Progress in cardiovascular anastomoses: will the vascular join replace Carrel's technique?

BACKGROUND: Vascular reconstructions are becoming challenging due to the comorbidity of the aging population and since the introduction of minimally invasive approaches. Many sutureless anastomosis devices have been designed to facilitate the cardiovascular surgeon's work and the vascular join (VJ) is one of these. We designed an animal study to assess its reliability and long-term efficacy. METHODS: VJ allows the construction of end-to-end and end-to-side anastomoses. It consists of two metallic crowns fixed to the extremity of the two conduits so that vessel edges are joined layer by layer. There is no foreign material exposed to blood. In adult sheep both carotid arteries were prepared and severed. End-to-end anastomoses were performed using the VJ device on one side and the classical running suture technique on the other side. Animals were followed-up with Duplex-scan every 3 months and sacrificed after 12 months. Histopathological analysis was carried out. RESULTS: In 20 animals all 22 sutureless anastomoses were successfully completed in less than 2 min versus 6 +/- 3 min for running suture. Duplex showed the occlusion of three controls and one sutureless anastomosis. Two controls and one sutureless had stenosis >50%. Histology showed very thin layer of myointimal hyperplasia (50 +/- 10 microm) in the sutureless group versus 300 +/- 27 microm in the control. No significant inflammatory reaction was detected. CONCLUSIONS: VJ provides edge-to-edge vascular repair that can be considered the most physiological way to restore vessel continuity. For the first time, in healthy sheep, an anastomotic device provided better results than suture technique.

A new approach in the treatment of high flow native AV fistula: the open-pore external scaffolding prosthesis

Objective: The vascular access steal syndrome is a complication occurring in 1-6% after native arterio-venous (AV) fistulas, often due to huge diameter of the vein. This results in very high flow, which could also be responsible for cardiac overload. The aim of this study is to evaluate the efficiency of a new approach in the treatment of this pathology using open-pore external scaffolding prosthesis.Methods: This a retrospective review of all patients presenting symptomatic high flow after native AV fistula between January 2007 and December 2009 in 3 vascular centers. Pre-operative duplex exam confirmed the diagnosis of high flow. The operation consisted in preparation of the whole fistula, measurement of the flow and section on the venous side. The vein was wrapped with this 6 to 8 mm open-pore external scaffolding prosthesis (ProVena, BBraun, Germany) according to its diameter and to the flow and then sutured. Measurement of the flow was repeated. Patients were followed by duplex exam at 1 week and at 1, 3, 6 and 12 months. Procedural success was defined as complete implantation of the prosthesis and reduction of the flow. Primary outcomes were reduction of the flow and recovery of the symptoms and secondary endpoint was patency of the fistula.Results: During the study period, 14 patients, with a mean age of 65・8 years old, have been operated with this technique.There were 2 native forearmfistulas and 12 on the armwith a mean pre-operative flow of 2600 ml/min (1800-3800). The mode of presentation was pain in 6 patients, neurological disorders in 10 and necrosis in 4. Moreover, 3 patients had cardiac insufficiency due to high flow in the fistula. The procedure was technically successful in 100% of cases. Re-intervention was necessary in 2 patients due to hematoma. Recovery of the initial symptoms occurred in 13 patients (93%). The mean flow reduction was 1200 ml/min (600-2000). In 1 patient, a persistent steal syndrome despite flow reduction to 1400 ml/min resulted in fistula closure 2 months later. At a mean follow-up of 22 months (4-35), all remaining patients (13/14) presented a patent fistula without recurrence.Conclusion: This new approach seems to be safe and effective in the treatment of symptomatic high flow native AV fistulas by significantly reducing the flow and avoiding closure of the vascular access. Longer follow-up with more patients are necessary to evaluate the risk of recurrence.

Homologous DNA pairing domain peptides of RecA protein: intrinsic propensity to form beta-structures and filaments.

The 20 amino acid residue peptides derived from RecA loop L2 have been shown to be the pairing domain of RecA. The peptides bind to ss- and dsDNA, unstack ssDNA, and pair the ssDNA to its homologous target in a duplex DNA. As shown by circular dichroism, upon binding to DNA the disordered peptides adopt a beta-structure conformation. Here we show that the conformational change of the peptide from random coil to beta-structure is important in binding ss- and dsDNA. The beta-structure in the DNA pairing peptides can be induced by many environmental conditions such as high pH, high concentration, and non-micellar sodium dodecyl sulfate (6 mM). This behavior indicates an intrinsic property of these peptides to form a beta-structure. A beta-structure model for the loop L2 of RecA protein when bound to DNA is thus proposed. The fact that aromatic residues at the central position 203 strongly modulate the peptide binding to DNA and subsequent biochemical activities can be accounted for by the direct effect of the aromatic amino acids on the peptide conformational change. The DNA-pairing domain of RecA visualized by electron microscopy self-assembles into a filamentous structure like RecA. The relevance of such a peptide filamentous structure to the structure of RecA when bound to DNA is discussed.

Purification and characterization of the human Rad51 protein, an analogue of E. coli RecA.

In bacteria, genetic recombination is catalysed by RecA protein, the product of the recA gene. A human gene that shares homology with Escherichia coli recA (and its yeast homologue RAD51) has been cloned from a testis cDNA library, and its 37 kDa product (hRad51) purified to homogeneity. The human Rad51 protein binds to single- and double-stranded DNA and exhibits DNA-dependent ATPase activity. Using a topological assay, we demonstrate that hRad51 underwinds duplex DNA, in a reaction dependent upon the presence of ATP or its non-hydrolysable analogue ATP gamma S. Complexes formed with single- and double-stranded DNA have been observed by electron microscopy following negative staining. With nicked duplex DNA, hRad51 forms helical nucleoprotein filaments which exhibit the striated appearance characteristic of RecA or yeast Rad51 filaments. Contour length measurements indicate that the DNA is underwound and extended within the nucleoprotein complex. In contrast to yeast Rad51 protein, human Rad51 forms filaments with single-stranded DNA in the presence of ATP/ATP gamma S. These resemble the inactive form of the RecA filament which is observed in the absence of a nucleotide cofactor.

Rapid prototyping of compliant human aortic roots for assessment of valved stents.

Adequate in-vitro training in valved stents deployment as well as testing of the latter devices requires compliant real-size models of the human aortic root. The casting methods utilized up to now are multi-step, time consuming and complicated. We pursued a goal of building a flexible 3D model in a single-step procedure. We created a precise 3D CAD model of a human aortic root using previously published anatomical and geometrical data and printed it using a novel rapid prototyping system developed by the Fab@Home project. As a material for 3D fabrication we used common house-hold silicone and afterwards dip-coated several models with dispersion silicone one or two times. To assess the production precision we compared the size of the final product with the CAD model. Compliance of the models was measured and compared with native porcine aortic root. Total fabrication time was 3 h and 20 min. Dip-coating one or two times with dispersion silicone if applied took one or two extra days, respectively. The error in dimensions of non-coated aortic root model compared to the CAD design was <3.0% along X, Y-axes and 4.1% along Z-axis. Compliance of a non-coated model as judged by the changes of radius values in the radial direction by 16.39% is significantly different (P<0.001) from native aortic tissue--23.54% at the pressure of 80-100 mmHg. Rapid prototyping of compliant, life-size anatomical models with the Fab@Home 3D printer is feasible--it is very quick compared to previous casting methods.

DNA structure-specific priming of ATR activation by DNA-PKcs.

Three phosphatidylinositol-3-kinase-related protein kinases implement cellular responses to DNA damage. DNA-dependent protein kinase catalytic subunit (DNA-PKcs) and ataxia-telangiectasia mutated respond primarily to DNA double-strand breaks (DSBs). Ataxia-telangiectasia and RAD3-related (ATR) signals the accumulation of replication protein A (RPA)-covered single-stranded DNA (ssDNA), which is caused by replication obstacles. Stalled replication intermediates can further degenerate and yield replication-associated DSBs. In this paper, we show that the juxtaposition of a double-stranded DNA end and a short ssDNA gap triggered robust activation of endogenous ATR and Chk1 in human cell-free extracts. This DNA damage signal depended on DNA-PKcs and ATR, which congregated onto gapped linear duplex DNA. DNA-PKcs primed ATR/Chk1 activation through DNA structure-specific phosphorylation of RPA32 and TopBP1. The synergistic activation of DNA-PKcs and ATR suggests that the two kinases combine to mount a prompt and specific response to replication-born DSBs.

The meiosis-specific recombinase hDmc1 forms ring structures and interacts with hRad51.

Eukaryotic cells encode two homologs of Escherichia coli RecA protein, Rad51 and Dmc1, which are required for meiotic recombination. Rad51, like E.coli RecA, forms helical nucleoprotein filaments that promote joint molecule and heteroduplex DNA formation. Electron microscopy reveals that the human meiosis-specific recombinase Dmc1 forms ring structures that bind single-stranded (ss) and double-stranded (ds) DNA. The protein binds preferentially to ssDNA tails and gaps in duplex DNA. hDmc1-ssDNA complexes exhibit an irregular, often compacted structure, and promote strand-transfer reactions with homologous duplex DNA. hDmc1 binds duplex DNA with reduced affinity to form nucleoprotein complexes. In contrast to helical RecA/Rad51 filaments, however, Dmc1 filaments are composed of a linear array of stacked protein rings. Consistent with the requirement for two recombinases in meiotic recombination, hDmc1 interacts directly with hRad51.

Fission yeast rad51 and dmc1, two efficient DNA recombinases forming helical nucleoprotein filaments.

Homologous recombination is important for the repair of double-strand breaks during meiosis. Eukaryotic cells require two homologs of Escherichia coli RecA protein, Rad51 and Dmc1, for meiotic recombination. To date, it is not clear, at the biochemical level, why two homologs of RecA are necessary during meiosis. To gain insight into this, we purified Schizosaccharomyces pombe Rad51 and Dmc1 to homogeneity. Purified Rad51 and Dmc1 form homo-oligomers, bind single-stranded DNA preferentially, and exhibit DNA-stimulated ATPase activity. Both Rad51 and Dmc1 promote the renaturation of complementary single-stranded DNA. Importantly, Rad51 and Dmc1 proteins catalyze ATP-dependent strand exchange reactions with homologous duplex DNA. Electron microscopy reveals that both S. pombe Rad51 and Dmc1 form nucleoprotein filaments. Rad51 formed helical nucleoprotein filaments on single-stranded DNA, whereas Dmc1 was found in two forms, as helical filaments and also as stacked rings. These results demonstrate that Rad51 and Dmc1 are both efficient recombinases in lower eukaryotes and reveal closer functional and structural similarities between the meiotic recombinase Dmc1 and Rad51. The DNA strand exchange activity of both Rad51 and Dmc1 is most likely critical for proper meiotic DNA double-strand break repair in lower eukaryotes.

Silver-assisted laser desorption ionization for high spatial resolution imaging mass spectrometry of olefins from thin tissue sections.

Silver has been demonstrated to be a powerful cationization agent in mass spectrometry (MS) for various olefinic species such as cholesterol and fatty acids. This work explores the utility of metallic silver sputtering on tissue sections for high resolution imaging mass spectrometry (IMS) of olefins by laser desorption ionization (LDI). For this purpose, sputtered silver coating thickness was optimized on an assorted selection of mouse and rat tissues including brain, kidney, liver, and testis. For mouse brain tissue section, the thickness was adjusted to 23 ± 2 nm of silver to prevent ion suppression effects associated with a higher cholesterol and lipid content. On all other tissues, a thickness of at 16 ± 2 nm provided the best desorption/ionization efficiency. Characterization of the species by MS/MS showed a wide variety of olefinic compounds allowing the IMS of different lipid classes including cholesterol, arachidonic acid, docosahexaenoic acid, and triacylglyceride 52:3. A range of spatial resolutions for IMS were investigated from 150 μm down to the high resolution cellular range at 5 μm. The applicability of direct on-tissue silver sputtering to LDI-IMS of cholesterol and other olefinic compounds presents a novel approach to improve the amount of information that can be obtained from tissue sections. This IMS strategy is thus of interest for providing new biological insights on the role of cholesterol and other olefins in physiological pathways or disease.

In vitro evaluation of staphylococcus aureus biofilm formation on bone grafts and bone substitues

Background: Bacteria form a biofilm on the surface of orthopaedic devices, causing persistent and infection. Little is known about biofilms formation on bone grafts and bone substitutes. We analyzed various representative materials regarding their propensity for biofilm formation caused by Staphylococcus aureus.Methods: As bone graft beta-tricalciumphosphate (b-TCP, CyclOsTM) and as bone substitute a tantalum metal mesh (trabecular metalTM) and PMMA (Pala-cosTM) were investigated. As test organism S. aureus (strain ATCC 29213) was used. Test materials were incubated with bacterial solution of 105 colony-forming units (cfu)/ml at 37°C for 24 h without shaking. After 24 h, the test materials were removed and washed 3 times in normal saline, followed by sonication in 50 ml Ringer solution at 40 kHz for 5 minutes. The resulting sonication fluid was plated in aliquots of 0.1 ml onto aerobe blood agar with 5% sheep blood and incubated at 37°C with 5% CO2 for 24 h. Then, bacterial counts were enumerated and expressed as cfu/ml. All experiments were performed in triplicate to calculate the mean ± standard deviation. The Wilcoxon test was used for statistical calculations.Results: The three investigated materials show a differing specific surface with b-TCB>trabecular metal>PMMA per mm2. S. aureus formed biofilm on all test materials as confirmed by quantitative culture after washing and sonication. The bacterial counts in sonication fluid (in cfu/ml) were higher in b-TCP (5.1 x 106 ± 0.6 x 106) and trabecular metal (3.7 x 106 ± 0.6 x 106) than in PMMA (3.9 x 104 ± 1.8 x 104), p<0.05.Conclusion: Our results demonstrate that about 100-times more bacteria adhere on b-TCP and trabecular metal than on PMMA, reflecting the larger surface of b-TCP and trabecuar metal compared to the one of PMMA. This in-vitro data indicates that bone grafts are susceptible to infection. Further studies are needed to evaluate efficient approaches to prevent and treat infections associated with bone grafts and substitutes, including modification of the surface or antibacterial coating.

Effects of polymer-coated multi-wall carbon nanotubes on mouse RAW 264.7 macrophages

Surface characteristics (area, chemical reactivity) play an important role in cell response to nanomaterials. The aim of this study was to evaluate the oxidative and inflammatory effects of multi−wall carbon nanotubes (MWCNT) uncoated (P0) or coated with carboxylic polyacid or polystyrene polybutadiene polymetacrylate of methyl polymers (P1 and P2 respectively) on murine macrophages (RAW 264.7 cell line). Carbon black nanoparticles (CB, diameter 95 nm) and crocidolite fibers (diameter: 80 nm, length: < 10 μm) were used as controls. Surface functional groups present on MWCNTs were analyzed by Knudsen flow reactor. The amount of acidic sites was P1> P0> P2, for basic sites was P0> P1>> P2 and for oxidizable sites was P0> P2> P1. In contact with cells, P2 formed smaller aggregates than P0 and P1, which were of similar size. Optical microscopy showed the formation of vacuoles after exposure only to P0, P1 and crocidolite. Incubation of cells with P0, P1 and crocidolite fibers induced a significant and similar decrease in metabolic activity, whereas P2 and CB had no effect. Cell number and membrane permeability were unmodified by incubation with the different particles. Incubation of macrophages with P0, P1 and crocidolite induced a dose− and time−dependent increase in mRNA expression of oxidative stress marker (HO−1, GPX1) and inflammatory mediators (TNF−a, MIP−2). No such responses were observed with P2 and CB. In conclusion, MWCNT coated with a carboxylic polyacid polymer exerted similar oxidative and inflammatory effects to uncoated MWCNT. By contrast, no such effects were observed with MWCNT coated with a polystyrene−based polymer. This kind of coating could be useful to decrease MWCNT toxicity.

Characterizing emission and breathing-zone concentrations following exposure cases to fluororesin-based waterproofing spray mists.

Measurements and simulations were performed to assess workers' exposure to solvent vapors and aerosols during the waterproofing of a tiled surface. This investigation followed two recent incidents in the same company where workers experienced acute respiratory illness after spraying a stain-repellent resin containing fluorinated polymers on stone-tiled walls and floors. Because the waterproofing activity had been done for years at the tile company without encountering any exposure problems prior to these cases, it was strongly suspected that the incidents were linked to a recent change in the composition of the coating mixture. Experimental measurements and simulations indicated that the emission rate of particles smaller than 10 microm may be estimated at 0.66 mg/sec (SD 0.10) for the old resin and at 0.37 mg/sec (SD 0.04) for the new one. The measurement of the solvent emission rate from surfaces coated with the two resins indicated that shortly after spraying, the emission was in the range of 18 to 20 mg/sec x m2 and was similar for both products. Solvent and overspray emission rates were introduced in a two-zone compartment model. The results obtained in the near-field indicate significant exposure to overspray mist (7 and 34 mg/m3 for new resin) and solvent vapors (80 to 350 ppm for the new resin). It was also shown that the introduction of the new resin tended to significantly decrease the levels of solvents and particulates in the workers' breathing zone. These results strongly suggest that cases of acute respiratory illness are related to the specific toxicity of the fluorinated polymer itself. The fact that the same polymer is used in various commercial products raises concern regarding other possible occupational and domestic exposures.

Interactions between cells and functionalized nanoparticles

In this present thesis Superparamagnetic Iron Oxide Nanoparticles (SPIONs) with 9 nm in diameter were selected as nanocarriers in order to study their potential application as drug delivery systems. Therefore the aim of the study was to demonstrate the proof of concept by establishing an efficient system of drug delivery, which would be a valuable tool in biomedical applications, such as the treatement of cancer, by reducing the side effects due to administration of a high concentration of therapeutic agents. As demonstrated in a previous study, the uptake of SPIONs by tumoral human cells was enhanced by the presence of amino groups on their surface. The stabilization of SPIONs were then performed and optimized by the coating of poly(vinylalcohol) and poly(vinylalcohol/vinylamine). Such nanoparticles were known as aminoPVA-SPIONs. The toxicity and the inflammatory reaction of aminoPVA-SPIONs were evaluated in order to establish their potentiel use in the human body. The results demonstrated that the human cells were able to invaginate aminoPVA-SPIONS without revealing any toxicity and inflammatory reaction. The analysis by transmission electron microscopy (TEM), scanning electron microscopy (SEM), cryo-TEM, confocal microscopy and histological staining (i.e. Prussian Blue) showed that the iron oxide core of SPIONs were located in the cytoplasm of cells and concentrated in vesicles. The evaluation of the mechanism of uptake of aminoPVA-SPIONs revealed that their uptake by monolayer cell culture was performed via an active mechanism, which was achieved by a clathrin-mediated endocytosis. Consequently, it was suggested that aminoPVA-SPIONs were good candidates as nanocarriers in drug delivery systems, which were able to reach the cytoplasm of cells. Their incubation with three-dimensional models mimicing tissues, such as differentiated rat brain cell-derived aggregates and spheroids, revealed that aminoPVA-SPIONs were able to invade into deep cell layers according to the stage of growth of these models. In the view of these promising results, drug-SPIONs were prepared by the functionalization of aminoPVA-SPIONs via a biological labile chemical bond by one of these three antineoplastic agents, which are widely used in clinical practice: 5-fluorourdine (Fur) (an antimetabolite), or camptothecin (CPT) (a topoisomerase inhibitor) or doxorubicin (DOX) (an anthracycline which interfere with DNA). The results shown that drug-SPIONs were internalized by human melanoma cells, as it was expected due the previous results with aminoPVA-SPIONs, and in addition they were active as anticancer agents, suggesting the efficient release of the drug from the drug-SPIONs. The results with CPT-SPIONs were the most promising, whereas DOX- SPIONs did not demonstrate a prononced activity of DOX. In conclusion, the results demonstrated that functionalized iron oxide nanoparticles are a promising tool in order to deliver therapeutic agents. - Dans le cadre de ce travail de thèse, les nanoparticules superparamagnétiques d'oxyde de fer (SPIONs) ayant un diamètre de 9 nm ont été choisies, afin d'étudier leur éventuelle utilisation dans un système de délivrance d'agents thérapeutiques. Ainsi le but de la thèse est de démontrer la faisabilité de fabriquer un système efficace de délivrance d'agents thérapeutiques, qui serait un outil intéressant dans le cadre d'une utilisation biomédicale, par exemple lors du traitement du cancer, qui pourrait réduire les effets secondaires provoqués par le dosage trop élevé de médicaments. Comme il a été démontré dans une précédente étude, l'invagination des SPIONs par des cellules humaines cancéreuses est améliorée par la présence de groupes fonctionnels amino à leur surface. La stabilisation des SPIONs est ainsi effectuée et optimisée par l'enrobage de poly(vinylalcool) et de (poly(vinylalcool/vinylamine), qui sont connues sous le nom de aminoPVA-SPIONs. La toxicité et la réaction inflammatoire des aminoPVA-SPIONs ont été évaluées dans le but de déterminer leur potentielle utilisation dans le corps humain. Les résultats démontrèrent que les cellules humaines sont capables d'invaginer les aminoPVAS-SPIONs sans induire une réaction toxique ou inflammatoire. L'analyse par la microscopie électronique en transmission électronique (TEM), la microscopie électronique à balayage (SEM), le cryo-microscopie électronique (SEM), la microscopie confocale et la coloration histologique (par ex, le bleu de Prusse) a montré que l'oxyde de fer des SPIONs est localisé dans le cytoplasme des cellules et est concentré dans des vesicules. L'évaluation du méchanisme d'invagination des aminoPVA-SPIONs ont révélé que leur invagination par des monocultures de cellules est effectué par un méchanisme actif, contrôlé par une endocytose induite par les clathrins. Par conséquent, les aminoPVA-SPIONs sont de bons candidats en tant que transporteurs (nanocamers) dans un système de délivrance d'agents thérapeuthique, capable d'atteindre le cytoplasme des cellules. Leur incubation avec des modèles tridimenstionnels imitant les tissues, tels que les aggrégats de cellules de cerveau différenciées et les sphéroïdes, a montré que les aminoPVA-SPIONs sont capable de pénétrer dans les couches profondes des modèles, selon l'état d'avancement de leur croissance. En vue de ces résultats prometteurs, les drug-SPIONs ont été préparés en fonctionalisant les aminoPVA-SPIONs par le biai d'une liaison chimique labile par un des trois agents thérapeutiques, déjà utilisé en pratique : 5-fluorourdine (Fur) (un antimétabolite), or camptothecin (CPT) (un inhibiteur de la topoisomerase) or doxorubicin (DOX) (un anthracycline qui interfère avec le DNA). Les résultats ont montré que les drug-SPIONs sont capable d'être internalisés par les mélanomes, comme il a été attendu d'après les résultats obtenus précédemment avec les aminoPVA-SPIONs, et de plus, les drug-SPIONs sont actifs, ce qui suggère un relargage efficace de l'agent thérapeutique du drug-SPIONs. Les résultats obtenus avec les CPT-SPIONs sont les plus prometteurs, tandis que ceux avec les DOX-SPIONs, ce n'est pas le cas, dont l'activité thérapeutique de DOX n'a pas été aussi efficace. En conclusion, les résultats ont pu démontrer que les nanoparticules d'oxyde de fer fonctionnalisées sont un outil prometteur dans la délivrance d'agents thérapeutiques.

Prevalence of patients' difficulties in swallowing solid oral dosage forms

Introduction Swallowing difficulties, or dysphagia, can occur in anyage group, although it is most common among elderly people. It canaffect patients' ability to take solid oral dosage forms, thus compromisingmedication adherence. Although literature is poor, availabledata show that prevalence in the general population ranges from 25 to60%. Prevalence in community pharmacies needs to be explored.Materials & Methods Community pharmacies were recruited from arandom selection in three Swiss states: Basel-Stadt (BS), Basel-Landschaft (BL) and Lausanne (LA). Patients' ability to swallowsolid oral medications was enquired with a semi-structured interview;the interviewer spent 4 h in each included pharmacy. Each consecutivepatient (18 years and older) entering the pharmacy with aprescription for at least 3 different solid oral forms was enrolled.Study was approved by the Lausanne ethics committee.Results Sixty pharmacies took part in the study (20 in BS, 10 in BL,30 in LA) between March and May 2010. Patient inclusion rate was77.8% (410/527). Prevalence of swallowing disorders was 22.4% (92/410). Patients with swallowing disorders were older (mean age: 67.5± 16 years vs. 63.0 ± 14 years, range 19-96; p = 0.03) and moreoften women (69.6% vs. 59.1%; Chi2 = 3.3, p = 0.04) than patientswithout swallowing disorders. They had on average 4.6 ± 2.7 drugswith a mean number of 5.5 ± 3.3 tablets or capsules to take daily,which didn't differ from the number of drugs taken by patientswithout swallowing difficulties (4.9 ± 2.5 drugs and 5.9 ± 3.5 tablets;n.s.). The difficulty was mainly related to the big size (63%) orthe quality of pill coating (rough, sticky, 14%). Twenty-one patients(37.5%) stated that their swallowing disorders resulted in nonadherence, rated as rarely (12 patients), sometimes (6 patients), veryoften (1 patient) or always (2 patients). According to patients, nopharmacist and only 2 physicians enquired about patients' swallowingissue.Discussion & Conclusion Swallowing difficulties are frequent amongpatients in community pharmacies in Switzerland with an estimatedprevalence of 22%. The problem resulted in non adherence or partialadherence in at least 35% of these patients. However, pharmacists andphysicians did not routinely inquire about the disorder. Guidelinesshould be developed for promoting systematic approaches of patientsin community pharmacies.