The use of shear stress for targeted drug delivery

Stenosed segments of arteries significantly alter the blood flow known from healthy vessels. In particular, the wall shear stress at critically stenosed arteries is at least an order of magnitude higher than in healthy situations. This alteration represents a change in physical force and might be used as a trigger signal for drug delivery. Mechano-sensitive drug delivery systems that preferentially release their payload under increased shear stress are discussed. Therefore, besides biological or chemical markers, physical triggers are a further principle approach for targeted drug delivery. We hypothesize that such a physical trigger is much more powerful to release drugs for vasodilation, plaque stabilization, or clot lysis at stenosed arteries than any known biological or chemical one

X-ray micro computed tomography for the visualization of an atherosclerotic human coronary artery

Atherosclerosis refers to narrowing or blocking of blood vessels that can lead to a heart attack, chest pain or stroke. Constricted segments of diseased arteries exhibit considerably increased wall shear stress, compared to the healthy ones. One of the possibilities to improve patient's treatment is the application of nano-therapeutic approaches, based on shear stress sensitive nano-containers. In order to tailor the chemical composition and subsequent physical properties of such liposomes, one has to know precisely the morphology of critically stenosed arteries at micrometre resolution. It is often obtained by means of histology, which has the drawback of offering only two-dimensional information. Additionally, it requires the artery to be decalcified before sectioning, which might lead to deformations within the tissue. Micro computed tomography (muCT) enables the three-dimensional (3D) visualization of soft and hard tissues at micrometre level. muCT allows lumen segmentation that is crucial for subsequent flow simulation analysis. In this communication, tomographic images of a human coronary artery before and after decalcification are qualitatively and quantitatively compared. We analyse the cross section of the diseased human coronary artery before and after decalcification, and calculate the lumen area of both samples

Immunological response to nitroglycerin-loaded shear-responsive liposomes in vitro and in vivo

Liposomes formulated from the 1,3-diamidophospholipid Pad-PC-Pad are shear- responsive and thus promising nano-containers to specifically release a vasodilator at stenotic arteries. The recommended preclinical safety tests for therapeutic liposomes of nanometer size include the in vitro assessment of complement activation and the evaluation of the associated risk of complement activation-related pseudo-allergy (CARPA) in vivo. For this reason, we measured complement activation by Pad-PC- Pad formulations in human and porcine sera, along with the nanopharmaceutical- mediated cardiopulmonary responses in pigs. The evaluated formulations comprised of Pad-PC-Pad liposomes, with and without polyethylene glycol on the surface of the liposomes, and nitroglycerin as a model vasodilator. The nitroglycerin incorporation efficiency ranged from 25% to 50%. In human sera, liposome formulations with 20 mg/mL phospholipid gave rise to complement activation, mainly via the alternative pathway, as reflected by the rises in SC5b-9 and Bb protein complex concentrations. Formulations having a factor of ten lower phospholipid content did not result in measurable complement activation. The weak complement activation induced by Pad- PC-Pad liposomal formulations was confirmed by the results obtained by performing an in vivo study in a porcine model, where hemodynamic parameters were monitored continuously. Our study suggests that, compared to FDA-approved liposomal drugs, Pad-PC-Pad exhibits less or similar risks of CARPA

The use of shear stress for targeted drug delivery

Stenosed segments of arteries significantly alter the blood flow known from healthy vessels. In particular, the wall shear stress at critically stenosed arteries is at least an order of magnitude higher than in healthy situations. This alteration represents a change in physical force and might be used as a trigger signal for drug delivery. Mechanosensitive drug delivery systems, that preferentially release their payload under increased shear stress, are discussed. Therefore, besides biological or chemical markers, physical triggers are a further principle approach for targeted drug delivery. We hypothesize that such physical trigger is much more powerful to release drugs for vasodilation, plaque stabilization or clot lysis at stenosed arteries than any known biological or chemical ones

Enseignement prégradué de la médecine d'urgence : étude comparative prospective contrôlée du programme de formation de la Faculté de Médecine et de l'Ecole d'Officier Sanitaire

Avec la réforme des études de médecine à la faculté de Médecine, un enseignement obligatoire de médecine d'urgence a été introduit. Pour évaluer l'acquisition des connaissances et compétences de cette discipline nous avons effectué une étude comparative prospective contrôlée entre les étudiants de la Faculté de Médecine de Genève et les aspirants à l'école d'officier sanitaire de Moudon. Les deux groupes ont été évalués avant et après une formation en médecine d'urgence de 4 semaines. Le collectif comprend 56 étudiants et 52 aspirants. Une évaluation orale structurée et standardisée suivie d'un examen pratique de réanimation et enfin un questionnaire à choix multiples ont été appliqués. Les deux groupes améliorent leurs performances aux examens oraux et pratiques. Aux examens écrits, seuls les étudiants améliorent de quelques peu les scores. Les deux systèmes ont un impact significatif. L'enseignement dans le milieu clinique semble renforcer davantage l'intérêt des étudiants pour la médecine d'urgence

Discrepancy between coronary angiography and autopsy finding

This article presents the case of a 71-year-old man who developed septic shock complicated by acute renal failure. Because of clinical suspicion of myocardial infarction, 24 hours before passing away, the patient had a coronary cineangiography. Limited incidences and views have been used to avoid contrast-induced nephropathy and no significant lesions were founded. However, the autopsy revealed significant stenosis of coronary arteries. This case report discusses the paradox of this finding

Emergency medicine training: a prospective, comparative study of an undergraduate clinical clerkship and an army programme

OBJECTIVES: To evaluate and compare the educational impact of the University of Geneva Faculty of Medicine (UGFM) emergency medicine clerkship training with that provided by the Swiss Army medical officer cadets school (ARMY). The assessment was designed to assess students' clinical knowledge and competency in major emergency situations, ACLS (Advanced Cardiac Life Support) and ATLS (Advanced Traumatic Life Support). METHODS: Prospectively, 56 UGFM students were compared with 52 ARMY officer cadets by a multiformat pre- and post-training examination. The exam consisted of a multiple-choice questionnaire (MCQ), a standardised vignette-based oral exam (SOE) and a standardised practical cardio-pulmonary resuscitation (CPR) exercise. RESULTS: Overall, on the pre- and post-training testing, total scores improved significantly for the UGFM by 10% (from 63 to 73%) and for the ARMY by 9% (from 60 to 69%). Knowledge assessed on the MCQ improved for the UGFM by 8% (64 to 72%) but not significantly for the ARMY. Performance on the SOE improved by 10% for UGFM (54 to 64%) and the ARMY (47 to 57%) as well as performance on the CPR, which improved by 15% for UGFM (72 to 87%) and 19% for the ARMY (67 to 86%). Post-training performance indicated that, respectively, UGFM scored significantly higher than the ARMY on the MCQ (72 and 68%) and the SOE (64 and 57%) but not on the CPR. Internal reliability indexes for the MCQ, SOE and CPR were respectively 0.72, 0.86 and 0.92. Correlations between the MCQ, SOE and CPR varied between 0.07 to 0.19. CONCLUSIONS: In general, the multimethod assessment seemed to provide a complementary approach to evaluation of the trainees' competency in emergency training. Except for the ARMY MCQ performance, both training programmes seemed to be effective in improving trainees' overall knowledge and clinical performance. The trainees' performances are reviewed and discussed in terms of the specific skills assessed on the SOE, the context of the trainees' expected level of performance, the teaching and evaluation approaches, and implications in establishing the equivalence of the two programmes

Detecting Heparin in Whole Blood for Point of Care Anticoagulation Control During Surgery

No abstract available