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International audience; Background: To describe the characteristics of the largest European study of MEC of salivary glands and to determine the prognostic factors for overall and disease free survival.Patients and methods: Patients with MEC were prospectively included in the Réseau d'Expertise Français sur les Cancers ORL Rares (REFCOR, French Network of Rare Head and Neck Tumors) database between 2009 and 2015.Results: A total of 292 patients were included. Tumors were classified as low grade in 175 cases (60%), intermediate in 39 (13%) and high grade in 78 (27%). Median follow-up was 26 months. The 5-year OS and DFS rates were respectively 83% and 69%. In multivariate analysis, age (p = 0.004), diabetes (p = 0.02) and advanced stage (p = 0.03) were found to have a significant negative impact on OS. Diabetes (p = 0.001), alcohol consumption (p = 0.003) and advanced stage (p = 0.001) were found to have a significant negative impact on DFS. Compare to low grade, high grade tended to have a negative impact on OS (p = 0.05) and had a significant effect on DFS (0.002) while intermediate grade had no significant influence on survival. The surgical treatment had a positive impact on both OS (p = 0.00005) and DFS (p = 0.0005). Postoperative radiotherapy had no impact in multivariate analysis.Conclusion: Advanced clinical stage, high grade tumor, high age, the impossibility of carrying out a complete surgical resection, and diabetes are the main prognostic factors in this prospective series of patients with MEC. Such findings open new research perspectives on the influence of these components on initial patient care.

Resume Objectifs Evaluer l’utilisation de la valeur de p et des termes « significatif », « non significatif » et « suggestif » dans le resume des articles scientifiques des Annales Europeennes d’Otorhinolaryngologie et de Pathologie Cervico-faciale. Materiel et methodes Revue systematique des articles scientifiques, consecutivement soumis et acceptes au decours de la periode janvier 2016 - fevier 2019. Objectif principal Description de l’utilisation de la valeur de p et des termes « significatif », « non significatif » et « suggestif » dans le resume. Objectifs secondaires Etude analytique recherchant : (i) un lien statistique entre la mention d’une valeur de p dans le resume et les caracteristiques des auteurs et des sujets traites, (ii) une utilisation inadaptee des termes « significatif », « non significatif » et « suggestif » (compte-tenu des valeurs de p mentionnees) et un lien statistique avec les caracteristiques des auteurs et des sujets traites. Resultats Au total, 91 articles etaient inclus. La valeur de p et les termes « significatif », « non significatif », « suggestif » etaient mentionnes, respectivement, dans 35,1 %, 41,7 %, 10,9 % et 0 % des resumes. La mention d’une valeur de p n’etait pas statistiquement liee aux caracteristiques des auteurs et des sujets traites. Une utilisation inadaptee, detaillee dans le corps de l’article, des termes « significatif », « non significatif » et « suggestif » etait notee dans 57,1, % des resumes avec 30,7 % de sur evaluation et 25,2 % de sous evaluation des resultats, sans lien statistique avec les caracteristiques des auteurs et des sujets traites. Conclusion Auteurs, redacteurs et relecteurs doivent preter plus d’attention au « spin » qui correspond a l’utilisation inappropriee des termes « significatif », « non significatif », « suggestif » dans le resume des articles soumis aux Annales Europeennes d’Otorhinolaryngologie et de Pathologie Cervico-faciale, afin d’ameliorer la rigueur, la qualite et la valeur de l’information scientifique fournie aux lecteurs.

International audience; Les leucoplasies et dysplasies des cordes vocales sont regroupées sous le nom de lésions épithéliales hyperplasiques du larynx « LEHL ». L’évaluation initiale et le suivi repose sur l’examen optique bénéficiant des apports de l’image en haute définition, de la stroboscopie et du Narrow Band Imaging. Le diagnostic est anatomopathologique avec la nouvelle classification OMS 2017 qui est simplifiée bas grade et haut grade. Statistiquement, le risque de cancérisation est de 20 % dans les 5 à 10 ans qui suivent le diagnostic initial, d’autant plus chez l’homme âgé de plus de 65 ans, mais ce risque est peu prévisible pour un patient donné. Les voies de recherche reposent sur l’étude des critères génétiques de la lésion et la caractérisation du microenvironnement tumoral. Le traitement des LEHL est exclusivement microchirurgical. Son étendue en profondeur est ajustée à l’infiltration de la lésion. Il s’agit d’une maladie chronique qui nécessite un suivi au long cours, qui peut être rendu difficile par la dysphonie résiduelle et les séquelles cordales des microchirurgies antérieures. Ces séquelles chirurgicales doivent être limitées autant que faire se peut par une maitrise du geste microchirurgical et de ses indications. En cas de séquelles, l’utilisation de biomatériaux tels la graisse autologue et l’acide hyaluronique peuvent avoir leur place. Les techniques de bio-ingénierie tissulaire annoncent des résultats prometteurs.

International audience; Vocal-fold leukoplakia and dysplasia are together designated "epithelial hyperplastic laryngeal lesions" (EHLL). Work-up and follow-up are founded on optical examination with high-definition imaging, stroboscopy and narrow-band imaging. Diagnosis is based on pathology, using the new 2017 WHO classification, dichotomizing "low grade" and "high grade". Statistically, the risk of cancerous progression is 20% within 5 to 10 years of diagnosis, or more in over-65 year-old males; risk for any given patient, however, is unpredictable. Research focuses on the genetic criteria of the lesion and characterization of the tumoral microenvironment. Treatment is exclusively microsurgical. Resection depth is adjusted according to infiltration. EHLL is a chronic disease, necessitating long-term follow-up, which may be hampered by residual dysphonia and surgical sequelae in the vocal folds. Sequelae need to be minimized by good mastery of microsurgical technique and indications. When they occur, biomaterials such as autologous fat and hyaluronic acid can be useful. Tissue bio-engineering is a promising field.

Hyperinsulinemic hypoglycemia syndrome (HIHG) is a rare complication of roux-en-Y gastric bypass surgery. The pathology is associated with an excessive function of pancreatic beta-cells, and requires pancreas resection in patients that are recalcitrant to nutritional and pharmacological interventions. The exact prevalence is not clearly understood and the underlying mechanisms not yet fully characterized. We herein sought to perform histological and molecular examination of pancreatic sections obtained from a patient who developed HIHG as a complication of gastric bypass compared to 3 weight-matched controls. We studied markers of cellular replication and beta-cell differentiation by immunohistochemistry and immunofluorescence. HIHG after gastric bypass was characterized by a profound increase in beta-cell mass. Cellular proliferation was increased in islets and ducts compared to controls, suggesting unrestrained proliferation in HIHG. We also detected beta-cell differentiation markers in duct cells and occasional duct cells displaying both insulin and glucagon immunoreactivity. These histological observations suggest that beta-cell differentiation from ductal progenitor cells could also underly beta-cell mass expansion in HIHG. Altogether, our results can be construed to demonstrate that HIHG after gastric bypass is characterized by abnormal beta-cell mass expansion, resulting from both unrestrained beta-cell replication and neogenesis.

La disnea laringea es una urgencia otorrinolaringologica frecuente desde el punto de vista tanto terapeutico (restitucion de la via aerea) como diagnostico. Es el reflejo de un aumento de las resistencias al flujo de aire en la via respiratoria al nivel de la laringe, organo de pequeno calibre. El diagnostico positivo se realiza por la demostracion de la triada sintomatica: bradipnea inspiratoria con tiraje y ruido inspiratorio laringeo (cornaje, estridor), lo que permite distinguirla de otras disneas. El diagnostico etiologico se basa esencialmente en el contexto (traumatico, infeccioso, intoxicacion, mixto) y las caracteristicas de aparicion de la disnea (aguda, progresiva). La etiologia es variada, organica o funcional, intrinseca o extrinseca, al nivel de una o de varias regiones de la laringe (subglotis, glotis y/o supraglotis). En caso de disnea laringea aguda, la busqueda de signos de gravedad se realiza a la vez que la de las circunstancias de aparicion. De este modo, los distintos cuadros caracteristicos dan lugar a un diagnostico y un tratamiento practico en funcion del grado de urgencia. El diagnostico etiologico se respalda con la exploracion fisica ORL, en la que la exploracion nasofibroendoscopica puede completarse con una endoscopia de las vias aerodigestivas superiores y pruebas complementarias en funcion de las etiologias sospechadas y del contexto.

International audience; BACKGROUND:Head and neck mucosal melanoma (HNMM) is aggressive and rare, with a poor prognosis because of its high metastatic potential. The two main subtypes are sinonasal (sinonasal mucosal melanoma [SNMM]) and oral cavity (oral cavity mucosal melanoma [OCMM]). Consensual therapeutic guidelines considering the primary tumour site and tumour-node-metastasis (TNM) stage are not well established.MATERIAL & METHODS:Patients with HNMM from the prospective national French Rare Head and Neck Cancer Expert Network database between 2000 and 2017 were included. Clinical characteristics, treatment modalities, outcomes and prognostic factors were analysed.RESULTS:In total, 314 patients were included. The 5-year overall survival (OS) and progression-free survival (PFS) rates were 49.4% and 24.7%, respectively, in the surgery group; no long-term survivors were observed when surgery was not feasible. Moreover, even after surgery, a high recurrence rate was reported with a median PFS of 22 months. In multivariate analysis, Union for International Cancer Control (UICC) stage and tumour site correlated with PFS and OS. Postoperative radiotherapy (PORT) improved the PFS but not OS in patients with small (T3) SNMM and OCMM tumours. Nodal involvement was more frequent in patients with OCMM (p < 10-4), although, as in SNMM, it was not a significant prognostic predictor.CONCLUSION:Even early HNMM was associated with poor oncologic outcomes due to distant metastases despite surgical resection with clear margins. Lymph node metastases had no impact on the prognosis, suggesting treatment de-escalation in cervical node management. PORT might be useful for local control.

Resume Objectifs Evaluer les defauts, le taux d’acceptation et les raisons du rejet des cas cliniques soumis pour publication aux European Annals of Otorhinolaryngology Head & Neck Diseases . Materiel et methodes Etude prospective realisee a partir de la relecture de 118 cas cliniques provenant de 29 pays consecutivement soumis aux European Annals of Otorhinolaryngology Head & Neck Diseases au decours de la periode 01/09/2014–31/09/2015. Resultats Les principaux defauts, notes dans 74,5 % des cas, lors de la relecture etaient l’absence d’originalite (plus de 15 cas cliniques identiques au cas soumis deja publies dans la litterature medicale) et l’absence d’apport de donnees nouvelles a la litterature medicale scientifique publiee sur le sujet. Apres relecture, 5 % des cas cliniques etaient acceptes, 7 % n’etaient pas re-adresses a la revue par les auteurs et 88 % etaient rejetes. En analyse monovariee, aucun lien statistique n’apparaissait entre l’acceptation ou le refus des cas cliniques et les variables analysees. Le delai pour accepter ou non l’article soumis a la revue variait de 1 a 7 mois avec une mediane a 1 mois. Au sein de 104 cas cliniques rejetes, les editeurs proposaient aux auteurs de re-soumettre leur travail dans les rubriques « lettre a l’editeur » ou « quel est votre diagnostic ? », dans 16,3 % des cas (17/104). Quinze de ces dix-sept travaux etaient re-adresses et dix (66,6 %) d’entre eux etaient acceptes apres relecture. Conclusion Le comite editorial des European Annals of Otorhinolaryngology Head & Neck Diseases espere que les donnees presentees ainsi que l’analyse de la litterature consacree a ce sujet fourniront aux auteurs une trame qui leur permettra d’eviter les erreurs qui conduisent au rejet de leur article et facilitera la publication rapide des cas cliniques qu’ils soumettront a notre revue, dans le futur.

Objectives To evaluate characteristics, suggested modifications and reasons for rejection in scientific articles submitted for publication in the European Annals of Otorhinolaryngology, Head and Neck Diseases. Materials and methods A prospective study analyzed the flaws noted by reviewers in 52 scientific articles submitted to the European Annals of Otorhinolaryngology, Head and Neck Diseases between August 31, 2014 and February 28, 2015. Results Fifteen flaws concerning content and 7 concerning form were identified. In more than 25% of submissions, major flaws were noted: purely descriptive paper; lack of contribution to existing state of knowledge; failure to define a clear study objective and/or analyze the impact of major variables; poorly structured Materials and methods section, lacking description of study population, objective and/or variables; lack of or inappropriate statistical analysis; Introduction verbose and/or misrepresenting the literature; excessively heterogeneous and/or poorly described study population; imprecise discussion, straying from the point, overstating the significance of results and/or introducing new results not mentioned in the Results section; description of the study population placed in the Results section instead of under Materials and methods; serious mistakes of syntax, spelling and/or tense; and failure to follow the Instructions to Authors. After review, 21.1% of articles were published, 65.3% rejected and 13.4% non-resubmitted within 3 months of review. On univariate analysis, the only variable increasing the percentage of articles accepted was the topic not being devoted to head and neck surgery (P = 0.03). Conclusion These results document the excessive flaw rate still to be found in manuscripts and demonstrate the continuing need for authors to master and implement the rules of scientific medical writing.

Resume Objectifs Evaluer les caracteristiques, les defauts et les raisons du rejet des articles scientifiques soumis pour publication aux European Annals of Otorhinolaryngology, Head & Neck Diseases. Materiel et methodes Etude prospective realisee a partir de la relecture de 52 articles scientifiques soumis aux European Annals of Otorhinolaryngology, Head & Neck Diseases au decours de la periode 31/08/2014–28/02/2015. Resultats Quinze types de defauts ayant trait au fond et sept ayant trait a la forme de l’article etaient identifies. Dans plus de 25 % des cas un defaut majeur (caractere purement descriptif de l’etude, absence d’apport aux donnees et publications deja existantes, non-definition d’un but precis et/ou absence d’etude de l’impact de variables majeures, chapitre materiel et methodes mal structure ne presentant pas la population etudiee et/ou le but de l’etude et/ou les variables analysees, absence d’analyse statistique et/ou tests statistiques incorrects, introduction vague, trop longue et/ou ne refletant pas la litterature, population analysee trop heterogene et/ou mal definie, discussion vague, hors sujet, surevaluant les resultats, sans rapport avec le but de l’etude ou les resultats et/ou presentant de nouveaux resultats, description de la population etudiee placee dans le chapitre resultat et non dans le chapitre materiel et methodes, existence de problemes majeurs de syntaxe, d’orthographe et/ou de temps des verbes, non-respect des conseils aux auteurs de la revue) etait note. Apres relecture, 21,1 % des articles etaient acceptes, 65,3 % etaient rejetes et 13,4 % n’etaient pas re-adresses a la revue par les auteurs trois mois apres la relecture. En analyse monovariee, seule la thematique non cervico-faciale augmentait le pourcentage d’articles acceptes (p = 0,03). Conclusion Cette etude souligne que le nombre d’auteurs qui meconnaissent et/ou ne respectent pas les regles de la redaction d’un article scientifique reste eleve.

Background: Burn injury represents a significant public health problem worldwide. More than in any other injury, the inflammation and catabolism associated with severe burns can exacerbate nutrient deficiencies resulting in impaired immune function and increased risk of developing infection, organ dysfunction and death. Consequently, over the last few decades numerous trials have evaluated the impact of different nutritional strategies in severe burn injury. Glutamine is of particular interest, as it appears vital for a number of key stress-response pathways in serious illness. The purpose of the current manuscript is to provide the rationale and protocol for a large clinical trial of supplemental enteral glutamine in 2700 severe burn-injured patients. Methods: We propose a multicentre, double-blind, pragmatic, randomized, clinical trial involving 80 tertiary intensive care unit (ICU) burn centres worldwide. We aim to enrol patients with deep second- and/or third-degree burns at moderate or high risk for death. We will exclude patients admitted > 72 h before screening and patients with advanced liver and kidney disease. The study intervention consists of enteral glutamine 0.5 g/kg/day vs. isocaloric maltodextran control delivered enterally. Primary outcome will be six-month mortality. Key secondary outcomes include time to discharge alive from hospital, ICU and hospital mortality, length of stay and health-related quality of life at six months. Significance: This study will be the first large international multicentre trial examining the effects of glutamine in burn patients. Negative or positive, the results of this trial will inform the clinical practice of burns care worldwide. Clinicaltrials.gov ID #NCT00985205, Lay Summary Patients with severe burns need to recover in a hospital burn unit for a long time and are at high risk of developing infections and dying. Proper nutrition and certain nutrients may improve survival in these patients and shorten their stay in the burn unit. Glutamine is a building block of protein that is normally made in the body and is found in different foods we eat. It is of great interest because it has several beneficial effects on the body during serious illness, such as with burn injury. In this study, we will look at the effect of glutamine supplementation on survival and time spent in hospital. A total of 80 burn units around the world will enrol 2700 patients with 2nd or 3rd degree burns over 4 years. Patients will receive either glutamine powder or a placebo through a feeding tube or mixed with food, from admission to the burn unit, until a week after the burn wound has healed. The main outcome for this study is survival at 6 months. Other outcomes include the time taken to be discharged from hospital alive and duration of stay in the burn unit. This study will be the first large international multicentre trial examining the effects of glutamine in burn patients. Glutamine may lead to better survival and less complications in burn patients, who have a devastating and disabling burn injury. If the trial is positive, the results will be used to inform how nutrition should be given to such patients worldwide.

Il monitoraggio puo essere definito dall’insieme delle tecniche che permettono di fornire al chirurgo un’informazione sulla funzione di un nervo cranico durante un intervento chirurgico. Esso e divenuto in questi ultimi anni uno strumento di aiuto nella chirurgia otorinolaringoiatrica, in particolare nella chirurgia cervicale, otologica o della base del cranio. Questa tecnica e stata inizialmente sviluppata per il monitoraggio della funzione facciale durante la chirurgia dello schwannoma vestibolare, poi si e ampliata ai settori della chirurgia dell’orecchio medio, della parotide e della tiroide. Essa permette di aiutare il chirurgo a individuare le strutture nervose, ma, soprattutto, di avvertirlo mediante un allarme ogni volta che il suo gesto e traumatizzante per il nervo. Parallelamente si sono sviluppate delle tecniche elettrofisiologiche di monitoraggio dell’attivita del nervo cocleare che, benche non scatenino un allarme in tempo reale, forniscono delle informazioni durante l’intervento sulla funzione uditiva e consentono di stabilire una prognosi sulla conservazione dell’udito al termine dell’intervento. Attraverso questo articolo, spiegheremo in dettaglio i metodi che permettono il monitoraggio motorio e sensoriale dei nervi della base del cranio, dalla loro origine fino al loro tragitto extracranico. Preciseremo le indicazioni del monitoraggio dei nervi nella chirurgia della base del cranio, in chirurgia otologica e in chirurgia cervicale, specificando i risultati attesi, ma anche e soprattutto i limiti di questi metodi, di cui il medico deve essere pienamente cosciente.

Resume Objectifs La classification histologique OMS 2005 propose de demembrer les adenocarcinomes nasosinusiens (ADK) en trois classes : intestinal type adenocarcinomas (ITAC), les bas grades et les hauts grades. Le but de cette etude etait de verifier la pertinence de ce classement sur le pronostic de patients traites pour ADK. Patients et methodes Tous les dossiers de patients traites consecutivement dans le service d’ORL du CHU de Montpellier pour ADK entre 1980 et 2003 ont ete retrospectivement revus. Chaque cas a beneficie d’une relecture anatomopathologique en se basant sur l’immunohistochimie conformement a la classification OMS 2005 en etudiant un panel de marqueurs : cytokeratine 7 (CK7), cytokeratine 20 (CK20), Villin, CDX2, EGFR. Les donnees epidemiologiques, les modalites de traitement et le suivi ont ete etudies. Les probabilites de survie ont ete calculees par la methode de Kaplan-Meier et la comparaison des courbes de survie par le test de log-rank. Resultats Soixante-deux dossiers ont ete colliges. Douze cas ont ete reclasses en carcinomes adenoides kystiques et exclus de l’etude. Sur les 50 cas restants, il y avait 36 ITAC, quatre ADK de bas grade et dix ADK de haut grade. Pour l’ensemble des ADK, la survie globale a cinq ans et sans recidive etaient respectivement de 64 et 52 %. L’analyse des trois sous-groupes d’ADK montre une survie globale a cinq ans de 72,2 % pour les ITAC, 100 % pour les bas grades et 20 % pour les hauts grades avec une difference significative (p = 0,044). Cette distinction sur le plan immunohistochimique est principalement basee sur l’expression de CK20 retrouvee dans 98 % des ITAC et absente dans les bas grades et les hauts grades. Conclusion La classification OMS 2005 des ADK nasosinusiens revet un interet pronostique en montrant une difference de profil evolutif entre les ITAC, les ADK de bas grade et de haut grade. De plus larges etudes sont souhaitables afin d’etudier le pronostic des differents sous-types d’ITAC.

Background Many authors have studied adult’s larynx modelization, but the mechanisms of newborn’s voice production have very rarely been investigated. After validating a numerical model with acoustic data, studies were performed on larynges of human fetuses in order to validate this model with aerodynamical experiments. Material and methods Anatomical measurements were performed and a simplified numerical model was built using Fluent ® with the vocal folds in phonatory position. The results obtained are in good agreement with those obtained by laser Doppler velocimetry (LDV) and high-frame rate particle image velocimetry (HFR-PIV), on an experimental bench with excised human fetus larynges. Results It appears that computing with first cry physiological parameters leads to a model which is close to those obtained in experiments with real organs.

Le cisti della laringe e i laringoceli formano un’entita nosologica eterogenea. La componente principale di queste patologie si sviluppa a spese del ventricolo laringeo, o ventricolo di Morgani, e della sua appendice anteriore, il sacculo. Si tratta di cisti sacculari, di laringoceli, di laringomucoceli e di laringopioceli. Il secondo quadro nosologico e rappresentato dalle cisti da inclusione o da ritenzione ghiandolare, che possono coinvolgere qualsiasi piano laringeo. Infine, si possono riscontrare alcune cisti estremamente rare per l’alterazione dello sviluppo embrionale, che conduce ad anomalie della cartilagine tiroide, alla cisti foraminale e alla duplicazione cistica della laringe. La sintomatologia dipende dall’eta di insorgenza, dalla sede e dal volume della cisti e da un’eventuale sovrainfezione. Numerose cisti sono asintomatiche. Viceversa, alcuni casi sono rivelati da una dispnea acuta minacciosa in un contesto talvolta infettivo. La terapia, al di fuori dell’urgenza, si basa sulla resezione endoscopica laser o, in sua mancanza, sulla marsupializzazione. Quando e presente un contingente extralaringeo predominante, questo e aggredito per via esterna. La terapia chirurgica adeguata offre buone possibilita di guarigione, ma le recidive sono sempre possibili, imponendo, allora, la realizzazione di procedure ripetute.

Los quistes de la laringe y los laringoceles constituyen una entidad nosologica heterogenea. El componente principal de estas afecciones se desarrolla a expensas del ventriculo laringeo o ventriculo de Morgani y de su apendice anterior, el saculo. Se trata de los quistes saculares, los laringoceles, los laringomucoceles y los laringopioceles. El segundo cuadro nosologico esta constituido por los quistes de inclusion o de retencion glandular, que pueden afectar a cualquier tramo laringeo. Por ultimo, algunos quistes muy infrecuentes pueden aparecer por anomalias del desarrollo embrionario que dan lugar a malformaciones del cartilago tiroides: quiste foraminal y duplicacion quistica de la laringe. La sintomatologia depende de la edad de aparicion, de la localizacion y del volumen del quiste, asi como de una posible sobreinfeccion. Muchos quistes son asintomaticos. Por el contrario, algunos casos se ponen de manifiesto por una disnea aguda potencialmente mortal en un contexto en ocasiones infeccioso. El tratamiento, fuera de la fase urgente, consiste en la reseccion endoscopica con laser o, en su defecto, en la marsupializacion. Cuando existe un componente extralaringeo predominante, este se trata por via externa. El tratamiento quirurgico adecuado ofrece buenas posibilidades de curacion, pero las recidivas siempre son posibles, lo que obliga a realizar intervenciones repetidas.

Objective:To report a rare case of a laryngeal paraganglioma related to succinate dehydrogenase gene mutation C.Method:A case report and a review of the world literature concerning succinate dehydrogenase mutations and laryngeal paraganglioma are presented.Results:We identified a laryngeal paraganglioma in a 38-year-old woman, related to a very rare, deleterious in exon 4 of the succinate dehydrogenase mutation C. This mutation was a non-sense mutation: c.183G >A leading to p.Trp61X. No other neuroendocrine tumour was identified in this case, but a thyroid papillary carcinoma was concomitantly discovered and cured.Conclusion:To our knowledge, this is the first report in the world literature of laryngeal paraganglioma related to a succinate dehydrogenase mutation C. The case presented underlines the fact that every patient with paraganglioma should be tested for succinate dehydrogenase genetic mutations, even if a family history of paraganglioma is absent, in order to enable appropriate clinical management and to improve our knowledge of familial paraganglioma.

Background: Although there are well-recognized fluctuations in the systemic concentration of cytokines and growth factors after burn injuries, the effect on wound-healing potential in patients is not well understood. The objective of this study was to characterize the proliferation rate and response of wound and dermal fibroblasts to cytokines in burn patients compared with normal subjects. Methods: Polyvinyl alcohol sponges were implanted subcutaneously in normal subjects and burn patients soon after admission. Sponges were removed for wound fibroblast explantation after 12 days. At the same time, a small piece of skin was excised for dermal fibroblast explantation. Fibroblast proliferation was then quantified after exposure to 10% fetal bovine serum, 1% fetal bovine serum, interleukin-1, transforming growth factor-β1, or interferon-a2b. Results: Normal subjects' dermal fibroblasts (n = 7) exposed to 10% fetal bovine serum showed significantly increased proliferation relative to normal subjects' wound fibroblasts (n = 3) (p < 0.0005), burn patients' dermal fibroblasts (n = 5) (p < 0.05), and burn patients' wound fibroblasts (n = 5) (p < 0.0001). Burn patients' dermal fibroblast proliferation was also significantly augmented relative to burn patients' wound fibroblasts (p < 0.005); however, there was no significant difference between the two wound fibroblast types. Proliferation of burn subjects' fibroblasts was significantly enhanced with the addition of interleukin-1 and significantly decreased for dermal fibroblasts with interferon-a2b. A significant elevation of proliferation with transforming growth factor-β1 was seen only with burn patients' dermal fibroblasts. Conclusions: The data suggest that systemic mediators markedly alter the proliferation potential of dermal fibroblasts but not of wound fibroblasts. However, the wound environment substantially alters both the proliferation rate and the responsiveness of fibroblasts to cytokines. Thus, the data support the value of using wound fibroblasts during preliminary in vitro experiments to investigate wound-healing modification by cytokine manipulation. (Plast. Reconstr. Surg.

Opioid drugs reportedly regulate the immune system via their effects on the hypothalamic- pituitary-adrenal (HPA) axis. The present study was carried out to assess the effects of chronic exposure to buprenorphine on HPA axis activation, corticosteroid-binding globulin (CBG), the main glucocorticoid (GC) carrier, and the immune system. Results show that buprenorphine, delivered by osmotic pump subcutaneously in C57BL/6 male mice during a 10-day period, caused a marked decrease in total corticosterone (CORT) levels at day 1 of exposure. CORT levels then increased with maximal values observed at day 5 of exposure. After day 5, total CORT levels gradually decreased and returned to control values. No significant changes were observed in CBG protein levels and mRNA expression in the liver. Since CBG levels remained unchanged, the percentage of free CORT values in buprenorphine mice did not differ from control values. Thus, the variations observed in the amount of free CORT were related only to changes measured in total CORT. These endocrine changes did not have a significant impact on the immune parameters measured. Total CD(4)+ and CD(8)+ splenic and thymic populations were not modulated by buprenorphine. However, splenocytes from mice exposed to buprenorphine after 5 days exhibited greater proliferation upon anti-TCR monoclonal antibody stimulation than saline-exposed mice. These results indicate that buprenorphine can be safely used because it did not have significant effects on GC availability for immune corticosensitive cells.

Garrel D, Patenaude J, Nedelec B, Samson L, Dorais J, Champoux J, D'Elia M, Bernier J. OBJECTIVE : Enteral glutamine supplements have been shown to reduce infectious morbidity in trauma patients, but their effect on burn patients is not known. The objective of this study was to measure the impact of enteral glutamine supplementation on infectious morbidity, length of care, and the immune system in burn patients. DESIGN : Double-blinded, randomized clinical trial. SETTING : Burn center. (...)

OBJECTIVES To provide a detailed, sequential analysis of insulin-like growth factor-1 and its binding proteins in adults during the acute phase after a major burn injury. DESIGN Descriptive, repeated measurements for quantitation and characterization of insulin-like growth factor-1 and its binding proteins in adult burn survivors. SETTING Burn center in a university hospital. PATIENTS A total of 17 severely burned (>15% total body-surface area burned) adult patients. INTERVENTIONS Venous blood was collected twice a day for 10 days and centrifuged, and the sera were stored at -80 degrees C until analysis. A series of 340 serum samples were analyzed by radioimmunoassay to determine the circulating concentration of insulin-like growth factor-1 and its major binding proteins (insulin-like growth factor-binding protein), by Western ligand blotting. To better understand the changes seen in systemic insulin-like growth factor-binding protein-3 levels by Western ligand blotting, a proteolysis assay was performed. MEASUREMENTS AND MAIN RESULTS Insulin-like growth factor-1 levels were reduced from day 0 and correlated with insulin-like growth factor-binding protein-1 and -2 (p

Previous studies from our laboratory established that low-fat diets prevent immunosuppression and reduce oxidative stress after a thermal injury. The purpose of the present study was to test the hypothesis that the type of dietary fatty acid influences splenocyte proliferation and oxidative stress following a burn injury. Female C3H/HeN mice were fed ad libitum six experimental diets (5% w/w lipids) differing in fatty acid composition for 10 days following a burn injury. Compared to the controls, burned mice fed whichever diet showed lower lymphoproliferative responses to concanavalin-A (Con-A) and lipopolysaccharide (LPS) (p

The thermogenic response to food (TRF) and substrate oxidation were studied in 12 endurance-trained and 13 untrained female subjects. Energy expenditure and substrate oxidation were calculated by indirect calorimetry before and for 6 h after an oral test meal and after the same meal given intragastrically on a separate occasion. The TRF was calculated after the oral meal, the obligatory component after the intragastric meal (OTRF), and the facultative component from the difference between the two. V˙o 2 max was measured on a treadmill and body composition by underwater weighing. The TRF and OTRF were significantly higher in trained than in untrained subjects: 223 ± 63 vs. 185 ± 50 kJ/6 h ( P< 0.03) and 174 ± 38 vs. 131 ± 37 kJ/6 h ( P < 0.01) for the TRF and OTRF in trained vs. untrained subjects, respectively. Multiple regression analysis showed that maximum O2 consumption (V˙o 2 max), but not percentage of body fat, was significantly related to OTRF ( r =0.68, P < 0.01). Trained subjects had higher fatty acid oxidation than untrained subjects before (0.6 vs. 0.4 mg · kg−1 · min−1, P < 0.05) and after the oral meal (13 ± 6 vs. 8 ± 4 g/6 h P < 0.05). These results demonstrate that 1) TRF is higher in trained than in untrained women; 2) this is due to a higher cost of nutrient digestion, absorption and storage; 3) the difference is related to higher V˙o 2 max; and 4) fatty acid oxidation is greater in trained women in both the postabsorptive and postprandial states. These observations suggest that endurance training induces metabolic changes that favor leanness.

To test the effects of the amount and type of fat in the nutritional support on serum insulin-like growth factor (IGF)-I concentrations in burn patients and to test the hypothesis that the serum proteolytic activity for insulin-like growth factor binding protein (IGFBP)-3 is a major mechanism for the decreased serum IGF-I observed in these patients.Randomized, double-blind trial of three different nutritional supports and analysis of serum IGF-I, IGFBP-3, and serum IGFBP-3 proteolysis.Burn center in a university hospital.A total of 23 severely burned (25% total body surface area burned) adult patients.Patients were randomly assigned to three types of nutritional support differing in the amount of energy derived from fat and the presence or absence of fish oil: Group I (control), 35% fat; Group II, 15% fat; Group III, 15% fat with 50% as fish oil. Nutritional support was both parenteral and enteral and was started within 24 hrs of admission.Serum IGF-I and IGFBP-3 were measured by radioimmunoassay every 3 days for 28 days in 23 severely burned adults. In six patients, IGFBP-3 was measured by ligand binding assay and the serum proteolytic activity for rhIGFBP-3 was measured as well. Serum IGF-I concentration was low in all subjects throughout the study period, but did increase with time (p.01); significantly higher values were found in Group III (p.05). Multivariate analysis showed that fish oil and low fat solutions were significantly correlated to serum IGF-I concentrations. Serum IGFBP-3 (radioimmunoassay) was higher than normal throughout the study with no difference between the groups. Between days 4 and 16, IGFBP-3 was cleaved into two fragments in all patients studied, and the molecular weights of the fragments were equal to those observed in the serum of a woman late in pregnancy. During this period of time, serum proteolytic activity for rhIGFBP-3 was30% in 24 of the 30 samples measured, whereas 20 of the 28 samples measured thereafter were normal (25%). Serum IGFBP-3 concentration from ligand binding assay was correlated with serum proteolytic capacity in all subjects (mean r2 = 0.77; p.01) and with serum IGF-I concentrations in five of six subjects (mean r2 = 0.81; p.01).In burn injury, serum IGF-I concentrations are sensitive to the amount and type of fat in their nutritional support. The presence of fish oil allowed for a more rapid recovery of serum IGF-I levels. The proteolysis of IGFBP-3 may be an important cause of the decreased serum IGF-I values and the protease(s) responsible for this seem to be similar to those observed in late pregnancy.

To analyze the effect of low-fat nutritional solutions, with or without fish oil, on serum interleukin (IL)-6, and to explore the relationships between IL-6, corticosteroid-binding globulin (CBG; the main cortisol carrier in plasma), and protein metabolism in severely burned adult patients.Randomized, double-blind study with control and low fat-fed groups.Burn center of Hôtel-Dieu Hospital of Montréal.Thirty-seven men and women with thermal burn injury over20% of body surface area and no other known medical condition.Within 24 hrs after admission, nutritional support was started through a gastroenteral tube inserted under endoscopic guidance. The goal for energy intake was calculated using the Curreri formula, and was adjusted with biweekly measurements of resting energy expenditure. Patients were randomly assigned to one of the following groups: control (35% of energy as fat); low fat 1 (15% of energy as fat); and low fat 2 (50% of fat in the form of fish oil).Tumor necrosis factor (TNF)-alpha and TNF-beta, IL-6, CBG, and cortisol free fraction were measured every 3 days for 28 days. Nitrogen balance and urinary 3-methylhistidine excretion were measured daily. IL-6 concentrations were high in all patients, with the highest value (460 +/- 111 units/mL) observed on day 4. Concentrations of IL-6 were higher in control patients than in low fat-fed patients between days 13 and 28, but not between days 1 and 13. Multivariate analysis showed that IL-6, total body surface area burned, and sepsis scores were independent predictors of CBG between days 1 and 13 (n = 170; p.00001). High IL-6 concentrations were predictors of low CBG concentrations and high cortisol free fractions. There was no relationship between IL-6, nitrogen balance, and 3-methylhistidine excretion. TNF-alpha and TNF-beta activity measurements by biological assay showed no correlation with other factors measured.a) Low-fat feeding, with or without fish oil, does not change the early production of IL-6 after burn injury; b) serum IL-6 is negatively correlated with CBG, which supports the hypothesis that this cytokine inhibits hepatic CBG production; and c) IL-6 does not appear to directly influence protein metabolism in burn patients.

Objective: To quantify the long-term effects of burns on muscle strength and to investigate the impact of the initial severity of the trauma on muscle strength. Design: Cross-sectional study comparing individuals with healed burns to nonburned control individuals matched for age, gender, body mass index, and physical activity level. Setting: Subjects were selected from the data bank of a burn center of a large Montreal teaching hospital and tested in a university laboratory. Patients: Thirty subjects (mean age, 36.3 ± 11.5yrs) with second- and third-degree burns covering 15% to 75% of total body surface area (TBSA) (mean, 35.5% ± 15.9%) were evaluated more than 1 year after discharge (mean, 37.3 ± 20.4 months; range, 15 to 92 months). Thirty unburned subjects were recruited from the community at large Main Outcome Measure: Maximal torque, work, and power developed by the elbow and knee flexors and extensors. Results: Subjects with burns of >30% of TBSA produced significantly less torque, work, and power in the quadriceps than control subjects (15.2% to 20.5% depending on velocity [p < .05]). The ability to develop muscle power at the elbow was also compromised in the severely burned subjects (19.2% in extension and 18.7% in flexion [p = .07]) at the faster velocities. No differences were observed between controls and patients with small burn injuries (TBSA of 30%) had weaker muscles even years after the trauma, suggesting either an inability to fully recover or insufficient rehabilitation.

The aim of this study was to determine the role of the autonomic nervous system (ANS) in obligatory and facultative components of the thermogenic response to food (TRF). Nineteen lean, healthy subjects participated in this study, which comprised two protocols, each exploring one component of the ANS. In the first experimental group, propranolol (prime: 80 micrograms/kg; continuous: 1 microgram.kg-1.min-1) was infused intravenously to inhibit sympathetic nervous activity (SNA), whereas in the second group atropine (prime: 5 micrograms/kg; continuous: 5 micrograms.kg-1.min-1) was used to inhibit parasympathetic nervous activity (PNA). The TRF was measured on four occasions: 1) after oral ingestion of a breakfast, during 0.9% NaCl perfusion, 2) after oral ingestion of the same breakfast, during the perfusion of one of the drugs, 3) after intragastric injection of a pureed form of the same meal as in part 1, during 0.9% NaCl perfusion, and 4) after intragastric feeding, during the administration of one of the drugs. Energy expenditure was measured by indirect calorimetry for 30 min before and 6 h after ingestion of the meal. Facultative TRF was defined as the difference between oral and intragastric TRF. Intragastric feeding significantly reduced TRF in both studies: 6.6 +/- 1.0 vs. 8.7 +/- 0.8% of the ingested energy in the SNA study and 5.5 +/- 1.6 vs. 7.4 +/- 3.1% in the PNA study. During propranolol infusion, TRF was significantly lower than it was during saline infusion after oral feeding (6.9 +/- 1.0% vs. 8.7 +/- 0.8% of ingested energy) but not after intragastric feeding. During atropine administration, TRF was reduced after both oral and intragastric feeding, although statistical significance was not reached in the latter. Atropine administration decreased gastric emptying (measured with an isotopic method) 2 h postingestion by 50%. These results show that the SNA is necessary for the facultative component of TRF to occur in humans. The role of the PNA appears to be related to its action on gastric emptying.

Rhinopharyngeal cancer is one of the best indications for conformal radiotherapy with modulated intensity. Due to the high dose gradient, accurate delineation of target volumes and organs at risk is a critical success factor with this technology. This requires a good knowledge of rhinopharyngeal radioanatomy and optimal imaging techniques.

To evaluate the possible actions of glucocorticoids on resting energy expenditure and the thermogenic response to food in man.The morning after administration of RU 486 or placebo, resting metabolic rate (RMR) and the thermogenic response to food (TRF), were measured after the ingestion of a standardized meal in 12 healthy male volunteers. Plasma glucose (PG) and insulin (PI) concentrations were also measured at regular intervals.1) After RU 486 administration, plasma cortisol was elevated throughout the test comparatively to placebo. 2) Fraction and concentration of free cortisol were also higher after RU 486 than after placebo. 3) Corticosteroid-binding-globulin (CBG) was similar in both experimentations. 4) RMR was not different after RU 486 (1656 +/- 144 kcal/day) or after placebo (1632 +/- 120 kcal/day). 5) TRF was not different after RU 486 or placebo (54 +/- 12 kcal vs 59 +/- 13 kcal over a 6 hour period for RU 486 and placebo, respectively). 6) Baseline glucose concentrations were similar at baseline but PG was higher 90 minutes postprandial with RU 486: 5.3 +/- 1.7 mmol/L vs 3.7 +/- 0.8 mmol/L for placebo. 7) Plasma insulin was similar at baseline but it was significantly higher at 90 minutes postprandial after RU 486 (347 +/- 143 vs 241 +/- 73 pmol/L for RU 486 and placebo, respectively).This study shows that acute inhibition of glucocorticoid action does not alter RMR and TRF in healthy men and that a mild deterioration of glucose tolerance follows the ingestion of RU 486.

Resting metabolic rate (RMR) is commonly predicted using the Harris-Benedict (HB) equations, but an overestimation of 10% to 15% is normally found. More recent studies have proposed equations with a better predictive value. In this study, we explore the relationship between measured RMR and HB in 67 healthy volunteers and in a data set from the literature and compared measured RMR with six more recent equations. Mean differences between RMR and HB were 21%, 12%, 10%, and 4% for the lowest to the highest RMR quartile, respectively, and 20%, 8%, 6%, and -4% for Owen's subjects. Among the six recent equations, only the World Health Organization (WHO) equations predicted RMR within 10% in 100% of the cases. Our results suggest that overestimation of RMR by HB is not a homogenous finding but is inversely related to RMR. This may have important implications for predicting RMR in women and in patients with diminished lean body mass. In addition, the WHO equations appear more precise than the HB equations.

Corticosteroid-binding globulin (CBG) is the main carrier of glucocorticoids in mammals. Serum CBG shows little physiological variation with the exception of pregnancy. Experimental inflammation and burn injury decrease serum CBG in rats and while the mechanism of this effect is unknown, in vitro experiments suggest that interleukin-6 may be involved. In severely burned patients, we have found that CBG was markedly decreased within a few hours postinjury. This decrease lasted about 2 weeks and was accompanied by an increase in the free fraction of serum cortisol. In addition, serum CBG responded to dietary manipulation in these patients, with low fat feeding resulting in higher serum CBG concentrations and lower serum-free cortisol values. This feeding suggests that during severe stress, CBG may be important in regulating the amount of cortisol reaching target tissues such as the immune system and wounds.

The optimal amount and type of fat in the nutrition support of burned patients have not been determined. The aim of this study was to test low-fat nutritional solutions, with or without fish oil, on protein metabolism, morbidity, and length of care in severely burned adults.In a prospective randomized clinical trial, 43 patients were assigned to one of the following groups: control (35% fat), low-fat solution (ie, 15% of total calories as fat), low-fat with fish oil, given for 30 days. Nitrogen balance, urinary 3-methylhistidine excretion, urinary cortisol, and clinical status were measured daily. Corticosteroid-binding globulin and total and free serum cortisol were measured every 3 days.Compared with controls, patients on low-fat support had fewer cases of pneumonia: 3/24 vs 7/13 (p = .02), better respiratory and nutrition status, and shorter time to healing: 1.2 vs 1.8 days/% burned area (p = 0.01). There was no difference in nitrogen balance between groups, and 3-methylhistidine excretion was higher and serum free cortisol was lower in log-fat--fed patients than in controls. There was no difference between the two low-fat groups in any of the parameters measured.This study showed that low-fat nutrition support decreases infectious morbidity and shortens length of stay in burn patients. Fish oil does not seem to add clinical benefit to low-fat solutions. In addition, this study provides the first evidence that nutrition intervention modulates cortisol-binding globulin and the concentration of free circulating cortisol after a severe stress.

Energy expenditure (EE) was measured one to five times by indirect calorimetry for 1 h after an overnight fast, and for 2 h after starting feeding in 19 severely burned patients (TBSA20 per cent) for a total of 36 tests. Twelve tube-fed volunteers served as controls. Thermogenic response to feeding (TRF) was calculated as the percentage of energy intake and hypermetabolism as the percentage of values obtained with the Harris-Benedict formula (%HB). Measured energy expenditure values were compared with values given by three predicting formulae. TRF was present in 10 out of the 33 measurements. Fasting EE was not different between the tests with and without TRF, but %HB was different between the two groups: 121.1 +/- 25.8 vs 157.8 +/- 32.0 per cent (tests with and without TRF, respectively (P0.01)). TRF was always absent when %HB was higher than 50. When TRF was present it was not statistically different from the control values. None of the three predicting formulae gave values within 10 per cent of the measured values in more than 25 per cent of the patients. We conclude that TRF is suppressed in burned patients with marked hypermetabolism, and that EE measured in the fed state reflects resting expenditure accurately in these patients. In addition, EE cannot be predicted from existing formulae.

OBJECTIVES Insulin-like growth factor-I (IGF-I) is a polypeptide growth factor that stimulates protein synthesis. The aims of this study were to determine (1) the effect of a severe burn on blood IGF-I levels and (2) the variables controlling IGF-I level variations during recovery of these hypermetabolic patients. PATIENTS Eleven patients, nine men and two women (age range 22-55 years) were studied for 25 days following a severe burn (18-75% of total body surface area, mean 36%). Nitrogen balances were recorded daily and total IGF-I levels were measured every 3 days. MEASUREMENTS IGF-I was extracted from serum using a validated formic acid-acetone methodology, then measured by a double antibody radioimmunoassay. IGF-I levels were compared to those of a reference healthy population. RESULTS Within 24 hours following injury, IGF-I levels were low in all patients when compared to normal values for the same age range (mean +/- SEM of all patients, 131 +/- 26 micrograms/l). They remained low for the first week (days 4 and 7, 109 +/- 16 micrograms/l), then increased to reach normal values at the end of the study period (days 10-16, 144 +/- 19 micrograms/l, P = 0.005 when compared to days 4-7; days 19-25, 206 +/- 30 micrograms/l, P = 0.008 when compared to days 10-16). IGF-I levels were negatively correlated with age in the second phase of recovery only (days 10-16, r = -0.70, P < 0.05; days 19-25, r = -0.75, P < 0.01) and with severity of burn between days 19 and 25 (r = -0.62, P < 0.05). The presence of bronchial burn injury tended to lower IGF-I blood concentration (P = 0.08). Whereas IGF-I concentrations increased in the later phase of recovery, nitrogen balances did not. As a result, there was no significant correlation between these parameters. CONCLUSIONS IGF-I levels followed a biphasic pattern in severely burned patients. They dropped dramatically in response to the traumatic shock, then increased during recovery. The degree of increase was dependent on the age of the patient and on the severity of the burn, but was not associated with an improvement in the nitrogen balance.

Possible changes in glucose tolerance and substrate oxidation after a high-carbohydrate, low-fat diet were studied in seven healthy volunteers. Each subject consumed two experimental diets for 1 week after 1 week on a stabilization diet; diet no. 1 11% fat and 64% carbohydrates, and diet no. 230% fat and 45% carbohydrates. At the end of each experimental week, plasma levels of glucose, insulin, and free fatty acids were measured before and every 30 minutes for 6 hours after a 75-g oral glucose challenge. At the same time, energy expenditure and substrate oxidation were measured by indirect calorimetry. Plasma lipid and lipoprotein levels were measured at the end of one stabilization period and at the end of each diet. Plasma glucose concentrations and areas under the curve of glucose concentrations were identical after the two experimental periods; the means ± standard deviation for the values at 120 minutes were 6.4 ± 0.3 and 6.4 ± 0.6 mmol/L after diets no. 1 and 2, respectively, and areas under the curve were 1,853 ± 115 and 1,862 ± 211 mmol · min/L after diets no. 1 and 2, respectively. Similarly, plasma concentrations of insulin and free fatty acids after glucose ingestion were unaffected by the dietary changes. Energy expenditure increased after glucose administration, and this thermic effect of glucose was identical after the two experimental diets at 4.2% ± 1.4%, and 3.9% ± 1.4% of ingested energy for diets no. 1 and 2, respectively. Substrate oxidation rates were also identical for both the fasted and post-glucose periods after the two diets. Total cholesterol, very-low-density lipoprotein (VLDL), and low-density lipoprotein (LDL) levels showed no significant change between the two diets, but plasma high-density lipoprotein (HDL) concentrations were lower after the high-carbohydrate diet at 1.02 ± 0.10 and 1.15 ± 0.10 mmol/L for diets no. 1 and 2, respectively (P < .05), and triglyceride concentrations were higher after each experimental diet than after the stabilization diet at 1.11 ± 0.04, 1.29 ± 17, and 0.87 ± 0.12 for diets no. 1 and 2 and the stabilization diet, respectively (P < .01). These data do not support the hypothesis of a metabolic adaptation toward increased glucose tolerance and glucose utilization induced by a high-carbohydrate, low-lipid diet in healthy subjects. Furthermore, changes observed in plasma lipoprotein concentrations favor the concept that such a diet may increase the risk for cardiovascular disease.

Corticosteroids exert inhibitory effects on wound healing. They circulate, largely bound to corticosteroid-binding globulin, and the plasma concentrations of this protein determine their bioavailability. The amount of corticosteroid-binding globulin in wounds and the related effects of burn injury are not known. We have therefore measured corticosteroid-binding globulin in serum and wound fluid obtained from subcutaneously implanted sponges, retrieved 1, 3, and 10 days after insertion in rats. The effect of burning was studied by comparing rats that had a small scald burn with sham-burned control rats. In serum, corticosteroid-binding globulin levels were lower in burned rats than in control animals: the difference was 22%, 28%, and 37% for days 1, 3, and 10, respectively (p < 0.05 for each comparison), and values at day 1 were lower than at days 3 and 10 in control rats (p < 0.05) but not in burned rats. In wound fluid, corticosteroid-binding globulin levels were lower in burned rats than in control animals: the difference was 23%, 24%, and 34% for days 1, 3, and 10, respectively (p < 0.01 for all comparisons), and the values were significantly higher (p < 0.05) at day 1 when compared with values at day 10 in both groups. We therefore conclude that a small burn injury has significant effects on levels of corticosteroid-binding globulin on serum and wound fluid corticosteroid-binding globulin. The decreased concentration of wound fluid corticosteroid-binding globulin at day 10 versus day 1, with a concomitant increase in serum corticosteroid-binding globulin, suggests an accelerated degradation of the protein within the wound; this phenomenon is exaggerated by the burn injury. This is supported by Western blot analysis, which revealed the appearance of a small polypeptide that reacts with an antiserum against rat corticosteroid-binding globulin in wound fluid at day 10.

The WHO 2005 histological classification separates sinonasal adenocarcinoma (ADC) into three classes: intestinal-type adenocarcinoma (ITAC), low-grade sinonasal ADC and high-grade sinonasal ADC. The goal of this study was to check the relevance of this classification on the prognosis of patients treated for ADC.All the files of patients treated consecutively in the ENT department of the Montpellier University Hospital for ADC between 1980 and 2003 were retrospectively re-examined. Each case was reviewed for anatomical and pathological data based on the immunohistochemistry results according to the WHO 2005 classification, with a study of a panel of markers: cytokeratin 7 (CK7), cytokeratin 20 (CK20), Villin, CDX2 and EGFR. The epidemiologic data, the methods of treatment and the follow-up were studied. The survival probabilities were calculated using the Kaplan-Meier method and the survival graphs were compared using a log-rank test.Sixty-two files were reviewed. Twelve patients were reclassified into the adenoid cystic carcinoma category and excluded from the study. In the 50 remaining cases, there were 36 ITAC cases, four low-grade ADC cases and 10 high-grade dedifferentiated carcinomas. For all of the ADC cases, the total survival at 5 years and without recurrence was 64 and 52%, respectively. The analysis of the three subgroups showed a total survival of 72.2% for ITAC, 100% for low-grade and 20% for high-grade ADC with a significant difference (p=0.044). This immunohistochemical distinction was mainly based on the expression of CK20 found in 98% of the ITAC cases and absent in low- and high-grade ADC patients.The WHO 2005 classification for sinonasal ADC provides a valuable prognosis by showing a difference in the progression profile between ITAC, low-grade ADC and high-grade ADC. Moreover, broader studies should be conducted to investigate the different subtypes of ITAC.

The effects of chronic administration of growth hormone-releasing factor (GRF) on wound healing were studied in rats. Cutaneous wound strength was measured by tensometry at 5, 10, and 14 days postwounding in rats implanted with a slow-release pellet which contained a compressed mixture of a fatty acid and [desamino Tyr1, D-Ala2, Ala15]hGRF(1-29)NH2 or the fatty acid alone. There was a significant increase in wound tensile strength in GRF-treated rats compared to controls at each measurement: Day 5, 130 +/- 12 vs 97 +/- 14 g; Day 10, 402 +/- 18 vs 280 +/- 11 g; Day 14, 830 +/- 17 vs 614 +/- 14 g (P less than 0.01 for each value). Granulation tissue obtained from subcutaneously implanted polyvinyl alcohol sponges encased in silicone tubing was also studied. The amount of collagen deposited in the granulation tissue was estimated by measuring the hydroxyproline (Hyp) content of sponges retrieved 5, 10, and 14 days postinsertion from GRF-treated and control rats. Hyp content (nmole/mg sponge) was similar in both treated and control animals at each measurement: Day 5, 1.7 +/- 0.2 vs 2.2 +/- 0.2; Day 10, 31.9 +/- 4.1 vs 26.7 + 0.4; and Day 14, 41.6 +/- 7.3 vs 38.5 +/- 4.4. Hyp/proline, Hyp/glycine, and glycine/total amino acid ratios, evaluated after 10 days, were also similar in both groups. Collagen from the granulation tissue of sponges retrieved after 14 days from treated and control rats was studied by electron microscopy (magnifications, 7,100 and 22,720).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute effect of the ingestion of 80 g each of casein, lactalbumin, and soybean isolate on serum and urinary uric acid concentrations was investigated in 10 healthy subjects. Serum and urinary uric acid concentrations were measured before and after the ingestion of proteins. Serum uric acid decreased significantly 3 h after ingestion of lactalbumin and casein but increased after soybean consumption. Urate clearance was significantly increased after ingestion of each of the three proteins. Multivariate analysis of urate clearance during lactalbumin and casein loads showed that independent correlation was obtained for serum alanine and urea concentration. These results demonstrate that, in addition to their known uricosuric effect, milk proteins acutely decrease serum uric acid concentration. Analysis of the effects of lactalbumin and casein on urinary uric acid elimination suggests that the uricosuric effect of proteins is a multifactorial phenomenon.

The possible influence of early enteral nutritional support on the length of care was explored retrospectively in 25 patients with burns greater than 20% total body surface area (TBSA). Patients were divided into two groups according to the time of their admission: group 1, from July 1986 to February 1987 (n = 12) and group 2, from July 1987 to January 1988 (n = 13). The only difference in treatment between the two groups was the start of early enteral nutritional support in group 2. Age, percent TBSA burned, surfaces of skin grafts, associated respiratory injury, and medical condition were identical in both groups. The following parameters were compared: lag time between hospital admission and the beginning of nutritional support, energy intake, nitrogen intake during the 4-week postadmission period, and length of care. A regression analysis including all patients was also performed to identify the factors associated with length of care. Lag time was shorter in group 2 than in group 1: 3 +/- 2 days versus 7 +/- 2 days (p less than 0.01). Group 2 received more energy than group 1 during the first 2 weeks after admission: 120 +/- 54 kj/kg/day versus 73 +/- 34 kj/kg/day (p less than 0.05) and 175 +/- 36 kj/kg/day versus 137 +/- 41 kj/kg/day (p less than 0.05) for the first and the second week, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Some insulin-resistant obese postmenopausal (PM) women are characterized by an android body fat distribution type and higher levels of lean body mass (LBM) compared to insulin-sensitive obese PM women. This study investigates the independent contribution of LBM to the detrimental effect of visceral fat (VF) levels on the metabolic profile. One hundred and three PM women (age: 58.0+/-4.9 years) were studied and categorized in four groups on the basis of their VF (higher vs. lower) and lean BMI (LBMI=LBM (kg)/height (m2); higher vs. lower). Measures included: fasting lipids, glucose homeostasis (by euglycemic/hyperinsulinemic clamp technique and 2-h oral glucose tolerance test (OGTT)), C-reactive protein (CRP) levels, fat distribution (by computed tomography (CT) scan), and body composition (by dual-energy X-ray absorptiometry). Women in the higher VF/higher LBMI group had lower glucose disposal and higher plasma insulin levels compared to the other groups. They also had higher plasma CRP levels than the women in the lower VF/lower LBMI group. VF was independently associated with insulin levels, measures of glucose disposal, and CRP levels (P