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Biomedical subjects

N Morel

Publications and source records attributed to N Morel.

At least 19 recordsLinked to original sources

[Microparticles during sepsis and trauma. A link between inflammation and thrombotic processes].

Sepsis and trauma lead to a sustained activation of monocytes and endothelium. In the vascular compartment, stimulated cells release microparticles. Circulating MP provide an additional procoagulant phospholipid surface enabling the assembly of the clotting enzymes complexes and thrombin generation. Their procoagulant properties rely on the exposition of phosphatidylserine, made accessible after cell stimulation and on the possible presence of tissue factor, the main cellular initiator of blood coagulation. Microparticles constitute the main reservoir of blood-borne tissue factor activity. At sites of endothelium injury, enhanced release or recruitment of procoagulant MP through P-selectin-PSGL-1 pathway could concentrate TF activity above a threshold allowing blood coagulation to be triggered. Converging evidences from experimental or clinical data highlight a role for MP harboring tissue factor in the initiation of disseminated intravascular coagulopathy. In these settings, the pharmacological modulation of MP levels or biological functions through activated protein C or factor VIIa allows challenging issues.

Apoptosis↗

[Use of activated recombinant FVII in the control of haemorrhage following trauma].

Uncontrolled haemorrhage is a major cause of death in trauma patients: sometimes inaccessible to surgery and often associated with coagulopathy. We report a case of severe blunt pelvic trauma associated with suicide. The conventional treatments were unsuccessful and embolization was impossible. The patient required massive blood product transfusion. A 100 microg/kg recombinant activated factor VII dose was infused, twice. After administration of the first dose, the blood requirement decreased dramatically. Further work and trials are required to assess the safety profile and dose regimen for this drug.

Coagulants↗

[Dehiscence of the anterior semicircular canal and otosclerosis: a case report].

UNLABELLED: The dehiscence of the anterior semicircular canal is a new clinical entity, it is necessary to consider this when a gusher occurs during stapedial surgery. CASE REPORT: We report a rare case of dehiscence of the anterior canal associated with otosclerosis. This was revealed by a gusher during the initial stapedectomy. At 3 months, an obliteration of the dehiscence was necessary by middle cranial fossa approach (persistant vestibular symptoms), seven months later. Revision stapedial surgery resulted in complete closure of the air-bone-gap. CONCLUSION: High resolution CT scans of the temporal bone are the key to diagnosis. It is necessary to appreciate this pathology with advances in canal and vestibular surgery.

Early Diagnosis↗

[Variable extent of platelet responsiveness to clopidogrel inhibition: "clopidogrel resistance"?].

During percutaneous coronary angioplasty, platelet inhibition by clopidogrel and aspirin has drastically decreased the risk of thrombotic occlusion of the stented vessels. However, despite the widespread use of these drugs, the incidence of acute or subacute stent thrombosis remains elevated, concerning 1 to 2% of the treated patients. Considerable differences in the responsiveness to clopidogrel could be observed, suggesting a possible underlying biological resistance. "Clopidogrel resistance" has recently been associated to an increased risk of thrombotic events following coronary angioplasty. Variations in enteric absorption, biotransformation in the liver by the CYP3A4, changes in the ADP receptor P2Y12, abnomalies of intraplatelet signal transduction, extent of platelet activation, class angina, diabetes mellitus may account for the considerable interindividual response variability widely reported. In this view, laboratory tests evaluating "clopidogrel resistance" might be useful tools for the identification and follow-up of patients at higher thrombotic risk. Indeed, in these patients, further platelet inhibition can be achieved by higher doses of clopidogrel.

Angioplasty, Balloon↗

[The significance of circulating microparticles in physiology, inflammatory and thrombotic diseases].

BACKGROUND: In multicellular organisms, apoptosis and subsequent microparticle shedding play a key role in homeostasis. Having long been considered as << cellular dust >>, microparticles released in biological fluids upon cell activation or apoptosis appear as multifunctional bioeffectors involved in the modulation of key functions including immunity, inflammation, hemostasis and thrombosis, angiogenesis. MP constitute reliable markers of vascular damage, accessible to biological detection whilst the cells they originate from remain sequestered in tissues or are promptly submitted to phagocytosis. RECENT FINDINGS: MP modulate biological functions of target cells through the transfer of cytoplasmic content, lipids and membrane receptors. The pharmacological modulation of circulating levels of microparticles could be of particular interest in thrombotic or inflammatory diseases, cancer or hemophilia. CONCLUSION: MP can now be viewed not only as a hallmark of cell damage but also as a true biological tool.

Adult↗

[Ossiculoplasty with KURZ titanium prosthesis].

OBJECTIVES: Report the functional and anatomic results of ossicular reconstruction by titanium prosthesis. MATERIALS AND METHODS: Retrospective chart reviews were performed for 111 patients who had undergone titanium ossicular implants between November 1998 and 2002 (61 PORP, 50 TORP). The anatomical and audiometric data were analyzed on average at 3 and 20 months. RESULTS: At 20 months, the improvement of air-bone-gap mean was 12.7 dB with better results at low frequencies. The global success rate was 66% (PORP 77%, TORP 52%). It decreased significantly in the open techniques. Extrusion rate was low (2/111) and the labyrinthization rate was 3.6%. Twenty patients required a surgical revision (18%). In 9 patients, the prosthesis was too short. At long-term follow-up, the gains were stable in 60 patients, improved in 32 patients and worsened in 19 patients. CONCLUSION: The success rate is higher in the group of the PORP with the closed technique. The stability of the TORP in open technique still remains problematic. In all cases, the risk of extrusion requires a large cartilage graft recovering the plate of the prosthesis. The high rate of luxation (9/111 prosthesis too short) has led us to increase slightly the length of the prosthesis (+1.22 mm mean).

Adolescent↗

[Vestibular neurotomy versus chemical labyrinthectomy for disabling Menière disease].

OBJECTIVE: To evaluate the efficiency on the vertigos and the impact on the audition of the vestibular neurotomy (VN) and the chemical labyrinthectomy (CL) in patients with severe Menière's disease, in order to determine the precise place for each technique in treatment algorithm. METHOD: Retrospective study of 71 VN (performed between 1986 and 2003) and 35 CL (performed between 1997 and 2003). These two treatments both aim at obtaining a vestibular deafferentation in order to free definitely the patient of vertigo manifestations. Vestibular results have been assessed by caloric tests performed before and 6 months after treatment. Subjective success was evaluated by searching for recurrent attacks of vertigo and by the AAO-HNS (American Academy of Otolaryngology-Head and Neck Society) scale of subjective evaluation of vertigos (follow-up of 6.4 years after VN and 2.4 years after CL). Pure tone audiometry before treatment and then 6 months later was performed. Complications of two types of treatment were recorded and evaluated. RESULTS: In 90% of the cases after VN and 86% of the cases after CL, caloric tests indicated a strong vestibular hyporeflexy (hypovalence > 90%). Attacks of vertigo reoccurred in 5.6% of the cases when the hyporeflexy was strong and 85.7% of the cases when it was weak. The quality of the vestibular results on vertigo depends on the degree of hypovalence after treatment. An improvement of the AAO-HNS scale have been obtained in 93% of the cases in the NV group and in 81% of the cases in the LC group. Attacks of vertigo were recurrent in 7% of the patients operated on by VN and 11.4% of the patients treated by CL. Mean pure tone auditory thresholds changed from 50.24 dB HL to 55.64 dB HL (p=0.003) in the VN group and from 69.11 dB HL to 74.51 dB HL (p=0.41) in the CL group. Comparison of the variations of the mean pure tone auditory thresholds before treatment and 6 months after the end of the treatment doesn't show any significant difference between the 2 groups (p > 0.05). Impairment of the audition superior to 20 dB HL was observed in 8.5% of the patients of each group. The auditive results are similar in the 2 groups. CONCLUSION: These two methods of treatment can not be strictly compared due to several bias in this study. Indeed more patients were treated by VN with a longer follow-up and only the patients with a class C or D audition according to the criteria of the AAO-HNS could be treated by CL. The VN provides a better control of the vertigos than the CL which is an efficient method of treatment in invalidating Meniere's disease. In all the cases, the quality of the results on vertigos depends on the degree of hypovalence after treatment. The auditive results are similar. Since the results of the two treatments are similar, the simplicity of CL encourages us to broaden the indications and to modify the place of the VN in the therapeutic algorithm of Menière's disease.

Adult↗

[Microparticles and cardiovascular disease].

Microparticles are membrane fragments liberated by activated or apoptopic cells. Thought for a long time to be cellular debris with no specific biologic function, in the vascular compartment they are a circulating reservoir of cellular effectors involved in thrombosis, inflammation, vascular remodelling and angiogenesis. High concentrations of circulating procoagulating microparticles found in many cardiovascular diseases indicate the importance of platelet, endothelial and monocytic activation and could contribute to the persistence of atherothrombotic disease. Pharmacological modulation of circulating microparticle concentrations could become a major therapeutic target in the future.

Blood Coagulation↗

[Skull vibratory test in partial vestibular lesions--influence of the stimulus frequency on the nystagmus direction].

INTRODUCTION: Results of the skull vibratory test (SVT) in partial unilateral vestibular peripheral lesions (PUVL) are different from the results in total vestibular lesions (TUVL). AIM: To reveal a correlation between the results of the analysis of the skull vibratory nystagmus (SVN) horizontal component and the side of the lesion; to correlate these results with the stimulus frequency. To find out a predictive correlation between the SVN horizontal and vertical components and the topography of a vestibular lesion. To appreciate the degree of vestibular deafferentation (extended to high frequencies) provoked by gentamicin labyrinthectomy and its efficiency in Meniere's disease. PATIENTS AND METHODS: 53 patients with a SVN and a PUVL were included and compared with 10 TUVL and 10 normal subjects. Protocol included a HST (2 Hz), a SVT at 30, 60 and 100 Hz and a caloric test. Recordings were performed with a 2D and 3D VNG device. RESULTS: In PUVL, SVN at 30, 60 and 100 Hz was obtained in 80, 90 and 90% of cases respectively. SVN is correlated with the side of the lesion at 30, 60 and 100 Hz respectively in 65%, 63%, 80% of cases. SVN is not correlated with the side of the lesion in 20% of Meniere's disease, in 8% of vestibular neuritis and in 6% of vestibular schwannoma. In PUVL HSN is correlated with the side of the lesion in 69% of cases. The direction of the HSN and of the SVN was different in 23% when the nystagmus attended at the same time for both tests. In PUVL the direction of the SVN is different at 100 Hz and 30 Hz in 16% of cases when they are concomittant on the same patient. After Gentamicine labyrinthectomy, the coherence of the results in caloric test, HSN and SVN (areflexy and lesional nystagmus beating toward the safe side) was correlated with the efficiency of the therapy. A SVN vertical component was met in 10% of PUVL (essentially in anterior canal dehiscence and few cases of partial labyrinthitis). The horizontal SVN SPV is significantly slower in PUVL than in TUVL patients (p=0.0004). CONCLUSIONS: The SVT is a vestibular global and rapid test which explores high frequencies. In PUVL the direction of SVN is not always predictive of the side of the lesion and is sometimes depending on the stimulus frequency, the state of the vestibular lesion, the vestibular structure concerned (1/2 circular canals or otolithic organs) and the kind of sensory cells implicated in the lesion. In TUVL The direction of the SVN is always coherent with the side of the lesion (this is useful to predict the efficiency of a Gentamicine Labyrinthectomy). A SVN vertical component can mean a lesion of the vertical canal in PUVL.

Adolescent↗

Scaling properties of contact area of pressure-sensitive adhesives.

Two new devices were developed to provide accurate measurements of both the contact area and the tack strength of pressure-sensitive adhesives (PSAs). The first one is the "mechano-optical tack tester" (MOTT), which was designed to apply controlled contact pressure by means of a quartz prism probe, for determined contact times, onto the surfaces of PSA samples. The contact area is measured by the reflection of light at the quartz probe surface, which is in contact with the adhesive. The second device is an "acoustic contact tester" (ACT) that measures the tack strength and the contact area between a silicate glass and an adhesive by the reflection of an acoustic wave. Two ultrasonic sensors of different acoustic wavelengths have been built in order to study the scaling effects of the contact kinetics between an adhesive and the probe. MOTT and ACT experiments on a commercial PSA show that the contact area is the main parameter that governs the tack properties of the PSA. The experiments and the modeling point out that the contact area depends on the compression stress, the roughness, the thickness, and the Young's modulus of the PSA. However, comparison of contact kinetics from MOTT and ACT experiments show that the contact area is a subjective parameter that depends on the wavelength of the reflected beam used for its measurement.

Journal Article↗

The pectoralis myofascial flap in pharyngolaryngeal surgery after radiotherapy.

Pharyngocutaneous fistula after total laryngectomy remains a hardly inevitable complication. The predisposing factors are not clearly identified, but prior radiotherapy seems to increase the risk of fistulae. The purpose of this retrospective study was to determine the value of the pectoralis myofascial flap in pharyngeal reconstruction in post-radiotherapy total laryngectomy in order to decrease the risk of fistula formation. The charts of 60 consecutive patients who had undergone total laryngectomy or pharyngolaryngectomy after radiotherapy were analyzed. Twenty-one variables were recorded for each patient. The overall rate of fistula formation was 38% (23% when a pectoralis myofascial flap was used to cover the pharynx and 50% when no flap was used, P = 0.06). The flap-related complications were exceptional. In the subgroup of patients with diabetes mellitus, a history of vascular disease or a poor nutritional status, the use of a flap reduced the fistula formation from 73 to 13% (P = 0.018). The pectoralis myofascial flap covering the pharyngeal sutures in postradiotherapy laryngectomy is particularly useful in a selected group of patients (with diabetes mellitus, history of vascular disease or poor nutritional status).

Age Factors↗

PrPSc accumulation in myocytes from sheep incubating natural scrapie.

Because variant Creutzfeldt-Jakob disease (vCJD) in humans probably results from consumption of products contaminated with tissue from animals with bovine spongiform encephalopathy, whether infectious prion protein is present in ruminant muscles is a crucial question. Here we show that experimentally and naturally scrapie-affected sheep accumulate the prion protein PrP(Sc) in a myocyte subset. In naturally infected sheep, PrP(Sc) is detectable in muscle several months before clinical disease onset. The relative amounts of PrP(Sc) suggest a 5,000-fold lower infectivity for muscle as compared to brain.

Animals↗

Neurotransmitter release: the dark side of the vacuolar-H+ATPase.

Vacuolar-H+ATPase (V-ATPase) is a complex enzyme with numerous subunits organized in two domains. The membrane domain V0 contains a proteolipid hexameric ring that translocates protons when ATP is hydrolysed by the catalytic cytoplasmic sector (V1). In nerve terminals, V-ATPase generates an electrochemical proton gradient that is acid and positive inside synaptic vesicles. It is used by specific neurotransmitter-proton antiporters to accumulate neurotransmitters inside their storage organelles. During synaptic activity, neurotransmitters are released from synaptic vesicles docked at specialized portions of the presynaptic plasma membrane, the active zones. A fusion pore opens that allows the neurotransmitter to be released from the synaptic vesicle lumen into the synaptic cleft. We briefly review experimental data suggesting that the membrane domain of V-ATPase could be such a fusion pore. We also discuss the functional implications for quantal neurotransmitter release of the sequential use of the same V-ATPase membrane domain in two different events, neurotransmitter accumulation in synaptic vesicles first, and then release from these organelles during synaptic activity.

Animals↗

Decreased expression of myocardial eNOS and caveolin in dogs with hypertrophic cardiomyopathy.

Because nitric oxide (NO) regulates cardiac and vessel contraction, we compared the expression and activity of the endothelial NO synthase (eNOS) and caveolin, which tonically inhibits eNOS in normal and hypertrophic cardiomyopathic hearts. NOS activity (L-[(3)H]citrulline formation), eNOS immunostaining, and caveolin abundance were measured in heart tissue of 23 mongrel dogs before and at 3 and 7 wk of perinephritic hypertension (PHT). Hemodynamic parameters in vivo and endothelial NO-dependent relaxation of macro- and coronary microvessels in vitro were assessed in the same animals. eNOS immunostaining and total calcium-dependent NOS activity decreased at 7 wk in all four heart cavities (in left ventricle, from 17.0 +/- 1.3 to 0.2 +/- 0.2 fmol. min(-1). mg protein(-1), P < 0.001). Caveolin-1 and -3 also decreased in PHT dog hearts. Accordingly, basal vascular tone was preserved, but maximal endothelial NO-dependent relaxation was impaired in all vessels from 7-wk PHT dogs. The latter had preserved systolic function but impaired diastolic relaxation [relaxation time constant (T(1)), 25.1 +/- 0.9 vs. 22.0 +/- 1 ms in controls; P < 0.05]. Peripheral infusion of the NOS inhibitor N(G)-nitro-L-arginine methyl ester increased mean aortic pressure in both groups and reduced diastolic (T(1), 31.9 +/- 1.4 ms) and systolic function in PHT dogs (DP40, 47.5 +/- 2.5 vs. 59.4 +/- 3.8 s(-1) in control animals). In conclusion, both eNOS and caveolin proteins are decreased in the hypertrophic hearts of PHT dogs. This is associated with altered maximal (but not basal) vascular relaxation and impaired diastolic function. Further degradation of cardiac function after NOS inhibition suggests a critical role of residual NOS activity, probably supported by the concurrent downregulation of caveolin.

Animals↗

Acetylcholinesterase H and T dimers are associated through the same contact. Mutations at this interface interfere with the C-terminal T peptide, inducing degradation rather than secretion.

Acetylcholinesterase (AChE) exists as AChE(H) and AChE(T) subunits, which differ by their C-terminal H or T peptides, generating glycophosphatidylinositol-anchored dimers and various oligomers, respectively. We introduced mutations in the four-helix bundle interface of glycophosphatidylinositol-anchored dimers, and analyzed their effect on the production and oligomerization of AChE(H), of AChE(T), and of truncated subunits, AChE(C) (without H or T peptide). Dimerization was reduced for all types of subunits, showing that they interact through the same contact zone; the formation of amphiphilic tetramers (Torpedo AChE(T)) and 13.5 S oligomers (rat AChE(T)) was also suppressed. Oligomerization appeared totally blocked by introduction of an N-linked glycan on the surface of helix alpha(7,8). Other point mutations did not affect the synthesis or the catalytic properties of AChE but reduced or blocked the secretion of AChE(T) subunits. Secretion of AChE(T) was partially restored by co-expression with Q(N), a secretable protein containing a proline-rich attachment domain (PRAD); Q(N) organized PRAD-linked tetramers, except for the N-glycosylated mutants. Thus, the simultaneous presence of an abnormal four-helix bundle zone and an exposed T peptide targeted the enzyme toward degradation, indicating a cross-talk between the catalytic and tetramerization domains.

Acetylcholinesterase↗

Cellular target of voltage and calcium-dependent K(+) channel blockers involved in EDHF-mediated responses in rat superior mesenteric artery.

1. We have investigated the cellular target of K(+) channel blockers responsible for the inhibition of the EDHF-mediated relaxation in the rat mesenteric artery by studying their effects on tension, smooth muscle cell (SMC) membrane potential and endothelial cell Ca(2+) signal ([Ca(2+)](endo)). 2. In arteries contracted with prostaglandin F(2 alpha) (2.5 - 10 microM), relaxation evoked by ACh (0.01 - 3 microM) was abolished by a combination of charybdotoxin (ChTX, 0.1 microM) plus apamin (Apa, 0.1 microM) and was inhibited by 68+/-6% (n=6) by 4-aminopyridine (4-AP, 5 mM). 3. ACh(0.001 - 3 microM) increased [Ca(2+)](endo) and hyperpolarized SMCs with the same potency, the pD(2) values were equal to 7.2+/-0.08 (n=4) and 7.2+/-0.07 (n=9), respectively. SMCs hyperpolarization to ACh (1 microM) was abolished by high K(+) solution or by ChTX/Apa. It was decreased by 66+/-5% (n=6) by 4-AP. 4. The increase in [Ca(2+)](endo) evoked by ACh (1 microM) was insensitive to ChTX/Apa but was depressed by 58+/-16% (n=6) and 27+/-4% (n=7) by raising external K(+) concentration and by 4-AP, respectively. 5. The effect of 4-AP on [Ca(2+)](endo) was not affected by increasing external K(+) concentration. In Ca-free/EGTA solution, the transient increase in [Ca(2+)](endo) evoked by ACh (1 microM) was abolished by thapsigargin (1 microM) and was decreased by 75+/-7% (n=5) by 4-AP. 6. These results show that inhibition of EDHF-evoked responses by 4-AP may be attributed to a decrease in the Ca(2+) release activated by ACh in endothelial cells. The abolition of SMCs hyperpolarization to ACh by ChTX/Apa is not related to an interaction with the [Ca(2+)](endo).

4-Aminopyridine↗

Pharmacological evidence of hypotensive activity of Marrubium vulgare and Foeniculum vulgare in spontaneously hypertensive rat.

The hypotensive effects of the water extract of Marrubium vulgare L. and Foeniculum vulgare L. were investigated in spontaneously hypertensive rats (SHR) and in normotensive Wistar-Kyoto rats (WKY). Oral administration of Marrubium or Foeniculum extract lowered the systolic blood pressure of SHR but not of WKY. In SHR, Foeniculum but not Marrubium treatment increased water, sodium and potassium excretion. Ex vivo as well as in vitro, Marrubium extract inhibited the contractile responses of rat aorta to noradrenaline and to KCl (100 mM). Inhibition was greater in aorta from SHR compared to WKY and was not affected by the NO synthase inhibitor N-nitro-L-arginine. Vascular effects of Foeniculum extract were less pronounced than those of Marrubium and were blocked by N-nitro-L-arginine. These results indicate that hypotensive activity of Marrubium and Foeniculum extracts seems to be mediated through different pathways: Foeniculum appeared to act mainly as a diuretic and a natriuretic while Marrubium displayed vascular relaxant activity.

Animals↗