Barriers in psychiatrists' mind to active smoking cessation promotion in severe psychiatric disorders.

BACKGROUND: Promoting the cessation of smoking in mental healthcare is a priority of international health organizations as it is the most cost-effective intervention in psychiatry. AIM: To explore the representations of psychiatrists on their role in active smoking cessation prevention in severe psychiatric disorders. METHODS: Psychiatrists and residents in psychiatry were recruited at a national level by professional mailings. RESULTS: One thousand four hundred and sixty participants were included in the study, and only 46% reported actively promoting smoking cessation. In multivariate analyses, participants aged<35years were more likely to promote cessation of tobacco smoking, as well as the two thirds who believe that psychiatry is a systemic discipline with complex interactions between brain, body and mind. Almost two thirds of those promoting tobacco cessation reported lacking time to combine psychiatric and physical examination during one session. The psychiatrists who reported not promoting tobacco smoking cessation also reported never dealing with physical health in case of the absence of a general practitioner and thinking that physical examination may have a negative impact on the therapeutic relationship. Almost all (96%) reported promoting the need for a general practitioner for their patients. We found no significant difference between the public and private sectors (P>0.05). INTERPRETATION: Young psychiatrists are more prone than their elders to promote smoking cessation but report lacking time to include it in their daily practice. Promotion of tobacco smoking cessation should be included in the components for quality evaluation for mental health services and specific sessions dedicated to this intervention.

Early-life factors associated with increased risk of disability pension in the national real-world schizophrenia FACE-SZ cohort study.

Among severe psychiatric disorders, schizophrenia has one of the highest impacts on professional and personal functioning with important indirect costs including disability pension allowance for the patients with the more severe forms of schizophrenia. To explore early-life factors associated with disability pension in schizophrenia. 916 patients were consecutively recruited at a national level in 10 expert centers and received a comprehensive standardized evaluation. Their disability pension status and early-life variables were reported from medical records and validated scales. Eight factors were explored: age, male sex, parental history of severe mental illness, childhood trauma exposure, education level, childhood ADHD, early age at schizophrenia onset and duration of untreated psychosis. 739 (80.7%) participants received a disability pension. In the multivariate model, early age at schizophrenia onset and low education level were associated with disability pension independently of age and sex while no significant association was found for parent history of severe mental illness, childhood trauma, childhood ADHD or duration of untreated psychosis. Low education level and early age at schizophrenia onset seem the best predictors of increased risk of disability pension in schizophrenia.

Non-invasive measurement of renal perfusion and oxygen metabolism to predict postoperative acute kidney injury in neonates and infants after cardiopulmonary bypass surgery.

BACKGROUND: The pathophysiology of acute kidney injury (AKI) after cardiopulmonary bypass surgery for congenital heart disease is not completely understood. The aim of this study was to carry out a prospective analysis of the diagnostic value of non-invasive monitoring of renal oxygenation and microcirculation by combining laser Doppler flowmetry and tissue spectrometry. METHODS: In 50 neonates and infants who underwent repair (n = 31) or neonatal palliation (n = 19) of congenital heart disease with cardiopulmonary bypass, renal oxygenation, and microcirculatory flow, the approximate renal metabolic rate of oxygen and Doppler-based renal resistive index were determined after surgery. Correlations between these parameters and the occurrence of AKI according to the Pediatric Risk, Injury, Failure, Loss, End Stage Renal Disease criteria were investigated. RESULTS: Acute kidney injury occurred in 45% of patients after repair and in 32% after palliation. Renal oxygenation was significantly lower and the approximate renal metabolic rate of oxygen significantly higher in patients with AKI (P < 0.05). The microcirculatory flow was significantly higher in patients with AKI after neonatal palliation (P < 0.05), whereas renal resistive index was significantly higher in patients with AKI after repair (P < 0.05). The sensitivity of renal oxygenation, metabolic rate of oxygen, microcirculation, and resistive index in predicting AKI was 78-80, 73-78, 64-83, and 71-74%, respectively, with a specificity of 63-65, 54-75, 64-78, and 46-74% (area under the curve: 0.73-0.75, 0.68-0.83, 0.52-0.68, and 0.60-0.75), respectively. CONCLUSIONS: Monitoring of renal oxygen metabolism allows early prediction of AKI in infants after cardiac surgery. In contrast, renal resistive index does not allow prediction of AKI after neonatal palliation with aortopulmonary shunt establishment.

Infrainguinal bypass for peripheral arterial occlusive disease: when arms save legs.

OBJECTIVES: Determine if arm veins are good conduits for infrainguinal revascularisation and should be used when good quality saphenous vein is not available. DESIGN: Retrospective study. MATERIALS AND METHODS: We evaluated a consecutive series of infrainguinal bypass (IB) using arm vein conduits from March 2001 to December 2006.We selected arm vein by preoperative ultrasound mapping to identify suitable veins. We measured vein diameter and assessed vein wall quality. We followed patients with systematic duplex imaging at 1 week, 1, 3, 6 and 12 months, and annually thereafter. We treated significative stenoses found during the follow-up. RESULTS: We performed 56 infrainguinal revascularisation using arm vein conduits in 56 patients. Primary patency rates at 1, 2 and 3 years were 65%, 51% and 47%. Primary assisted patencies at 1, 2 and 3 years were 96%, 96% and 82%. Secondary patency rates at 1, 2 and 3 years were 92%, 88% and 88%. The three-year limb salvage rate was 88%. CONCLUSIONS: We conclude that infrainguinal bypass using arm vein for conduits gives good patency rates, if selected by a preoperative US mapping to use the best autogenous conduit available.

Mussel-mimetic tissue adhesive for fetal membrane repair: a standardized ex vivo evaluation using elastomeric membranes.

OBJECTIVE: Iatrogenic preterm premature rupture of membranes (iPPROM), the main complication of invasive interventions in the prenatal period, seriously limits the benefit of diagnostic or surgical prenatal procedures. This study aimed to evaluate preventive plugging of punctured fetal membranes in an ex vivo situation using a new mussel-mimetic tissue adhesive (mussel glue) to inhibit leakage. METHODS: A novel biomechanical test device that tests the closure of injured membranes under near-physiological conditions was used. Mussel glue, a poly(ethylene glycol)-based hydrogel, was used to seal membrane defects of up to 3 mm in mechanically well-defined elastomeric membranes with three different degrees of stiffness. RESULTS: Elastomeric test membranes were successfully employed for testing mussel glue under well-defined conditions. Mussel glue plugs were distended by up to 94%, which translated to an improved sealing efficiency on elastomeric membranes with high stiffness. For the stiffest membrane tested, a critical burst pressure of 48 mbar (36 mmHg) was accomplished in this ex vivo setting. CONCLUSIONS: Mussel glue appears to efficiently seal membrane defects under well-standardized ex vivo conditions. As repaired membranes resist pressures measured in amniotic cavities, mussel glue might represent a novel sealing method for iatrogenic membrane defects.

Essential requirement for c-kit and common gamma chain in thymocyte development cannot be overruled by enforced expression of Bcl-2.

The thymus in mice lacking both the receptor tyrosine kinase c-kit and the common cytokine receptor gamma chain (gamma(c)) is alymphoid because these receptors provide essential signals at the earliest stages of thymocyte development. The signals transduced by these receptors potentially regulate proliferation, survival, or differentiation, but the contribution of each receptor to distinct intracellular signaling cascades is only poorly defined. Here, we have examined whether enforced expression of Bcl-2 can rescue thymocyte development in c-kit and gamma(c) single or double mutant mice. A bcl-2 transgene (E(mu)-bcl-2-25; expressed in the T cell lineage) was introduced into (a) c-kit and gamma(c) wild-type (c-kit+gamma(c)+bcl+), (b) c-kit-deficient (c-kit(-)gamma(c)+bcl+), (c) gamma(c)-deficient (c-kit+gamma(c)-bcl+), or (d) c-kit and gamma(c) double-deficient mice (c-kit-gamma(c)-bcl+). The bcl-2 transgene was functionally active in wild-type and c-kit or gamma(c) single mutants, as it promoted survival of ex vivo isolated thymocytes, including pro-T cells. In vivo, however, transgenic Bcl-2 did not release T cell precursors from their phenotypic block and failed to increase progenitor or total thymocyte cellularity in c-kit or gamma(c) single or double mutants. These data argue strongly against a role for Bcl-2 as a key mediator in signaling pathways linked to cytokine and growth factor receptors driving early thymocyte development.

Thrombomodulin improves early outcomes after intraportal islet transplantation.

Primary islet nonfunction due to an instant blood mediated inflammatory reaction (IBMIR) leads to an increase in donor islet mass required to achieve euglycemia. In the presence of thrombin, thrombomodulin generates activated protein C (APC), which limits procoagulant and proinflammatory responses. In this study, we postulated that liposomal formulations of thrombomodulin (lipo-TM), due to its propensity for preferential uptake in the liver, would enhance intraportal engraftment of allogeneic islets by inhibiting the IBMIR. Diabetic C57BL/6J mice underwent intraportal transplantation with B10.BR murine islets. In the absence of treatment, conversion to euglycemia was observed among 29% of mice receiving 250 allo-islets. In contrast, a single infusion of lipo-TM led to euglycemia in 83% of recipients (p = 0.0019). Fibrin deposition (p < 0.0001), neutrophil infiltration (p < 0.0001), as well as expression TNF-alpha and IL-beta (p < 0.03) were significantly reduced. Significantly, thrombotic responses mediated by human islets in contact with human blood were also reduced by this approach. Lipo-TM improves the engraftment of allogeneic islets through a reduction in local thrombotic and inflammatory processes. As an enzyme-based pharmacotherapeutic, this strategy offers the potential for local generation of APC at the site of islet infusion, during the initial period of elevated thrombin production.

Clinical pharmacology of 1,4-butanediol and gamma-hydroxybutyrate after oral 1,4-butanediol administration to healthy volunteers.

1,4-Butanediol (BD) is converted to gamma-hydroxybutyrate (GHB) after ingestion, and is associated with cases of dependence, coma, and death. The pharmacology of BD after oral ingestion has not been described in humans. Eight healthy volunteers (five men) were administered 25 mg/kg BD in a single oral dose after an overnight fast in a double-blinded, placebo-controlled, crossover study. Vital signs were monitored, and serial blood samples collected over 24 h for gas chromatography-mass spectrometry analysis of BD and GHB levels. Subjective mood and symptoms responses were assessed by visual analog scale. All subjects completed the study without significant adverse effects. BD was quickly absorbed and cleared, with time to maximal plasma concentration of 24+/-12 min, and elimination half-life (T(1/2)) of 39.3+/-11 min. BD was extensively converted to GHB, with a mean maximum GHB concentration of 45.6+/-19.7 mg/l reached 39.4+/-11.2 min after BD ingestion. GHB T(1/2) averaged 32.3+/-6.6 min. Some subjects exhibited slow oral clearance of BD, which tended to correlate with a variant haplotype of the alcohol dehydrogenase gene ADH-IB G143A. Mean CL/F was 151.5+/-176.5 ml/min kg for four subjects with variant haplotype versus 598.8+/-446.6 ml/min kg for four wild-type subjects (P=0.061). Subjects reported feeling less awake and alert, less able to concentrate, and more lightheaded in the first 90 min after BD ingestion. Pulse oximetry readings were lower 45 min after BD dosing with a mean oxygen saturation of 98.5% with BD versus 99.6% with placebo (P=0.031). Transient increases in mean systolic and diastolic blood pressure were observed, but other vital signs remained unchanged. BD was extensively converted to GHB after oral administration, but significant inter-individual variability in the rate of metabolism, possibly related to variants in ADH-IB, was observed. At the modest dose studied, significant clinical effects were not seen.

Contrast-induced nephrotoxicity: clinical landscape.

Over 80 million doses of iodinated intravascular contrast media (CM) were administered in the most recent tabulations of 2003, corresponding to approximately 8 million liters, making it one of the highest volume medical drugs used compared to any other pharmaceutical. The evolution of CM has focused on minimizing adverse events by eliminating ionicity, increasing hydrophilicity, lowering osmolality and increasing the number of iodine atoms per molecule. Contrast media are classified into three general categories based on their osmolality relative to blood: high osmolar (5 times or greater than blood), low osmolar (2-3 times blood) and iso-osmolar (the same as blood). All imaging modalities that employ CM, especially computerized tomography (CT), have shown rapid growth. In the last two decades, the use of CT scanning has increased by 800%. From 1979 to 2002, the number of cardiac catheterization procedures in the USA increased by 390% and in Europe from 1992 to 1999 by 112%. There is a general consensus that renal insufficiency and diabetes are major risk factors for contrast-induced nephropathy (CIN), particularly when co-existing. The US Renal Data System documents a 'relentless' increase in kidney failure, projecting a 90% increase by 2010. Diabetes affects 194 million people worldwide and the number is anticipated to increase by 75% by 2025. The unavoidable conclusion is that patient exposure and prevalence of risk factors for CIN will continue to increase.

Clinical results of autologous infrainguinal revascularization using grafts originating distal to the femoral bifurcation in patients with mild inflow disease.

AIM: Chronic critical limb ischemia (CLI) often requires venous bypass grafting to distal arterial segments. However, graft patency is influenced by the length and quality of the graft and occasionally patients may have limited suitable veins. We investigated short distal bypass grafting from the superficial femoral or popliteal artery to the infrapopliteal, ankle or foot arteries, despite angiographic alterations of inflow vessels, providing that invasive pressure measurement at the site of the planned proximal anastomosis revealed an inflow-brachial pressure difference of

[New treatments in vascular diseases]. / Nouveautés en chirurgie vasculaire.

In superficial venous insufficiency, surgery remains the treatment of choice. Endovenous therapies are a minimal invasive alternative, whose long-term results are not demonstrated yet. In the treatment of abdominal aortic aneurysm, endovascular repair (EVAR) and laparoscopic approach are comparatively studied with open repair, to define their precise indications. In occlusive arterial disease, endovascular treatment offers inferior results in term of durability and patency, however with a decrease in morbidity and mortality.

[Management of critical limb ischemia]. / Prise en charge de l'ischémie critique des membres inférieurs.

Critical limb ischemia (CLI) is the leading cause of major leg amputation. Diabetes, smoking and end stage renal disease are the main risk factors for CLI. Despite their reduced survival rate, most CLI patients should be treated by surgical or endovascular arterial reconstruction, since amputation rate with conservative treatment alone is as high as 95% at 1 year in surviving patients with tissue loss, and can be reduced to 25% with successful reconstruction. When arterial reconstruction is impossible or fails, spinal cord stimulation also allows to avoid major amputation in up to 75% of precisely selected patients. Timely management and multidisciplinary approach are advised to reduce the risk of major amputation.

Cytotoxicity of radiocontrast agents on polarized renal epithelial cell monolayers.

OBJECTIVE: Radiocontrast-induced nephropathy is a clinically important complication of coronary angiography. The cellular mechanisms of radiocontrast-induced renal dysfunction are not clear. Since tubular transport functions depend on the polarity of renal epithelial cells, we investigated the effects of radiocontrast agents on polarized tubular cells in vitro. METHODS: We studied the effects of iso-iodine concentrations (37 and 74 mg iodine/ml) of an ionic (diatrizoate) and a non-ionic (iopamidol) monomeric radiocontrast agent and of hyperosmolal mannitol control solutions on filter-grown renal epithelial cell (MDCK, LLCPK) monolayers in vitro. The cytotoxicity was assayed by measurement of cell viability, transepithelial resistance, inulin permeability and (polarized) cellular enzyme release. The polarized MDCK cell phenotype was assessed by transmission electron microscopy and indirect immunofluorescence microscopy using monoclonal antibodies against specific apical (gp135) and basal (gp60, uvomorulin) MDCK surface markers. RESULTS: The radiocontrast agents reduced cell viability to a greater extent than hyperosmolal mannitol solutions in both cell lines; diatrizoate was more toxic than iopamidol. LLCPK cells were more susceptible to radiocontrast cytotoxicity than MDCK cells. This cytotoxicity was associated with an alteration of MDCK cell polarity as assessed by the redistribution of surface marker proteins. CONCLUSIONS: Diatrizoate is more toxic than iopamidol, which is partly related to its higher osmolality. The cytotoxicity of radiocontrast agents induces a redistribution of polarized membrane proteins which could contribute to the pathophysiology of radiocontrast-induced nephropathy.

Polarized expression of heterologous membrane proteins transfected in a human endothelial-derived cell line.

The generation and maintenance of cell polarity in endothelial cells is poorly understood, partly because of a lack of a permanent endothelial in vitro model system. Here we evaluated the spontaneously immortalized human endothelial-derived cell line ECV304 as an in vitro model system for the study of the polarized expression of heterologous membrane proteins. Several stable ECV304 clones were generated by calcium phosphate transfection/G418 selection with cDNAs encoding membrane proteins of known cell surface distribution in the epithelial Madin Darby canine kidney (MDCK) cell line: influenza hemagglutinin and uvomorulin/E-cadherin were used as markers for the apical, respectively lateral cell membrane, the human lymphocyte surface marker CD7 served as an example of a circumferentially distributed membrane protein. Analysis of the transfected ECV304 clones using conventional and confocal immunofluorescence microscopy and immunoelectron microscopy revealed the same membrane distribution of the heterologous proteins in ECV304 cells as in MDCK cells. This polarized expression of heterologous membrane proteins in the endothelial-derived ECV304 cell line indicates efficient protein sorting/membrane trafficking mechanisms. The apical, lateral and basal cell membrane domains could be distinguished in ECV304 cells by confocal immunofluorescence microscopy. The permanent endothelial-derived ECV304 cell line may be a useful in vitro model system for the study of endothelial cell polarity.

Effect of gamma-hydroxybutyrate on the reactivity of pial arteries before and after ischemia.

The effect of gamma-hydroxybutyrate (GHB) on the reactivity of pial arteries to local metabolic factors was tested in chloralose-anesthetized cats before or after a period of transient ischemia induced by air embolism. The vascular reactions were determined during the perivascular microapplication of artificial CSFs with increasing concentrations of adenosine (10(-11)-10(-3) M), H+ (pH 5.1-7.6), or K+ (0-10 mM). During nonischemic conditions the pial arterial reactivity to adenosine and H+, but not to K+, was significantly increased by GHB (250 mg/kg i.v.) when compared with the control reactivity. After cerebral ischemia the reactivity to adenosine was abolished with and without the administration of GHB prior to air embolism. The reactivity to K+ was partly preserved but not increased by GHB when compared with previous results without GHB. In contrast GHB improved the postischemic reactivity to perivascular H+ that had been found to be abolished in previous experiments without GHB. The perivascular microapplication of GHB showed no influence of GHB on the vascular diameter. An important finding of the present study is the demonstration of an increase in cerebrovascular reactivity, which may give scope for therapeutic improvement of the regulation of CBF in pathophysiological conditions.

Effect of the muscarinic agonist carbachol on pial arteries in vivo after endothelial damage by air embolism.

Reactions of pial arteries to the muscarinic agonist carbachol were tested in vivo in chloralose anesthetized cats before and after endothelial damage. Moderate endothelial damage was induced by arterial air embolism and verified by electron microscopy for the vessels tested. The experiments had three phases; First, the normal reactivity of pial arteries to carbachol (10(-7) to 10(-5) M) was tested using the microapplication technique, then, after air embolism, the reactivity was reinvestigated at the same vessel. Finally, pial arteries were taken out for scanning electron microscopy. The results show carbachol (10(-6) and 10(-5) M) induced significant dilations under control conditions, also after repetition at the same vessel. After air embolism, the reactions to carbachol were abolished. Morphologic data revealed that whereas control pial arteries showed intact endothelium, the embolized vessels revealed various degrees of endothelial alterations. All showed flattening of endothelial nuclei, to a greater or lesser degree, and in many cases, the endothelium had a wrinkled appearance; several arteries showed severe degradation of the intercellular junctions. It is concluded that (a) carbachol-induced muscarinic vasodilatation of pial arteries in vivo can be abolished after a morphologically verified endothelial lesion--thus confirming in vitro studies in larger arteries and (b) disturbed vascular function does not require rubbing of the endothelium, but occurs already with moderate endothelial damage.

Effect of gamma-hydroxybutyrate on local and global glucose metabolism in the anesthetized cat brain.

This study addresses three topics in the chloralose-anesthetized cat: (a) distribution of local CMRglc: values ranging from 5 to 109 mumols/100 g/min were found in 37 brain structures and the mean CMRglc over all examined structures was 30.6 mumols/100 g/min; (b) effect of gamma-hydroxybutyrate (GHB, 250 mg/kg i.v.) on local CMRglc, which was significantly (p less than 0.05) depressed in 16 of 37 structures, most prominently in the auditory system, and the mean CMRglc over all structures after GHB was 20.4 mumols/100 g/min; and (c) global values of CMRglc, CMRO2, and CBF before and after GHB: in these experiments, a modified Kety-Schmidt technique was employed measuring saturation/desaturation of inhaled H2 and concentrations of glucose and oxygen in aortic and sagittal sinus blood. CBF and CMRO2 were not altered after GHB, whereas CMRglc was significantly decreased from 35.7 to 28.8 mumols/100 g/min. The values of CMRglc obtained with both techniques (autoradiography and the Kety-Schmidt technique) are concordant, especially when considering the different sampling areas of both methods. The main finding of the present study is a reduction in cerebral glucose consumption after GHB, irrespective of the technique of measurement. This reduction occurs at an unchanged CMRO2 and CBF.

Pure motor hemiplegia due to pyramidal infarction.

A 77-year-old man suddenly developed left hemiplegia without sensory impairment, visual or speech difficulties, loss of consciousness, or ataxia. He died one month later of pulmonary embolism, and a cystic infarction in the right medullary pyramid was the only lesion in the corticospinal system.

Pure motor hemiplegia due to cerebral cortical infarction.

Although pure motor hemiplegia has not been reported after cerebral cortical infarction, occasional exceptions may occur. We provide three such examples. Necropsy study confirmed the site of lesion in one patient, and laboratory results (EEG and computerized axial tomography) suggested cortical involvement in the other two patients.

Antigen-receptor junctional diversity in growth-factor-receptor mutant mice.

Precursor lymphocytes undergo expansion prior to immunoglobulin (Ig) or T cell receptor (TCR) rearrangements. Development of thymocytes, but not B cells, is entirely blocked in mice lacking both the receptor-tyrosine-kinase c-kit and the common cytokine receptor gamma chain (gamma c). In c-kit-gamma c-mice, TCR beta rearrangements are limited to mono- or oligoclonal DJ junctions. Here, effects of lack of c-kit or gamma c, or both, on the junctional diversity of TCR gamma and delta, and Ig VH(DH)JH loci were analyzed. All rearrangements were present in wildtype and mutant mice. However, sequencing of the junctions revealed monoclonal TCR gamma (V gamma 2 J gamma 1) and TCR delta (V delta 1(D delta)J delta 2) joints in c-kit-gamma c-, but not c-kit+ gamma c- or wildtype thymocytes. In contrast to TCR beta, gamma and delta loci, VHDHJH junctions were more diverse in c-kit-gamma c-mice. Thus, the two analyzed growth factor receptors mediate signaling pathways required for progenitor expansion and generation of junctional diversity at TCR loci, but have less influence on the diversity of IgH junctions.