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Biomedical subjects

J Bonnet

Publications and source records attributed to J Bonnet.

At least 19 recordsLinked to original sources
PubMed2006

[The French preliminary experience of the use of a seed-projector for exclusive iodine 125 prostate brachytherapy: feasibility and acute toxicity].

PURPOSE: To analyse a new technique for prostate brachytherapy with permanent Iodine implants characterized by the use of a seed projector after a 3D dosimetric peroperative treatment planning (FIRST technique). PATIENTS AND METHOD: 395 patients have been treated in France with this technique in six radiotherapy centres between November 2002 and December 2005 for a localized prostate cancer. RESULTS: Thirteen patients (3.3%) developped a urinary retention, and respectively 7.8 and 26.5% an acute RTOG grade 3 and 2 toxicity. The 6-weeks IPSS score was equal or lower to 15 in 73% with a 11 median IPSS value. A failure of the loading with the seed-projector, leading to a manual loading of the seeds, occurred in 9 patients (2.3%) in two centres, directly related to the loading procedure with the seed-projector in 5 cases. The median duration of the procedure was reduced by 30 minutes for the patients treated in 2005. CONCLUSIONS: This multicenter study establishes the feasibility of the routine use of a seed projector for permanent iodine 125 prostate implants with an initial tolerance similar to the best results published for other implants techniques.

Brachytherapy↗
PubMed2006

Contraceptive counselling and social representations: a qualitative study.

BACKGROUND: Contraceptive use is a complex issue and several studies have been conducted in an effort to understand user behaviour. It is of interest to explore the representations of professionals who give advice on contraception, since their views could have an impact on contraceptive use. METHODS: Individual in-depth interviews of 65 healthcare professionals likely to provide contraceptive advice to patients at a Swiss maternity unit. RESULTS: 83% of healthcare professionals interviewed were favourable to contraception in general while being highly critical of its practical efficacy. The methods most often spontaneously cited were oral contraceptive pills, male condom, intrauterine devices and hormonal implants. Theoretically, all methods should be proposed during contraceptive counselling but in practice interviewees have different social representations of user groups and associate them with specific contraceptive methods. Personal experience appears to play a bigger role than scientific knowledge. CONCLUSIONS: The counsellor's social representations probably play an important role in determining user behaviour. These representations should be taken into consideration in the training of healthcare professionals in this field.

Adult↗
PubMed2005

Farnesylated RhoB inhibits radiation-induced mitotic cell death and controls radiation-induced centrosome overduplication.

Our previous results demonstrated that expressing the GTPase ras homolog gene family, member B (RhoB) in radiosensitive NIH3T3 cells increases their survival following 2 Gy irradiation (SF2). We have first demonstrated here that RhoB expression inhibits radiation-induced mitotic cell death. RhoB is present in both a farnesylated and a geranylgeranylated form in vivo. By expressing RhoB mutants encoding for farnesylated (RhoB-F cells), geranylgeranylated or the CAAX deleted form of RhoB, we have then shown that only RhoB-F expression was able to increase the SF2 value by reducing the sensitivity of these cells to radiation-induced mitotic cell death. Moreover, RhoB-F cells showed an increased G2 arrest and an inhibition of centrosome overduplication following irradiation mediated by the Rho-kinase, strongly suggesting that RhoB-F may control centrosome overduplication during the G2 arrest after irradiation. Overall, our results for the first time clearly implicate farnesylated RhoB as a crucial protein in mediating cellular resistance to radiation-induced nonapoptotic cell death.

Animals↗
PubMed2005

Lysyl oxidase deficiency: a new cause of human arterial dissection.

Spontaneous coronary artery dissection is a rare cause of myocardial ischaemia. The underlying mechanism is unknown but some dissections are associated with extracellular matrix disorganisation of genetic origin. A deficiency in extracellular matrix protein cross links has rarely been studied. A single clinical case of spontaneous coronary artery dissection is reported. Lysyl oxidase (LOX) and extracellular matrix organisation were investigated by skin immunohistology and polymerase chain reaction of LOX expression. Both approaches found a dramatic LOX decrease. LOX deficiency has a major role in human arterial wall organisation during development. The suspected mechanism is an elastin or collagen polymer cross linking deficiency.

Adult↗
PubMed2003

[Brachytherapy for coronary restenosis: state of art in 2003].

Based on therapeutic approach for benign diseases, vascular brachytherapy decreases smooth vascular muscle cells proliferation and multiplication which lead to the formation of the neo-intima. The radioactive positive action affects arterial recoil due to post angioplasty vessel injury. Randomised studies has shown good angiographic results up to 6 months of follow-up, with 50% in-stent restenosis rate decrease and on the analysed segment as well. Decrease on Mace and TLR show statistically significance. Results don't correlate with emitter and bêta emitters had been introduced in France recently. Vascular brachytherapy is actually indicated for in-stent restenosis, there is no evidence to perform this treatment for de novo lesion. Geographic miss, source centering, late thrombosis and pullback procedure may interfere with treatment quality. IVUS allows best target volume determination to a higher quality level. Internationals guidelines such as Eva-Gec-Estro recommendations could increase treatment safety and enable development of an optimal technique.

Angioplasty, Balloon, Coronary↗
PubMed2002

An open-label study of thalidomide for maintenance therapy in responders to infliximab in chronically active and fistulizing refractory Crohn's disease.

BACKGROUND: Infliximab, a chimeric monoclonal antibody to tumour necrosis factor-alpha, is a new potent therapy for active Crohn's disease, but induces short-lived improvements. AIM: To evaluate the efficacy of thalidomide, a drug with anti-tumour necrosis factor-alpha activity, for the maintenance of infliximab-induced response in refractory Crohn's disease. METHODS: Fifteen patients with severe, refractory disease (10 females, five males; mean age, 40 years; eight with luminal disease, two with fistulizing disease and five with both luminal and fistulizing disease) were started on thalidomide (100 mg daily), 29 +/- 10 days after they had responded to infliximab (5 mg/kg infusions). RESULTS: The median follow-up period was 238 days (range, 10-458 days) from the initiation of thalidomide and 265 days (range, 10-537 days) from the last infliximab infusion. The median Crohn's disease activity indices were 322 (range, 170-525), 119 (range, 24-503) and 35 (range, -60-360) before infliximab, at the initiation of thalidomide and at the end of follow-up, respectively. Remission rates on thalidomide were 92%, 83% and 83% at 3, 6 and 12 months, respectively, after the last infliximab infusion (Kaplan-Meier). Four patients (two in remission) stopped thalidomide for suspected adverse effects. Side-effects (drowsiness, rash and peripheral neuropathy) were mild and mostly transient. CONCLUSIONS: Thalidomide appears to be an effective and relatively safe drug to maintain response to infliximab in chronically active and fistulizing refractory Crohn's disease.

Adult↗
PubMed2001

Development of an enzyme-linked immunoassay for the quantification of YKL-40 (cartilage gp-39) in guinea pig serum using hen egg yolk antibodies.

An indirect competition immunoassay for the quantification of YKL-40 (cartilage gp-39, Chondrex) in guinea pig serum has been developed using egg yolk antibodies (IgY). The immune response of hens to YKL-40 was verified by immunoblot analyses. Highly specific antibodies were obtained 30 days after the first injection. The ELISA was developed in 96-well microtiter plates with quadruplicate determinations for each point. The assay was based on the ability of YKL-40 present in serum to displace the binding of antibodies to the coated antigen. An inhibition mixture containing standard YKL-40 or guinea pig serum, diluted 1/5, and primary antibodies, diluted 1/5000, was allowed to equilibrate for 2 h at room temperature and dispensed for 16 h at 4 degrees C in wells coated with 1 microg/ml of YKL-40. Detection was achieved by the addition of rabbit anti-chicken antibodies conjugated to peroxidase followed by tetramethylbenzidine. Specificity was assessed by parallelism between a dilution curve of serum and standard YKL-40. The sensitivity of detection was 10 ng/ml. Intra- and interassay coefficients of variation were both 8.7%. The analytical recovery was 101.5+/-5.4% (mean+/-standard deviation (SD), n=9). The YKL-40 concentration in serum from 12 adult guinea pigs was 330+/-216 ng/ml (mean+/-SD) with a lower value of 164 ng/ml and an upper value of 982 ng/ml. In contrast to the rat, a dilution curve of rabbit serum gave parallelism with the guinea pig standard, suggesting recognition of a similar epitope. Possible applications of the assay in the guinea pig include disease models where YKL-40 is overexpressed and could be used as a marker, i.e. osteoarthritis, rheumatoid arthritis, cancer, liver fibrosis, atherosclerosis and more generally, pathologies with increased tissue remodeling.

Adipokines↗
PubMed2001

Effects of ceramide on aggrecanase activity in rabbit articular cartilage.

Ceramide participates in signal transduction of IL-1 and TNF, two cytokines likely involved in cartilage degradation in osteoarthritis. We previously showed that ceramide stimulates proteoglycan degradation, mRNA expression of matrix metalloproteinase (MMP)-1, -3, and -13, and pro-MMP-3 production in rabbit cartilage. Since aggrecan, the main cartilage proteoglycan, can be cleaved by metalloproteinases both of MMP and aggrecanase type, the aim of this study was to determine if ceramide stimulates aggrecanase action and, if that is the case, in which measure aggrecanase mediates the degradative effect of ceramide. To this end, antibodies were used against the C terminal aggrecan neoepitopes generated by aggrecanases (NITEGE(373)) and MMPs (DIPEN(341)). Ceramide C(2) at 10(-5) to 10(-4) M dose-dependently increased NITEGE signal, without changing that of DIPEN, in cultured explants of rabbit cartilage. The effects of 10(-4) M C(2) on NITEGE signal and proteoglycan degradation were similarly antagonized by the metalloproteinase inhibitor batimastat, with return to the basal level at 10(-6) M. These results show that, similarly to IL-1 and TNF, ceramide-induced aggrecan degradation is mainly due to aggrecanases. That no increase of MMP activity was detected, despite stimulation of MMP expression, was probably due to lack of proenzyme conversion to mature form, since addition of a MMP activator to C(2)-treated cartilage increased both DIPEN signal and proteoglycan degradation. These findings support the hypothesis that cytokine-induced ceramide could play a mediatory role in situations of increased degradation of cartilage matrix.

Aggrecans↗
PubMed2001

Encapsulation of deoxyribonucleic acid molecules in silica and hybrid organic-silica gels.

The encapsulation of small DNA molecules was attempted in pure silica and in hybrid polyvinyl alcohol-silica gels. The materials which were obtained were examined by nitrogen adsorption, and by 29Si and 31P NMR spectroscopy. The extraction of the DNA molecules from the gels was examined in a buffer aqueous solution as well as in an acidic medium. The results suggested that the DNA molecules remained trapped inside the gels due to a permanent bonding to the gel network.

Journal Article↗
PubMed2001

Kinetics of adventitial repair in the rat carotid model.

BACKGROUND: Discrepancies between success in experimental animals with a variety of pharmacologic strategies and failure with such agents in clinical trials have raised questions concerning the mechanism of restenosis. Recent observations suggest a potential implication for the adventitial (Adv) layer in neointimal formation. METHODS: The purpose of this study was to examine the Adv changes in the rat carotid artery subjected to balloon injury. These changes were characterized by morphometric, immunohistochemical, and electron microscopy analyses, with special attention devoted to early time-points post-injury. RESULTS: We report that the most important adventitial changes occurred in the first 48 h post-injury. Within 2 h there was extensive cell-loss by apoptosis and oncosis in the Adv and in the media; this was followed by the rapid onset of proliferation and a parallel slow increase in Adv thickening, reaching a maximum at 7 days. We further demonstrate an early migration of these Adv cells to the media and neointima. Moreover, we characterize the Adv cell phenotype with a panel of antibodies. Within 48 h after injury, a population of Adv cells expressed alpha-actin and vinculin with a maximum expression 7 days post-injury. At that time, these Adv cells started to express smooth muscle myosin heavy chain, a specific marker of smooth muscle cells. In parallel, we report an impaired production of elastic fibres in the Adv and medial layer. CONCLUSIONS: We reported a detailed time-course of adventitial changes after rat carotid injury (cell death, proliferation, migration and differentiation) that supports an important role of adventitia in neointima formation.

Analysis of Variance↗
PubMed2001

[Aortic atheroma: not a sensitive indicators for coronary artery disease in patients with mitral valve disease].

Aortic atheroma detected by transoesophageal echocardiography has been reported to be a good prognostic marker for coronary disease on angiography. The value of this detection in valvular heart disease would be to avoid preoperative coronary angiography in asymptomatic patients. The aim of this study was to assess the prognostic value of aortic atheroma in a population with a low prevalence of coronary artery disease in whom transoesophageal echocardiography was systematically performed. In addition, calcification of the aortic knuckle, a marker of atherosclerosis, was analysed by simple chest X-ray. One hundred and ninety two patients (103 men, 89 women; mean age: 63.1 +/- 15 years), operated for mitral valve replacement, underwent transoesophageal echocardiography, angiography, within 6 months, and chest X-ray. The cardiovascular risk factors, presence of aortic atherome, angiographic coronary artery disease and aortic calcification were studied. Aortic atheroma was observed in 72 patients (37.5%), usually in the descending thoracic aorta (73.6%). Coronary stenosis was observed in 36 patients (18.7%). On univariate analysis, aortic atherome predicted coronary stenosis with a sensitivity of 53%, specificity of 66% and positive predictive value of 26% and negative predictive value of 86%, compared with chest X-ray: 71%, 65%, 33% and 90%, respectively. In multivariate analysis, only hypercholesterolaemia, smoking and age predicted the presence of coronary artery disease. The presence of aortic atheroma was not predictive (p = 0.3). The authors conclude that aortic atheroma does not predict the presence of coronary artery disease in a patient population with mitral valve disease and a low prevalence of coronary artery disease. Simple chest X-ray has almost the same diagnostic value. The association of these two investigations does not give sufficient negative predictive values to avoid coronary angiography.

Age Factors↗
PubMed2000

1,3-Diaryl-4,5,6,7-tetrahydro-2H-isoindole derivatives: a new series of potent and selective COX-2 inhibitors in which a sulfonyl group is not a structural requisite.

Novel tetrahydro-2H-isoindoles have been prepared and evaluated as inhibitors of the COX-2 isoenzyme. A 1,3-diaryl substitution on the central polycyclic ring system and absence of a sulfonyl moiety are the two structural features of this chemical series. A short and easy synthetic pathway produced several derivatives which were shown to be potent and selective COX-2 vs COX-1 inhibitors (IC(50) = 0. 6-100 nM for COX-2, 100->1000 nM for COX-1). Structural modifications established that a bicyclic ring appended to the pyrrole nucleus and 4,4'-difluoro substitution on the phenyl rings were optimal for high inhibitory potency. Activity was confirmed in the human whole blood assay and subsequently in the murine air-pouch model in which in vivo PGE2 inhibitory activity was evaluated with respect to gastric tolerance (ED(50) for inhibition of exudate PGE2 of 3 mg/kg and gastric PGE2 of 20 mg/kg). Gastric tolerance was further assessed after administration to mice of high doses (up to 400 mg/kg) of the inhibitors by measurement of gastric damage. This panel of studies allowed selection of a number of tetrahydro-2H-isoindoles which were compared in the adjuvant-induced arthritis model. Compounds 32 and 37 showed the most potent activity with ED(50) values for edema inhibition in the noninjected paw of 0. 35 and 0.15 mg/kg/day, respectively, after oral administration. In addition, this interesting antiinflammatory profile was accompanied by a protective effect against arthritis-induced osteopenia, the decrease being 50% with a dose of 0.25 mg/kg/day.

Administration, Oral↗
PubMed2000

An overlapping CArG/octamer element is required for regulation of desmin gene transcription in arterial smooth muscle cells.

The desmin gene encodes an intermediate filament protein that is present in skeletal, cardiac, and smooth muscle cells. This study shows that the 4-kb upstream region of the murine desmin promoter directs expression of a lacZ reporter gene throughout the heart from E7.5 and in skeletal muscle and vascular smooth muscle cells from E9. 5. The distal fragment (-4005/-2495) is active in arterial smooth muscle cells but not in venous smooth muscle cells or in the heart in vivo. It contains a CArG/octamer overlapping element (designated CArG4) that can bind the serum response factor (SRF) and an Oct-like factor. The desmin distal fragment can replace a SM22alpha regulatory region (-445/-126) that contains two CArG boxes, to cis-activate a minimal (-125/+65) SM22alpha promoter fragment in arterial smooth muscle cells of transgenic embryos. lacZ expression was abolished when mutations were introduced into the desmin CArG4 element that abolished the binding of SRF and/or Oct-like factor. These data suggest that a new type of combined CArG/octamer element plays a prominent role in the regulation of the desmin gene in arterial smooth muscle cells, and SRF and Oct-like factor could cooperate to drive specific expression in these cells.

3T3 Cells↗
PubMed2000

Early and long-term (one-year) effects of the association of aspirin and oral anticoagulant on thrombi and morbidity after replacement of the mitral valve with the St. Jude medical prosthesis: a clinical and transesophageal echocardiographic study.

OBJECTIVES: The aim of the study was to test the value of low dose aspirin associated with standard oral anticoagulants (OAC) after mechanical mitral valve replacement (MMRV) to reduce strands, thrombi and thromboembolic events. BACKGROUND: Strands and thrombi are thought to increase the risk of embolic events after MMVR, particularly in the immediate postoperative period. METHODS: Two hundred twenty-nine patients were prospectively recruited: 109 patients (group A+) were randomly assigned to aspirin (200 mg per day) with OAC and 120 patients (group A-) to OAC alone (international normalized ratio 2.5 to 3.5). All patients were subjected to multiplane transesophageal echocardiography at nine days and five months and were followed up for one year. RESULTS: At nine days and five months, there was a high and comparable incidence of strands in the two groups (group A+: 44%, 58%; group A-: 49%, 63%). However, the incidence of nonobstructive periprosthetic valve thrombi was significantly lower in group A+ at 9 days: 5% versus 13%, p = 0.03. Total thromboembolic events were reduced in group A+ (9% vs. 25%, p = 0.004) although there was an increased incidence of gastrointestinal hemorrhage (7% vs. 0%). Overall mortality was 9% in group A+ and 4% in group A-. Valve-related events were similar in both groups. Early thrombi, but not strands, were associated with higher morbidity, especially thromboembolic events (30% vs. 13%, p = 0.003). CONCLUSIONS: One year after MMVR, the association of aspirin with OAC reduced thrombi and thromboembolic events, but not morbidity, due to an increase in hemorrhagic complications.

Administration, Oral↗