The effect of the N-methyl-D-aspartate receptor antagonist dextromethorphan on perioperative brain injury in children undergoing cardiac surgery with cardiopulmonary bypass: results of a pilot study.

Experimental evidence indicates a role of the N-methyl-D-aspartate receptor in the pathogenesis of brain injury occurring during cardiac surgery with cardiopulmonary bypass (CPB). Dextromethorphan is a noncompetitive antagonist of this receptor with a favorable safety profile. Thirteen children age 3-36 months undergoing cardiac surgery with expected CPB of 60 minutes or more were randomly assigned to treatment with dextromethorphan (36-38 mg/kg/day) or placebo administered by naso-gastric tube. Dextromethorphan was absorbed well and reached putative therapeutic levels in blood and cerebrospinal fluid. Adverse effects were not observed. Mild hemiparesis developed after operation in one child of each group, and severe encephalopathy in one of the placebo group. Sharp waves were recorded in postoperative continuous electroencephalography in all placebo (n = 7) but only in 2/6 dextromethorphan treated children (p = 0.02). Pre- and postoperative cranial magnetic resonance imaging (MRI) revealed less pronounced ventricular enlargement in the dextromethorphan group (not significant). An increase of periventricular white matter lesions was visible in two placebo-treated children only. No elevations of cerebrospinal fluid enzymes were observed in either group. Although children with dextromethorphan showed less abnormalities in electroencephalography and MRI, dissimilarities of the treatment groups by chance diminished conclusions to possible protective effects of dextromethorphan at this time.

Sex difference and the role of leptin in the association between high-sensitivity C-reactive protein and adiposity in two different populations.

Elevated high-sensitivity C-reactive protein (hs-CRP) concentration is associated with an increased risk of cardiovascular disease but this association seems to be largely mediated via conventional cardiovascular risk factors. In particular, the association between hs-CRP and obesity has been extensively demonstrated and correlations are stronger in women than men. We used fractional polynomials-a method that allows flexible modeling of non linear relations-to investigate the dose/response mathematical relationship between hs-CRP and several indicators of adiposity in Caucasians (Switzerland) and Africans (Seychelles) surveyed in two population-based studies. This relationship was non-linear exhibiting a steeper slope for low levels of hs-CRP and a higher level in women. The observed sex difference in the relationship between hs-CRP and adiposity almost disappeared upon adjustment for leptin, suggesting that these sex differences might be partially mediated, by leptin. All these relationship were similar in Caucasians and Africans. This is the first report on a non-linear relation, stratified by gender, between hs-CRP and adiposity.

Sex biased spatial strategies relying on the integration of multimodal cues in a rat model of schizophrenia: impairment in predicting future context?

Male and female Wistar rats were treated postnatally (PND 5-16) with BSO (l-buthionine-(S,R)-sulfoximine) to provide a rat model of schizophrenia based on transient glutathione deficit. In the watermaze, BSO-treated male rats perform very efficiently in conditions where a diversity of visual information is continuously available during orientation trajectories [1]. Our hypothesis is that the treatment impairs proactive strategies anticipating future sensory information, while supporting a tight visual adjustment on memorized snapshots, i.e. compensatory reactive strategies. To test this hypothesis, BSO rats' performance was assessed in two conditions using an 8-arm radial maze task: a semi-transparent maze with no available view on the environment from maze centre [2], and a modified 2-parallel maze known to induce a neglect of the parallel pair in normal rats [3-5]. Male rats, but not females, were affected by the BSO treatment. In the semi-transparent maze, BSO males expressed a higher error rate, especially in completing the maze after an interruption. In the 2-parallel maze shape, BSO males, unlike controls, expressed no neglect of the parallel arms. This second result was in accord with a reactive strategy using accurate memory images of the contextual environment instead of a representation based on integrating relative directions. These results are coherent with a treatment-induced deficit in proactive decision strategy based on multimodal cognitive maps, compensated by accurate reactive adaptations based on the memory of local configurations. Control females did not express an efficient proactive capacity in the semi-transparent maze, neither did they show the significant neglect of the parallel arms, which might have masked the BSO induced effect. Their reduced sensitivity to BSO treatment is discussed with regard to a sex biased basal cognitive style.

Outcomes of disconnective surgery in intractable pediatric hemispheric and subhemispheric epilepsy.

Objectives: To study the outcome of disconnective epilepsy surgery for intractable hemispheric and sub-hemispheric pediatric epilepsy. Methods: A retrospective analysis of the epilepsy surgery database was done in all children (age <18 years) who underwent a peri-insular hemispherotomy (PIH) or a peri-insular posterior quadrantectomy (PIPQ) from April 2000 to March 2011. All patients underwent a detailed pre surgical evaluation. Seizure outcome was assessed by the Engel's classification and cognitive skills by appropriate measures of intelligence that were repeated annually. Results: There were 34 patients in all. Epilepsy was due to Rasmussen's encephalitis (RE), Infantile hemiplegia seizure syndrome (IHSS), Hemimegalencephaly (HM), Sturge Weber syndrome (SWS) and due to post encephalitic sequelae (PES). Twenty seven (79.4%) patients underwent PIH and seven (20.6%) underwent PIPQ. The mean follow up was 30.5 months. At the last follow up, 31 (91.1%) were seizure free. The age of seizure onset and etiology of the disease causing epilepsy were predictors of a Class I seizure outcome. Conclusions: There is an excellent seizure outcome following disconnective epilepsy surgery for intractable hemispheric and subhemispheric pediatric epilepsy. An older age of seizure onset, RE, SWS and PES were good predictors of a Class I seizure outcome.

Sumoylated PPARalpha mediates sex-specific gene repression and protects the liver from estrogen-induced toxicity in mice.

As most metabolic studies are conducted in male animals, understanding the sex specificity of the underlying molecular pathways has been broadly neglected; for example, whether PPARs elicit sex-dependent responses has not been determined. Here we show that in mice, PPARalpha has broad female-dependent repressive actions on hepatic genes involved in steroid metabolism and immunity. In male mice, this effect was reproduced by the administration of a synthetic PPARalpha ligand. Using the steroid oxysterol 7alpha-hydroxylase cytochrome P4507b1 (Cyp7b1) gene as a model, we elucidated the molecular mechanism of this sex-specific PPARalpha-dependent repression. Initial sumoylation of the ligand-binding domain of PPARalpha triggered the interaction of PPARalpha with GA-binding protein alpha (GABPalpha) bound to the target Cyp7b1 promoter. Histone deacetylase and DNA and histone methylases were then recruited, and the adjacent Sp1-binding site and histones were methylated. These events resulted in loss of Sp1-stimulated expression and thus downregulation of Cyp7b1. Physiologically, this repression conferred on female mice protection against estrogen-induced intrahepatic cholestasis, the most common hepatic disease during pregnancy, suggesting a therapeutic target for prevention of this disease.

A novel device for reducing hemolysis provoked by cardiotomy suction during open heart cardiopulmonary bypass surgery: a randomized prospective study.

Since the inception of cardiopulmonary bypass (CPB), little progress has been made concerning the design of cardiotomy suction (CS). Because this is a major source of hemolysis, we decided to test a novel device (Smartsuction [SS]) specifically aimed at minimizing hemolysis during CPB in a clinical setting. Block randomization was carried out on a treated group (SS, n=28) and a control group (CTRL, n=26). Biochemical parameters were taken pre-, peri-, and post CPB and were compared between the two groups using the Student's t-test with statistical significance when P<0.05. No significant differences in patient demographics were observed between the two groups. Lactate dehydrogenase (LDH) and plasma free hemoglobin (PFH) pre-CPB were comparable for the CTRL and SS groups, respectively. LDH peri-CPB was 275+/-100 U/L versus 207+/-83 U/L for the CTRL and SS groups, respectively (P<0.05). PFH was 486+/-204 mg/L versus 351+/-176 mg/L for the CTRL and SS groups, respectively (P<0.05). LDH post CPB was 354+/-116 U/L versus 275+/-89 U/L for the CTRL and SS groups, respectively (P<0.05). PFH was 549+/-271 mg/L versus 460+/-254 mg/L for the CTRL and SS groups, respectively (P<0.05). Preoperative hematocrit (Hct) of 43+/-5% (CTRL) versus 37+/-5% (SS), and hemoglobin (Hb) of 141+/-16 g/L (CTRL) versus 122+/-17 g/L (SS) were significantly lower in the SS group. However, when normalized (N), the SS was capable of conserving Hct, Hb, and erythrocyte count perioperatively. Erythrocytes (N) were 59+/-5% (CTRL) versus 67+/-9% (SS); Hct (N) was 59+/-6% (CTRL) versus 68+/-9% (SS), and Hb (N) was 61+/-6% (CTRL) versus 70+/-10% (SS) (all P<0.05). This novel SS device evokes significantly lowered blood PFH and LDH values peri- and post CPB compared with the CTRL blood using a CS system. The SS may be a valuable alternative compared to traditional CS techniques.

Gas emission during laparoscopic colorectal surgery using a bipolar vessel sealing device: A pilot study on four patients.

BACKGROUND: Dissection during laparoscopic surgery produces smoke containing potentially toxic substances. The aim of the present study was to analyze smoke samples produced during laparoscopic colon surgery using a bipolar vessel sealing device (LigaSuretrade mark). METHODS: Four consecutive patients undergoing left-sided colectomy were enrolled in this pilot study. Smoke was produced by the use of LigaSuretrade mark. Samples (5,5l) were evacuated from the pneumoperitoneum in a closed system into a reservoir. Analysis was performed with CO2-laser-based photoacoustic spectroscopy and confirmed by a Fourier-transform infrared spectrum. The detected spectra were compared to the available spectra of known toxins. RESULTS: Samples from four laparoscopic sigmoid resections were analyzed. No relevant differences were noted regarding patient and operation characteristics. The gas samples were stable over time proven by congruent control measurements as late as 24 h after sampling. The absorption spectra differed considerably between the patients. One broad absorption line at 100 ppm indicating H2O and several unknown molecules were detected. With a sensitivity of alpha min ca 10-5 cm-1 no known toxic substances like phenol or indole were identified. CONCLUSION: The use of a vessel sealing device during laparoscopic surgery does not produce known toxic substances in relevant quantity. Further studies are needed to identify unknown molecules and to analyze gas emission under various conditions.

IRM opératoire et chirurgie de l'épilepsie [Intraoperative MRI and epilepsy surgery].

Intraoperative imaging, in particular intraoperative MRI, is a developing area in neurosurgery and its role is currently being evaluated. Its role in epilepsy surgery has not been defined yet and its use has been limited. In our experience with a compact and mobile low-field intraoperative MRI system, a few epilepsy surgeries have been performed using this technique. As the integration of imaging and functional data plays an important role in the planning of epilepsy surgery, intraoperative verification of the surgical result may be highly valuable. Therefore, teams that have access to intraoperative MRI should be encouraged to use this technique prospectively to evaluate its current relevance in epilepsy surgery.

Clinical review: practical recommendations on the management of perioperative heart failure in cardiac surgery.

Acute cardiovascular dysfunction occurs perioperatively in more than 20% of cardiosurgical patients, yet current acute heart failure (HF) classification is not applicable to this period. Indicators of major perioperative risk include unstable coronary syndromes, decompensated HF, significant arrhythmias and valvular disease. Clinical risk factors include history of heart disease, compensated HF, cerebrovascular disease, presence of diabetes mellitus, renal insufficiency and high-risk surgery. EuroSCORE reliably predicts perioperative cardiovascular alteration in patients aged less than 80 years. Preoperative B-type natriuretic peptide level is an additional risk stratification factor. Aggressively preserving heart function during cardiosurgery is a major goal. Volatile anaesthetics and levosimendan seem to be promising cardioprotective agents, but large trials are still needed to assess the best cardioprotective agent(s) and optimal protocol(s). The aim of monitoring is early detection and assessment of mechanisms of perioperative cardiovascular dysfunction. Ideally, volume status should be assessed by 'dynamic' measurement of haemodynamic parameters. Assess heart function first by echocardiography, then using a pulmonary artery catheter (especially in right heart dysfunction). If volaemia and heart function are in the normal range, cardiovascular dysfunction is very likely related to vascular dysfunction. In treating myocardial dysfunction, consider the following options, either alone or in combination: low-to-moderate doses of dobutamine and epinephrine, milrinone or levosimendan. In vasoplegia-induced hypotension, use norepinephrine to maintain adequate perfusion pressure. Exclude hypovolaemia in patients under vasopressors, through repeated volume assessments. Optimal perioperative use of inotropes/vasopressors in cardiosurgery remains controversial, and further large multinational studies are needed. Cardiosurgical perioperative classification of cardiac impairment should be based on time of occurrence (precardiotomy, failure to wean, postcardiotomy) and haemodynamic severity of the patient's condition (crash and burn, deteriorating fast, stable but inotrope dependent). In heart dysfunction with suspected coronary hypoperfusion, an intra-aortic balloon pump is highly recommended. A ventricular assist device should be considered before end organ dysfunction becomes evident. Extra-corporeal membrane oxygenation is an elegant solution as a bridge to recovery and/or decision making. This paper offers practical recommendations for management of perioperative HF in cardiosurgery based on European experts' opinion. It also emphasizes the need for large surveys and studies to assess the optimal way to manage perioperative HF in cardiac surgery.

Identification and characterization of sex-linked proteins of Schistosoma mansoni

The proteins of adults worms (male and female) of two isolates (BH and RJ) of Shistosoma mansoni were extracted using Triton X-114 phase separation. The SDS-polyacrilamide gel electrophoresis profiles of the three phases (detergent, aqueous and insoluble proteins) obtained were compared after Coomassie blue and silver staining, surface radioiodination and Western blotting. No major differences were detected between the 2 isolates. Of the 25 or more proteins which partitioned into the detergent phase, only about 8 proteins could be surface radiodinated on live adult worms. A comparison was also made between the profiles of mael and females worms, isolated from bisexually infected mice. Two major female-specific and one male-specific band were detected by silver and/or Coomassie staining. The female bands, 32 KDa and 18 KDa, partitioned into the detergent and aqueous phase, respectively. The male-specific band of 42 KDa remained in the insoluble phase. Antigenic differences between male and females protins were detected by Western vlotting using a sera from infected Nectomys squamipes.

Relationship between Health-Related Quality of Life, Pain, and Functional Disability in Neuropathic Pain Patients with Failed Back Surgery Syndrome.

ABSTRACT Objectives: Patients with failed back surgery syndrome (FBSS) and chronic neuropathic pain experience levels of health-related quality of life (HRQoL) that are considerably lower than those reported in other areas of chronic pain. The aim of this article was to quantify the extent to which reductions in (leg and back) pain and disability over time translate into improvements in generic HRQoL as measured by the EuroQoL-5D and SF-36 instruments. Methods: Using data from the multinational Prospective, Randomized, Controlled, Multicenter Study of Patients with Failed Back Surgery Syndrome trial, we explore the relationship between generic HRQoL-assessed using two instruments often used in clinical trials (i.e., the SF-36 and EuroQol-5D)-and disease-specific outcome measures (i.e., Oswestry disability index [ODI], leg and back pain visual analog scale [VAS]) in neuropathic patients with FBSS. Results: In our sample of 100 FBSS patients, generic HRQoL was moderately associated with ODI (correlation coefficient: -0.462 to -0.638) and mildly associated with leg pain VAS (correlation coefficient: -0.165 to -0.436). The multilevel regression analysis results indicate that functional ability (as measured by the ODI) is significantly associated with HRQoL, regardless of the generic HRQoL instrument used. On the other hand, changes over time in leg pain were significantly associated with changes in the EuroQoL-5D and physical component summary scores, but not with the mental component summary score. Conclusions: Reduction in leg pain and functional disability is statistically significantly associated with improvements in generic HRQoL. This is the first study to investigate the longitudinal relationship between generic and disease-specific HRQoL of neuropathic pain patients with FBSS, using multinational data.

Asynchronous growth and competition in a two-sex age-structured population model

Asynchronous exponential growth has been extensively studied in population dynamics. In this paper we find out the asymptotic behaviour in a non-linear age-dependent model which takes into account sexual reproduction interactions. The main feature of our model is that the non-linear process converges to a linear one as the solution becomes large, so that the population undergoes asynchronous growth. The steady states analysis and the corresponding stability analysis are completely made and are summarized in a bifurcation diagram according to the parameter R0. Furthermore the effect of intraspecific competition is taken into account, leading to complex dynamics around steady states.

Gender Inequality and the Sex Ratio in Three Emerging Economies

The aim of this paper is to study inequality and deprivations as reflected in the human sex ratio (commonly defined as the number of males per 100 females). The particular focus is on three emerging economies, viz., Russia, India and China. The paper compares and contrasts the experiences of these countries and discusses policy issues. It is noted that while the feminist perspective on the issues surrounding the sex ratio is important, it would be wrong to view these issues always or exclusively through the prism of that perspective . It is also suggested that India and China probably have better prospects of sustained economic growth in the foreseeable future than does Russia.