Tightening force and torque of nonlocking screws in a reverse shoulder prosthesis.

BACKGROUND: Reversed shoulder arthroplasty is an accepted treatment for glenohumeral arthritis associated to rotator cuff deficiency. For most reversed shoulder prostheses, the baseplate of the glenoid component is uncemented and its primary stability is provided by a central peg and peripheral screws. Because of the importance of the primary stability for a good osteo-integration of the baseplate, the optimal fixation of the screws is crucial. In particular, the amplitude of the tightening force of the nonlocking screws is clearly associated to this stability. Since this force is unknown, it is currently not accounted for in experimental or numerical analyses. Thus, the primary goal of this work is to measure this tightening force experimentally. In addition, the tightening torque was also measured, to estimate an optimal surgical value. METHODS: An experimental setup with an instrumented baseplate was developed to measure simultaneously the tightening force, tightening torque and screwing angle, of the nonlocking screws of the Aquealis reversed prosthesis. In addition, the amount of bone volume around each screw was measured with a micro-CT. Measurements were performed on 6 human cadaveric scapulae. FINDINGS: A statistically correlated relationship (p<0.05, R=0.83) was obtained between the maximal tightening force and the bone volume. The relationship between the tightening torque and the bone volume was not statistically significant. INTERPRETATION: The experimental relationship presented in this paper can be used in numerical analyses to improve the baseplate fixation in the glenoid bone.

Caval collapse during cardiopulmonary bypass: a reproducible bench model.

OBJECTIVES: During open heart surgery, so-called atrial chatter, a phenomenon due to right atria and/or caval collapse, is frequently observed. Collapse of the cava axis during cardiopulmonary bypass (CPB) limits venous drainage and may result downstream in reduced pump flow on (lack of volume) and upstream in increased after-load (stagnation), which in turn may both result in reduced or even inadequate end-organ perfusion. The goal of this study was to reproduce venous collapse in the flow bench. METHODS: In accordance with literature for venous anatomy, a caval tree system is designed (polyethylene, thickness 0.061 mm), which receives venous inflow from nine afferent veins. With water as medium and a preload of 4.4 mmHg, the system has an outflow of 4500 ml/min (Scenario A). After the insertion of a percutaneous venous cannula (23-Fr), the venous model is continuously served by the afferent branches in a venous test bench and venous drainage is augmented with a centrifugal pump (Scenario B). RESULTS: With gravity drainage (siphon: A), spontaneously reversible atrial chatter can be generated in reproducible fashion. Slight reduction in the outflow diameter allows for generation of continuous flow. With augmentation (B), irreversible collapse of the artificial vena cava occurs in reproducible fashion at a given pump speed of 2300 ± 50 RPM and a pump inlet pressure of -112 mmHg. Furthermore, bubbles form at the cannula tip despite the fact that the entire system is immersed in water and air from the environment cannot enter the system. This phenomenon is also known as cavitation and should be avoided because of local damage of both formed blood elements and endothelium, as well embolization. CONCLUSIONS: This caval model provides a realistic picture for the limitations of flow due to spontaneously reversible atrial chatter vs irreversible venous collapse for a given negative pressure during CPB. Temporary interruption of negative pressure in the venous line can allow for recovery of venous drainage. This know-how can be used not only for testing different cannula designs, but also for further optimizing perfusion strategies.

Enclouage verrouillé du tibia [Interlocking nailing of the tibia]

Centromedullary nailing is a well-established method of treatment for diaphyseal long bone fractures. The indications have been broadened greatly since the introduction in 1974 of interlocking centromedullary nailing. The purpose of this paper is to review our first results with locked intramedullary nailing of the tibia. We report our experience with the first 19 cases of interlocking tibia nails (15 fractures, 1 delayed union, 2 pseudarthrosis, 1 osteotomy). On the extension table, the insertion of the nail and the placement of the interlocking screws did not cause any problem. In 3 cases, a proximal screw had to be removed within two weeks because of spontaneous displacement. Complications have been noticed in three patients (15.8%) (pulmonary embolism on day 1, and compartment syndrome two days later in one case, sciatic nerve neuroapraxia in the other two). The other patients have been mobilized 24 to 48 hours after surgery. 94% of the fractures were consolidated 4 months post-operatively, with no major deformation. Interlocking tibia nailing seems to be an attractive method in the treatment of certain fractures of the tibia. Early mobilisation and weight-bearing are provided. The indications, the technical aspects as well as the dangers of the method must be carefully respected in order to avoid complications and poor results.

Reversed shoulder arthroplasty baseplate fixed according to the three major columns principle

Introduction: Glenoid bone volume and bone quality can render the fixation of a reversed shoulder arthroplasty (RSA) basis plate hazardous. Cadaveric study at our institution has demonstrated that optimal baseplate fixation could be achieved with screws in three major columns. Our aim is to review our early rate of aseptic glenoid loosening in a series of baseplates fixed according to this principle. Methods: Between 2005 and 2008, 48 consecutive RSA (Reversed Aequalis) were implanted in 48 patients with an average age of 74.4 years (range, 56 to 86 years). There were 37 women and 11 men. Twenty-seven primary RSAs were performed for cuff tear arthropathy, 3 after failed rotator cuff surgery, 6 for failed arthroplasties, 7 for acute fractures and 5 after failed ORIF. All baseplate fixations were done using a nonlocking posterior screw in the scapular spine, a nonlocking anterior screw in the glenoid body, a locking superior screw in the coracoid and a locking inferior screw in the pillar. All patients were reviewed with standardized radiographs. We reported the positions of the screws in relation to the scapular spine and the coracoid process in two different views. We defined screw positions as totally, partially or out of the target. Finally, we reported aseptic glenoid loosening which was defined as implant subsidence. Results: Four patients were lost to follow-up. Thus 44 shoulders could be reviewed after a mean follow-up of 16 months (range, 9 to 32 months). Thirty-seven (84%) screws were either partially or totally in the spine. Thus, 7 (16%) scapular spine screws were out of the target. No coracoid screw was out of the target. At final follow-up control, we reported no glenoid loosening. Conclusion: Early glenoid loosening occurred before the two years follow-up and is most of time related to technical problems and/or insufficient glenoid bone stock and bone quality. Our study demonstrate that baseplate fixation of a RSA according to the three columns principle is a reproducible technique and a valuable way to prevent early glenoid loosening.

Appropriate management of special situations in Crohn's disease (upper gastro-intestinal; extra-intestinal manifestations; drug safety during pregnancy and breastfeeding): results of a multidisciplinary international expert panel-EPACT II

Introduction: High-grade evidence is lacking for most therapeutic decisions in Crohn's disease. Appropriateness criteria were developed for upper gastro-intestinal, extra-intestinal manifestations and drug safety during conception, pregnancy and breastfeeding in patients with Crohn's disease, to assist the physician in clinical decision making. Methods: The European Panel on the Appropriateness of Crohn's Disease Therapy (EPACT II), a multidisciplinary international European expert panel, rated clinical scenarios based on evidence from the published literature and panelists' own clinical expertise. Median ratings (on a 9-point scale) were stratified into three categories: appropriate (7-9), uncertain (4-6 with or without disagreement) and inappropriate (1-3). Experts were also asked to rank appropriate medications by priority. Results: Proton pump inhibitors, steroids, azathioprine/6-mercaptopurine and infliximab are appropriate for upper gastro-duodenal Crohn's disease; for stenosis, endoscopic balloon dilation is the first-tine therapy, although surgery is also appropriate. Ursodeoxycholic acid is the only appropriate treatment for primary sclerosing cholangitis. Infliximab is appropriate for Pyoderma gangrenosum, ankylosing spondylitis and uveitis, steroids for Pyoderma gangrenosum and ankylosing spondylitis, adalimumab for Pyoderma gangrenosum and ankylosing spondylitis, cyclosporine-A/tacrolimus for Pyoderma gangrenosum. Mesalamine, sulfasalazine, prednisone, azathioprine/6-mercaptopurine, ciprofloxacin, and probiotics, may be administered safety during pregnancy or for patients wishing to conceive, with the exception that mate patients considering conception should avoid sulfasalazine. Metronidazol is considered safe in the 2nd and 3rd trimesters whereas infliximab is rated safe in the 1st trimester but uncertain in the 2nd and 3rd trimesters. Methotrexate is always contraindicated at conception, during pregnancy or during breastfeeding, due to its known teratogenicity. Mesalamine, prednisone, probiotics and infliximab are considered safe during breastfeeding. Conclusion: EPACT II recommendations are freely available online (www.epact.ch). The validity of these criteria should now be tested by prospective evaluation. (C) 2009 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

Caution on the storage of waters and aqueous solutions in plastic containers for hydrogen and oxygen stable isotope analysis

RATIONALE The choice of containers for storage of aqueous samples between their collection, transport and water hydrogen (2H) and oxygen (18O) stable isotope analysis is a topic of concern for a wide range of fields in environmental, geological, biomedical, food, and forensic sciences. The transport and separation of water molecules during water vapor or liquid uptake by sorption or solution and the diffusive transport of water molecules through organic polymer material by permeation or pervaporation may entail an isotopic fractionation. An experiment was conducted to evaluate the extent of such fractionation. METHODS Sixteen bottle-like containers of eleven different organic polymers, including low and high density polyethylene (LDPE and HDPE), polypropylene (PP), polycarbonate (PC), polyethylene terephthalate (PET), and perfluoroalkoxy-Teflon (PFA), of different wall thickness and size were completely filled with the same mineral water and stored for 659?days under the same conditions of temperature and humidity. Particular care was exercised to keep the bottles tightly closed and prevent loss of water vapor through the seals. RESULTS Changes of up to +5 parts per thousand for d2H values and +2.0 parts per thousand for d18O values were measured for water after more than 1?year of storage within a plastic container, with the magnitude of change depending mainly on the type of organic polymer, wall thickness, and container size. The most important variations were measured for the PET and PC bottles. Waters stored in glass bottles with Polyseal (TM) cone-lined PP screw caps and thick-walled HDPE or PFA containers with linerless screw caps having an integrally molded inner sealing ring preserved their original d2H and d18O values. The carbon, hydrogen, and oxygen stable isotope compositions of the organic polymeric materials were also determined. CONCLUSIONS The results of this study clearly show that for precise and accurate measurements of the water stable isotope composition in aqueous solutions, rigorous sampling and storage procedures are needed both for laboratory standards and for unknown samples. Copyright (c) 2012 John Wiley & Sons, Ltd.

Pivotal role for a tail subunit of the RNA polymerase II mediator complex CgMed2 in azole tolerance and adherence in Candida glabrata.

Antifungal therapy failure can be associated with increased resistance to the employed antifungal agents. Candida glabrata, the second most common cause of invasive candidiasis, is intrinsically less susceptible to the azole class of antifungals and accounts for 15% of all Candida bloodstream infections. Here, we show that C. glabrata MED2 (CgMED2), which codes for a tail subunit of the RNA polymerase II Mediator complex, is required for resistance to azole antifungal drugs in C. glabrata. An inability to transcriptionally activate genes encoding a zinc finger transcriptional factor, CgPdr1, and multidrug efflux pump, CgCdr1, primarily contributes to the elevated susceptibility of the Cgmed2Δ mutant toward azole antifungals. We also report for the first time that the Cgmed2Δ mutant exhibits sensitivity to caspofungin, a constitutively activated protein kinase C-mediated cell wall integrity pathway, and elevated adherence to epithelial cells. The increased adherence of the Cgmed2Δ mutant was attributed to the elevated expression of the EPA1 and EPA7 genes. Further, our data demonstrate that CgMED2 is required for intracellular proliferation in human macrophages and modulates survival in a murine model of disseminated candidiasis. Lastly, we show an essential requirement for CgMed2, along with the Mediator middle subunit CgNut1 and the Mediator cyclin-dependent kinase/cyclin subunit CgSrb8, for the high-level fluconazole resistance conferred by the hyperactive allele of CgPdr1. Together, our findings underscore a pivotal role for CgMed2 in basal tolerance and acquired resistance to azole antifungals.

Pharmacovigilance update [Pharmacovigilance update]

Main pharmacovigilance signals and alerts issued in 2009 are reviewed. Efalizumab was withdrawn from the market due to increased risks, including progressive multifocal leukoencephalopathy (PML) and questionable efficacy. New cases of PML are still being reported with rituximab and natalizumab. Rare cases of pure red cell aplasia have been observed with mycophenate. Gastrointestinal perforation, severe skin rashes and various ocular disorders have been reported during erlotinib use. Severe skin rashes have been related to etravirine. Acute renal failure and pancreatitis can occur with exenatide. A link between sitagliptin and pancreatitis is suspected. Raised concerns of causality between insuline glargine and malignant tumors are not supported by strong evidence. Proton pump inhibitors seem to blunt clopidogrel benefit. Aliskiren can cause angioedema.

Genes involved in the astrocyte-neuron lactate shuttle (ANLS) are specifically regulated in cortical astrocytes following sleep deprivation in mice.

STUDY OBJECTIVES: There is growing evidence indicating that in order to meet the neuronal energy demands, astrocytes provide lactate as an energy substrate for neurons through a mechanism called "astrocyte-neuron lactate shuttle" (ANLS). Since neuronal activity changes dramatically during vigilance states, we hypothesized that the ANLS may be regulated during the sleep-wake cycle. To test this hypothesis we investigated the expression of genes associated with the ANLS specifically in astrocytes following sleep deprivation. Astrocytes were purified by fluorescence-activated cell sorting from transgenic mice expressing the green fluorescent protein (GFP) under the control of the human astrocytic GFAP-promoter. DESIGN: 6-hour instrumental sleep deprivation (TSD). SETTING: Animal sleep research laboratory. PARTICIPANTS: Young (P23-P27) FVB/N-Tg (GFAP-GFP) 14Mes/J (Tg) mice of both sexes and 7-8 week male Tg and FVB/Nj mice. INTERVENTIONS: Basal sleep recordings and sleep deprivation achieved using a modified cage where animals were gently forced to move. MEASUREMENTS AND RESULTS: Since Tg and FVB/Nj mice displayed a similar sleep-wake pattern, we performed a TSD in young Tg mice. Total RNA was extracted from the GFP-positive and GFP-negative cells sorted from cerebral cortex. Quantitative RT-PCR analysis showed that levels of Glut1, α-2-Na/K pump, Glt1, and Ldha mRNAs were significantly increased following TSD in GFP-positive cells. In GFP-negative cells, a tendency to increase, although not significant, was observed for Ldha, Mct2, and α-3-Na/K pump mRNAs. CONCLUSIONS: This study shows that TSD induces the expression of genes associated with ANLS specifically in astrocytes, underlying the important role of astrocytes in the maintenance of the neuro-metabolic coupling across the sleep-wake cycle.

Antibiotic treatment of experimental endocarditis due to methicillin-resistant Staphylococcus epidermidis.

The natural history and treatment of experimental endocarditis due to heterogeneous and homogeneous methicillin-resistant Staphylococcus epidermidis was investigated. Amoxicillin/clavulanate or vancomycin were administered for 3 days via a computerized pump to mimic human drug kinetics in animals. After challenge with the minimum inoculum producing 90% of infections (ID90), bacteria in the vegetations grew logarithmically for 16 h. Then, bacterial densities stabilized (at approximately 10(8) cfu/g) and growth rates sharply declined. Both regimens cured &gt; or = 60% of endocarditis (due to heterogeneous or homogeneous bacteria) when started 12-16 h after infection, although the bacterial densities in the vegetations had increased by 20 times in between. In contrast, treatment started after 24 h failed in most animals, while bacterial densities had not increased any more. Thus, while both regimens were equivalent, the therapeutic outcome was best predicted by growth rates in the vegetations, not by bacterial densities. These observations highlight the importance of phenotypic tolerance developing in vivo.

Lésions endothéliales des ballons de contre-pulsion intra-aortique [Endothelial lesions caused by intra-aortic counterpulsation balloons]

Intra-aortic balloon pump (IABP) is the most frequently used mechanical circulatory support. Repeated trauma on the aortic wall has been reported as a cause of balloon perforation by endothelial denudation of atheromatous plaque. This study analyses the effect of IABP on the endothelium of the calf aorta. In 12 calves (mean weight: 72 +/- 6 kg) an IABP was inserted by femoral route and left during 6 hours on internal mode with a frequency of 80 cycles/min. The animals were sacrificed after the procedure (n = 4), at postoperative day (POD) 7 (n = 4), and at POD 14 (n = 4). In the aorta facing the balloon, nine transmural samples were taken proximally (n = 3), at mid height (n = 3) and distally (n = 3), for histological analysis of the percentage of aortic surface covered with endothelium. The percentage of aortic surface covered with endothelium at POD 0, 7 and 14 was proximally: 72.5 +/- 27.5%, 83.7 +/- 16.9% and 93.3 +/- 8.9% respectively; at mid-height: 50.8 +/- 30.7%, 65 +/- 25% and 95 +/- 5%; and distally: 31.4 +/- 20.1%, 48.3 +/- 34.4% and 85 +/- 10%. A large portion of the aortic endothelium is abraded after 6 hours of IAB pumping. This effect is more important at the distal level of the aorta. After two weeks, most of the endothelium has regenerated.

The TetR-type MfsR protein of the integrative and conjugative element (ICE) ICEclc controls both a putative efflux system and initiation of ICE transfer.

Integrative and conjugating elements (ICE) are self-transferable DNAs widely present in bacterial genomes, which often carry a variety of auxiliary genes of potential adaptive benefit. One of the model ICE is ICEclc, an element originally found in Pseudomonas knackmussii B13 and known for its propensity to provide its host with the capacity to metabolize chlorocatechols and 2-aminophenol. In this work, we studied the mechanism and target of regulation of MfsR, a TetR-type repressor previously found to exert global control on ICEclc horizontal transfer. By using a combination of ICEclc mutant and transcriptome analysis, gene reporter fusions, and DNA binding assays, we found that MfsR is a repressor of both its own expression and that of a gene cluster putatively coding for a major facilitator superfamily efflux system on ICEclc (named mfsABC). Phylogenetic analysis suggests that mfsR was originally located immediately adjacent to the efflux pump genes but became displaced from its original cis target DNA by a gene insertion. This resulted in divergence of the original bidirectional promoters into two separated individual regulatory units. Deletion of mfsABC did not result in a strong phenotype, and despite screening a large number of compounds and conditions, we were unable to define the precise current function or target of the putative efflux pump. Our data reconstruct how the separation of an ancestor mfsR-mfsABC system led to global control of ICEclc transfer by MfsR.

Valved stents for transapical pulmonary valve replacement.

OBJECTIVES: Pulmonary valve insufficiency remains a leading cause for reoperations in congenital cardiac surgery. The current percutaneous approach is limited by the size of the access vessel and variable right ventricular outflow tract morphology. This study assesses the feasibility of transapical pulmonary valve replacement based on a new valved stent construction concept. METHODS: A new valved stent design was implanted off-pump under continuous intracardiac echocardiographic and fluoroscopic guidance into the native right ventricular outflow tract in 8 pigs (48.5 +/- 6.0 kg) through the right ventricular apex, and device function was studied by using invasive and noninvasive measures. RESULTS: Procedural success was 100% at the first attempt. Procedural time was 75 +/- 15 minutes. All devices were delivered at the target site with good acute valve function. No valved stents dislodged. No animal had significant regurgitation or paravalvular leaking on intracardiac echocardiographic analysis. All animals had a competent tricuspid valve and no signs of right ventricular dysfunction. The planimetric valve orifice was 2.85 +/- 0.32 cm(2). No damage to the pulmonary artery or structural defect of the valved stents was found at necropsy. CONCLUSIONS: This study confirms the feasibility of direct access valve replacement through the transapical procedure for replacement of the pulmonary valve, as well as validity of the new valved stent design concept. The transapical procedure is targeting a broader patient pool, including the very young and the adult patient. The device design might not be restricted to failing conduits only and could allow for implantation in a larger patient population, including those with native right ventricular outflow tract configurations.

Molecular determinants of vesicular storage and release of the gliotransmitter D-serine from cortical astrocytes

Neuron-astrocyte reciprocal communication at synapses has emerged as a novel signalling pathway in brain function. Astrocytes sense the level of synaptic activity and, in turn, influence its efficacy through the regulated release of 'gliotransmitters' such as glutamate, ATP or D-serine. A calcium-dependent exocytosis is proposed to drive the release of gliotransmitters but its existence is still debated. Over the last years, we have been studying the molecular determinants governing D-serine release from glia using different approaches. Using a novel bioassay for D-serine, we have been able to show that D-serine release occurs mainly through a calcium- and SNARE proteindependent mechanism just supporting the idea that this amino acid is released by exocytosis from glia. We next have pursued our exploration by confocal imaging and tracking of the exocytotic routes for Dserine- mediated gliotransmission and have shown that D-serine releasable pools are confined to synaptobrevin2/cellubrevin-bearing vesicles. To shed light onto the mechanisms controlling the storage and the release of gliotransmitters and namely D-serine, we have developed a new method for the immunoisolation of synaptobrevin 2- positive vesicles from rat cortical astrocytes in culture while preserving their content in gliotransmitters. The purified organelles are clear round shape vesicles of excellent purity with homogeneous size (40 nm) as judged by electron microscopy. Immunoblotting analysis revealed that isolated vesicles contain most of the major proteins already described for neuron-derived vesicles like synaptic vesicle protein 2 (SV2) and the proton pump H?-ATPase. In addition, we have analyzed the content for various amino acids of these vesicles by means of chiral capillary electrophoresis coupled to laser-induced fluorescence detection. The purified vesicles contain large amount of D-serine. We also detect peaks corresponding to unidentified compounds that may correspond to others amino acids. Postembedding immunogold labelling of the rat neocortex further revealed the expression of D-serine in astrocytes processes contacting excitatory synapses. Finally, we have examined the uptake properties for Dserine and glutamate inside the isolated glial vesicles. Our results provide significant support for the existence of an uptake system for D-serine in secretory glial vesicles and for the storage of chemical substances like D-serine and glutamate. 11th International Congress on Amino Acids, Peptides and Proteins 763 123

Résistances thérapeutiques dans les mouvements anormaux [Resistance to treatment in movement disorders].

Therapeutic strategies for essential tremor (ET) and Parkinson's disease (PD) can be divided into two successive steps, one based on oral medications and the other, more invasive, using pumps or functional neurosurgery. When ET becomes refractory to propranolol, primidone and other, second-choice compounds, deep brain stimulation of the VIM nucleus of the thalamus can be considered. When PD becomes resistant to dopamine replacement therapy using various combinations of dopaminergic agents, then three options can be discussed: first, a subcutaneous apomorphine mini-pump, second, a jejunal levodopa-delivery system by means of percutaneous gastrostomy, and third, bilateral deep brain stimulation of the subthalamic nucleus. The above interventions are successful in about 80% of cases.