Biomedical subjects
Publications and source records attributed to Thierry Lefèvre.
As prisoners in their living habitat, parasites should be vulnerable to destruction by the predators of their hosts. But we show here that the parasitic gordian worm Paragordius tricuspidatus is able to escape not only from its insect host after ingestion by a fish or frog but also from the digestive tract of the predator. This remarkable tactic enables the worm to continue its life cycle.
Raman microspectroscopy has been used to quantitatively study the effect of a mechanical deformation on the conformation and orientation of Samia cynthia ricini (S. c. ricini) silk fibroin. Samples were obtained from the aqueous solution stored in the silk gland and stretched at draw ratios (lambda) ranging from 0 to 11. Using an appropriate band decomposition procedure, polarized and orientation-insensitive spectra have been analyzed to determine order parameters and the content of secondary structures, respectively. The data unambiguously show that, in response to mechanical deformation, S. c. ricini fibroin undergoes a cooperative alpha-helix to beta-sheet conformational transition above a critical draw ratio of 4. The alpha-helix content decreases from 33 to 13% when lambda increases from 0 to 11, while the amount of beta-sheets increases from 15 to 37%. In comparison, cocoon silk is devoid of alpha-helical structure and always contains a larger amount of beta-sheets. Although the presence of isosbestic points in different spectral regions reveals that the conformational change induced by mechanical deformation is a two-state process, our results suggest that part of the glycine residues might be incorporated into beta-poly(alanine) structures. The beta-sheets are initially isotropically distributed and orient along the fiber axis as lambda increases, but do not reach the high level of orientation found in the cocoon fiber. The increase in the orientation level of the beta-sheets is found to be concomitant with the alpha --> beta conformational conversion, whereas alpha-helices do not orient under the applied strain but are rather readily converted into beta-sheets. The components assigned to turns exhibit a small orientation perpendicular to the fiber axis in stretched samples, showing that, overall, the polypeptide chains are aligned along the stretching direction. Our results suggest that, in nature, factors other than stretching contribute to the optimization of the amount of beta-sheets and the high degree of orientation found in natural cocoon silk.
Separating effects due to molecular conformation from those due to orientation in the spectra of oriented samples obtained by Raman microspectroscopy is a complex issue. To solve this problem, we propose a procedure to calculate an orientation-insensitive spectrum (so-called isotropic spectrum) from polarized spectra obtained by Raman microspectroscopy that is valid for systems that exhibit a uniaxial symmetry. The method has first been tested on highly oriented samples of high-density polyethylene (HDPE). Polarized and isotropic spectra of a highly oriented HDPE cylindrical rod and an isotropic HDPE sample have been compared. The differences in the relative intensities, which occur in the polarized spectra and are due to orientation of the polyethylene chains, are nearly cancelled in the isotropic spectra, showing that the orientation-insensitive spectrum adequately represents the molecular conformation without contributions of orientation. Second, spectra of silk fibroins have been compared in the amide I region for Bombyx mori cocoon silk fibers and methanol-treated regenerated fibroin films. The similarity of the shape of the amide I band of the isotropic spectra indicates that the secondary structure of the fibroins is very close in both samples. These experimental results support the conclusion that the molecular conformation can be efficiently characterized from the intensity and the shape of Raman bands in the orientation-insensitive spectrum.
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OBJECTIVES: The aim of this research was to determine the influence of bifurcation lesions on the outcome of patients undergoing percutaneous coronary intervention (PCI) in the recent era. BACKGROUND: The treatment of bifurcation lesions by PCI has been associated with an increased complication rate. Whether recent improvements of interventional practice have translated into improved outcomes in this patient subgroup is unknown. METHODS: The 11,482 patients enrolled in the Prevention of Restenosis with Tranilast and its Outcomes (PRESTO) were stratified according to the presence (n = 1,412) or absence (n = 10,068) of at least one bifurcation lesion treated by PCI. Baseline characteristics and outcome of patients undergoing PCI for bifurcation lesions were compared to those of patients treated for nonbifurcation lesions. RESULTS: Patients treated for bifurcation lesions were less likely to have prior myocardial infarction (MI), prior coronary artery bypass graft surgery, and had a higher proportion of current stable angina (p < 0.01 for all comparisons). Bifurcation lesions involved more frequently the left anterior descending coronary artery and were more complex (angulated, eccentric, ostial, and tortuous) than nonbifurcation lesions. Percutaneous coronary intervention of bifurcation lesions was characterized by less frequent stent implantation (71% vs. 80%); PCI of bifurcation lesions was associated with an increased rate of combined end point death/MI/target vessel revascularization (TVR) at nine months (18% vs. 15%, p = 0.002) because of increased rates of TVR (17% vs. 14%, p < 0.001), whereas death (1%) and MI (1%) were not different between groups. CONCLUSIONS: Percutaneous coronary intervention of bifurcation lesions is associated with higher TVR at follow-up. However, the risk of death, MI, death/MI was similar in patients treated for bifurcation or nonbifurcation lesions.
OBJECTIVES: The goal of this study was to evaluate the safety and performance of the Multi-Link Frontier coronary bifurcation stent system (Guidant Corp., Santa Clara, California), a novel dedicated device designed for permanent side branch (SB) access, stent delivery by simultaneous kissing balloon inflation, and optimal main branch (MB) and SB ostium scaffolding. BACKGROUND: The treatment of coronary bifurcation lesions remains challenging, and various approaches using stents have been proposed. METHODS: The primary end point was the 180-day incidence of major adverse cardiac events (MACE) per intent-to-treat analysis. Secondary end points included device success, 30-day MACE, angiographic restenosis, and target lesion revascularization (TLR) rates at 180 days. RESULTS: After a learning phase of two cases per center, 105 patients were prospectively included in 11 centers. The left anterior descending coronary artery/diagonal bifurcation was the target in 80% of cases. The Frontier stent was successfully implanted in 96 patients (91%), and procedural success was obtained in 93%. Two patients suffered in-hospital myocardial infarction (MI) secondary to SB occlusion, and one patient underwent elective coronary artery bypass grafting. At 30 days and 6 months, the MACE rates were 2.9% and 17.1% (no death, no subacute stent thrombosis, Q-wave MI 1.0% and 1.9%, non-Q-wave MI 1.0% and 1.9%, TLR 1.0% and 13.3%). The MB in-stent restenosis was 25.3%, in-segment 29.9%. The SB restenosis was 29.1%. The overall restenosis rate for any branch was 44.8%. CONCLUSIONS: The results of this Frontier registry demonstrate the safety and performance of this dedicated stent system for the treatment of bifurcation lesions. The device can be successfully implanted in more than 90% of all cases, with a high procedural success rate and low 30-day and 6-month MACE rates.
OBJECTIVES: We sought to compare, in a prospective randomized multicenter study, the effect of adjunctive thrombectomy using X-Sizer (eV3, White Bear Lake, Minnesota) before percutaneous coronary intervention (PCI) versus conventional PCI in patients with acute myocardial infarction (AMI) for <12 h and Thrombolysis In Myocardial Infarction (TIMI) flow grade 0 to 1. The primary end point was the magnitude of ST-segment resolution after PCI. BACKGROUND: Despite a high rate of TIMI flow grade 3 achieved by PCI in patients with AMI, myocardial reperfusion remains relatively low. Distal embolization of thrombotic materials may play a major role in this setting. METHODS: We conducted a prospective, randomized, multicenter study in patients with AMI <12 h and initial TIMI flow grade 0 to 1 who were treated with primary PCI. The magnitude of ST-segment resolution 1 h after PCI was the primary end point. RESULTS: A total of 201 patients were included. Treatment groups were comparable by age (61 +/- 13 years), diabetes (22%), previous MI (8%), anterior MI (52%), onset-to-angiogram (258 +/- 173 min), and glycoprotein IIb/IIIa inhibitor use (59%). The magnitude of ST-segment resolution was greater in the X-Sizer group compared with the conventional group (7.5 vs. 4.9 mm, respectively; p = 0.033) as ST-segment resolution >50% (68% vs. 53%; p = 0.037). The occurrence of distal embolization was reduced (2% vs. 10%; p = 0.033) and TIMI flow grade 3 was obtained in 96% vs. 89%, respectively (p = 0.105). Myocardial blush grade 3 was similar (30% vs. 31%; p = NS). Six-month clinical outcome was comparable (death, 6% vs. 4% and major adverse cardiac and cerebral events, 13% vs. 13%, respectively). By multivariate analysis, independent predictors of ST-segment resolution >50% were: younger age, non-anterior MI, use of the X-Sizer, and a short time interval from symptom onset. CONCLUSIONS: Reducing thrombus burden with X-Sizer before stenting leads to better myocardial reperfusion, as illustrated by a reduced risk of distal embolization and better ST-segment resolution.
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This prospective multicenter study was conducted to compare the incidence of significant vascular complications delaying hospital discharge after coronary angiography and percutaneous coronary intervention (PCI) between the radial approach (n = 192) and the femoral approach (n = 185) in octogenarians, a rapidly growing population with numerous risk factors for complications. By intention-to-treat analysis, the incidence of vascular complications was found to be significantly less in the radial group (1.6% vs 6.5%, p = 0.03), without any decrease in the efficacy of PCI and only a slight increase in procedure duration for coronary angiography. All vascular complications, except for 1, occurred in patients treated with the transfemoral approach.
Two-dimensional (2D) correlation spectroscopy establishes correlations between intensity variations in a series of spectra obtained by the application of an external perturbation. However, spectral effects (wavenumber shift or bandwidth change) are known to generate apparent asynchronisms in 2D maps. Surprisingly, spectral effects are often neglected in the literature when interpreting experimental maps, which can lead to erroneous conclusions. In an attempt to evaluate the contribution of these effects and that of true asynchronisms on 2D maps, the heat-induced aggregation of glutamyl-tRNA synthetase (GluRS) was studied as a typical example of the application of Fourier transform infrared (FTIR) spectroscopy in the amide I region. The data were compared with those obtained from a mutant protein that differs by one amino acid. To determine whether the aggregation mechanisms are identical for both proteins, the experimental 2D maps were compared to simulations based on curve fitting of the initial and final spectra of the series, which allows change in position and bandwidth of the components to be taken into account. Intermediate spectra were generated using a convenient function that mimics the spectral evolution. The speed and the delay of each component were controlled. Apart from the appearance of turns that occur for the mutant and not for GluRS, the aggregation mechanisms of both proteins seems to be essentially identical. In particular, the loss of alpha-helices seems to be concomitant with the formation of intermolecular beta-sheets, whereas the loss of intramolecular beta-sheets is delayed. Since the experimental maps are satisfactorily simulated when almost all the components are in phase, it appears that many of the asynchronous features are mainly due to spectral effects. Thus, one has to be aware that true asynchronisms are not necessarily at the origin of peaks observed in asynchronous maps.
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Oil-in-water emulsions stabilized with beta-lactoglobulin (beta-lg) were made using a homogenizer or a high-speed blender. The protein was studied by Fourier transform infrared (FTIR) spectroscopy in the raw emulsion, in the bulk phase, and at the interface, as a function of pH, oil content, and homogenizing pressure. Results show that the amount of adsorbed protein varies with the available interfacial area. The protein that remains in the aqueous phase exhibit no spectral change, which suggests that homogenization causes no conformational modification or reversible ones. Strong and irreversible changes were observed in the adsorbed protein. Our findings reveal the formation of intermolecular antiparallel beta-sheets upon adsorption due to the protein self-aggregation. As deduced from transmission electronic microscopy, this surface aggregation leads to the formation of continuous and homogeneous membranes coating the globules. The structure of the adsorbed proteins is unaffected by the homogenizing pressures used in our study and slightly modified by the pH. FTIR spectroscopy allows to characterize the type of aggregates formed at the interface. An analysis of the spectra of beta-lg heat-induced gels shows that the aggregates at the interface are very close at a molecular scale to those that constitute particulate gels near the protein's isoelectric point. Since the type of aggregates is similar when the emulsion water phase is pure D(2)O and D(2)O at pD 4.4, the interface not only seems to induce aggregation, but seems to determine the type of aggregation as well. The mechanism that drives the formation of particulate aggregates (rather than fine-stranded ones) may reside in strong protein-protein interactions that are promoted by adverse oil-protein interactions.
To obtain molecular insights into the action mode of antimicrobial activity of pediocin PA-1, the interactions between this bacteriocin and dimyristoylphosphatidylcholine (DMPC) or dimyristoylphosphatidylglycerol (DMPG) model membranes have been investigated in D(2)O at pD 6 by Fourier transform infrared spectroscopy. The interactions were monitored with respect to alteration of the secondary structure of pediocin, as registered by the amide I' band, and phospholipid conformation, as revealed by the methylene nu(s)(CH(2)) and carbonyl nu(C;O) stretching vibrations. The results show that no interaction between pediocin and DMPC occurs. By contrast, pediocin undergoes a structural reorganization in the presence of DMPG. Upon heating, pediocin self-aggregates, which is not observed for this pD in aqueous solution. The gel-to-crystalline phase transition of DMPG shifts to higher temperatures with a concomitant dehydration of the interfacial region. Our results indicate that pediocin is an extrinsic peptide and that its action mechanism may lie in a destabilization of the cell membrane.
OBJECTIVES: We sought to determine whether direct stenting might prevent the adverse events associated with stent implantation during primary angioplasty and to compare it with conventional stent implantation in patients with acute myocardial infarction (AMI). BACKGROUND: No trial has demonstrated that stents favorably influence mortality rate. Recent studies have even suggested a negative impact of stents on coronary blood flow and clinical outcome. METHODS: Of 409 patients treated by primary angioplasty with stent implantation in our center, 206 (50%) were enrolled in this randomized, single-center trial and allocated to direct stent implantation (n = 102) or stent implantation after balloon pre-dilation (n = 104). The study end points included angiographic results (final corrected Thrombolysis In Myocardial Infarction [TIMI] frame count and a composite end point of slow and no-reflow or distal embolization), an electrocardiogram marker of myocardial reperfusion assessment (ST-segment resolution) and in-hospital clinical outcome (death and recurrent infarction). RESULTS: Direct stent implantation failed in eight patients but succeeded after pre-dilation in all. A non-significant increase in TIMI flow grade 3 was achieved after direct stenting (95.1% vs. 93.3%, p = 0.74) without significant difference in the corrected TIMI frame count (31.5 +/- 17 and 35.2 +/- 20 frames after direct and conventional stent, respectively, p = 0.42). The composite angiographic end point was significantly reduced by direct stent implantation (11.7% vs. 26.9%, p = 0.01). ST-segment resolution was also significantly improved after direct stent (no ST-segment resolution in 20.2% vs. 38.1% after direct and conventional stent, respectively, p = 0.01). Death and/or recurrent infarction occurred in six patients after conventional stent implantation and in two patients after direct stenting (p = 0.28). CONCLUSIONS: In selected patients with AMI, direct stenting can be applied safely and effectively. This strategy may result in a significant reduction of microvascular injury, as suggested by improved ST-segment resolution after reperfusion with major potential clinical consequences.
Treatment of bifurcation lesions remains a technical challenge. Among 13 stents previously tested in a bench study, the Bestent seemed of particular interest in this indication as it provided good access to the side branch after stent implantation in the main branch associated with a satisfactory coverage of the lesion after kissing balloon inflation. The use of Bestent implanted in the main branch or both branches for treatment of bifurcation lesions involving a side branch > or = 2.2 mm in diameter was prospectively evaluated in a dual-center prospective study with a prospective 6-month clinical follow-up. All angiographic documents were analyzed by an independent corelab (CORISIS). Between 11 September 1997 and 21 February 1998, 96 patients were consecutively included (mean age, 63.7 +/- 11.4 years; 81.3% male; 58.3% with unstable angina and 6.3% acute myocardial infarction). The lesion involved the left anterior descending-diagonal coronary bifurcation in 55% of cases, left circumflex-marginal 23%, posterior descending-postero-lateral 12%, distal left main 6%, and others 4%. The main branch (proximal reference diameter: 3.43 +/- 0.45 mm) was stented in 98% of cases and the side branch (2.72 +/- 0.38 mm) in 38% (both branches in 34% of cases). T-stenting or provisional T-stenting was used in 88% of cases and final kissing balloon inflation was performed in 78% of cases. Procedural success was obtained in 100% of cases in the main branch and 98% in both branches. Major cardiac and cerebral events (MACCE) during hospitalization occurred in 4.2% of cases, non-Q-wave myocardial infarction (MI) in 3.1%, Q-wave MI in 1.0%, repeat PTCA in 2.1%; there were no major access site complication, no emergency coronary artery bypass grafting operation, no death. At 6-month follow-up, total MACCE rate was 14.6% (Q-wave MI, 3.1%; non-Q-wave MI, 3.1%; target vessel revascularization, 9.4%; death, 2.1%). Patients with target vessel revascularization (TVR) had restenosis of both branches in 22.2% of cases, main branch in 22.2%, and side branch in 55.6%. This study shows that using a simple strategy of provisional T-stenting of the side branch in the majority of cases, the Bestent can be used for treating bifurcation lesions with a high rate of success and an acceptable rate of TVR at 6-month follow-up.
Although transradial angioplasty has been shown to have no major entry site-related complications, its clinical applicability for balloon angioplasty and stenting in acute myocardial infarction (AMI) is unclear. In order to assess the feasibility, safety, and clinical outcome of transradial access for coronary angioplasty (PTCA) and stenting during AMI, transradial angioplasty for AMI was registered on a prospective database at two European sites (A and B) with experience in the radial approach (RA); 6 Fr catheters with an inner lumen of at least 0.064" and low-profile rapid-exchange balloons were used. Primary success rates and procedural complications of 6 Fr RA were determined and compared to 6 Fr femoral approach (FA) procedures. A total of 1,224 AMI patients entered the registry. Study site A enrolled 185 RA patients (13.6% AMI) and study site B 92 RA patients (63.4%). Patient baseline demographics were similar in both study centers and showed no differences between RA and FA patients, except a more frequent use of abciximab in study site B compared to A. PTCA was successful in > 95% of both RA and FA patients. Total procedural time did not differ between RA and FA patients. Severe access site-related bleeding complications, however, were observed in FA patients only: study site A used closure devices routinely and found 2% severe bleedings; study site B used no closure device for FA patients and observed 7% severe bleedings. In selected patients and in experienced hands, transradial PTCA in AMI has a high success rate, is clinically safe, and could become an attractive alternative access site for patients being at high or even low risk for bleeding complications.
The gastroepiploic artery has been successfully used as an arterial conduit in selected patients undergoing CABG with acceptable immediate and long-term results. Myocardial ischemia may occur during the follow-up period as a result of spasm, occlusion, or stenosis at the anastomosis site. Because of tortuosity and in order to avoid graft spasm and to obtain good extra backup support, we require low-profile wide-lumen guiding catheters for deep intubation and increased procedural success. In the case presented here, a gastroepiploic graft stenosis was treated by balloon angioplasty performed through a less invasive approach combining transradial access and use of 5 Fr guiding catheter.