The effect of force applied to the left paratracheal oesophagus on air entry into the gastric antrum during positive-pressure ventilation using a facemask.

Cricoid force is widely applied to decrease the risk of pulmonary aspiration and gastric antral insufflation of air during positive-pressure ventilation, yet its efficacy remains controversial. We compared manual oesophageal compression at the low left paratracheal and cricoid levels for the prevention of gastric antral air insufflation during positive-pressure ventilation by facemask in patients scheduled for elective surgery under general anaesthesia. After gaining written consent, participants were randomly allocated by sealed envelope to one of three groups: oesophageal compression by 30 N paratracheal force (paratracheal group); oesophageal compression by 30 N cricoid force (cricoid group); or no oesophageal compression (control group). Gastric insufflation of air was assessed before and after positive-pressure ventilation by ultrasound measurement of the antral cross-sectional area and/or presence of air artefacts in the antrum. The primary outcome measure was the proportion of participants with ultrasound evidence of gastric insufflation. We recruited 30 patients into each group. Before facemask ventilation, no air artefacts were visible in the antrum in any of the participants. After facemask ventilation of the participant's lungs, no air artefacts were seen in the paratracheal group, compared with six subjects in the cricoid group and eight subjects in the control group (p = 0.012). Our results suggest that oesophageal compression can be achieved by the application of manual force at the low left paratracheal level and that this is more effective than cricoid force in preventing air entry into the gastric antrum during positive-pressure ventilation by facemask.

F376A/M388A-solulin, a new promising antifibrinolytic for severe haemophilia A.

INTRODUCTION: Haemophilia is a major bleeding disorder due to a deficiency of procoagulant factor VIII (type A) or IX (type B). The treatment is substitutive and based on infusion of factor concentrates. Main limitations of this therapy are cost, short factor half-life and the development of inhibitors (up to 30% of severe HA patients). An important aggravating factor of haemophilia is due to a premature fibrinolysis, directing attention to the therapeutic potential of suitable antifibrinolytics. Thrombomodulin (TM) is a key player of the coagulation cascade by activating protein C (an inhibitor of thrombin generation, thus antagonizing coagulation) and of the fibrinolytic cascade by activating thrombin activatable fibrinolysis inhibitor TAFI (thus reducing fibrinolysis). Solulin is a soluble form of TM that shows both capabilities. AIM: Here, we developed a new generation of solulin variants (F376A-, M388A- and F376A/M388A-solulin) with a decreased ability to activate protein C and a conserved capacity to activate TAFI. METHODS: We produced and characterized solulin variants in vitro. In addition, F376A/M388A-solulin was tested ex vivo, using blood samples of haemophilic A patients, with thromboelastography. RESULTS: The solulin variants (F376A, M388A and the double-mutant F376A/M388A) lost their abilities to activate protein C but are still capable to activate TAFI. Thrombelastography showed increased clot firmness and stability, that, as opposed to wild-type solulin, was maintained even at high concentrations of F376A/M388A-solulin (100 nm). CONCLUSION: In sum, these results open new opportunities for the development of specific medication for haemophilic patients.

Intense visible emission from ZnO/PAAX (X = H or Na) nanocomposite synthesized via a simple and scalable sol-gel method.

Intense visible nano-emitters are key objects for many technologies such as single photon source, bio-labels or energy convertors. Chalcogenide nanocrystals have ruled this domain for several decades. However, there is a demand for cheaper and less toxic materials. In this scheme, ZnO nanoparticles have appeared as potential candidates. At the nanoscale, they exhibit crystalline defects which can generate intense visible emission. However, even though photoluminescence quantum yields as high as 60% have been reported, it still remains to get quantum yield of that order of magnitude which remains stable over a long period. In this purpose, we present hybrid ZnO/polyacrylic acid (PAAH) nanocomposites, obtained from the hydrolysis of diethylzinc in presence of PAAH, exhibiting quantum yield systematically larger than 20%. By optimizing the nature and properties of the polymeric acid, the quantum yield is increased up to 70% and remains stable over months. This enhancement is explained by a model based on the hybrid type II heterostructure formed by ZnO/PAAH. The addition of PAAX (X = H or Na) during the hydrolysis of ZnEt2 represents a cost effective method to synthesize scalable amounts of highly luminescent ZnO/PAAX nanocomposites.

["Heart, arteries and women" an innovative care pathway for women at high risk: First evaluation at one year]. / Le circuit « cœur, artères et femmes ¼ chez la femme à haut risque cardiovasculaire : première évaluation à un an.

INTRODUCTION: Cardiovascular diseases remain the first cause of death in women. To improve women's health cardiologists and gynaecologists should work together on women's specific cardiovascular risk factor. METHOD: Our study evaluated a care pathway named "heart, arteries and women". One hundred and ninety-one women were included for vascular (n=55) or hypertensive (n=136) explorations from January the first to December the 31st of 2013. We studied their clinical presentation and medical management. RESULTS: All women were at high cardiovascular risk (38% of them at very high risk). The average age was 52 years old. A woman on three had experienced high blood pressure or diabetes during pregnancy. One on two was postmenopausal woman. We stopped twelve estrogen-progesterone contraceptions; 60% didn't have gynaecological follow-up; 146 had high blood pressures (73% at night, 50% had no dipping blood pressure profile and 15 were newly diagnosed for hypertension). Sleep apnoea syndrome was suspected in half women. Medical therapies were optimized especially for women with atheroma in which 30 to 46% were properly treated (P=0.0005). Only 18% of the gynecologists received conclusive reports. CONCLUSION: At one year, our care pathway "heart, arteries and women" allowed to optimize medical therapy and clinical management. Everyone should be aware of this program.

High nonlinear figure-of-merit amorphous silicon waveguides.

The nonlinear response of amorphous silicon waveguides is reported and compared to silicon-on-insulator (SOI) samples. The real part of the nonlinear coefficient γ is measured by four-wave-mixing and the imaginary part of γ is characterized by measuring the nonlinear loss at different peak powers. The combination of both results yields a two-photon-absorption figure of merit of 4.9, which is more than 7 times higher than for the SOI samples. Time-resolved measurements and simulations confirm the measured nonlinear coefficient γ and show the absence of slow free-carrier effects versus ns free-carrier lifetimes in the SOI samples.

Hydrolysis of factor VIII mediated by catalytic antibodies occurs in haemophilia A patients with or without factor VIII inhibitors.

The major complication of the substitutive treatment of haemophilia A (HA) is the development of antifactor VIII (FVIII) antibodies. Most of these antibodies neutralize FVIII procoagulant activity, and are identified as FVIII inhibitor. A subgroup of these antibodies, 'catalytic antibodies', catalyses the FVIII hydrolysis. We investigated the frequency and the activity of catalytic antibodies, according to the phenotype of HA and the presence or absence of FVIII inhibitor. IgG from 16 patients with inhibitor and 17 patients without inhibitor were purified. Rates of FVIII hydrolysis and inhibitor titres were evaluated. Anti-FVIII catalytic antibodies were detected in 63.6% of patients with HA, irrespective of the HA phenotype and the presence of FVIII inhibitor. The frequency was significantly higher for severe HA patients (73.3%) and patients with inhibitor (87.5%), but their FVIII-proteolytic activity was not significantly different from patients with mild or moderate HA and patients without inhibitor. The evolution of both catalytic and inhibitory activities was studied for 11 patients with FVIII inhibitor. We observed two profiles. In the profile 1, 18.2% of patients, the catalytic activity and the inhibitor titre coevolved. In contrast, a dissociated evolution of these two parameters was observed in 72.8% patients in profile 2. These data confirm the importance of anti-FVIII catalytic activity in patients with severe, moderate and mild HA. Interestingly, most of the patients presented a dissociated profile, suggesting that anti-FVIII antibodies might not systematically act as FVIII inhibitors.

Use of antimicrobial agents in livestock.

Antimicrobial agents, especially antibacterial agents, are used throughout the world, across a diverse array of extensive and intensive livestock production systems, to protect the health and welfare of livestock and to improve their performance. While some agents that are used in livestock belong to classes that have no counterpart in human medicine, this is not the case for the most widely used agents: the tetracyclines, penicillins, macrolides and sulphonamides. Many bacterial diseases of livestock cause devastating losses of animal life and productivity. As a result, their keepers can lose their livelihoods and see a dramatic reduction in income, so there is often a great sense of urgency to treat affected animals early. However, there are a large number of bacterial pathogens that cause disease and it is frequently difficult to reach a conclusive diagnosis prior to instituting treatment. There are many ways in which existing uses of antimicrobial agents can be improved, amongst the most important are increased utilisation of veterinary professional services, the introduction of enhanced infection control measures, improved point-of-care diagnostic tests, and the application of physiologically based population pharmacokinetic-pharmacodynamic modelling.

[Tako-Tsubo syndrome during normal human immunoglobolin perfusion]. / Syndrome Tako-tsubo au décours d'une perfusion d'immunoglobuline humaine normale (Tégeline(®)).

This is a case of an 82 year old female patient with myasthenia gravis, who following treatment with Human Normal Immunoglobulin (Tegeline(®)), developed dyspnoea, chest pain without cardiac insufficiency, inverted T wave on ECG with slight increase in Troponine T 0.43ng/mL (<0.2ng/mL normal value in our hospital) and marked increase in Pro-BNP 4900 (Nl≤450pg/mL for an age greater than 65 years old). Her coronary angiogram showed hypokinesia of apical area but was otherwise normal. Also, MRI ruled out inflammatory and ischemic cardiac diseases. The most likely diagnosis for us was Tako-Tsubo syndrome in relation with injection of Human Normal Immunoglobulin (Tegeline(®)) according to the Mayo clinic criteria.

[Acquired von Willebrand syndrome: from diagnosis to treatment]. / Le syndrome de Willebrand acquis: du diagnostic au traitement.

Acquired von Willebrand syndrome is a rare bleeding disorder, which has been related in various diseases including lymphoproliferative disorders or autoimmune diseases. Its diagnosis is an important step before treatment of patients and particularly in case of bleeding. We report four cases from Caen Hemophilia Treatment Center, diagnosed and treated from 1999 to 2008. Mucocutaneous bleeds in every case were the same as in hereditary von Willebrand disease. All patients had no personal or family history of bleeding. Phenotype was identified as type 2 von Willebrand disease with a loss of high molecular weight multimers. Anti-von Willebrand factor inhibitor screening was positive for three patients. The etiological diagnosis was one chronic lymphocytic leukaemia, two monoclonal gammapathies of undetermined significance (MGUS) and one undetermined case. The management of patients need two stages: first infusions of factor von Willebrand/factor VIII concentrates to stop bleeds, then treatment of the underlying disease such as chemotherapy, corticotherapy and treatment with high doses of polyvalents immunoglobulins. In every case, treatment was effective and improved patient's quality of life.

A portrait of Staphylococcus aureus from the other side of the Mediterranean Sea: molecular characteristics of isolates from Western Algeria.

Algerian hospitals have experienced a dramatic increase in methicillin-resistant Staphylococcus aureus (MRSA) prevalence in recent years. To investigate this phenomenon, we have determined molecular characteristics of 61 methicillin-resistant or -susceptible strains isolated between 2003 and 2007 in Oran Hospital. Susceptible isolates were related to diverse genetic backgrounds, of which clone with sequence type (ST) 8 accounted for most of the samples. Resistance to methicillin was almost limited to two international spreading clones; the most frequent, ST80, contained isolates producing Panton-Valentine leukocidine, with SCCmec type IV. The increase of MRSA prevalence observed in Western Algeria, in outpatients as well as in hospitalized patients, is linked to dissemination of ST80 strains usually considered as community-acquired MRSA.

FISH mapping of de novo apparently balanced chromosome rearrangements identifies characteristics associated with phenotypic abnormality.

We report fluorescence in situ hybridization (FISH) mapping of 152, mostly de novo, apparently balanced chromosomal rearrangement (ABCR) breakpoints in 76 individuals, 30 of whom had no obvious phenotypic abnormality (control group) and 46 of whom had an associated disease (case group). The aim of this study was to identify breakpoint characteristics that could discriminate between these groups and which might be of predictive value in de novo ABCR (DN-ABCR) cases detected antenatally. We found no difference in the proportion of breakpoints that interrupted a gene, although in three cases, direct interruption or deletion of known autosomal-dominant or X-linked recessive Mendelian disease genes was diagnostic. The only significant predictor of phenotypic abnormality in the group as a whole was the localization of one or both breakpoints to an R-positive (G-negative) band with estimated predictive values of 0.69 (95% CL 0.54-0.81) and 0.90 (95% CL 0.60-0.98), respectively. R-positive bands are known to contain more genes and have a higher guanine-cytosine (GC) content than do G-positive (R-negative) bands; however, whether a gene was interrupted by the breakpoint or the GC content in the 200 kB around the breakpoint had no discriminant ability. Our results suggest that the large-scale genomic context of the breakpoint has prognostic utility and that the pathological mechanism of mapping to an R-band cannot be accounted for by direct gene inactivation.

Factor VIII (FVIII) gene mutations in 120 patients with hemophilia A: detection of 26 novel mutations and correlation with FVIII inhibitor development.

BACKGROUND: As the publication of the sequence of the factor VIII gene (FVIII) in 1984, a large number of mutations that cause hemophilia A (HA) have been identified. Thanks to the advances in the detection of mutations, it is now possible to identify a putative FVIII sequence alteration in the vast majority of patients with HA. OBJECTIVES: Our main objective was to report on the spectrum of FVIII mutations and their distribution throughout the gene in 120 patients with HA. METHODS: Screening of FVIII mutations was performed using direct sequencing. Newly described missense mutations were further studied by molecular modeling. RESULTS: A total of 47 different HA causative FVIII mutations have been identified, 26 of which are described for the first time. These novel mutations include 14 missense and six nonsense mutations, two small deletions, one large deletion and three splice-site mutations. We further investigated the development of FVIII-specific inhibitors in all patients with HA. We found that four novel mutations (Ser882X, Tyr1786Ser, Ala2218Thr and a splice-site defect in intron 22) were associated with inhibitor development. CONCLUSION: These data extend our insight into the mechanisms by which novel amino acid substitutions may lead to HA, and how HA patient genotypes influence the risk of FVIII inhibitor development.

[Does antiaggregant therapy have a place in type II heparin-induced thrombocytopenia?]. / L'antiagrégation a-t-elle une place en cas de thrombopénie tardive induite par l'héparine?

We report a case of type II heparin-induced thrombocytopenia, which occurred after heart surgery in a 71-year-old female patient with several cardiovascular risk factors. The diagnosis of heparin-induced thrombopenia was suspected because association of multifocal arterial and venous thrombosis and detection of antiplatelet-factor 4 antibodies with a drop of more than 50% in the platelet count. Until diagnostic of heparin-induced thrombocytopenia was made, clopidogrel was introduced because of well-documented ischemia in middle-cerebral artery territory. The platelets subsequently increased by near 30%. The diagnosis of heparin-induced thrombocytopenia was finally confirmed a few days later by detection of antiplatelet-factor 4 antibodies associated with a positive platelet aggregation test for unfractionated heparin. Heparin was replaced by sodium danaparoid. These measures did not change the unfavorable outcome and death of the patient. The increase in the platelet count after fortuitous clopidogrel introduction raises the question of the role of antiaggregant agents in association with anticoagulants for the treatment of type II heparin-induced thrombocytopenia.

Comparison of the effects of intrathecal ropivacaine, levobupivacaine, and bupivacaine for Caesarean section.

BACKGROUND: This study aimed to detect if intrathecal (i.t.) ropivacaine and levobupivacaine provided anaesthesia (satisfactory analgesia and muscular relaxation) and postoperative analgesia of similar quality to bupivacaine in patients undergoing Caesarean section. METHODS: Ninety parturients were enrolled. A combined spinal-epidural technique was used. Patients were randomly assigned to receive one of the following isobaric i.t. solutions: bupivacaine 8 mg (n=30), levobupivacaine 8 mg (n=30), or ropivacaine 12 mg (n=30), all combined with sufentanil 2.5 microg. An i.t. solution was considered effective if an upper sensory level to pinprick of T4 or above was achieved and if intraoperative epidural supplementation was not required. Sensory changes and motor changes were recorded. RESULTS: Anaesthesia was effective in 97, 80, and 87% of patients in the bupivacaine 8 mg, levobupivacaine 8 mg, and ropivacaine 12 mg groups, respectively. Bupivacaine 8 mg was associated with a significantly superior success rate to that observed in the levobupivacaine group (P<0.05). It also provided a longer duration of analgesia and motor block (P<0.05 vs levobupivacaine and ropivacaine). CONCLUSIONS: The racemic mixture of bupivacaine combined with sufentanil remains an appropriate choice when performing Caesarean sections under spinal anaesthesia.

Structure and texture of anisotropic nematic gels.

Anisotropic nematic gels are prepared via in situ polymerization of diacrylate monomers in an oriented nematic liquid crystal (LC) matrix. The structure of the gels is studied from micrometer to nanometer scales by optical microscopy, small angle neutron scattering, and theta/2theta light scattering. A strong anisotropy is evidenced at all scales without electric field for both mesogenic and nonmesogenic monomers. The gel network can be pictured as an ordered but strongly distorted and polydisperse structure with two characteristic sizes: the mean size of the polymer objects and a correlation length between these objects, corresponding to the mean-size of the LC domains, which are estimated from neutron and light scattering results to be of the order of some tens of nanometers and some micrometers, respectively. Moreover, a sheet-like structure of the polymer network is evidenced. When an electric field is applied, one part of the LC switches while the other part remains anchored to the polymer network. The electric field dependence of the volume fraction of anchored LC is estimated from the analysis of the light scattering data. We emphasize systematic correlations between structure and electro-optical properties of the gels.

Efficacy of selamectin against biting lice on dogs and cats.

The efficacy of selamectin was evaluated against naturally acquired Trichodectes canis infestations on dogs and against Felicola subrostratus infestations on cats. Twenty dogs and 18 cats were randomly allocated to treatment with either a placebo or selamectin (6 mg/kg), administered topically once only on day 0. The treatment had no adverse effects in either the dogs or the cats. Efficacy was assessed by counting the live lice (adults and nymphs) on each animal by using a coat-parting technique on days -3, 7, 14, 21, 28, 35 and 42 for the dogs, and on days -1, 7, 21, 35 and 42 for the cats. On day 43, the number of live lice on each dog was also assessed by using a whole-body combing technique. Selamectin was 100 per cent effective in killing biting lice on the dogs and cats throughout the period of assessment; the louse counts on the treated dogs and cats were significantly lower than the pretreatment counts (P = 0.0001) and were also significantly lower than on the placebo-treated dogs (P < 0.05) and cats (P = 0.0001). There was a marked reduction in the prevalence of clinical signs associated with ectoparasite infestation in the treated dogs and no clinical signs were observed in any of the treated cats.

Cost related to replacement therapy during hospitalization in haemophiliacs with or without inhibitors: experience of six French haemophilia centres.

Replacement therapy in haemophiliacs has a major economic impact on health establishments. We assessed in this prospective study the cost of clotting factor concentrate therapy for haemophilia A or B patients. We compared the overall costs of treated patients with or without inhibitors. In six French haemophilia centres, 278 consecutive hospitalizations were collected and analysed between June 97 and June 99. Haemophilia must be considered as the main cost factor during hospitalization. The severity of bleeds and surgical procedures increase the total cost. Furthermore, the daily and total costs are closely linked to the presence or the absence of inhibitors. This study should enable the hospital administration to evaluate the necessary resources to the clotting factor therapy in haemophiliacs with or without inhibitors during hospitalization.