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Biomedical subjects

M Hamon

Publications and source records attributed to M Hamon.

At least 19 recordsLinked to original sources
PubMed2006

Cardiac baroreflex facilitation evoked by hypothalamus and prefrontal cortex stimulation: role of the nucleus tractus solitarius 5-HT2A receptors.

We previously showed that serotonin (5-HT2) receptor activation in the nucleus of the tractus solitarius (NTS) produced hypotension, bradycardia, and facilitation of the baroreflex bradycardia. Activation of the preoptic area (POA) of the hypothalamus, which is involved in shock-evoked passive behaviors, induces similar modifications. In addition, previous studies showed that blockade of the infralimbic (IL) part of the medial prefrontal cortex, which sends projections to POA, produced an inhibitory influence on the baroreflex cardiac response. Thus, to assess the possible implication of NTS 5-HT2 receptors in passive cardiovascular responses, we analyzed in anesthetized rats the effects of NTS inhibition and NTS 5-HT2 receptor blockade on the cardiovascular modifications induced by chemical (0.3 M D,L-homocysteic acid) and electrical (50 Hz, 150-200 microA) stimulation of IL or POA. Intra-NTS microinjections of muscimol, a GABAA receptor agonist, prevented the decreases in blood pressure and heart rate normally evoked by IL or POA activation. In addition, we found that intra-NTS microinjection of R(+)-alpha-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenylethyl)]-4-piperidine-methanol, a specific 5-HT2A receptor antagonist, did not affect the decreases in cardiovascular baseline parameters induced by IL or POA stimulation but prevented the facilitation of the aortic baroreflex bradycardia normally observed during IL (+65 and +60%) or POA (+70 and +69%) electrical and chemical stimulation, respectively. These results show that NTS 5-HT2A receptors play a key role in the enhancement of the cardiac response of the baroreflex but not in the changes in basal heart rate and blood pressure induced by IL or POA stimulation.

Animals↗
PubMed2006

[Imaging of acute stroke].

Acute stroke patients represent an important diagnostic and therapeutic challenge. Patients with brain damage in the ischemic, but not yet infarcted, phase have the greatest potential for recovery. Here we review the most commonly employed diagnostic tools that are currently used before stroke therapy. While computed tomography is pertinent to differentiate ischemic from hemorrhagic stroke, this technique cannot be used as an etiological screening too. The ischemic origin of symptoms can be confirmed with magnetic resonance imaging which also contributes to for therapeutic decision making, prognosis assessment and etiological screening.

Acute Disease↗
PubMed2006

[Mechanism of thrombosis: physiopathology, role of thrombin and its inhibition by modern therapies].

Although the number of cardiological interventional procedures is in constant progression, they still carry a considerable risk of thrombotic complications. The different antithrombotic strategies in force reduce their incidence but at the price of an excess of bleeding complications. In order to improve the benefit/risk ratio, new antithrombotic drugs have been developed. The thrombin antagonists have a choice role because, in addition to its effect of fibrinogen, thrombin plays a fundamental part in the initiation and maintenance of the thrombosis, both by activating the clotting factors and by stimulating the platelets. Unfractionated heparin was the thrombin inhibitor of choice for many years in interventional cardiology but the improvement of our knowledge of the mechanisms of thrombosis has helped define its limitations. Direct inhibitors of thrombin such as bivalirudine avoid most of these disadvantages. One of their main advantages is their efficacy within the constituted clot itself, whereas heparin, in the absence of antithrombin, has a deleterious effect. The reversibility of the effect of bivalirudine probably plays a role in maintaining the haemostatic equilibrium providing an antithrombotic effect at least as effective as that of heparin but with a reduced risk of bleeding and without any specific biological surveillance. These advantages have been confirmed in the initial clinical trials but further studies aim t widen their application to patients selected with a higher risk of thrombotic events.

Angioplasty, Balloon, Coronary↗
PubMed2006

Do transient ischemic attacks with diffusion-weighted imaging abnormalities correspond to brain infarctions?

BACKGROUND AND PURPOSE: Our aim was to determine whether diffusion-weighted imaging (DWI) changes associated with transient ischemic attack (TIA) are reversible or correspond to permanent tissue injury. METHODS: Among 103 consecutive patients admitted for TIA, 36 (34.9%) had abnormalities on initial DWI (delay from TIA = 30 +/- 33 hours [mean +/- SD]). Thirty-three patients (59 DWI lesions) had an MR imaging follow-up (delay from TIA = 10.6 +/- 5 months) including fluid-attenuated inversion recovery, T2, DWI, and 3D T1-weighted sequences. For each lesion, we recorded the quantitative parameters on initial DWI (volume, apparent diffusion coefficient [ADC]) and performed a comparison between reversible and irreversible lesions. RESULTS: MR imaging failed to detect any permanent injury in 7 patients and identified subsequent infarct in regions corresponding to the original DWI abnormalities in 26 patients (79%). Of the 59 lesions initially identified on DWI, 45 (76.3%) were associated with permanent injury on follow-up MR imaging. The DWI volume was significantly larger (0.91 +/- 1.7 versus 0.21 +/- 0.21 cm(3), P = .003) and the ADC ratio values lower (79 +/- 15% versus 91 +/- 9%, P = .001) in lesions with subsequent infarct than in those that were fully reversible. CONCLUSION: By showing that most patients with DWI-positive TIAs share the same imaging outcome as stroke patients, our data provide additional support for the redefinition of TIA, which considers that all cases of transient deficit with characteristic neuroimaging abnormalities should be diagnosed as a stroke.

Adult↗
PubMed2005

Deficiency of the 5-hydroxytryptamine transporter gene leads to cardiac fibrosis and valvulopathy in mice.

BACKGROUND: Serotonin (5-hydroxytryptamine; 5-HT) overproduction is responsible for cardiac valvular disease in patients with carcinoid tumors. Reduced 5-HT inactivation is one proposed mechanism of the valvulopathy observed in individuals treated with the appetite suppressants fenfluramine and phentermine. One key protein limiting systemic availability of 5-HT is the 5-HT transporter (5-HTT) expressed by platelets and pulmonary vascular cells; 5-HTT is responsible for 5-HT uptake and subsequent inactivation of the amine passing through the lung. Here we investigated whether 5-HTT-deficient (5-HTT-KO) mice developed structural and/or functional cardiac abnormalities and valvulopathy. METHODS AND RESULTS: Cardiac endothelial cells expressed large amounts of 5-HTT in wild-type mice. 5-HTT deficiency appeared to be associated with marked interstitial, perivascular, and valvular fibrosis as evidenced by staining of cardiac collagen in 5-HTT-KO mice. Histological analysis provided evidence for valvulopathy characterized by valvular hyperplasia and prominent fibrosis at the attachment site and base of the leaflets. Echocardiography revealed an increase in left ventricular lumen diameter and a decrease in left ventricular diameter fractional shortening. Although 5-HT1B receptors mediated the 5-HT-induced collagen secretion by human cardiac myofibroblasts, the contribution of this receptor type to valvulopathy was ruled out because double-KO mice deficient in both 5-HTT and 5-HT1B receptors showed the same cardiac alterations as 5-HTT-KO mice. CONCLUSIONS: The present results establish a link between 5-HTT and the development of cardiac fibrosis and valvulopathy in vivo. 5-HTT-KO mice represent an especially relevant model for studying the mechanisms by which 5-HT induces valvulopathy.

Animals↗
PubMed2005

Functional interaction between nucleus tractus solitarius NK1 and 5-HT3 receptors in the inhibition of baroreflex in rats.

OBJECTIVE: Previous data showed that in the nucleus tractus solitarius (NTS), 5-HT(3) receptors are critically involved in the inhibition of cardiac baroreceptor reflex response occurring during the defense reaction. Since stimulation of NTS NK(1) receptors has been found to inhibit the baroreflex bradycardia, we examined in this study whether this reflex response is inhibited during the defense reaction via an interaction between NK(1) and 5-HT(3) receptors. METHODS: For this purpose, we analyzed in urethane-anaesthetized rats the effects of intra-NTS GR205171, a selective NK(1) receptor antagonist, on the baroreflex bradycardia inhibition observed either during the defense reaction triggered by electrical stimulation of the dorsal periaqueductal grey matter (dPAG) or after NTS 5-HT(3) receptor activation. RESULTS: Intra-NTS GR205171, reversed, in dose-dependent manner, the inhibitory effect of dPAG stimulation on baroreflex bradycardia. This reversion was of 49% when both sinus carotid and aortic baroreceptors were stimulated by phenylephrine, and of 84% when aortic depressor nerve was stimulated. Similarly, intra-NTS GR205171 reversed partially or almost totally the inhibitory effect of local microinjections of phenylbiguanide, a 5-HT(3) receptor agonist, on baroreflex bradycardia induced either by phenylephrine administration or aortic nerve stimulation, respectively. CONCLUSION: These results strongly suggest that NK(1) receptors contribute downstream to the 5-HT(3) receptor-mediated inhibition of the aortic but not carotid cardiac baroreflex response occurring during the defense reaction, therefore implying that baroreceptor afferent inputs may be differentially modulated depending on their origin. This differentiation may be useful for a better understanding of baroreflex dysfunction in disease-induced conditions.

Animals↗
PubMed2005

[Neuroimaging characteristics of intracerebral haematoma].

The objective of brain imaging is to identify the hematoma according to its different stages and to find a potential underlying cause because of the risk of recurrence and the possibilities of treatment. In emergency, the diagnosis of hematoma is often obtained by CT scan, however today MRI has proved to be more accurate than CT to detect hemorrhage and to identify an underlying etiology. In some cases, according to the patient age, the medical history and the location of the hematoma, it may be necessary to perform a conventional angiography in order to exclude an intracranial vascular malformation. The aim of this review is to detail the different aspects of intracerebral hemorrhages according to the sequences and the temporal evolution, and to describe special findings which can help to identify an underlying etiology.

Cerebral Hemorrhage↗
PubMed2005

[Neuroimaging characteristics of cerebral infarcts].

Over the last years, technical advances in neuroimaging have allowed drastic improvements in the assessment of acute ischemic cerebral events. Beyond conventional morphological analysis, diffusion-weighted and perfusion-weighted MRI now enable routine functional assessment of brain tissue; spectroscopy and diffusion tensor imaging still remains in the domain of clinical research. During acute ischemia events, diffusion-weighted MRI can detect the movements of water molecules and cytotoxic edema related to cell injury enabling rapid diagnosis and early assessment of cerebral ischemia. In conjunction with perfusion imaging, which detects hypoperfusion areas, diffusion-weighted MRI provides a means to identify areas of penumbra ischemia. More recent multislice computed tomographic (CT) scans with multimodal analysis are also very competitive for assessment of cerebral ischemia (non-enhanced CT, CT angiography and perfusion CT). The purpose of this paper is to describe the CT and MRI patterns during the different stages of cerebral infarcts.

Acute Disease↗
PubMed2005

[Quantitative relationships between ADC and perfusion changes in acute ischemic stroke using combined diffusion-weighted imaging and perfusion MR (DWI/PMR)].

UNLABELLED: MR-based diffusion- and perfusion-weighted imaging (DWI/PWI) has become the standard imaging technique to assess the individual brain pathophysiological status in acute ischemic stroke. The finding of a "mismatch" with larger PWI than DWI abnormality is thought to reflect the presence of tissue at-risk of infarction, i.e., penumbra. However, there has been no detailed study of the quantitative relationships between perfusion and diffusion changes in stroke patients. According to the experimental concept of penumbra, the ADC would be expected to remain unchanged despite decreasing perfusion until a critical threshold is reached. We have tested this hypothesis directly in man. METHODS: DWI/PWI was performed in 7 patients with MCA territory stroke within 4-10 hrs from onset. Mismatch was defined on diffusion and rMTT maps, and circular ROIs were positioned within the ADC lesion (D), the mismatch area (M), and the normal appearing cortex (N); mirror ROIs were also obtained, and affected/unaffected ratios for ADC and rCBF were computed for each ROI. RESULTS: The mean (+/-1 SD) ADC ratios were 0.60 +/- 0.09, 0.95 +/- 0.10 and 1.02 +/- 0.04 in L, M and N, respectively; the corresponding rCBF ratios were 0.32 +/- 0.12, 0.75 +/- 0.14 and 0.97 +/- 0.09, respectively. The relationship was non-linear, with the rCBF but not the ADC ratio for M being significantly lower (p < 0.01) than that for N. A threshold for decline in ADC was apparent around 0.50 rCBF ratio. COMMENT: These results directly document in man that the ADC declines only after hypoperfusion has reached a certain degree (about 50%), consistent with the concept of the ischaemic penumbra.

Acute Disease↗
PubMed2005

[Diffusion MR imaging of the central nervous system: clinical applications].

Diffusion-weighted MR imaging is a technique in which image contrast is determined by the motion of water molecules within tissues. This motion is characterized by the apparent diffusion coefficient (ADC). This technique is particularly useful for the early detection of cerebral infarction but many other diseases of the central nervous system are associated with a change in water diffusion and may be assessed by diffusion-weighted MR imaging. This is an easy and fast pulse sequence providing useful data for early diagnosis and prognosis as well as information about underlying pathophysiology. After an overview of the basic concepts of diffusion imaging and the knowledge required for image interpretation, we will assess the potential value of this technique for the diagnosis of the main diseases of the central nervous system.

Brain Diseases↗
PubMed2004

High frequency monitoring of the coastal marine environment using the MAREL buoy.

The MAREL Iroise data buoy provides physico-chemical measurements acquired in surface marine water in continuous and autonomous mode. The water is pumped 1.5 m from below the surface through a sampling pipe and flows through the measuring cell located in the floating structure. Technological innovations implemented inside the measuring cell atop the buoy allow a continuous cleaning of the sensor, while injection of chloride ions into the circuit prevents biological fouling. Specific sensors for temperature, salinity, oxygen and fluorescence investigated in this paper have been evaluated to guarantee measurement precision over a 3 month period. A bi-directional link under Internet TCP-IP protocols is used for data, alarms and remote-control transmissions with the land-based data centre. Herein, we present a 29 month record for 4 parameters measured using a MAREL buoy moored in a coastal environment (Iroise Sea, Brest, France). The accuracy of the data provided by the buoy is assessed by comparison with measurements of sea water weekly sampled at the same site as part of SOMLIT (Service d'Observation du Milieu LIToral), the French network for monitoring of the coastal environment. Some particular events (impact of intensive fresh water discharges, dynamics of a fast phytoplankton bloom) are also presented, demonstrating the worth of monitoring a highly variable environment with a high frequency continuous reliable system.

Automation↗
PubMed2004

Family-based association study of the serotonin-6 receptor gene (C267T polymorphism) in schizophrenia.

The expression of serotonin type 6 receptor (5-HT(6)) in limbic and cortical regions of the brain, and its high affinity for atypical antipsychotics suggest that its encoding gene may play a role in the pathogenesis of schizophrenia. We firstly performed a meta-analysis of the C267T polymorphism of the 5-HT(6) gene in schizophrenia, based on four different case/control studies, and showed that the allelic distribution is not significantly different between patients and controls, even when taking into account the role of between samples heterogeneity. We then recruited 103 trios (patients with Diagnostic and Statistical Manual Mental Disorders, 4th ed. (DSM-IV) diagnosis of schizophrenia and their parents), and investigated the C267T polymorphism of the 5-HT(6) receptor gene with regard to family-based association study approach (haplotype relative risk (HRR) and transmission disequilibrium test (TDT)). We found no excess of transmission of one allele from the parents to their affected children, using the HRR (P = 0.60), as well as no evidence for linkage between C267T polymorphism and schizophrenia, using the TDT (P = 0.71). Furthermore, the 267T allele frequency was comparable in the different subgroups defined on age at onset, family history of schizophrenia, treatment response, and subtypes of patients based on positive versus negative predominant symptoms. These data do not support the idea that the 5-HT(6) receptor gene plays a major role in the etiopathogenesis of schizophrenia.

Alleles↗
PubMed2004

Long-term treatment with the antioxidant drug EGb 761 at senescence restored some neurobehavioral effects of chronic ultramild stress exposure seen in young mice.

In this study, we compared the effects of chronic ultramild stress (CUMS) exposure on decision-making behavior in a validated test, and on the stress responsive serotoninergic and dopaminergic systems in four age groups of B6D2F1 female mice (5-6, 11-12, 17-18 and 23-24 months old). The levels of serotonin (5-HT) and its metabolite 5-hydroxyindolacetic acid (5-HIAA) were measured in the brain stem, the cortex, the striatum and the hippocampus; the levels of dopamine (DA) and its metabolite dihydroxyphenylacetic acid (DOPAC) were measured in the brain stem and the striatum. The influence of a long-term treatment with the extract of Ginkgo biloba leaves EGb 761 (Tanakan) on age- and stress-related changes was also investigated in the two oldest age groups. In the absence of drug treatment, middle-age mice were the least efficient in making a decision, and senescent mice exhibited reduced levels of both 5-HT and DA and their metabolites in all the brain areas examined. CUMS facilitated evaluation and choice behavior in all age groups, but induced age-dependent reduction of hesitation, acceleration of information processing and reduction in serotoninergic neurotransmission. In senescent mice, EGb 761 reduced the impact of stress on evaluation and hesitation, and restored some stress-related neurobehavioral changes that were only seen in young mice, i.e. acceleration of information processing and reduction in brain 5-HIAA levels. Restoration of some plasticity of the serotoninergic systems might contribute to the stress alleviating influence of EGb 761 in old age.

3,4-Dihydroxyphenylacetic Acid↗
PubMed2004

Chronic treatment with imipramine reverses immobility behaviour, hippocampal corticosteroid receptors and cortical 5-HT(1A) receptor mRNA in prenatally stressed rats.

Prenatal stress in the rat induces enhanced reactivity of the hypothalamus-pituitary-adrenal (HPA) axis, disturbances in a variety of circadian rhythms and increased anxiety-like behaviour. Such abnormalities parallel those found in human depressed patients. Prenatally stressed (PS) rats could represent, therefore, an interesting animal model for the evaluation of the efficacy of pharmacotherapeutic intervention in psychiatric disorders that has often been addressed using control animals. In the present study, PS and non-stressed rats were chronically treated with the tricyclic antidepressant imipramine (10 mg/kg i.p. for 21 days) and assessed in the forced swim test. Glucocorticoid receptor binding sites in the hippocampus were measured and 5-HT(1A) receptor mRNA levels in the frontal cortex were also assessed. PS rats were characterised by increased immobility in the forced swim test, reduced hippocampal corticosteroid receptor binding and increased levels of cortical 5-HT(1A) mRNA. All these parameters were significantly reversed by chronic imipramine treatment. Conversely, no significant effects were observed for non-stressed rats. All these effects are consistent with the expected pharmacotherapy of depression-like abnormalities in PS rats. These results further indicate that PS rats are a relevant animal model of depression.

Animals↗
PubMed2004

Altered neurotensin mrna expression in mice lacking the dopamine transporter.

Psychostimulants and antipsychotic drugs increase mRNA expression of the neuropeptide neurotensin (NT) in the striatum and nucleus accumbens. In the present study, we used mice lacking the dopamine transporter (DAT) to investigate the consequences of a chronic hyperdopaminergic state on NT gene expression. NT mRNA expression was examined under basal conditions and after administration of haloperidol or amphetamine using in situ hybridization with a digoxigenin-labeled NT cRNA probe. DAT-/- mice exhibited a striking increase in the number of NT mRNA-expressing perikarya in the substantia nigra and ventral tegmental area, as well as a less pronounced increase in the lateral septum compared with wild-type littermates. No changes were detected in other regions expressing NT mRNA. Acute administration of haloperidol (1 mg/kg) induced a significant increase in the number of NT mRNA-expressing neurons in the dorsomedial and dorsolateral striatum of wild-type mice but failed to stimulate NT gene expression in DAT mutants. In contrast, a higher dose of haloperidol (5 mg/kg) stimulated striatal NT mRNA expression both in DAT+/+ and DAT-/- mice. Amphetamine (10 mg/kg) increased the number of hybridized neurons in the nucleus accumbens shell and fundus striati of wild-type and DAT-/- mice, indicating that the drug acted through a target other than DAT, such as the serotonin or the norepinephrine transporters. The up-regulation of NT mRNA observed in DAT-/- mice may represent an adaptive mechanism in response to constitutive hyperdopaminergia. These results illustrate the profound alterations in the NT system induced by chronic stimulation of DA receptors and underscore the potential clinical relevance of NT/DA interactions in schizophrenia and drug abuse.

Amphetamine↗
PubMed2004

Prevention of diazepam withdrawal syndrome by nifedipine-behavioural and neurochemical studies.

Our studies aimed at investigating whether the dihydropyridine calcium antagonist, nifedipine, could prevent anxiogenic-like consequences of diazepam withdrawal in rats. Animals withdrawn from chronic diazepam (2 mg/kg/day i.p. for 2 weeks) drank significantly less water than did control rats in the unfamiliar arm of a Y maze. This anxiogenic-like effect could be prevented by acute administration of nifedipine (at 10 mg/kg i.p., but not at lower doses), which, on its own, did not change water intake in naive rats. Given chronically in combination with diazepam for the second half of a 2-week treatment with this drug, nifedipine (at the daily dose of 5 mg/kg i.p.) also suppressed the reduction of water intake normally observed on diazepam withdrawal. Biochemical measurements showed that acutely, as well as chronically, administered nifedipine increased 5-HT turnover in the hippocampus of diazepam-treated rats, thereby suggesting that the prevention of diazepam withdrawal-induced anxiogenic behaviour by the calcium antagonist might be underlain by serotoninergic mechanisms.

Animals↗
PubMed2004

[Interest of PET/CT scan fusion to assess mandible involvement in oral cavity and oro pharyngeal carcinomas].

UNLABELLED: The aim of the study is to assess mandible involvement in oral cavity and oropharyngeal carcinomas. OBJECTIVE: To evaluate interest of fusion of Positron Emission Tomography (PET) with Computed Tomography scan (CT scan). METHOD: Eight patients were included in this prospective study. Each patient underwent PET and CT scan of the head and neck before surgery including tumorectomy and mandibulectomy. We compared results of PET- CT fusion with histologic examinations. RESULTS: Oral cavity (6), oropharyngeal (2) carcinoma: Mandibular invasion was suspected by PET-CT in 3 cases, but was confirmed in histological examination in only 2 cases. In 5 cases, PET-CT did not find mandibular invasion; this was confirmed in histological examination in all cases. Sensibility of PET-CT fusion was 100%, specificity was 83%. Positive predictive value was 66% and negative predictive value was 100%. DISCUSSION: PET-CT fusion provided maximal sensitivity. Specificity was better than for MRI but less than CT-scan. There were no false negatives and the false positive rate was 33%. CONCLUSION: PET-CT fusion is interesting to predict mandible involvement. Further studies are necessary to confirm these preliminary results.

Aged↗