92 resultados para CONTINUOUS POSITIVE AIRWAY PRESSURE


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Purpose: In vitro studies in porcine eyes have demonstrated a good correlation between induced intraocular pressure variations and corneal curvature changes, using a contact lens with an embedded microfabricated strain gauge. Continuous 24 hour-intraocular pressure (IOP) monitoring to detect large diurnal fluctuation is currently an unmet clinical need. The aims of this study is to evaluate precision of signal transmission and biocompatibility of 24 hour contact lens sensor wear (SENSIMED Triggerfish®) in humans. Methods: After full eye examination in 10 healthy volunteers, a 8.7 mm radius contact lens sensor and an orbital bandage containing a loop antenna were applied and connected to a portable recorder. Best corrected visual acuity and position, lubrication status and mobility of the sensor were assessed after 5 and 30 minutes, 4, 7 and 24 hours. Subjective comfort was scored and activities documented in a logbook. After sensor removal full eye examination was repeated, and the registration signal studied. Results: The comfort score was high and did not fluctuate significantly, except at the 7 hour-visit. The mobility of the contact lens was minimal but its lubrication remained good. Best corrected visual acuity was significantly reduced during the sensor wear and immediately after its removal. Three patients developed mild corneal staining. In all but one participant we obtained a registration IOP curve with visible ocular pulse amplitude. Conclusions: This 24 hour-trial confirmed the functionality and biocompatibility of SENSIMED Triggerfish® wireless contact lens sensor for IOP-fluctuation monitoring in volunteers. Further studies with a range of different contact lens sensor radii are indicated.

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Selectome (http://selectome.unil.ch/) is a database of positive selection, based on a branch-site likelihood test. This model estimates the number of nonsynonymous substitutions (dN) and synonymous substitutions (dS) to evaluate the variation in selective pressure (dN/dS ratio) over branches and over sites. Since the original release of Selectome, we have benchmarked and implemented a thorough quality control procedure on multiple sequence alignments, aiming to provide minimum false-positive results. We have also improved the computational efficiency of the branch-site test implementation, allowing larger data sets and more frequent updates. Release 6 of Selectome includes all gene trees from Ensembl for Primates and Glires, as well as a large set of vertebrate gene trees. A total of 6810 gene trees have some evidence of positive selection. Finally, the web interface has been improved to be more responsive and to facilitate searches and browsing.

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Elevated blood pressure is a common, heritable cause of cardiovascular disease worldwide. To date, identification of common genetic variants influencing blood pressure has proven challenging. We tested 2.5 million genotyped and imputed SNPs for association with systolic and diastolic blood pressure in 34,433 subjects of European ancestry from the Global BPgen consortium and followed up findings with direct genotyping (N ≤ 71,225 European ancestry, N ≤ 12,889 Indian Asian ancestry) and in silico comparison (CHARGE consortium, N = 29,136). We identified association between systolic or diastolic blood pressure and common variants in eight regions near the CYP17A1 (P = 7 × 10(-24)), CYP1A2 (P = 1 × 10(-23)), FGF5 (P = 1 × 10(-21)), SH2B3 (P = 3 × 10(-18)), MTHFR (P = 2 × 10(-13)), c10orf107 (P = 1 × 10(-9)), ZNF652 (P = 5 × 10(-9)) and PLCD3 (P = 1 × 10(-8)) genes. All variants associated with continuous blood pressure were associated with dichotomous hypertension. These associations between common variants and blood pressure and hypertension offer mechanistic insights into the regulation of blood pressure and may point to novel targets for interventions to prevent cardiovascular disease.

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Meropenem, a carbapenem antibiotic displaying a broad spectrum of antibacterial activity, is administered in Medical Intensive Care Unit to critically ill patients undergoing continuous veno-venous haemodiafiltration (CVVHDF). However, there are limited data available to substantial rational dosing decisions in this condition. In an attempt to refine our knowledge and propose a rationally designed dosage regimen, we have developed a HPLC method to determine meropenem after solid-phase extraction (SPE) of plasma and dialysate fluids obtained from patients under CVVHDF. The assay comprises the simultaneous measurement of meropenem's open-ring metabolite UK-1a, whose fate has never been studied in CVVHDF patients. The clean-up procedure involved a SPE on C18 cartridge. Matrix components were eliminated with phosphate buffer pH 7.4 followed by 15:85 MeOH-phosphate buffer pH 7.4. Meropenem and UK-1a were subsequently desorbed with MeOH. The eluates were evaporated under nitrogen at room temperature (RT) and reconstituted in phosphate buffer pH 7.4. Separation was performed at RT on a Nucleosil 100-5 microm C18 AB cartridge column (125 x 4 mm I.D.) equipped with a guard column (8 x 4 mm I.D.) with UV-DAD detection set at 208 nm. The mobile phase was 1 ml min(-1), using a step-wise gradient elution program: %MeOH/0.005 M tetrabutylammonium chloride pH 7.4; 10/90-50/50 in 27 min. Over the range of 5-100 microg ml(-1), the regression coefficient of the calibration curves (plasma and dialysate) were >0.998. The absolute extraction recoveries of meropenem and UK-1a in plasma and filtrate-dialysate were stable and ranged from 88-93 to 72-77% for meropenem, and from 95-104 to 75-82% for UK-1a. In plasma and filtrate-dialysate, respectively, the mean intra-assay precision was 4.1 and 2.6% for meropenem and 4.2 and 3.7% for UK-1a. The inter-assay variability was 2.8 and 3.6% for meropenem and 2.3 and 2.8% for UK-1a. The accuracy was satisfactory for both meropenem and UK-1a with deviation never exceeding 9.0% of the nominal concentrations. The stability of meropenem, studied in biological samples left at RT and at +4 degrees C, was satisfactory with < 5% degradation after 1.5 h in blood but reached 22% in filtrate-dialysate samples stored at RT for 8 h, precluding accurate measurements of meropenem excreted unchanged in the filtrate-dialysate left at RT during the CVVHDF procedure. The method reported here enables accurate measurements of meropenem in critically ill patients under CVVHDF, making dosage individualisation possible in such patients. The levels of the metabolite UK-1a encountered in this population of patients were higher than those observed in healthy volunteers but was similar to those observed in patients with renal impairment under hemodialysis.

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OBJECTIVE: Fabry disease is an X-linked disorder resulting from alpha-galactosidase A deficiency. The cardiovascular findings include left ventricular hypertrophy (LVH) and increased intima-media thickness of the common carotid artery (CCA IMT). The current study examined the possible correlation between these parameters. To corroborate these clinical findings in vitro, plasma from Fabry patients was tested for possible proliferative effect on rat vascular smooth muscle cells (vascular smooth muscle cell [VSMC]) and mouse neonatal cardiomyocytes. METHODS AND RESULTS: Thirty male and 38 female patients were enrolled. LVH was found in 60% of men and 39% of women. Increased CCA IMT was equally present in males and females. There was a strong positive correlation between LV mass and CCA IMT (r2=0.27; P<0.0001). VSMC and neonatal cardiomyocyte proliferative response in vitro correlated with CCA IMT (r2=0.39; P<0.0004) and LV mass index (r2=0.19; P=0.028), respectively. CONCLUSIONS: LVH and CCA IMT occur concomitantly in Fabry suggesting common pathogenesis. The underlying cause may be a circulating growth-promoting factor whose presence has been confirmed in vitro.

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Ambulatory blood pressure (BP) monitoring is increasingly used in the evaluation of hypertensive patients. The ability to monitor BP throughout the day and night allows the detection of abnormal nocturnal BP patterns, the most common being a "nondipping" pattern, which is associated with increased cardiovascular risk; its correction appears to have a positive impact on cardiovascular outcome. Antihypertensive treatment should be individually adjusted to control BP during both daytime and nighttime. However, drug-induced lowering of nocturnal BP, if excessive, could amplify the morning BP surge in patients with daytime BP elevation, increasing the risk of developing a cardiovascular event. Ambulatory BP monitoring therefore represents a unique tool to establish the most appropriate antihypertensive drug regimen for the individual patient.

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Résumé de l'article : L'hyperplasie intimale est un processus de remodelage vasculaire ubiquitaire après une lésion, pouvant menacer la perméabilité de tout type de reconstruction vasculaire. Les mécanismes physiopathologiques impliqués dans le développement de l'hyperplasie intimale ne sont que partiellement élucidés. Il est par conséquent nécessaire d'effectuer des recherches complémentaires afin d'en améliorer la compréhension et ainsi permettre l'élaboration de nouvelles stratégies thérapeutiques médicamenteuses. La culture de veines en milieu statique permet le développement de l'hyperplasie intimale. Ce modèle maintient la viabilité tissulaire, comme décrit précédemment dans d'autres études, mais empêche l'analyse des paramètres hémodynamiques. La mise au point d'un modèle de perfusion in vitro permettant la perfusion de segments vasculaires représente une approche expérimentale intégrant les différents facteurs hémodynamiques. Le système de perfusion (Ex Vivo Vein Support System) que nous avons élaboré conserve l'intégrité pariétale ainsi que les propriétés vasomotrices des veines pour une durée de 14 jours. Cette étude démontre que les deux modèles permettent le développement de l'hyperplasie intimale. Toutefois, les propriétés vasomotrices ainsi que l'influence des paramètres hémodynamiques ne peuvent être analysées que par l'utilisation du système de perfusion. Ce dernier a permis de perfuser des vaisseaux humains sans contamination bactérienne tout en maintenant l'intégrité cellulaire. Ce modèle de perfusion se rapproche plus des conditions hémodynamiques rencontrées in vivo que le modèle statique. Abstract : Background. Intimal hyperplasia (IH) is a vascular remodeling process which often leads to failure of arterial bypass or hemodialysis access. Experimental and clinical work have provided insight in IH development; however, further studies under precise con-trolled conditions are required to improve therapeutic strategies to inhibit IH development. Ex vivo perfusion of human vessel segments under standardized hemodynamic conditions may provide an adequate experimental approach for this purpose. Therefore, chronically perfused venous segments were studied and compared to traditional static culture procedures with regard to functional and histomorphologic characteristics as well as gene expression. Materials and methods. Static vein culture allowing high tissue viability was performed as previously described. Ex vivo vein support system (EVVSS) was performed using a vein support system consisting of an incubator with a perfusion chamber and a pump. EVVSS allows vessel perfusion under continuous flow while maintaining controlled hemodynamic conditions. Each human saphenous vein was divided in two parts, one cultured in a Pyrex dish and the other part perfused in EVVSS for 14 days. Testing of vasomotion, histomorphometry, expression of CD 31, Factor VIII, MIB 1, α-actin, and PAI-1 were determined before and after 14 days of either experimental conditions. Results, Human venous segments cultured under traditional or perfused conditions exhibited similar IH after 14 days as shown by histomorphometry. Smooth-muscle cell ( SMC) was preserved after chronic perfusion. Although integrity of both endothelial and smooth-muscle cells appears to be maintained in both culture conditions as confirmed by CD31, factor VIII and α-actin expression, a few smooth-muscle cells in the media stained positive for factor VIII. Cell-proliferation marker MIB-1 was also detected in the two settings and PAI-1 mRNA expression and activity increased significantly after 14 days of culture and perfusion. Conclusion. This study demonstrates the feasibility to chronically perfuse human vessels under sterile conditions with preservation of cellular integrity and vascular contractility. To gain insights into the mechanisms leading to IH, it will now be possible to study vascular remodeling not only under static conditions but also in hemodynamic environment mimicking as closely as possible the flow conditions encountered in reconstructive vascular surgery.

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The general strategy to perform anti-doping analyses of urine samples starts with the screening for a wide range of compounds. This step should be fast, generic and able to detect any sample that may contain a prohibited substance while avoiding false negatives and reducing false positive results. The experiments presented in this work were based on ultra-high-pressure liquid chromatography coupled to hybrid quadrupole time-of-flight mass spectrometry. Thanks to the high sensitivity of the method, urine samples could be diluted 2-fold prior to injection. One hundred and three forbidden substances from various classes (such as stimulants, diuretics, narcotics, anti-estrogens) were analysed on a C(18) reversed-phase column in two gradients of 9min (including two 3min equilibration periods) for positive and negative electrospray ionisation and detected in the MS full scan mode. The automatic identification of analytes was based on retention time and mass accuracy, with an automated tool for peak picking. The method was validated according to the International Standard for Laboratories described in the World Anti-Doping Code and was selective enough to comply with the World Anti-Doping Agency recommendations. In addition, the matrix effect on MS response was measured on all investigated analytes spiked in urine samples. The limits of detection ranged from 1 to 500ng/mL, allowing the identification of all tested compounds in urine. When a sample was reported positive during the screening, a fast additional pre-confirmatory step was performed to reduce the number of confirmatory analyses.

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OBJECTIVES: The diagnosis of pheochromocytoma relies on the measurement of plasma free metanephrines assay whose reliability has been considerably improved by ultra-high pressure liquid chromatography tandem mass spectrometry (UHPLC-MS/MS). Here we report an analytical interference occurring between 4-hydroxy-3-methoxymethamphetamine (HMMA), a metabolite of 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy"), and normetanephrine (NMN) since they share a common pharmacophore resulting in the same product ion after fragmentation. DESIGN AND METHODS: Synthetic HMMA was spiked into plasma samples containing various concentrations of NMN and the intensity of the interference was determined by UPLC-MS/MS before and after improvement of the analytical method. RESULTS: Using a careful adjustment of chromatographic conditions including the change of the UPLC analytical column, we were able to distinguish both compounds. HMMA interference for NMN determination should be seriously considered since MDMA activates the sympathetic nervous system and if confounded with NMN may lead to false-positive tests when performing a differential diagnostic of pheochromocytoma.

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Elevated levels of γ-glutamyltransferase (GGT) have been associated with elevated blood pressure (BP) and diabetes. However, the causality of these relations has not been addressed. The authors performed a cross-sectional analysis (2003-2006) among 4,360 participants from the population-based Cohorte Lausannoise (CoLaus) Study (Lausanne, Switzerland). The rs2017869 variant of the γ-glutamyltransferase 1 (GGT1) gene, which explained 1.6% of the variance in GGT levels, was used as an instrument for Mendelian randomization (MR). Sex-specific GGT quartiles were strongly associated with both systolic and diastolic BP (all P's < 0.0001). After multivariable adjustment, these relations were attenuated but remained significant. Using MR, the authors observed no positive association of GGT with BP (systolic: β -5.68, 95% confidence interval (CI): -11.51, 0.16 (P = 0.06); diastolic: β = -2.24, 95% CI: -5.98, 1.49 (P = 0.24)). The association of GGT with insulin was also attenuated after multivariable adjustment but persisted in the fully adjusted model (β = 0.07, 95% CI: 0.04, 0.09; P < 0.0001). Using MR, the authors also observed a positive association of GGT with insulin (β = 0.19, 95% CI: 0.01, 0.37; P = 0.04). In conclusion, the authors found evidence for a direct causal relation of GGT with fasting insulin but not with BP.

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BACKGROUND: Spontaneous ventilation, mechanical controlled ventilation, apneic intermittent ventilation, and jet ventilation are commonly used during interventional suspension microlaryngoscopy. The aim of this study was to investigate specific complications of each technique, with special emphasis on transtracheal and transglottal jet ventilation. METHODS: The authors performed a retrospective single-institution analysis of a case series of 1,093 microlaryngoscopies performed in 661 patients between January 1994 and January 2004. Data were collected from two separate prospective databases. Feasibility and complications encountered with each technique of ventilation were analyzed as main outcome measures. RESULTS: During 1,093 suspension microlaryngoscopies, ventilation was supplied by mechanical controlled ventilation via small endotracheal tubes (n = 200), intermittent apneic ventilation (n = 159), transtracheal jet ventilation (n = 265), or transglottal jet ventilation (n = 469). Twenty-nine minor and 4 major complications occurred. Seventy-five percent of the patients with major events had an American Society of Anesthesiologists physical status classification of III. Five laryngospasms were observed with apneic intermittent ventilation. All other 24 complications (including 7 barotrauma) occurred during jet ventilation. Transtracheal jet ventilation was associated with a significantly higher complication rate than transglottal jet ventilation (P < 0.0001; odds ratio, 4.3 [95% confidence interval, 1.9-10.0]). All severe complications were related to barotraumas resulting from airway outflow obstruction during jet ventilation, most often laryngospasms. CONCLUSIONS: The use of a transtracheal cannula was the major independent risk factor for complications during jet ventilation for interventional microlaryngoscopy. The anesthetist's vigilance in clinically detecting and preventing outflow airway obstruction remains the best prevention of barotrauma during subglottic jet ventilation.

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Background: Little is known on the relative importance of growth at different periods between birth and adolescence on blood pressure (BP). Objective: To assess the association between birth weight, change in body weight (growth) and BP across the entire span of childhood and adolescence. Methods: School-based surveys were conducted annually between 1998 and 2006 among all children in four school grades (kindergarten, 4th, 7th, and 10th year of compulsory school) in the Seychelles, Indian Ocean. Height and weight and BP were measured. Three cohorts of children examined twice were analyzed: 1606 children surveyed at age 5.5 and 9.1, 2557 at age 9.2 and 12.5, and 2065 at age 12.5 and 15.5, respectively. Weights at birth and at one year were extracted from medical files. Weights were expressed as Z-scores and growth was defined as a change in weight Z-scores (corresponding to weight centile crossing). The association between BP (at age 5.5, 9.2, 12.5, and 15.5) and weight at different times was assessed by linear regression. Using results of regression models of BP on all successive weights, life course plots were drawn by plotting regression coefficients against age at which weight was measured. The figure shows a life course plot of systolic BP in boys aged 15.5. Results: Without adjustment for current weight (at the time of BP measurement), birth weight was not associated with current BP, irrespective of age, excepted for girls at age 15.5 for whom a modest positive association was found. When adjusted for current weight, birth weight was negatively and modestly associated with current BP. BP was strongly associated with current weight, irrespective of age. Life course plots showed that BP was strongly associated with growth during the few preceding years but not with growth during earlier years, except for growth during the first year of life which tended to be associated with systolic BP. Conclusions: Our findings suggest that BP during childhood and adolescence is mainly determined by current body weight and recent growth.

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In a prospective investigation of 17 children with severe croup, we analyzed the effect of epinephrine inhalations and mild sedation with chloral hydrate on transcutaneous carbon dioxide pressure (tcPCO2), pulse oximetry measurements, and croup scores. There was a highly significant reduction (p less than 0.001) in the tcPCO2 values and croup scores after inhalation of epinephrine. The changes in the tcPCO2 values correlated with the clinical findings. Mild sedation also significantly improved the croup scores but failed to influence the tcPCO2 values. There was not statistically significant difference in pulse oximetry saturation, fraction of administered oxygen, heart rate, or respiratory rate before and after inhalation of epinephrine or chloral hydrate administration. Monitoring tcPCO2 appears to be a reliable and objective tool for managing patients with upper airway obstruction, whereas croup scores may be misleading.

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Summary: Particulate air pollution is associated with increased cardiovascular risk. The induction of systemic inflammation following particle inhalation represents a plausible mechanistic pathway. The purpose of this study was to assess the associations of short-term exposure to ambient particulate matters of aerodynamic diameter less than 10 μm (PM10) with circulating inflammatory markers in 6183 adults in Lausanne, Switzerland. The results show that short-term exposure to PM10 was associated with higher levels of circulating IL-6 and TNF-α. The positive association of PM10 with markers of systemic inflammation materializes the link between air pollution and cardiovascular risk. Background: Variations in short-term exposure to particulate matters (PM) have been repeatedly associated with daily all-cause mortality. Particle-induced inflammation has been postulated to be one of the important mechanisms for increased cardiovascular risk. Experimental in-vitro, in-vivo and controlled human studies suggest that interleukin 6 (IL-6) and tumor-necrosis-factor alpha (TNF-α) could represent key mediators of the inflammatory response to PM. The associations of short-term exposure to ambient PM with circulating inflammatory markers have been inconsistent in studies including specific subgroups so far. The epidemiological evidence linking short-term exposure to ambient PM and systemic inflammation in the general population is scarce. So far, large-scale population-based studies have not explored important inflammatory markers such as IL-6, IL-1β or TNF-α. We therefore analyzed the associations between short-term exposure to ambient PM10 and circulating levels of high-sensitive CRP (hs-CRP), IL-6, IL-1β and TNF-α in the population-based CoLaus study. Objectives: To assess the associations of short-term exposure to ambient particulate matters of aerodynamic diameter less than 10 μm (PM10) with circulating inflammatory markers, including hs-CRP, IL-6, IL-1β and TNF-α, in adults aged 35 to 75 years from the general population. Methodology: All study subjects were participants to the CoLaus study (www.colaus.ch) and the baseline examination was carried out from 2003 to 2006. Overall, 6184 participants were included. For the present analysis, 6183 participants had data on at least one of the four measured circulating inflammatory markers. The monitoring data was obtained from the website of Swiss National Air Pollution Monitoring Network (NABEL). We analyzed data on PM10 as well as outside air temperature, pressure and humidity. Hourly concentrations of PM10 were collected from 1 January 2003 to 31 December 2006. Robust linear regression (PROC ROBUSTREG) was used to evaluate the relationship between cytokine inflammatory and PM10. We adjusted all analyses for age, sex, body mass index, smoking status, alcohol consumption, diabetes status, hypertension status, education levels, zip code, and statin intake. All data were adjusted for the effects of weather by including temperature, barometric pressure, and season as covariates in the adjusted models. We performed simple and multiple logistic regression analyses. Descriptive statistical analysis used the Wilcoxon rank sum test (for medians). All data analyses were performed using SAS software (version 9.2; SAS Institute Inc., Cary, NC, USA), and a two-sided significance level of 5% was used. Results: PM10 levels averaged over 24 hours were significantly and positively associated with continuous IL-6 and TNF-α levels, in the whole study population both in unadjusted and adjusted analyses. For each cytokine, there was a similar seasonal pattern, with wider confidence intervals in summer than during the other seasons, which might partly be due to the smaller number of participants examined in summer. The associations of PM10 with IL-6 and TNF-α were also found after having dichotomized these cytokines into high versus low levels, which suggests that the associations of PM10 with the continuous cytokine levels are very robust to any distributional assumption and to potential outlier values. In contrast with what we observed for continuous IL-1β levels, high PM10 levels were significantly associated with high IL-1β. PM10 was significantly associated with IL-6 and TNF-α in men, but with TNF-α only in women. However, there was no significant statistical interaction between PM10 and sex. For IL-6 and TNF-α, the associations tended to be stronger in younger people, with a significant interaction between PM10 and age groups for IL-6. PM10 was significantly associated with IL-6 and TNF-α in the healthy group and also in the "non-healthy" group, although the statistical interaction between healthy status and PM10 was not significant. Conclusion: In summary, we found significant independent positive associations of short-term exposure to PM10 with circulating levels of IL-6 and TNF-α in the adult population of Lausanne. Our findings strongly support the idea that short-term exposure to PM10 is sufficient to induce systemic inflammation on a broad scale in the general population. From a public health perspective, the reported association of elevated inflammatory cytokines with short-term exposure to PM10 in a city with relatively clean air such as Lausanne supports the importance of limiting urban air pollution levels.

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OBJECTIVES: To explore the association of short-term exposure to particulate matter with aerodynamic diameters less than 10 μm (PM10) with pulse pressure, SBP, and DBP taking outdoor temperature into account in two large population-based studies in Switzerland. METHODS: We used data from the Bus Santé study including 5605 adults in Geneva and the CoLaus study including 6183 adults in Lausanne. PM10 and meteorological data were measured from fixed monitoring stations. We analyzed the association of short-term exposure to PM10 (on the day of examination visit and up to 7 days before) with pulse pressure, SBP, and DBP by linear regression, controlling for potential confounders and effect modifiers. RESULTS: Average PM10 levels were 22.4 μg/m in Geneva and 31.7 μg/m in Lausanne. In adjusted models, for each 10 μg/m increase in 7-day PM10 average, pulse pressure and SBP increased by 0.583 (95% confidence interval, 0.296-0.870) mmHg and 0.490 (0.056-0.925) mmHg in Geneva, and 0.183 (0.017-0.348) mmHg and 0.036 (0.042-0.561) mmHg in Lausanne, respectively. Stronger associations of pulse pressure and SBP with PM10 were observed when outdoor temperature was above 5°C. CONCLUSION: Positive associations of pulse pressure and SBP with short-term exposure to PM10 were found and replicated in the Swiss adult population. Our results suggest that even low levels of air pollution may substantially impact cardiovascular risk in the general population.