CYP17A1 Enzyme activity is linked to ambulatory blood pressure in a family-based population study.

BACKGROUND: Genome-wide association studies have linked CYP17A1 coding for the steroid hormone synthesizing enzyme 17α-hydroxylase (CYP17A1) to blood pressure (BP). We hypothesized that the genetic signal may translate into a correlation of ambulatory BP (ABP) with apparent CYP17A1 activity in a family-based population study and estimated the heritability of CYP17A1 activity. METHODS: In the Swiss Kidney Project on Genes in Hypertension, day and night urinary excretions of steroid hormone metabolites were measured in 518 participants (220 men, 298 women), randomly selected from the general population. CYP17A1 activity was assessed by 2 ratios of urinary steroid metabolites: one estimating the combined 17α-hydroxylase/17,20-lyase activity (ratio 1) and the other predominantly 17α-hydroxylase activity (ratio 2). A mixed linear model was used to investigate the association of ABP with log-transformed CYP17A1 activities exploring effect modification by urinary sodium excretion. RESULTS: Daytime ABP was positively associated with ratio 1 under conditions of high, but not low urinary sodium excretion (P interaction <0.05). Ratio 2 was not associated with ABP. Heritability estimates (SE) for day and night CYP17A1 activities were 0.39 (0.10) and 0.40 (0.09) for ratio 1, and 0.71 (0.09) and 0.55 (0.09) for ratio 2 (P values <0.001). CYP17A1 activities, assessed with ratio 1, were lower in older participants. CONCLUSIONS: Low apparent CYP17A1 activity (assessed with ratio 1) is associated with elevated daytime ABP when salt intake is high. CYP17A1 activity is heritable and diminished in the elderly. These observations highlight the modifying effect of salt intake on the association of CYP17A1 with BP.

Heritability, determinants and reference values of renal length: a family-based population study.

OBJECTIVES: In this population-based study, reference values were generated for renal length, and the heritability and factors associated with kidney length were assessed. METHODS: Anthropometric parameters and renal ultrasound measurements were assessed in randomly selected nuclear families of European ancestry (Switzerland). The adjusted narrow sense heritability of kidney size parameters was estimated by maximum likelihood assuming multivariate normality after power transformation. Gender-specific reference centiles were generated for renal length according to body height in the subset of non-diabetic non-obese participants with normal renal function. RESULTS: We included 374 men and 419 women (mean ± SD, age 47 ± 18 and 48 ± 17 years, BMI 26.2 ± 4 and 24.5 ± 5 kg/m(2), respectively) from 205 families. Renal length was 11.4 ± 0.8 cm in men and 10.7 ± 0.8 cm in women; there was no difference between right and left renal length. Body height, weight and estimated glomerular filtration rate (eGFR) were positively associated with renal length, kidney function negatively, age quadratically, whereas gender and hypertension were not. The adjusted heritability estimates of renal length and volume were 47.3 ± 8.5 % and 45.5 ± 8.8 %, respectively (P < 0.001). CONCLUSION: The significant heritability of renal length and volume highlights the familial aggregation of this trait, independently of age and body size. Population-based references for renal length provide a useful guide for clinicians. KEY POINTS: • Renal length and volume are heritable traits, independent of age and size. • Based on a European population, gender-specific reference values/percentiles are provided for renal length. • Renal length correlates positively with body length and weight. • There was no difference between right and left renal lengths in this study. • This negates general teaching that the left kidney is larger and longer.

Blood pressure change and outcome in acute ischemic stroke: the impact of baseline values, previous hypertensive disease and previous antihypertensive treatment.

BACKGROUND: Management of blood pressure (BP) in acute ischemic stroke is controversial. The present study aims to explore the association between baseline BP levels and BP change and outcome in the overall stroke population and in specific subgroups with regard to the presence of arterial hypertensive disease and prior antihypertensive treatment. METHODS: All patients registered in the Acute STroke Registry and Analysis of Lausanne (ASTRAL) between 2003 and 2009 were analyzed. Unfavorable outcome was defined as modified Rankin score more than 2. A local polynomial surface algorithm was used to assess the effect of BP values on outcome in the overall population and in predefined subgroups. RESULTS: Up to a certain point, as initial BP was increasing, optimal outcome was seen with a progressively more substantial BP decrease over the next 24-48 h. Patients without hypertensive disease and an initially low BP seemed to benefit from an increase of BP. In patients with hypertensive disease, initial BP and its subsequent changes seemed to have less influence on clinical outcome. Patients who were previously treated with antihypertensives did not tolerate initially low BPs well. CONCLUSION: Optimal outcome in acute ischemic stroke may be determined not only by initial BP levels but also by the direction and magnitude of associated BP change over the first 24-48 h.

Relation between intraoperative EMG values and final pedicle screw position as seen on CT images

Introduction: Intraoperative EMG based neurophysiological monitoring is increasingly used to assist pedicle screw insertion. We carried out a study comparing the final screw position in the pedicle measured on CT images in relation to its corresponding intraoperative muscle compound action potential (CMAP) values. Material and methods: A total of 189 screws were inserted in thoracolumbar spines of 31 patients during instrumented fusion under EMG control. An observer, blinded to the CMAP value, assessed the horizontal and vertical 'screw edge to pedicle edge' distance perpendicular to the longitudinal axis of the screw on reformatted CT reconstructions using OsiriX software. These distances were analysed with their corresponding CMAP values. Data from 62 thoracic and 127 lumbar screws were processed separately. Interobserver reliability of distance measurements was assessed. Results: No patient suffered neurological injury secondary to screw insertion. Distance measurements were reliable (paired t-test, P = 0.13/0.98 horizontal/vertical). Two screws had their position altered due to low CMAP values suggesting close proximity of nerve tissue. Seventy five percent of screws had CMAP results above 10mA and had an average distance of 0.35cm (SD 0.23) horizontally and 0.46cm (SD 0.26) vertically from the pedicle edge. Additional 12% had a distance from the edge of the pedicle less than 0mm indicating cortical breach but had CMAP values above 10mA. A poor correlation between CMAP values and screw position was found. Discussion: In this study CMAP values above 10mA indicated correct screw position in the majority of cases. The zone of 10-20mA CMAP carries highest risk of a misplaced screw despite high CMAP value (17% of screws this CMAP range). In order to improve accuracy of EMG predictive value further research is warranted including improvement of probing techniques.

Measurement with an automated oscillometric wrist device with position sensor leads to lower values than measurements obtained with an automated oscillometric arm device from the same manufacturer in elderly persons

Introduction : Le monitoring de la tension artérielle à domicile est recommandé par plusieurs guidelines et a été montré être faisable chez la personne âgée. Les manomètres au poignet ont récemment été proposés pour la mesure de la tension artérielle à domicile, mais leur précision n'a pas été au préalable évaluée chez les patients âgés. Méthode : Quarante-huit participants (33 femmes et 15 hommes, moyenne d'âge 81.3±8.0 ans) ont leur tension artérielle mesurée avec un appareil au poignet avec capteur de position et un appareil au bras dans un ordre aléatoire et dans une position assise. Résultats : Les moyennes de mesures de tension artérielle étaient systématiquement plus basses avec l'appareil au poignet par rapport à celui du bras pour la pression systolique (120.1±2.2 vs. 130.5±2.2 mmHg, P < 0.001, moyenneidéviation standard) et pour la pression diastolique (66.011.3 vs. 69.7±1.3 mmHg, P < 0.001). De plus, une différence de lOmmHg ou plus grande entre l'appareil au bras et au poignet était observée dans 54.2 et 18,8% des mesures systoliques et diastoliques respectivement. Conclusion : Comparé à l'appareil au bras, l'appareil au poignet avec capteur de position sous-estimait systématiquement aussi bien la tension artérielle systolique que diastolique. L'ampleur de la différence est cliniquement significative et met en doute l'utilisation de l'appareil au poignet pour monitorer la tension artérielle chez la personne âgée. Cette étude indique le besoin de valider les appareils de mesures de la tension artérielle dans tous les groupes d'âge, y compris les personnes âgées.

Measurement with an automated oscillometric wrist device with position sensor leads to lower values than measurements obtained with an automated oscillometric arm device from the same manufacturer in elderly persons.

OBJECTIVE: Home blood pressure (BP) monitoring is recommended by several clinical guidelines and has been shown to be feasible in elderly persons. Wrist manometers have recently been proposed for such home BP measurement, but their accuracy has not been previously assessed in elderly patients. METHODS: Forty-eight participants (33 women and 15 men, mean age 81.3±8.0 years) had their BP measured with a wrist device with position sensor and an arm device in random order in a sitting position. RESULTS: Average BP measurements were consistently lower with the wrist than arm device for systolic BP (120.1±2.2 vs. 130.5±2.2 mmHg, P<0.001, means±SD) and diastolic BP (66.0±1.3 vs. 69.7±1.3 mmHg, P<0.001). Moreover, a 10 mmHg or greater difference between the arm and wrist device was observed in 54.2 and 18.8% of systolic and diastolic measures, respectively. CONCLUSION: Compared with the arm device, the wrist device with position sensor systematically underestimated systolic as well as diastolic BP. The magnitude of the difference is clinically significant and questions the use of the wrist device to monitor BP in elderly persons. This study points to the need to validate BP measuring devices in all age groups, including in elderly persons.

Formation of chlorite during thrust fault reactivation. Record of fluid origin and P-T conditions in the Monte Perdido thrust fault (southern Pyrenees)

The chemical and isotopic compositions of clay minerals such as illite and chlorite are commonly used to quantify diagenetic and low-grade metamorphic conditions, an approach that is also used in the present study of the Monte Perdido thrust fault from the South Pyrenean fold-and-thrust belt. The Monte Perdido thrust fault is a shallow thrust juxtaposing upper Cretaceous-Paleocene platform carbonates and Lower Eocene marls and turbidites from the Jaca basin. The core zone of the fault, about 6 m thick, consists of intensely deformed clay-bearing rocks bounded by major shear surfaces. Illite and chlorite are the main hydrous minerals in the fault zone. Illite is oriented along cleavage planes while chlorite formed along shear veins (< 50 mu m in thickness). Authigenic chlorite provides essential information about the origin of fluids and their temperature. delta O-18 and delta D values of newly formed chlorite support equilibration with sedimentary interstitial water, directly derived from the local hanging wall and footwall during deformation. Given the absence of large-scale fluid flow, the mineralization observed in the thrust faults records the P-T conditions of thrust activity. Temperatures of chlorite formation of about 240A degrees C are obtained via two independent methods: chlorite compositional thermometers and oxygen isotope fractionation between cogenetic chlorite and quartz. Burial depth conditions of 7 km are determined for the Monte Perdido thrust reactivation, coupling calculated temperature and fluid inclusion isochores. The present study demonstrates that both isotopic and thermodynamic methods applied to clay minerals formed in thrust fault are useful to help constrain diagenetic and low-grade metamorphic conditions.

MPI-DING reference glasses for in situ microanalysis: New reference values for element concentrations and isotope ratios

[1] We present new analytical data of major and trace elements for the geological MPI-DING glasses KL2-G, ML3B-G, StHs6/80-G, GOR128-G, GOR132-G, BM90/21-G, T1-G, and ATHO-G. Different analytical methods were used to obtain a large spectrum of major and trace element data, in particular, EPMA, SIMS, LA-ICPMS, and isotope dilution by TIMS and ICPMS. Altogether, more than 60 qualified geochemical laboratories worldwide contributed to the analyses, allowing us to present new reference and information values and their uncertainties ( at 95% confidence level) for up to 74 elements. We complied with the recommendations for the certification of geological reference materials by the International Association of Geoanalysts (IAG). The reference values were derived from the results of 16 independent techniques, including definitive ( isotope dilution) and comparative bulk ( e. g., INAA, ICPMS, SSMS) and microanalytical ( e. g., LA-ICPMS, SIMS, EPMA) methods. Agreement between two or more independent methods and the use of definitive methods provided traceability to the fullest extent possible. We also present new and recently published data for the isotopic compositions of H, B, Li, O, Ca, Sr, Nd, Hf, and Pb. The results were mainly obtained by high-precision bulk techniques, such as TIMS and MC-ICPMS. In addition, LA-ICPMS and SIMS isotope data of B, Li, and Pb are presented.

New anthropometry-based age- and sex-specific reference values for urinary 24-hour creatinine excretion based on the adult Swiss population (epublish)

BACKGROUND: Urinary creatinine excretion is used as a marker of completeness of timed urine collections, which are a keystone of several metabolic evaluations in clinical investigations and epidemiological surveys. METHODS: We used data from two independent Swiss cross-sectional population-based studies with standardised 24-hour urinary collection and measured anthropometric variables. Only data from adults of European descent, with estimated glomerular filtration rate (eGFR) ≥60 ml/min/1.73 m2 and reported completeness of the urinary collection were retained. A linear regression model was developed to predict centiles of the 24-hour urinary creatinine excretion in 1,137 participants from the Swiss Survey on Salt and validated in 994 participants from the Swiss Kidney Project on Genes in Hypertension. RESULTS: The mean urinary creatinine excretion was 193 ± 41 μmol/kg/24 hours in men and 151 ± 38 μmol/kg/24 hours in women in the Swiss Survey on Salt. The values were inversely correlated with age and body mass index (BMI). CONCLUSIONS: We propose a validated prediction equation for 24-hour urinary creatinine excretion in the general European population, based on readily available variables such as age, sex and BMI, and a few derived normograms to ease its clinical application. This should help healthcare providers to interpret the completeness of a 24-hour urine collection in daily clinical practice and in epidemiological population studies.

Femoroacetabular impingement: normal values of the quantitative morphometric parameters in asymptomatic hips.

OBJECTIVE: To determine the means and the reference intervals of the quantitative morphometric parameters of femoroacetabular impingement (FAI) in normal hips with high-resolution computed tomography (CT). METHODS: We prospectively included 94 adult individuals who underwent CT for thoracic, abdominal or urologic pathologies. Patients with a clinical history of hip pathology and/or with osteoarthritis on CT were excluded. We calculated means and 95 % reference intervals for imaging signs of cam-type (alpha angle at 90° and 45° and femoral head-neck offset) and pincer-type impingement (acetabular version angle, lateral centre-edge angle and acetabular index). RESULTS: The 95 % reference interval limits were all far beyond the abnormal thresholds found in the literature for cam-type and to a lesser extent for pincer-type FAI. The upper limits of the reference intervals for the alpha angles (at 90°/45°) were 68°/83° (men) and 69°/84° (women), compared to thresholds from the literature (50°, 55° or 60°). Reference intervals were similar between genders for cam-type parameters, and slightly differed for pincer-type. CONCLUSION: The 95 % reference intervals of morphometric measurements of FAI in asymptomatic hips were beyond the abnormal thresholds, which was especially true for cam-type FAI. Our results suggest the need for redefining the current morphometric parameters used in the diagnosis of FAI. KEY POINTS: ? 95 % reference intervals limits of FAI morphotype were beyond currently defined thresholds. ? Reference intervals of pincer-type morphotype measurements were close to current definitions. ? Reference intervals of cam-type morphotype measurements were far beyond the current definitions. ? Current morphometric definitions of cam-type morphotype should be used with care.

Physical activity in daily life is associated with lower adiposity values than doing weekly sports in Lc65+ cohort at baseline.

BACKGROUND: Overweight and obesity prevalence is the highest at age 65-75 years in Lausanne (compared with younger classes). We aimed to describe 1) eating habits, daily physical activity (PA), and sports frequency in community-dwelling adults aged 65-70, 2) the links of these behaviors with socio-economic factors, and 3) with adiposity. METHODS: Cross-sectional analysis of Lc65+ cohort at baseline, including 1260 adults from the general population of Lausanne aged 65-70 years. Eating habits (8 items from MNA) and PA (sports frequency and daily PA: walking and using stairs) were assessed by questionnaires. Body mass index (BMI), supra-iliac (SISF), triceps skin-folds (TSF), waist circumference (WC), and WHR were measured. RESULTS: Prevalence of overweight (BMI 25.0-29.9 kg/m2), obesity (BMI ≥ 30.0 kg/m2), and abdominal obesity was 53%, 24%, and 45% in men; 35%, 23%, and 45% in women.Intake of fruits or vegetables (FV) ≥ twice/day was negatively associated with male sex (prevalence 81% versus 90%, chi-square P < 0.001). The proportion avoiding stairs in daily life was higher among women (25%) than among men (20%, chi-square P=0.003).In multivariate analyses among both sexes, eating FV, using stairs in daily life ("stairs"), and doing sports ≥ once/week were significantly negatively associated with financial difficulties (stairs: OR=0.54, 95% CI=0.40-0.72) and positively with educational level (stairs: OR=1.68, 95% CI=1.17-2.43 for high school).For all five log-transformed adiposity indicators in women, and for all indicators except SISF and TSF in men, a gradual decrease in adiposity was observed from category "no stairs, sports < once/week" (reference), to "no stairs, sports ≥ once/week", to "stairs, sports < once/week", and "stairs, sports ≥ once/week" (for example: WC in men, respectively: ß= -0.03, 95% CI= -0.07-0.02; ß= -0.06, 95% CI= -0.09- -0.03; ß= -0.10, 95% CI= -0.12- -0.07). CONCLUSIONS: In this population with high overweight and obesity prevalence, eating FV and PA were strongly negatively associated with financial difficulties and positively with education. Using stairs in daily life was more strongly negatively associated with adiposity than doing sports ≥ once/week.

Pediatric CT: how to compare the Present DRL Values? : 12.10

Purpose: To determine dose thresholds, in term of CTDIvol, where subtle anatomical structures of pediatric CT images becomes no more detectable and compare them to the most recent Reference Dose Levels (DRL) proposed in the UK, Germany and Switzerland. Materials and methods: A GE LightSpeed-Ultra scanner (MSCT 8 slices) was used to perform chest and abdomen acquisitions on 8 patients (age range 2 to 16 years old) to provide a set of gold standard images. Dose reductions were then simulated by introducing image noise on raw data to provide simulated CT images with CTDIvol ranging from 2 to 22 mGy. All images were reviewed and scored independently by four experienced radiologists using the VGA methodology (Visual Grading Analysis) to determine the dose threshold where a significant loss of normal anatomy conspicuity appeared. Data were analyzed with ANOVA and Tukey HSD tests, a p >0.05 was considered to be significant. Results: No significant difference in VGA scoring appeared for CTDIvol leading to image noise levels lower than 10 and 25 HU for respectively abdominal and chest acquisitions. These data can thus be used to set the AEC (automatic exposure control) system of units having similar noise properties than the GE LightSpeed-Ultra used in this study. The present DRLs proposed for pediatric CT acquisitions are compatible with an excellent image quality level. Conclusion: The differences of DRL values proposed in Europe for pediatric acquisitions are marginal and assure a very good image quality level. The results of this study allow to further optimize the acquisition protocol by giving Noise Index value to set the AEC device.