Prospective monitoring of cefepime in intensive care unit adult patients.

INTRODUCTION: Cefepime has been associated with a greater risk of mortality than other beta-lactams in patients treated for severe sepsis. Hypotheses for this failure include possible hidden side-effects (for example, neurological) or inappropriate pharmacokinetic/pharmacodynamic (PK/PD) parameters for bacteria with cefepime minimal inhibitory concentrations (MIC) at the highest limits of susceptibility (8 mg/l) or intermediate-resistance (16 mg/l) for pathogens such as Enterobacteriaceae, Pseudomonas aeruginosa and Staphylococcus aureus. We examined these issues in a prospective non-interventional study of 21 consecutive intensive care unit (ICU) adult patients treated with cefepime for nosocomial pneumonia. METHODS: Patients (median age 55.1 years, range 21.8 to 81.2) received intravenous cefepime at 2 g every 12 hours for creatinine clearance (CLCr) >or= 50 ml/min, and 2 g every 24 hours or 36 hours for CLCr < 50 ml/minute. Cefepime plasma concentrations were determined at several time-points before and after drug administration by high-pressure liquid chromatography. PK/PD parameters were computed by standard non-compartmental analysis. RESULTS: Seventeen first-doses and 11 steady states (that is, four to six days after the first dose) were measured. Plasma levels varied greatly between individuals, from two- to three-fold at peak-concentrations to up to 40-fold at trough-concentrations. Nineteen out of 21 (90%) patients had PK/PD parameters comparable to literature values. Twenty-one of 21 (100%) patients had appropriate duration of cefepime concentrations above the MIC (T>MIC >or= 50%) for the pathogens recovered in this study (MIC <or= 4 mg/l), but only 45 to 65% of them had appropriate coverage for potential pathogens with cefepime MIC >or= 8 mg/l. Moreover, 2/21 (10%) patients with renal impairment (CLCr < 30 ml/minute) demonstrated accumulation of cefepime in the plasma (trough concentrations of 20 to 30 mg/l) in spite of dosage adjustment. Both had symptoms compatible with non-convulsive epilepsy (confusion and muscle jerks) that were not attributed to cefepime-toxicity until plasma levels were disclosed to the caretakers and symptoms resolved promptly after drug arrest. CONCLUSIONS: These empirical results confirm the suspected risks of hidden side-effects and inappropriate PK/PD parameters (for pathogens with upper-limit MICs) in a population of ICU adult patients. Moreover, it identifies a safety and efficacy window for cefepime doses of 2 g every 12 hours in patients with a CLCr >or= 50 ml/minute infected by pathogens with cefepime MICs <or= 4 mg/l. On the other hand, prompt monitoring of cefepime plasma levels should be considered in case of lower CLCr or greater MICs.

Left recurrent laryngeal nerve palsy associated with silicosis.

Left recurrent laryngeal nerve palsy usually results from invasion or compression of the nerve caused by diseases localized within the aortopulmonary window. This study reports the case of a 76-yr-old male with vocal cord paralysis due to lymph node involvement by silicosis. This rare entity was identified by video-mediastinoscopy, which revealed a granulomatous and fibrosed recurrent lymph node encasing the nerve. The nerve was dissected and released from scar tissues. Progressive clinical improvement was observed followed by total and durable recovery of the voice after 15 weeks follow-up.

Effect of n-3 fatty acids on cerebral markers and the inflammatory response in sepsis

Introduction ICM+ software encapsulates our 20 years' experience in brain monitoring. It collects data from a variety of bedside monitors and produces time trends of parameters defi ned using confi gurable mathematical formulae. To date it is being used in nearly 40 clinical research centres worldwide. We present its application for continuous monitoring of cerebral autoregulation using near-infrared spectroscopy (NIRS). Methods Data from multiple bedside monitors are processed by ICM+ in real time using a large selection of signal processing methods. These include various time and frequency domain analysis functions as well as fully customisable digital fi lters. The fi nal results are displayed in a variety of ways including simple time trends, as well as time window based histograms, cross histograms, correlations, and so forth. All this allows complex information from bedside monitors to be summarized in a concise fashion and presented to medical and nursing staff in a simple way that alerts them to the development of various pathological processes. Results One hundred and fi fty patients monitored continuously with NIRS, arterial blood pressure (ABP) and intracranial pressure (ICP), where available, were included in this study. There were 40 severely headinjured adult patients, 27 SAH patients (NCCU, Cambridge); 60 patients undergoing cardiopulmonary bypass (John Hopkins Hospital, Baltimore) and 23 patients with sepsis (University Hospital, Basel). In addition, MCA fl ow velocity (FV) was monitored intermittently using transcranial Doppler. FV-derived and ICP-derived pressure reactivity indices (PRx, Mx), as well as NIRS-derived reactivity indices (Cox, Tox, Thx) were calculated and showed signifi cant correlation with each other in all cohorts. Errorbar charts showing reactivity index PRx versus CPP (optimal CPP chart) as well as similar curves for NIRS indices versus CPP and ABP were also demonstrated. Conclusions ICM+ software is proving to be a very useful tool for enhancing the battery of available means for monitoring cerebral vasoreactivity and potentially facilitating autoregulation guided therapy. Complexity of data analysis is also hidden inside loadable profi les, thus allowing investigators to take full advantage of validated protocols including advanced processing formulas.

Early production of IL-4 in susceptible mice infected with Leishmania major rapidly induces IL-12 unresponsiveness.

Previous results have documented a burst of IL-4 mRNA that peaks in draining lymph nodes of susceptible BALB/c mice 16 h after infection with Leishmania major. The importance of this early IL-4 response in subsequent Th2 cell maturation is supported by observations showing that 1) neutralization of IL-4 at the initiation of infection or 2) administration of IL-12, which results in an inhibition of the 16 h IL-4 mRNA burst, inhibits Th2 cell development. However, both treatments are effective in hampering Th2 cell development only if given at a time when IL-4 has been produced for &lt;48 h. At this time after infection, lymph node CD4+ T cells from BALB/c mice no longer respond to IL-12. This IL-12 unresponsiveness is prevented in mice treated with anti-IL-4 Abs at the initiation of infection. Finally, the inhibition of Th2 development in BALB/c mice treated with anti-IL-4 Abs at the onset of infection results from maintenance of IL-12 responsiveness, since it requires IL-12. Together, these results reveal a narrow window of time, between 16 h and &lt;48 h after infection, during which IL-4 produced rapidly in BALB/c mice renders T cells unresponsive to IL-12, allowing their differentiation toward the Th2 phenotype.

Immediate and delayed effects of subchronic Paraquat exposure during an early differentiation stage in 3D-rat brain cell cultures.

Xenobiotic exposure is a risk factor in the etiology of neurodegenerative disease. It was recently hypothesized that restricted exposure during brain development could predispose for a neurodegenerative disease later in life. As neuroinflammation contributes to progressive neurodegeneration, it is suspected that neurodevelopmental xenobiotic exposure could elicit a neuroinflammatory process, which over time may assume a detrimental character. We investigated the neurotoxic effects of paraquat (PQ) in three-dimensional whole rat brain cell cultures, exposed during an early differentiation stage, comparing immediate effects-directly post exposure-with long-term effects, 20 days after interrupted PQ-administration. Adverse effects and neuroinflammatory responses were assessed by measuring changes in gene- and protein-expression as well as by determining cell morphology changes. Differentiating neural cultures were highly susceptible to PQ and showed neuronal damage and strong astrogliosis. After the 20-day washout period, neurons partially recovered, whereas astrogliosis persisted, and was accompanied by microglial activation of a neurodegenerative phenotype. Our data shows that immediate and long-term effects of subchronic PQ-exposure differ. Also, PQ-exposure during this window of extensive neuronal differentiation led to a delayed microglial activation, of a character that could promote further pro-inflammatory signals that enable prolonged inflammation, thereby fueling further neurodegeneration.

Gene therapy regenerates protein expression in cone photoreceptors in Rpe65(R91W/R91W) mice.

Cone photoreceptors mediate visual acuity under daylight conditions, so loss of cone-mediated central vision of course dramatically affects the quality of life of patients suffering from retinal degeneration. Therefore, promoting cone survival has become the goal of many ocular therapies and defining the stage of degeneration that still allows cell rescue is of prime importance. Using the Rpe65(R91W/R91W) mouse, which carries a mutation in the Rpe65 gene leading to progressive photoreceptor degeneration in both patients and mice, we defined stages of retinal degeneration that still allow cone rescue. We evaluated the therapeutic window within which cones can be rescued, using a subretinal injection of a lentiviral vector driving expression of RPE65 in the Rpe65(R91W/R91W) mice. Surprisingly, when applied to adult mice (1 month) this treatment not only stalls or slows cone degeneration but, actually, induces cone-specific protein expression that was previously absent. Before the intervention only part of the cones (40% of the number found in wild-type animals) in the Rpe65(R91W/R91W) mice expressed cone transducin (GNAT2); this fraction increased to 64% after treatment. Correct S-opsin localization is also recovered in the transduced region. In consequence these results represent an extended therapeutic window compared to the Rpe65(-/-) mice, implying that patients suffering from missense mutations might also benefit from a prolonged therapeutic window. Moreover, cones are not only rescued during the course of the degeneration, but can actually recover their initial status, meaning that a proportion of altered cones in chromophore deficiency-related disease can be rehabilitated even though they are severely affected.

First aid in burn injuries with counterintuitive warm water improves outcome

Objective: Cooling is considered a panacea in burn injury. However, burn injuries are characterized by an ischemic zone prone to progression, a phenomenon that can substantially increase morbidity. Cold-induced vasoconstriction potentially aggravates ischemia and promotes progression. Therefore we compared the effect of warm (37°C) and cold (17°C) water on burn progression. Methods: The comb burn model creates 4 rectangular burned surfaces separated by 3 unburned interspaces that become necrotic if untreated. After heating in boiling water the template was applied for 60 seconds on 24 Wistar rats randomized into 3 groups: no treatment (CON); treatment for 20 minutes with cold water (17°C: CW) or warm water (37°C: WW). Burn progression in surface (planimetry) and Departmenth (histology), as well as microcirculatory perfusion (laser Doppler flowmetry) were assessed after 1h, as well as 1, 4, and 7 days. Results: Both CW and WW delayed burn progression without reducing the final burn Departmenth (deep dermis). In contrast, only WW but not CW increased dermal perfusion (81 ± 2% (WW) vs. 62 ± 2% (CW) and 63 ± 1% (CON), p< 0·05) already 1 hour after burn induction. The difference observed after one hour led to a complete flow recovery during the observation period and translated into increased interspace survival, respectively less necrosis with WW(65 ± 4% vs. 81 + 4% (CW) and 91 ± 2% (CON), p< 0·05) after 7 days. Conclusions: Application of warm water significantly improved dermal perfusion, increased interspace survival, and delayed burn progression.However it didn't alter the ultimate burn Departmenth of the actually burned area. Therefore, warm water can create a therapeutic window for targeted nonsurgical treatment of burn progression.

Validation of two echocardiographic indexes to improve the diagnosis of complex coarctations.

OBJECTIVES: Coarctation of the aorta is one of the most common congenital heart defects. Its diagnosis may be difficult in the presence of a patent ductus arteriosus, of other complex defects or of a poor echocardiographic window. We sought to demonstrate that the carotid-subclavian artery index (CSA index) and the isthmus-descending aorta ratio (I/D ratio), two recently described echocardiographic indexes, are effective in detection of isolated and complex aortic coarctations in children younger and older than 3 months of age. The CSA index is the ratio of the distal aortic arch diameter to the distance between the left carotid artery and the left subclavian artery. It is highly suggestive of a coarctation when it is <1.5. The I/D ratio defined as the diameter of the isthmus to the diameter of the descending aorta, suggests an aortic coarctation when it is less than 0.64. METHODS: This is a retrospective cohort study in a tertiary care children's hospital. Review of all echocardiograms in children aged 0-18 years with a diagnosis of coarctation seen at the author's institution between 1996 and 2006. An age- and sex-matched control group without coarctation was constituted. Offline echocardiographic measurements of the aortic arch were performed in order to calculate the CSA index and I/D ratio. RESULTS: Sixty-eight patients were included in the coarctation group, 24 in the control group. Patients with coarctation had a significantly lower CSA index (0.84+/-0.39 vs 2.65+/-0.82, p<0.0001) and I/D ratio (0.58+/-0.18 vs 0.98+/-0.19, p<0.0001) than patients in the control group. Associated cardiac defects and age of the child did not significantly alter the CSA index or the I/D ratio. CONCLUSIONS: A CSA index less than 1.5 is highly suggestive of coarctation independent of age and of the presence of other cardiac defects. I/D ratio alone is less specific than CSA alone at any age and for any associated cardiac lesion. The association of both indexes improves sensitivity and permits diagnosis of coarctation in all patients based solely on a bedside echocardiographic measurement.

Radiolarian biochronology and Pacific origin of Jurassic-Cretaceous oceanic terranes in Costa Rica and Puerto Rico

AbstractAs demonstrated during several recent geological conferences, there is still a large debate concerning the origins of the Mesozoic oceanic remnants on the Caribbean Plate. The geodynamic models describing the Mesozoic history of the Caribbean realm can be divided into two main categories based on the origin of the Caribbean Plate: 1) An in situ origin between the Americas; 2) A Pacific origin and an eastward transport relative to the Americas. The study of the ribbon-bedded radiolarite is a key in determining the origins of associated Mesozoic oceanic terranes and may help to achieve a general agreement regarding the basic principles on the evolution of the Caribbean Plate. The Early Jurassic to early Late Cretaceous Bermeja Complex of Puerto Rico, witch contains serpentinized peridotite, altered basalt, amphibolite, and chert (Mariquita Chert Formation), and the contemporaneous Santa Rosa Accretionary Complex, which crops out in several half-windows along the south shores of the Santa Elena Peninsula in northwestern Costa Rica, are two of these little-known and crucial ophiolitic mélanges. The Manzanillo and Matambú fore-arc Terranes of the Nicoya Peninsula in the northwestern Costa Rica, which contain Late Cretaceous to Early Paleogene radiolarian-bearing siliceous mudstones and cherts associated with arc-derived mafic to intermediate volcaniclastics, bring important information on the history of the western active margin of the Caribbean Plate. A systematic radiolarian study of these three regions is presented herein in three different articles.The radiolarian biochronology of the Mariquita Chert Formation of the Bermeja Complex presented in this work indicate an early Middle Jurassic to early Late Cretaceous (late Bajocian-early Callovian to middle Albian-middle Cenomanian) age for the Mariquita Chert Formation. The illustrated assemblages contain 150 species, of which 3 are new (Pantanellium karinae, Loopus bermejaense, and L. boricus), and belonging to 59 genera. A review of the previous radiolarian published works on this formation and the results of this study suggest that the Bermeja Complex ranges in age from Middle Jurassic to early Late Cretaceous (late Aalenian to middle Cenomanian) and also reveal a possible feature of the complex, which is the youngling of radiolarian cherts from north to south, evoking a polarity of accretion. On the basis of a currently exhaustive inventory of the ribbonbedded radiolaritic facies on the Caribbean Plate, a re-examination of the distribution of Middle Jurassic sediments associated with oceanic crust from the Caribbean realm, and a paleoceanographical argumentation on the water currents, we come to the conclusion that the radiolarite and associated Mesozoic oceanic terranes of the Caribbean Plate are of Pacific origin. The previous argument for a Pacific origin of the Bermeja Complex presented by Montgomery et al. (1994a), based on their radiolarian age and their estimation of the oldest Proto-Caribbean oceanic crust, is nowadays seriously questionable, owing to the recent progresses in radiolarian biostratigraphy and new discoveries on the age of the first oceanic crust spreading between the Americas. Furthermore, we interpret the radiolarian Parvicingulidae-rich assemblages in the low-latitude Caribbean context as potential indicators of upwelling or land nutrients inputs, instead of indicators of paleolatitudes,as firstly stated by Pessagno and Blome (1986). Eventually, a discussion on the origin of the cherts of the Mariquita Formation illustrated by Middle Jurassic to middle Cretaceous geodynamic models of the Pacific and Caribbean realms bring up the possibility that the rocks of the Bermeja Complex are remnants of two different oceans.The Santa Rosa Accretionary Complex contains various oceanic assemblages of alkaline basalt, radiolarite and polymictic breccias. The radiolarian biochronology (19 illustrated assemblages, 232 species belonging to 63 genera) presented in this work indicate an Early Jurassic to early Late Cretaceous (early Pliensbachian to earliest Turonian) age for the sediments associated with oceanic basalts or recovered from blocks in breccias or megabreccias from the Santa Rosa Accretionary Complex. This study brings to light the Early Jurassic age of a sequence of ribbon-bedded radiolarite, which was previously thought to be of Cretaceous age, intruded by alkaline basalts sills. The presence of Early Jurassic large reworked blocks of radiolarite in a polymictic megabreccia, firstly reported by De Wever et al. (1985) is confirmed. Therefore, the alkaline basalt associated with these radiolarites could be of Jurassic age. In the Carrizal tectonic window, Middle Jurassic radiolarian chert blocks and Early Cretaceous brick-red ribbon-bedded radiolarites overlying pillow basalts are interpreted as fragments of a Middle Jurassic oceanic basement accreted to an Early Cretaceous oceanic plate, in an intra-oceanic subduction context. Whereas, knobby radiolarites and black shale at Playa Carrizal are indicative of a shallower middle Cretaceous paleoenvironment. Other younger oceanic remnants documented the rapid approach of the site of sedimentation to a subduction trench during the late Early Cretaceous (AlbianCenomanian), maybe early Late Cretaceous (Turonian).In total, 60 species belonging to 34 genera were present in relatively well-preserved radiolarian faunas from volcaniclastics and associated pelagic and hemipelagic rocks of the Matambú and Manzanillo terranes, ranging in age from Late Cretaceous to Early Paleogene (middle Turonian-Santonian to late Thanetian-Ypresian). This study shows that radiolarians can provide significant biostratigraphic control in the Nicoya Peninsula where very similar lithologies of different ages are present. Two radiolarian samples directly date the Berrugate Formation for the first time (middle Turonian-Santonian and Coniacian-Santonian). These ages allow to determine a volcanic arc activity on the western edge of the future Caribbean Plate at least since the Santonian that could have lasted through the middle Turonian-early Campanian interval by stratigraphic superposition. Moreover on the basis of these radiolarian ages, the Loma Chumico Formation of Albian age, and the Berrugate Formation of middle Turonian-early Maastrichtian age, can now be clearly differentiated. Two samples from the Sabana Grande Formation give a Coniacian-Santonian age and a Coniacian-Campanian age and indicate that there is a stratigraphic gap of ~10 million years between this formation and the underlying Albian Loma Chumico Formation.RésuméComme cela a pu se vérifier à plusieurs reprises lors de conférences géologiques récentes, le débat sur l'origine des terrains océaniques mésozoïques de la Plaque Caraïbes est toujours d'actualité. Les modèles géodynamiques décrivant l'histoire de la région caraïbes peuvent être classés en deux catégories basées sur l'origine de la Plaque Caraïbes : 1) Une origine in situ entre les Amériques ; 2) Une origine Pacifique et un transport vers l'est, par rapport aux Amériques. L'étude des radiolarites rubanées est capitale pour la détermination de l'origine des terrains océaniques allochtones du Mésozoïque et peut être utile pour parvenir à un compromis général concernant les principes basiques de l'évolution de la Plaque Caraïbes. Le complexe de Bermeja à Porto Rico qui est constitué de péridotites serpentinisées, de basaltes altérés, d'amphibolites et de cherts (Formation des Cherts de Mariquita), et le Complexe d'Accrétion de Santa Rosa qui affleure dans plusieurs demi-fenêtres tectoniques au sud de la Péninsule de Santa Elena au nord-ouest du Costa Rica sont deux de ces mélanges ophiolitiques peu décrits et déterminants. Les terrains de fore-arc de Manzanillo et de Matambu dans la Péninsule de Nicoya au nord-ouest du Costa Rica qui sont composés de calcaires siliceux et de cherts riches en radiolaires associés à du matériel volcanique d'arc mafique à intermédiaire, apportent d'importantes informations sur l'histoire de la marge active occidentale de la Plaque Caraïbe. Une étude systématique des radiolaires de ces trois régions est présentée dans ce travail sous forme de trois articles.La biochronologie des radiolaires de la Formation des Cherts de Mariquita du Complexe d'Accrétion de Santa Rosa présentée dans ce travail indique un âge Jurassique Moyen inférieur à Crétacé Supérieur inférieur (Bajocien supérieur-Callovien inférieur à Albien moyen-Cénomanien moyen) pour la Formation des Cherts de Mariquita. Les assemblages illustrés contiennent 150 espèces, parmis lesquelles 3 sont nouvelles (Pantanellium karinae, Loopus bermejaense et L. boricus), et appartenant à 59 genres différents. Une révision des travaux publiés précédemment sur les radiolaires de cette formation, ainsi que les résultats de cette étude suggèrent que le Complexe de Bermeja a un âge allant du Jurassique moyen au Crétacé Supérieur inférieur (Aalénien supérieur à Cénomanien moyen) et révèle aussi une caractéristique éventuelle du complexe qui est le rajeunissement des radiolarites du nord au sud, évoquant une polarité d'accrétion. Sur la base d'un inventaire actuellement exhaustif du facies radiolaritique rubané sur la Plaque Caraïbes, d'un nouvel examen de la distribution globale des sédiments du Jurassique Moyen associés à de la croûte océanique et d'une argumentation paléocéanographique sur les courants, nous arrivons à la conclusion que les radiolarites et les unités tectoniques océaniques du Mésozoïque associées de la Plaque Caraïbes sont d'origine pacifique. L'argument antérieur pour une origine pacifique du Complexe de Bermeja présenté par Montgomery et al. (1994a), basé sur leur âge à radiolaire et leur estimation de l'âge de la plus vieille croûte océanique des Proto-Caraïbes, est sérieusement remis en question aujourd'hui, en raison des progrès récents de la biostratigraphie des radiolaires et des nouvelles découvertes concernant l'âge du début de l'océanisation entre les Amériques. En outre, dans le contexte de basses latitudes des Caraïbes, nous interprétons les assemblages à radiolaires riches en Parvicingulidae comme étant des indicateurs potentiels d'apports en nutriments des zones d'uppwelling ou des terres, plutôt que des indicateurs de paléolatitudes, comme exposer pour la première fois par Pessagno et Blome (1986). Finalement, une discussion sur l'origine des cherts de la Formation de Mariquita illustrée par des modèles géodynamiques du Jurassique Moyen au Crétacé moyen des régions pacifique et caraïbes, fait poindre la possibilité que les roches du Complexe de Bermeja proviennent de deux océans différents.Le Complexe d'Accrétion de Santa Rosa contient plusieurs assemblages océaniques différents de basaltes alcalins, radiolarites et brèches polymictes. La biochronologie des radiolaires (19 assemblages illustrés, 232 espèces appartenant à 63 genres) présentée dans ce second travail indique un âge Jurassique Inférieur à Crétacé Supérieur inférieur (Pliensbachien inférieur à Turonien initial) pour les sédiments associés aux basaltes océaniques ou provenant de blocs dans des brèches ou des mégabrèches du Complexe d'Accrétion de Santa Rosa. Cette étude met en évidence l'âge Jurassique Inférieur d'une séquence de radiolarites rubanées entrecoupée de sills de basaltes alcalins, dont l'âge estimé était précédemment le Crétacé.La présence de blocs plurimétriques de radiolarites d'âge Jurassique Inférieur remaniés dans une mégabrèche polymicte, dont la présence avait été signalée par De Wever et al. (1985), est confirmée. Par conséquent, les basaltes alcalins associés à ces radiolarites pourraient aussi être d'âge Jurassique. Dans la fenêtre tectonique de Carrizal, des blocs de radiolarites d'âge Jurassique Moyen et des radiolarites du Crétacé Inférieur recouvrant des basaltes en coussins sont interprétés comme des fragments d'une croûte océanique d'âge Jurassique Moyen accrétés à une plaque océanique d'âge Crétacé Inférieur, dans un contexte de subduction intra-océanique. Alors que dans la même zone, les radiolarites « noueuses » et les argiles noires associées sont interprétées comme des indicateurs d'un milieu peu profond au Crétacé. D'autres fragments océaniques plus jeunes documentent une approche rapide du lieu de sédimentation vers une fosse de subduction pendant le Crétacé Inférieur supérieur (Albien-Cénomanien), peut-être Crétacé Supérieur (Turonien).Au total, 60 espèces appartenant à 34 genres ont été déterminées à partir de faunes à radiolaires relativement bien préservées, extraites de roches volcanoclastiques et pélagiques à hémipélagiques associées, provenant des terrains de Matambu et Manzanillo et ayant des âges compris entre le Crétacé Supérieur et le Paléogène Inférieur (Turonien moyen-Santonien à Thanétien supérieur-Yprésien). Cette étude montre que les radiolaires peuvent fournir un contrôle stratigraphique significatif dans la Péninsule de Nicoya, où des lithologies similaires, mais d'âges différents sont présentes. Deux échantillons à radiolaires permettent de dater la Formation de Berrugate pour la première fois (Turonien moyen-Santonien et Coniacien-Santonien). Ces âges permettent d'établir une activité volcanique d'arc le long de la marge occidentale de la futur Plaque Caraïbes au moins depuis le Santonien et qui pourrait avoir durée jusqu'au Turonien moyen-Campanien inférieur. De plus, sur la base de ces âges à radiolaires, la Formation de Loma Chumico d'âge Albien, et la Formation de Berrugate d'âge Turonien moyen-Maastrichtien inférieur, peuvent maintenant être différenciées. Deux échantillons de la Formation de Sabana Grande donnent des âges Coniacien-Santonien et Coniacien-Campanien et indiquent qu'il existe une lacune stratigraphique d'environ 10 millions d'années entre cette formation et la Formation de Loma Chumico sous-jacente d'âge Albien.

Detection of HIV drug resistance during antiretroviral treatment and clinical progression in a large European cohort study.

OBJECTIVE(S): To investigate the relationship between detection of HIV drug resistance by 2 years from starting antiretroviral therapy and the subsequent risk of progression to AIDS and death. DESIGN: Virological failure was defined as experiencing two consecutive viral loads of more than 400 copies/ml in the time window between 0.5 and 2 years from starting antiretroviral therapy (baseline). Patients were grouped according to evidence of virological failure and whether there was detection of the International AIDS Society resistance mutations to one, two or three drug classes in the time window. METHODS: Standard survival analysis using Kaplan-Meier curves and Cox proportional hazards regression model with time-fixed covariates defined at baseline was employed. RESULTS: We studied 8229 patients in EuroSIDA who started antiretroviral therapy and who had at least 2 years of clinical follow-up. We observed 829 AIDS events and 571 deaths during 38,814 person-years of follow-up resulting in an overall incidence of new AIDS and death of 3.6 per 100 person-years of follow-up [95% confidence interval (CI):3.4-3.8]. By 96 months from baseline, the proportion of patients with a new AIDS diagnosis or death was 20.3% (95% CI:17.7-22.9) in patients with no evidence of virological failure and 53% (39.3-66.7) in those with virological failure and mutations to three drug classes (P = 0.0001). An almost two-fold difference in risk was confirmed in the multivariable analysis (adjusted relative hazard = 1.8, 95% CI:1.2-2.7, P = 0.005). CONCLUSION: Although this study shows an association between the detection of resistance at failure and risk of clinical progression, further research is needed to clarify whether resistance reflects poor adherence or directly increases the risk of clinical events via exhaustion of drug options.

Temporal changes in mosquito abundance (Culex pipiens), avian malaria prevalence and lineage composition

Background: Knowledge on the temporal dynamics of host/vector/parasite interactions is a pre-requisite to further address relevant questions in the fields of epidemiology and evolutionary ecology of infectious diseases. In studies of avian malaria, the natural history of Plasmodium parasites with their natural mosquito vectors, however, is mostly unknown. Methods: Using artificial water containers placed in the field, we monitored the relative abundance of parous females of Culex pipiens mosquitoes during two years (2010-2011), in a population in western Switzerland. Additionally, we used molecular tools to examine changes in avian malaria prevalence and Plasmodium lineage composition in female C. pipiens caught throughout one field season (April-August) in 2011. Results: C. pipiens relative abundance varied both between years and months, and was associated with temperature fluctuations. Total Plasmodium prevalence was high and increased from spring to summer months (13.1-20.3%). The Plasmodium community was composed of seven different lineages including P. relictum (SGS1, GRW11 and PADOM02 lineages), P. vaughani (lineage SYAT05) and other Plasmodium spp. (AFTRU5, PADOM1, COLL1). The most prevalent lineages, P. vaughani (lineage SYAT05) and P. relictum (lineage SGS1), were consistently found between years, although they had antagonistic dominance patterns during the season survey. Conclusions: Our results suggest that the time window of analysis is critical in evaluating changes in the community of avian malaria lineages infecting mosquitoes. The potential determinants of the observed changes as well as their implications for future prospects on avian malaria are discussed.

Neurologie [Therapeutic advances in neurology].

The neurology field has been greatly improved in 2008. The therapeutic window of intravenous thrombolysis for acute ischemic stoke is extended to 4 h 30. New studies show that the clinical progression of Parkinson's disease might be slowed by some medication. Deep brain stimulation may be beneficial early in the course of the disease. Tysabri and Fingolimod in multiple sclerosis are discussed. The pharmacopoeia for epilepsy is in constant development with new products recently released in Switzerland. CGRP receptor antagonists are about to be launched as a promising acute migraine treatment. The pharmacological approach in amyotrophic lateral sclerosis patients might be improved according to research results.

Immune response to HIV.

PURPOSE OF REVIEW: Major advances have been made in the delineation of HIV-specific immune response and in the mechanisms of virus escape. The kinetics of the immunological and virological events occurring during primary HIV infection indicate that the establishment of the latent HIV reservoir, the major obstacle to HIV eradication likely occurs during the very early stages of primary infection, that is, the 'eclipse phase', prior to the development of the HIV-specific immune response which has limited efficacy in the control of the early events of infection. Therefore, the window of opportunity to develop effective interventions either to clear HIV during primary infection or to prevent rebound of HIV in patients successfully treated who stop antiretroviral therapy is very narrow. RECENT FINDINGS: Genetic factors most strongly associated with nonprogressive infection are human leukocyte antigen (HLA) class I alleles and particularly HLA-B5701. CD4 and CD8 T-cell responses with polyfunctional profile are associated with nonprogressive infection. Broader neutralizing antibodies are detected 3-4 years after infection, generated only in 20% of individuals but show no efficacy in the control of HIV replication. SUMMARY: In the present review, we shall discuss the different components of the HIV-specific immune response elicited by the infection, the kinetics of these responses during primary infection and the changes following transition to the chronic phase of infection, and the functional profile of 'effective' versus 'noneffective' HIV-specific immune responses.

Comparison of fat suppression strategies in 3D spiral coronary magnetic resonance angiography.

PURPOSE: In the present study, the impact of the two different fat suppression techniques was investigated for free breathing 3D spiral coronary magnetic resonance angiography (MRA). As the coronary arteries are embedded in epicardial fat and are adjacent to myocardial tissue, magnetization preparation such as T(2)-preparation and fat suppression is essential for coronary discrimination. MATERIALS AND METHODS: Fat-signal suppression in three-dimensional (3D) thin- slab coronary MRA based on a spiral k-space data acquisition can either be achieved by signal pre-saturation using a spectrally selective inversion recovery pre-pulse or by spectral-spatial excitation. In the present study, the performance of the two different approaches was studied in healthy subjects. RESULTS: No significant objective or subjective difference was found between the two fat suppression approaches. CONCLUSION: Spectral pre-saturation seems preferred for coronary MRA applications due to the ease of implementation and the shorter cardiac acquisition window.

Continuous determination of optimal cerebral perfusion pressure in traumatic brain injury.

OBJECTIVES: We have sought to develop an automated methodology for the continuous updating of optimal cerebral perfusion pressure (CPPopt) for patients after severe traumatic head injury, using continuous monitoring of cerebrovascular pressure reactivity. We then validated the CPPopt algorithm by determining the association between outcome and the deviation of actual CPP from CPPopt. DESIGN: Retrospective analysis of prospectively collected data. SETTING: Neurosciences critical care unit of a university hospital. PATIENTS: A total of 327 traumatic head-injury patients admitted between 2003 and 2009 with continuous monitoring of arterial blood pressure and intracranial pressure. MEASUREMENTS AND MAIN RESULTS: Arterial blood pressure, intracranial pressure, and CPP were continuously recorded, and pressure reactivity index was calculated online. Outcome was assessed at 6 months. An automated curve fitting method was applied to determine CPP at the minimum value for pressure reactivity index (CPPopt). A time trend of CPPopt was created using a moving 4-hr window, updated every minute. Identification of CPPopt was, on average, feasible during 55% of the whole recording period. Patient outcome correlated with the continuously updated difference between median CPP and CPPopt (chi-square=45, p<.001; outcome dichotomized into fatal and nonfatal). Mortality was associated with relative "hypoperfusion" (CPP<CPPopt), severe disability with "hyperperfusion" (CPP>CPPopt), and favorable outcome was associated with smaller deviations of CPP from the individualized CPPopt. While deviations from global target CPP values of 60 mm Hg and 70 mm Hg were also related to outcome, these relationships were less robust. CONCLUSIONS: Real-time CPPopt could be identified during the recording time of majority of the patients. Patients with a median CPP close to CPPopt were more likely to have a favorable outcome than those in whom median CPP was widely different from CPPopt. Deviations from individualized CPPopt were more predictive of outcome than deviations from a common target CPP. CPP management to optimize cerebrovascular pressure reactivity should be the subject of future clinical trial in severe traumatic head-injury patients.