Detection of colorectal carcinoma by emission-computerized tomography after injection of 123I-labeled Fab or F(ab')2 fragments from monoclonal anti-carcinoembryonic antigen antibodies.

This clinical study was based on experimental results obtained in nude mice grafted with human colon carcinoma, showing that injected 131I-labeled F(ab')2 and Fab fragments from high affinity anti-carcinoembryonic antigen (CEA) monoclonal antibodies (MAb) gave markedly higher ratios of tumor to normal tissue localization than intact MAb. 31 patients with known colorectal carcinoma, including 10 primary tumors, 13 local tumor recurrences, and 21 metastatic involvements, were injected with 123I-labeled F(ab')2 (n = 14) or Fab (n = 17) fragments from MAb anti-CEA. The patients were examined by emission-computerized tomography (ECT) at 6, 24, and sometimes 48 h after injection using a rotating dual head scintillation camera. All 23 primary tumors and local recurrences except one were clearly visualized on at least two sections of different tomographic planes. Interestingly, nine of these patients had almost normal circulating CEA levels, and three of the visualized tumors weighed only 3-5 g. Among 19 known metastatic tumor involvements, 14 were correctly localized by ECT. Two additional liver and several bone metastases were discovered by immunoscintigraphy. Altogether, 86% of the tumor sites were detected, 82% with F(ab')2 and 89% with Fab fragments. The contrast of the tumor images obtained with Fab fragments suggests that this improved method of immunoscintigraphy has the potential to detect early tumor recurrences and thus to increase the survival of patients. The results of this retrospective study, however, should be confirmed in a prospective study before this method can be recommended for the routine diagnosis of cancer.

Search for nonstandard Higgs boson in diphoton events at p anti-p collisions

We estimate the attainable limits on the coupling of a nonstandard Higgs boson to two photons taking into account the data collected by the Fermilab collaborations on diphoton events. We based our analysis on a general set of dimension-6 effective operators that give rise to anomalous couplings in the bosonic sector of the standard model. If the coefficients of all blind operators have the same magnitude, indirect bounds on the anomalous triple vector-boson couplings can also be inferred, provided there is no large cancellation in the Higgs-gamma-gamma coupling.

Place des antiarthrosiques symptomatiques d'action lente dans l'arthrose (sulfate de chondroïtine, glucosamine, acide hyaluronique) [Role of slow-acting anti-arthritic agents in osteoarthritis (chondroitin sulfate, glucosamine, hyaluronic acid)].

Osteoarthritis (OA) is one of the major causes of pain and of outpatient's clinics. 15 years ago, physiopathology of OA and its potential therapeutic targets were announced to be better understood, but the results of therapeutic trials were finally not as convincing as expected. Slow Acting Drugs (SADs) are part of the treatments evaluated in OA. Even if evidence based medicine is low, positive effects of SADs have been observed. We can reasonably propose these treatments for a short test period. It can sometimes enable us to decrease the dosage of others treatment such as NSAIDs. In any case, the physician must properly inform the patient about products available in Switzerland and must be aware of degrees of purity and costs of the products available on the intemet.

The anti-apoptotic factor Bcl-2 can functionally substitute for the B cell survival but not for the marginal zone B cell differentiation activity of BAFF.

The TNF family ligand B cell-activating factor (BAFF, BLyS, TALL-1) is an essential factor for B cell development. BAFF binds to three receptors, BAFF-R, transmembrane activator and CAML interactor (TACI), and B cell maturation antigen (BCMA), but only BAFF-R is required for successful survival and maturation of splenic B cells. To test whether the effect of BAFF is due to the up-regulation of anti-apoptotic factors, TACI-Ig-transgenic mice, in which BAFF function is inhibited, were crossed with transgenic mice expressing FLICE-inhibitory protein (FLIP) or Bcl-2 in the B cell compartment. FLIP expression did not rescue B cells, while enforced Bcl-2 expression restored peripheral B cells and the ability to mount T-dependent antibody responses. However, many B cells retained immaturity markers and failed to express normal amounts of CD21. Marginal zone B cells were not restored and the T-independent IgG3, but not IgM, response was impaired in the TACI-IgxBcl-2 mice. These results suggest that BAFF is required not only to inhibit apoptosis of maturating B cells, but also to promote differentiation events, in particular those leading to the generation of marginal zone B cells.

Prolonged remission of juvenile-onset respiratory papillomatosis: a post-expositional role of the tetravalent anti-HPV vaccine?

Juvenile-onset recurrent respiratory papillomatosis (JORRP) is an HPV-related neoplasm affecting primarily the larynx. JORRP often requires repeated surgical debridement, which yield variable but generally moderate remission periods. We report the case of a 6-year-old boy with severe course JORRP since the age of 2, requiring tracheostomy, that underwent prolonged remission and was decannulated some months after administration of the HPV vaccine. The post-exposure use for the anti-HPV vaccine in JORRP is a topic of capital interest but still poorly characterized. Some published cases suggest a potential post-exposure role of the vaccine in JORRP, but prospective multicentric trials are still needed.

La construction des identités politiques des reines séleucides

Apamè, Stratonice et Laodice(s) sont les différents protagonistes de cette thèse qui s'attache à saisir comment les souveraines séleucides participent au pouvoir. Principalement centré sur les identités politiques des reines que l'épigraphie grecque et akkadienne nous permet de re-construire, ce travail se développe chronologiquement. Il débute en 324, lors des noces Suse - qui virent Séleucos épouser la bactrienne Apamè, pour se terminer en 177 par la mention de la reine Laodice, la mère du roi Séleucos IV. Nous avons, par ce travail, démontré que les reines séleucides participent pleinement au pouvoir et ce dès le début de la constitution du royaume. Les souveraines mobilisent l'administration, écrivent aux cités, possèdent une autonomie financière grâce aux domaines qu'elles détiennent et disposent de réseaux d'influence personnels. Les identités qu'elles se construisent les lient notamment à la fécondité et leur permettent d'avoir un domaine d'action politique particulier inaccessible au roi. Elles sont en ce sens des partenaires politiques indispensables qui soutiennent à la fois la perpétuation du pouvoir royal et le maintien du territoire séleucide. Si par ce travail nous avons focalisé notre attention sur les basilissai, le cas de la première épouse d'Antiochos II nous a permis de mettre en évidence la polygamie des souverains, l'organisation « hiérarchique » des différentes épouses du roi ainsi que les stratégies développées par le pouvoir séleucide pour désigner celle dont sera issus le successeur. Enfin, le pouvoir séleucide, tel que nous l'avons décrit, ne permet plus de défendre les hypothèses de répudiation ou de régence des souveraines séleucides avancées pour les cas des épouses d'Antiochos II et d'Antiochos III.

Anti-Hellenism and Anti-Classicism in Oscar Wilde's Works. The Second Pole of a Paradoxical Mind.

Thanks to a powerful intellectual weapon, paradox, Oscar Wilde also discovers the dark side of both Classicism and Hellenism. An accurate analysis of his works from the point of view of the Classical Tradition shows an Oscar Wilde who is quite different from the usual Philhellenic one and, above all, from the Platonic one. The aim of this article is to approach a theme which has been hardly studied by classical philologists, that is, anti-classicism and anti-hellenism as an intellectual urge.

Association of pharmacogenetic markers with premature discontinuation of first-line anti-HIV therapy: an observational cohort study.

BACKGROUND: Poor tolerance and adverse drug reactions are main reasons for discontinuation of antiretroviral therapy (ART). Identifying predictors of ART discontinuation is a priority in HIV care. METHODS: A genetic association study in an observational cohort to evaluate the association of pharmacogenetic markers with time to treatment discontinuation during the first year of ART. Analysis included 577 treatment-naive individuals initiating tenofovir (n = 500) or abacavir (n = 77), with efavirenz (n = 272), lopinavir/ritonavir (n = 184), or atazanavir/ritonavir (n = 121). Genotyping included 23 genetic markers in 15 genes associated with toxicity or pharmacokinetics of the study medication. Rates of ART discontinuation between groups with and without genetic risk markers were assessed by survival analysis using Cox regression models. RESULTS: During the first year of ART, 190 individuals (33%) stopped 1 or more drugs. For efavirenz and atazanavir, individuals with genetic risk markers experienced higher discontinuation rates than individuals without (71.15% vs 28.10%, and 62.5% vs 14.6%, respectively). The efavirenz discontinuation hazard ratio (HR) was 3.14 (95% confidence interval (CI): 1.35-7.33, P = .008). The atazanavir discontinuation HR was 9.13 (95% CI: 3.38-24.69, P < .0001). CONCLUSIONS: Several pharmacogenetic markers identify individuals at risk for early treatment discontinuation. These markers should be considered for validation in the clinical setting.

In vivo evaluation of the anti-tumoral effect of sunitinib eluting beads in the rabbit VX2 tumor model

Purpose: To study the anti-tumoral effect of sunitinib eluting beads in the rabbit VX2 tumor modelMaterials: VX2 tumor were implanted in the left liver lobe of New-Zealand white rabbits. Seven animals received 0.2ml of DC Beads loaded with 6mg of sunitinb (group 1), 6 animals received 0.2ml of DC Beads (group 2) and 6 animals received NaCl 0.9% intra arterially in the left hepatic artery. One animal in each group was sacrificed at 24 hours and the others were left to survive. Liver enzyme were measured daily. In group 1 plasmatic sunitinib concentration were measured daily by LC MS/MS tandem mass spectroscopy. At day 15 all living animals were sacrficed. After sacrifice, or premature euthanasia the livers were harvested for determination of the VEGF receptor tyrosine kinase activity by western blot and histopathological examination.Results: In group 1, no animal died during follow-up. In group 2 and 3, respectively 2 and 3 animals died during follow-up. In group 1 plasmatic sunitinib level remained under therapeutic concentration during the whole experiment. There was an evident lack of phosphorylation of the RTK In group 1 and there was an augmentation of the RTK phosphorylation in group 2 at 24 hours. No difference in RTK activity was noticable at 15 days. From the histopathological point of view it was unpossible to differentiate treatment induced from spontaneous necrosis of tumors.Conclusions: Administration of sunitinib eluting Beads in VX2 carrying rabbits inhibits the activation of RTK's triggered by ischemia. It also seems to prolong survival of the treated animals.

Analyse comparative des ressources financières des partis politiques suisses

Les partis politiques ont comme vocation de structurer le débat démocratique et de constituer un trait d'union entre le citoyen et l'Etat. En Suisse, ils sont fortement sollicités en raison de l'importante quantité de scrutins organisés chaque année aux échelons communal, cantonal et national, mais leur organisation reste très peu professionnalisée. Comme ils doivent par ailleurs faire face à l'effritement de leur base partisane et à l'inflation des coûts de la politique, le risque est grand qu'ils soient mis en difficulté dans l'accomplissement de leur tâche d'intégration et de formation de l'opinion. Cette étude se concentre sur les pratiques de financement des partis cantonaux et nationaux du PDC, du PRD, du PS, de l'UDC et des Verts. S'appuyant sur les données empriques récoltées en 1997 et en 2007, elle décrit dans quelle mesure les moyens financiers des partis ont évolué au cours des dix dernières années. Les analyses portent sur le volume et l'origine des fonds et elles permettent notamment de saisir comment s'articulent les clivages en matière de financement. Die politischen Parteien haben die Aufgabe, die demokratische Debatte zu strukturieren und ein verbindendes Element zwischen dem Bürger und dem Staat zu bilden. In der Schweiz werden sie angesichts der grossen Anzahl jährlich auf kommunaler, kantonaler und nationaler Ebene durchgeführten Wahlgänge besonders stark beansprucht, ihre Organisationen sind aber wenig professionalisiert. Da sich die Parteien heute mit abnehmenden Parteienbindungen und steigenden Kosten der Politik konfrontiert sehen, steigt das Risiko, dass sie ihre Aufgaben der Integration und der politischen Meinungsbildung kaum mehr wahrnehmen können. Diese Arbeit konzentriert sich auf die Finanzierungspraktiken der kantonalen und nationalen Parteien CVP, FDP, SP, SVP und Grüne. Die Analysen stützen sich ab auf empirische Angaben zu Herkunft und Umfang der Parteifinanzen, die in den Jahren 1997 und 2007 erhoben wurden und erlauben es, die Unterschiede hinsichtlich der Finanzierung zu erläutern.