Deep hypothermia and rewarming alters glutamate levels and glycogen content in cultured astrocytes.

BACKGROUND: Deep hypothermia has been associated with an increased incidence of postoperative neurologic dysfunction after cardiac surgery in children. Recent studies suggest an excitotoxic mechanism involving overstimulation of glutamate receptors. Extracellular glutamate uptake occurs primarily by astrocytes. Astrocytes also store glycogen, which may be used to sustain the energy-consuming glutamate uptake. Extracellular glutamate and glycogen content were studied during temperature changes mimicking cardiopulmonary bypass in vivo. METHODS: Primary cultures of cerebral cortical astrocytes were used in a specially designed incubator allowing continuous changes of temperature and ambient gas concentrations. The sequence of events was as follows: normothermia, rapid cooling (2.8 degrees C/min) followed by 60 min of deep hypothermia (15 degrees C), followed by rewarming (3.0 degrees C/min) and subsequent 5 h of mild hyperthermia (38.5 degrees C). Two different conditions of oxygenation were studied: (1) normoxia (25% O2, 70% N2, 5% CO2); or (2) hyperoxia (95% O2, 5% CO2). The extracellular glutamate concentrations and intracellular glycogen levels were measured at nine time points. RESULTS: One hundred sixty-two cultures were studied in four independent experiments. The extracellular concentration of glutamate in the normoxic group increased significantly from 35+/-10 nM/mg protein at baseline up to 100+/-15 nM/mg protein at the end of 5 h of mild hyperthermia (P < 0.05). In contrast, extracellular glutamate levels did not vary from control in the hyperoxic group. Glycogen levels decreased significantly from 260+/-85 nM/mg protein at baseline to < 25+/-5 nM/mg protein at the end of 5 h in the normoxic group (P < 0.05) but returned to control levels after rewarming in the hyperoxic group. No morphologic changes were observed in either group. CONCLUSION: The extracellular concentration of glutamate increases, whereas the intracellular glycogen content decreases when astrocytes are exposed to a sequence of deep hypothermia and rewarming. This effect of hypothermia is prevented when astrocytes are exposed to hyperoxic conditions.

Tonotopic mapping of human auditory cortex.

Since the early days of functional magnetic resonance imaging (fMRI), retinotopic mapping emerged as a powerful and widely-accepted tool, allowing the identification of individual visual cortical fields and furthering the study of visual processing. In contrast, tonotopic mapping in auditory cortex proved more challenging primarily because of the smaller size of auditory cortical fields. The spatial resolution capabilities of fMRI have since advanced, and recent reports from our labs and several others demonstrate the reliability of tonotopic mapping in human auditory cortex. Here we review the wide range of stimulus procedures and analysis methods that have been used to successfully map tonotopy in human auditory cortex. We point out that recent studies provide a remarkably consistent view of human tonotopic organisation, although the interpretation of the maps continues to vary. In particular, there remains controversy over the exact orientation of the primary gradients with respect to Heschl's gyrus, which leads to different predictions about the location of human A1, R, and surrounding fields. We discuss the development of this debate and argue that literature is converging towards an interpretation that core fields A1 and R fold across the rostral and caudal banks of Heschl's gyrus, with tonotopic gradients laid out in a distinctive V-shaped manner. This suggests an organisation that is largely homologous with non-human primates. This article is part of a Special Issue entitled Human Auditory Neuroimaging.

Modified Blalock Taussig shunt: a not-so-simple palliative procedure.

OBJECTIVES: Thirty-two consecutive isolated modified Blalock Taussig (BT) shunts performed in infancy since 2004 were reviewed and analysed to identify the risk factors for shunt intervention and mortality. METHODS: Sternotomy was the only approach used. Median age and weight were 10.5 (range 1-74) days and 2.9 (1.9-4.4) kg, respectively. Shunt palliation was performed for biventricular hearts (Tetralogy of Fallot/double outlet right ventricle/transposition of great arteries_ventricular septal defect_pulmonary stenosis/pulmonary atresia_ventricular septal defect/others) in 21, and univentricular hearts in 11, patients. Hypoplastic left heart syndrome patients were excluded. Two procedures required cardiopulmonary bypass. Median shunt size was 3.5 (3-4) mm and median shunt size/kg body weight was 1.2 (0.9-1.7) mm/kg. Reduction in shunt size was necessary in 5 of 32 (16%) patients. RESULTS: Three of 32 (9%) patients died after 3 (1-15) days due to cardiorespiratory decompensation. Lower body weight (P = 0.04) and bigger shunt size/kg of body weight (P = 0.004) were significant risk factors for mortality. Acute shunt thrombosis was observed in 3 of 32 (9%), none leading to death. Need for cardiac decongestive therapy was associated with univentricular hearts (P < 0.001), bigger shunt size (P = 0.054) and longer hospital stay (P = 0.005). Twenty-eight patients have undergone a successful shunt takedown at a median age of 5.5 (0.5-11.9) months, without late mortality. CONCLUSIONS: Palliation with a modified BT shunt continues to be indicated despite increased thrust on primary corrective surgery. Though seemingly simple, it is associated with significant morbidity and mortality. Effective over-shunting and acute shunt thrombosis are the lingering problems of shunt therapy.

Evolution of the Pelagonian carbonate platform complex and the adjacent oceanic realm in response to plate tectonic forcing (Late Triassic and Jurassic), Evvoia, Greece

The Late Triassic and Jurassic platform and the oceanic complexes in Evvoia, Greece, share a complementary plate-tectonic evolution. Shallow marine carbonate deposition responded to changing rates of subsidence and uplift, whilst the adjacent ocean underwent spreading, and then convergence, collision and finally obduction over the platform complex. Late Triassic ocean spreading correlated with platform subsidence and the formation of a long-persisting peritidal passive-margin platform. Incipient drowning occurred from the Sinemurian to the late Middle Jurassic. This subsidence correlated with intra-oceanic subduction and plate convergence that led to supra-subduction calc-alkaline magmatism and the formation of a primitive volcanic arc. During the Middle Jurassic, plate collision caused arc uplift above the carbonate compensation depth (CCD) in the oceanic realm, and related thrust-faulting, on the platform, led to sub-aerial exposures. Patch-reefs developed there during the Late Oxfordian to Kimmeridgian. Advanced oceanic nappe-loading caused platform drowning below the CCD during the Tithonian, which is documented by intercalations of reefal turbidites with non-carbonate radiolarites. Radiolarites and bypass-turbidites, consisting of siliciclastic greywacke, terminate the platform succession beneath the emplaced oceanic nappe during late Tithonian to Valanginian time.

The auditory pathway in cat corpus callosum.

The cortical auditory fields of the two hemispheres are interconnected via the corpus callosum. We have investigated the topographical arrangement of auditory callosal axons in the cat. Following circumscribed biocytin injections in the primary (AI), secondary (AII), anterior (AAF) and posterior (PAF) auditory fields, labelled axons have been found in the posterior two-thirds of the corpus callosum. Callosal axons labelled by small individual cortical injections did not form a tight bundle at the callosal midsagittal plane but spread over as much as one-third of the corpus callosum. Axons originating from different auditory fields were roughly topographically ordered, reflecting to some extent the rostro-caudal position of the field of origin. Axons from AAF crossed on average more rostrally than axons from AI; the latter crossed more rostrally than axons from PAF and AII. Callosal axons originating in a discrete part of the cortex travelled first in a relatively tight bundle to the telo-diencephalic junction and then dispersed progressively. In conclusion, the cat corpus callosum does not contain a sector reserved for auditory axons, nor a strictly topographically ordered auditory pathway. This observation is of relevance to neuropsychological and neuropathological observations in man.

Blood profile during and after hemoglobin substitute administration.

The in vivo effects of Diaspirin Crosslinked Hemoglobin (DCLHb, Baxter Healthcare Corp.) on hematology and biochemistry are unknown. This study includes 6 calves (71.2+/-1.3 kg). In each animal a total of 2 litres of blood was exchanged for the same amount of hydroxylethyl starch (Haes, Fresenius) (n=3) or DCLHb (n=3), which is equivalent to 28cc/kg of blood substitute, over a period of 5 hours. The animals were allowed to survive 7 days. Blood samples were taken hourly during the perfusion protocol, at postoperative day (POD) 1, 2 and 7. ANOVA test was used for repeated measurements. Blood cell profiles were similar in both groups. Peak methemoglobinemia was 4.2% in the DCLHb group. Osmolarity was significantly higher in the DCLHb group with the greatest difference at POD 1 and 2. Postmortem analysis of the major organs did not show any sign of hemoglobin deposit in the DCLHb group. In the given setup DCLHb can be administered in a large quantity with good hematological tolerance and without any deposits in major organs. A prolonged plasma expander effect was observed.

Interventions motivationnelles: psychose et cannabis [Motivational interventions: psychosis and cannabis]

Cannabis use by people suffering from schizophrenia increase relapse rate and reduce adhesion to treatment. Motivational interventions could reduce cannabis misuse. The motivational interviewing principles and techniques are presented in a concrete way as well as the required adaptations to bypass cognitive deficits associated with schizophrenia.

Procedure for human saphenous veins ex vivo perfusion and external reinforcement.

The mainstay of contemporary therapies for extensive occlusive arterial disease is venous bypass graft. However, its durability is threatened by intimal hyperplasia (IH) that eventually leads to vessel occlusion and graft failure. Mechanical forces, particularly low shear stress and high wall tension, are thought to initiate and to sustain these cellular and molecular changes, but their exact contribution remains to be unraveled. To selectively evaluate the role of pressure and shear stress on the biology of IH, an ex vivo perfusion system (EVPS) was created to perfuse segments of human saphenous veins under arterial regimen (high shear stress and high pressure). Further technical innovations allowed the simultaneous perfusion of two segments from the same vein, one reinforced with an external mesh. Veins were harvested using a no-touch technique and immediately transferred to the laboratory for assembly in the EVPS. One segment of the freshly isolated vein was not perfused (control, day 0). The two others segments were perfused for up to 7 days, one being completely sheltered with a 4 mm (diameter) external mesh. The pressure, flow velocity, and pulse rate were continuously monitored and adjusted to mimic the hemodynamic conditions prevailing in the femoral artery. Upon completion of the perfusion, veins were dismounted and used for histological and molecular analysis. Under ex vivo conditions, high pressure perfusion (arterial, mean = 100 mm Hg) is sufficient to generate IH and remodeling of human veins. These alterations are reduced in the presence of an external polyester mesh.

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.

Influence of socioeconomic factors on delays, management and outcome amongst patients with acute myocardial infarction undergoing primary percutaneous coronary intervention.

The outcome after primary percutaneous coronary intervention (pPCI) for ST-elevation myocardial infarction (STEMI) is strongly affected by time delays. In this study, we sought to identify the impact of specific socioeconomic factors on time delays, subsequent STEMI management and outcomes in STEMI patients undergoing pPCI, who came from a well-defined region of the French part of Switzerland. A total of 402 consecutive patients undergoing pPCI for STEMI in a large tertiary hospital were retrospectively studied. Symptom-to-first-medical-contact time was analysed for the following socioeconomic factors: level of education, origin and marital status. Main exclusion criteria were: time delay beyond 12 hours, previous treatment with fibrinolytic agents or patients immediately referred for coronary artery bypass graft surgery. Therefore, 222 patients were finally included. At 1 year, there was no difference in mortality between the different socioeconomic groups. Furthermore, there was no difference in management characteristics between them. Symptom-to-first-medical-contact time was significantly longer for patients with a low level of education, Swiss citizens and unmarried patients, with median differences of 23 minutes, 18 minutes and 13 minutes, respectively (p <0.05). Nevertheless, no difference was found regarding in-hospital management and clinical outcome. This study demonstrates that symptom-to-first-medical-contact time is longer amongst people with a lower educational level, Swiss citizens and unmarried people. Because of the low mortality rate in general, these differences in delays did not affect clinical outcomes. Still, tertiary prevention measures should particularly focus on these vulnerable populations.

Bridge to life: the Lifebridge B2T extracorporeal life support system in an in vitro trial.

Extracorporeal life support systems (ECLS) have become common in cardiothoracic surgery, but are still "Terra Incognita" in other medical fields due to the fact that perfusion units are normally bound to cardiothoracic centres. The Lifebridge B2T is an ECLS that is meant to be used as an easy and fast-track extracorporeal cardiac support to provide short-term perfusion for the transport of a patient to a specialized centre. With the Lifebridge B2T it is now possible to provide extracorporeal bypass for patients in hospitals without a perfusion unit. The Lifebridge B2T was tested on three calves to analyze the handling, performance and security of this system. The Lifebridge B2T safely can be used clinically and can provide full extracorporeal support for patients in cardiac or pulmonary failure. Flows up to 3.9 +/- 0.2l/min were reached, with an inflow pressure of -103 +/- 13mmHg, using a 21Fr. BioMedicus (Medtronic, Minneapolis, MN, USA) venous cannula. The "Plug and Play" philosophy, with semi-automatic priming, integrated check-list, a long battery time of over two hours and instinctively designed user interface, makes this device very interesting for units with high-risk interventions, such as catheterisation labs. If a system is necessary in an emergency unit, the Lifebridge can provide a high security level, even in centres not acquainted with cardiopulmonary bypass.

Laparoscopic surgery for coeliac artery compression syndrome: current management and technical aspects.

Objectives: The study aims to assess the feasibility and midterm outcome of trans-peritoneal laparoscopy for coeliac artery compression syndrome (CACS).Design: Retrospective chart review involving four European vascular surgery departments and two surgical teams.Materials and methods: charts for patients who underwent laparoscopy for symptomatic CACS between December 2003 and November 2009 were reviewed. Preoperative computed tomography (CT) angiography and postoperative duplex scan and/or CT angiography were performed.Results: Eleven consecutive patients (nine women) with a median age of 52 years (interquartile range: 42.5-59 years) underwent trans-peritoneal laparoscopy for CACS. All patients had a history of postprandial abdominal pain; weight loss exceeded 10% of the body mass in eight cases. Preoperative CT angiography revealed coeliac trunk stenosis >70% in all cases. One patient had additional aortitis and inferior mesenteric artery occlusion, while another patient presented with an occluded superior mesenteric artery. Two conversions occurred (one difficult dissection and one aorto-hepatic bypass needed for incomplete release of CACS). The median blood loss was 195 ml (range: 50-900 ml) and median operative time was 80 min (interquartile range: 65-162.5 years). Symptoms improved immediately in 10/11 patients (no residual stenosis) while one remained unchanged despite a residual stenosis treated by a percutaneous angioplasty. Symptoms reappeared in one patient due to coeliac axis occlusion. The mean follow-up period was 35 +/- 23 months (range: 12-78 months).Conclusion: Our study demonstrates that trans-peritoneal laparoscopy for treating median arcuate ligament syndrome is safe and feasible. Additional patients and a longer follow-up are needed for long-term assessment of this laparoscopic technique. (C) 2011 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

Foot skin blood flow following infrainguinal revascularization for critical lower limb ischemia.

INTRODUCTION: The aim of this study was to assess the blood flow in the feet before and after lower limb revascularization using laser Doppler imaging (LDI). METHODS: Ten patients with critical lower limb ischemia were prospectively enrolled from June to October 2004. All patients underwent successful unilateral surgical interventions including above-knee bypass, distal bypass and endarterectomy. Skin blood flow (SBF) over the plantar surface of both forefeet and heels was measured by LDI 24h before and 10 days after revascularization, expressed in perfusion units (PU), and reported as mean+/-SD. RESULTS: Measurements in the forefoot and heel were similar. Before revascularization mean SBF was significantly lower in the ischemic foot (130+/-71 PU) compared to the contralateral foot (212+/-68 PU), p<0.05. After revascularization a significant increase of the SBF in the forefoot (from 135+/-67 to 202+/-86 PU, p=0.001) and hindfoot (from 148+/-58 to 203+/-83, p=0.001) was observed on the treatment side. However, a large decrease of the SBF was seen in forefoot and hindfoot on the untreated side (from 250+/-123 PU to 176+/-83 and from 208+/-116 to 133+/-40, p=0.001, respectively). CONCLUSION: This study confirms the benefits of revascularization in patients with nonhealing foot lesions due to critical limb ischemia. A significant increase of the SBF was observed on the treatment side. However, an unexpected decrease was observed on the untreated side.

Benefits of endoscopic vein harvesting.

The purpose of this study was to evaluate and compare the benefits of endoscopic saphenous vein harvesting (EVH) with the traditional incision technique (TIT) for coronary artery bypass grafting (CABG) in respect to the technical procedure and clinical outcome. In a prospective nonrandomized, case-matched study the greater saphenous vein was harvested for CABG in 22 patients using the endoscopic technique and in 18 patients with the traditional method. Comparisons were made for the operating time, length of incision and vein harvested, graft quality, postoperative complications, and pain assessment. Patient demographics were well matched. EVH required smaller incisions than did the TIT (10.5 +/- 6.6 vs. 31.2 +/- 7.8 cm, respectively; p < 0.0001). Harvest time and vein quality were comparable in the two groups. Total vein operating time was shorter following the endoscopic technique (60 +/- 24 vs. 100 +/- 35 minutes, respectively; p < 0.0001). EVH had fewer complications (NS), and postoperative pain was significantly less (p = 0.0034). The major advantages of endoscopic vein harvesting are a significant reduction of postoperative pain and strikingly better cosmetic results. Wound complications seem to be less frequent.

Changes in volume, surface estimate, three-dimensional shape and total number of neurons of the human primary visual cortex from midgestation until old age.

Macroscopic features such as volume, surface estimate, thickness and caudorostral length of the human primary visual cortex (Brodman's area 17) of 46 human brains between midgestation and 93 years were studied by means of camera lucida drawings from serial frontal sections. Individual values were best fitted by a logistic function from midgestation to adulthood and by a regression line between adulthood and old age. Allometric functions were calculated to study developmental relationships between all the features. The three-dimensional shape of area 17 was also reconstructed from the serial sections in 15 cases and correlated with the sequence of morphological events. The sulcal pattern of area 17 begins to develop around 21 weeks of gestation but remains rather simple until birth, while it becomes more convoluted, particularly in the caudal part, during the postnatal period. Until birth, a large increase in cortical thickness (about 83% of its mean adult value) and caudorostral length (69%) produces a moderate increase in cortical volume (31%) and surface estimate (40%) of area 17. After birth, the cortical volume and surface undergo their maximum growth rate, in spite of a rather small increase in cortical thickness and caudorostral length. This is due to the development of the pattern of gyrification within and around the calcarine fissure. All macroscopic features have reached the mean adult value by the end of the first postnatal year. With aging, the only features to undergo significant regression are the cortical surface estimate and the caudorostral length. The total number of neurons in area 17 shows great interindividual variability at all ages. No decrease in the postnatal period or in aging could be demonstrated.