation of NT-proBNP, that followed the same kinetic of hsTnT but in smaller proportion. We noticed variations statistically significant between T0 and T1 and between T0 and T3 for NT-proBNP. These increases of cardiac biomarkers were significant but reasonable and could not allow us to talk about cellular necrosis or irreversible injury. Conclusion: Our results show that stress generated by a cycling race could be the cause for the different metabolic variations observed. Troponin T stays without a doubt the most specific marker for stress related to myocardial tissue. Its increase can then be considered as being of interest. [less ▲]

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See detailDetermination of urinary metanephrine, normetanephrine and methoxymetanephrine by liquid chromatography-electrospray tandem mass spectrometry.
LE GOFF, Caroline ULg; PEETERS, Stéphanie ULg; NETCHACOVITCH, Matthieu ULg et al

in Biochimica Clinica (2013, May), 37(SS), 316

Background: The aim of this work was to develop and validate a method for the determination of metanephrine (M), normetanephrine (NM) and methoxymetanephrine (METHO) in urine by liquid chromatography ... [more ▼]

Background: The aim of this work was to develop and validate a method for the determination of metanephrine (M), normetanephrine (NM) and methoxymetanephrine (METHO) in urine by liquid chromatography-tandem mass spectrometry (LCMS-MS) on the Triple Quad TQ 5500 from AB SCIEX. In fact, the determination of M and NM concentrations is used in clinical diagnosis of pheochromocytoma, a rare but potentially fatal tumor arising primarily from the chromaffin cells of the adrenal medulla. Methods: The samples were made of 24 hours acidified urines after centrifugation. Sample preparation was performed by hydrolysing and purifying by extraction column. After that, labeled M, NM and METHO were added as internal standard. Samples were analysed by liquid chromatography-electrospray tandem mass spectrometry. We determined the repeatability, reproducibility, accuracy profile and recovery on pooling urines samples from 9 volunteers analysed in triple run. Results: The results of the precision evaluation are shown in table. The repeatability did not exceed 8.4 % for M, 6.8% for NM and 10.8% for METHO. The concentration range was 71-781 µg/24h, 71-853 µg/24h and 20-854µg/24h for the M, NM and METHO respectively. The total precision did not exceed 12.5%, 11.8% and 8.8% for M, NM and METHO. The limit of quantification (LOQ) were 33.77µg/24h, 14.49µg/24H and 19.81 µg/24H for M, NM and METHO respectively. The accuracy varied from 99.69 to 100.2% for a range of 71 to 781 µg/24h, from 93.32 to 100.2% for a range of 71-853 µg/24h and from 99.85 to 100.6% for the range 20-854µg/24h for M, NM and METHO respectively. The recovery were 99.96% (95% CI for the mean: 96.5-103.4), 99.75% (96.5-102.9) and 100.08 (95.97-104.2) for the M, NM and METHO respectively. Conclusions: We have successfully developed and validated an LCMS-MS method to determine urinary M, NM and METHO on the TQ 5500 from AB SCIEX. It represents a convincing alternative to the HPLC method for a faster and reliable measurement of urinary M, NM and METHO. [less ▲]

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See detailComparison between Perkin-Elmer and Chromsytem Vitamin D kit on TQ 5500 from AB SCIEX
LE GOFF, Caroline ULg; PEETERS, Stéphanie ULg; CRINE, Yannick ULg et al

in Biochimica Clinica (2013, May), 37(SS), 471

Background: Twenty-five hydroxy-vitamin D (25(OH) D) determination is now routinely prescribed in the Laboratory. Recently, different new methods have been available for this determination. Among them ... [more ▼]

Background: Twenty-five hydroxy-vitamin D (25(OH) D) determination is now routinely prescribed in the Laboratory. Recently, different new methods have been available for this determination. Among them, LCMS/MS methods have emerged in some laboratories. However these methods are generally “home-brewed” and an important variability between them can be seen on different external quality controls, mainly due to a lack of standardization. Recently, Perkin-Elmer (PE) (Turku, Finland) and Chromsystem (CS) (Grafelfing, Germany) launched a standardised method for 25(OH )D determination on LCMS/MS. The aim of our study was to compare these methods on the AB SCIEX TQ5500 (Framingham, Massachusetts, USA) LCMS/MS to measure 25(OH) D3. Methods All the samples were treated according to our preanalyitical procedure: after sampling, they were spun at +4°c at 3500G, aliquoted and kept frozen at -20°c until determination. A method comparison was assessed with CS and PE for the measurement of the 25(OH)D3. We selected 110 remnant samples with 25(OH)D3 levels ranging from 1.6 to 136.7 ng/ml with the PE method to cover the range of usually values Slope and intercept were calculated using Passing and Bablock linear regression and we compared the methods with the Bland and Altman plots. Results For CS, the method is linear up to 250 µg/L, the LOQ is 3.6 µg/L, the intra-assay CV is < 5% and the inter-assay is < 7%. For PE, the method is linear up to 314 µg/L, the LOQ is 3.4 µg/L, the intra-assay CV is < 7.8% and the inter-assay is < 8.5%. On the whole range of measure (n=110), the regression equation is PE = 0.8521+0.9226 (CS) (95%CI of the intercept: (-0.0048;1.37) and 95% CI of the slope (0.89;0.95). The Bland and Altman plot does not show any bias between the two methods (mean difference CS-PE= -2.5 ng/ml) and the standard deviation of the mean is 3,98 ng/ml Conclusion: The performances of these methods are comparable on our new TQ 5500 from AB SCIEX. For now, there is no consensus on a “reference” method for vitamin D quantification. We notice only that the values obtained by CS are systematically a little bit lower than PE’s values, especially for results below 20 ng/ml. However, we have no clear explanation for such behaviour. [less ▲]

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See detailMDRD VERSUS CKD-EPI EQUATIONS TO ESTIMATE GLOMERULAR FILTRATION RATE IN OBESE PATIENTS
BOUQUEGNEAU, Antoine ULg; CAVALIER, Etienne ULg; Krzesinski, Jean-Marie ULg et al

in Nephrology Dialysis Transplantation (2013, April 18), 28(supplément 1), 117-139

Introduction and Aims: Obesity is recognized as a risk factor both for the development and progression of chronic kidney disease (CKD). Estimating glomerular filtration rate (GFR) is thus especially ... [more ▼]

Introduction and Aims: Obesity is recognized as a risk factor both for the development and progression of chronic kidney disease (CKD). Estimating glomerular filtration rate (GFR) is thus especially important to follow these patients. We have tested the performances of two creatinine-based equations, namely the MDRD and CKD-EPI equations, in an obese population. Conclusions :Both in the global and subgroup analyses, the CKD-EPI equation did not outperform the MDRD study equation. The performances of both equations were worse in CKD patients. These two conclusions were still valid if indexed GFR was considered. [less ▲]

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See detailEnzymatic but not compensated Jaffe methods reach the desirable specifications of NKDEP at normal levels of creatinine. results of the French multicentric evaluation
Boutten, Anne; Bargnoux, Anne-Sophie; Carlier, Marie-Christine et al

in Clinica Chimica Acta (2013), 419

The French Society of Clinical Biochemistry conducted this study to compare the accuracy and performances of the best creatinine enzymatic assays and the compensated Jaffe methods from the same ... [more ▼]

The French Society of Clinical Biochemistry conducted this study to compare the accuracy and performances of the best creatinine enzymatic assays and the compensated Jaffe methods from the same manufacturers. Creatinine was measured in 3 serum pools with creatinine levels of 35.9±0.9 μmol/L, 74.4±1.4 μmol/L, and 97.9±1.7 μmol/L (IDMS determination). The performances of the assays (total error that includes the contribution of bias and imprecision) were evaluated using Monte-Carlo simulations and compared against desirable NKDEP criteria. The enzymatic assays always fell within the desirable total Error of 7.6%. By contrast, this requirement was never obtained for the compensated Jaffe methods at the critical level of 74.4±1.4 μmol/L. Only the compensated Jaffe creatinine on Olympus analyzer reached this specification at 35.9±0.9 and 97.9±1.7 μmol/L levels. This study demonstrates that, despite substantial improvement regarding traceability to the IDMS reference method and precision, compensated Jaffe creatinine methods, by contrast to enzymatic ones, do not reach the desirable specifications of NKDEP at normal levels of creatinine. [less ▲]

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See detailMeasuring 25-hydroxyvitamin D: where are we standing in 2013?
CAVALIER, Etienne ULg

Conference (2013, March 27)

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See detailCreatinine - or cystatin C - based equations to estimate glomerular filtration in the general population: impact on the epidemiology of chronic kidney disease
DELANAYE, Pierre ULg; CAVALIER, Etienne ULg; Moranne, Olivier et al

in BMC Nephrology (2013), 14

Chronic kidney disease (CKD) is a major issue in public health. Its prevalence has been calculated using estimation of glomerular filtration rate (GFR) by the creatinine-based equations developed in the ... [more ▼]

Chronic kidney disease (CKD) is a major issue in public health. Its prevalence has been calculated using estimation of glomerular filtration rate (GFR) by the creatinine-based equations developed in the Modified Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) study. Recently, new equations based either on cystatin C (CKD-EPI Cys) or both cystatin and creatinine (CKD-EPI mix) have been proposed by the CKD-EPI consortium. The aim of this study was to measure the difference in the prevalence of stage 3 CKD, defined as an estimated GFR less than 60 mL/min/1.73 m2, in a population using these four equations. METHODS: CKD screening was performed in the Province of Liege, Belgium. On a voluntary basis, people aged over 50 years have been screened. GFR was estimated by the four equations. Stage 3 CKD was defined as a GFR less than 60 mL/min/1.73 m2. RESULTS: The population screened consisted of 4189 people (47% were men, mean age 63 +/- 7y). Their mean serum creatinine and plasma cystatin C levels were 0.88 +/- 0.21 mg/dL and 0.85 +/- 0.17 mg/L, respectively. The prevalence of CKD in this population using the MDRD, the CKD-EPI, the CKD-EPI Cys and the CKD-EPI mix equations was 13%, 9.8%, 4.7% and 5%, respectively. The prevalence of CKD was significantly higher with the creatinine-based (MDRD and the CKD-EPI) equations compared to the new cystatin C-based equations. CONCLUSIONS: Prevalence of CKD varies strongly depending on the method used to estimate GFR. Such discrepancies are of importance and must be confirmed and explained by additional studies, notably by studies using GFR measured with a reference method [less ▲]

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See detailParathormone and bone-specific alkaline phosphatase for the follow-up of bone turnover in hemodialysis patients : Is it so simple?
DELANAYE, Pierre ULg; DUBOIS, Bernard ULg; JOURET, François ULg et al

in Clinica Chimica Acta (2013), 417

Background: Chronic Kidney Disease (CKD) is associated with mineral and bone disorders (MBD). International guidelines suggest that levels of serum parathormone (PTH) or bone-specific alkaline phosphatase ... [more ▼]

Background: Chronic Kidney Disease (CKD) is associated with mineral and bone disorders (MBD). International guidelines suggest that levels of serum parathormone (PTH) or bone-specific alkaline phosphatase (b-ALP) can be used to evaluate MBD in dialysis patients. The evidence remains moderate and based on transversal studies. <br />Methods: We retrospectively investigated the variations of PTH (ΔPTH) and b-ALP (Δb-ALP) serum concentrations over a short (6-weeks) and a long (one-year) period in a monocentric hemodialysis population. The proportion of patients reaching the critical difference (CD) (50% for PTH and 25% for b-ALP) was calculated. <br />Results: Seventy-seven patientswere included. A significant correlation between PTHand b-ALP levelswas found at baseline (r=0.51). By contrast, no correlation was observed between ΔPTH and Δb-ALP over a 6-week interval (r=0.07). The CD for PTH and b-ALP was reached by 19 and 11 patients, respectively, with 2 patients showing consistent variations of both biomarkers. One year later, measurements were repeated in 48 survivors. <br />No correlation was found between ΔPTH and Δb-ALP (r=0.27). The CD for PTH or b-ALP was reached by 24 patients and 28 patients, respectively, with 6 patients (12.5%) showing opposite results for both biomarkers. <br />Conclusion: This study shows the lack of correlation between ΔPTH and Δb-ALP over time in patients under chronic hemodialysis. [less ▲]

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See detailVitamin D testing and clinical practice
CAVALIER, Etienne ULg

Conference (2013, January 31)

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See detailA randomised, double-blinded, placebo-controlled, parallel study of vitamin D3 supplementation with different schemes based on multiples of 25,000 IU doses
CAVALIER, Etienne ULg; Faché, W; Souberbielle, Jean-Caude

in International Journal of Endocrinology (2013)

Vitamin D (VTD) treatment is recommended in patients presenting different causes of diseases. To treat these patients, physicians rely on the different available pharmaceutical forms present in their ... [more ▼]

Vitamin D (VTD) treatment is recommended in patients presenting different causes of diseases. To treat these patients, physicians rely on the different available pharmaceutical forms present in their country. Unfortunately, even in a given country, there is no consensus on the best way to treat the patients. In Belgium, VTD is mostly prescribed as ampoules containing 25,000 IU of VTD. In this randomised controlled study, we evaluated whether four therapeutic schemes using multiples of 25,000 IU of VTD according to basal vitamin D concentration were able to increase or maintain the 25(OH)D serum level above 30 ng/mL. We randomized 175 subjects who received the drug () or placebo (). Total duration of the study was 12 weeks. Doses ranged from 4167 to 1667 IU/day. Blood sampling was performed at baseline and each 4 visits. In the treated (placebo) subjects, mean 25(OH)D serum concentration was 18.7 (19.1) ng/mL at baseline and 31.5 (20.7) ng/mL at w-12. At the end of the study, 57.1% of the subjects treated with VTD presented 25(OH)D serum concentration ≥30 ng/mL, whereas 94.3% were ≥20 ng/mL. In conclusion, the doses administered were safe and increased or maintained the 25(OH)D concentration ≥20 ng/mL. However, concentrations ≥30 ng/mL were only achieved in 57.1% of the subjects. [less ▲]

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See detailSkin color is relevant to vitamin D synthesis
LIBON, Florence ULg; CAVALIER, Etienne ULg; NIKKELS, Arjen ULg

in Dermatology (2013), 227(3), 250-4

BACKGROUND: Whether dark skin produces less vitamin D after UVB radiation than fair skin remains controversial. OBJECTIVE: To compare 25-hydroxyvitamin D [25-(OH)-D] levels after a single UVB exposure in ... [more ▼]

BACKGROUND: Whether dark skin produces less vitamin D after UVB radiation than fair skin remains controversial. OBJECTIVE: To compare 25-hydroxyvitamin D [25-(OH)-D] levels after a single UVB exposure in fair (phototype II-III) and black-skinned (phototype VI) volunteers. METHODS: Fair-skinned volunteers (n = 20, 4 males/16 females, mean age: 23.2 years) and black-skinned (n = 11, 6 males/5 females, mean age: 23.8 years) received a single total body UVB exposure (0.022 J/cm(2)). The 25-(OH)-D levels were measured on days 0, 2 and 6. RESULTS: On day 0, all volunteers were severely vitamin D deficient. On day 2, 25-(OH)-D levels of fair-skinned volunteers increased significantly (median: 11.9-13.3 ng/ml, p < 0.0001), but not in black-skinned people (median: 8.60-8.55 ng/ml, p = 0.843). Again, on day 6, 25-(OH)-D levels of fair-skinned volunteers increased significantly (median: 11.9-14.3 ng/ml, p < 0.0001), but not in black-skinned people (median: 8.60-9.57 ng/ml, p = 0.375). CONCLUSION: This study suggests that skin pigmentation negatively influences vitamin D synthesis. [less ▲]

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See detailLa vitamine D et la peau
LIBON, Florence ULg; CAVALIER, Etienne ULg; NIKKELS, Arjen ULg

in Revue Médicale de Liège (2013), 68(9), 458-464

Vitamin D is well known for its beneficial effects on phosphocalcic homeostasis. The discovery of the role of vitamin D in cancers, infections, cardiovascular or autoimmune pathologies have promoted ... [more ▼]

Vitamin D is well known for its beneficial effects on phosphocalcic homeostasis. The discovery of the role of vitamin D in cancers, infections, cardiovascular or autoimmune pathologies have promoted interest for this molecule. Skin and vitamin D are closely related. The skin is not only the site of vitamin D synthesis, but also a target organ as calcitriol plays an important hormonal and regulatory role, acting on cell proliferation, differentiation and immunomodulation. Furthermore, vitamin D influences the incidence and therapeutic response of certain dermatoses. In addition, many medical situations, mainly dermatological, require strict photoprotection and may therefore indirectly be responsible for a vitamin D deficiency in patients. The current role of vitamin D in skin cancers, inflammatory and autoimmune skin diseases is summarized. [less ▲]

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