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Biomedical subjects

A Leon

Publications and source records attributed to A Leon.

At least 19 recordsLinked to original sources
PubMed2006

[Brain injury during severe sepsis].

Sepsis-associated encephalopathy is a global cerebral dysfunction induced by the systemic response to inflammation and infection, without a liver or renal injury. Alteration of consciousness, from confusion to coma, is the main clinical symptom. This encephalopathy is associated with an increase in mortality due to sepsis. Its physiopathology is unknown. There is frequently an increased permeability of the blood-brain barrier, which might explain a role of endotoxins on cerebral metabolism. Changes in neurotransmitter release or concentrations (norepinephrine, serotonin, dopamine, GABA) have been reported. There is not any specific treatment of septic encephalopathy. In most cases, this syndrome is rapidly reversible after the treatment of sepsis.

Blood-Brain Barrier↗
PubMed2006

Emergence delirium in adults in the post-anaesthesia care unit.

BACKGROUND: Emergence delirium in the post-anaesthesia care unit (PACU) is poorly understood. The goal of this prospective study was to determine frequency and risk factors of emergence delirium in adults after general anaesthesia. METHODS: In this prospective study, 1,359 consecutive patients were included. Contextual risk factors and occurrence of delirium according to the Riker sedation scale were documented. Groups were defined for the analysis according to the occurrence or not of agitation, then after exclusion of patients with preoperative anxiety and neuroleptics, or both, and antidepressants or benzodiazepines treatments. RESULTS: Sixty-four (4.7%) patients developed delirium in the PACU, which can go from thrashing to violent behaviour and removal of tubes and catheters. Preoperative anxiety was not found to be a risk factor. Preoperative medication by benzodiazepines (OR=1.910, 95% CI=1.101-3.315, P=0.021), breast surgery (OR=5.190, 95% CI=1.422-18.947, P=0.013), abdominal surgery (OR=3.206, 95% CI=1.262-8.143, P=0.014), and long duration of surgery increased the risk of delirium (OR=1.005, 95% CI=1.002-1.008, P=0.001), while a previous history of illness and long-term treatment by antidepressants decreased the risk (respectively, OR=0.544, 95% CI=0.315-0.939, P=0.029 and OR=0.245, 95% CI=0.084-0.710, P=0.010). CONCLUSIONS: Preoperative benzodiazepines, breast and abdominal surgery and surgery of long duration are risk factors for emergence delirium.

Abdomen↗
PubMed2006

QN1/KIAA1009: a new essential protein for chromosome segregation and mitotic spindle assembly.

We previously reported the involvement of QN1 (quail neuroretina 1) protein in cell cycle control during retinal development. We show here that QN1 is an ATPase conserved through evolution, from fugu to humans. We show that chicken/quail QN1 protein is orthologous to the KIAA1009 protein in humans, the function of which was not known. We demonstrate here for the first time that QN1/KIAA1009 protein is located at the spindle poles of the mitotic apparatus and at centrosomes during mitosis. The siRNA-mediated depletion of KIAA1009 led to abnormal mitosis with chromosome segregation defects and abnormal centrosome separation leading to the death of PC12 and MCF7 cells. Thus, QN1/KIAA1009 is a new microtubule-associated ATPase involved in cell division.

Adenosine Triphosphatases↗
PubMed2006

Intrathoracic fat in HIV-infected patients.

BACKGROUND: The impact of HIV infection or antiretroviral therapy on the intrathoracic fat compartment is unknown. METHODS: Consecutive clinically stable HIV-infected adult patients, irrespective of exposure to antiretroviral therapy, and non-HIV-infected healthy volunteers, both without clinical evidence of body fat changes consistent with lipodystrophy and adjusted for age, gender and body mass index, were recruited for this study. Thoracic and abdominal fat was assessed by computed tomography and compared between patients and controls. RESULTS: There were nine women (33%) and 18 men (67%) in each group. Nineteen patients (70%) had been taking antiretrovirals for a median of 8 months (interquartile range: 6-11). Among the HIV-infected patients, intrathoracic fat (median; interquartile range) did not differ significantly between treated (6.7 cm(2); 4.5-8.3 cm(2)) and untreated (6.9 cm(2); 5.7-10.9 cm(2)) individuals (P=0.288). However, intrathoracic fat content (median; interquartile range) was higher in HIV-infected patients (6.8 cm(2); 5.6-10.5 cm(2)) than in controls (5.6 cm(2); 3.9-6.7 cm(2)) (P=0.025). Intrathoracic fat was positively correlated with intra-abdominal fat both in patients (rho=0.6, P=0.002) and in controls (rho=0.7, P=0.004). CONCLUSION: In HIV-infected adults without clinical evidence of lipodystrophy, intrathoracic fat content was higher than in healthy persons and positively correlated with intra-abdominal fat content.

Abdomen↗
PubMed2006

Peripheral levels of BDNF and NGF in primary headaches.

Neurotrophins, such as brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), have been implicated in the generation and modulation of pain. To investigate whether alterations in neurotrophin levels can be detected in subjects suffering from nociceptive disorders, such as primary headaches, we determined the peripheral (platelet and plasma) levels of BDNF and NGF in patients suffering from migraine, with or without aura, or cluster headache (CH), in the interictal phase, and in healthy volunteers. All primary headaches patients studied showed significantly decreased platelet levels of BDNF (migraine vs. controls P<0.001; CH vs. controls P<0.01), while a selective reduction of platelet NGF was observed in migraine sufferers and not in CH patients compared with control subjects (migraine vs. controls P<0.001). These changes were not accompanied by significant modifications of neurotrophin plasma levels. Our findings show for the first time that changes in peripheral levels of neurotrophines (BDNF and NGF) occur in patients suffering from different types of primary headaches, suggesting a potential involvement of BDNF and NGF in the pathophysiology of these disorders, and raising the possibility that differences in peripheral neurotrophins may help to distinguish migraine biologically from CH.

Adult↗
PubMed2005

Aspirin prevention of NMDA-induced neuronal death by direct protein kinase Czeta inhibition.

Abstract Aspirin has been shown to protect against glutamate neurotoxicity via the nuclear factor kappaB pathway. Some studies have implicated the atypical protein kinase C (PKC) zeta (zeta) isoform in cell protection, but the mechanism involved remains unclear. We show here that aspirin exerts at least some of its effects through PKCzeta, decreasing the NMDA-induced activation, cleavage and nuclear translocation of this molecule. Aspirin (acetylsalicylic acid) directly inhibited the protein kinase activity of PKCzeta, whereas salicylic acid did not. This direct effect of aspirin on purified human PKCzeta is consistent with PKCzeta inhibition preventing the NMDA-induced death of cortical neurones. Caspase-3 inhibition blocked the cleavage and nuclear translocation of PKCzeta, whereas caspase-1-inhibition did not. Thus, PKCzeta (protein kinase Mzeta) regulates nuclear events essential for the initiation of the apoptotic pathway. Aspirin protects cells against NMDA-induced apoptosis by means of a novel mechanism targeting PKCzeta, a key molecule in inflammatory responses and neurodegeneration.

Animals↗
PubMed2004

Elevated levels of circulating trace amines in primary headaches.

BACKGROUND: Trace amines, including tyramine, octopamine, and synephrine, are closely related to classic biogenic amines. They have been hypothesized to promote migraines and other types of primary headaches, but there is no direct evidence supporting this hypothesis. METHODS: Using a multichannel electrochemical high-performance liquid chromatography system, the authors evaluated whether changes in circulating trace amines occur in subjects with migraine (with or without aura) during headache-free periods as well as in patients with cluster headache (CH) during the remission and active phases as compared with healthy control subjects. RESULTS: Plasma levels of all trace amines were significantly higher in CH patients, in both the remission and the active phases, when compared with control subjects or subjects with migraine. In addition, intraplatelet levels of octopamine, synephrine, and tyramine were higher in CH patients than in control subjects. In migraine patients, plasma levels of octopamine and synephrine were higher compared with controls, although in migraine with aura, the difference was not significant. CONCLUSIONS: Whereas the elevation of plasma trace amine levels in both migraine and CH supports the hypothesis that disorders of biogenic amine metabolism may be a characteristic biochemical trait in primary headache sufferers, the observation that such alterations are more prominent in patients with CH than migraine patients suggests that they may reflect sympathetic or hypothalamic dysfunction.

Adolescent↗
PubMed2004

Autologous stem-cell transplantation in diffuse large B-cell non-Hodgkin's lymphoma not achieving complete response after induction chemotherapy: the GEL/TAMO experience.

BACKGROUND: Here we evaluate the results of high-dose chemotherapy and autologous stem-cell transplantation (HDC/ASCT) in 114 patients included in the GEL/TAMO registry between January 1990 and December 1999 with diffuse large B-cell lymphoma who failed to achieve complete remission (CR) with front-line conventional chemotherapy. PATIENTS AND METHODS: Sixty-eight per cent had a partial response (PR) and 32% failed to respond to front-line therapy. At transplant, 35% were chemoresistant and 29% had two to three adjusted International Prognostic Index (a-IPI) risk factors. RESULTS: After HDC/ASCT, 57 (54%) of 105 patients evaluable for response achieved a CR, 16 (15%) a PR and 32 (30%) failed. Nine patients were not assessed for response because of early death due to toxicity. With a median follow-up of 29 months for alive patients, the survival at 5 years is 43%, with a disease-free survival for complete responders of 63%. The lethal toxicity was 8%. Multivariate analysis revealed a-IPI and chemoresistance to be predicting factors. CONCLUSIONS: Our results show that one-third of patients who do not obtain a CR to front-line chemotherapy may be cured of their disease with HDC/ASCT. However, most chemoresistant patients pretransplant failed this therapy. For this population, as well as for those who presented with adverse factors of the a-IPI, pretransplant novel therapeutic modalities need to be tested.

Adolescent↗
PubMed2003

Elusive amines and primary headaches: historical background and prospectives.

Although the role of trace amines such as tyramine, octopamine and synephrine in the pathogenesis of migraine has been debated for decades, this issue remains still unresolved. In spite of a relevant body of work, the inability to demonstrate specific receptors for these compounds and the lack of sensitive non-radioactive methods for the detection of trace amines in biological samples have limited their investigation in humans. However, the recent identification of a new, large family of G protein-coupled receptors, some of which bind and are activated by trace amines, has focused renewed attention on these compounds. This discovery, together with the possibility of providing novel insights for evaluation of the pathophysiological role of trace amines in primary headaches, may offer new opportunities for pharmacological strategies acting on these receptors. In light of the new scientific background, this review outlines a historical perspective and summarizes evidence supporting a role of trace amines in the pathogenesis of migraine and cluster headache.

Amines↗
PubMed2003

Is ilioinguinal/iliohypogastric nerve block always totally safe in children?

We report a case of accidental puncture of the small bowel during an ilioinguinal/iliohypogastric nerve block procedure for hernia repair. The diagnosis was made a few days later during a laparoscopic exploration owing to the progressive onset of clinical and radiological intestinal obstruction. A large, obstructing subserosal haematoma was found without any apparent perforation of the mucosa, and the damaged loop was resected. Such a complication has already been reported once in the literature after use of a long bevel needle for the puncture. This case is the first reported using an atraumatic short bevel needle. We discuss the technical aspects of the procedure and underline the fact that regional anaesthesia in children is never totally risk free.

Child↗
PubMed2003

Use of Fourier-transform infrared spectroscopy for typing of Candida albicans strains isolated in intensive care units.

Comparative studies of Candida albicans strains are essential for proving cross-infections in epidemiological investigations. Typing of C. albicans strains is mainly based on genotypic methods. Fourier-transform infrared (FTIR) spectroscopy is described in this study as a novel phenotypic approach to the typing of C. albicans. The first step in the approach was the standardization of sample preparation (culture conditions and sampling parameters) and acquisition and classification parameters (spectral acquisition, spectral window selection, classification algorithm, and heterogeneity threshold). The second step consisted of validating the established parameters with a set of 79 strains of C. albicans isolated over 4 months from nine patients hospitalized in two intensive care units. Strains were isolated from multiple anatomical sites with repeated sampling. FTIR spectroscopy results were compared to randomly amplified polymorphic DNA (RAPD) results; this analysis showed that the amplification patterns of strains isolated from a given patient were identical and that different patients had different profiles. FTIR spectroscopy data were analyzed by hierarchical clustering performed with the second-derivative spectra. This classification revealed nine groups, one per patient. Only one spectrum out of 79 was misclassified by the FTIR spectroscopy method. RAPD and FTIR spectroscopy results were in good agreement, showing that, when nosocomial candidiasis transmission is suspected and urgent information is needed, this technique may be useful as a quick identification tool to give solid clues before confirmation by a genotypic method.

Adult↗
PubMed2002

H(2)O(2) induces upregulation of Fas and Fas ligand expression in NGF-differentiated PC12 cells: modulation by cAMP.

Fas, (APO-1/CD95), a transmembrane glycoprotein belonging to the tumor necrosis (TNF) receptor superfamily, transduces apoptotic death upon crosslinking by its cognate ligand (FasL). As upregulation of Fas/FasL expression occurs in neuropathological conditions (e.g., stroke, central nervous system [CNS] trauma and seizures) associated with oxidative damage, we questioned whether reactive oxygen species (ROS) can directly affect Fas and FasL expression in neuronal cells. Utilizing rat PC12 cells neuronally differentiated with nerve growth factor (NGF), we observed that concentrations of H(2)O(2) inducing apoptotic cell death rapidly trigger the expression of Fas mRNA and protein as well as FasL mRNA. Although NGF-addition to naive PC12 downregulated constitutive Fas and FasL transcription, the H(2)O(2)-induced Fas and FasL mRNA upregulation invariably occurred either in the presence or in the absence of NGF. Similarly, phorbol 1,2-myristate 1, 3-acetate (PMA), a potent protein kinase C (PKC) activator, did not modify Fas and FasL mRNA upregulation subsequent to H(2)O(2) exposure. On the contrary, forskolin and dibutyryl cAMP, which elevate intracellular cAMP by independent mechanisms, both counteracted H(2)O(2)-induced Fas, but not FasL, mRNA upregulation and increased constitutive expression of FasL mRNA. Altogether, our data show that oxidative stress is a major stimulus in eliciting Fas and FasL expression in NGF-differentiated PC12 cells. Moreover, we describe here for the first time the existence of cAMP-dependent mechanism(s) modulating Fas and FasL expression.

Animals↗
PubMed2001

Low-volume nodal metastases detected at retroperitoneal lymphadenectomy for testicular cancer: pattern and prognostic factors for relapse.

PURPOSE: To determine the incidence, pattern, and predictive factors for relapse in patients with low-volume nodal metastases (stage pN1) at retroperitoneal lymphadenectomy (RPLND) and identify who may benefit from chemotherapy in the adjuvant or primary setting. PATIENTS AND METHODS: Fifty-four patients with testicular nonseminomatous germ cell tumor had low-volume retroperitoneal metastases (pathologic stage pN1, 1997 tumor-node-metastasis classification) resected at RPLND, 50 of whom were managed expectantly without adjuvant chemotherapy. The dissection was bilateral in 12 and was a modified template in 38 patients. Retroperitoneal metastases were limited to microscopic nodal involvement in 14 patients. Follow-up ranged from 1 to 106 months (median, 31.4 months). RESULTS: Eleven patients (22%) suffered a relapse at a median follow-up of 1.8 months (range, 0.6 to 28 months). The most frequent form of recurrence was marker elevation in nine (18%) patients. Persistent marker elevation after orchiectomy and before retroperitoneal lymphadenectomy was a significant independent predictor of relapse (relative risk, 8.0; 95% confidence interval, 2.3 to 27.8; P =.001). Four of five (80%) patients with elevated markers (alpha-fetoprotein alone in three, alpha-fetoprotein and beta human chorionic gonadotropin in one) suffered a relapse, compared with seven of 45 (15.6%) patients with normal markers. CONCLUSION: Clinical stage I and IIA patients with normal markers who have low-volume nodal metastases have a low incidence of relapse and can be managed by observation only if compliance can be assured. In contrast, patients with elevated markers before retroperitoneal lymphadenectomy have a high rate of relapse and should be considered for primary chemotherapy.

Actuarial Analysis↗
PubMed2001

Dynamic light scattering from lyotropic lamellar phases subjected to a flow field.

Dynamic light scattering experiments on lyotropic lamellar phases of brine and surfactant subjected to a flow field have been realized. The obtained results reveal that the relaxation times measured depend strongly on the velocity of the flow. This dependence is indicative of an increase of the effective elasticity modulus K and a decrease of the effective compressibility modulus (-)B of the lamellar phase with the flow velocity. This leads to the conclusion that the shear can induce a suppression of the undulation fluctuations of the bilayers of the lamellar phase. Our results show also that the rigidity of the membranes decreases as the salt concentration of the sample increases.

Biophysics↗
PubMed2001

Synthesis, characterization and biological evaluation of a novel "3 + 1" mixed ligand 99mTc complex having an aliphatic thiol as coligand.

A novel "3 + 1" mixed ligand 99mTc complex with N,N-bis(2-mercaptoethyl)-N'N'-diethyl-ethilenediamine as ligand and 1-octanethiol as coligand was prepared and evaluated as potential brain radiopharmaceutical. Preparation at tracer level was accomplished by substitution, using 99mTc-glucoheptonate as precursor and a coligand/ligand ratio of 5. Under these conditions the labeling yield was over 80% and a major product with radiochemical purity >80% was isolated by HPLC methods and used for biological evaluation. Chemical characterization at carrier level was developed using the corresponding rhenium and 99gTc complexes. Results were consistent with the expected "3 + 1" structure and X-ray diffraction study demonstrated that the complex adopted a distorted trigonal bipyramidal geometry. All sulphur atoms underwent ionization leading to the formation of a neutral compound. Biodistribution in mice demonstrated early brain uptake, fast blood clearance and excretion through hepatobiliary system. Although brain/blood ratio increased significantly with time, this novel 99mTc complex did not exhibit ideal properties as brain perfusion radiopharmaceutical since brain uptake was too low.

Animals↗
PubMed2001

Biventricular pacing using two pacemakers and the triggered VVT mode.

Pacemaker dependent patients exhibit interventricular conduction delay due to right ventricular lead placement. The addition of a transvenous coronary sinus lead for biventricular pacing has been shown to be effective. Venous stenosis and thrombosis postpacemaker implantation can occur in up to 35% of patients. This report describes a patient with a preexisting left-sided dual chamber pacemaker and chronic left subclavian vein occlusion that was upgraded to a biventricular system byplacing a coronary sinus lead and single chamber ventricular triggered pacemaker on the opposite side.

Aged↗
PubMed2001

The effect of variation in the interval between right and left ventricular activation on paced QRS duration.

Pacing of the RV and LV is a promising technique for treating patients with dilated cardiomyopathy and bundle branch block. The salutary effects of biventricular pacing may be due to resynchronization of LV activation. Currently, available biventricular pacemakers and implanted defibrillators produce simultaneous ventricular output pulses. The purpose of the current study was to assess the effects of variation in the timing of RV and LV activation, using the paced QRS duration as a marker of resynchronization. Twenty-six patients undergoing transvenous biventricular pacemaker implantation were studied. After stable lead positions were achieved, activation of the LV and RV was varied over a range of +/- 50 ms and the QRS duration measured on a 12-lead ECG. Only 6 (23%) of the 26 patients had maximal shortening of the paced QRS with simultaneous activation of the LV and RV. The shortest paced QRS duration was most often produced by an LV to RV interval of -30 ms (LV activation preceding RV activation). Optimization of LV to RV interval resulted in an additional 13% shortening of the paced QRS compared to simultaneous activation (P < 0.0001). Patients with leads located on the lateral or anterolateral walls of the LV were more likely to benefit from preexcitation of the LV than did patients with leads in the posterior position. Results of this study suggest that the ability to program the LV to RV interval may be useful to optimize the benefit of biventricular pacing.

Bundle-Branch Block↗