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N Bonnet

Publications and source records attributed to N Bonnet.

At least 19 recordsLinked to original sources

Doping dose of salbutamol and exercise: deleterious effect on cancellous and cortical bones in adult rats.

Animal studies suggest that bone remodeling is under beta-adrenergic control via the sympathetic nervous system. To our knowledge, the impact of beta-agonist substances, at doping doses, has not been studied in adult rats. The purpose of this study was to examine the effects of salbutamol injections with or without treadmill exercise on trabecular and cortical bone in adult rats. Adult (36 wk of age) female Wistar rats (n = 56) were treated with salbutamol (3 mg.kg(-1).day(-1) sc, 5 days/wk) or vehicle (sham) with or without subsequent treadmill exercise (13 m/min, 60 min/day, 5 days/wk) for 10 wk. Tibial and femoral bone mineral density was analyzed by dual-energy X-ray absorptiometry. Metaphysic trabecular bone structure was analyzed by micro-CT at the time of the animals' death. Bone cell activities were assessed histomorphometrically. After 10 wk, the increase in bone mineral density was less in salbutamol-treated than in sham rats (+3.3% vs. +12.4%, P < 0.05), and trabecular parameters were altered and bone resorption was increased in salbutamol-treated rats compared with controls. The negative effect on bone architecture in salbutamol-treated rats persisted, even with treadmill exercise. These results confirm the deleterious effect of beta(2)-agonists on bone mass during chronic treatment and describe its effects on bone mechanical properties in adult rats. Bone loss occurred independently of a salbutamol-induced anabolic effect on muscle mass and was equally severe in sedentary and exercising rats, despite a beneficial effect of exercise on the extrinsic and intrinsic energy to ultimate strain. These bone effects may have important consequences in athletes who use salbutamol as a doping substance.

Adrenergic beta-Agonists↗

Electron tomography of amplified nanogold immunolabelling: Improvement of quality based on alignment of projections with sinograms and use of post-reconstruction deconvolution.

Electron tomography of immunolabelled proteins identified with amplified nanogold particles imaged by Scanning and Transmission Electron Microscopy within thick sections is a powerful method to investigate the three-dimensional organization of complex cellular machineries. In order to increase the overall quality of the reconstructed cube, we have developed two methods that improve the tomographic reconstruction process. We first performed a very precise alignment of the projections before reconstruction with a technique using sinograms. After reconstruction, we propose to compute image restoration by calculating the Point Spread Function of the projection/back-projection system and to use it to deblur the reconstructed cubes. Improvement in the quality of the reconstructed cubes is demonstrated on images of nucleolar proteins tagged with EGFP and immunolabelled with nanogold particles.

Gold↗

Dose effects of propranolol on cancellous and cortical bone in ovariectomized adult rats.

Animal studies suggest that bone remodeling is under beta-adrenergic control via the sympathetic nervous system. The purpose of this study was to examine the preventive effect of different doses of nonspecific beta-blockers (propranolol) on trabecular and cortical bone envelopes in ovariectomized rats. Six-month-old female Wistar rats were ovariectomized (OVX, n = 60) or sham-operated (n = 15). Then, OVX rats were subcutaneously injected with 0.1 (n = 15), 5 (n = 15), or 20 (n = 15) mg/kg propranolol or vehicle (n = 15) for 10 weeks. Tibial and femoral bone mineral density (BMD) were analyzed longitudinally by dual-energy X-ray absorptiometry. At death, the left tibial metaphysis and L(4) vertebrae were removed, and microcomputed tomography (Skyscan 1072; Skyscan, Aartselaar, Belgium) was performed for trabecular bone structure investigation. Histomorphometry analysis was performed on the right proximal tibia to assess bone cell activities. After 10 weeks, OVX rats had decreased BMD and trabecular parameters and increased bone turnover, as well as cortical porosity compared with the sham group (p < 0.001). Bone architecture alteration was preserved by 0.1 mg/kg propranolol due to higher trabecular number and thickness (+50.35 and +6.81%, respectively, than OVX; p < 0.001) and lower cortical pore number (-52.38% than OVX; p < 0.001). Animals treated by 0.1 mg/kg propranolol had a lower osteoclast surface and a higher osteoblast activity compared with OVX. Animals treated by 20 mg of propranolol did not significantly differ from OVX rats. Animals treated by 5 mg of propranolol have been partially preserved from the ovariectomy. These results showed a dose effect of beta-blockers. The lower the dose of propranolol breeding, the better the preventive effect against ovariectomy.

Animals↗

[What's new in mechanical circulatory assistance: from clinical indications to material].

Over the years, mechanical circulatoryassistance has progressively improved with the evolution of the clinical indications and the introduction of new devices. The management of situations of extreme emergency, cardiac arrest, acute myocardial infarction with cardiogenic shock, drug overdose, acute myocarditis, postoperative cardiac failure and post-transplantation right ventricular failure, may be undertaken with relatively simple systems such as the ECMO, in the catheter laboratory or at the bedside in the intensive care unit. These systems enable stabilisation of the circulatory problems in order to pass a difficult situation and then withdraw the assistance when myocardial function has been restored. When this is not possible and there is no contra-indication to cardiac transplantation, patients may benefit from more complex assistance devices as a bridge to transplantation. Many continuous flow pumps have been introduced recently. These small mono, left ventricular, assist devices provide improved patient comfort and suggest wider indications of long duration assist devices.

Heart Failure↗

Abnormal ion content, hydration and granule expansion of the secretory granules from cystic fibrosis airway glandular cells.

The absence or decreased expression of cystic fibrosis transmembrane conductance regulator (CFTR) induces increased Na(+) absorption and hyperabsorption of the airway surface liquid (ASL) resulting in a dehydrated and hyperviscous ASL. Although the implication of abnormal airway submucosal gland function has been suggested, the ion and water content in the Cystic Fibrosis (CF) glandular secretory granules, before exocytosis, is unknown. We analyzed, in non-CF and CF human airway glandular cell lines (MM-39 and KM4, respectively), the ion content in the secretory granules by electron probe X-ray microanalysis and the water content by quantitative dark field imaging on freeze-dried cryosections. We demonstrated that the ion content (Na(+), Mg(2+), P, S and Cl(-)) is significantly higher and the water content significantly lower in secretory granules from the CF cell line compared to the non-CF cell line. Using videomicroscopy, we observed that the secretory granule expansion was deficient in CF glandular cells. Transfection of CF cells with CFTR cDNA or inhibition of non-CF cells with CFTR(inh)-172, respectively restored or decreased the water content and granule expansion, in parallel with changes in ion content. We hypothesize that the decreased water and increased ion content in glandular secretory granules may contribute to the dehydration and increased viscosity of the ASL in CF.

Cell Line, Transformed↗

Severe bone alterations under beta2 agonist treatments: bone mass, microarchitecture and strength analyses in female rats.

AIMS: Beta2 adrenergic agonists are widely used in therapeutics and as doping agents by athletes. However, their effects on bone tissue, especially bone microarchitecture, remain poorly understood. Using three-dimensional (3D) microtomography, dual-energy X-ray absorptiometry, biomechanical testing and enzyme-linked immunosorbent assay, we evaluated the effects of two beta2 agonists, clenbuterol and salbutamol, on bone in growing rats. METHODS: Twelve-week-old Wistar female rats (N = 39), divided in 3 groups, received during 6 weeks either salbutamol (4 mg/kg/day), clenbuterol (2 mg/kg/day) or normal saline (0.5 ml/kg/day) by subcutaneous injections. RESULTS: After 6 weeks, the salbutamol and clenbuterol groups displayed lower bone mineral content (BMC), femoral length and cortical width than controls. Clenbuterol treatment further reduced bone mineral density. Bone microarchitecture was clearly altered by clenbuterol, as evidenced by lower trabecular number (-40.40%; P < 0.001), connectivity and trabecular bone volume (-42.85%; P < 0.001), leading to lower ultimate force. Clenbuterol significantly increased muscle mass (P < 0.01) and reduced fat mass when compared to controls. Salbutamol did not seem to have any effect on bone microarchitecture or body composition. Both beta2 agonists increased the bone resorption marker (C-terminal collagen crosslinks) without any change of a bone formation marker. At the end of the treatment, a drop in leptin was seen in the clenbuterol group only. Leptin levels were correlated with BMC (r = 0.69, P = 0.003). CONCLUSION: These results confirm the deleterious effect of beta2 agonists on bone mass and show the negative effects of clenbuterol on trabecular bone microarchitecture. Bone loss occurred independently from muscle mass but was related to fat mass. A leptin-mediated effect on bone tissue seems likely. These pathophysiological effects may have important consequences in human therapeutics and doping.

Adrenergic beta-Agonists↗

[Pseudo-aneurysms of the ascending aorta in patients previously operated for acute aortic dissection].

Pseudo-aneurysms of the ascending aorta are a rare but serious complication of surgery for acute dissection of the aorta. The diagnostic methods and surgical technique have changed in recent years. The authors report their experience over a period of 20 years. From January 1981 to December 2001, 21 patients underwent reoperation for pseudo-aneurysms of the ascending aorta. The average age was 54.2 +/- 3 years. Diagnosis is no longer based on aortography but on transthoracic or oesophageal multiplane echocardiography, thoracic spiral computed tomography or magnetic resonance imaging. Four patients presented with a recent history of severe pulmonary oedema. The risk associated with reopening the sternum is avoided by current operative techniques. The authors have chosen anterograde perfusion of the cervical arteries by direct canulation for cerebral protection. The operative mortality at one month is high (30%). All patients who had pulmonary oedema or cardiogenic shock in the immediate preoperative period died. There were no neurological complications. Twelve patients survived and one has to undergo a further operation for recurrence of the pseudo-aneurysm. The authors conclude that patients operated for dissection of the aorta must be followed up. It is important to resect as much as possible of the pathological aorta during the initial operation to avoid the risk of pseudo-aneurysm formation, at least in the proximal segment of the ascending aorta.

Aortic Dissection↗

[Post-myocardial infarction cardiogenic shock and circulatory assistance].

Post-myocardial infarction cardiogenic shock still carries a very poor prognosis despite the rapid recourse to effective methods of myocardial revascularisation. Circulatory assistance devices allow restoration of adequate haemodynamics with limitation of myocardial work. In the most severe cases, implantation of intra-thoracic devices is associated with a 70% survival rate in the latest series, providing they are used early. However, in many cases, the essential problem is to stabilise the patient's haemodynamic status, sometimes even before myocardial revascularisation. In these situations, implantation of a peripheral femoro-femoral extra corporeal circulation (ECMO: extra corporeal membrane oxygenation) re-establishes an appropriate cardiac output andprovides time to transfer the patient, to perform coronary revascularisation or to assess neurological status, before deciding on the indications for more complicated assist systems. This "bridge to bridge" concept avoids the risk of implanting complicated assist devices in cerebrally dead patients or in those with multi-organ failure beyond treatment. Conversely, it gives some patients with apparent contraindications to complicated assist systems or who are unable to benefit from these systems for geographical reasons, a chance to survive. In early cardiogenic shock, the ECMO which has a low rate of complications, could safely promote myocardial recovery.

Assisted Circulation↗

Cleft palate associated with an unbalanced karyotype in piglets sired by a heterozygous carrier boar with a balanced constitutional reciprocal translocation.

The progeny of a commercial (Landrace x Duroc) x Large White boar contained a number of piglets with cleft palates. Chromosomal analyses of five affected piglets showed that they all had an identical unbalanced karyotype with partial monosomy of chromosome 16 and partial trisomy of chromosome 3, whereas the normal piglets in the litters had balanced karyotypes. The chromosomal imbalance was the direct result of a constitutional balanced reciprocal translocation carried by their heterozygote sire, described, according to the standard nomenclature, as t(3;16)(q23;q22).

Animals↗

Gap junction communication between cells aggregated on a cellulose-coated polystyrene: influence of connexin 43 phosphorylation.

The appropriate functioning of tissues and organ systems depends on intercellular communication such as gap junctions formed by connexin (Cx) protein channels between adjacent cells. We have previously shown that Swiss 3T3 cells aggregated on hydrophilic cellulose substratum Cuprophan (CU) establish short linear gap junctions composed of Cx 43 in cell surface plaques. This phenomenon seems to depend on the high intracellular cyclic AMP (cAMP) concentration triggered by attachment of the cells to CU. We have now used a cellulose-coated polystyrene inducing the same cell behaviour to analyse the gap junction communication between aggregated cells. The transfer of the dye Lucifer Yellow (LY) between cells showed that cells aggregated on cellulose substratum rapidly (within 90 min) establish functional gap junctions. Inhibitors of cAMP protein kinase (PKI) or protein kinase C (GF109203X) both inhibited the diffusion of LY between neighbouring cells. Western blot analysis showed that this change in permeability was correlated with a decrease in Cx 43 phosphorylation. Thus, cellulose substrata seem to induce cell-cell communication through Cx 43 phosphorylation modulated by PKA and PKC. To understand the mechanisms by which a substratum regulates gap junctional communication is critically important for the emerging fields of tissue engineering and biohybrid devices.

Animals↗

[Long term survival with the Bentall button operation in 150 patients].

Between May 1980 and May 2000, 150 patients (123 males and 27 females) underwent surgery with the same surgeon for ascending aortic replacement with a valvular conduit and coronary reimplantation with the aid of a collar of aortic wall (button technique). The average age was 50 +/- 16 years. Within this population, 114 patients had isolated annulo-ectasial disease, 36 had Marfan syndrome and 20 had dissection (5 acute and 15 chronic). A carbon fibre valve with 2 leaflets was implanted in 124 patients, a mono-leaflet valve in 20 and 6 others required a heterograft due to their age or a contra-indication to anticoagulation. The associated procedures were: 12 arch replacements, 5 myocardial revascularisations, 4 mitral replacements, 1 tricuspid plasty, 1 inter-atrial communication closure. In 30 patients (20%) there was a cardiovascular surgical re-intervention. The operative and first month mortality amounted to one sudden death on the 19th day, ie 0.6%. Three patients were lost to follow up. The average survival was 7.87 +/- 5.37 years (minimum 1, maximum 20 years). The actuarial survival was 85% at 10 years and 60% at 20 years. These figures are much higher than those reported in our previous statistics from 1994 when the percentage of survivors at 12 years was only 61%. In the group of patients undergoing surgery before 60 years of age, the survival at 14 years was 94% and 81% at 20 years. Only four late re-interventions were attributable to the Bentall procedure, of which 2 were left coronary ostium stenoses. The rate of thrombosis and embolism was 0.42 per 100 patient-years and the rate of haemorrhagic accidents was identical, including minor accidents. This considerable improvement in long-term prognosis is explicable by the adoption of a single operative technique, considered to be the best, with the best myocardial protection thanks to coronary retro-perfusion and cold or hot cardioplegia, and also without doubt with the best medical survival.

Adolescent↗

Bridge to transplantation with the Jarvik-7 (CardioWest) total artificial heart: a single-center 15-year experience.

BACKGROUND: At our institution, the total artificial heart (TAH) Jarvik-7 (CardioWest) has been used since 1986 as a bridge to transplantation for the most severely ill patients with terminal congestive heart failure. METHODS: Between 1986 and 2001, 127 patients (108 males, mean age 38 +/- 13) were bridged to transplantation with the Jarvik-7 TAH. All were in terminal biventricular failure despite high-dose inotropic support. Nine patients had a body surface area (BSA) of <1.6 m(2). In Group I patients (78%), the etiology of cardiac failure was dilated cardiomyopathy, either idiopathic (n = 60) or ischemic (n = 38). The other 29 patients (Group II) had disease of miscellaneous origin. We analyzed our experience with regard to 3 time periods: 1986 to 1992 (n = 63); 1993 to 1997 (n = 36); and 1998 to 2001 (n = 33). RESULTS: Although Group II patients represented 30% of indications before 1992, they comprised only 15% during the 2 subsequent periods. Duration of support for transplant patients increased dramatically after 1997, reaching 2 months for the most recent period (5 to 271 days). In Group I, the percentage of transplanted patients increased from 43% before 1993 to 55% between 1993 and 1997, and reached 74% thereafter. The major cause of death was multiorgan failure (67%). The clinical thromboembolic event rate was particularly low with no instance of cerebrovascular accident and 2 transient ischemic attacks. Total bleeding complication rate was 26%, including 2 deaths related to intractable hemorrhage and 2 others related to atrial tamponade. The cumulative experience was 3,606 total implant days with only 1 instance of mechanical dysfunction. CONCLUSIONS: TAH is a safe and efficient bridge for patients with terminal congestive heart failure awaiting cardiac transplantation.

Adolescent↗

[Valvular replacement with the Bicarbon mechanical valve. Results after 7 years in 104 patients].

OBJECTIVE: Study of the medium term results of aortic and mitral valve replacement with the Bicarbon' prosthesis. METHOD: From 1990 to 1996, 109 valves were implanted (70 in aortic position, 31 in mitral position and 4 double replacements). The average age was 61 years and 75% were male. According to the NYHA, 59% of patients were stage III or IV. The average pre-operative ejection fraction was 59.6%. There was re-intervention in 21.1% of patients and 35.3% had an associated procedure during the intervention. RESULTS: The average follow up was 5.4 +/- 1.98 years in 98 patients (that is 522 patient years). One patient died post-operatively and 19 died later. The overall survival at 7 years was 69.4 +/- 6.3%. Complications, expressed in patient years, were 1.15% for thrombo-embolic complications, 2.1% for haemorrhagic complications. 0.38% for endocarditis, 1.72% for non-infectious peri-prosthetic leaks, and 0.76% for re-interventions. At 7 years, the absence of thrombo-embolic, haemorrhagic, endocarditis, and re-intervention complications was 91.8 +/- 4.2%, 85.3 +/- 4.8%, 95.8 +/- 3.2%, 93.8 +/- 3.5% respectively. According to the NYHA, 95% of patients were in stage 1 or II (p < 0.001). CONCLUSION: Valvular replacement in the aortic or mitral position with the Bicarbon' valve is satisfactory as much in terms of survival as of clinical complications.

Aortic Valve↗

Cardiac surgery in patients receiving long term hemodialysis. Short and long term results.

AIM: Cardiac surgery carries a high risk in hemodialysis patients and has been questioned for its results; the purpose of this study is to focus on the short and long term results in our institution. METHODS: We retrospectively analyzed the data from 124 hemodialysis patients who underwent cardiac surgery in our unit between January 1980 and December 1998; 14.5% were diabetic; 46% had isolated coronary artery disease (group 1); 29.8% had valvular disease alone (group 2); 14.5% valve and coronary disease (group 3) and 9.6% miscellaneous disease at highest risk (group 4). We analyzed the relationship between several variables (age, sex, hypertension, diabetes, previous myocardial infarction, type of disease, preoperative ejection fraction) and operative mortality (30 days) and late survival. RESULTS: The overall operative mortality was 16.9%. The only risk factor was the type of cardiac disease: operative mortality was higher in groups 3 and 4 combined than in groups 1 and 2 combined (30% versus 12.7%, p=0.07). Ninety-nine patients were followed until January 2002. Late survival rate was 46.6+/-5% at 6 years for all patients, it was significantly better in groups 1 and 2 combined than in groups 3 and 4 combined. The only risk factor for late mortality was arterial hypertension. Fifty-seven patients are still alive, 46 in groups 1 and 2, 11 in groups 3 and 4. Progression of coronary lesions occurred in 6 patients and valvular lesions in 3 patients. The remainder are doing well. CONCLUSION: Cardiac surgery seems to be justified by the severity of the lesions. Its actual results can perhaps, be improved by earlier detection of cardiac disease and better prevention of myocardial hypertrophy and cardiac calcifications.

Age Factors↗

[Fulminating myocarditis: myocardial recovery after circulatory assistance].

The clinical expression of acute myocarditis is variable from paucisymptomatic to fulminating forms which are usually lethal within days. The latter presentation takes the form of very acute cardiac failure. During this phase, the severity of myocardial dysfunction may be such that death ensues. However, if the patient survives, paradoxically, these forms have a better long-term prognosis with complete recovery of myocardial function being possible after the acute phase. The authors report a typical case of fulminating myocarditis with electromechanical dissociation, which recovered completely after a period of circulatory assistance. This case illustrates the rapidity of deterioration of the haemodynamic status and the importance of organ dysfunction despite early management. In a review of the literature, the authors found about 150 reported cases of acute myocarditis treated with circulatory assistance. In the best series, about half the patients were weaned off the circulatory assistance without having to undergo cardiac transplantation. However, the potential recovery of myocardial function is difficult to predict.

Adult↗

[Remodelling the aortic root by resection of the ascending aorta and non-coronary sinus in annular dilatation of the aorta and acute dissection of the descending aorta. 29 observations].

The first conservative surgical procedures of the native aortic valve in annular dilatation were performed by Yacoub and David [1, 2]. These so-called remodelling and inclusion procedures provided hope for a normal life without long-term anticoagulant therapy for patients with Marfan's syndrome, with protection from the complication of an acute dissection of the ascending aorta. The authors reported their experience in the Archives des Maladies du Coeur et des Vaisseaux in 1999, with excellent results [3]. However, a certain number of cases are encountered in which the Yacoub and David procedures cannot be performed because of the presence of a pseudo-bicuspid valve, isolated asymmetrical dilatation of the non-coronary sinus or acute dissection of the aorta without dilatation of the aortic root. In these forms, the authors have developed a technique of remodelling the aortic root with conservation of the native valve by resecting the ascending aorta and non-coronary sinus, rather than carrying out a Bentall procedure. Twenty-nine cases of this type have been treated in this way for three different indications: aneurysm of the ascending aorta with bicuspid aortic valve, aneurysm of the ascending aorta with aortic insufficiency and extension to the posterior sinus, and type A acute dissection of the aorta.

Adult↗

Quantitative cell dispersion analysis: new test to measure tumor cell aggressiveness.

Tumor progression requires the dispersion of epithelial cells from neoplastic clusters and cell invasion of adjacent stromal connective tissue. Aiming at demonstrating the precise relationships between cell dispersion and cell invasion, related respectively to expression of E-cadherin/catenin complex and matrix metalloproteinases (MMPs), we developed an original in vitro model of cell dispersion analysis. Our study reports the validation of this model that allowed us to analyze and quantify the cell cohesion level by means of time-lapse videomicroscopy and computer analysis based on the observation of spatial and temporal cell distribution. Our model was able to distinguish 2 groups among different human bronchial and mammary epithelial cells previously characterized for the expression of E-cadherin/catenin complex and MMPs and their invasive capacity in the Boyden chamber assay. The first group (16HBE14o(-), MCF-7, T47D) that expressed membranous E-cadherin and beta-catenin, and was negative for MMP-2 expression and non-invasive, displayed a highly cohesive pattern corresponding to a cluster spatial distribution. The second group (Beas2B, BZR, BZR-T33, MDA-MB-231, MDA-MB-435, BT549 and HS578T) that was invasive and showed lack of expression of E-cadherin and a cytoplasmic redistribution of beta-catenin, displayed a dispersed pattern corresponding to a random spatial distribution. Downregulation of E-cadherin by a blocking antibody induced a more random distribution. Conversely, expression of E-cadherin by cDNA transfection induced a cluster distribution. Moreover, tumor cell lines that co-expressed MT1-MMP and MMP-2 (Beas2B, BZR, BZR-T33, MDA-MB-435, BT549 and HS578T) showed a more dispersed pattern than tumor cell lines that did not express MMP-2 (MDA-MB-231). In conclusion, we demonstrated that the spatial group behavior of cell lines, i.e., their cohesion/dispersion ability, reflects their invasive properties. Thus, this model of cell dispersion analysis may represent a new test to measure tumor cell aggressiveness.

Breast↗