Biodegradable fibre scaffolds incorporating water-soluble drugs and proteins.

A new type of biodegradable drug-loaded fibre scaffold has been successfully produced for the benefit of water-soluble drugs and proteins. Model drug loaded calcium carbonate (CaCO3) microparticles incorporated into poly(lactic acid-co-glycolic acid) (PLGA) fibres were manufactured by co-precipitation of CaCO3 and the drug molecules, followed by electrospinning of a suspension of such drug-loaded microparticles in a PLGA solution. Rhodamine 6G and bovine serum albumin were used as model drugs for our release study, representing small bioactive molecules and protein, respectively. A bead and string structure of fibres was achieved. The drug release was investigated with different drug loadings and in different pH release mediums. Results showed that a slow and sustained drug release was achieved in 40 days and the CaCO3 microparticles used as the second barrier restrained the initial burst release.

[Long term aspirin in stable coronary disease with an indication for anticoagulation: is it reasonable?]. / Aspirine à vie et maladie coronarienne stable avec indication à une anticoagulation: est-ce bien raisonnable?

In patients with both stable coronary disease and atrial fibrillation, a baseline treatment of aspirin and an oral anticoagulant is often prescribed due to the proven benefits of each therapy on cardiovascular and thromboembolic events and mortality. However, recent cohort studies in this population have shown that adding aspirin to an oral anticoagulant is not associated with a reduction in recurrence of coronary or thromboembolic events, but significantly increases the bleeding risk. In these patients, in particular when their bleeding risk is high, aspirin withdrawal may be considered.

[Diagnostic instruments of delirium]. / Outils diagnostiques de l'état confusionnel aigu.

Delirium is a frequent medical problem in hospitalized patients and is often underdiagnosed in spite its high morbidity and mortality. Early diagnosis and treatment are mandatory. Amongst diagnostic instruments currently available, the Confusion Assessment Method (CAM) appears to be the best bedside tool due to its performance and rapidity of use. An adaptation for intensive care patients, CAM-ICU, has also been validated.

[Can antiplatelet therapy be continued in upper gastrointestinal bleeding?]. / Peut-on poursuivre un traitement antiagrégant en cas d'hémorragie digestive haute?

During a gastro-intestinal bleeding, treatment options regarding antiplatelet agents depend on the indication. In primary prevention, treatment can reasonably be stopped regarding the low expected benefit. In secondary prevention, experts recommend resuming treatment after a five-day interruption. In patients with a coronary stent, the decision is made on a case by case basis and requires close multidisciplinary collaboration between internists, cardiologists and gastroenterologists.

[Enteral nutrition: nasogastric tube or percutaneous endoscopic gastrostomy?]. / Nutrition entérale: sonde nasogastrique ou gastrostomie percutanée endoscopique?

When enteral nutrition is indicated to prevent or to treat a patient with denutrition choosing between a nasogastric tube (NGT) and a percutaneous endoscopic gastrostomy (PEG) is not always an easy decision. In neurological patients with swallowing disturbances or in patients with head and neck tumors, PEG is associated with lower rates of feeding tube dislodgement, while NGT has lower rates or morbidity. A meta-analysis showed that the interruption of nutrition is less frequent with PEG but there is no difference in terms of mortality and aspiration pneumonia between PEG and NGT. The European Society for Clinical Nutrition and Metabolism recommends PEG when enteral nutrition is expected to last more than 3 weeks.

Toll-like receptor 2 is critical for induction of Reg3 beta expression and intestinal clearance of Yersinia pseudotuberculosis.

OBJECTIVE: Yersinia pseudotuberculosis causes ileitis and mesenteric lymphadenitis by mainly invading the Peyer's patches that are positioned in the terminal ileum. Whereas toll-like-receptor 2 (TLR2) controls mucosal inflammation by detecting certain microbiota-derived signals, its exact role in protecting Peyer's patches against bacterial invasion has not been defined. DESIGN: Wild-type, Tlr2-, Nod2- and MyD88-deficient animals were challenged by Y pseudotuberculosis via the oral or systemic route. The role of microbiota in conditioning Peyer's patches against Yersinia through TLR2 was assessed by delivering, ad libitum, exogenous TLR2 agonists in drinking water to germ-free and streptomycin-treated animals. Bacterial eradication from Peyer's patches was measured by using a colony-forming unit assay. Expression of cryptdins and the c-type lectin Reg3 beta was quantified by quantitative reverse transcriptase polymerase chain reaction analysis. RESULTS: Our data demonstrated that Tlr2-deficient mice failed to limit Yersinia dissemination from the Peyer's patches and succumbed to sepsis independently of nucleotide-binding and oligomerisation domain 2 (NOD2). Recognition of both microbiota-derived and myeloid differentiation factor 88 (MyD88)-mediated elicitors was found to be critically involved in gut protection against Yersinia-induced lethality, while TLR2 was dispensable to systemic Yersinia infection. Gene expression analyses revealed that optimal epithelial transcript level of the anti-infective Reg3 beta requires TLR2 activation. Consistently, Yersinia infection triggered TLR2-dependent Reg3 beta expression in Peyer's patches. Importantly, oral treatment with exogenous TLR2 agonists in germ-free animals was able to further enhance Yersinia-induced expression of Reg3 beta and to restore intestinal resistance to Yersinia. Lastly, genetic ablation of Reg3 beta resulted in impaired clearance of the bacterial load in Peyer's patches. CONCLUSIONS: TLR2/REG3 beta is thus an essential component in conditioning epithelial defence signalling pathways against bacterial invasion.

Clinical supervisors' perceived needs for teaching communication skills in clinical practice.

BACKGROUND: Lack of faculty training is often cited as the main obstacle to post-graduate teaching in communication skills. AIMS: To explore clinical supervisors' needs and perceptions regarding their role as communication skills trainers. METHODS: Four focus group discussions were conducted with clinical supervisors from two in-patient and one out-patient medical services from the Geneva University Hospitals. Focus groups were audio taped, transcribed verbatim and analyzed in a thematic way using Maxqda software for qualitative data analysis. RESULTS: Clinical supervisors said that they frequently addressed communication issues with residents but tended to intervene as rescuers, clinicians or coaches rather than as formal instructors. They felt their own training did not prepare them to teach communication skills. Other barriers to teach communication skills include lack of time, competing demands, lack of interest and experience on the part of residents, and lack of institutional priority given to communication issues. Respondents expressed a desire for experiential and reflective training in a work-based setting and emphasised the need for a non-judgmental learning atmosphere. CONCLUSIONS: Results suggest that organisational priorities, culture and climate strongly influence the degree to which clinical supervisors may feel comfortable to teach communication skills to residents. Attention must be given to these contextual factors in the development of an effective communication skills teaching program for clinical supervisors.

[Introduction of platelet additive solution in platelet concentrates: towards a decrease of blood transfusion reactions]. / L'introduction de solutions de conservation dans les concentrés plaquettaires : vers une diminution des réactions transfusionnelles.

Platelet concentrates (PC) are used in thrombocytopenia for curative or preventive treatment for hemorrhagic risk. Since five years, additive solutions have been added in PCs for several reasons; one of them is to present an interest in the intolerance in plasma reactions. The literature data have shown that these solutions entail fewer allergic reactions than PCs kept in plasma. This study was reviewed on three years of transfusion in France. The main objective of this study was to see if there was a difference in frequency when these PCs were in solution or not. All adverse reactions in recipients (ARR) occurring among PCs recipients (with and without additive solution) were analysed. The categories of ARR specifically studied were: allergies, febril non haemolytic reactions (FNHR) and the category "unknown". This study shows that there is significantly lower incidence of allergies by introducing solution. For all ARRs, there is also a decrease in their frequency when PCs are in additive solution, it is significant except for the apheresis platelet concentrates. For categories FNHR and "unknown", the results are opposed and/or not significant. This study confirms that introduction of additive solutions in PCs is able to reduce some allergic transfusion reactions.

[Headache: physical exam or CT?]. / Céphalées: clinique ou imagerie ?

The life time prevalence of headache is more than 90% in the general population. The majority of patients presenting to physicians suffer from migraine. A simple clinical predictive score based on five questions will allow clinicians to confirm this diagnosis and will prevent further investigations. In all other circumstances, evidence is not sufficient to develop prediction rules to exclude secondary headache. However, neuroimaging should be performed in patients with a unexplained abnormal finding on the neurological examination.

[Images and men: performance of the internist in interpreting chest radiography]. / Des images et des hommes: performance de l'interniste dans l'interprétation d'un cliché thoracique.

Chest radiography is a common investigation used frequently by practitioners as well as hospital doctors. Among many factors, experiences, level of training and radiological specialization influence the accuracy of its interpretation. Prospective studies observe a low discordant interpretation rate between radiologists and non-radiologists and allow the non-specialist to rely on its own interpretation for urgent clinical decision-making. However, radiologist's expertise remains the reference in interpreting chest radiography, plays a key-role in continuous training of non-specialist, and guarantees the quality of patients' care.

[Improving patient's medication knowledge at hospital discharge]. / Amélioration de la connaissance de son traitement par le patient à la sortie de l'hôpital.

The period following hospital discharge is a time of vulnerability regarding the continuity of care and carries the highest risk of patient errors and confusion with medications. Strategies to improve knowledge and understanding of medications at discharge are necessary and may result in safer use, better compliance, and reduced health care expenditures. In our service of general internal medicine, a structured patient-centered discharge interview, performed by the resident caring for the patient and reinforced by a simple and individualized treatment card, increased patients' knowledge of their discharge medications.

Toscana virus meningitis case in Switzerland: an example of the ezVIR bioinformatics pipeline utility for the identification of emerging viruses.

Toscana virus (TOSV) represents a frequent cause of viral meningitis in the Mediterranean Basin that remains neglected in neighbouring countries. We report a documented TOSV meningitis case in a traveller returning from Tuscany to Switzerland. While routine serological and PCR assays could not discriminate between TOSV and Sandfly fever Naples virus infection, a high-throughput sequencing performed directly on the cerebrospinal fluid specimen and analysed with the ezVIR pipeline provided an unequivocal viral diagnostic. TOSV could be unequivocally considered as the aetiological agent, proving the potential of ezVIR to improve standard diagnostics in cases of infection with uncommon or emerging viruses.

Prospective evaluation of patients with syncope: a population-based study.

PURPOSE: To determine the diagnostic yield of a standardized sequential evaluation of patients with syncope in a primary care teaching hospital. PATIENTS AND METHODS: All consecutive patients who presented to the emergency department with syncope as a chief complaint were enrolled. Their evaluation included initial and routine clinical examination, including carotid sinus massage, as well as electrocardiography and basic laboratory testing. Targeted tests, such as echocardiography, were used when a specific entity was suspected clinically. Other cardiovascular tests (24-hour Holter monitoring, ambulatory loop recorder ECG, upright tilt test, and signal-averaged electrocardiography) were performed in patients with unexplained syncope after the initial steps. Electrophysiologic studies were performed in selected patients only as clinically appropriate. Follow-up information on recurrence and mortality were obtained every 6 months for as long as 18 months for 94% (n = 611) of the patients. RESULTS: After the initial clinical evaluation, a suspected cause of syncope was found in 69% (n = 446) of the 650 patients, including neurocardiogenic syncope (n = 234, 36%), orthostatic hypotension (n = 156, 24%), arrhythmia (n = 24, 4%), and other diseases (n = 32, 5%). Of the 67 patients who underwent targeted tests, suspected diagnoses were confirmed in 49 (73%) patients: aortic stenosis (n = 8, 1%), pulmonary embolism (n = 8, 1%), seizures/stroke (n = 30, 5%), and other diseases (n = 3). Extensive cardiovascular workups, which were performed in 122 of the 155 patients in whom syncope remained unexplained after clinical assessment, provided a suspected cause of syncope in only 30 (25%) patients, including arrhythmias in 18 (60%), all of whom had abnormal baseline ECGs. The 18-month mortality was 9% (n = 55, including 8 patients with sudden death); syncope recurred in 15% (n = 95) of the patients. CONCLUSION: The diagnostic yield of a standardized clinical evaluation of syncope was 76%, greater than reported previously in unselected patients. Electrocardiogram-based risk stratification was useful in guiding the use of specialized cardiovascular tests.

Adhesion molecule phenotype of T lymphocytes in inflamed CNS.

The phenotype of T cells in the central nervous system (CNS) in two models of chronic inflammation (experimental allergic encephalomyelitis and Corynebacterium parvum-induced inflammation) was compared to that of T cells in gut and chronically inflamed subcutaneous tissue and lung. CNS T cells display a similar phenotype in both inflammatory models, and are phenotypically unique compared to T cells from the other inflamed tissues. T cells from inflamed CNS are mainly CD4+ and are the only population examined that express a typical activated/memory phenotype: CD44high/LFA-1high/ICAM-1high/CD45RBlow. The CNS T cells are alpha4beta7-integrin(negative), but express alpha4-integrin and activated beta1 integrin, suggesting expression of the alpha4beta1-heterodimer in an activated state. In contrast, most T cells in gut express low levels of activated beta1 integrin. The CNS T cells lack expression of alpha6 and alphaE integrin chains and L-selectin. In inflamed CNS and inflamed subcutaneous tissue, approximately 50% of T cells express high affinity ligands for P-selectin while fewer than 10% express high affinity ligands for E-selectin. In summary, our data show that, independent of the inflammatory stimulus, T cells recruited into the inflamed CNS are phenotypically distinct from T cells in other inflamed tissues. This finding leads us to hypothesize the existence of a phenotypically distinct 'CNS-seeking' T lymphocyte population.

PCR detection of aminoglycoside resistance genes: a rapid molecular typing method for Acinetobacter baumannii.

Aminoglycoside resistance is common among strains of Acinetobacter baumannii responsible for nosocomial infections, and inactivation of these antibiotics by enzymatic modification is the main mechanism. Different types of aminoglycoside acetyltransferases (AAC), nucleotidyltransferases (ANT), and phosphotransferases (APH) are synthesized by clinical isolates, and several enzymes can be produced by a single strain. Using a multiplex PCR procedure carried out on bacterial thermolysates, we analyzed the aminoglycoside resistance gene content of strains belonging to eight clusters identified by pulsed-field gel electrophoresis. In a single reaction were combined three primer pairs in order to amplify the genes coding for AAC(6')-Ih, AAC(3)-I, and AAC(3)-II, three primer pairs for the genes coding for ANT(2'')-I, APH(3')-VI, and rRNA 16S as internal control, and finally two primer pairs for the genes coding for AAC(6')-Ib and APH(3')-I. According to the aminoglycoside resistance gene patterns, the strains of the eight clusters were distributed into seven classes. This simple and rapid (< 8 h) fingerprinting technique could be a useful tool for the epidemiological investigation of A. baumannii nosocomial infections.

Tubular arrays in cerebrospinal fluid cells: their location within smooth endoplasmic reticulum cisternae.

Unique ultrastructural formations termed tubular arrays have been reported in a variety of renal diseases, viral infections, malignant tumors, and other circumstances. This report describes identical structures in monocytes in the cerebrospinal fluid in a case of pneumococcal meningitis. The occurrence, previously unreported, of tubular arrays in this infection and this kind of cell supports the growing view that tubular arrays probably do not represent viral components, but rather a general reactive phenomenon of the cell. In addition, ultrastructural findings are presented suggesting that tubular arrays appear to be located in the cisternae of the endoplasmic reticulum with major involvement of its smooth compartment.

Characterization of IS1541-like elements in Yersinia enterocolitica and Yersinia pseudotuberculosis.

We characterized Yersinia enterocolitica and Yersinia pseudotuberculosis insertion sequences related to insertion sequence 1541, recently identified in Yersinia pestis. For each of the two species, two insertion sequence copies were cloned and sequenced. Genetic elements from Y. pseudotuberculosis were almost identical to insertion sequence 1541, whereas these from Y. enterocolitica were less related. Phylogenetic analysis of the putative transposases encoded by insertion sequences from the three pathogenic members of the genus Yersinia showed that they clustered with those encoded by Escherichia coli and Salmonella enterica elements belonging to the insertion sequence 200/insertion sequence 605 group. Insertion sequences originating from Y. pestis and Y. pseudotuberculosis constitute a monophyletic lineage distinct from that of Y. enterocolitica.

Growth of Yersinia pseudotuberculosis in mouse spleen despite loss of a virulence plasmid of mol. wt 47 X 10(6).

A highly virulent strain of Yersinia pseudotuberculosis (LD50 c. 10(2) bacteria/mouse) harboured two plasmids with mol. wt of 47 X 10(6) and 61 X 10(6). The role of these plasmids in virulence was studied in mice with derived strains cured of plasmids. It was confirmed that the plasmid of mol. wt 47 X 10(6) played a major function in virulence. This was shown both by the increase of the LD50 and the lower rate of multiplication in the spleen obtained with strains cured of the plasmid of mol. wt 47 X 10(6). The plasmid of mol. wt 61 X 10(6) did not play any role in virulence. This work also demonstrates that the strain cured of the plasmid of mol. wt 47 X 10(6) and the plasmid-free strain were able to multiply in the spleens of infected mice during a 7-day period. This suggests that virulence factors not associated with plasmids are also responsible for the bacterial growth in tissues in vivo.

Protection against Yersinia infection induced by non-virulence-plasmid-encoded antigens.

Specific immunity against Yersinia was induced by plasmid-encoded antigens not associated with virulence. Mice were immunised with viable bacteria from a virulence-plasmid-cured strain of Y. pseudotuberculosis. This antigenic stimulation generated specific protection against virulence-plasmid-harbouring strains of Y. pseudotuberculosis and Y. pestis, demonstrating that protection can be generated by organisms lacking plasmid-encoded virulence antigens.