Cardio-pulmonary interaction in premature newborn with nasal continuous positive airways pressure (n-CPAP) respiratory assistance evaluated with echocardiography

Introduction: Nasal continuous positive airways pressure (n-CPAP) is an effective treatment in premature infants with respiratory distress. The cardio-pulmonary interactions secondary to n-CPAP are well studied in adults, but less well described in premature infants. We postulated that there could be important interactions with regard to the patent ductus arteriosus (PDA). Methods: Prospective study, approved by the local ethic committee. Premature infants less than 32 weeks gestation, _7 days-old, needing n-CPAP for respiratory distress, but without the need of additional oxygen were included in the study. Every patient had a first echocardiography with n-CPAP and then n-CPAP was retrieved. 3 hours later the echocardiography was repeated by the same investigator and then the patient replaced on n-CPAP. Results: 14 premature newborn were included, mean gestational age of 28 _ 2 weeks, mean weight 1.1 _ 0.3 Kg and height 39 _ 3 cm. Echocardiographic measurements are depicted in Table 1. Significant finding were observed between measurement on n- CPAP or without n-CPAP: on end diastolic left ventricular diameter (12.8 _ 1.6 mm vs. 13.5 _ 2 mm), on end systolic left ventricular diameter (8.4 _ 1.3 mm vs. 9.1 _ 1.5 mm), left atrium diameter (8.9 _ 2.2 mm vs. 10.4 _ 2.5 mm), maximal velocity on tricuspid valve (46 _ 10 cm/s vs. 51 _ 9 cm/s), calculated Qp (3.7 _ 0.8 L/min/m2 vs. 4.3 _ 0.8 L/min/m2). Only three patients have demonstrated a PDA during the study. Conclusion: Positive end expiratory pressure (Peep) has hemodynamic effects which are: reduction of systemic and pulmonary venous return as shown by the changes on tricuspid valve inflow,on the calculated Qp and finally on the diameter of the left atrium and left ventricle.We found in premature infants the same hemodynamic effects than those described in adults but with lower Peep values. This could be due to the particular elasticity and weakness of the thoracic wall of premature infants. Interestingly the flow through a PDA seems also to be diminished with Peep, but the number of patients is insufficient to conclude. Further investigation will be needed to better understand these interactions. Table 1. Echocardiographic measurement (mean (SD)). With n-CPAP Without n-CPAP p value RV ED diameter (mm) 6.3 (1.7) 6.04 (1.1) NS LV ED diameter (mm) 12.8 (1.6) 13.5 (2.0) _0.05 LV ES diameter (mm) 8.4 (1.3) 9.1 (1.5) _0.05 SF (%) 34 (5) 33 (6) NS Ao valve diameter (mm) 7.4 (1.3) 7.4 (1.2) NS LA diameter (mm) 8.9 (2.2) 10.4 (2.5) _0.05 Vmax Ao (cm/s) 70 (16) 71 (18) NS Vmax PV (cm/s) 69 (15) 72 (16) NS Vmax TV (cm/s) 46 (10) 51 (9) _0.05 Vmax MV (cm/s) 53 (17) 54 (18) NS Qp (L/min/m2) 3.7 (0.8) 4.3 (0.8) _0.05 Qs (L/min/m2) 4.0 (0.8) 4.0 (0.7) NS Qp/Qs 0.92 (0.14) 1.09 (0.23) _0.05 RV: right ventricle, LV: left ventricle, ED: end diastolic, ES: end systolic, SF: shortening fraction,Ao: aortic valve, LA: left atrium,Vmax: maximum Doppler Velocity, Qp: pulmonary output, Qs: systemic output, NS: non significant.

Who is at low risk for cardiovascular disease?: an assessment of different definitions

Purpose: to assess the prevalence and trends of low cardiovascular risk factor (RF) profile in the Swiss population according to different definitions. Methods: Population-based cross-sectional study of 6170 subjects (3241 women) aged 35-75 years living in Lausanne, Switzerland. Trends were assessed using data from the Swiss MONICA population surveys conducted in 1984-6 (N = 3300), 1988-9 (N = 3331) and 1992-3 (N = 3133) and restricted to the same age group. Seven different definitions of low RF profile were used. Results: prevalence of low RF profile varied between 6.5% (95% confidence interval: 5.9-7.1) and 9.7% (9.0-10.5) depending on the definition used (see fig. 1). The prevalence was inversely related to the number of criteria used and higher than in other countries. Irrespective of the definition used, the prevalence of low RF profile was higher in women and in physically active participants, and decreased with increasing age or in the presence of a family history of cardiovascular disease. The prevalence of low RF profile increased from 3.8% (3.1- 4.5) in 1984-6 to 6.7% (6.1-7.3) in 2003-6; using another definition, the results were 5.9% (5.1-6.8) and 9.7% (9.0-10.5), respectively (see fig. 2). Conclusion: the prevalence of low RF profile varies according to the criteria used; this prevalence is relatively high and increasing in the Swiss population, which might partly explain the low and decreasing trend in cardiovascular mortality rates.

Prolonged survival for patients with newly diagnosed, inoperable glioblastoma with 3-times daily ultrafractionated radiation therapy.

Ultrafractionation of radiation therapy is a novel regimen consisting of irradiating tumors several times daily, delivering low doses (<0.75 Gy) at which hyperradiosensitivity occurs. We recently demonstrated the high efficiency of ultrafractionated radiotherapy (RT) on glioma xenografts and report here on a phase II clinical trial to determine the safety, tolerability, and efficacy of an ultrafractionation regimen in patients with newly and inoperable glioblastoma (GBM). Thirty-one patients with histologically proven, newly diagnosed, and unresectable supratentorial GBM (WHO grade IV) were enrolled. Three daily doses of 0.75 Gy were delivered at least 4 hours apart, 5 days per week over 6-7 consecutive weeks (90 fractions for a total of 67.5 Gy). Conformal irradiation included the tumor bulk with a margin of 2.5 cm. The primary end points were safety, toxicity, and tolerability, and the secondary end points were overall survival (OS) and progression-free survival (PFS). Multivariate analysis was used to compare the OS and PFS with the EORTC-NCIC trial 26981-22981/CE.3 of RT alone vs radiation therapy and temozolomide (TMZ). The ultrafractionation radiation regimen was safe and well tolerated. No acute Grade III and/or IV CNS toxicity was observed. Median PFS and OS from initial diagnosis were 5.1 and 9.5 months, respectively. When comparing with the EORTC/NCIC trial, in both PFS and OS multivariate analysis, ultrafractionation showed superiority over RT alone, but not over RT and TMZ. The ultrafractionation regimen is safe and may prolong the survival of patients with GBM. Further investigation is warranted and a trial associating ultra-fractionation and TMZ is ongoing.

Deux livres des venins , ausquels il est amplement discouru des bestes venimeuses, thériaques, poisons & contre-poisons, par Jacques Grévin,... Ensemble les oeuvres de Nicandre,... traduictes en vers françois

Comprend : [Œuvres]

Application of low temperature thermochronology to understanding cooling and exhumation in the Central Swiss Alps

THESIS ABSTRACT : Low-temperature thermochronology relies on application of radioisotopic systems whose closure temperatures are below temperatures at which the dated phases are formed. In that sense, the results are interpreted as "cooling ages" in contrast to "formation ages". Owing to the low closure-temperatures, it is possible to reconstruct exhumation and cooling paths of rocks during their residence at shallow levels of the crust, i.e. within first ~10 km of depth. Processes occurring at these shallow depths such as final exhumation, faulting and relief formation are fundamental for evolution of the mountain belts. This thesis aims at reconstructing the tectono-thermal history of the Aar massif in the Central Swiss Alps by means of zircon (U-Th)/He, apatite (U-Th)/He and apatite fission track thermochronology. The strategy involved acquisition of a large number of samples from a wide range of elevations in the deeply incised Lötschen valley and a nearby NEAT tunnel. This unique location allowed to precisely constrain timing, amount and mechanisms of exhumation of the main orographic feature of the Central Alps, evaluate the role of topography on the thermochronological record and test the impact of hydrothermal activity. Samples were collected from altitudes ranging between 650 and 3930 m and were grouped into five vertical profiles on the surface and one horizontal in the tunnel. Where possible, all three radiometric systems were applied to each sample. Zircon (U-Th)/He ages range from 5.1 to 9.4 Ma and are generally positively correlated with altitude. Age-elevation plots reveal a distinct break in slope, which translates into exhumation rate increasing from ~0.4 to ~3 km/Ma at 6 Ma. This acceleration is independently confirmed by increased cooling rates on the order of 100°C/Ma constrained on the basis of age differences between the zircon (U-Th)/He and the remaining systems. Apatite fission track data also plot on a steep age-elevation curve indicating rapid exhumation until the end of the Miocene. The 6 Ma event is interpreted as reflecting tectonically driven uplift of the Aar massif. The late Miocene timing implies that the increase of precipitation in the Pliocene did not trigger rapid exhumation in the Aar massif. The Messinian salinity crisis in the Mediterranean could not directly intensify erosion of the Aar but associated erosional output from the entire Alps may have tapered the orogenic wedge and caused reactivation of thrusting in the Aar massif. The high exhumation rates in the Messinian were followed by a decrease to ~1.3 km/Ma as evidenced by ~8 km of exhumation during last 6 Ma. The slowing of exhumation is also apparent from apatite (U-Th)1He age-elevation data in the northern part of the Lötschen valley where they plot on a ~0.5km/Ma line and range from 2.4 to 6.4 Ma However, from the apatite (U-Th)/He and fission track data from the NEAT tunnel, there is an indication of a perturbation of the record. The apatite ages are youngest under the axis of the valley, in contrast to an expected pattern where they would be youngest in the deepest sections of the tunnel due to heat advection into ridges. The valley however, developed in relatively soft schists while the ridges are built of solid granitoids. In line with hydrological observations from the tunnel, we suggest that the relatively permeable rocks under the valley floor, served as conduits of geothermal fluids that caused reheating leading to partial Helium loss and fission track annealing in apatites. In consequence, apatite ages from the lowermost samples are too young and the calculated exhumation rates may underestimate true values. This study demonstrated that high-density sampling is indispensable to provide meaningful thermochronological data in the Alpine setting. The multi-system approach allows verifying plausibility of the data and highlighting sources of perturbation. RÉSUMÉ DE THÈSE : La thermochronologie de basse température dépend de l'utilisation de systèmes radiométriques dont la température de fermeture est nettement inférieure à la température de cristallisation du minéral. Les résultats obtenus sont par conséquent interprétés comme des âges de refroidissement qui diffèrent des âges de formation obtenus par le biais d'autres systèmes de datation. Grâce aux températures de refroidissement basses, il est aisé de reconstruire les chemins de refroidissement et d'exhumation des roches lors de leur résidence dans la croute superficielle (jusqu'à 10 km). Les processus qui entrent en jeu à ces faibles profondeurs tels que l'exhumation finale, la fracturation et le faillage ainsi que la formation du relief sont fondamentaux dans l'évolution des chaînes de montagne. Ces dernières années, il est devenu clair que l'enregistrement thermochronologique dans les orogènes peut être influencé par le relief et réinitialisé par l'advection de la chaleur liée à la circulation de fluides géothermaux après le refroidissement initial. L'objectif de cette thèse est de reconstruire l'histoire tectono-thermique du massif de l'Aar dans les Alpes suisses Centrales à l'aide de trois thermochronomètres; (U-Th)/He sur zircon, (U-Th)/He sur apatite et les traces de fission sur apatite. Afin d'atteindre cet objectif, nous avons récolté un grand nombre d'échantillons provenant de différentes altitudes dans la vallée fortement incisée de Lötschental ainsi que du tunnel de NEAT. Cette stratégie d'échantillonnage nous a permis de contraindre de manière précise la chronologie, les quantités et les mécanismes d'exhumation de cette zone des Alpes Centrales, d'évaluer le rôle de la topographie sur l'enregistrement thermochronologique et de tester l'impact de l'hydrothermalisme sur les géochronomètres. Les échantillons ont été prélevés à des altitudes comprises entre 650 et 3930m selon 5 profils verticaux en surface et un dans le tunnel. Quand cela à été possible, les trois systèmes radiométriques ont été appliqués aux échantillons. Les âges (U-Th)\He obtenus sur zircons sont compris entre 5.l et 9.4 Ma et sont corrélés de manière positive avec l'altitude. Les graphiques représentant l'âge et l'élévation montrent une nette rupture de la pente qui traduisent un accroissement de la vitesse d'exhumation de 0.4 à 3 km\Ma il y a 6 Ma. Cette accélération de l'exhumation est confirmée par les vitesses de refroidissement de l'ordre de 100°C\Ma obtenus à partir des différents âges sur zircons et à partir des autres systèmes géochronologiques. Les données obtenues par traces de fission sur apatite nous indiquent également une exhumation rapide jusqu'à la fin du Miocène. Nous interprétons cet évènement à 6 Ma comme étant lié à l'uplift tectonique du massif de l'Aar. Le fait que cet évènement soit tardi-miocène implique qu'une augmentation des précipitations au Pliocène n'a pas engendré cette exhumation rapide du massif de l'Aar. La crise Messinienne de la mer méditerranée n'a pas pu avoir une incidence directe sur l'érosion du massif de l'Aar mais l'érosion associée à ce phénomène à pu réduire le coin orogénique alpin et causer la réactivation des chevauchements du massif de l'Aar. L'exhumation rapide Miocène a été suivie pas une diminution des taux d'exhumation lors des derniers 6 Ma (jusqu'à 1.3 km\Ma). Cependant, les âges (U-Th)\He sur apatite ainsi que les traces de fission sur apatite des échantillons du tunnel enregistrent une perturbation de l'enregistrement décrit ci-dessus. Les âges obtenus sur les apatites sont sensiblement plus jeunes sous l'axe de la vallée en comparaison du profil d'âges attendus. En effet, on attendrait des âges plus jeunes sous les parties les plus profondes du tunnel à cause de l'advection de la chaleur dans les flancs de la vallée. La vallée est creusée dans des schistes alors que les flancs de celle-ci sont constitués de granitoïdes plus durs. En accord avec les observations hydrologiques du tunnel, nous suggérons que la perméabilité élevée des roches sous l'axe de la vallée à permi l'infiltration de fluides géothermaux qui a généré un réchauffement des roches. Ce réchauffement aurait donc induit une perte d'Hélium et un recuit des traces de fission dans les apatites. Ceci résulterait en un rajeunissement des âges apatite et en une sous-estimation des vitesses d'exhumation sous l'axe de la vallée. Cette étude à servi à démontrer la nécessité d'un échantillonnage fin et précis afin d'apporter des données thermochronologiques de qualité dans le contexte alpin. Cette approche multi-système nous a permi de contrôler la pertinence des données acquises ainsi que d'identifier les sources possibles d'erreurs lors d'études thermochronologiques. RÉSUMÉ LARGE PUBLIC Lors d'une orogenèse, les roches subissent un cycle comprenant une subduction, de la déformation, du métamorphisme et, finalement, un retour à la surface (ou exhumation). L'exhumation résulte de la déformation au sein de la zone de collision, menant à un raccourcissement et un apaissessement de l'édifice rocheux, qui se traduit par une remontée des roches, création d'une topographie et érosion. Puisque l'érosion agit comme un racloir sur la partie supérieure de l'édifice, des tentatives de corrélation entre les épisodes d'exhumation rapide et les périodes d'érosion intensive, dues aux changements climatiques, ont été effectuées. La connaissance de la chronologie et du lieu précis est d'une importance capitale pour une quelconque reconstruction de l'évolution d'une chaîne de montagne. Ces critères sont donnés par un retraçage des changements de la température de la roche en fonction du temps, nous donnant le taux de refroidissement. L'instant auquel les roches ont refroidit, passant une certaine température, est contraint par l'application de techniques de datation par radiométrie. Ces méthodes reposent sur la désintégration des isotopes radiogéniques, tels que l'uranium et le potassium, tous deux abondants dans les roches de la croûte terrestre. Les produits de cette désintégration ne sont pas retenus dans les minéraux hôtes jusqu'au moment du refroidissement de la roche sous une température appelée 'de fermeture' , spécifique à chaque système de datation. Par exemple, la désintégration radioactive des atomes d'uranium et de thorium produit des atomes d'hélium qui s'échappent d'un cristal de zircon à des températures supérieures à 200°C. En mesurant la teneur en uranium-parent, l'hélium accumulé et en connaissant le taux de désintégration, il est possible de calculer à quel moment la roche échantillonnée est passée sous la température de 200°C. Si le gradient géothermal est connu, les températures de fermeture peuvent être converties en profondeurs actuelles (p. ex. 200°C ≈ 7km), et le taux de refroidissement en taux d'exhumation. De plus, en datant par système radiométrique des échantillons espacés verticalement, il est possible de contraindre directement le taux d'exhumation de la section échantillonnée en observant les différences d'âges entre des échantillons voisins. Dans les Alpes suisses, le massif de l'Aar forme une structure orographique majeure. Avec des altitudes supérieures à 4000m et un relief spectaculaire de plus de 2000m, le massif domine la partie centrale de la chaîne de montagne. Les roches aujourd'hui exposées à la surface ont été enfouies à plus de 10 km de profond il y a 20 Ma, mais la topographie actuelle du massif de l'Aar semble surtout s'être développée par un soulèvement actif depuis quelques millions d'années, c'est-à-dire depuis le Néogène supérieur. Cette période comprend un changement climatique soudain ayant touché l'Europe il y a environ 5 Ma et qui a occasionné de fortes précipitations, entraînant certainement une augmentation de l'érosion et accélérant l'exhumation des Alpes. Dans cette étude, nous avons employé le système de datation (U-TH)/He sur zircon, dont la température de fermeture de 200°C est suffisamment basse pour caractériser l'exhumation du Néogène sup. /Pliocène. Les échantillons proviennent du Lötschental et du tunnel ferroviaire le plus profond du monde (NEAT) situé dans la partie ouest du massif de l'Aar. Considérés dans l'ensemble, ces échantillons se répartissent sur un dénivelé de 3000m et des âges de 5.1 à 9.4 Ma. Les échantillons d'altitude supérieure (et donc plus vieux) documentent un taux d'exhumation de 0.4 km/Ma jusqu'à il y a 6 Ma, alors que les échantillons situés les plus bas ont des âges similaires allant de 6 à 5.4 Ma, donnant un taux jusqu'à 3km /Ma. Ces données montrent une accélération dramatique de l'exhumation du massif de l'Aar il y a 6 Ma. L'exhumation miocène sup. du massif prédate donc le changement climatique Pliocène. Cependant, lors de la crise de salinité d'il y a 6-5.3 Ma (Messinien), le niveau de la mer Méditerranée est descendu de 3km. Un tel abaissement de la surface d'érosion peut avoir accéléré l'exhumation des Alpes, mais le bassin sud alpin était trop loin du massif de l'Aar pour influencer son érosion. Nous arrivons à la conclusion que la datation (U-Th)/He permet de contraindre précisément la chronologie et l'exhumation du massif de l'Aar. Concernant la dualité tectonique-érosion, nous suggérons que, dans le cas du massif de l'Aar, la tectonique prédomine.

Current concepts and management of glioblastoma.

Glioblastoma is the most common malignant primary brain tumor in adults. Its often rapid clinical course, with many medical and psychosocial challenges, requires a multidisciplinary management. Modern multimodality treatment and care improve patients' life expectancy and quality of life. This review covers major aspects of care of glioblastoma patients with a focus on the management of common symptoms and complications. We aim to provide a guide for clinicians confronted with glioblastoma patients in their everyday practice. Ann Neurol 2011;

Adverse life events among community-dwelling persons aged 65-70 years: gender differences in occurrence and perceived psychological consequences.

OBJECTIVES: To describe the occurrence of selected adverse life events in young-old men and women, as well as their perceived psychological consequences. METHODS: In 2005, 1,422 participants in the Lausanne Cohort 65+ study, born in 1934-1938, self-reported whether they experienced any of 26 life events during the preceding year. Most participants (N = 1,309, 92%) completed the geriatric adverse life events scale during a face-to-face interview, by rating the level of stress associated with each event, as well as its impact on their psychological well-being. RESULTS: Overall, 72% of the participants experienced at least one of the 26 events in the preceding year (range 1-9). Disease affecting the respondent (N = 525) or a close relative (N = 276) was most frequent, as well as the death of a friend or non-close relative (N = 274). Women indicated a higher frequency of events (mean 2.1 vs. 1.7 events, P < 0.001), as well as a higher level of stress and a stronger negative impact on well-being than men. In multivariate analyses adjusting for self-rated health, depressive symptoms and comorbidity, female gender remained significantly associated with the level of stress and negative impact on psychological well-being. CONCLUSION: This exploratory study shows that several types of adverse life events frequently occur at age 65-70, with gender differences both in the frequency of reporting and consequences of these events. However, information on this topic is limited and studies based on different populations and designs are needed to better understand the impact of such events.

Combined radiohormonotherapy in node positive lymph node prostate cancer

Purpose: Pelvic radiation therapy (RT) represents a therapeutic option in the treatment of node-positive prostate cancer but it remains controversial, because of its high rate toxicities. New radiation technique such as IMRT may reduce these complications. In this study, we aimed to assess the rate of toxicities according to CTC-NCI.v3 in such patients treated with either 3DCRT or IMRT (Tomotherapy).Methods and Materials: From January 2008 to December 2010, data were analyzed from 30 consecutive patients including 29 node-positive prostate cancer undergoing definitive or adjuvant RT (IMRT and/or 3DCRT) after radical prostatectomy and lymphadenectomy combined to hormonal therapy. Median age was 66 years (range : 52-83). Median preoperative PSA value was 12 ng/ml (range: 2.72-165). According to the pT-classification, there were 4 pT2, 7 pT3a, 10 pT3b, and 1 pT4 patients. Pathologic positive lymph nodes were found in 23 patients. Radiologic positive lymph nodes were found in 5 patients. Two patients were node negative. Gleason score was ranging between 7 to 10. Twelve patients were treated by Tomotherapy including 4 with simultaneous integrated boost (SIB). Eighteen patients were treated by Tomotherapy including 2 with SIB to the whole pelvis and 3DCRT boost to the prostate. V50% for bladder and rectum were recorded. Acute and late toxicities were assessed according to CTC-NCI.v3 classification.Results: With a median follow-up of 17 months, only one patient presented nodal and metastatic failure. Urinary incontinence was graded 1 after surgery for 6 patients and grade 2 in two. Sexual impuissance was noted in 3 patients. Acute toxicities during RT were proctitis grade 0 in 23 patients (76.5%), grade 1 in 7 (23.5%). Nocturia grade 1 in 9 patients. Interruption of treatment was seen in only case because of grade 3 urinary incontinence. Late effects included erectile dysfunction in 5 patients (83%) and one patient had grade 3proctitis requiring colostomy 3 months after RT. Median Dose-Volume Histogram according to radiation techniques V50% bladder V50% rectum Tomotherapy (IMRT) 36.25 Gy 39 Gy Tomotherapy + 3DCRT 41.26 Gy 39.18 GyConclusion: Based on our above-mentioned findings, there is no a significant difference in morbidity in patients treated with Tomotherapy or Tomotherapy with 3DCRT boost.

Quantification of typical antipsychotics in human plasma by ultra-high performance liquid chromatography tandem mass spectrometry for therapeutic drug monitoring.

A selective and sensitive method was developed for the simultaneous quantification of seven typical antipsychotic drugs (cis-chlorprothixene, flupentixol, haloperidol, levomepromazine, pipamperone, promazine and zuclopenthixol) in human plasma. Ultra-high performance liquid chromatography (UHPLC) was used for complete separation of the compounds in less than 4.5min on an Acquity UPLC BEH C18 column (2.1mm×50mm; 1.7μm), with a gradient elution of ammonium formate buffer pH 4.0 and acetonitrile at a flow rate of 400μl/min. Detection was performed on a tandem quadrupole mass spectrometer (MS/MS) equipped with an electrospray ionization interface. A simple protein precipitation procedure with acetonitrile was used for sample preparation. Thanks to the use of stable isotope-labeled internal standards for all analytes, internal standard-normalized matrix effects were in the range of 92-108%. The method was fully validated to cover large concentration ranges of 0.2-90ng/ml for haloperidol, 0.5-90ng/ml for flupentixol, 1-450ng/ml for levomepromazine, promazine and zuclopenthixol and 2-900ng/ml for cis-chlorprothixene and pipamperone. Trueness (89.1-114.8%), repeatability (1.8-9.9%), intermediate precision (1.9-16.3%) and accuracy profiles (<30%) were in accordance with the latest international recommendations. The method was successfully used in our laboratory for routine quantification of more than 500 patient plasma samples for therapeutic drug monitoring. To the best of our knowledge, this is the first UHPLC-MS/MS method for the quantification of the studied drugs with a sample preparation based on protein precipitation.

A Th17- and Th2-skewed Cytokine Profile in Cystic Fibrosis Lungs Represents a Potential Risk Factor for Pseudomonas aeruginosa Infection.

Rationale: Cystic fibrosis (CF) is characterized by progressive pulmonary inflammation that is infection-triggered. Pseudomonas aeruginosa represents a risk factor for deterioration of lung function and reduced life expectancy. Objectives: To assess T-cell cytokine/chemokine production in clinically stable children with CF and evaluate the association between T-cell subtypes and susceptibility for infection with P. aeruginosa. Methods: T-cell cytokine/chemokine profiles were measured in bronchoalveolar lavage fluid (BALF) from children with CF (n = 57; 6.1 ± 5.9 yr) and non-CF control subjects (n = 18; 5.9 ± 4.3 yr). Memory responses to Aspergillus fumigatus and P. aeruginosa were monitored. High-resolution computed tomography-based Helbich score was assessed. In a prospective observational trial the association between BALF cytokine/chemokine profiles and subsequent infection with P. aeruginosa was studied. Measurements and Main Results: Th1- (INF-γ), Th2- (IL-5, IL-13), Th17- (IL-17A), and Th17-related cytokines (IL-1β, IL-6) were significantly up-regulated in airways of patients with CF. IL-17A, IL-13, and IL-5 were significantly higher in BALF of symptomatic as compared with clinically asymptomatic patients with CF. IL-17A and IL-5 correlated with the percentage of neutrophils in BALF (r = 0.41, P < 0.05 and r = 0.46, P < 0.05, respectively). Th17- (IL-17A, IL-6, IL-1β, IL-8) and Th2-associated cytokines and chemokines (IL-5, IL-13, TARC/CCL17), but not IFN-γ levels, significantly correlated with high-resolution computed tomography changes (Helbich score; P < 0.05). P. aeruginosa- and A. fumigatus-specific T cells from patients with CF displayed significantly higher IL-5 and IL-17A mRNA expression. IL-17A and TARC/CCL17 were significantly augmented in patients that developed P. aeruginosa infection within 24 months. Conclusions: We propose a role for Th17 and Th2 T cells in chronic inflammation in lungs of patients with CF. High concentrations of these cytokines/chemokines in CF airways precede infection with P. aeruginosa.

Prevalência e comorbidade de dor e fadiga em mulheres com câncer de mama

O estudo analisou a prevalência e a comorbidade de dor e fadiga em mulheres com câncer de mama. Trata-se de estudo transversal, com amostra, não probabilística de 182 mulheres em tratamento ambulatorial para câncer de mama, entrevistadas no período de julho 2006 a março de 2007. Fadiga, avaliada pela Escala de Fadiga de Piper, foi dividida em duas categorias (escore 0,1-4,9 e >5-10). Dor, avaliada pela escala de 0-10, foi categorizada do mesmo modo que fadiga. Fadiga ocorreu em 94 mulheres (51,6%), sendo >5 em 44 (46,8%) delas. Dor ocorreu em 86 mulheres (47,2%), sendo >5 em 50 (58,1%). Fadiga e dor correlacionaram-se (r=0,38, p=0,003) e a comorbidade fadiga e dor foi de 38,3%. Dor intensa acentuou a fadiga (p=0,089) e fadiga intensa acentuou a dor (p=0,016). Tais dados são inéditos em nosso meio, confirmam a existência de um cluster de sintoma e dos prejuízos decorrentes dessa comorbidade.

Inferring the degree of incipient speciation in secondary contact zones of closely related lineages of Palearctic green toads (Bufo viridis subgroup).

Reproductive isolation between lineages is expected to accumulate with divergence time, but the time taken to speciate may strongly vary between different groups of organisms. In anuran amphibians, laboratory crosses can still produce viable hybrid offspring >20 My after separation, but the speed of speciation in closely related anuran lineages under natural conditions is poorly studied. Palearctic green toads (Bufo viridis subgroup) offer an excellent system to address this question, comprising several lineages that arose at different times and form secondary contact zones. Using mitochondrial and nuclear markers, we previously demonstrated that in Sicily, B. siculus and B. balearicus developed advanced reproductive isolation after Plio-Pleistocene divergence (2.6 My, 3.3-1.9), with limited historic mtDNA introgression, scarce nuclear admixture, but low, if any, current gene flow. Here, we study genetic interactions between younger lineages of early Pleistocene divergence (1.9 My, 2.5-1.3) in northeastern Italy (B. balearicus, B. viridis). We find significantly more, asymmetric nuclear and wider, differential mtDNA introgression. The population structure seems to be molded by geographic distance and barriers (rivers), much more than by intrinsic genomic incompatibilities. These differences of hybridization between zones may be partly explained by differences in the duration of previous isolation. Scattered research on other anurans suggests that wide hybrid zones with strong introgression may develop when secondary contacts occur <2 My after divergence, whereas narrower zones with restricted gene flow form when divergence exceeds 3 My. Our study strengthens support for this rule of thumb by comparing lineages with different divergence times within the same radiation.

Smoked cannabis and doping control: looking for the wrong target analyte?

Introduction: Since 2004, cannabis is prohibited by the World Anti-Doping Agency (WADA) for all sports in competition. In the years since then, about half of all positive doping cases in Switzerland have been related to cannabis consumption. In most cases, the athletes plausibly claim to have consumed cannabis several days or even weeks before competition and only for recreational purposes not related to competition. In doping analysis, the target analyte in urine samples is 11-nor-delta-9-tetrahydrocannabinol- 9-carboxylic acid (THC-COOH), the reporting threshold for laboratories is 15 ng/mL. However, the wide detection window of this long-term THC metabolite in urine does not allow a conclusion concerning the time of consumption or the impact on the physical performance. Aim: The purpose of the present pharmacokinetic study on volunteers was to evaluate target analytes with shorter urinary excretion time. Subsequently, urines from athletes tested positive for cannabis should be reanalyzed including these analytes. Methods: In an one-session clinical trial (approved by IRB, Swissmedic, and Federal Office of Public Health), 12 healthy, male volunteers (age 26 ± 3 yrs, BMI 24 ± 2 kg/m2) with cannabis experience (> once/month) smoked a Cannabis cigarette standardized to 70 mg THC/cigarette (Bedrobinol® 7%, Dutch Office for Medicinal Cannabis) following a paced-puffing procedure. Plasma and urine was collected up to 8 h and 11 days, respectively. Total THC, 11-hydroxy-THC (THC-OH), and THC-COOH were determined after enzymatic hydrolyzation followed by SPE and GC/MS-SIM. The limit of quantitation (LOQ) for all analytes was 0.1 ng/mL. Visual analog scales (VAS) and vital functions were used for monitoring psychological and somatic side-effects at every timepoint of specimen collection (up to 480 min). Results: Eight puffs delivered a mean THC dose of 45 mg. Mean plasma levels of total THC, THC-OH and THC-COOH were measured in the range of 0.1-20.9, 0.1-1.8, and 1.8-7.5 ng/mL, respectively. Peak concentrations were observed at 5, 10, and 90 min. Mean urine levels were measured in the range of 0.1-0.7, 0.10-6.2, and 0.1-13.4 ng/mL, respectively. The detection windows were 2-8, 2-96, and 2-120 h. No or only mild effects were observed, such as dry mouth, sedation, and tachycardia. Besides high to very high THC-COOH levels (0-978 ng/mL), THC (0.1-24 ng/mL) and THC-OH (1-234 ng/mL) were found in 90 and 96% of the cannabis-positive urines from athletes. Conclusion: Instead of or in addition to THC-COOH, the pharmacologically active THC and THC-OH should be the target analytes for doping urine analysis. This would allow the estimation of more recent Cannabis consumption, probably influencing performance during competition. Keywords: cannabis, doping, clinical trial, plasma and urine levels, athlete's samples