[French national overview of the inclusion of environmental criteria in the public purchasing of health products (drugs and sterile medical devices)]. / Prise en compte des critères environnementaux dans la commande publique des produits de santé.

OBJECTIVES: Healthcare products (HP) have a significant carbon footprint that must be included by regulation in the facility's purchasing policy. A national overview of the inclusion of environmental criteria (EC) in the public procurement (PP) of HP in hospitals has been carried out. METHODS: Thirty EC were identified in the literature. Two questionnaires were proposed: (i) for buyers that analyze the level of "importance" and "ease of application" for public tenders (PT), and (ii) for suppliers that declare their commitments and evidence. RESULTS: Six regional buyers and 28 suppliers participated. Buyers recognize the "importance" of sustainable development (SD) but are more reticent about the "applicability" of EC in PT. The environmental rating remains low: on average 4.38 (0.25-10.00) % of the total rating. Only 12 EC are integrated within some PT. Suppliers report a high and diversified commitment to SD: 18 suppliers sent 474 evidence. Buyers and suppliers converge on the optimization of primary packaging and the establishment of a minimum order or delivery group. CONCLUSIONS: Since the efficiency of PP is inevitable, EC that combines SD and savings should be prioritized. The integration of additional EC, simple and easily documented, allowing cost containment for both suppliers and buyers, is possible to promote sustainable purchasing.

Chromatin three-dimensional interactions mediate genetic effects on gene expression.

Studying the genetic basis of gene expression and chromatin organization is key to characterizing the effect of genetic variability on the function and structure of the human genome. Here we unravel how genetic variation perturbs gene regulation using a dataset combining activity of regulatory elements, gene expression, and genetic variants across 317 individuals and two cell types. We show that variability in regulatory activity is structured at the intra- and interchromosomal levels within 12,583 cis-regulatory domains and 30 trans-regulatory hubs that highly reflect the local (that is, topologically associating domains) and global (that is, open and closed chromatin compartments) nuclear chromatin organization. These structures delimit cell type-specific regulatory networks that control gene expression and coexpression and mediate the genetic effects of cis- and trans-acting regulatory variants on genes.

Azadinium poporum from the Argentine Continental Shelf, Southwestern Atlantic, produces azaspiracid-2 and azaspiracid-2 phosphate.

The marine dinophycean genus Azadinium has been identified as the primary source of azaspiracids (AZA), a group of lipophilic phycotoxins known to accumulate in shellfish. Blooms of Azadinium in the southern Atlantic off Argentina have been described from the 1990s, but due to a lack of cultures, the diversity of South-Atlantic Azadinium has not yet been fully explored and their toxin production potential is completely unknown. During a spring 2010 research cruise covering the El Rincón (ER) estuarine system (North Patagonian coast, Argentina, Southwestern Atlantic) a search was conducted for the presence of Azadinium. Although neither Azadinium cells nor AZA in field plankton samples were detected, 10 clonal strains of Azadinium poporum were successfuly established by incubation of sediment samples. Argentinean A. poporum were more variable in size and shape than the type description but conformed to it by the presence of multiple pyrenoids with starch sheath, in plate pattern and arrangement, and in the position of the ventral pore located on the left side of the pore plate. In contrast to all previous description of A. poporum, isolates of the Argentinean A. poporum possessed a distinct field of pores on the second antapical plate. Conspecificity of the Argentinean isolates with A. poporum was confirmed by molecular phylogeny of concatenated ITS and LSU rDNA sequences, where all Argentinean isolates together with some Chinese A. poporum strains formed a well-supported ribotype clade within A. poporum. All isolates produced AZA with the same profile, consisting of AZA-2 as the major compound and, to a lesser extent, its phosphated form. This is the first report of a phosphated marine algal toxin. This first confirmation of the presence of AZA producing Azadinium in the Argentinean coastal area underlines the risk of AZA shellfish contamination episodes in the Southwestern Atlantic region.

Induction chemotherapy before surgery for unresectable head and neck cancer.

OBJECTIVE: To preoperatively reduce tumour size in patients with locally advanced and/or non-resectable squamous cell carcinoma with induction chemotherapy in order to achieve surgical excision with clear margins and preserve quality of life. METHODOLOGY: In this study, 16 patients with locally advanced and/or non-resectable squamous cell carcinoma underwent induction chemotherapy with docetaxel, cisplatin, and 5-fluorouricil or paclitaxel, carboplatin, and cetuximab. RESULTS: Over 80% of patients responded to induction chemotherapy. Histological examination of the 14 surgical specimens showed a total absence of residual cancer cells in 37.5% of cases. CONCLUSION: Concurrent radiation and chemotherapy is the standard treatment for locally advanced head and neck squamous cell carcinoma; however, induction chemotherapy may be beneficial in select patients.

Phytochemical screening, total phenolic content and antioxidant activity of Byrsonima species.

The species of the Byrsonima genus (Malpighiaceae) have been used in folk medicine to treat gastrointestinal disorders, asthma and skin infections. In this study, the total phenolic content, antioxidant activity and phytochemical screening were carried out in polar extracts of Byrsonima coccolobifolia, Byrsonima verbascifolia and Byrsonima intermedia. The presence of tannins and flavonoids in the samples and high phenols content was observed. B. coccolobifolia and B. intermedia species showed the best results of antioxidant action. It was analysed the correlation between the methods, and there was a great correlation between phenolic content and antioxidant assay, showing that the phenolic substances contribute to the antioxidant activities of these plants.

[Utilisation of immunosuppressants in the prevention of a graft versus host reaction: report by the SFGM-TC]. / Immunosuppresseurs dans la prévention de la réaction du greffon contre l'hôte : rapport de la SFGM-TC.

In the attempt to harmonize clinical practices between different French transplantation centers, the French Society of Bone Marrow Transplantation and Cell Therapy (SFGM-TC) set up the fourth annual series of workshops which brought together practitioners from all member centers and took place in September 2013 in Lille. Here we report our recommendations regarding the use of immunosuppressive treatment in the prevention of graft versus host disease: report by the SFGM-TC.

A novel application for bolus remifentanil: blunting the hemodynamic response to Mayfield skull clamp placement.

OBJECTIVE: Neurosurgery often requires skull immobilization with a Mayfield clamp, which often causes brief intense nociceptive stimulation, hypertension and tachycardia. Blunting this response may help prevent increased intracranial pressure, cerebral aneurysm or vascular malformation rupture, and/or myocardial stress. While various interventions have been described to blunt this response, no reports have compared administration of a propofol versus a remifentanil bolus. METHODS: We retrospectively analyzed the hemodynamic response to Mayfield placement in over 800 patients who received a prior propofol or remifentanil bolus from 2004 to 2010. RESULTS: Patients who received remifentanil experienced a 55% smaller increase in heart rate (p < 0.0001) and a 40% smaller increase in systolic blood pressure (p < 0.0001) after Mayfield placement than patients who received propofol. These data were retrospectively obtained from patients who were not randomized to receive remifentanil versus propofol, and hence these data could be subject to possible confounding. Nonetheless, these differences remained significant after multivariate analysis for possible confounding variables. CONCLUSIONS: Thus, a remifentanil bolus is more effective than a propofol bolus in blunting hemodynamic responses to Mayfield placement, and possibly for other short, intense nociceptive stimuli.

[How to handle unexpected biological abnormalities observed in the pre-donation workup for hematopoietic stem cell transplantation: an SFGM-TC report on pre-transplant cytomegalovirus, Epstein-Barr virus, Toxoplasma gondii, or syphilis IgM positive serology test]. / Conduite à tenir devant une anomalie biologique découverte lors du bilan pré-don cellules souches hématopoïétiques: sérologie IgM positive pour le cytomégalovirus, le virus d'Epstein-Barr, la toxoplasmose, ou la syphilis.

In the attempt to harmonize clinical practices between different French transplantation centers, the French Society of Bone Marrow Transplantation and Cell Therapy (SFGM-TC) set up the third annual series of workshops which brought together practitioners from all member centers and took place in October 2012 in Lille. Here we report our results and recommendations regarding the management of pre-transplant donor's cytomegalovirus, Epstein-Barr virus, Toxoplasma gondii, or syphilis IgM positive serology test.

[How to handle unexpected biological abnormalities observed in the pre-donation workup for hematopoietic stem cell transplantation: an SFGM-TC report on pre-transplant positive pregnancy test and monoclonal gammapathy]. / Conduite à tenir devant un problème du donneur de cellules souches hématopoïétiques: test de grossesse positif et gammapathie monoclonale.

In the attempt to harmonize clinical practices between different French transplantation centers, the French Society of Bone Marrow Transplantation and Cell Therapy (SFGM-TC) set up the third annual series of workshops which brought together practitioners from all member centers and took place in October 2012 in Lille. Here we report our results and recommendations regarding the management of common issues related to the donor: pre-transplant pregnancy and monoclonal gammopathy.

[Constraints of the dentist are consistent with the results of an optimal irradiation with modulated intensity in N0 oropharyngeal cancer]. / Les contraintes du chirurgien dentiste sont compatibles avec les résultats d'une irradiation optimale avec modulation d'intensité dans les cancers de l'oropharynx de stade N0.

PURPOSE: We compared intensity-modulated radiotherapy and 3D-conformal irradiation in oropharyngeal cancers according to the requirement of dentists. MATERIAL AND METHODS: From the files of seven patients with cancer of the oropharynx, two dosimetry plannings for 3D-conformal radiotherapy and intensity-modulated radiotherapy with tomotherapy were performed. The dose distributions in the target volumes and organs at risk in relation to the dental sphere were compared. RESULTS: For the planning target volume of the primitive tumour sites, average values of V95%, D2%, D98% and of the conformal index were statistically in favour of tomotherapy. For the planning target volume of node areas, averages values of V95%, D2%, D98% were statistically in favour of tomotherapy. For ipsi- and controlateral parotide glands, average values of V15Gy, V26Gy, V30Gy, V40Gy were significantly lower for tomotherapy. For the submaxillary glands, average values of mean doses and V40Gy were statistically in favour of tomotherapy. For the buccal cavity, the average values of V45Gy were statistically in favour of tomotherapy. For ipsi- and controlateral masseter muscles, the average values of mean doses were statistically in favour of tomotherapy. For the ipsi- and controlateral temporomandibular joints, average values of mean doses and V60Gy were statistically in favour of tomotherapy. For mandibular bone, average values of mean doses and V40Gy, V50Gy, V60Gy and V70Gy were statistically in favour of tomotherapy. For maxillary bone, average values of V40Gy, V50Gy and V60Gy were statistically in favour of tomotherapy. CONCLUSION: The radiation oncologist can constrain the intensity-modulated radiotherapy dosimetry to the needs of dentists to prevent or improve dental care and quality of life.

[Fulminant alveolar hemorrhage: evolution of giant cell arteritis to ANCA-positive vasculitis?]. / Hémorragie intra-alvéolaire fulminante : transformation d'une maladie de Horton en vascularite ANCA-positive?

INTRODUCTION: Giant cell arteritis (GCA) is a granulomatous vasculitis of the large and medium size vessels with a remarkable sensitivity to corticosteroids, although it may be dependent to therapy. In rare cases, a vasculitis of the medium or small-size vessels may mimic, be associated to, or follow GCA. We report a case of GCA dependent to corticosteroids that was followed five years after diagnosis by an alveolar hemorrhage leading to the diagnosis of a possible Wegener's granulomatosis. EXEGESIS: A 70-year-old man had a diagnosis of GCA fulfilling the ACR criteria in 1999. Temporal artery biopsy revealed a typical histological pattern. The initial response to corticosteroids was excellent, but the patient became dependent to corticosteroids, so he was given methotrexate from 2002. Severe alveolar haemorrhage occurred in December 2004, leading to the diagnosis of possible ANCA positive, anti-proteinase 3 positive Wegener's granulomatosis. CONCLUSION: ANCA-positive vasculitis may complicate the course of GCA. This evolution should be rapidly recognized, because its treatment differs to that of GCA.

[Late outcome of 89 patients with soft-tissue sarcomas treated by surgery and three different radiotherapy schedules]. / Résultats à long terme d'une série de 89 patients suivis pour un sarcome des tissus mous traités par chirurgie conservatrice et trois modalités d'irradiation postopératoire.

PURPOSE: To evaluate the outcome of patients treated for soft tissue sarcoma using three different post-operative radiotherapy schedules. METHODS AND MATERIALS: Between 1990 and 2003, 89 patients (median age 50.8 years) presenting with soft tissue sarcoma (located to the limbs for 66 of them) underwent post-conservative-surgery radiotherapy. Pathology was liposarcoma in 35 cases and 54 others tumors. Tumors grades (FNCLCC classification) were 1, 2, 3 or unknown in 29, 32, 19 and 9 cases, respectively. Surgery was considered as complete in 68 patients. Irradiation was normofractionated (NF) in 62 cases, hyperfractionated (BF) in 19 cases and hypofractionated (HF) in 8 cases. For all the patients, median delivered dose was 61 Gy [34-76 Gy]. RESULTS: Median follow-up of alive patients was 73,8 months [3-184]. Five-year local control (LC) and overall survival (OS) rates were 85.5 and 71.2% respectively. According to multifactorial analysis, favourable prognostic factors were for local control, complete surgery (P=0.0075) and for overall survival, complete surgery (P=0.0267), grade 1 tumor (P=0.012) and absence of distant recurrence (P=0.0488). There was no statistical evidence of difference for the five-year LC and OS rates between the patients who received NF, BF or HF. There were few complications and there were comparable in the three groups. CONCLUSIONS: This retrospective serie showed similar results for all the schedules. There is no evidence to recommend bifractionation. Hypofractionation should be used only in selected patients with poor performans status.

Towards a virtual fruit focusing on quality: modelling features and potential uses.

The fruit is a hierarchically organized organ composed of cells from different tissues. Its quality, defined by traits such as fruit size and composition, is the result of a complex chain of biological processes. These processes involve exchanges (transpiration, respiration, photosynthesis, phloem and xylem fluxes, and ethylene emission) between the fruit and its environment (atmosphere or plant), tissue differentiation, and cell functioning (division, endoreduplication, expansion, metabolic transformations, and vacuolar storage). In order to progress in our understanding of quality development, it is necessary to analyse the fruit as a system, in which processes interact. In this case, a process-based modelling approach is particularly powerful. Such a modelling approach is proposed to develop a future 'virtual fruit' model. The value of a virtual fruit for agronomists and geneticists is also discussed.

[Rituximab induced remission of pemphigus vulgaris: 2 cases]. / Pemphigus vulgaire évolutif sous corticoïdes et immunosuppresseurs: rémission sous rituximab. Deux observations.

INTRODUCTION: Pemphigus vulgaris frequently requires corticoids and immuno-suppressive drugs. The disease and the side effects of the drugs severely affect the quality of life, and sometime the vital prognosis of the patients. Other treatments than corticosteroids and immunosuppressive drugs are needed. EXEGESIS: We report 2 additional cases of pemphigus vulgaris uncontrolled by corticoids and immuno-suppressive drugs that responded spectacularly to rituximab. One patient had a recently onset disease, that was active despite 1,5 mg/kg/day prednisone and 1,5 g/day mycophenolate. She had a complete remission during 15 months after rituximab treatment. At relapse, another rituximab cycle led to a prompt remission. The other patient had longstanding pemphigus vulgaris complicated by cutaneous infections on prednisone (20 mg/d), immunosuppressive drugs and intravenous immune globulins. She had a prompt and complete remission after rituximab. CONCLUSION: Rituximab seems to be a promising drug for refractory pemphigus vulgaris. The benefit to risk ratio of this drug in this new indication must be precisely documented.

Combined general-epidural anesthesia decreases the desflurane requirement for equivalent A-line ARX index in colorectal surgery.

BACKGROUND: The present study used the A-line ARX index, derived from auditory evoked potential measurements, to examine the effect of epidural lidocaine on the end-tidal concentration of desflurane during general anesthesia. METHODS: Thirty ASA I-II patients scheduled for elective colorectal surgery were included and randomized, in a double-blinded fashion, to receive general anesthesia, and 15 ml of either 2% lidocaine (group GE, n=15) or normal saline (group GS, n=15) was administered epidurally with a maintenance infusion rate of 6 ml h-1. After a 10-min high-flow oxygen wash-in period, desflurane was titrated to a target A-line ARX index (AAI) of 20+/-5. RESULTS: Epidural lidocaine reduced the end-tidal concentration of desflurane required to maintain an adequate clinical effect by 42% compared to general anesthesia alone (2.6% vs. 4.5%, respectively; P<0.001). The initial mean value of AAI was 87.8 (range 78-99) in group GE and 88.13 (79-99) in group GS before general anesthesia induction, the AAI values were approximately 19.7 (15-25) in group GE and 20.2 (16-25) in group GS during anesthesia maintenance, and returned to 84.53 (77-98) in group GE and 86.87 (79-98) in group GS when the patients regained consciousness in the recovery room. No statistical difference in the AAI values was observed either before, during, or after emergence of anesthesia. No patient reported intraoperative awareness. CONCLUSIONS: Lower-than-expected concentrations of volatile anesthetics are sufficient to maintain appropriate a clinical anesthesia effect during combined general-epidural anesthesia under auditory-evoked potential monitoring.

Development of a new state-of-the-art beamline optimized for monochromatic single-crystal and powder X-ray diffraction under extreme conditions at the ESRF.

A new state-of-the art synchrotron beamline fully optimized for monochromatic X-ray diffraction at high pressure and high (or low) temperature is presented. In comparison with the old high-pressure beamline ID30, this new beamline exhibits outstanding performance in terms of photon flux and focusing capabilities. The main components of this new instrument will be described in detail and compared with the performance of beamline ID30. In particular, the choices in terms of X-ray source, X-ray optics, sample environment and detectors are discussed. The first results of the beamline commissioning are presented.

Comparative value of tumour grade, hormonal receptors, Ki-67, HER-2 and topoisomerase II alpha status as predictive markers in breast cancer patients treated with neoadjuvant anthracycline-based chemotherapy.

The aim of this study was to evaluate the predictive value of five different biological factors in breast cancer patients treated with neoadjuvant anthracycline-based chemotherapy: (1) tumour grade scored according to the Elston-Ellis classification, (2) hormonal receptor (HR) status; (3) tumour cell proliferation evaluated by Ki-67 staining, (4) HER-2 and topoisomerase II alpha (TopoIIalpha) expression evaluated by immunohistochemistry (IHC), (5) HER-2 and TopoIIalpha amplification evaluated by real-time polymerase chain reaction (PCR). 119 patients with operable breast cancer were treated with six cycles of FEC (100 5-fluorouracil (5-FU) 500 mg/m2, Epirubicin 100 mg/m2, Cyclophosphamide 500 mg/m2). Tumour response was assessed clinically and by computed tomography (CT) scan, then by pathological assessment. The clinical overall response (OR) was 80%, with 19% of complete responders (CR). The radiological OR was 71%, with 16% of CR. A pathological CR was demonstrated in 13% of the patients according to the Sataloff classification. In the multivariate analysis, the absence of HR expression and Ki-67 > or = 20% were predictive for a clinical CR. A high tumour grade was predictive for a pathological CR. Overexpression or amplification of HER2 or Topollcalpha were not predictive of response.

Do genetic make-up and growth manipulation affect tomato fruit size by cell number, or cell size and DNA endoreduplication?

This work investigated the link between genetic and developmental controls of fruit size and composition. On two isogenic lines (CF12-C and CF14-L), differing by fruit weight and sugar content quantitative trait loci (QTLs) identified previously, basal and tip fruits were characterized at anthesis and at maturity through their growth, dry matter and sugar content, number and size of cells and nuclei DNA content. The influence of competition was assessed by removing either basal or tip ovaries at anthesis. On an intact inflorescence, CF12-C fruits grew less than CF14-L fruits, with 1.67 fewer cell layers and similar cell size, suggesting that genes controlling cell division may be responsible for this fruit size variation. Truss thinning masked the QTL effect on fruit size, mainly by reducing the difference in cell number between the two lines and by promoting cell expansion in tip fruits, so that fruit growth was similar at both positions and for both lines. Thus, in these lines, cell number exerts a control on final fruit size only when there is competition among fruits. Different responses of basal and tip fruits after flower removal suggested that this treatment induced changes in hormonal relationships within the truss. No fixed relationship between DNA endoreduplication and cell size was found, as while cell size and dry matter and sugar contents differed with tomato lines, fruit position and truss size, endoreduplication patterns were the same. CF12-C fruits had a higher dry matter (+0.3% of fresh weight) and carbohydrates (+8% of dry matter) content than CF14-L fruits. The percentage dry matter was independent of truss size but decreased slightly from basal to tip fruits.

High-dose, single-agent irinotecan as first-line therapy in the treatment of metastatic colorectal cancer.

PURPOSE: The efficacy and safety of single-agent, high-dose irinotecan (CPT-11, Campto) 500 mg/m(2) every 3 weeks were investigated as first-line treatment for advanced colorectal cancer (CRC). PATIENTS AND METHODS: Patients were enrolled into the study to receive a first cycle of therapy with irinotecan at a dose of 350 mg/m(2) every 3 weeks, which could be escalated to 500 mg/m(2) for the second and subsequent cycles depending on toxicity. Efficacy, safety and pharmacokinetics were determined in the intent to treat (ITT) population and the high-dose population (i.e. patients who had received at least three cycles of irinotecan, the second and third at 500 mg/m(2)). RESULTS: Of 49 patients enrolled into the study (ITT population), 31 (63%) received at least three cycles of treatment with cycles 2 and 3 at an irinotecan dose of 500 mg/m(2) (the high-dose population). The response rates (RR) for the ITT and high-dose populations were 24.5% and 35.5%, respectively. The main grade 3/4 toxicities per cycle in the ITT and high-dose populations were neutropenia 22% and 17%, febrile neutropenia 5% and 3%, and diarrhoea 12% and 7%, respectively. The pharmacokinetics of irinotecan and its metabolite SN-38 were investigated in 31 patients in cycle 1 and 22 patients in cycle 2. Irinotecan clearance and SN-38 exposure were not sufficiently correlated with toxicity in cycle 1 to identify patients for dose increase in subsequent cycles. The exposure to irinotecan and SN-38 increased in proportion to dose from 350 to 500 mg/m(2). CONCLUSION: These results suggest that high-dose irinotecan can be safely administered as first-line monotherapy to approximately two-thirds of patients who present with advanced CRC following a selective first cycle.

Multicentre phase II study of oxaliplatin as a single-agent in cisplatin/carboplatin +/- taxane-pretreated ovarian cancer patients.

BACKGROUND: This multicentre phase II open-label study evaluated safety and antitumour activity of oxaliplatin in cisplatin or carboplatin (cis/carboplatin) +/- taxane-pretreated advanced ovarian cancer (AOC) patients. PATIENTS AND METHODS: Forty-eight patients received oxaliplatin 130 mg/M2 intravenously every 3 weeks, 94% having a performance status (PS) 0-1. All were pretreated with cis/carboplatin and 21 (44%) with paclitaxel. The median number of involved organs was two, 18 (38%) had liver metastasis, 23 (48%) were platinum-resistant and 14 (29%) were taxane-resistant. Forty-two patients were evaluable for a response, 18 (43%) were platinum-resistant and 11 (26%) were taxane-resistant. RESULTS: A total of 253 cycles was administered (median: 5.5/patient). Median cumulative oxaliplatin dose was 666 mg/m2. National Cancer Institute-Common Toxicity Criteria toxicity analysis showed that seven patients (15%) had grade 3/4 thrombocytopenia, two patients (4%) had grade 3 neutropenia, and one patient had grade 3 anaemia. Eleven patients (23%) experienced grade 3 neurosensory toxicity. Of the 29 patients with peripheral neuropathy at the end of treatment, 55% had recovered or improved 1 month later. Eleven objective responses (two complete) were obtained in the 42 evaluable patients [ORR 26%, 95% confidence interval (CI) 14% to 42%], with 10/24 (42%, 95% CI 22% to 63%) in platinum-sensitive, and 1 of 18 (5.6%, 95% CI 0% to 27%) in platinum-resistant patients. Median response duration was 9.2 months (95% CI 6.6% to 11.8%), and median progression-free and overall survival in all treated patients were 4.3 months (95% CI 3.0% to 5.7%) and 15.0 months (95% CI 11.1% to 18.8%), respectively. CONCLUSION: Oxaliplatin has a good safety profile and is active in cis/carboplatin +/- paclitaxel-pretreated AOC patients.