RED BLOOD CELL MICROPARTICLES: ROLE IN TRANSFUSION MEDICINE?

RésuméLes microparticules sont des vésicules phospholipidiques de moins d‟un micromètre relâchées dans le sang par différents types cellulaires, comme les cellules endothéliales, les plaquettes ou encore les globules blancs et rouges. Elles sont bioactives et impliquées dans de nombreux processus physiologiques incluant l‟hémostase. De plus, un nombre élevé de microparticules circulantes dans le sang a été observé dans différentes pathologies.Dans le domaine de la transfusion, les microparticules de globules rouges ont été détectées dans les concentrés érythrocytaires. Le but de cette recherche était de caractériser les microparticules de globules rouges et d‟évaluer si ces dernières avaient un rôle en transfusion. Pour ce faire, une approche globale utilisant différentes techniques comme la cytométrie de flux, la protéomique, la microscopie ainsi que des tests d‟hémostase de routines, a été adoptée.Le présent travail de thèse a démontré que les microparticules de globules rouges s‟accumulent dans les concentrés érythrocytaires pendant le stockage. Leur bioactivité a été démontrée de part leur rôle actif dans le processus de la coagulation. En effet, lors de test de génération de thrombine, elles peuvent non seulement supporter ce processus de coagulation, mais aussi le déclencher par un mécanisme inconnu sous certaines circonstances. Les microparticules de globules rouges présentent aussi des antigènes de groupes sanguins à leur surface, toutefois, leur implication potentielle dans l‟induction d‟une réponse immunitaire n‟est pas connue. Bien que le mécanisme de formation et d‟émissions des microparticules par les globules rouges ne soit pas complètement élucidé, il a été démontré qu‟elles n‟ont pas toutes le même contenu protéique et donc qu‟elles pourraient avoir des fonctions différentes.Au vu des résultats, notamment par leur implication dans la coagulation, il est fort probable que la présence de microparticules puisse affecter la qualité des produits sanguins, et causer des réactions transfusionnelles.

Discriminating irritable bowel syndrome from inflammatory bowel disease: what is the role of biomarkers in daily practice?

Background and Aims: Discriminating irritable bowel syndrome (IBS) from inflammatorybowel disease (IBD) can be a clinical challenge as symptoms can overlap. We and othershave recently shown that fecal calprotectin (FC) is more accurate for discriminating IBSfrom IBD compared to C-reactive protein (CRP) and blood leukocytes. Data on the biomarkersused in daily gastroenterological practice are lacking. We therefore aimed to assess whichbiomarkers are used by gastroenterologists in their daily practice for discriminating IBSfrom IBD.Methods: A questionnaire was sent to all board certified gastroenterologists inSwitzerland focusing on demographic informations, number of IBS patients treated in thetime period from May 2009 to April 2010, and the specific biomarkers evaluated fordiscriminating IBS from IBD.Results: Response rate was 57% (153/270). Mean physician'sage was 50±9years, mean duration of gastroenterologic practice 14±8years, 52% of themwere working in private practice and 48% in hospitals. Thirty-nine percent had taken careof more than 100 IBS patients in the last 12 months, 37% had seen 41-100 and 24% hadseen 1-40 IBS patients. Gastroenterologists in private practice more frequently took care ofat least 40 IBS patients in a year compared to hospital-based gastroenterologists (P<0.001).The following biomarkers were determined for discriminating IBS from IBD: CRP 100%,FC 79%, hematogram (red blood cells and leukocytes) 70%, iron status (ferritin, transferrinsaturation) 59%, erythrocyte sedimentation rate 2.7%, protein electrophoresis 0.7%, andalpha-1 antitrypsin clearance 0.7%. There was a trend for using FC more often in privatepractice than in hospital (P = 0.08). Twenty-four percent of gastroenterologists had usedFC in the workup of more than 70% of patients classified as IBS, 22% had used FC in 30-70% of IBS patients, 39% in less than 30%, and 15% had never used FC for the work-upof suspected IBS. Eighty-nine percent of gastroenterologists considered FC to be superiorto CRP for discriminating IBS from IBD, 87% thought that patient's compliance for fecalsampling is high, and 51% judged the fee of USD 60 for a FC test as appropriate.Conclusions:FC is widely used in clinical practice to discriminate IBS from IBD. In accordance with thescientific evidence, the majority of gastroenterologists consider FC to be more accurate thanCRP for discriminating IBS from IBD. Gastroenterologists in private practice take care ofsignificantly more IBS patients than colleagues in hospital.

Estimating arterial blood gases with the EABC® System (“Earlobe Arterialized Blood Collector”) in critically ill patients. A validation study.

The Earlobe Arterialized Blood Collector® is a minimally invasive system able to perform arterialized capillary blood gas analysis from the earlobe (EL). A prospective validation study was performed in 55 critical ill patients. Sampling failure rate was high (53.6%). Risk factors were age > 65 years, diabetes, vasoactive drug therapy and noradrenaline (NA) doses above 0.22 μg / kg / min. Multivariate analysis showed age > 65 years was the only factor independently associated with failure. Concordance analysis with arterial blood gases and Bland-Altman agreement evaluation were insufficient for validating the new system for all gasometrical variables.

Effect of weight reduction in moderately overweight patients on recorded ambulatory blood pressure and free cytosolic platelet calcium.

Although platelet cytosolic calcium has been shown to decrease during pharmacological treatment of hypertension, there is no evidence that cytosolic calcium also falls during a nonpharmacological reduction in blood pressure. To provide such evidence, we examined prospectively the relation between platelet cytosolic calcium and ambulatory blood pressure during weight reduction in moderately overweight (body mass index [BMI] greater than 25), mildly hypertensive individuals. The experimental group (responders: BMI reduction greater than 5%) consisted of 19 patients who lost 8.5 +/- 2.9 kg (mean +/- SD, p less than 0.05) during a 10-week hypocaloric diet, whereas the control group (nonresponders: BMI reduction less than 5%) consisted of 12 patients who showed no relevant change in body weight (-2.0 +/- 1.3 kg) during the same period of time. The moderate weight loss of the responders decreased blood pressure by 14/5 mm Hg (p less than 0.05), as measured by ambulatory monitoring, which renders a placebo effect unlikely. This nonpharmacological reduction in blood pressure was accompanied by a proportional 11% decrease (p less than 0.05) in platelet cytosolic calcium and also by significant (p less than 0.05) decreases in plasma catecholamines and serum cholesterol. These findings establish the concept of a nonpharmacological reduction in free cytosolic platelet calcium in humans and add further evidence suggesting a link between intracellular calcium homeostasis and blood pressure regulation.

Interindividual variability of the clinical pharmacokinetics of methadone: implications for the treatment of opioid dependence

Methadone is widely used for the treatment of opioid dependence. Although in most countries the drug is administered as a racemic mixture of (R)- and (S)- methadone, (R)-methadone accounts for most, if not all, of the opioid effects. Methadone can be detected in the blood 15-45 minutes after oral administration, with peak plasma concentration at 2.5-4 hours. Methadone has a mean bioavailability of around 75% (range 36-100%). Methadone is highly bound to plasma proteins, in particular to alpha(1)-acid glycoprotein. Its mean free fraction is around 13%, with a 4-fold interindividual variation. Its volume of distribution is about 4 L/kg (range 2-13 L/kg). The elimination of methadone is mediated by biotransformation, followed by renal and faecal excretion. Total body clearance is about 0.095 L/min, with wide interindividual variation (range 0.02-2 L/min). Plasma concentrations of methadone decrease in a biexponential manner, with a mean value of around 22 hours (range 5-130 hours) for elimination half-life. For the active (R)-enantiomer, mean values of around 40 hours have been determined. Cytochrome P450 (CYP) 3A4 and to a lesser extent 2D6 are probably the main isoforms involved in methadone metabolism. Rifampicin (rifampin), phenobarbital, phenytoin, carbamazepine, nevirapine, and efavirenz decrease methadone blood concentrations, probably by induction of CYP3A4 activity, which can result in severe withdrawal symptoms. Inhibitors of CYP3A4, such as fluconazole, and of CYP2D6, such as paroxetine, increase methadone blood concentrations. There is an up to 17-fold interindividual variation of methadone blood concentration for a given dosage, and interindividual variability of CYP enzymes accounts for a large part of this variation. Since methadone probably also displays large interindividual variability in its pharmacodynamics, methadone treatment must be individually adapted to each patient. Because of the high morbidity and mortality associated with opioid dependence, it is of major importance that methadone is used at an effective dosage in maintenance treatment: at least 60 mg/day, but typically 80-100 mg/day. Recent studies also show that a subset of patients might benefit from methadone dosages larger than 100 mg/day, many of them because of high clearance. In clinical management, medical evaluation of objective signs and subjective symptoms is sufficient for dosage titration in most patients. However, therapeutic drug monitoring can be useful in particular situations. In the case of non-response trough plasma concentrations of 400 microg/L for (R,S)-methadone or 250 microg/L for (R)-methadone might be used as target values.

Fitness, sport et pression artérielle [Fitness, sports and blood pressure].

Blood pressure is lowered for a few hours after aerobic exercise, but also after resistance exercise, although for a shorter period of time. An exercise program can significantly lower resting and ambulatory BP measurements. Multiple mechanisms interact for the BP lowering effect, such as decreased total peripheral resistance, enhanced endothelial function, diminished sympathetic or rennin plasmatic activity, structural vascular modifications and baroreceptor reflex modulation. New exercises like eccentric or isometric (handgrip) contractions are promising. Resistance activities have long been considered dangerous for blood vessels because of increased arterial stiffness, but if the intensity remains moderate and aerobic exercises are integrated, then the effects are altogether beneficial.

Using 80 kVp versus 120 kVp in perfusion CT measurement of regional cerebral blood flow.

Perfusion CT studies of regional cerebral blood flow (rCBF), involving sequential acquisition of cerebral CT sections during IV contrast material administration, have classically been reported to be achieved at 120 kVp. We hypothesized that using 80 kVp should result in the same image quality while significantly lowering the patient's radiation dose, and we evaluated this assumption. In five patients undergoing cerebral CT survey, one section level was imaged at 120 kVp and 80 kVp, before and after IV administration of iodinated contrast material. These four cerebral CT sections obtained in each patient were analyzed with special interest to contrast, noise, and radiation dose. Contrast enhancement at 80 kVp is significantly increased (P < .001), as well as contrast between gray matter and white matter after contrast enhancement (P < .001). Mean noise at 80 kVp is not statistically different (P = .042). Finally, performance of perfusion CT studies at 80 kVp, keeping mAs constant, lowers the radiation dose by a factor of 2.8. We, thus, conclude that 80 kVp acquisition of perfusion CT studies of rCBF will result in increased contrast enhancement and should improve rCBF analysis, with a reduced patient's irradiation.

Blood plasma lipidomic signature of epicardial fat in healthy obese women.

OBJECTIVES: A lipidomic approach was employed in a clinically well-defined cohort of healthy obese women to explore blood lipidome phenotype ascribed to body fat deposition, with emphasis on epicardial adipose tissue (EAT). METHODS: The present investigation delivered a lipidomics signature of epicardial adiposity under healthy clinical conditions using a cohort of 40 obese females (age: 25-45 years, BMI: 28-40 kg/m(2) ) not showing any metabolic disease traits. Lipidomics analysis of blood plasma was employed in combination with in vivo quantitation of mediastinal fat depots by computerized tomography. RESULTS: All cardiac fat depots correlated to indicators of hepatic dysfunctions (ALAT and ASAT), which describe physiological connections between hepatic and cardiac steatosis. Plasma lipidomics encompassed overall levels of lipid classes, fatty acid profiles, and individual lipid species. EAT and visceral fat associated with diacylglycerols (DAG), triglycerides, and distinct phospholipid and sphingolipid species. A pattern of DAG and phosphoglycerols was specific to EAT. CONCLUSIONS: Human blood plasma lipidomics appears to be a promising clinical and potentially diagnostic readout for patient stratification and monitoring. Association of blood lipidomics signature to regio-specific mediastinal and visceral adiposity under healthy clinical conditions may help provide more biological insights into obese patient stratification for cardiovascular disease risks.

Close-Clearance Conditions Near Railroad Tracks: A report to the Iowa Legislature as per Section 24, HF2614, Seventy-Ninth General Assembly, December 6, 2002

Close-Clearance Conditions Near Railroad Tracks for the Iowa Department of Transportation

Phase-sensitive black-blood coronary vessel wall imaging.

Black-blood MR coronary vessel wall imaging may become a powerful tool for the quantitative and noninvasive assessment of atherosclerosis and positive arterial remodeling. Although dual-inversion recovery is currently the gold standard, optimal lumen-to-vessel wall contrast is sometimes difficult to obtain, and the time window available for imaging is limited due to competing requirements between blood signal nulling time and period of minimal myocardial motion. Further, atherosclerosis is a spatially heterogeneous disease, and imaging at multiple anatomic levels of the coronary circulation is mandatory. However, this requirement of enhanced volumetric coverage comes at the expense of scanning time. Phase-sensitive inversion recovery has shown to be very valuable for enhancing tissue-tissue contrast and for making inversion recovery imaging less sensitive to tissue signal nulling time. This work enables multislice black-blood coronary vessel wall imaging in a single breath hold by extending phase-sensitive inversion recovery to phase-sensitive dual-inversion recovery, by combining it with spiral imaging and yet relaxing constraints related to blood signal nulling time and period of minimal myocardial motion.

Blood pressure changes in acute ischemic stroke and outcome with respect to stroke etiology.

OBJECTIVE: Previous research suggested that proper blood pressure (BP) management in acute stroke may need to take into account the underlying etiology. METHODS: All patients with acute ischemic stroke registered in the ASTRAL registry between 2003 and 2009 were analyzed. Unfavorable outcome was defined as modified Rankin Scale score >2. A local polynomial surface algorithm was used to assess the effect of baseline and 24- to 48-hour systolic BP (SBP) and mean arterial pressure (MAP) on outcome in patients with lacunar, atherosclerotic, and cardioembolic stroke. RESULTS: A total of 791 patients were included in the analysis. For lacunar and atherosclerotic strokes, there was no difference in the predicted probability of unfavorable outcome between patients with an admission BP of <140 mm Hg, 140-160 mm Hg, or >160 mm Hg (15.3 vs 12.1% vs 20.8%, respectively, for lacunar, p = 015; 41.0% vs 41.5% vs 45.5%, respectively, for atherosclerotic, p = 075), or between patients with BP increase vs decrease at 24-48 hours (18.7% vs 18.0%, respectively, for lacunar, p = 0.84; 43.4% vs 43.6%, respectively, for atherosclerotic, p = 0.88). For cardioembolic strokes, increase of BP at 24-48 hours was associated with higher probability of unfavorable outcome compared to BP reduction (53.4% vs 42.2%, respectively, p = 0.037). Also, the predicted probability of unfavorable outcome was significantly different between patients with an admission BP of <140 mm Hg, 140-160 mm Hg, and >160 mm Hg (34.8% vs 42.3% vs 52.4%, respectively, p < 0.01). CONCLUSIONS: This study provides evidence to support that BP management in acute stroke may have to be tailored with respect to the underlying etiopathogenetic mechanism.