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Biomedical subjects

T Lefèvre

Publications and source records attributed to T Lefèvre.

At least 19 recordsLinked to original sources

Hairworm anti-predator strategy: a study of causes and consequences.

One of the most fascinating anti-predator responses displayed by parasites is that of hairworms (Nematomorpha). Following the ingestion of the insect host by fish or frogs, the parasitic worm is able to actively exit both its host and the gut of the predator. Using as a model the hairworm, Paragordius tricuspidatus, (parasitizing the cricket Nemobius sylvestris) and the fish predator Micropterus salmoïdes, we explored, with proteomics tools, the physiological basis of this anti-predator response. By examining the proteome of the parasitic worm, we detected a differential expression of 27 protein spots in those worms able to escape the predator. Peptide Mass Fingerprints of candidate protein spots suggest the existence of an intense muscular activity in escaping worms, which functions in parallel with their distinctive biology. In a second step, we attempted to determine whether the energy expended by worms to escape the predator is traded off against its reproductive potential. Remarkably, the number of offspring produced by worms having escaped a predator was not reduced compared with controls.

Animals↗

[Drug-eluting stents in complex lesions].

Interventional cardiology has evolved tremendously over the past two years with the advent of drug-eluting stents. The RAVEL trial was the first randomized study conducted with sirolimus-eluting stents in a selected population of patients in whom a 0% rate of binary restenosis was achieved. The objective of the SIRIUS trial conducted in a more complex patient population was to test the efficacy of the sirolimus-eluting stent in high-risk settings such as coronary bifurcation lesions.

Angioplasty, Balloon, Coronary↗

Stent placement compared with balloon angioplasty for small coronary arteries: in-hospital and 6-month clinical and angiographic results.

BACKGROUND: Stenting has been demonstrated to be superior to balloon angioplasty in de novo focal lesions located in large native vessels. However, in small vessels, the benefit of stenting remains questionable. METHODS AND RESULTS: A total of 381 symptomatic patients with de novo focal lesion located on a small coronary segment vessel (<3 mm) were randomly assigned to either stent implantation (192 patients; 197 lesions) or standard balloon angioplasty (189 patients; 198 lesions). The primary end point was the angiographic restenosis rate at 6 months, as determined by quantitative coronary angiography. On intention-to-treat analysis, angiographic success rate and major adverse cardiac events were comparable: 97.9% and 4.6% versus 93.9% and 5.8% in the stent group and the balloon group, respectively. After the procedure, a larger acute gain was achieved with stent placement (1.35+/-0.45 versus 0.94+/-0.47 mm, P=0.0001), resulting in a larger minimal lumen diameter (2.06+/-0.42 versus 1.70+/-0.46 mm, P=0.0001). At follow-up (obtained in 91% of patients), angiographic restenosis rate was 21% in the stent group versus 47% in the balloon group (P=0.0001), a risk reduction of 55%. Repeat target lesion revascularization was less frequent in the stent group (13% versus 25%, P=0.0006). CONCLUSIONS: Elective stent placement in small coronary arteries with focal de novo lesions is safe and associated with a marked reduction in restenosis rate and subsequent target lesion revascularization rate at 6 months.

Angioplasty, Balloon, Coronary↗

Conformational rearrangement of beta-lactoglobulin upon interaction with an anionic membrane.

Interactions between beta-lactoglobulin (beta-lg) and dimyristoylphosphatidylglycerol (DMPG) bilayers were studied using one- and two-dimensional infrared spectroscopy above (pD 7.4) and below (pD 4.4) the protein's (beta-lg's) isoelectric point (pI=5.2). The aim of the study was threefold: (1) gain a better understanding of beta-lg-phospholipid interaction; (2) provide information relative to the structure of beta-lg as it interacts with membranes; (3) determine whether the conformational modifications of the protein in the presence of lipids are strictly caused by thermal effects or whether they are modulated by the chain-melting phase transition. At pD 7.4, the lipid thermotropism, the acyl-chain order, and the membrane interfacial region were essentially unaffected by the presence of beta-lg, whereas the protein amide I region showed dramatic alterations. The results suggested the predominance of beta-sheets and alpha-helix elements, with a lost of structural integrity. At pD 4.4, beta-lg induced an approximately 2 degrees C downshift of the transition temperature, whereas the conformational order of the lipid chain decreased in the gel phase and increased in the liquid-crystalline phase. The hydration state of the DMPG C==O groups increased in the liquid-crystalline phase. The conformation of beta-lg at pD 4.4 in the presence of DMPG showed similarities with that observed at pD 7.4, but an increase in the alpha-helix content and a reduced thermal stability were noticed. In contrast to the protein alone, beta-lg aggregates in the presence of DMPG at pD 4.4 above 50 degrees C. At both pD values, the charged surface of the membrane seemed to be the main factor for inducing protein conformational changes by altering the intramolecular interactions that stabilize the native structure. However, protein incorporation within the membrane seemed to be involved at pD 4.4. The two-dimensional analysis performed with spectra recorded upon heating showed that spectral intensity changes at pD 4.4 and 7.4 occurred at the same frequencies in the amide I' region. The heat-induced structural changes of beta-lg were not correlated with the conformational modifications of the phospholipids along the phase transition, indicating that the thermal behavior of the protein was not modulated by the lipid chain melting, but rather represented the heat-induced protein rearrangement in the presence of DMPG.

Animals↗

Coronary angiography through the radial or the femoral approach: The CARAFE study.

In a previous study, the radial approach for coronary angiography was shown to be associated with a lower success rate and longer procedural and X-ray times compared to the femoral approach. However, this approach is associated with a steep learning curve. A series of 210 consecutive nonselected patients were randomized to femoral versus right radial approach or femoral versus left radial approach by two experienced operators. Clinical characteristics were similar in the three groups. Technical failure occurred in one patient in the right radial group with subsequent crossover to left radial artery. The number of coronary catheters used was lower in the right radial group (1.4 +/- 0.7 vs. 2.1 +/- 0.4 for the two other groups). The procedural duration was longer with left radial (14.2 +/- 3.3 min; P < 0.05) approach than with right radial (12.4 +/- 5.8 min) and femoral (11.2 +/- 3.3 min) without significant differences between femoral and right radial. X-ray exposure was shorter in the femoral group (3.1 +/- 1.7 min) than in both radial groups (right: 3.8 +/- 2.2 min; left: 4.2 +/- 1.7 min). The angiographic quality was not different between the three groups for RCA, but was less good for LCA through right radial approach. Bed rest and hospital stay were shorter in the two radial groups. The comfort was judged better with the transradial approach. An ad hoc PTCA was performed in 45.7% of femoral patients, 41.4% of right radial, and 44.3% of left radial with immediate sheath withdrawal (closure device for femoral group). There were no severe complications in the three groups, but two patients from the femoral group were discharged later because of vascular complications. The total cost of coronary angiography was higher in the femoral group. In conclusion, after the learning period, transradial coronary angiography can be performed with a high success rate, low rate of complication, and good angiographic quality. It is associated with a slight increase in procedural (LR) and fluoroscopy times, but permits earlier ambulation and discharge, improves patient comfort, and reduces the cost.

Aged↗

Amplatzing a 6 Fr Judkins right guiding catheter for increased success in complex right coronary artery anatomy.

Stent supported angioplasty is being performed in an increasing number of patients and, with advances in device technology, more morphologically complex lesions are being treated. In such a setting, it is extremely important to deliver the device to the target lesion. We describe a new technique that allows successful stent delivery in complex right coronary anatomy using the Judkins right guiding catheter. Cathet Cardiovasc Intervent 2001;53:405-409.

Aged↗

The problem of arteria lusoria in right transradial coronary angiography and angioplasty.

The retroesophageal right subclavian artery (arteria lusoria) is one of the anatomical abnormalities encountered by interventional cardiologists who perform right transradial procedures. We report on 11 patients with arteria lusoria in whom 14 right transradial coronary angiography or angioplasty procedures were attempted among a series of 3,730 consecutive right transradial attempts. This abnormality can be easily detected by angiographic visualization, in the anteroposterior projection, of the angle of the catheter when it engages the ascending aorta, and by manual angiography at the ostium of the right subclavian artery. In such a case, catheterization of the ascending aorta may be difficult or even impossible (7.1%). Selective catheterization of both coronary arteries is more difficult, takes longer, and requires more catheters. The Judkins catheters are recommended, although they are seldom used for the left coronary artery via the right radial approach, for both arteries. All catheter exchanges should be performed on long guidewires.

Aged↗

Outcome after combined reperfusion therapy for acute myocardial infarction, combining pre-hospital thrombolysis with immediate percutaneous coronary intervention and stent.

BACKGROUND: Primary therapies in acute myocardial infarction (thrombolysis and angioplasty) have inherent limitations which may be overcome by combining them. So far, no trial has demonstrated a clinical benefit in combining mechanical and pharmacological treatment strategies. METHODS: From January 1995 to December 1999, out of 1010 patients admitted to our institution for acute myocardial infarction, 148 had received pre-hospital full dose thrombolysis within 12 h of onset. One hundred and thirty-one patients were included and underwent immediate angioplasty and stenting when suitable, independent of the infarct-artery patency (TIMI grade flow 0-3). In-hospital outcome was assessed and clinical information was collected for a mean (+/-SD) of 2+/-1 years. RESULTS: Ninety-minute angiography revealed a patent (TIMI grade 3) infarct artery in 65 patients (49%). Immediate angioplasty was performed in 119 patients (91%) with stent implantation in 114 (96%). Angioplasty achieved TIMI 2, 3 flow in 98%, and complete patency (TIMI 3 flow) in 92%. Six other patients underwent deferred revascularization (surgery in one patient, angioplasty in five) and six received medical treatment. Stent thrombosis and reinfarction occurred in three patients (2.3%). In-hospital death occurred in six patients (4.6%), including four patients presenting with cardiogenic shock. Major bleeding was observed in 2.3% of cases. No patient had emergency surgery. Freedom from death and reinfarction at 2 years was 90% and freedom from death, reinfarction and target vessel revascularization was 83%. CONCLUSION: A strategy of combined reperfusion using full dose pre-hospital thrombolysis and immediate angioplasty with stent implantation in a non-selected acute myocardial infarction population is safe and achieves high and early patency rates. This preliminary experience suggests that a combined strategy in acute myocardial infarction may have a significant impact on both early and long-term outcomes.

Angioplasty, Balloon, Coronary↗

Stenting of bifurcation lesions: a rational approach.

The occurrence of stenosis in or next to coronary bifurcations is relatively frequent and generally underestimated. In our experience, such lesions account for 15%-18% of all percutaneous coronary intervention > (PCI). The main reasons for this are (1) the coronary arteries are like the branches of a tree with many ramifications and (2) because of axial plaque redistribution, especially after stent implantation, PCI of lesions located next to a coronary bifurcation almost inevitably cause plaque shifting in the side branches. PCI treatment of coronary bifurcation lesions remains challenging. Balloon dilatation treatment used to be associated with less than satisfactory immediate results, a high complication rate, and an unacceptable restenosis rate. The kissing balloon technique resulted in improved, though suboptimal, outcomes. Several approaches were then suggested, like rotative or directional atherectomy, but these techniques did not translate into significantly enhanced results. With the advent of second generation stents, in 1996, the authors decided to set up an observational study on coronary bifurcation stenting combined with a bench test of the various stents available. Over the last 5 years, techniques, strategies, and stent design have improved. As a result, the authors have been able to define a rational approach to coronary bifurcation stenting. This bench study analyzed the behavior of stents and allowed stents to be discarded that are not compatible with the treatment of coronary bifurcations. Most importantly, this study revealed that stent deformation due to the opening of a strut is a constant phenomenon that must be corrected by kissing balloon inflation. Moreover, it was observed that the opening of a stent strut into a side branch could permit the stenting, at least partly, of the side branch ostium. This resulted in the provocative concept of "stenting both branches with a single stent." Therefore, a simple approach is currently implemented in the majority of cases: stenting of the main branch with provisional stenting of the side branch. The technique consists of inserting a guidewire in each coronary branch. A stent is then positioned in the main branch with a wire being "jailed" in the side branch. The wires are then exchanged, starting with the main branch wire that is passed through the stent struts into the side branch. After opening the stent struts in the side branch, kissing balloon inflation is performed. A second stent is deployed in the side branch in the presence of suboptimal results only. Over the last 2 years, this technique has been associated with a 98% angiographic success rate in both branches. Two stents are used in 30%-35% of cases and final kissing balloon inflation is performed in > 95% of cases. The in-hospital major adverse cardiac events (MACE) rate is around 5% and 7-month target vessel revascularization (TVR) is 13%. Several stents specifically designed for coronary bifurcation lesions are currently being investigated. The objective is to simplify the approach for all users. In the near future, the use of drug-eluting stents should reduce the risk of restenosis.

Blood Vessel Prosthesis Implantation↗

Interaction of beta-lactoglobulin with phospholipid bilayers: a molecular level elucidation as revealed by infrared spectroscopy.

Fourier transform infrared (FTIR) spectroscopy has been used to study, at a molecular level, the interactions between beta-lactoglobulin (BLG), the most abundant globular protein in milk, and some lipids (sphingomyelin, SM; dimyristoylphosphatidylcholine, DMPC; dipalmytoylphosphatidylcholine, DPPC; dimyristoylphosphatidylserine-sodium salt, DMPS; dipalmitoylphosphatidylserine-sodium salt, DPPS) constituting the milk fat globule membrane (MFGM). The interactions were monitored with respect to alteration in the secondary structure of BLG, as registered by the amide I' band, and phospholipid conformation, as revealed by the acyl chain and carbonyl bands. The results show that neither the conformation nor the thermotropism of neutral bilayers containing DMPC or DPPC is affected by BLG. Reciprocally, the secondary structure and thermal behaviour of pure BLG remain the same in the presence of PC. These results suggest that no interaction occurs between PC and BLG, in agreement with previous studies. However, it is found that BLG interacts with neutral bilayers constituted by milk SM lipids, increasing gauche conformers and thus conformational disorder of the lipid acyl chains. This perturbing effect has been attributed to a partial penetration of BLG into the hydrophobic core of the bilayer, which allows hydrophobic interactions between BLG and SM. Moreover, the fact that SM possesses the same headgroup of PC implies that the head group does not prevent the occurrence of BLG-lipid interactions and other lipid regions can control the binding of BLG to lipids. Furthermore, BLG was found to interact electrostatically with charged bilayers containing PS, leading to a rigidification of the lipid hydrocarbon chains and a dehydration of the interfacial region. This last effect suggests that the protein limits the accessibility of water molecules to the interfacial region of the phospholipids by its presence at the membrane surface.

Animals↗

Transcatheter closure of apical ventricular muscular septal defect combined with arterial switch operation in a newborn infant.

This report describes a case of transposition of the great arteries and apical muscular ventricular septal defect in a newborn infant successfully treated by transcatheter closure of the septal defect with the Amplatzer duct occluder device followed by an arterial-switch operation within the first 2 weeks of life. Cathet. Cardiovasc. Intervent. 49:173-176, 2000.

Angiography↗

Stenting of bifurcation lesions: classification, treatments, and results.

Percutaneous transluminal balloon coronary angioplasty (PTCA) of coronary bifurcations is associated with a low success rate, high rate of complications, and high incidence of target vessel revascularization (TVR). The strategy of systematic coronary stenting in bifurcation lesions involving a side branch >/= 2.2 mm in diameter was prospectively evaluated in a single-center observational study during a 35-month inclusion period. All patients meeting these criteria were consecutively included. Bifurcation lesions and treatment were predefined in the study. The study included 366 patients (12.1% of PTCA) with 373 bifurcation lesions, mean age 63.7 +/- 11.6 years, 79.2% male, 46.7% with unstable angina, and 8.3% acute MI. The left anterior descending/diagonal bifurcation was involved in 55.2% of cases, circumflex/marginal 22. 2%, PDA/PLA 10.4%, left main bifurcation in 6.8%, and others 5.4%. The main branch (2.78 +/- 0.42 mm reference diameter) was stented in 96.3% of cases and the side branch (2.44 +/- 0.43 mm) in 63.2% (the two branches were stented in 59.5% of cases). Procedural success was obtained in 96.3% in both branches and 99.4% in the main branch. At1-month follow-up, The major cardiac event rate (MACE) was 4.8% (death 1.1%, emergency CABG 0.6%, Q-wave MI 0.9%, acute or subacute closure 1.4%, repeat PTCA 1.1%, and non-Q-wave MI 2.3%). At 7-month follow-up, the total MACCE rate was 21.6%, including a TVR rate of 17.2%. Analysis of the 7-month outcome according to two study periods (period I, 1 January 1996 to 31 August 1997, 182 patients; period II, 1 September 1997 to 30 June 1998, 127 patients) showed that the TVR rate decreased from 20.6% to 13.8% (P = 0.04) and the MACE rate from 29.2% to 17.1% (P < 0.01) in period I and II, respectively. This was associated by univariate analysis with an increasing use of tubular stents deployed in the main branch (94.2% vs. 59.1%, P < 0.001) and kissing balloon inflation after coronary stenting (75.4% vs. 18.1%, P < 0.001). Bifurcation lesions are frequent. Procedural success of coronary stenting is high with a low rate of in-hospital MACE. TVR rate at follow-up is relatively low. In-hospital and follow-up results are influenced not only by the learning curve but also by the use of tubular stents in the main branch and final kissing balloon inflation.

Aged↗

Molecular differences in the formation and structure of fine-stranded and particulate beta-lactoglobulin gels.

In order to reveal at a molecular level differences between fine-stranded and particulate gels, we present an Fourier transform infrared spectroscopic study of the thermal behavior of beta-lactoglobulin (beta-lg) in salt-free D(2)O solutions and low ionic strength at different pDs. Differences are found in the denaturation mechanism, in the unfolded state of the protein, in the aggregate formation, and in the strength of the intermolecular interactions. For fine-stranded gels (pD 2.8 and 7.8), heating induces the dissociation of the dimers into monomers. The protein undergoes extensive structural modifications before aggregation begins. Aggregation is characterized by the appearance of a new band attributed to intermolecular beta-sheets which is located in the 1613-1619 cm(-1) range. For particulate gels (pD 4.4 and 5.4), the protein structure is almost preserved up to 75-80 degrees C with no splitting of the dimers. The band characteristic of aggregation originates from the component initially located at 1623 cm(-1), suggesting that at the beginning of aggregation, globular beta-lg in the dimeric form associate to constitute oligomers with higher molecular mass. Aggregation may result in the association of globular slightly denatured dimers, leading to the formation of spherical particles rather than linear strands. The aggregation band is always located in the 1620-1623 cm(-1) range for particulate gels showing that hydrogen bonds are weaker for these aggregates than for fine-stranded ones. This has been related to a more extensive protein unfolding for fine-stranded gels that allows a closer alignment of the polypeptide chains, and then to the formation of much stronger hydrogen bonds. Small differences are also found in protein organization and in intermolecular hydrogen bond strength vs pD within the same type of gel. Protein conformation and protein-protein interactions in the gel state may be responsible of the specific macroscopic properties of each gel network. A coarse representation of the different modes of gelation is described.

Animals↗