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Background: Walking rehabilitation is the cornerstone of patients with peripheral arterial disease (PAD) treatment. In order to propose a personalised walking rehabilitation program to each patient, it is important to know the PAD-patients walking characteristics. Such data are lacking in the literature. The aim of this study was to analyse the spontaneous walking characteristics of PAD patients. Patients and Methods: This study was conducted between May 2016 and March 2018. Walking characteristics (cadence, stride, number of daily walking episodes, duration of an episode, distance covered during an episode, daily total walking duration and distance, walking speed) were recorded by Withings Pulse O2® activity trackers for one week in patients with asymptomatic or symptomatic PAD. Walking intensity was classified as ambling pace (<2 METs), slow walking (2-3 METs) and active walking (>3 METs). Study protocol has been approved by an independent ethics committee. Results: Eighty-seven patients were included (males 87%, mean age 66 ± 9 years, intermittent claudication 86%, right ankle brachial index (ABI) = 0.80 ± 0.19 and left ABI = 0.79 ± 0.15). The mean recording duration was 8 ± 1.2 days. Most of the steps were shuffling pace (shuffling pace 55.7%, active walking 32.8%, slow walking 11.5%). There was no significant difference between weekdays and weekend days nor for cadence, stride, episode duration, distance covered during an episode, number of daily walking episodes, daily total walking duration and distance. The average duration of active walking episodes was 3 minutes. Duration of active walking was less than 3 minutes in 66% of patients with a mean duration of 1 minute and 55 seconds. Conclusion: Analysis of PAD patients spontaneous walking characteristics with an activity tracker can get the maximum active walking duration achieved by each patient and be useful to offer a personalised walking rehabilitation program.

Introduction: Objective Structured Clinical Examinations (OSCEs) assess professional performance in a simulated environment. Following their integration into the reform of the 2nd cycle of medical studies (R2C), this pedagogical modality was implemented in France. This study investigates the variability of students' OSCE scores, as well as their inter-rater reproducibility., Methods: This single-center retrospective study covered several sessions of evaluative OSCE circuits conducted between January 2022 and June 2023. Variables collected were: baseline situation family, competency domain, presence of a standardized participant for stations; gender and professional status for evaluators; scores (global, clinical and communication skills), number of previously completed OSCE circuits and faculty scores for students., Results: The variability of the overall score was explained mainly (79.7%, CI95% [77.4; 82.0]) by the station factor. The student factor and the circuit factor explained 7.5% [12.9; 20.2] and<0.01% [2.10 -13 ; 2.10 -9 ] respectively. The inter-rater intra-class correlation coefficient was 87.2% [86.4; 87.9] for the global score. Station characteristics (starting situation, domain) and evaluator characteristics (gender, status) were significantly associated with score variations., Conclusion: This first study on the variability of OSCE circuit scores in France shows good reproducibility with influence of station characteristics. In order to standardize circuits, variability linked to the domain competency should be considered as well., (Copyright © 2024 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Powders are usually dispensed, blended, and transferred between different manufacturing steps in so-called Intermediate Bulk Containers (IBCs), and discharge from an IBC plays a critical role in the ability to manufacture high-quality tablets. To better understand IBC discharge, the flow behavior of selected excipients was comprehensively characterized using a number of techniques including the Hausner ratio/Carr's index, Erweka flow test, FlowPro flow test, shear test and wall friction test as well as FT4 powder rheometer experiments. Jenike's hopper design methodology was then used to predict the minimum non-arching outlet diameter and the mode of flow. Furthermore, the discharge rate from an IBC was predicted using a simple model that takes into account gravity and aerodynamic drag. The predictions were experimentally verified by measuring the discharge rate from a 20 L IBC using five commonly-used excipients. The small-scale Erweka flow test provided the best prediction of the full-scale IBC discharge experiment. Furthermore, a simple model that relied only on the particle size of the material and the diameter of the discharge opening was found to predict the IBC discharge rate remarkably well., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Characterisation of arterial Doppler waveforms is a persistent problem and a source of confusion in clinical practice. Classifications have been proposed to address the problem but their efficacy in clinical practice is unknown. The aim of the present study was to compare the efficacy of the categorisation rate of Descotes and Cathignol, Spronk et al. and the simplified Saint-Bonnet classifications., Methods: This is a multicentre prospective study where 130 patients attending a vascular arterial ultrasound were enrolled and Doppler waveform acquisition was performed at the common femoral, the popliteal, and the distal arteries at both sides. Experienced vascular specialists categorized these waveforms according to the three classifications., Results: of 1033 Doppler waveforms, 793 (76.8%), 943 (91.3%) and 1014 (98.2%) waveforms could be categorized using Descotes and Cathignol, Spronk et al. and the simplified Saint-Bonnet classifications, respectively. Differences in categorisation between classifications were significant (Chi squared test, p < 0.0001). Of 19 waveforms uncategorized using the simplified Saint-Bonnet classification, 58% and 84% were not categorized using the Spronk et al. and Descotes and Cathignol classifications, respectively., Conclusions: The results of the present study suggest that the simplified Saint-Bonnet classification provides a superior categorisation rate when compared with Spronk et al. and Descotes and Cathignol classifications.

Peripheral arterial disease is a result of atheroma. This disease is frequent in subjects with vascular risk factors. This disease is also frequent in low income countries. The detection and the diagnosis of peripheral arterial disease is obtained by calculating the ankle brachial index. Patients with peripheral arterial disease are not always symptomatic thus explaining how this disease is under diagnosed. The symptoms can be absent, and especially in case of diabetes or in women. In case of peripheral arterial disease, atheroma often involves other arterial vascular networks especially the coronaries. An adapted treatment reduces the morbi-mortality linked to this disease. This treatment is based on the correction of the vascular risk factors and especially tobacco cessation, walking rehabilitation and drugs (antiplatelet agent, statin, renin angiotensin system blocker). In case of rest or critic ischemia, the first-line treatment is a revascularisation. In peripheral arterial disease, management of patients is often non optimal and therapeutic targets fairly often obtained., (Copyright © 2020. Published by Elsevier Masson SAS.)

A multivariate TOF-SIMS methodology has been developed and applied to quantify surface composition and chemical distribution for dry powder blends. Surface properties are often critical to the behavior of powder formulations, especially in the case of dry powders for inhalation, as surface properties directly affect inter-particulate forces and, hence, the dispersibility of the formulation. The mass spectrum at each pixel was fit to a linear combination of reference spectra obtained by non-negatively constrained alternating least squares. From the pixel compositions, average surface coverage and a range of other image features were calculated. Two kinds of systems have been examined: 1) binary blends of lactose particles and coating agents, and 2) blends of different inhalation drugs with carrier lactose. For both kinds of systems, detailed insight into the surface composition and structure could be derived. For the former study, TOF-SIMS results were compared with a complementary surface analysis technique, XPS., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The objective of this study was to characterize the rheology of a pharmaceutical material in the context of the µ(I)-rheology model and to use this model to predict powder flow in a manufacturing operation that is relevant to pharmaceutical manufacturing. The rheology of microcrystalline cellulose spheres was therefore characterized in terms of the μ(I)-rheology model using a modified Malvern Kinexus rheometer. As an example of an important problem in pharmaceutical manufacturing, the flow of these particles from a hopper was studied experimentally and numerically using a continuum Navier-Stokes solver based on the Volume-Of-Fluid (VOF) interface-capturing numerical method. The work shows that the rheology of this typical pharmaceutical material can be measured using a modified annular shear rheometer and that the results can be interpreted in terms of the μ(I)-rheology model. It is demonstrated that both the simulation results and the experimental data show a constant hopper discharge rate. It is noted that the model can suffer from ill-posedness and it is shown how an increasingly fine grid resolution can result in predictions that are not entirely physically realistic. This shortcoming of the numerical framework implies that caution is required when making a one-to-one comparison with experimental data., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Polymer films based on mixtures of ethyl cellulose (EC) and hydroxypropyl cellulose (HPC) have been widely used to coat pellets and tablets to modify the release profile of drugs. For three different EC/HPC films we used 1 H and 19 F MRI in combination with a designed release cell to monitor the drug, polymer and water in 5 dimensional (5D) datasets; three spatial, one diffusion or relaxation and a temporal dimension, in real time. We observed that the water inflow through the films correlated with the initiation of the dissolution of the drug in the tablet beneath the film. Leaching of the pore forming HPC further accelerated water penetration and resulted in a drug release onset after a hydrostatic pressure was generated below the film indicated by positional changes of the film. For the more permeable film, both water ingress and drug egress showed a large variability of release over the film surface indicating the heterogeneity of the system. Furthermore, the 1 H diffusion dataset revealed the formation of a gel layer of HPC at the film surface. We conclude that the setup presented provides a significant level of details, which are not achieved with traditional methods., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Mannitol and lactose are commonly used fillers in pharmaceutical tablets, available in several commercial grades that are produced using different manufacturing processes. These grades significantly differ in particulate and powder properties that impact tablet manufacturability. Choice of sub-optimum type or grade of excipient in tablet formulation can lead to manufacturing problems and difficulties, which are magnified during a continuous manufacturing process. Previous characterization of tableting performance of these materials was limited in scope and under conditions not always realistic to the commercial production of tablets. This work seeks to comprehensively characterize the compaction properties of 11 mannitol and 5 lactose grades using a compaction simulator at both slow and fast tableting speeds. These include tabletability, compressibility, tablet brittleness, die-wall stress transmission, and strain rate sensitivity. A chemometrical analysis of data, using the partial least square technique, was performed to construct a model to provide accurate prediction of tablet tensile strength for mannitol grades. Such knowledge facilitates the selection of suitable tablet filler to attain high quality tablet products., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Appropriate selection of excipient grade during tablet formulation development depends on thorough knowledge in their compaction and flow properties. Each chemically unique pharmaceutical excipient is usually available in several commercial grades that are widely different in powder properties, which influence their performance for a specific formulation application. In this work, 11 grades of mannitol were systematically characterized, in terms of their particulate, flow and tableting properties, and compared against 5 grades of lactose. Principal component analysis (PCA) identified significant correlations among selected variables, such as particle size, surface area, flowability, wall friction, plasticity parameter, tensile strength, and tablet brittleness. PCA also revealed similar grades of the two excipients, which may be used to select replacement grade, if needed, based on similarity in their overall properties., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Lower extremity peripheral artery disease is a frequent disease. Arterial Doppler waveforms analysis is a key element in vascular medicine, especially to diagnose lower peripheral artery disease. Although Doppler waveforms are often used, descriptions are highly heterogeneous. This review presents the simplified Saint-Bonnet classification that is tought to vascular medicine residents in order to homogenize arterial flow description., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Peripheral artery disease of the lower limbs (PAD) is a common disease. Evaluation of PAD is primarily based on non-invasive examinations with analysis of the arterial Doppler signal being a key element. However, the description of arterial Doppler waveforms morphologies varies considerably across medical schools and from country to country. In order to overcome this issue, the French College of Teachers for Vascular Medicine (Collège des Enseignants de Médecine Vasculaire; CEMV) has summarised the published data on Doppler waveforms analysis and proposes a new "Saint-Bonnet" classification system to describe Doppler waveforms morphologies. The simplified Saint-Bonnet classification comprises eight types and allows taking into account if the Doppler signal does not revert to baseline. This classification, which is based on previous classifications, could improve the descriptions of both physiological and pathological waveforms, recorded in lower limb arteries. According to the reviewed literature, recommendations about the use of Doppler waveforms are proposed. This statement is a preamble to reach an international consensus on the subject, which would standardize the description of arterial waveforms and improve the management of PAD patients.

The structure of a material, in particular the extremes of crystalline and amorphous forms, significantly impacts material performance in numerous sectors such as semiconductors, energy storage, and pharmaceutical products, which are investigated in this paper. To characterize the spatial distribution for crystalline-amorphous forms at the uppermost molecular surface layer, we performed time-of-flight secondary-ion mass spectroscopy (ToF-SIMS) measurements for quench-cooled amorphous and recrystallized samples of the drugs indomethacin, felodipine, and acetaminophen. Polarized light microscopy was used to localize crystallinity induced in the samples under controlled conditions. Principal component analysis was used to identify the subtle changes in the ToF-SIMS spectra indicative of the amorphous and crystalline forms for each drug. The indicators of amorphous and crystalline surfaces were common in type across the three drugs, and could be explained in general terms of crystal packing and intermolecular bonding, leading to intramolecular bond scission in the formation of secondary ions. Less intramolecular scission occurred in the amorphous form, resulting in a greater intensity of molecular and dimer secondary ions. To test the generality of amorphous-crystalline differentiation using ToF-SIMS, a different recrystallization method was investigated where acetaminophen single crystals were recrystallized from supersaturated solutions. The findings indicated that the ability to assign the crystalline/amorphous state of the sample using ToF-SIMS was insensitive to the recrystallization method. This demonstrates that ToF-SIMS is capable of detecting and mapping ordered crystalline and disordered amorphous molecular materials forms at micron spatial resolution in the uppermost surface of a material.

Competing Interests: H. Maisonneuve est rédacteur adjoint de La Presse médicale, rédacteur du blog www.redactionmedicale.fr, auteur d’ouvrages sur la rédaction, et gérant de la SARL Hervé Maisonneuve Medical Writing. A. Boiteux est directrice des rédactions des revues professionnelles de santé d’Elsevier Masson (1998-2009), présidente de l’Association nationale des journalistes d’information médicale et professionnelle de santé (ANJIMPS), membre du comité de rédaction du site ResoCHU, associée de la SARL Productive Partners. C. Boissier et F. Stora sont chefs de projet à la Haute Autorité de santé. H. Nabarette est conseiller technique à la Haute Autorité de santé.

Understanding how the pore structure influences the mass transport through a porous material is important in several applications, not the least in the design of polymer film coatings intended to control drug release. In this study, a polymer film made of ethyl cellulose and hydroxypropyl cellulose was investigated. The 3D structure of the films was first experimentally characterized using confocal laser scanning microscopy data and then mathematically reconstructed for the whole film thickness. Lattice Boltzmann simulations were performed to compute the effective diffusion coefficient of water in the film and the results were compared to experimental data. The local porosities and pore sizes were also analyzed to determine how the properties of the internal film structure affect the water effective diffusion coefficient. The results show that the top part of the film has lower porosity, lower pore size, and lower connectivity, which results in a much lower effective diffusion coefficient in this part, largely determining the diffusion rate through the entire film. Furthermore, the local effective diffusion coefficients were not proportional to the local film porosity, indicating that the results cannot be explained by a single tortuosity factor. In summary, the proposed methodology of combining microscopy data, mass transport simulations, and pore space analysis can give valuable insights on how the film structure affects the mass transport through the film.

Drug release from oral pharmaceutical formulations can be modified by applying a polymeric coating film with controlled mass transport properties. Interaction of the coating film with water may crucially influence its composition and permeability to both water and drug. Understanding this interaction between film microstructure, wetting, and mass transport is important for the development of new coatings. We present a novel method for controlled wetting of polymer coating films in an environmental scanning electron microscope, providing direct visual information about the processes occurring as the film goes from dry to wet. Free films made of phase-separated blends of water-insoluble ethyl cellulose (EC) and water-soluble hydroxypropyl cellulose (HPC) were used as a model system, and the blend ratio was varied to study the effect on the water transport properties. Local variations in water transport through the EC/HPC films were directly observed, enabling the immediate analysis of the structure-mass transport relationships. The leaching of HPC could be studied by evaporating water from the films in situ. Significant differences were observed between films of varying composition. The method provides a valuable complement to the current approach of making distinct diffusion and microscopy experiments for studying the dynamic interaction of polymer films with water.

Quantifying the stiffness properties of soft tissues is essential for the diagnosis of many cardiovascular diseases such as atherosclerosis. In these pathologies it is widely agreed that the arterial wall stiffness is an indicator of vulnerability. The present paper focuses on the carotid artery and proposes a new inversion methodology for deriving the stiffness properties of the wall from cine-MRI (magnetic resonance imaging) data. We address this problem by setting-up a cost function defined as the distance between the modeled pixel signals and the measured ones. Minimizing this cost function yields the unknown stiffness properties of both the arterial wall and the surrounding tissues. The sensitivity of the identified properties to various sources of uncertainty is studied. Validation of the method is performed on a rubber phantom. The elastic modulus identified using the developed methodology lies within a mean error of 9.6%. It is then applied to two young healthy subjects as a proof of practical feasibility, with identified values of 625 kPa and 587 kPa for one of the carotid of each subject.

The major aim of this work was to study the effect of two process parameters, temperature and coating flow, on permeability to water and structure of free films sprayed from mixtures of ethyl cellulose (EC), hydroxypropyl cellulose (HPC), and ethanol. The films were sprayed in a new spraying setup that was developed to mimic the film coating process in a fluid bed and to provide well controlled conditions. EC and HPC phase separated during the film drying process, and EC- and HPC-rich domains were formed. The process parameters had a great impact on the structure and the permeability to water of the films. The longer the time before the film structure was locked by a high film viscosity, that is, the lower the temperature and the higher the coating flow, the larger the domains and the lower the film permeability. The effective diffusion coefficient of water in the films varied by about six times within the range of the process parameters studied. Structures of sprayed films and water effective diffusion coefficients in sprayed films were compared to those of cast films. For the cast films, the domains were bigger, and the permeability to water was significantly lower compared to those of the sprayed films. The results indicate that the process parameters can be used as a mean to regulate structure and permeability of coating films undergoing phase separation., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Background: Sleep-disordered breathing (SDB) has emerged as an independent risk factor for carotid atherosclerosis (CA) and cerebrovascular disease in middle-aged subjects. Currently, there is no study providing a causal relationship between SDB and cerebrovascular lesions in elderly., Objective: To assess the impact of SDB on CA in a cohort of healthy elderly subjects., Methods: Seven hundred and fifty-five participants of a cross-sectional study on the association between SDB and cardiovascular morbidity, aged 68yr at study entry, were examined. All subjects underwent carotid ultrasonography and risk factors for atherosclerosis including smoking, metabolic syndrome and hypertension were examined. An apnea + hypopnea index (AHI)>15 was considered indicative of SDB., Results: Presence of carotid lesion was found in 35% of the sample, predominantly in men and in overweight subjects. The most frequent alteration was arteriosclerosis present in 74% of cases, with stenosis >50% found in only 9% of subjects. No significant difference in the prevalence of carotid lesion was found between subjects with and without SDB, subjects with an AHI>30, even though, having a slight increase in CA. At the logistic regression analysis, male gender (p<0.001), systolic and diastolic blood pressure (p<0.001), dyslipidemia (p=0.003) and hypertension (p=0.009) were the variables independently associated with carotid lesions even in severe cases., Conclusion: The incidence of CA in healthy elderly subjects is mediated more by gender, metabolic factors and hypertension than by presence of SDB. Further clinical studies including extensive evaluation of all atherosclerotic factors are needed to elucidate the predisposing role of SDB for cerebrovascular risk., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Nuclear magnetic resonance (NMR) cryoporometry and scanning electron microscopy (SEM) image analysis have been used to investigate the size and shape distribution of pores in pharmaceutical coatings. The coatings were made from a mixture of hydroxypropylcellulose (HPC) and ethylcellulose (EC). Upon solvent evaporation from a solution consisting of both the polymers, a solid polymer film is formed, which after removal of the water-soluble HPC consists of a skeleton of EC. A change in the amount of HPC enables modification of the water permeability through the films. By means of NMR cryoporometry, the presence of small pores (radius below 400 nm) was revealed with no significant change in the pore size distribution (PSD) as the HPC content in the films were changed. NMR cryoporometry showed the presence of channels of a characteristic 30-nm length scale in the films that contained more than 22% HPC. Below this threshold, the lack of interconnecting channels seems to prevent complete HPC dissolution and thereby the water permeability. SEM image analysis showed pore sizes that ranged from hundreds of nanometers up to few micrometers. Above the 22% threshold, further increase of HPC in the films resulted in an increased pore volume and wider PSD., (Copyright © 2012 Wiley Periodicals, Inc.)

In this paper, we present a new approach for velocity vector imaging and time-resolved measurements of strain rates in the wall of human arteries using MRI and we prove its feasibility on two examples: in vitro on a phantom and in vivo on the carotid artery of a human subject. Results point out the promising potential of this approach for investigating the mechanics of arterial tissues in vivo., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Background/objective: To examine the effect of graduated compression stockings (GCS) on the properties of the venous vascular system, as characterized by venous capacitance (VC) and venous outflow (VO), in the lower extremities of individuals with spinal cord injury (SCI), according to injury level., Methods: Nine male subjects with SCI (5 with low paraplegia [LP], 4 with high paraplegia [HP]) performed 2 plethysmography tests: with and without graduated compression knee-length stockings (pressure of 21 mm/Hg). The VC, VO, and cardiovascular parameters (heart rate and blood pressure) were evaluated with and without GCS., Results: The VC and VO were lower in patients with HP than in those with LP. For all subjects, VC was significantly lower (-14%) with GCS than without (1.77 +/- 1.18 vs 1.53 +/- 1.09 vol%, P < 0.01). On the contrary, VO did not differ significantly when wearing or not wearing GCS., Conclusions: This study demonstrated that 21-mm/Hg knee-length GCS are sufficient to prevent venous distension in individuals with SCI, even those with longstanding paraplegia, by significantly decreasing venous capacitance. This intervention may help to prevent deep vein thrombosis.

A 2(8/12)-year old boy suffered from hemiplegia secondary to a post-varicella arteriopathy. His clinical status improved and after 4 years of follow-up he had no recurrent stroke or transient ischemic attack. Regular improvement of arterial lesions, demonstated by serial transcranial Doppler investigations, excluded a progressive arteriopathy. Aspirin therapy was initiated and continued during 2,5 years. Transcranial Doppler is a portable, non-invasive tool that can be easily used on a regular basis to follow-up children with post-varicella arteriopathy.

The equilibrium residence times of the nonionic surfactant nonylphenol ethoxylate (NP100) in a latex dispersion were determined using NMR diffusometry. At 16% w/w particle concentration and 0.12, 0.43 and 0.81% w/w NP100, the residence times of the surfactant were 0.16, 1.02 and 4.73 s in solution (tau(A)) and 0.3, 0.37 and 0.61 s on the surface of the particles (tau(B)), respectively. At even higher particle concentration (>45% w/w), tau(A) and tau(B) were 1.47 and 2.2 s. Calculating the number of collisions that ought to result in adsorbed species, at 16% w/w, only 2, 5 and 2 per thousand (corresponding to 0.12, 0.43 and 0.81% w/w NP100) resulted in adsorption, whereas at >45% w/w, only 12 per thousand resulted in adsorption, which suggested that the surfactant was irreversibly adsorbed on the particles. The small increase in collision frequency with increased particle concentration could be a result of a diffusion controlled adsorption, while an energy barrier for desorption controlled the overall exchange dynamics in the dispersion. The slow dynamics in the dispersion was controlled, mainly by the nonylphenol group, which gave NP100 a strong preference to surfaces. In addition, the chain length of the poly(ethylene glycol) (PEG) group changed the solution behavior from being that of a typical surfactant to that of a polymer.

Atherosclerosis is a ubiquitous inflammatory disease. Patients presenting an acute atherothrombotic event (acute coronary syndrom, stroke, aortic aneurysm, ...) have an increased risk of events in remote arterial territories affected by atherosclerosis. These patients could benefit from systematic screening of asymptomatic atherosclerotic lesions to avoid these complications. For each atherosclerotic territory (coronary artery, carotid artery, aorta, peripheral arteries including renal arteries), we review the methods for screening asymptomatic atherothrombotic lesions which could justify specific treatments: coronary artery stenosis > or = 50%, carotid artery stenosis > or = 60%, renal artery stenosis > or = 50%, and abdominal aortic aneurysm > or = 30 mm. This review shows that non invasive methods (ie, echography, tomodensitometry) are widely available for diagnosis of asymptomatic lesions in carotid and renal arteries, and in the aorta. Despite its invasive caracteristic, coronarory angiography remains the gold-standard for the diagnosis of coronary artery disease. However, cardiac multi-slices CT-scan appears a promising technique for asymptomatic patients.

Immature dendritic cells (DCs) derived from CD34+ progenitor cells or peripheral monocytes, are used as in vitro sensitization models in many chemical allergen treatment studies. During the sensitization, DCs follow maturation process and gain the capacity to migrate to lymph nodes where they stimulate T cells. Chemokine receptor allows DCs to migrate along chemotactic gradients. In this work, we used immature DCs from peripheral monocytes to evaluate the influence of allergens on chemokine receptor and surface-marker expression. We tested the sensitizers dinitrochlorobenzene, Bandrowski's base, and coumarin, as well as the tolerogen dichloronitrobenzene, the irritant sodium dodecyl sulfate and the solvent dimethyl sulfoxide. All skin sensitizers up-regulated the co-stimulatory molecule CD86 and increased the CD83+ cell population. No expression of the chemokine receptors CCR2, CCR3, CCR6, or CXCR5 was observed on DCs exposed to the tested chemicals. The strong allergen dinitrochlorobenzene slightly increased CCR7 expression on DCs but down-regulated CCR1 surface expression. CCR1 down-regulation was not mediated by a classical maturation pathway, as it was unaffected by the corticosteroid dexamethasone.

Unlabelled: Peripheral resistance of lower limb arteries is not a common clinical measurement despite easy-to-apply non-invasive techniques. The aim of our trial has been to test this new parameter as a marker of arterial lesions., Material and Methods: In this prospective study, hemodynamic data acquired non-invasively [Ankle brachial index (ABI), peak systolic velocity (PSV), end-diastole velocity (VTD) and peripheral artery quality] in patients with lower limb arterial disease were compared with the resistance index measured in the common femoral artery (Arbeille index: IR=VTD/PSV)., Results: Between February 1, 2003 and April 30, 2003, 150 measurements of resistance index were made in 99 individuals with ischemia following a strain (69% men, 31% women, average age 64.8+/-15.2 years). Forty-one of the resistance measurements (27%) were also made in patients with arterial disease factors (diabetics, renal replacement therapy). The resistance index was closely associated with end-diastole velocity. (r=-0.76; DDL=148; p<0.01) as well as peripheral artery quality (r=0.81; DDL=148; p<0.01); on the contrary the resistance index was not affected by the arterial disease factors (0.3+/-0.1 vs 0.33+/-0.12; p=NS)., Conclusion: These findings suggest that the hemodynamic impact might be evaluated more precisely diabetics and renal replacement therapy patients whose hemodynamic parameters are difficult to assess due to their arterial disease factors. Prospective studies are needed to determine the role of the resistance index in the follow up of these patients, and its contribution in comparison with the measurement of end-diastole velocity.

The breakdown of tolerance to autologous bacterial flora has been implicated as a major factor contributing to the initiation and perpetuation of chronic inflammation in inflammatory bowel diseases (IBD). To test whether bacterial DNA is at the origin of inflammation in IBD, we have examined the response of lamina propria (LPMC) or peripheral mononuclear cells (PBMC) and purified T cells from IBD patients and control patients to stimulations with a set of oligodeoxynucleotides (ODNs) characterized by the presence or absence of cytosine-guanosine dinucleotides (CpG) and/or 3' poly-guanosine (poly-G) extension. Furthermore we have evaluated the costimulatory activities of these ODNs on T cells activated via CD2 or CD3 pathway. We demonstrated that CpG ODNs induce higher proliferation of LPMC from inflammatory intestinal mucosa compared to healthy mucosa. We confirmed that CpG ODNs do not directly costimulate peripheral blood T cells activated by CD3 pathway. Finally, we revealed that CpG or non-CpG ODNs with 3' poly-G extension inhibit completely CD2 activation of purified PB or LP T-cells whereas only CpG ODNs without poly-G extension enhance proliferation and IFN-gamma production of PB T cells stimulated by CD2 pathway only in presence of NK and NK T cells. Our data suggest that NK T cells may be the primary target of ODNs and play a crucial role in indirect T-cell activation by ODN.

Superficial vein thrombosis (SVT) risk factors are close to those of venous thromboembolism (VTE). Diagnosis is made in a clinical setting but ultrasonography is useful to eliminate concomitant deep vein thrombosis (DVT). For SVT of the lower limbs, which is the main location, varicose veins represent the principal cause but underlying conditions (e.g.: autoimmune diseases, malignancy or thrombophilia) must be sought in idiopathic, migrant or recurrent SVT and in the absence of varicose veins. Concomitant DVT and pulmonary embolism can occur in approximately 15% and 5% respectively. Historical treatments consist of anti-inflammatory agents plus elastic stockings and, in case of varicose veins, thrombectomy and stripping. Other treatments (anticoagulants, vein ligation) were assessed to limit the VTE risk. A one-month prophylactic dose of low molecular weight heparin plus elastic stockings could be the appropriate strategy in most cases. Other studies are needed before definitive conclusions can be drawn.

Formation of solid solution particles in the Solution Enhanced Dispersion by Supercritical fluids (SEDS) process from a model drug and two different types of carriers, mannitol and Eudragit E100 was evaluated. The crystal properties of samples and molecular interactions were investigated with DSC and FTIR, respectively. The effect of co-crystallisation of drug and mannitol on dissolution rate was studied. Even if a true one-phase solid dispersion was not obtained, the crystal structure of both drug and mannitol was mutually affected by the presence of the other. The drug was not in highly crystalline form in the co-precipitates. The interactions between the drug and mannitol could also be identified as hydrogen bonding between the amine or hydroxyl groups of the drug and the hydroxyl groups of mannitol. These interactions and changes in the crystal structure are probably directly related to the increase in the dissolution rate observed. A true solid solution was obtained when the drug was co-processed with Eudragit E100. A clear interaction between the acid hydroxyl group of the drug and the basic carbonyl group on the Eudragit E100 was observed. SEDS was shown to be an effective process for forming intimate blends and solid solutions for the drug and two different types of carriers.

Objectives: Intermittent claudication is one of the clinical symptoms of peripheral arterial disease (PAD). The presence of PAD is a high risk marker of cardiac events and stroke. The PAD screening can be enhanced by the use of questionnaires. The Edinburgh Questionnaire presents in its English version better diagnostic performances compared to the Rose (WHO) Questionnaire. The aim of this study is to precise the performances of the French version of the Edinburgh Questionnaire among a population consulting general practitioners., Methods: Four centers instructed 10 general practitioners each to the measurement of ankle pressure with a Doppler stethoscope. The physicians administrated the Questionnaire to 10 consecutive consultants in a same day, and measured the pressure on posterior tibial, dorsalis pedis and humeral arteries. With a second questionnaire they collected data concerning age, weight, height, and the presence of major risk factors. The same protocol was repeated a second day on new patients. The diagnosis of PAD was based on an ankle-arm index lower than 0.85 for at least on limb., Results: The population studied consisted of 727 subjects (351 females and 376 males). The mean age was at 58.3 +/- 16.1 years (ranging from 18 to 83.3 years). The sensitivity of the Questionnaire is at 47% (95% CI: 32.3-61.7%), the specificity at 98.8% (95% CI: 97.5-99.4%), the positive and negative predictive values are respectively at 73.3% (95% CI: 54.1-87.7%) and 94.8% (95% CI: 94.7-97.6%). Among this population of general practitioners consultants, the prevalence of a low ankle-arm index under 0.85 is at 6.7%., Discussion: The French version of the Edinburgh Questionnaire maintains the very good specificity of the English version. The lower sensitivity could be explained by the choice of the gold standard, namely the ankle-arm index which includes asymptomatic patients with authentic PAD. The use of this Questionnaire can be recommended for the screening of this disease as well as in epidemiological studies.

Context: The carotid intima-media thickness (CIT) is correlated with the prevalence of cardiovascular diseases. We studied the relationship between the thickness of the carotid intima-media and the existence of myocardial ischemia, detected by scintigraphy in a population of type 2 diabetic patients without coronary antecedents., Methods: We conducted repeated Doppler measurements of the CIT of primitive carotid arteries in 52 diabetic patients aged 49 to 75. All these asymptomatic patients, without coronary antecedents, diabetic for more than 10 years and exhibiting at least one cardiovascular risk factor, had undergone myocardial scintigraphy., Results: The CIT was greater in the group with positive scintigraphies and is the best predictive factor of the presence of ischemia. For a CIT value < 0.55 mm, the negative predictive value of the CIT was of 77% with 80% sensitivity; in non-smokers the predictive negative value increased to 92% with 95% sensitivity., Conclusions: Reliable and reproducible, measurement of CIT correlates well with myocardial scintigraphy and could be an interesting alternative screening policy in asymptomatic, type 2 diabetic patients.

Chemokines and their receptors are involved in the migration of different mononuclear cells. Among them macrophages-derived chemokines (MDC) and thymus-and activation regulated chemokine (TARC) belong to a new cluster of genes involve in Th2 lymphocytes homing. Cytokines appear to play a significant role in pathogenesis of inflammatory bowel diseases with an excessive Th1 response in chronic lesions of Crohn's disease (CD) and a Th2 pattern in both earlier mucosal CD lesions and in mucosa of ulcerative colitis (UC). Here we demonstrate that RNAm coding for MDC and TARC are expressed in mucosa from CD and UC patients. Using real-time fluorescent RT-PCR, MDC and TARC mRNA were increased in CD inflamed mucosa. Moreover MDC and TARC transcripts were increased in inflamed CD specimen compared to non-involved CD mucosa. These differences both discriminate CD from UC patients. Additionally, MDC protein was produced in isolated mononuclear cells from peripheral blood (PBMC) or mucosa (LPMC) from UC and CD patients: spontaneously, MDC production from PBMC was increased in CD compared to UC patients. MDC production from CD PBMC was also higher than that found in healthy controls. Together, these data indicate that MDC should be involved in the lymphocytes homing in mucosa from CD patients.

The most severe stages of arteriopathy often involve multifocal macrovascular lesions leading to defective perfusion of the distal tissues and subsequent dysfunction of the microcirculation. Diabetic autonomous neuropathy facilitates and aggravates this endothelial dysfunction. Loss of vasomotricity, platelet and white cell activation, and cytokine release lead to an obstruction of the capillaries and alteration or even destruction of the endothelium. At this stage, the lesions are irreversible and tissue vitality is definitively compromised. The goal of medical treatment is to delay the development of dysfunction and subsequent destruction of the microcirculation before, during and after restoration of sufficient flow through the macrocirculation lesions by angioplasty and/or surgery. Extrapolating from in vitro and animal studies, two mediators, EDRF (NO) and prostacycline, could theoretically inactivate inappropriate activated cells and re-establish flow. Besides their vasodilator proprieties, NO and prostacycline have a synergetic inhibitory effect on platelet and leukocyte activation. The role of platelet antiaggregates and heparins in this stage of severe chronic ischemia remains to be determined. The relative failures of therapeutic drug trials conducted since the end of the eighties demonstrates the importance of intervening before the microcirulation disorders become too severe. Until new compounds are developed, therapeutic progress can be achieved by more precise and earlier detection of alterations in the microcirculation to enable optimal management of arteriopathy of the lower limbs with surgery or angioplasty.

Endovascular repair of abdominal aortic aneurysms (AAA) requires regular surveillance for early detection of endograft failure. CT scanning is the gold standard surveillance procedure. The purpose of this study was to assess the reliability of color duplex ultrasound (CDU) in comparison to CT scanning for detection of endoleaks and changes in aneurysmal diameter. From November 1996 to September 1999, a total of 41 patients treated by aortic endografting underwent regular surveillance with both CT scanning and CDU. There were 39 men and 2 women with a mean age of 71 years (range, 50-83). Endovascular treatment involved deployment of a straight aorto-aortic stent in 6 cases, bifurcated stent in 33, and aorta-to-unilateral iliac artery stent in 2. Stent deployment failed in one case; the procedure was conversion to open surgery. Primary or secondary endoleaks were detected in 17 patients (42%). Our findings indicated that CDU is less reliable than the CT scan for detection of endoleaks, but that reliability of CDU for surveillance of aneurysmal diameter is fair.

The reference list presented here is a selection of educative objectives performed by the French "Collège des Enseignants de Médecine Vasculaire" for the different levels of the medical initial education course. It was produced through a collective procedure, after selecting the most relevant topics and setting up writing rules based upon docimology, and favoring practical rather than theoretical objectives. The main topics are peripheral obstructive arterial disease, polyatherosclerosis, atherosclerosis risk factors, venous thromboembolic disease, thrombophilia, chronic venous insufficiency, lymphatic insufficiency, leg ulcers, vascular acrosyndromes, cerebrovascular diseases and connective tissue diseases, vascular occupational diseases, vascular adverse effects of drugs, diabetic vascular disease, the vascular consequences of hypertension, vascular malformations and angiodysplasia, inflammatory arterial diseases, and vascular explorations. As a whole they include about 300 objectives for the five teaching levels. We hope that this list will help stimulate production of training courses and documents strongly needed in this field.

Connective tissue diseases are the most important organic causes of Raynaud's phenomenon, and systemic sclerosis is the most frequent one. Careful history taking and clinical examination eventually lead to further investigations where capillaroscopy and specific autoantibodies tests have the best performances to reach diagnosis. Our understanding of local regulation of blood flow has been improved discovery of new neuromediators and local substances derived from endothelium. These compounds have direct implications for medical therapy and represent new hopes for the treatment of Raynaud's phenomenon which, however, remains difficult and incomplete for most patients.