Biomedical subjects
Publications and source records attributed to S Dupont.
The authors conducted an open study of levetiracetam as add-on therapy in nine patients with well-defined progressive myoclonic epilepsies and refractory myoclonus. Myoclonus was evaluated semiquantitatively (territory, intensity, daily living activities). Five patients had improvement of their myoclonus score. Levetiracetam may benefit myoclonus in progressive myoclonic epilepsy.
As personality may predispose, precipitate or perpetuate substance abuse and/or dependence, and as it is considered to remain stable across the years in a given subject, potential links with the drug of choice may help screen future patients before drug consumption. The present study compared three groups: 42 patients with heroin dependence (mean age: 31.2; standard deviation (SD): 5.5; 10 females), 37 patients with alcohol dependence (mean age 44.2; SD: 9.1; 9 females) and 83 subjects from a random population sample (mean age: 38.8; SD: 6.9; 20 females). Personality was measured by Cloninger's Temperament and Character Inventory (TCI). Pillai's MANCOVA with age as a covariate and gender as a cofactor was highly significant. Univariate ANOVA analyses using TCI dimensions as dependent variable showed most variables to vary in parallel for the two patient groups in comparison with controls. Post-hoc tests showed heroin patients to score higher in Novelty-Seeking and Self-Directedness than alcohol patients. Sub-dimensions Exploratory Excitability, Fear of the Uncertain, Responsibility, Congruent Second Nature and Transpersonal Identification were also significantly different in the two patient samples. Logistic regression showed Exploratory Excitability to segregate up to 76% of heroin patients from alcohol patients. In conclusion, personality profiles were linked to some preferential choice of drug and personality screening might be tested in preventive strategies.
The role of adrenaline in the nervous control of bioluminescence in three brittlestar species, Amphiura filiformis, Amphipholis squamata, and Ophiopsila aranea, was assessed by testing two different beta-adrenergic antagonists (propranolol and labetalol) over a wide concentration range (10(-10)-10(-3)M). We compared the effects of analogues (active vs. inactive) of the same substance (L- and D-enantiomers of propranolol). Propranolol presented both specific and nonspecific effects: (i) nonspecific effects were observed at the higher concentrations tested (10(-4) and 10(-3)M) in all three species; (ii) specific effects were detected only at the lower concentrations tested (10(-6)-10(-5)M). In A. squamata, the involvement of adrenaline in the nervous control of luminescence is supported by propranolol and labetolol specific inhibition. The neuropharmacological implications of nonspecific effects, the involvement of adrenaline and the interspecific differences in the brittlestar nervous control of bioluminescence are discussed.
OBJECTIVES: To identify and describe the main psychological tendencies which emerge in women undertaking a Voluntary Pregnancy Termination (VPT) and, more specifically, those tendencies which can have an effect upon the patient-physician relationship. POPULATION AND METHODS: Psychological sessions with patients and participation, as an assistant psychologist, in the medical consultations of a random cross-section of 507 women, minors included, seeking a VPT at the Schiltigheim Medical Surgery and Obstetrics Centre between November 2002 and June 2003. RESULTS AND DISCUSSION: The study revealed a recurrent tendency in women to become psychologically defensive in reaction to VPT and to repress their emotions as well as the natural development of maternal tendencies that accompany the experience of pregnancy. This obstacle to psychological engagement seems to be associated, according to the case in hand, to a particular form of pathological mourning of the pregnancy, to a factor of recourse to action (especially amongst adolescents) or to later difficulties in dealing with further pregnancies. CONCLUSION: Taking into consideration the psychological effects observed amongst a large number of women undertaking VPT and the role which doctors and care teams can have in the identification and prevention of these effects, this study proposes various work guidelines enabling these patients to be attented to in a way that is respectful of the psychological aspects of their experience.
The development of MRI has modified clinical practices for patients with epilepsy. MRI examinations are highly contributive to the detection of structural brain abnormalities, and have a major impact on the management of patients with epilepsy. In addition to its major diagnostic role, MRI may help to assess prognosis in patients with refractory partial epilepsy. Structural abnormalities such as hippocampal sclerosis or malformations of cortical development are associated with medically refractory epilepsy. Furthermore, finding a focal lesion on MRI is a good prognostic factor in refractory patients who are candidates for surgery. The sensitivity of MRI to detect small brain lesions is currently excellent, but may be further improved by the use of high-resolution imaging, and new techniques such as quantitative methods or statistical parametric mapping (SPM). In the future, new emerging MR techniques will undoubtedly greatly contribute to improved presurgical management of patients with refractory partial epilepsy.
OBJECTIVE: Patients with medically intractable epilepsy are potential candidates for surgery if the epileptogenic tissue is localized and resectable. Surgical therapy can eliminate seizures but is very expensive. We followed a prospective adult cohort of intractable epileptic patients in order to perform a cost-effectiveness analysis. POPULATION AND METHODS: Adult patients with a suspected partial medically intractable and operable epilepsy were eligible for evaluation, explorations and/or surgery. Clinical and economical data were collected at the inclusion and every 6 months over at least two years. Two patient groups were analyzed: some underwent a surgery, others did not. Clinical data were compared between both groups. As the data collection was not yet complete, we compared the surgery to a continuation of the preoperative medical management in a cost-effectiveness analysis. Direct medical and nonmedical costs were evaluated according to a societal perspective. The effectiveness was defined as one year without seizure. We assessed the incremental cost-effectiveness ratio (ICER) for the first two years after the surgery. We also modeled long-term costs and effectiveness and extrapolated the results over the patients' lifetime with a Markov model. We computed the ICER and performed a sensitivity analysis. Indirect costs were measured in physical units and intangible costs were assessed with quality-of-life measures (QOLIE-31, SEALS). Data were compared before and after surgery. RESULTS: Among the 286 patients included, 119 did not enter in the analysis: 7 were not eligible, 44 not operable, 31 did not present a follow-up, 37 still underwent exams. Finally, 89 underwent a surgical treatment, and 78 were medically treated. Disease was more severe in surgical patients than in medical patients: seizures frequency, depressive disorders and cognitive impairment were greater. One year after the surgery, 83% patients were seizure free. During the year before inclusion and the year after surgery, direct costs were mainly due to hospitalization. During the second year after surgery, the cost of antiepileptic drugs predominated. One additional year without seizure costs 23 531 euro one year after surgery and 9533 euro two years after surgery. In a long-term perspective, the surgery became cost-effective between 7 and 8 years after the surgery. CONCLUSION: Surgical therapy is a cost-effective treatment in a middle-term even without indirect costs consideration.
Little is known about the functional anatomy of the insula. Several experimental data suggest that the organization of the insular connections from the different insular cytoarchitectonic regions is related to different functional domains within the insula, and recent electrophysiological and neuroimaging studies have shown the existence of an anterior-posterior organization within the insular cortex. To further investigate this point, we carried out a positron emission tomography (PET) study using fluorodeoxyglucose ((18)F-FDG) in patients with medial temporal lobe epilepsy who experienced emotional or visceral symptoms that are supposed to be elicited in the insula. The aim of our study was to assess the existence of a functional insular somatotopic organization. FDG-PET studies were carried out in 18 epileptic patients. Data were analyzed using statistical parametric mapping (SPM96). The results showed that the emotional symptoms were correlated with hypometabolism in the anterior part of the ipsilateral insular cortex, while visceral symptoms were correlated with hypometabolism in the posterior part ( p=0.001). This neuroimaging study demonstrates that the anterior part of the insular cortex corresponding to the agranular cortex subserves emotional functions while the posterior part of the insular cortex corresponding to the granular cortex subserves ascending visceral symptoms.
Historically, the hippocampus belongs to the limbic lobe described by Broca or to the Papez circuit. His role was first restricted to emotions. The observations that medial temporal lobe (MTL) damage led also to mnemonic dysfunction have been advanced greatly by the study of brain-damaged patients and experimental animals studies. Functional imaging, either positron emission tomography or functional MRI, has helped to change this historical concepts. Recent findings have converged on the observation that hippocampal or parahippocampal regions could be consistently activated in verbal or visuospatial memory paradigms. Furthermore, these functional neuroimaging studies have also stressed the importance of the prefrontal cortical activations in such memory processes. These results show that memory is subserved by a more widely distributed cortical network than expected.
Human African trypanosomosis (HAT) remains a major public health problem in Subsaharan Africa. The region around the town of Bonon in middle western Côte d'Ivoire is a highly endemic HAT zone. The purpose of this study was to assess the role of travelling of infected patients in transmission of HAT. The study population included a total of 96 patients in whom HAT had been diagnosed actively or passively between 1999 and 2000. Information on each patient's residence and workplaces, i.e. water site, and farm field, was used to calculate the mean distance traveled and mean number of places visited daily by each patient. Findings indicated that both parameters, i.e., distance traveled and number of places visited, were significantly higher for patients living in Bonon than those living in hamlets or homesteads. Based on analysis of patient movements the endemic zone could be divided into three subdivisions with different modes of disease transmission. This study was performed as a preliminary step for a larger investigation designed to allow specific targeting of HAT hot spots based mainly on a geographic information system.
Although estradiol (E(2)) has been recognized to exert several vasculoprotective effects in several species, its effects in mouse vasomotion are unknown, and consequently, so is the estrogen receptor subtype mediating these effects. We investigated the effect of E(2) (80 microg/kg/day for 15 days) on NO production in the thoracic aorta of ovariectomized C57Bl/6 mice compared with those given placebo. E(2) increased basal NO production. In contrast, the relaxation in response to ATP, to the calcium ionophore A23187, and to sodium nitroprusside was unaltered by E(2), whereas acetylcholine-elicited relaxation was decreased. The abundance of NO synthase I, II, and III immunoreactive proteins (using Western blot) in thoracic aorta homogenates was unchanged by E(2). To determine the estrogen receptor (ER) subtype involved in these effects, transgenic mice in which either the ERalpha or ERbeta has been disrupted were ovariectomized and treated, or not, with E(2). Basal NO production was increased and the sensitivity to acetylcholine decreased in ERbeta knockout mice in response to E(2), whereas this effect was abolished in ERalpha knockout mice. Finally, these effects of E(2) on vasomotion required long-term and/or in vivo exposure, as short-term incubation of aortic rings with 10 nmol/L E(2) in the isolated organ chamber did not elicit any vasoactive effects. In conclusion, this study demonstrates that ERalpha, but not ERbeta, mediates the beneficial effect of E(2) on basal NO production.
The recent advent of new functional neuroimaging techniques such as functional magnetic resonance imaging (fMRI) makes it possible to examine cerebral activations in healthy individuals. In the present study, we attempted to examine the anatomical distribution of neocortical and mediotemporal activations in control subjects during episodic memory tasks over 24 h. BOLD (blood oxygenation-level-dependent) fMRI data were collected from 10 control subjects. Twenty-two contiguous images covering the whole brain were acquired using an EPI echoplanar sequence. Subjects were instructed to learn a list of 17 words, and to recall it immediately and after a 24-h interval. Individual and group analyses were performed using SPM96. The results demonstrated that a similar left occipito-temporofrontal network was activated during both immediate and 24-h-delayed retrieval conditions. In addition, the 24-h-delayed retrieval also activated a larger parietal region and the right hippocampus. These findings suggest that fMRI is a reliable method with which to perform anatomical studies.
To determine the contributions of estrogen receptor (ER)alpha and ERbeta in bone growth and remodeling in male and female mice, we generated and analyzed full knockouts for each receptor, and a double ER knockout. Although suppression of the ligand to the ERs (i.e., estradiol) after menopause or gonadectomy in females led to a catastrophic increase in bone turnover and concomitant bone loss, deletion of one or both ERs failed to show such an effect. Complete deletion of ERalpha led to a decrease, not an increase, in bone turnover and an increase, not a decrease, in trabecular bone volume in both male and female animals. Deletion of ERbeta led to different responses in males, where bone was unaffected, and in females, where bone resorption was decreased and trabecular bone volume increased. In contrast, deletion of both ERs led to a profound decrease in trabecular bone volume in females, which was associated with a decrease, not an increase, in bone turnover. Finally, deletion of ERalpha, but not ERbeta, led to major changes in circulating levels of estradiol and/or testosterone, indirectly affecting bone remodeling and bone mass. Thus, only ERalpha was shown to regulate bone remodeling in males, whereas in females both receptor subtypes influenced this process and could, at least under basal knockout conditions, compensate for each other.
OBJECTIVE: Functional MRI (fMRI ) was used to investigate right medial temporal lobe epilepsy (RTLE) effects on verbal memory. METHODS: BOLD fMRI data were collected from seven right sided MTLE patients (RTLE) and compared with the data previously acquired from seven left sided MTLE patients (LTLE) and 10 control subjects. Twenty two contiguous images covering the whole brain were acquired using an EPI echoplanar sequence. Subjects were instructed to learn a list of 17 words, and to recall it immediately and at 24 hours interval. Group analyses were performed using SPM96. RESULTS: RTLE patients retrieval performances were significantly impaired as compared with the performance of control subjects. As compared with control subjects and LTLE patients, RTLE patients exhibited a different pattern of hemispheric activations and a global decrease in left hemisphere functional activity. CONCLUSION: MTLE cannot be considered as a model of pure well lateralised hippocampal dysfunction. The verbal memory impairment depicted in RTLE patients may be considered as the witness of a bilateral impairment of the neuroanatomical circuits subserving memory.
The case of a young female with an acute idiopathic low cerebrospinal fluid pressure is presented. Clinical-imaging manifestations were typical and two consecutive blood patches resulted in a complete and durable resolution of the symptomatology. We present a review of the various investigation and therapeutic techniques.
Investigative strategies for partial epilepsy have evolved greatly since the advent of morphological MRI. MRI currently provides the most extensive and sensitive information for detecting and localizing brain anomalies. Technical progress has included new sequences (3D acquisition, inversion-recovery, fast spin-echo), new imaging planes (through the greater diameter of the hippocampus for temporal epilepsy, orbitao-meatal for extra-temporal epilepsy), high-resolution imaging, and better signal-noise ratio in addition to new procedurs such as NMR spectroscopy, diffusion/perfusion imaging, or functional MRI. One of the principal aims of MRI is to detect potentially epileptogenic brain anomalies useful for the detection and localization of the epileptic focus. MRI sensitivity is much greater than brain computed tomography, which excepting specific cases, is no longer contributive. Hippocampal sclerosis is a typical example of an epilepsy-related brain anomaly (mesial temporal lobe epilepsy) whose diagnosis has been changed by MRI. This entity was described by Bouchet and Cazauvieilh in 1825 who related anatomic postmortem findings to the clinical expression. Reliable diagnosis of hippocampal sclerosis can now be achieved with MRI, contributing to the diagnosis of mesial temporal lobe epilepsy. MRI can also contribute precious prognostic information, useful for both drug and surgical treatment. It has been demonstrated that the degree of response to drug treatment is not univocal and that certain lesions such as hippocampal sclerosis are generally associated with drug resistance. Sensitivity to drug therapy also varies with the type of cerebral dysgenesia. It has also been demonstrated that the a brain lesion identified at MRI is generally a factor of good prognosis after surgery. Continuing improvements in MRI techniques, widespread availability of technical facilities and new derived techniques contribute greatly to the usefulness of MRI for investigating partial epilepsy.
Recurrent transitory consciousness loss represents a neurological diagnostic difficulty. A 56 year old man was hospitalised for recurrent stupor episodes. Explorations allowed to exclude hepatic, renal or respiratory failures, epilepsy or sleep disorder. During a stuporous state, since the patient was clearly awakened by flumazenil administration, the retained diagnosis was idiopathic recurrent stupor, a rare and not well-known disease. The authors discuss the possible effect of a treatment with zolpidem, though its pharmacokinetic characteristics did not correspond to the patient manifestations, and the possible responsibility of endogenous benzodiazepines in the genesis of this trouble.
Estrogens are powerful modulators of neuronal physiology and in humans may affect a broad range of functions, including reproductive, emotional, and cognitive behaviors. We studied the contribution of estrogen receptors (ERs) in modulation of emotional processes and analyzed the effects of deleting ERalpha or ERbeta in mice. Behavior consistent with increased anxiety was observed principally in ERbeta mutant females and was associated with a reduced threshold for the induction of synaptic plasticity in the basolateral amygdala. Local increase of 5-hydroxytryptamine 1a receptor expression in medial amygdala may contribute to these changes. Our data show that, particularly in females, there is an important role for ERbeta-mediated estrogen signaling in the processing of emotional behavior.
BACKGROUND: The atheroprotective effect of 17beta-estradiol (E(2)) has been suggested in women and clearly demonstrated in animals through both an effect on lipid metabolism and a direct effect on the cells of the arterial wall. It has been shown, for example, that E(2) promotes endothelium-dependent relaxation and accelerates reendothelialization in rats. Similar studies have been undertaken in mice to appreciate the molecular mechanism of this process. METHODS AND RESULTS: We report here a model of electric carotid injury adapted from that described by Carmeliet et al (1997) that allows us to precisely evaluate the reendothelialization process. We demonstrate that E(2) accelerates endothelial regeneration in castrated female wild-type mice. In ovariectomized transgenic mice in which either the estrogen receptor (ER)-alpha or ERbeta gene has been disrupted, E(2) accelerated reendothelialization in female ERbeta knockout mice, whereas this effect was abolished in female ERalpha knockout mice. CONCLUSIONS: This study demonstrates that ERalpha but not ERbeta mediates the beneficial effect of E(2) on reendothelialization and potentially the prevention of atherosclerosis.