Conical Fourier shell correlation applied to electron tomograms.

The resolution of electron tomograms is anisotropic due to geometrical constraints during data collection, such as the limited tilt range and single axis tilt series acquisition. Acquisition of dual axis tilt series can decrease these effects. However, in cryo-electron tomography, to limit the electron radiation damage that occurs during imaging, the total dose should not increase and must be fractionated over the two tilt series. Here we set out to determine whether it is beneficial fractionate electron dose for recording dual axis cryo electron tilt series or whether it is better to perform single axis acquisition. To assess the quality of tomographic reconstructions in different directions here we introduce conical Fourier shell correlation (cFSCe/o). Employing cFSCe/o, we compared the resolution isotropy of single-axis and dual-axis (cryo-)electron tomograms using even/odd split data sets. We show that the resolution of dual-axis simulated and cryo-electron tomograms in the plane orthogonal to the electron beam becomes more isotropic compared to single-axis tomograms and high resolution peaks along the tilt axis disappear. cFSCe/o also allowed us to compare different methods for the alignment of dual-axis tomograms. We show that different tomographic reconstruction programs produce different anisotropic resolution in dual axis tomograms. We anticipate that cFSCe/o can also be useful for comparisons of acquisition and reconstruction parameters, and different hardware implementations.

DNA hypermethylation analysis in sputum for the diagnosis of lung cancer: training validation set approach.

BACKGROUND: Lung cancer has the highest mortality of all cancers. The aim of this study was to examine DNA hypermethylation in sputum and validate its diagnostic accuracy for lung cancer. METHODS: DNA hypermethylation of RASSF1A, APC, cytoglobin, 3OST2, PRDM14, FAM19A4 and PHACTR3 was analysed in sputum samples from symptomatic lung cancer patients and controls (learning set: 73 cases, 86 controls; validation set: 159 cases, 154 controls) by quantitative methylation-specific PCR. Three statistical models were used: (i) cutoff based on Youden's J index, (ii) cutoff based on fixed specificity per marker of 96% and (iii) risk classification of post-test probabilities. RESULTS: In the learning set, approach (i) showed that RASSF1A was best able to distinguish cases from controls (sensitivity 42.5%, specificity 96.5%). RASSF1A, 3OST2 and PRDM14 combined demonstrated a sensitivity of 82.2% with a specificity of 66.3%. Approach (ii) yielded a combination rule of RASSF1A, 3OST2 and PHACTR3 (sensitivity 67.1%, specificity 89.5%). The risk model (approach iii) distributed the cases over all risk categories. All methods displayed similar and consistent results in the validation set. CONCLUSIONS: Our findings underscore the impact of DNA methylation markers in symptomatic lung cancer diagnosis. RASSF1A is validated as diagnostic marker in lung cancer.

Electron diffraction study of lipids in non-lesional stratum corneum of atopic eczema patients.

Skin barrier impairment is thought to be an important factor in the pathogenesis of atopic eczema (AE). The skin barrier is located in the stratum corneum (SC), consisting of corneocytes embedded in lipids. Ceramides, cholesterol and free fatty acids are the major lipid classes and are crucial for the skin barrier function, but their role in relation to AE is indistinct. Filaggrin is an epidermal barrier protein and common mutations in the filaggrin gene strongly predispose for AE. However, there is no strong evidence that filaggrin mutations are related to the reduced skin barrier in AE. In this study, electron diffraction is used in order to study the lipid organization of control SC and non-lesional SC of AE patients in vivo. An increased presence of the hexagonal lipid organization was observed in non-lesional SC of AE patients, indicating a less dense lipid organization. These changes correlate with a reduced skin barrier function as measured with transepidermal water loss but do not correlate with the presence of filaggrin mutations. These results are indicative for the importance of the lipid organization for a proper skin barrier function.

Increased prevalence of psoriasis in patients with coronary artery disease: results from a case-control study.

BACKGROUND: The incidence of myocardial events has been reported to be increased in patients with psoriasis. OBJECTIVES: To investigate whether psoriasis is an independent risk factor for coronary artery disease (CAD). METHODS: We compared the prevalence of psoriasis between case patients with a diagnosis of CAD based on coronary angiography findings and control patients with no CAD referred to the emergency surgery department for an acute noncardiovascular condition. Case and control patients were examined for the presence of psoriasis by two dermatologists. The prevalence of psoriasis was compared among patients with CAD according to CAD severity. Five-hundred cases and 500 age- and sex-matched controls were included. RESULTS: Using matched univariate analysis, the prevalence of psoriasis was about twofold higher in CAD case patients than in control patients [8·0% vs. 3·4%, odds ratio (OR) 2·64; 95% confidence interval (CI) 1·42-4·88]. Using unconditional multivariate analysis, the association of psoriasis with CAD appeared to be borderline significant (OR 1·84; 95% CI 0·99-3·40). Psoriasis in patients with CAD was significantly associated with three-vessel involvement relative to one-or two-vessel involvement (13·1% vs. 6·1%; OR 3·07; 95% CI 1·50-6·25). CONCLUSIONS: The prevalence of psoriasis is twofold higher in patients with CAD than in control patients without CAD. It is associated with a more severe coronary artery involvement.

Localization of fluorescently labeled structures in frozen-hydrated samples using integrated light electron microscopy.

Correlative light and electron microscopy is an increasingly popular technique to study complex biological systems at various levels of resolution. Fluorescence microscopy can be employed to scan large areas to localize regions of interest which are then analyzed by electron microscopy to obtain morphological and structural information from a selected field of view at nm-scale resolution. Previously, an integrated approach to room temperature correlative microscopy was described. Combined use of light and electron microscopy within one instrument greatly simplifies sample handling, avoids cumbersome experimental overheads, simplifies navigation between the two modalities, and improves the success rate of image correlation. Here, an integrated approach for correlative microscopy under cryogenic conditions is presented. Its advantages over the room temperature approach include safeguarding the native hydrated state of the biological specimen, preservation of the fluorescence signal without risk of quenching due to heavy atom stains, and reduced photo bleaching. The potential of cryo integrated light and electron microscopy is demonstrated for the detection of viable bacteria, the study of in vitro polymerized microtubules, the localization of mitochondria in mouse embryonic fibroblasts, and for a search into virus-induced intracellular membrane modifications within mammalian cells.

Is the duration of dual antiplatelet therapy (DAPT) excessive in post-angioplasty in chronic coronary syndrome? Data from the France-PCI registry (2014-2019).

Background: while the duration of dual antiplatelet therapy (DAPT) following coronary angioplasty for chronic coronary syndrome (CCS) recommended by the European Society of Cardiology has decreased over the last decade, little is known about the adherence to those guidelines in clinical practice in France. Aim: To analyze the real duration of DAPT post coronary angioplasty in CCS, as well as the factors affecting this duration. Methods: Between 2014 and 2019, 8.836 percutaneous coronary interventions for CCS from the France-PCI registry were evaluated, with 1 year follow up, after exclusion of patients receiving oral anticoagulants, procedures performed within one year of an acute coronary syndrome, and repeat angioplasty. Results: Post-percutaneous coronary intervention (PCI) DAPT duration was > 12 months for 53.1% of patients treated for CCS; 30.5% had a DAPT between 7 and 12 months, and 16.4% a DAPT ≤ 6 months. Patients with L-DAPT (>12 months) were at higher ischemic risk [25.0% of DAPT score ≥2 vs. 18.8% DAPT score ≥2 in S&I-DAPT group (≤12 months)]. The most commonly used P2Y12 inhibitor was clopidogrel (82.2%). The prescription of ticagrelor increased over the period. Conclusions: post-PCI DAPT duration in CCS was higher than international recommendations in the France PCI registry between 2014 and 2019. More than half of the angioplasty performed for CCS are followed by a DAPT > 12 months. Ischemic risk assessment influences the duration of DAPT. This risk is probably overestimated nowadays, leading to a prolongation of DAPT beyond the recommended durations, thus increasing the bleeding risk.

[stent thrombosis : A won battle ? (data from the France PCI registry)]. / Thrombose de stent : une bataille gagnée ? (Données du registre France PCI).

GOAL: The aim of the study is to assess the incidence, risk factors and prognosis of definite stent thrombosis (ST) at 1 year in the France PCI multicenter prospective registry. PATIENTS AND METHODS: Only patients who underwent coronary angioplasty with at least one stent implantation between 1st January 2014 and 31 December 2019 were included. The population was separated into 2 groups: the "ST" group with stent thrombosis and the "control" group without stent thrombosis. RESULTS: 35,435 patients were included. 256 patients (0.72%) presented a ST at 1 year. The rate of ST decreased significantly in acute coronary syndrome (1.5% in 2014 vs. 0.73% in 2019; p = 0.05) but not in chronic coronary syndrome (0.46% in 2014 vs 0.40%; p = 0.98). The risk factors are young age (65.8 years vs 68.2; p = 0.002), clinical context (35.27% vs 16.68%; p = 0.0001), diabetes (35.2 % vs 26.4%; p = 0.002), renal failure (11.7% vs 8%; p = 0.009) and history of coronary angioplasty (28.63% vs 21.86%; p = 0.009) and peripheral arterial disease (14.5% vs 10.1%; p = 0.021), LV dysfunction (37% vs 27.5%; p = 0.003), mean length (39.6 mm vs 31, 7mm; p <0.0001) and the mean number of stents per procedure (1.9 vs 1.6; p <0.0001), a TIMI flow ≤1 pre procedure (21.5% vs 12.4%; p <0.0001) and an intrastent restenosis (11% vs 6%; p <0.0001). The 1-year mortality of the ST group was significantly higher than that of the control group (19.14% vs 5.82%; p <0.0001). CONCLUSION: Since 2014, the incidence of ST at 1 year has been decreasing but remains stuck at a floor level of 0.54% in 2019. The battle for ST seems to have been partly won and its risk factors well identified, but its mortality is still high.

Monitoring Alzheimer Amyloid Peptide Aggregation by EPR.

Plaques containing the aggregated beta-Amyloid (Abeta) peptide in the brain are the main indicators of Alzheimer's disease. Fibrils, the building blocks of plaques, can also be produced in vitro and consist of a regular arrangement of the peptide. The initial steps of fibril formation are not well understood and could involve smaller aggregates (oligomers) of Abeta. Such oligomers have even been implicated as the toxic agents. Here, a method to study oligomers on the time scale of aggregation is suggested. We have labeled the 40 residue Abeta peptide variant containing an N-terminal cysteine (cys-Abeta) with the MTSL [1-oxyl-2,2,5,5-tetramethyl-Delta-pyrroline-3-methyl] methanethiosulfonate spin label (SL-Abeta). Fibril formation in solutions of pure SL-Abeta and of SL-Abeta mixed with Abeta was shown by Congo-red binding and electron microscopy. Continuous-wave 9 GHz electron paramagnetic resonance reveals three fractions of different spin-label mobility: one attributed to monomeric Abeta, one to a multimer (8-15 monomers), and the last one to larger aggregates or fibrils. The approach, in principle, allows detection of oligomers on the time scale of aggregation.

Position paper of French Interventional Group (GACI) for TAVI in France in 2018.

Aortic stenosis is a frequent disease in the elderly. Its prevalence is 0.4% with a sharp increase after the age of 65, and its outcome is very poor when the patient becomes symptomatic. The interventional procedure known as TAVI (trans-catheter aortic valve implantation), which was developed in France and carried out for the first time in Rouen by Prof. Alain Cribier and his team in 2002, has proven to be a valid alternative to surgical aortic valve replacement. At first, this technique was shown to be efficient in patients with contra-indications to surgical treatment or deemed to be at high surgical risk. Given the very promising outcomes achieved as a result of close heart team collaboration, appropriate patient selection, simplified procedures and reduced complication rates, transfemoral (TF) TAVI is now preferred in symptomatic intermediate risk patients>75 years old according to the latest ESC guidelines. In 2017, in France, TAVI is currently performed in 50 centers with on-site cardiac surgery. The 2016 TAVI outcomes recorded in the French national TAVI registry (France TAVI) are very encouraging and show that for 7133 patients treated (age 83.4±7 years, logistic Euroscore 14%), 87% of whom via the TF approach, cross-over to surgery was very low (0.5%) with a 3.0% in-hospital mortality rate. The substantial increase in TAVI indications and the improvement of its outcomes may in the near future call for a reconsideration of the number of high volume centers authorized to carry out this technique.

Detection of Alpha-Toxin and Other Virulence Factors in Biofilms of Staphylococcus aureus on Polystyrene and a Human Epidermal Model.

BACKGROUND & AIM: The ability of Staphylococcus aureus to successfully colonize (a)biotic surfaces may be explained by biofilm formation and the actions of virulence factors. The aim of the present study was to establish the presence of 52 proteins, including virulence factors such as alpha-toxin, during biofilm formation of five different (methicillin resistant) S. aureus strains on Leiden human epidermal models (LEMs) and polystyrene surfaces (PS) using a competitive Luminex-based assay. RESULTS: All five S. aureus strains formed biofilms on PS, whereas only three out of five strains formed biofilms on LEMs. Out of the 52 tested proteins, six functionally diverse proteins (ClfB, glucosaminidase, IsdA, IsaA, SACOL0688 and nuclease) were detected in biofilms of all strains on both PS and LEMs. At the same time, four toxins (alpha-toxin, gamma-hemolysin B and leukocidins D and E), two immune modulators (formyl peptide receptor-like inhibitory protein and Staphylococcal superantigen-like protein 1), and two other proteins (lipase and LytM) were detectable in biofilms by all five S. aureus strains on LEMs, but not on PS. In contrast, fibronectin-binding protein B (FnbpB) was detectable in biofilms by all S. aureus biofilms on PS, but not on LEMs. These data were largely confirmed by the results from proteomic and transcriptomic analyses and in case of alpha-toxin additionally by GFP-reporter technology. CONCLUSION: Functionally diverse virulence factors of (methicillin-resistant) S. aureus are present during biofilm formation on LEMs and PS. These results could aid in identifying novel targets for future treatment strategies against biofilm-associated infections.

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.

Balloon angioplasty for the treatment of coronary in-stent restenosis: immediate results and 6-month angiographic recurrent restenosis rate.

OBJECTIVES: The purpose of this prospective study was to evaluate the immediate results and the 6-month angiographic recurrent restenosis rate after balloon angioplasty for in-stent restenosis. BACKGROUND: Despite excellent immediate and mid-term results, 20% to 30% of patients with coronary stent implantation will present an angiographic restenosis and may require additional treatment. The optimal treatment for in-stent restenosis is still unclear. METHODS: Quantitative coronary angiography (QCA) analyses were performed before and after stent implantation, before and after balloon angioplasty for in-stent restenosis and on a 6-month systematic coronary angiogram to assess the recurrent angiographic restenosis rate. RESULTS: Balloon angioplasty was performed in 52 patients presenting in-stent restenosis. In-stent restenosis was either diffuse (> or =10 mm) inside the stent (71%) or focal (29%). Mean stent length was 16+/-7 mm. Balloon diameter of 2.98+/-0.37 mm and maximal inflation pressure of 10+/-3 atm were used for balloon angioplasty. Angiographic success rate was 100% without any complication. Acute gain was lower after balloon angioplasty for in-stent restenosis than after stent implantation: 1.19+/-0.60 mm vs. 1.75+/-0.68 mm (p=0.0002). At 6-month follow-up, 60% of patients were asymptomatic and no patient died. Eighteen patients (35%) had repeat target vessel revascularization. Angiographic restenosis rate was 54%. Recurrent restenosis rate was higher when in-stent restenosis was diffuse: 63% vs. 31% when focal, p=0.046. CONCLUSIONS: Although balloon angioplasty for in-stent restenosis can be safely and successfully performed, it leads to less immediate stenosis improvement than at time of stent implantation and carries a high recurrent angiographic restenosis rate at 6 months, in particular in diffuse in-stent restenosis lesions.

Angioscopic evaluation of rotational atherectomy followed by additional balloon angioplasty versus balloon angioplasty alone in coronary artery disease: a prospective, randomized study.

OBJECTIVES: This study sought to compare, by angioscopy, the morphologic changes induced by rotational atherectomy, followed by additional angioplasty, with those observed after balloon angioplasty alone. BACKGROUND: Rotational atherectomy and balloon angioplasty act by different mechanisms, which could explain the difference in morphologic changes induced by these two techniques. METHODS: The study group included 50 patients with 50 lesions who were randomly assigned to undergo rotational atherectomy (n = 24) or balloon angioplasty (n = 26). Rotational atherectomy with a single burr (approximately equal to 70% of coronary diameter) was systematically followed by additional balloon angioplasty. Angioscopy was performed immediately after the procedure. Abnormal angioscopic findings were 1) flaps, graded from 1 to 3 (1 = intimal flap; 2 = flap protruding into < 50% of the lumen; 3 = flap protruding into > or = 50% of the lumen); 2) thrombi, graded from 1 to 3 (1 = flat deposits; 2 = protruding but nonocclusive thrombus; 3 = occlusive thrombus); 3) subintimal hemorrhage; 4) longitudinal dissection. The two groups were comparable for clinical and angiographic baseline data. RESULTS: On angioscopy, flaps were observed less frequently after rotational atherectomy followed by additional balloon angioplasty (8 [33%] of 24 lesions) than after balloon angioplasty alone (14 [54%] of 26 lesions, p = 0.08) and were also less severe (grade 1 in 6 lesions, grade 2 in 2 and grade 3 in none vs. grade 1 in 4 lesions, grade 2 in 5 and grade 3 in 5). Longitudinal dissections were also significantly less frequent: one versus six (p = 0.05). There was no difference in the incidence of angioscopic thrombi (p = 0.16) or subintimal hemorrhage (p = 0.15), but the power to detect a significant difference was low for these variables (37% and 26%, respectively). CONCLUSIONS: Rotational atherectomy followed by additional balloon angioplasty leads to fewer angioscopic dissections and a trend toward fewer intimal flaps than balloon angioplasty alone. However, our angioscopic differences did not lead to an outcome difference between the two groups.

Improved myocardial ischemic response and enhanced collateral circulation with long repetitive coronary occlusion during angioplasty: a prospective study.

OBJECTIVES: The goal of the study was to evaluate the progressive increase in ischemic threshold with multiple sequential transient coronary occlusions and to assess the role of the collateral circulation in adaptation to ischemia. BACKGROUND: It has been observed that the duration of balloon inflations during coronary angioplasty can be gradually prolonged during subsequent dilations with a reduction in patient symptoms and diminished ischemic electrocardiographic (ECG) changes. Although the mechanism has not been fully explained, recruitment of coronary collateral circulation induced by repeated coronary occlusion has been reported. The stimuli for recruitment and the natural history of coronary collateral circulation are not understood. METHODS: Seventeen patients with isolated stenosis of the left anterior descending coronary artery and a normal left ventricle were enrolled. Angioplasty consisted of five successive prolonged inflations. Sequential changes in clinical, intracoronary ECG and left ventricular indexes of myocardial ischemia were examined. Coronary collateral channels were evaluated during balloon inflations by ipsilateral and contralateral injections of contrast medium and hemodynamically by occlusion pressure. RESULTS: An improved tolerance to myocardial ischemia with repetitive coronary occlusions was demonstrated by a significant reduction of angina, ST segment deviation, left ventricular filling pressure and less impairment of ejection fraction. Left ventricular wall motion abnormalities remained unchanged. Collateral angiographic grade did not change in 7 patients and increased in 10. CONCLUSIONS: This study confirms a progressive adaptation of myocardial ischemia to repetitive coronary occlusions and supports the concept that sequential episodes of myocardial ischemia are a stimulating factor for the recruitment of collateral channels in humans. These results also suggest that enhancement of recruitable collateral circulation might be an underlying mechanism of myocardial ischemic preconditioning.

Dobutamine stress echocardiography in orthotopic heart transplant recipients. VACOMED Research Group.

OBJECTIVES: This study sought to determine whether dobutamine stress echocardiography could accurately identify coronary artery disease after heart transplantation. BACKGROUND: After heart transplantation, coronary artery disease is related to either diffuse concentric intimal thickening or focal stenosis and may be underdiagnosed by coronary angiography. METHODS: We enrolled 41 patients, a mean (+/- SD) of 40 +/- 20 months after heart transplantation, at the time of their routine control coronary angiogram. Three patients were excluded because of poor echogenicity on the angiogram and one because of ventricular premature beats. Standard echocardiographic views were acquired at baseline and at incremental dobutamine infusion levels (from 5 to a maximal dose of 40 micrograms/kg body weight per min at 3-min intervals). Regional wall motion score was calculated from a 16-segment model, and each segment was graded from 1 (normal) to 4 (dyskinesia). Coronary angiography was performed 24 h after dobutamine stress echocardiography, and angiograms were analyzed in blinded manner. RESULTS: Twenty-three (62%) of 37 patients had normal coronary angiographic findings. Dobutamine stress echocardiography showed abnormalities in only 2 of 23 patients. Fourteen patients (38%) had abnormal angiographic findings, seven of whom had stenoses > 50%. Dobutamine stress echocardiography correctly identified the corresponding hypoperfused segments in these seven patients. More of interest were the other seven patients, of whom three had angiographic nonsignificant stenoses (< 50%), and four had minor diffuse coronary irregularities. Dobutamine stress echocardiography showed hypokinesia in five of these seven patients despite nonsignificant lesions at coronary angiography. The respective overall sensitivity and specificity of dobutamine stress echocardiography were 86% and 91%. At follow-up, 2 of the 37 patients had an acute myocardial infarction. Both had abnormal findings on dobutamine stress echocardiography: One had normal coronary angiographic results, and one had significant coronary lesions. CONCLUSIONS: Dobutamine stress echocardiography is a useful technique for the diagnosis of coronary artery disease after heart transplantation. These preliminary results indicate that dobutamine stress echocardiography may have a predictive value for further ischemic events in heart transplant recipients.

A comparison of systematic stenting and conventional balloon angioplasty during primary percutaneous transluminal coronary angioplasty for acute myocardial infarction. STENTIM-2 Investigators.

OBJECTIVES: In a multicenter, randomized trial, systematic stenting using the Wiktor stent was compared to conventional balloon angioplasty with provisional stenting for the treatment of acute myocardial infarction (AMI). BACKGROUND: Primary angioplasty in AMI is limited by in-hospital recurrent ischemia and a high restenosis rate. METHODS: A total of 211 patients with AMI <12 h from symptom onset, with an occluded native coronary artery, were randomly assigned to systematic stenting (n = 101) or balloon angioplasty (n = 110). The primary end point was the binary six-month restenosis rate determined by core laboratory quantitative angiographic analysis. RESULTS: Angiographic success (Thrombolysis in Myocardial Infarction [TIMI] flow grade 3 and residual diameter stenosis <50%) was achieved in 86% of the patients in the stent group and in 82.7% of those in the balloon angioplasty group (p = 0.5). Compared with the 3% cross-over in the stent group, cross-over to stenting was required in 36.4% of patients in the balloon angioplasty group (p = 0.0001). Six-month binary restenosis (> or = 50% residual stenosis) rates were 25.3% in the stent group and 39.6% in the balloon angioplasty group (p = 0.04). At six months, the event-free survival rates were 81.2% in the stent group and 72.7% in the balloon angioplasty group (p = 0.14), and the repeat revascularization rates were 16.8% and 26.4%, respectively (p = 0.1). At one year, the event-free survival rates were 80.2% in the stent group and 71.8% in the balloon angioplasty group (p = 0.16), and the repeat revascularization rates were 17.8% and 28.2%, respectively (p = 0.1). CONCLUSIONS: In the setting of primary angioplasty for AMI, as compared with a strategy of conventional balloon angioplasty, systematic stenting using the Wiktor stent results in lower rates of angiographic restenosis.

The 5 A projection structure of the transmembrane domain of the mannitol transporter enzyme II.

The uptake of mannitol in Escherichia coli is controlled by the phosphoenolpyruvate dependent phosphotransferase system. Enzyme II mannitol (EIIMtl) is part of the phosphotransferase system and consists of three covalently bound domains. IICMtl, the integral membrane domain of EIIMtl, is responsible for mannitol transport across the cytoplasmic membrane. In order to understand this molecular process, two-dimensional crystals of IICMtl were grown by reconstitution into lipid bilayers and their structure was investigated by cryo-electron crystallography. The IICMtl crystals obey p22121 symmetry and have a unit cell of 125 Ax65 A, gamma=90 degrees. A projection structure was determined at 5 A resolution using both electron images and electron diffractograms. The unit cell contains two IICMtl dimers with a size of about 40 Ax90 A, which are oriented up and down in the crystal. Each monomer exhibits six domains of high density which most likely correspond to transmembrane alpha-helices and cytoplasmic loops.

Thallium-gated SPECT in patients with major myocardial infarction: effect of filtering and zooming in comparison with equilibrium radionuclide imaging and left ventriculography.

UNLABELLED: The effect of filtering and zooming on 201TI-gated SPECT was evaluated in patients with major myocardial infarction. METHODS: Rest thallium (TI)-gated SPECT was performed with a 90 degrees dual-head camera, 4 h after injection of 185 MBq 201TI in 32 patients (mean age 61 +/- 11 y) with large myocardial infarction (33% +/- 17% defect on bull's eye). End diastolic volume (EDV), end systolic volume (ESV) and left ventricular ejection fraction (LVEF) were calculated using a commercially available semiautomatic validated software. First, images were reconstructed using a 2.5 zoom, a Butterworth filter (order = 5) and six Nyquist cutoff frequencies: 0.13 (B5.13), 0.15 (B5.15), 0.20 (B5.20), 0.25 (B5.25), 0.30 (B5.30) and 0.35 (B5.35). Second, images were reconstructed using a zoom of 1 and a Butterworth filter (order = 5) (cutoff frequency 0.20 [B5.20Z1]) (total = 32 x 7 = 224 reconstructions). LVEF was calculated in all patients using equilibrium radionuclide angiocardiography (ERNA). EDV, ESV and LVEF were measured with contrast left ventriculography (LVG). RESULTS: LVEF was 39% +/- 2% (mean +/- SEM) for ERNA and 40% +/- 13% for LVG (P = 0.51). Gated SPECT with B5.20Z2.5 simultaneously offered a mean LVEF value (39% +/- 2%) similar to ERNA (39% +/- 2%) and LVG (40% +/- 3%), optimal correlations with both ERNA (r = 0.83) and LVG (r = 0.70) and minimal differences with both ERNA (-0.9% +/- 7.5% [mean +/- SD]) and LVG (1.1% +/- 10.5%). As a function of filter and zoom choice, correlation coefficients between ERNA or LVG LVEF, and gated SPECT ranged from 0.26 to 0.88; and correlation coefficients between LVG and gated SPECT volumes ranged from 0.87 to 0.94. There was a significant effect of filtering and zooming on EDV, ESV and LVEF (P < 0.0001). Low cutoff frequency (B5.13) overestimated LVEF (P < 0.0001 versus ERNA and LVG). Gated SPECT with 2.5 zoom and high cutoff frequencies (B5.15, B5.20, B5.25, B5.30 and B5.35) overestimated EDV and ESV (P < 0.04) compared with LVG. This volume overestimation with TI-gated SPECT in patients with large myocardial infarction was correlated to the infarct size. A zoom of 1 underestimated EDV, ESV and LVEF compared with a 2.5 zoom (P < 0.02). CONCLUSION: Accurate LVEF measurement is possible with TI-gated SPECT in patients with major myocardial infarction. However, filtering and zooming greatly influence EDV, ESV and LVEF measurements, and TI-gated SPECT overestimates left ventricular volumes, particularly when the infarct size increases.

Insights on the mechanism of balloon valvuloplasty in aortic stenosis.

An analysis of the mechanisms of action of balloon valvuloplasty in adult aortic stenosis (AS), based on postmortem studies on fresh specimens and on clinical experience with 300 consecutive cases, is reported. When maximally inflated, a 20-mm diameter balloon (occupying a 3.14 cm2 cross-sectional area) significantly enlarges the stenosed valve orifice by 3 mechanisms: stretching of valve tissue, rupturing of commissural fusion and breaking of calcific deposits. These last 2 mechanisms are the most effective, in both tricuspid and bicuspid forms of AS, to render the cusps more flexible and able to open during systole and to close at the time of ventricular diastole. The marked increase in valve area obtained by the dilatation procedure was clearly demonstrated on fresh postmortem specimens and also on postmortem examination of cases that had had balloon valvuloplasty during life. Stretching alone may give only a temporary increase in valve area with an elastic return of the leaflets to their initial stenosing position and may explain, at least in part, the occurrence of restenosis. Inflation of the balloon is well tolerated with no deleterious decrease in blood pressure in two-thirds of the cases because the balloon opens the commissures, allowing blood ejection through these openings. It does not produce calcific emboli, probably because calcium deposits remain imbedded in the leaflets, covered by the endothelium. Finally, it very infrequently produces acute severe aortic regurgitation. Careful choice of balloon size is necessary to obtain on effective opening; most often a 20-mm diameter balloon but sometimes a balloon up to 23 mm is used.(ABSTRACT TRUNCATED AT 250 WORDS)

Results of percutaneous transluminal valvuloplasty in 218 adults with valvular aortic stenosis.

The results of balloon aortic valvuloplasty (BAV) in 218 adult patients with valvular aortic stenosis (AS) are reported. In most cases, 3 transcutaneously introduced balloons of successively increasing size were used. Tolerance was excellent in 64%, whereas a decrease in blood pressure below 60 mm Hg during inflation was observed in 36%. The left ventricular-aortic peak to peak gradient decreased from 72 +/- 25 to 29 +/- 14 mm Hg (p less than 0.001) and the aortic valve area increased from 0.52 +/- 0.18 to 0.93 +/- 0.33 cm2 (p less than 0.001). The final aortic valve area was greater than or equal to 1 cm2 in 69 patients (32%). In only 6 cases (3%) the aortic valve area did not change or increased by less than 10%. A clear improvement in the results was observed with gained experience and better catheters. There was 1 death and 1 stroke in the procedure room, and 3 strokes after BAV. Nine patients died shortly after the procedure. There were local complications (hematoma or thrombosis) at the femoral puncture site in 28 (13%) patients. Clinical follow-up was obtained for 144 patients (mean 8 months). There were 24 deaths. In the 120 remaining cases, symptomatic improvement was good in 84%, with decrease or disappearance of dyspnea, angina or both. This study demonstrates that BAV is feasible in adult AS at a low risk and is able to produce marked clinical improvement in most cases.