Systematic dosimetric evaluation of risk of osteoradionecrosis (DERO): First results of dose reporting for preventing teeth osteoradionecrosis after head and neck irradiation.

PURPOSE: OsteoRadioNecrosis (ORN) is a late complication of radiation for head and neck cancer. Predicting ORN is a major challenge. We developed DERO (Dosimetric Evaluation of Risk of ORN), a semi-automatic tool which reports doses delivered to tooth-bearing sectors, to guide post-therapeutic dental care. We present the method and the first results of a 125-patient prospective cohort. MATERIAL AND METHODS: Dosimetric data of patients treated with IMRT for head and neck cancer were prospectively segmented to the DERO algorithm. Four arches corresponding to 8-tooth sectors were semi-automatically generated. Thirty-two cylindrical Regions Of Interest (ROI) corresponding to each tooth and surrounding periodontium were created by linear interpolation. Mean doses (Dmean) of ROI were extracted and included in a database, along with data about primary tumor site, laterality and dose values from organs at risk. Dmean to tooth sectors were computed for molar sectors, (teeth X5 to X8) and anterior sectors (teeth X1 to X4). An individual dose map was generated and delivered to patients and dentists. RESULTS: Dosimetric data from 125 patients treated with Tomotherapy® were prospectively collected and analyzed: 9 parotid tumors (PA), 41 Sub-Hyoid tumors (larynx, hypopharynx) (SH), 43 Oropharynx tumors (OR), 32 Oral Cavity tumors (OC). Irradiation was unilateral for 100% of PA tumors (9), 12% of OR tumors (5) and 47% of OC tumors (15). For unilateral cervical irradiation, Dmean in ipsilateral molar sectors was 54Gy for OC tumors, 45Gy for OR tumors, 20Gy for PA tumors. For Oral Cavity bilateral irradiation, Dmean was high in all tooth sectors, 49 to 55Gy. For SH tumors, Dmean in molar sectors was 27Gy. A dose gradient of 10 to 20Gy was observed between molar and anterior sectors whether radiation was uni or bilateral. CONCLUSION: Mandibular molar sectors of Oropharynx and Oral Cavity tumors were exposed to high Dmean of 40 to 50Gy. On the other hand, tooth sectors received lower doses for SH radiation. The DERO tool guide post-radiation dental care with a personalized dosimetric cartography to patient. With data update and patient follow-up, we will be able to determine ORN risk after head and neck radiation.

Does anti-inflammatory drugs modify the severe odontogenic infection prognosis? A 10-year's experience.

BACKGROUND: Numerous biochemical datas support the noxious role of anti-inflammatory drugs on immune response. Those observations are often put forward for unfavorable evolution of odontogenic infection but has never been really proven in clinic. The aim of this study is to try to clarify this role based on the collection of the clinical course of odontogenic infections over a 10-year analysis period. MATERIAL AND METHODS: The investigators implemented a prospective observational study. The sample was composed of patients managed between January 2004 and December 2014 for severe odontogenic infection based on three criteria: hospital admission, intravenous antibiotic therapy, tooth extraction and collections drainage under general anesthesia. Clinical and pharmacological data were collected at admission, during hospitalization until discharged home. The population was first separated into two groups patients with or without anti-inflammatory drugs on admission, then on four groups (non-steroidal anti-inflammatory drugs, corticosteroids drugs, both and none on admission). Analysis were performed each time by univariate analysis, multivariate analysis and propensity score matching. RESULTS: Six hundred and fifty-three patients were included in the study, 329 (50%) patients report orally anti-inflammatory treatment before presenting to hospital, 50 (7.6%) received corticosteroids, 242 (37%) received NSAIDs and 37 (5.6%) both. Evolution is worsening for patients under anti-inflammatory drugs in term of hospitalization in ICU (p=0.016), number of surgeries (p=0.003), risk of tracheotomy (p=0.036), duration of hospitalization (p=0.005) and spaces involved by the infection (p<0.001). When separating patients into 4 groups, dysphonia and odynophagia are more frequent for patients under corticosteroid and NSAID (35.14%, p<0.001), mediastinal erythema is more frequent for patients under corticosteroid (16%, p=0.004), fever is more frequent for patients under NSAID (35.5%, p=0.032), pain is higher for patients under corticosteroids (p=0.024). But, in order to reduce bias, linked to factors of gravity, a regression weighted by propensity scores was performed and any group of patients is different from the others. CONCLUSIONS: Patients under anti-inflammatory drugs have more severe dental infection on admission and their complex evolution seems to be linked to the severity of infection on admission.

Are routine microbiological samplings in acute dental infections justified? Our 10-year real-life experience.

PURPOSE: Most patients with severe odontogenic infections are successfully treated with large spectrum probabilistic antibioc therapy, drainage of the collections and tooth treatment or extraction and are discharged home before antibiotic sensitivity results were available. The investigators hypothesized whether bacteriological sampling should be systematically performed in the management of patients with severe odontogenic infections. METHODS: The investigators implemented a prospective observational study. The sample was composed of patients managed between January 2004 and December 2014 for severe odontogenic infection based on three criteria: hospital admission, intravenous antibiotic therapy, tooth extraction and collections drainage under general anesthesia. The predictor variable was the results of bacteriological sampling, culture and sensitivity. The outcome variable was antibiotic therapy adaptation according to antibiotic sensitivity results. RESULTS: The sample was composed of 653 patients; 386 (59%) were male and 267 (41%) female, with a mean age of 37 years (range 18-88); 378 (58%) patients had been receiving oral antibiotics before admission to hospital, for a mean duration of 4.1 days (range 1 - 30). About 535 (81.9%) patients had swabs taken during surgery. Microorganisms were observed in 477 (89.1%) patients but in 377 (70.5%) they were polymorphic oropharyngeal flora. After culture, at least one antibiogram was obtained for 91 (17%) patients and the results led to antibiotic therapy being adapted in 23 (4.3%) patients. CONCLUSION: The results suggest that bacteriological analysis had an impact on evolution in less than 5% of patients. Future studies will focus on the patients for whom the bacteriological analysis is essential.

[Exclusive radiotherapy for a facial basal cell carcinoma with trigeminal ganglion involvement]. / Radiothérapie exclusive d'un carcinome basocellulaire de la face avec atteinte du ganglion de Gasser.

Basal cell carcinomas with symptomatic perineural invasion are rare entities. We report the case of a 60year-old man (with a grafted kidney), surgically treated in 2007 for a sclerodermiform basal cell carcinoma infiltrating the left nostril. Five years later, a painful left hemifacial hypoesthesia associated with an ulcus rodens of the nasolabial fold appeared. A biopsy confirmed a recurrence. MRI showed an enhancement of the trigeminal ganglion. The patient had a trigeminal perineural invasion secondary to a cutaneous basal cell carcinoma. He received a local intensity-modulated radiotherapy alone (70Gy in 33 sessions), administered from the skin tumour to the skull base. Three years after the end of treatment, the patient is in radiological and clinical remission, with partial recovery of the hypoesthesia. Evolution was marked by iterative corneal ulcers and decreased visual acuity. Modalities of treatment by surgery and/or radiation therapy and complications are poorly described in the literature.

Bulk and interfacial stresses in suspensions of soft and hard colloids.

We explore the influence of particle softness and internal structure on both the bulk and interfacial rheological properties of colloidal suspensions. We probe bulk stresses by conventional rheology, by measuring the flow curves, shear stress versus strain rate, for suspensions of soft, deformable microgel particles and suspensions of near hard-sphere-like silica particles. A similar behaviour is seen for both kinds of particles in suspensions at concentrations up to the random close packing volume fraction, in agreement with recent theoretical predictions for sub-micron colloids. Transient interfacial stresses are measured by analyzing the patterns formed by the interface between the suspensions and their solvent, due to a generalized Saffman-Taylor hydrodynamic instability. At odds with the bulk behaviour, we find that microgels and hard particle suspensions exhibit vastly different interfacial stress properties. We propose that this surprising behaviour results mainly from the difference in particle internal structure (polymeric network for microgels versus compact solid for the silica particles), rather than softness alone.

[Intermaxillary intraoperative fixation of mandibular fractures: arch bars or fixation screws?]. / Blocage maxillo-mandibulaire peropératoire des fractures de mandibule : arcs ou vis de blocage ?

INTRODUCTION: The gold standard management of mandibular fractures is open reduction and osteosynthesis associated with intermaxillary fixation. The use of intermaxillary fixation screws for 20 years has considerably reduced the number of intermaxillary fixation with arch bars. The aim of our review was to identify current indications and contraindications of each technique. INTERMAXILLARY FIXATION TECHNIQUES: We present a short history and compare the two techniques with recently published assets, drawbacks, and complications. DISCUSSION: The indications of intermaxillary fixation screws are uni- or bifocal fractures without or with minimal displacement. Their use is contraindicated in any other type of fracture, which should still be treated with arch bar fixation.

[Watch out for headaches at the end of a pregnancy! Do not miss an autoimmune hypositys]. / Attention aux céphalées de fin de grossesse! Ne pas méconnaître une hypophysite.

We report the case of a 21-year-old pregnant women (36 WA) presenting intensive headaches and visual disturbances. Those sellar compression symptoms have made us suppose the diagnosis of autoimmune hypophysitis. MRI has confirmed the typical aspect of symmetric enlargement of the pituitary gland with a strong and homogenous enhancement after gadolinium. This pathology associated to a high morbidity and mortality due to partial or complete deficit of the anterior pituitary hormones, shall be reminded more often.

[What is new about endometriosis?]. / Quelles nouveautés sur l'endométriose ?

Endometriosis concerns 6 to 10 % of the female population, and is responsible for severe pelvic pain and infertility. This estrogen dependant disease, is characterized by the presence of endometrial tissue outside of the uterus cavity. Although his physiopathology remains poorly understood, recent data have focused on angiogenesis, which could represent a key factor for the growing of lesions of endometriosis. New antiangiogenesis treatments represent a therapeutic hope, and have been tested in vitro or in vivo in mice. Those drugs have proven their efficacy on endometriotic lesions. Secondly, several hypothesis are discussed to explain infertility in endometriosis. In particular, a direct impact of peritoneal fluid from women with endometriosis on sperm DNA could be involved.

[What are the factors affecting fertility in 2008?]. / Quels sont les facteurs qui modifient la fertilité en 2008 ?

The number of infertile couples to be cared for in infertility centres is estimated to be between 1 to 6 %. This figure has been rising over the past years. During the 24th annual meeting of the ESHRE (European society of Human Reproduction) in Barcelona, changes in the population of infertile couples have been analysed. The major trend is an increase in women's age but also in men's age when desiring their first child. This mean rise has reached more than two years for women's age, over the past 10 years. The negative influence of the woman's age on fertility, especially after 35 years, is clearly established. However, new data in men suggest that an age higher than 35 years could be linked to an increased rate of miscarriages. The concept of preconceptionnal care in order to detect comorbidities, especially smoking, overweight and diabetes has been emphasized. Furthermore, the influence of current lifestyles on fertility, a potential role of endocrine disrupters, represent new concerns, which are in line with a policy of preventive care of infertility. Lastly, patients undergoing treatment with gonadotoxic drugs represent a 'new" population in fertility clinics. Techniques of testicular and ovarian preservation, especially frozen oocytes, must be disseminated and improved in order to prevent infertility in those patients.

Protein localization in the plant Golgi apparatus and the trans-Golgi network.

This review presents plant-specific characteristics of the Golgi apparatus and discusses their impact on retention of membrane proteins in the Golgi or the trans-Golgi network (TGN). The plant Golgi consists of distinct stacks of cisternae that actively move throughout the cytoplasm. The Golgi apparatus is a very dynamic compartment and the site for maturation of N-linked glycans. It is also a factory for complex carbohydrates that are part of the cell wall. The TGN is believed to be the site from where vacuolar proteins are sorted by receptors towards each type of vacuole. To maintain the structure and specific features of the Golgi, resident proteins ought to be maintained in the proper Golgi cisternae or in the TGN. Two families of membrane proteins will be taken as examples for Golgi/TGN retention: (i) the enzymes involved in N-glycosylation processes and (ii) a vacuolar sorting receptor. Although the number of available plant proteins localized in Golgi/TGN is low, the basis of retention appears to be shared over all kingdoms and may result from pure retention and recycling mechanisms. In this review, we will summarize the characteristics of a plant Golgi and will discuss especially their consequences on on the study of this highly dynamic structure. We then choose membrane proteins with a single transmembrane domain to illustrate the signals and mechanisms involved in plants to localize and maintain proteins in the Golgi and the TGN.

Inhibition of [3H] gamma-aminobutyric acid release from guinea-pig hippocampal synaptosomes by serotonergic agents.

We studied the effects of (m-trifluoromethyl-phenyl)piperazine (TFMPP) and quipazine on the K(+)-evoked [3H]GABA release from guinea-pig hippocampal synaptosomes loaded with [3H]GABA.TFMPP and quipazine inhibited the K(+)-evoked release of [3H]GABA dose-dependently (IC50 = 153 and 123 microM, respectively). Serotonergic antagonists such as methiothepin (0.1, 0.3 and 1 microM), ketanserin (0.1, 0.3 and 1 microM), dihydroergotamine (0.1 microM), metergoline (0.1 and 0.3 microM), methysergide (0.3 microM), propranolol (1 microM) and yohimbine (1 microM) did not significantly alter the inhibitory effect of TFMPP on [3H]GABA release suggesting that neither 5-HT1 nor 5-HT2 receptors are involved in this process. By contrast, the effect of TFMPP was diminished by selective 5-HT3 receptor antagonist: MDL 72222 (0.3 microM), tropisetron (0.3 and 1 microM), ondansetron (0.3 microM) and metoclopramide (1 microM). Tropisetron (1 microM) and ondansetron (0.3 microM) also inhibited significantly the quipazine effect whereas methiothepin (1 microM), dihydroergotamine (0.1 microM), yohimbine (1 microM) and ketanserin (1 microM) were ineffective on the quipazine inhibition of [3H]GABA release. Our results show a serotonergic modulatory effect on the K(+)-evoked [3H]GABA release from guinea-pig hippocampal synaptosomes by receptors which are neither 5-HT1, 5-HT2 or 5-HT4. They appear to be pharmacologically related to the 5-HT3 type but different from the 5-HT3 ionic channel receptors.

Antagonism by antidepressant drugs of the inhibitory effect of trifluoromethylphenylpiperazine (TFMPP) on [3H]acetylcholine release in rat or guinea-pig hippocampal synaptosomes.

The effects of antidepressant drugs on the m-trifluoromethylphenylpiperazine (TFMPP)-induced inhibition of K(+)-evoked [3H]acetylcholine (3H-ACh) release were studied in rat or guinea-pig hippocampal synaptosomes. The serotonergic agonist TFMPP dose-dependently inhibited the K(+)-evoked release of 3H-ACh in rat hippocampus (IC50 = 53 microM). Chlorimipramine (5-500 nM), a typical tricyclic antidepressant, and minaprine (1-100 nM), an atypical antidepressant drug, partially antagonized the effect of TFMPP on 3H-ACh release in a dose-dependent manner. Other antidepressants (imipramine, citalopram, indalpine, fluoxetine, fluvoxamine, oxaprotiline, mianserine, nomifensine), at concentrations ranging from 10 to 500 nM, produced similar effects. Drugs with no antidepressant effect, such as chlorpromazine, clobazam, and cocaine (50, 100 and 500 nM), were without significant influence on the TFMPP effect. In guinea-pig hippocampal synaptosomes, minaprine (50 nM) also reduced the TFMPP-induced inhibition of 3H-ACh release, whilst clobazam (50 nM) was inactive. These results suggest that antidepressant drugs interact in vitro with heterologous serotonergic presynaptic receptors on cholinergic nerve terminals in rat and guinea-pig hippocampus.

The inhibitory effect of trifluoromethylphenylpiperazine on [3H]acetylcholine release in guinea pig hippocampal synaptosomes is mediated by a 5-hydroxytryptamine1 receptor distinct from 1A, 1B, and 1C subtypes.

The effect of the serotonergic receptor agonist 1-(m-trifluoromethylphenyl)piperazine (TFMPP) was studied on the K(+)-evoked [3H]acetylcholine [( 3H]ACh) release from guinea pig hippocampal synaptosomes loaded with [3H]choline. TFMPP (5-1,000 microM) inhibited the evoked ACh release in a dose-dependent manner (IC50 = 81.8 microM). The inhibitory effect of TFMPP was mimicked by CGS-12066B (10, 30, and 100 microM), a 5-hydroxytryptamine1B (5-HT1B)/5-HT1D receptor agonist; 1-(m-chlorophenyl)piperazine (100 microM), a 5-HT1C/5-HT1B receptor agonist; and 5-carboxamidotryptamine (10 microM), a nonselective 5-HT1 receptor agonist. 8-Hydroxy-2-(di-n-propylamino)tetralin (10 and 100 microM), a 5-HT1A receptor agonist, and quipazine (10 and 100 microM), a 5-HT2 receptor agonist, did not have any significant effect. Serotonergic antagonists, such as dihydroergotamine (0.1 and 1 microM), metergoline (0.1 microM), methysergide (0.5 and 1 microM), or yohimbine (1 and 10 microM), blocked the TFMPP effect dose-dependently. In contrast, methiotepine (0.3 and 1 microM), propranolol (1 microM), ketanserin (0.1 microM), mesulergine (0.1 microM), ICS 205930 (0.1 and 1 microM), and spiroperidol (1 and 7 microM) did not affect the TFMPP-induced inhibition of the evoked ACh release. These data suggest that, in guinea pig hippocampus, the K(+)-evoked ACh release is modulated by a 5-HT1 receptor distinct from the 5-HT1A, 5-HT1B, and 5-HT1C subtypes.