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Biomedical subjects

F Mercier

Publications and source records attributed to F Mercier.

At least 19 recordsLinked to original sources
PubMed2006

A prospective study of the evolution of lamivudine resistance mutations in patients with chronic hepatitis B treated with lamivudine.

Lamivudine resistance has been described in subjects with chronic hepatitis B infections, associated with mutations in the viral polymerase gene. The objective of this study was to estimate the emergence rate of lamivudine-resistant viral strains and their consequences over a 2-year period. We evaluated 283 lamivudine-naïve subjects with chronic hepatitis B. Clinical and virological features were assessed at inclusion and every 6 months thereafter. Viral DNA was characterized using polymerase chain reaction (PCR)-based sequencing. Potential risk factors for the emergence of lamivudine resistance mutations were assessed using logistic regression analysis. The annualized incidence rate for viral polymerase mutations was 22%. The only independent risk factor identified was high viral load, at inclusion. Detectable viral DNA and elevated transaminases were more frequent in subjects harbouring mutant viral strains, and these underwent a lower rate of hepatitis B e seroconversion. All subjects responded favourably to treatment, with no difference in symptoms between the two groups. This prospective cohort study identified lamivudine-resistant mutations emerging in 22% of subjects, yearly, which were apparently not associated with clinical aggravation over the study period.

Adolescent↗
PubMed2005

Synthesis and biological evaluation of N-methyl-laudanosine iodide analogues as potential SK channel blockers.

Neuronal action potentials are followed by an afterhyperpolarisation (AHP), which is mediated by small conductance Ca2+-activated K+ channels (SK channels or KCa2 channels). This AHP plays an important role in regulating neuronal activity and agents modulating AHP amplitude could have a potential therapeutic interest. It was previously shown that N-methyl-bicuculline iodide blocks SK channels but its GABA) activity represents a serious drawback. In view of the structural analogy between bicuculline and laudanosine 14, several N-quaternary analogues of the latter were developed. It was shown that N-methyl-laudanosine 15 (NML) and N-ethyl-laudanosine 16 induce a reversible and relatively specific blockade of the apamin sensitive AHP in dopaminergic neurones with mean IC50s of 15, and 47 microM, respectively. Laudanosine 14, N-butyl-17 and N-benzyl-18 derivatives were less potent. In order to find pharmacophore elements, modifications were performed at different positions such as C-1, C-6 and C-7. Intracellular recordings on rat midbrain dopaminergic neurones were made in order to evaluate the putative blockade of SK channels by these molecules. Simplified structures such as tetrahydroisoquinoline derivatives with H or Me at C-1 1-6 presented no significant activity at 300 microM. The presence of a 1-(3,4-dimethoxybenzyl) moiety seems an important feature. Indeed, compound 8 showed a blockade of the AHP of only 33% at 300 microM while compound 13 blocked it by 67%, respectively, at the same concentration. Binding experiments were also performed. Binding affinities for SK channels are in good agreement with electrophysiological data. These results indicate that the presence of a charged nitrogen group is an essential point for the affinity on SK channels. Finally, because of the similar activity of both enantiomers of NML 19 and 20, the interaction site may present a symmetrical configuration.

Animals↗
PubMed2004

[Recombinant activated factor VII as a life-saving therapy for severe postpartum haemorrhage unresponsive to conservative traditional management].

Postpartum haemorrhage remains the main cause of maternal morbidity and mortality. Treatment aims at maintaining hemodynamic circulation and preventing shock by stopping blood loss both medically and surgically. We report two cases of major postpartum haemorrhage due to uterine atony. Patients developed haemorrhagic shock and severe coagulation disorders (nadir values of PTT were <10% and fibrinogen was <0.1 g/l). Well-codified medical (ocytocin, sulprostone) and surgical management (ligation of both hypogastic arteries in the two cases completed by staged uterine ligation in one case) failed to stop bleeding. Recently, several case reports described successful use of recombinant activated factor VII (rFVIIa) in scheduled surgery, trauma and major postpartum haemorrhage. Thus, after transfusion of more than one blood mass and failure of surgical haemostasis to stop bleeding, rFVIIa (60 microg/kg) was given. A single iv bolus injection stopped ongoing diffuse haemorrhage in the two cases. No further transfusion was required afterwards in both patients. RFVIIa might thus be a strong complementary agent in the management of major postpartum haemorrhage. Optimal dose, timing and safety characteristics of rVIIa administration remain to be determined. One patient developed four weeks later thrombosis of both ovarian veins, a complication that can be related to either rFVIIa or to the staged uterine ligations performed during surgery.

Adult↗
PubMed2003

Modulation of small conductance calcium-activated potassium (SK) channels: a new challenge in medicinal chemistry.

Small conductance calcium-activated potassium (SK) channels are found in many types of neurons as well as in some other cell types. These channels are selective for K(+) and open when intracellular Ca(2+) rises to omega 500 nM. In neurons, this occurs during and after an action potential. Activation of SK channels hyperpolarizes the membrane, thus reducing cell excitability for several tens or hundreds of milliseconds. This phenomenon is called a afterhyperpolarization (AHP). Three subtypes of SK channels (SK1, SK2, SK3) have been cloned and exhibit a differential localization in the brain. SK channels may play a role in physiological and pathological conditions. They may be involved in the control of memory and cognition. Moreover, they are heavily expressed in the basal ganglia (in particular in the substantia nigra, pars compacta) and in the limbic system, suggesting that they may modulate motricity and emotional behaviour. Based on these facts, SK channel subtypes may be a suitable target for developing novel therapeutic agents, but more work is needed to validate these targets. Hence, there is a great need for selective ligands. Moreover, although the risk of peripheral side-effects for SK channel modulators appears to be low, some questions remain to be investigated. Currently, different molecules are known as SK channel modulators. Apamin is a very potent peptidic agent; it produces a strong blockade of these targets which is only very slowly reversible and it has limited selectivity. Dequalinium was found to be an effective blocker. Different chemical modulations on the dequalinium structure led to the discovery of highly potent bis-quinolinium derivatives such as UCL 1684. Other bis-(2-amino-benzimidazole) derivatives are in development. On the other hand, quaternary salts of bicuculline were reported to be effective in inhibiting AHPs. More recent developments on structurally-related molecules revealed that methyl-laudanosine is a new interesting tool for exploring SK channel pharmacology. Finally, a family of compounds has been shown to facilitate SK channel opening. Such compounds may be useful in treating disorders involving neuronal hyperexcitability.

Animals↗
PubMed2002

Synthesis of new tricyclic phosphines and phosphinites by intramolecular Diels-Alder reactions of trivalent phospholes.

Phospholes bearing an allyl-X substituent at phosphorus tend to undergo an intramolecular Diels-Alder cycloaddition (IMDA) leading to the corresponding tricyclic derivative. When X = O or NR, the IMDA easily takes place at room temperature. When X = CH2, the IMDA slowly takes place around 110-140 degrees C, as a function to the substitution pattern of the dienic system. Two tricyclic derivatives (X = O and CH2) have been characterized by X-ray crystal structure analysis of the P-sulfides.

Journal Article↗
PubMed2001

Connexin 26 and basic fibroblast growth factor are expressed primarily in the subpial and subependymal layers in adult brain parenchyma: roles in stem cell proliferation and morphological plasticity?

The gap junction protein connexin 26 (Cx26) has been detected previously in the parenchyma of the developing brain and in the developing and adult meninges, but there is no clear evidence for the presence of this connexin in adult brain parenchyma. Confocal mapping of Cx26 through serial sections of the meningeal-intact rat brain with four antibodies revealed an intense Cx26 immunoreactivity in both parenchyma and extraparenchyma. In the extraparenchyma, a continuum of Cx26-immunoreactive puncta was observed throughout the three meningeal layers, the perineurium of cranial nerves, and meningeal projections into the brain, including sheaths of blood vessels and stroma of the choroid plexus. In the parenchyma, Cx26-immunoreactive puncta were located primarily in subependymal, subpial, and perivascular zones and were associated primarily with glial fibrillary acidic protein-positive (GFAP+) astrocytes, the nuclei of which are strongly immunoreactive for basic fibroblast growth factor (bFGF). Although it was found to a lesser extent than in astrocytes, bFGF immunoreactivity also was intense in the nuclei of meningeal fibroblasts. In addition, we have found a close correlation between the distribution of Cx26 and vimentin immunoreactivities in the meninges and their projections into the brain. We previously showed vimentin and S100beta immunoreactivities through a network of meningeal fibroblasts in the three layers of meninges, perivascular cells, and ependymocytes and in a population of astrocytes. The related topography of this network with GFAP+ astrocytes has also been demonstrated. Considering that connexin immunoreactivity may reflect the presence of functional gap junctions, the present results are consistent with our hypothesis that all of these various cell types may communicate in a cooperative network.

Animals↗
PubMed2001

Enhancing the dienic reactivity of phospholes: an improved access to trivalent 7-phosphanorbornenes.

A structural comparison of 1-cyano- and 1-alkoxy-3,4-dimethylphospholes with 1-benzylphosphole has led to some unexpected conclusions. There is no univocal relationship between phosphole aromaticity and pyramidality at phosphorus. It has been found that both the highly pyramidal 1-cyanophosphole 1 (sigma(CPC angles) = 290 degrees), and the much less pyramidal 1-alkoxyphosphole 6 (sigma(CPC angles) = 310 degrees) have a low Bird aromaticity index (27 for both molecules), when compared to 1-benzylphosphole (sigma(CPC angles) = 303 degrees, BI = 35.5). This low aromaticity is correlated with a high reactivity of the diene in both 1 and 7 (similar to 6) toward acrylonitrile. Good stereochemical control is observed with 7, which gives exclusively the anti,endo [4 + 2] cycloadducts with acrylonitrile and diethyl vinylphosphonate.

Journal Article↗
PubMed2001

Management in intractable obstetric haemorrhage: an audit study on 61 cases.

OBJECTIVE: To refine the indications of bilateral hypogastric artery ligation (BHAL) and angiographic selective embolisation (ASE) in intractable obstetric haemorrhage. DESIGN: an audit study. SETTING: Tertiary care university hospital. POPULATION AND METHODS: Retrospective analysis of 61 cases of obstetric intractable post partum haemorrhage (PPH) initially managed either by hysterectomy or a conservative approach in a tertiary referral centre between 1983 and 1998. Procedures were reviewed as a primary (P) or secondary (S) attempt to arrest the haemorrhagic process. RESULTS: Ten hysterectomies (5 P, 5 S), 49 BHAL (48 P, 1 S) and 9 ASE (8 P, 1S) were successfully performed in arresting the haemorrhagic process. There were 7 maternal deaths, 5 following hysterectomy and 2 following a conservative approach. Atony of the uterus was the main cause of haemorrhage (n=21) and genital tract laceration was associated with the worst prognosis. Time-elapse between delivery and surgery appears to be the main prognostic factor. Nine patients became pregnant 1 to 4 years later following a conservative approach. CONCLUSIONS: ASE seems to be indicated in haemodynamically stable patients with birth canal trauma or uterine atony and clotting anomalies. BHAL is indicated when haemorrhage occurs after a cesarean section or when the patient is haemodynamically unstable. BHAL should be taught to Junior doctors in an attempt to decrease the number of patients transferred in tertiary referral centers for intractable PPH. This might also decrease the number of hysterectomies in intractable PPH.

Adult↗
PubMed2000

Immunocytochemical basis for a meningeo-glial network.

Evidence is presented here for a cellular network that courses through all layers of meninges, the vasculature of both the brain and meninges, and extends into the brain parenchyma. Confocal mapping of calcium-binding protein S100beta immunoreactivity (S100beta-ir) and of the intermediate filament vimentin-ir through serial sections of the meningeal-intact adult rat brain revealed this network. In all tissues examined, S100beta-ir and vimentin-ir were primarily colocalized, and were found in cells with elongated processes through which these cells contacted one another to form a network. The location of labeling and the morphology of the cells labeled were consistent with the possibility that this network consists of fibroblasts in the meninges and the walls of large blood vessels, of pericytes at the level of capillaries, and of ependymocytes and a population of astrocytes in the brain parenchyma. At many sites along the borders of the brain parenchyma itself and of the brain blood vessels, it was possible to detect S100beta-ir and vimentin-ir cell processes that cross the basal laminae. This suggested the probable means by which the S100beta-ir cells of the extraparenchymal tissues anatomically contact the cells that express the same markers in the brain. Privileged anatomical relationships of the S100beta/vimentin network with the glial fibrillary acidic protein (GFAP) astrocytes further suggested that, together, they form the structural basis for a general meningeo-glial network. This organization challenges the current model of brain architecture, calls for a reconsideration of the role of meninges and vascular tissues, and appears to reflect the existence of hitherto unsuspected systems of communication.

Animals↗
PubMed1999

Aortic dissection of Kommerell's diverticulum in Marfan's syndrome.

We report a surgical case of chronic aortic dissection with an entrance tear on Kommerell's diverticulum, a rare embryologic anomaly, with an extension to the arteria lusoria, in a patient with Marfan's syndrome. The operation consisted of aortic root and arch replacement with reimplantation of the right subclavian artery in the right carotid artery under circulatory arrest and deep hypothermia.

Adult↗
PubMed1999

Smooth muscle differentiation in human vein wall at valvular level: comparison with nonvalvular wall and correlation with venous function.

The aim of this study was to evaluate local differences in smooth muscle differentiation in venous valves of patients suffering from chronic venous insufficiency, in relation to functional hemodynamic parameters measured by echo Doppler. These functional parameters did not correlate with smooth muscle differentiation at the valvular site. These results failed to support an initiating role of valvular structure in the development of chronic venous insufficiency. However, this work stresses differences in cellular differentiation of valve wall and nonvalvular smooth muscle cells in culture, and we found histologic differences in the structure of endovein and media (connective tissue relative content) between valvular and nonvalvular venous wall. The presence of smooth muscle cells in the valve cusp was demonstrated by smooth muscle alpha-actin-specific labeling and was observed to be restricted to one side of the valve cusp.

Actins↗
PubMed1999

Long-term outcome in patients under 40 years after revascularization for chronic lower limb ischaemia.

BACKGROUND: In order to find out if surgical or endoluminal treatment changes the long-term results of atherosclerotic occlusive disease in patients of under 40 years of age we reviewed 17 consecutive patients. METHODS: Their mean age was 36.5. Patients with Buerger's disease or inflammatory arteriopathy were excluded. All patients were extremely heavy smokers. The indications for surgical procedures were disabling claudication (less than 100 meters) for 11 patients, rest pain for 4 patients and grangrene of a lower limb for 2 patients. The lesions were aorto-iliac in 12 cases and femoro-popliteal in 5. Ten surgical procedures were performed (5 aorto-femoral bypasses, 1 ilio-femoral bypass associated with an aorto-renal bypass, 2 femoropopliteal bypasses, 1 aorto-iliac endarteriectomy, 1 femoral endarteriectomy). On the other hand there were 7 endoluminal procedures (1 aortic, 4 iliac, 1 femoral and 1 popliteal). RESULTS: The mean follow-up was 97.3+/-50 months (range, from 34 to 216 months). Two patients died by 57 and 132 months respectively. At 5 years the survival rate was 94%; the primary patency rate was 59%; the secondary patency rate was 81% and the limb salvage rate was 94%. At 10 years these rates were respectively 94%, 44%, 54% and 75%. A total of 21 reoperations were performed. During follow-up 11 patients were better, 2 were stable and 4 were worse with 2 limbs lost. CONCLUSIONS: These bad results suggest keeping the surgical and endoluminal indications for patients younger than 40 years with threatened limbs.

Adult↗
PubMed1998

Influence of the status of the contralateral carotid artery on the outcome of carotid surgery.

From 1985 to 1995, 747 carotid arteries were operated on in 694 patients, who were under general anesthesia and continuous electroencephalogram (EEG) monitoring. These patients were divided into three groups according to contralateral carotid status. Group 1 consisted of 58 patients who had contralateral occlusion; group 2, 53 patients who had contralateral stenosis and bilateral staged surgery; and group 3, 583 patients who had nonstenotic contralateral internal carotid artery. All groups were similar with regard to age and sex ratio. There were more asymptomatic patients in group 3 than in group 1 (39.9% vs. 25.8%) (p < 0.05), and less preoperative strokes in group 2 than in the other groups (3.7% vs. 17.2% and 13. 6%, respectively) (p < 0.05). Among risk factors, smoking was less frequent in group 3 (59.5%) than in group 1 (82.7%) and group 2 (77%) (p < 0.01), and coronary artery disease was more frequent in group 2 (60%) than in group 1 (32.7%) and Group 3 (26.4%) (p < 0.01). EEG changes occurred more frequently in group 1 (25.8%) than in group 2 [5.6% (first stage) and 3.8% (second stage)] and in group 3 (4.9%) (p < 0.01). A shunt was used only when EEG changes did not disappear after pharmacologic increasing of central blood pressure, which occurred more frequently in group 1 (10.3%) than in group 2 (0%) and group 3 (0.3%) (p < 0.05). The combined morbidity/mortality rate was similar for groups 1 and 3 (1.7% and 1.5%, respectively), however, transient morbidity was more frequent in group 1 (6.9%) than in group 3 (1.5%) (p < 0.05). The combined morbidity/mortality rate was higher in group 2 than in group 3 (7.5% vs. 1.5%) (p < 0. 05), and all strokes in group 2 were seen during the second-stage operation. In conclusion, contralateral carotid artery occlusion had minimal influence over carotid surgery results. Selective use of a shunt based on EEG monitoring prevented ischemic strokes, with minimal neurologic morbidity. Contralateral carotid stenosis did not affect operative strategy for first stage, but we noted a higher incidence of strokes during the second procedure.

Aged↗