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Biomedical subjects

C Moret

Publications and source records attributed to C Moret.

At least 19 recordsLinked to original sources

[Thrombus of the left lateral sinus spreading to the internal jugular vein].

Cerebral venous thrombosis is an uncommon event which presents a wide spectrum of sometimes extraneurological signs different from the classical clinical presentation. We report the cases of two middle-aged women who developed thrombosis of the left lateral sinus spread-ing to the internal jugular vein from the sigmoid sinus. The time course of the symptoms suggested that intracranial thrombosis occurred first. No infectious or neoplastic local disease could be found but both women were taking oral contraceptives. Medical treatment led to good reperfusion of the intracranial sinuses but occlusion of the jugular vein persisted despite prolonged oral anticoagulants. Long-term outcome was favorable with residual benign epilepsy in one patient, and occurrence of an arteriovenous fistula in the other.

Anticoagulants↗

The possible role of 5-HT(1B/D) receptors in psychiatric disorders and their potential as a target for therapy.

Serotonin (5-hydroxytryptamine, 5-HT) is implicated in several psychiatric diseases. Is this also true for 5-HT(1B/D) receptors? These receptors are found in high density in substantia nigra, globus pallidus, striatum and basal ganglia and in other brain regions. This ubiquity makes 5-HT(1B/D) receptors responsible for many physiological and behavioural functions. This review focuses on the role of 5-HT(1B) receptors in the regulation of 5-HT release and synthesis. Microdialysis experiments performed on freely moving animals are an interesting in vivo model to study the function of the terminal 5-HT(1B) autoreceptor. Synthesis of 5-HT, estimated by the measurement of the accumulation of 5-hydroxytryptophan (5-HTP) ex vivo or in vitro, is modulated by the 5-HT(1B) autoreceptors. Many reports have shown that chronic administration with selective serotonin reuptake inhibitors leads to the desensitisation of the terminal 5-HT(1B) autoreceptors. With the help of some animal models of depression and anxiety and with some data from clinical studies it has been hypothesised that 5-HT(1B) receptors may be supersensitive in depression, anxiety and obsessive compulsive disorder. Thus, since the dysfunction of 5-HT(1B) receptors may be involved in some pathological states, particularly in the psychiatric field, these receptors represent important potential targets for drugs to treat mental diseases.

Animals↗

[Radioanatomy of the cerebral cortex. Practical guide of identification].

Cerebral sulci identification process is based on several formal rules: it consists a series of steps allowing the identification of the major sulci. The process may be variable for each of us and we propose to read the images in certain order starting with the frontal lobe and its superior frontal gyrus than precentral and central gyri followed by the lateral fissure. Then the insular, lateral parietal and medial hemispheric regions. Finally the major sulci within the temporal and occipital lobes are described in the frontal plane. This presentation indicates the principal rules of cerebral lobes'identification, the basis of variability perception and the localization of small lesions allowing an accurate correlation with clinical findings and a suitable therapeutic procedure.

Cerebral Cortex↗

Five-year outcome in patients with isolated proximal left anterior descending coronary artery stenosis treated by angioplasty or left internal mammary artery grafting. A prospective trial.

BACKGROUND: Percutaneous transluminal coronary angioplasty (PTCA) and coronary artery bypass surgery (CABG) improve the clinical status of patients with isolated proximal left anterior descending coronary artery stenosis. At 2 years, only additional revascularization was more frequently required after PTCA. METHODS AND RESULTS: We monitored 134 patients randomized to PTCA (n=68) or CABG (n=66) for </=5 years. End points were death, myocardial infarction, need for additional revascularization, clinical status, and medical treatment. At 5 years, 6 patients (9%) had died in the PTCA group versus 2 (3%) in the CABG group (P=0.12). One patient in each group died of a cardiac cause. Myocardial infarction was more frequent after PTCA (15% versus 4%; P=0.0001), but Q-wave infarction was not (6% in the PTCA group versus 3% in the CABG group; P=0.8). Additional revascularization was required in 38% of patients in the PTCA group versus 9% in the CABG group (P=0.0001). Functional status was comparable, with 6% of patients after PTCA and 3% after CABG in functional class III or IV. Finally, after PTCA or CABG, 62% and 91% of patients, respectively, were free of events (P=0.0001). CONCLUSIONS: The 5-year prognosis of patients with isolated proximal left anterior descending coronary artery stenosis is good. Both PTCA and CABG improve clinical status, but revascularization was needed more frequently after PTCA. There is an excess incidence of non-Q-wave myocardial infarction in the PTCA group that does not affect the vital or symptomatic outcome.

Angioplasty, Balloon, Coronary↗

[Dysembryoplastic neuroepithelial tumors. Analysis of 16 cases].

OBJECTIVES: We report on 16 cases of dysembryoplastic Neuroepithelial tumor (DNT) treated in the Nancy University Hospital from 1987 to 1997. PATIENTS AND METHODS: There were 9 males and 7 females. Mean age at onset of symptoms was 9.5 years (range: 3 months to 29 years) and the mean age at surgery was 16 years. Nine patients experienced partial complex seizures, 5 patients generalized seizures, 1 patient partial seizures with secondary generalization and one patient ataxia. The diagnosis of DNT was made under consideration of clinical, radiological and neuropathological features. All patients underwent surgery. RESULTS: Removal of the tumor was complete for 10 patients, subtotal or partial for 6 patients. Histological examination revealed that 7 cases were specific forms of DNT due to the presence of the specific glioneuronal element. For the 9 remained cases, the diagnosis of DNT could only be made with the consideration of clinical and radiological features. Mean post-surgical follow-up was 3.5 years (range: 1-8 years). Eight patients were seizures-free, 7 had a significative reduction in seizures frequency with minimal anti-convulsivant treatment. The patient with ataxia remained unchanged. For the patients with partial resection of the tumor, follow-up MRI and CT scan showed no significant growth of the remnant and the remaining patients have had no recurrence to date. CONCLUSION: The recognition of this surgically curable entity is mandatory. Knowledge of the good prognosis associated with the DNT is essential to avoid deleterious side effects of overtreatment by radiotherapy and/or chemotherapy.

Adolescent↗

[Diffusion imaging in asymptomatic focal vasospasm. Apropos of a case].

We report a case of an asymptomatic vasospasm with a focal, reversible apparent diffusion coefficient (ADC) decrease after a middle cerebral artery aneurysm rupture. This isolated decrease of ADC has not yet been reported in this pathological situation. It could be interesting to predict the risk of ischemic delayed complications of vasospasm.

Adult↗

[MRI aspects of spinal cord abscesses. Report of 5 cases and review of the literature].

The spinal canal is an uncommon site for abscess formation resulting from bloodstream disseminated infection. Prognosis is often unfavorable. Rapid treatment is essential for satisfactory neurological recovery. Abscesses within the spinal canal are thus diagnostic and therapeutic emergencies. The neuro-infectious and inflammatory manifestations and laboratory findings vary considerably and are insufficient for diagnosis. MRI plays a decisive role. The most commonly reported signs are the presence of an intramedullary collection giving a low-intensity signal on T1-weighted images and a high-intensity signal on T2-weighted images with peripheral contrast uptake and generally extended adjacent medullary edema. We report here five cases of spinal canal abscesses diagnoses with MRI at different stages of development (pre-suppurative myelitis in two cases, constituted abscess in three cases). For each case we reviewed the clinical course and describe the details of the imaging findings. In our series, the collected abscesses presented as round lesions within the canal with contrast uptake. It is noteworthy that the periependymal gray matter adjacent to the lesion also took up the contrast agent in all patients with a collected abscess. This sign has not been described previously and appears to be a going argument orienting the diagnosis towards an infectious rather than tumoral formation.

Abscess↗

[Percutaneous versus surgical revascularization of isolated lesions of the proximal anterior interventricular artery. Five-year follow-up of a prospective randomized study].

The authors report the results of 5 years follow-up of 134 patients who benefited from percutaneous transluminal coronary angioplasty 5PTCA) or surgical intervention with implantation of the internal mammary artery as treatment of an isolated lesions of the proximal left anterior descending artery with normal left ventricular function. Sixty-eight patients underwent PTCA (group 1) and 66 had surgical bypass (group 2). The demographic data of the two groups was comparable. The incidence of the following events was analysed: death, myocardial infarction, indication for further revascularisation and functional class. At 5 years, the global mortality was 6% (8% in group 1 and 2% in group 2) but cardiac mortality was only 1% (1 patient in each group). The cumulative incidence of myocardial infarction was higher after angioplasty (15% vs 5%) but was mainly related to acute occlusions or acute coronary syndromes during angioplasty. However, the incidence of Q wave infarction was similar in the two groups. During follow-up, 32 patients (26 in group 1 and 6 in group 2) required one or more additional revascularisation procedures of the left anterior descending or of another artery. The proportion of asymptomatic patients at 5 years was high and similar in both groups. Finally, the proportion of patients without events during follow-up was 56% in group 1 and 86% in group 2. Despite the risk of restenosis and reoperation associated with angioplasty, this technique is an acceptable therapeutic alternative to surgical revascularisation in patients with isolated stenosis of the left anterior descending artery. Therefore, the therapeutic decision depends on the individual case, the availability of treatment and the patient's preference during consultation.

Angioplasty, Balloon, Coronary↗

5-HT1B receptor antagonist properties of novel arylpiperazide derivatives of 1-naphthylpiperazine.

A new series of arylpiperazide derivatives of 1-naphthylpiperazine of general formula 4 has been prepared and evaluated as 5-HT1B antagonists. Binding experiments at cloned human 5-HT1A, 5-HT1B, and 5-HT1D receptors show that these derivatives are potent and selective ligands for 5-HT1B/1D subtypes with increased binding selectivity versus the 5-HT1A receptor when compared to 1-naphthylpiperazine (1-NP). Studies of inhibition of the forskolin-stimulated cAMP formation mediated by the human 5-HT1B receptor demonstrate that the nature of the arylpiperazide substituent modulates the intrinsic activity of these 1-NP derivatives. Among them, 2-[[8-(4-methylpiperazin-1-yl)naphthalen-2-yl]oxy] -1-(4-o-tolylpiperazin-1-yl)ethanone (4a) was identified as a potent neutral 5-HT1B antagonist able to antagonize the inhibition of 5-HT release induced by 5-CT (5-carbamoyltryptamine) in guinea pig hypothalamus slices. Moreover, 4a was found to potently antagonize the hypothermia induced by a selective 5-HT1B/1D agonist in vivo in the guinea pig following oral administration (ED50 = 0.13 mg/kg).

Animals↗

Ex vivo inhibitory effect of the 5-HT uptake blocker citalopram on 5-HT synthesis.

Serotonin (5-hydroxytryptamine, 5-HT) synthesis was determined in vivo by measuring the accumulation of 5-hydroxytryptophan (5-HTP) in rat frontal cortex after inhibition of aromatic amino acid decarboxylase by administrative of m-hydroxybenzylhydrazine (NSD 1015) (100 mg/kg, i.p.). The selective 5-HT reuptake inhibitor, citalopram, the 5-HT1A agonists, (+/-) 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT), ipsapirone, gepirone and the 5-HT1A/B agonist, 7-trifluoromethyl-4(4-methyl-1-piperazinyl-pyrolo[1,2-a]-quinox ali ne (CGS 12066B), the 5-HT1A/B ligands and beta-adrenoceptor antagonists, (+/-) pindolol and (+/-) alprenolol, and the non-selective 5-HT ligands, m-chlorophenylpiperazine (mCPP) and metergoline, all inhibited the synthesis of 5-HT. The 5-HT1A/5-HT2 antagonist, spiperone, alone, had no effect on basal 5-HT synthesis, however it attenuated the effect of 8-OH-DPAT by 56% and CGS 12066B by 39% but only barely that of citalopram by 17%. The selective 5-HT1A antagonist, WAY 100635, which did not modify by itself 5-HT synthesis, had no effect on citalopram-induced reduction of 5-HT synthesis. Neither the 5-HT2 agonist, (+/-)1-(2,5-dimethoxy-4-indophenyl)-2-aminopropane (DOI) nor the 5-HT2 antagonist, ritanserin, had any effect on the synthesis of 5-HT. In addition, ritanserin did not modify the inhibitory effect of citalopram. Methiothepin was the only compound to increase 5-HT synthesis. These results suggest that the effect of citalopram on the synthesis of 5-HT is not mediated by 5-HT1A or 5-HT2 receptors and that other receptors may be involved.

Animals↗

Effects of milnacipran and pindolol on extracellular noradrenaline and serotonin levels in guinea pig hypothalamus.

Milnacipran, a dual noradrenaline (NA) and serotonin (5-hydroxytryptamine, 5-HT) uptake inhibitor, increased extracellular levels of NA and 5-HT in hypothalamus of freely moving guinea pigs as measured by microdialysis. The basal levels of both monoamines, which were tetrodotoxin sensitive, were increased in a dose-dependent manner and to a similar extent after the intraperitoneal administration of milnacipran (10 and 40 mg/ kg i.p.). Levels of the NA metabolite 4-hydroxy-3-methoxyphenylglycol (MHPG) were decreased by milnacipran at 10 and 40 mg/kg i.p., whereas those of the 5-HT metabolite 5-hydroxyindoleacetic acid (5-HIAA) showed no effect. Subcutaneous injection of 5-HT1A and beta-adrenergic receptor antagonist (-)-pindolol alone, at 10 mg/kg, had no effect on the extracellular levels of NA or 5-HT. The concomitant administration of (-)-pindolol (10 mg/kg s.c.) with milnacipran (10 mg/kg i.p.) increased severalfold the effect of milnacipran on the extracellular levels of NA and 5-HT. These results indicate that milnacipran, by blocking the uptake of NA and 5-HT, increases virtually equipotently the extracellular levels of NA and 5-HT, confirming previous in vitro studies. In addition, the antagonism of 5-HT1A autoreceptors by (-)-pindolol potentiates the action of milnacipran on both NA and 5-HT systems, without modifying the ratio of these activities.

Adrenergic beta-Antagonists↗

Autoradiographic localization of 5-HT1E and 5-HT1F binding sites in rat brain: effect of serotonergic lesioning.

5-carboxamidotryptamine (5-CT)-insensitive binding sites labelled by [3H]5-hydroxytryptamine (5-HT) in the presence of 100 nM 5-CT and 100 nM mesulergine, were examined by semi-quantitative autoradiography in rat brain. Under these conditions most of the labelled sites correspond to 5-HT1E and 5-HT1F sites. The 5-CT-insensitive binding is located mainly in cortical layer V, caudate-putamen, interpeduncular nucleus and claustrum. In cortex and caudate-putamen, a large proportion of 5-CT-insensitive sites is displaced by 250 nM sumatriptan and can be attributed to the presence of 5-HT1F receptors. A low, but significant, level of displacement by sumatriptan was observed in the choroid plexus. Lesions of serotonergic neurones by intracerebroventricular 5,7-dihydroxytryptamine injection does not significantly modify the densities of 5-HT1E or 5-HT1F binding sites. Our findings suggest that the 5-HT1F receptor has a limited distribution in rat brain, mainly located on non-serotonergic neurones.

Animals↗

[Unusual facial clefts].

After briefly review facial morphogenesis, the authors define facial clefts, distinguishing primary clefts, secondary clefts, and residual clefts. They discuss the uncertainties surrounding the embryology and clinical features of palpebral colobomas. The various pathogenetic concepts are analysed: amniotic hypothesis, vascular hypothesis, fusion defect. The various classifications of rare facial clefts are reviewed, with particular emphasis on Tessier's classification and the so-called Milan classification. The general principles of surgical treatment are described together with the various skeletal and soft tissues procedures.

Craniofacial Abnormalities↗

Effects of acute and repeated administration of citalopram on extracellular levels of serotonin in rat brain.

The effects of acute (2 days) and repeated (21 days) administration (50 mg/kg in the diet) of the selective serotonin (5-HT, 5-hydroxytryptamine) reuptake inhibitor, citalopram, on extracellular levels of 5-HT and their modulation by terminal autoreceptors in the hypothalamus of freely moving rats were compared in vivo by microdialysis. When studied without washout, extracellular levels of 5-HT were increased by both acute and repeated citalopram administration. In rats treated repeatedly, extracellular 5-HT levels were 43% (but not significantly) greater than in those treated acutely. Extracellular levels of 5-HT in control and citalopram-treated rats were similar when measured after 24 h washout. The enhancing effect of non-selective serotonergic autoreceptor antagonists, methiothepin (100 microM) or 1-(1-naphthyl)piperazine (NP) (10 microM), administered through the microdialysis probe, after 24 h washout, was similar in both control and chronically treated groups. These results suggest that repeated administration of citalopram followed by a washout of 24 h does not lead to desensitization of the terminal autoreceptor as measured in vivo in contrast to the effects we have shown previously in vitro. In rats treated chronically with citalopram without washout, methiothepin had a greater maximal effect on 5-HT outflow in comparison to rats receiving acute citalopram treatment. This finding suggests that a 5-HT autoreceptor antagonist or a combination of such a drug with a 5-HT uptake inhibitor would produce a greater increase of extracellular levels of 5-HT in hyposerotonergic states such as depression.

Animals↗

Preclinical pharmacology of milnacipran.

Milnacipran (Ixel) is a new antidepressant which has been developed for its selective inhibition of both serotonin and noradrenaline reuptake and its lack of affinity for neurotransmitter receptors. It inhibits virtually equipotently the reuptake of serotonin and noradrenaline both in vitro and in vivo, as demonstrated by the antagonism of centrally acting monoamine displacers. It has no effect on dopamine reuptake. In addition, milnacipran has been shown by intracerebral microdialysis to increase the extracellular levels of both serotonin and noradrenaline after acute administration. Milnacipran is devoid of interactions at any known neurotransmitter receptor or ion channel. In particular, and unlike tricyclic antidepressants, it does not act at noradrenergic, muscarinic or histaminergic receptors. Contrary to tricyclic antidepressants, chronic administration of milnacipran does not modify beta-adrenoceptor binding or second messenger function. Milnacipran is active on various animal models of depression such as the forced swimming test in the mouse, learned helplessness in the rat and the olfactory bulbectomized rat model. This pharmacological profile, associated with an excellent bioavailability in man, was predicted to be that required for a powerful and well-tolerated antidepressant. Subsequent clinical development has shown this prediction to be well founded.

Adrenergic Uptake Inhibitors↗

In vitro and in vivo activity of 1-(1-naphthyl)piperazine at terminal 5-HT autoreceptors in guinea-pig brain.

The effect of 1-(1-naphthyl)piperazine (NP) on the 5-HT terminal autoreceptor modulating 5-HT release was investigated in vitro and in vivo. In vitro 5-HT release was measured in slices of guinea-pig substantia nigra and hypothalamus prelabelled with 3H-5-HT, superfused with Krebs solution and depolarized electrically. NP, at 0.1 and 1 mumol/l, did not modify the calcium-dependent release of 3H-5-HT elicited by electrical stimulation using a frequency of 5 Hz, however at 0.1 mumol/l NP shifted to the right the inhibition curve of the non-selective autoreceptor agonist, 5-carboxamidotryptamine, in both regions. In hypothalamus when using lower frequencies (1 Hz or 0.2 Hz) or under pseudo-one-pulse stimulation, NP decreased the release of 3H-5-HT at 1 mumol/l. In vivo microdialysis was used to measure extracellular levels of endogenous 5-HT in the substantia nigra of freely moving guinea-pigs. The endogenous release of 5-HT was tetrodotoxin (TTX)-sensitive, indicating a neuronal origin of this efflux. NP, administered through the microdialysis probe (1-100 mumol/l), increased the levels of extracellular 5-HT in concentration-dependent and TTX-sensitive manner. These results suggest that in vitro NP acts as a 5-HT autoreceptor partial (ant)agonist in the substantia nigra and hypothalamus of guinea-pigs, and as a full antagonist in vivo. However, NP administered systemically at 10 mg/kg i.p., did not modify the levels of extracellular 5-HT in the substantia nigra. This lack of systemic effect of NP probably results from its interaction at other receptors that modify 5-HT neurotransmission.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗