Clinicobiological progression and prognosis of oral squamous cell carcinoma in relation to the tumor invasive front: impact on prognosis

CONCLUSION: There are several factors that influence the final outcome when treating oral squamous cell carcinoma (OSCC). Invasive front phenomena and more importantly their clinicopathological translation can have a direct impact on survival, and subsequently on the decision for an adjuvant treatment. OBJECTIVES: In recent years, the concept of tumor-host interaction has been the subject of substantial efforts in cancer research. Tumoral behavior may be better understood when studying the changes occurring at the tumor-host interface. This study evaluated the influence of several clinicopathological features on the outcome of OSCCs. METHODS: The clinical records and pathology specimens of 54 patients with OSCC treated by primary resection were reviewed retrospectively. The pathologic features reviewed were: invasive front grading (IFG), stromal reaction, lymphovascular invasion (LVI), perineural invasion (PNI), margin status, and depth of invasion. RESULTS: High IFGs had a significant relationship with pT status and pN status. High IFGs were strongly correlated with nodal metastases (odds ratio (OR) = 4.77; confidence interaval (CI) = 1.37-16.64). Concerning survival, IFG had a strong impact on disease-free survival in patients treated unimodally, as did the depth of invasion in the same group. Lymphovascular involvement was found to have a negative impact on overall survival in patients treated multimodally.

Intra-individual variation in body temperature and pectoral muscle size in nestling Alpine swifts Apus melba in response to an episode of inclement weather

The Alpine swift (Apus melba) forages on insects caught exclusively on the wing, implying that dependent nestlings face acute food shortage in periods of cold and rainy weather. Therefore, there should be strong selection on nestling swifts to evolve physiological strategies to cope with periods of undernutrition. We have investigated intra-individual changes in nestling pectoral muscle and body temperature in response to a 1-week period of inclement weather. The pectoral muscle is the largest reserves of proteins, and nestlings have to devote a large amount of energy in the maintenance of body temperature. The results show that nestling pectoral muscle size and body temperature were significantly reduced during the episode of inclement weather. Assuming that these physiological changes are adaptive, our study suggests that nestling swifts spare energy by a pronounced reduction (up to 18 degrees C) in body temperature and use proteins from the pectoral muscle as a source of extra energy to survive prolonged periods of fasting.

Intra- and intersexual selection and their potential consequences on fitness-relevant traits in several fish species

Résumé : Les mécanismes de sélection sexuelle, en particulier la compétition entre mâles (sélection inter-sexuelle) et le choix des femelles (sélection intra-sexuelle), peuvent fortement influencer le succès reproducteur d'un individu, c'est-à-dire son nombre de descendants. On observe ainsi que les mâles dominants et les mâles élaborant des caractères sexuels secondaires marqués ont un succès reproducteur élevé. Toutefois, le succès reproducteur ne suffit pas pour garantir une contribution génétique élevée, parce que la fitness dépend également de la performance des descendants (c'est-à-dire de leur survie et de leur propre succès reproducteur). Si cette performance dépend en partie des gènes paternels, les males ont un avantage certain à signaler leur qualité aux femelles afin d'atteindre des taux de reproduction élevé. Ce mécanisme de signalisation est connu sous le nom de 'good genes hypothesis', toutefois très peu d'études ont clairement démontré le lien entre la qualité génétique des individus et la signalisation. De plus, la performance des descendants peut aussi dépendre des effets génétiques de compatibilité entre mâles et femelles ('compatible genes'). C'est-à-dire que certains allèles paternels n'apporteraient un avantage aux descendants qu'en combinaison avec certains allèles maternels. Nous avons déterminé, durant la période de reproduction, le statut de dominance des mâles pour deux espèces de poissons d'eau douce : la truite (Salmo trotta) et le vairon (Phoxinus phoxinus), puis nous avons évalué la relation entre le succès reproducteur et le statut de dominance et/ou la quantité de signalisation des caractères sexuels secondaires. Nous avons également fécondés artificiellement des oeufs de truites et de corégones (Coregonus palaea), en croisant chaque mâle avec chaque femelle (full-factorial breeding design). Ce type de design autorise la quantification précise des effets génétiques et permet de séparer les effets de 'good genes' et de 'compatible genes'. Cela a été fait sous différentes intensités de stress bactérien, ainsi que dans des conditions naturelles, et nous avons pu ainsi tester si certains indicateurs de qualité génétique des mâles ('good genes') étaient liés a) à la dominance et/ou b) à l'expression des caractères sexuels secondaires des mâles comme l'intensité mélanique ou la taille des tubercules sexuels. En outre, nous cherchons à savoir si la survie des descendants est liée à certaines combinaison des gènes du complexe d'histocompatibilité majeur (MHC) et/ou à la parenté génétique des parents, les deux traits étant soupçonnés d'avoir des influences génétique de compatibilité (`compatible genes') à la performance des descendants. Nous avons constaté que la dominance des mâles est directement liée à la taille et au poids des mâles (truites, vairons), mais également aux caractères sexuels secondaires (tubercules). De plus, les mâles vairons dominant ont eu un succès de fécondation plus élevés que les mâles subordonnés. Nous montrons que les truites et corégones mâles diffèrent dans leur qualité génétique, qui a été mesurée avéc la survie embryonnaire, le temps avant l'éclosion et enfin la croissance juvénile. Contrairement aux prédictions, la dominance (ou les traits indicatifs de dominance) n'était liée à la qualité génétique, dans aucun des traitements, et ne fonctionne donc pas comme indicateur de qualité. Par contre, la qualité génétique était liée aux caractères sexuels secondaires, particulièrement par la teinte mélanique chez les truites. Les embryons de truites issus de pères sombres survivaient mieux que ceux issus de pères clairs dans des environnements difficiles, de plus leur croissance était plus élevée lors de leur première année dans des conditions naturelles. La taille des juvéniles lors de leur première année est un trait important lié au succès dans la compétition pour des ressources telles qu'abri ou nourriture. De plus, les femelles truites peuvent augmenter la survie de leurs descendants en choisissant des mâles selon leur type de MHC ou selon leur degré de parenté. En outre, chez les corégones, la morphologie des tubercules sexuels ne semble pas signaler la qualité génétique. Nous avons également remarqué que l'exposition à des pathogènes non-létaux pouvait influencer la performance des alevins à court et long terme, probablement en affaiblissant leur système immunitaire. Cette thèse montre que les mâles diffèrent dans leur qualité génétique et que différents mécanismes de sélection inter- ou intra-sexuelle (par exemple la préférence pour des mâles sombres, pour des génotypes MHC ou pour des couples avec degré de parenté basse) pouvait avoir un effet positif sur la qualité des descendants, bien que cet effet génétique pouvait changer au cours du temps et entre différents environnements. Contrairement à nos attentes, le résultat de la compétition intra-sexuelle (la hiérarchie de dominance entre mâles) n'était pas lié à la qualité génétique individuelle ('good genes'). Dans ce sens, ce travail permet également de contribuer à l'explication du fait que la sélection sexuelle, de par sa forte sélection directionnelle, ne conduit pas à la diminution de la variance génétique, mais plutôt à la maintenance du polymorphisme génétique. Summary : Sexual selection mechanisms, especially male-male competition (inteasexual selection) and female mate choice (inteasexual selection), can strongly influence individual mating success, often resulting in dominant males and males with elaborate secondary sexual characters having higher fertilisation success. However, siring a high number of offspring alone does not guarantee high individual fitness, as fitness does also strongly depend on offspring performance (i.e. survival, fecundity). If this superiority in offspring performance depends on paternally inherited genes, the fathers are expected to signal this potential indirect benefit to females in order to attain high mating rates. This mechanism is also known as the 'good genes' hypothesis of sexual selection but until now most studies failed to conclusively show the relation of an individual genetic quality and its potential signalling traits. Further, offspring performance could also depend on compatible gene effects. These are alleles that increase offspring performance only in combination with other specific alleles. We first determined male dominance status from intrasexual competition during mating season for brown trout (Salmo trutta) and European minnows (Phoxinus phoxinus). For minnows we additionally checked if dominance and/or secondary sexual traits were linked to fertilisation success. Further, we artificially fertilised brown trout and alpine whitefish (Coregonus palaea) eggs, following full factorial breeding designs, enabling to properly measure `good gene' and `compatible gene' effects on offspring performance. This was done under different intensities of natural stressors, as well as under natural conditions. This procedure allowed us to test if the obtained male genetic quality measures (good genes effects) were indicated by a) dominance or lay traits linked to dominance and/or by b) secondary sexual characteristics such as melanin-based male skin darkness or breeding tubercles. Further, we investigated if offspring survival was linked to the MHC (major histocompatibility complex) gene combinations and/or to the parental genetic relatedness, as both traits were shown to have 'compatible gene' effects that may influence offspring performance. We found that male dominance in intrasexual competition was positively linked to body size, body weight (brown trout, minnows) but also to elaborate secondary sexual characteristics (breeding tubercles in minnows). Further, dominant minnow males did have an increased fertilisation success compared to subordinate ones. We show that brown trout and whitefish males do usually differ in their genetic quality, which was measured as embryo survival, hatching timing and finally as juvenile growth. Contrary to prediction male dominance or dominance indicating traits do not function as a quality signal as they were not linked to genetic quality. This result was constant when measuring genetic quality under different levels of natural stressors and under natural conditions (brown trout). On the other hand genetic quality seemed to be indicated by secondary sexual characteristics, specifically by melanin-based skin darkness in brown trout as brown trout embryos sired by darker fathers had increased survival rates when raised under harsh conditions and. they grew larger as juveniles after one year of growth in a natural stream, which is an important trait influencing success of juveniles in competition for hidings, food and other resources. Furthermore, brown trout females may increase the survival of their embryos when choosing males according to their MHC genotypes or to the general genetic relatedness between themselves and their potential mates. In whitefish on the other hand breeding tubercle morphology did not seem to signal genetic quality. Eventually, we saw that anon-lethal exposure to pathogens might influence short term and long term offspring performance probably by weakening an exposed individual's immune system. This thesis shows that males usually differ in their genetic quality and that different inter- or intrasexual selection mechanisms (e.g. mate selection favouring dark males, preference for MHC genotype combinations or for unrelated mates) may have strong positive effects on genetically dependent offspring performance but that such genetìc effects can change over time and environments. In contrast to our a priori expectations, the outcome of intrasexual selection, namely male dominance hierarchies, with dominant males often having high fertilisation success, was not linked to individual genetic quality (`good genes'). In this sense the present thesis may also be a helpful contribution to understand why sexual selection does not lead to rapid loss of genetic variation by strong directional selection but could even lead to the maintenance of genetic variation in natural populations.

Urinary analysis of 16(5alpha)-androsten-3alpha-ol by gas chromatography/combustion/isotope ratio mass spectrometry: implications in anti-doping analysis.

We present a method for the analysis of urinary 16(5alpha)-androsten-3alpha-ol together with 5beta-pregnane-3alpha,20alpha-diol and four testosterone metabolites: androsterone (Andro), etiocholanolone (Etio), 5alpha-androstane-3alpha,17beta-diol (5alphaA), 5beta-androstane-3alpha,17beta-diol (5betaA) by means of gas chromatography/combustion/isotopic ratio mass spectrometry (GC/C/IRMS). The within-assay and between-assay precision S.D.s of the investigated steroids were lower than 0.3 and 0.6 per thousand, respectively. A comparative study on a population composed of 20 subjects has shown that the differences of the intra-individual delta(13)C-values for 16(5alpha)-androsten-3alpha-ol and 5beta-pregnane-3alpha,20alpha-diol are less than 0.9 per thousand. Thereafter, the method has been applied in the frame of an excretion study following oral ingestion of 50 mg DHEA initially and oral ingestion of 50mg pregnenolone 48 h later. Our findings show that administration of DHEA does not affect the isotopic ratio values of 16(5alpha)-androsten-3alpha-ol and 5beta-pregnane-3alpha,20alpha-diol, whereas the isotopic ratio values of 5beta-pregnane-3alpha,20alpha-diol vary by more 5 per thousand upon ingestion of pregnenolone. We have observed delta(13)C-value changes lower than 1 per thousand for 16(5alpha)-androsten-3alpha-ol, though pregnenolone is a precursor of the 16-ene steroids. In contrast to 5beta-pregnane-3alpha,20alpha-diol, the 16-ene steroid may be used as an endogenous reference compound when pregnenolone is administered.

Cost-effectiveness of full-course oral levofloxacin in severe community-acquired pneumonia.

Oral levofloxacin is as efficient as sequential antibiotic treatment in community-acquired pneumonia (CAP). The current authors assessed whether oral levofloxacin treatment of patients with severe CAP, followed-up for 30 days, would save money. Over a 12-month period, 129 hospitalised patients with severe non-intensive care unit CAP were randomly assigned to receive either oral levofloxacin or sequential antibiotic treatment. Direct and indirect costs were compared over a 30-day period from several perspectives. CAP resolved in 71 out of 77 oral levofloxacin (92%) and in 34 out of 37 sequential antibiotic treatment patients (92%). Patients' characteristics, treatment duration, hospital length of stay and mortality were similar in both groups. Drug acquisition costs were 1.7-times smaller in oral levofloxacin patients, who were less often transferred to rehabilitation centres, but they used more physicians' visits during follow-up and their total costs were lower. As only a minority of patients was still active, inability to work and, hence, indirect costs were similar in both groups. In this study, oral levofloxacin for severe non-intensive care unit community-acquired pneumonia was equally effective as sequential antibiotic treatment, but did not lead to major costs savings except for drug acquisition costs. External factors linked with patients' characteristics and/or medical practice are likely to play a role and should be addressed.

Is intra-operative blood fllow predictive for early failure of radiocephalic arteriovenous fistula ?

Rapport de Synthèse : Introduction : Depuis plus de 50 ans, les fistules artérioveineuses radiocéphaliques (FAV) restent le meilleur accès d'hémodialyse en termes de perméabilité et de complications. Néanmoins, l'échec précoce dû aux thromboses ou à la non maturation entraîne leur abandon chez un nombre significatif de patients. Cette étude prospective est destinée à investiguer la mesure peropératoire du débit sanguin dans les FAV comme valeur prédictive d'échec précoce. Méthode : Nous avons sélectionné des patients nécessitant la confection d'une FAV pour hémodialyse en se basant sur le repérage veineux effectué par ultrason dans la période préopératoire. La mesure du débit sanguin dans la FAV a été réalisée systématiquement après la réalisation de l'anastomose en utilisant une sonde mesurant le temps de transit des globules rouges. Durant le suivi, le débit a été estimé par ultrason à des intervalles réguliers. Résultats : Nous avons réalisés 58 FAV chez 58 patients avec un suivi moyen de 30 jours. La thrombose et non maturation a été observée chez 8 patients (14%) et 4 patients (7%) respectivement. La valeur de débit peropératoire des fistules sans échec précoce était significativement plus élevée que dans les fistules avec échec précoce (230 v. 98 mL/min ; Ρ = 0.007), tout comme à une semaine (753 vs 228 mL/min ; P=0.0008) et 4 semaines (915 vs 245 mL/min, P<0.0001j. La mesure du débit avec une valeur seuil à 120 mL/min présente une sensibilité de 67%, une spécificité de 75% et une valeur prédictive positive de 91%. Conclusions : Un débit sanguin < 120mL/min a une bonne valeur prédictive positive d'échec précoce dans les FAV. Durant la procédure, cette valeur seuil, doit être utilisée pour sélectionner de manière appropriée les FAV nécessitant durant la même intervention une correction immédiate afin d'améliorer le débit. Une étude consécutive devra investiguer les origines des débits faibles des FAV objectivés durant leur confection.

The oral cancer epidemic in central and eastern Europe.

To monitor recent trends in oral and pharyngeal cancer mortality in 38 European countries, we analyzed data provided by the World Health Organization over the period 1975-2004. Joinpoint analysis was used to identify significant changes in trends. In the European Union (EU), male mortality rates rose by 2.1% per year between 1975 and 1984, by 1.0% between 1984 and 1993, and declined by 1.3% between 1993 and 2004, to reach an overall age-standardized rate of 6.1/100,000 in 2000-2004. Mortality rates were much lower in women, and the rate in the EU rose by 0.9% per year up to 2000, and levelled off to 1.1/100,000 in 2000-2004. In France and Italy - which had the highest rates in the past - male rates have steadily declined during the last two decades (annual percent change, APC=-4.8% in 1998-2004 in France, and -2.6% in 1986-2003 in Italy). Persisting rises were, however, observed in several central and eastern European countries, with exceedingly high rates in Hungary (21.1/100,000; APC=6.9% in 1975-1993 and 1.4% in 1993-2004) and Slovakia (16.9/100,000; APC=0.14% in 1992-2004). In middle aged (35 to 64) men, oral and pharyngeal cancer mortality rates in Hungary (55.2/100,000) and Slovakia (40.8/100,000) were comparable to lung cancer rates in several major European countries. The highest rates for women were in Hungary (3.3/100,000; APC=4.7% in 1975-2004) and Denmark (1.6/100,000; APC=1.3% in 1975-2001). Oral and pharyngeal cancer mortality essentially reflects the different patterns in tobacco smoking and alcohol drinking, including drinking patterns and type of alcohol in central Europe. (c) 2009 UICC.

Correlation of intra- and extraepidermal CD8 T cell numbers with development of psoriatic epidermal pathology

The development of psoriatic plaques is T cell dependent. Recently, Th17 CD4 T cells have been proposed to be the main effector cells. However, development of psoriasis is critically dependent on accumulation of epidermal T cells, among the majority express CD8. Here we show that numbers of epidermal CD8 T cells correlated with development of psoriasis in human biopsies, and that blockade of CD8 T cells by depleting antibodies inhibited development of psoriasis in the AGR xenotransplantation mouse model. In human dermis, both CD4 and CD8 T cell numbers correlated significantly with epidermal pathology, indicating a role for dermal CD4 T cells in orchestrating the development of psoriasiform changes induced by epidermis-infiltrating CD8 T cells.

Revision of the genus acrochordiceras hyatt, 1877 (Ammonoidea, Middle Triassic): Morphology, biometry, biostratigraphy and intra-specific variability

The family Acrochordiceratidae Arthaber, 1911 ranges in age from latest Spathian to the middle/late Anisian boundary, and it represents a major component of ammonoid faunas during that time. The middle Anisian genus Acrochordiceras Hyatt, 1877 is the most widespread taxon of the family and occurs abundantly worldwide within the low paleolatitude belt. However, there is a profusion of species names available for Acrochordiceras. This excessive diversity at the species level essentially results from the fact that sufficiently large samples were not available, thus leading to a typological approach to its taxonomy. Based on new extensive collections obtained from the Anisian (Middle Triassic) Fossil Hill Member (Star Peak Group, north-west Nevada) for which a high resolution biostratigraphic frame is available, the taxonomy and biostratigraphy of the genus Acrochordiceras Hyatt, 1877 is herein revised with respect to its intra-specific variation. Morphological and biometric studies (c. 550 bedrock-controlled specimens were measured) show that only one species occurs in each stratigraphic level. Continuous ranges of intra-specific variation of studied specimens enable us to synonymize Haydenites Diener, 1907, Silesiacrochordiceras Diener, 1916 and Epacrochordiceras Spath, 1934 with Acrochordiceras Hyatt, 1877. Three stratigraphically successive species are herein recognized in the low paleolatitude middle Anisian faunas from Nevada: A. hatschekii (Diener, 1907), A. hyatti Meek, 1877 and A. carolinae Mojsisovics, 1882. Moreover, an assessment of intra-specific variation of the adult size range does not support recognition of a dimorphic pair (Acrochordiceras and Epacrochordiceras) as previously suggested by other workers (Epacrochordiceras is the compressed and weakly ornamented end-member variant of Acrochordiceras). The successive middle Anisian species of Acrochordiceras form an anagenetic lineage characterized by increasing involution, adult size and intra-specific variation. This taxonomic revision based on new bedrock-controlled collections is thus an important prerequisite before studying the evolution of the group.

Peut-on évaluer te risque hémorragique tors d'anticoagutation orale [Oral anticoagulation and the risk of major bleeding]

Oral anticoagulants are frequently used in clinical practice. The most important complication of oral anticoagulation is major bleeding. The incidence of major bleeding is about 2-3%/year in randomized controlled trials but may be considerably higher under real life conditions. Major bleeding risk in patients receiving oral anticoagulants depends on factors related to anticoagulation itself (intensity and quality), patient-related factors (demographic characteristics and comorbid diseases), and concomitant treatments with antiplatelet or non-steroidal anti-inflammatory drugs. The role of clinical prediction rules for major bleeding is discussed.

Tibial component positioning in total knee arthroplasty: bone coverage and extensor apparatus alignment.

Correct positioning of the tibial component in total knee arthroplasty (TKA) must take into account both an optimal bone coverage (defined by a maximal cortical bearing with posteromedial and anterolateral support) and satisfactory patellofemoral tracking. Consequently, a compromise position must be found by the surgeon during the operation to simultaneously meet these two requirements. Moreover, tibial tray positioning depends upon the tibial torsion, which has been shown to act mainly in the proximal quarter of the tibia. Therefore, the correct application of the tibial tray is also theoretically related to the level of bone resection. In this study, we first quantified the torsional profile given by an optimal bone coverage for a symmetrical tibial tray design and for an asymmetrical one. Then, for the two types of tibial trays, we measured the angle difference between optimal bone coverage and an alignment on the middle of the tibial tubercule. Results showed that the values of the torsional profile given by the symmetrical tray were more scattered than those from the asymmetrical one. However, determination of the mean differential angle between the position providing optimal bone coverage and the one providing the best patellofemoral tracking indicated that the symmetrical prosthetic tray offered the best compromise between these two requirements. Although the tibiofemoral joint is known to be asymmetric in both shape and dimension, the asymmetrical tray chosen in this study was found to fulfill this compromise with more difficulty.

The biochemistry of drug metabolism-an introduction: part 7. Intra-individual factors affecting drug metabolism.

This review on intra-individual factors affecting drug metabolism completes our series on the biochemistry of drug metabolism. The article presents the molecular mechanisms causing intra-individual differences in enzyme expression and activity. They include enzyme induction by transcriptional activation and enzyme inhibition on the protein level. The influencing factors are of physiological, pathological, or external origin. Tissue characteristics and developmental age strongly influence enzyme-expression patterns. Further influencing factors are pregnancy, disease, or biological rhythms. Xenobiotics, drugs, constituents of herbal remedies, food constituents, ethanol, and tobacco can all influence enzyme expression or activity and, hence, affect drug metabolism.

Administration intra-vitréenne de liposomes pour la vectorisation de principes actifs [The use of liposomes as intravitreal drug delivery system].

Liposomes are vesicular lipidic systems allowing encapsulation of drugs. This article reviews the relevant issues in liposome structure (composition and size), and their influence on intravitreal pharmacokinetics. Liposome-mediated drug delivery to the posterior segment of the eye via intravitreal administration has been addressed by several authors and remains experimental. Liposomes have been used for intravitreal delivery of antibiotics, antivirals, antifungal drugs, antimetabolites, and cyclosporin. Encapsulation of these drugs within liposomes markedly increased their intravitreal half-life, and reduced their retinal toxicity. Liposomes have also shown an attractive potential for retinal gene transfer by intravitreal delivery of plasmids or oligonucleotides.