Suivi thérapeutique de l'imatinib

* Le monitoring (suivi) joue un rôle important pour un traitement et son évaluation - pour autant qu'il se base sur la mesure de marqueurs cliniques adéquats ou de substituts validés. * Pour ce qui est du traitement d'imatinib, le «therapeutic drug monitoring» (TDM) semble être une option utile pour le contrôle du traitement de la LMC. Il utilise la concentration plasmatique de ce médicament comme marqueur. * Les concentrations plasmatiques d'imatinib varient considérablement d'un patient à l'autre sous un même schéma posologique, en raison de la variabilité interindividuelle de sa pharmacocinétique. Il a été démontré que l'exposition plasmatique était en corrélation avec le résultat clinique des patients LMC - aussi bien pour la réponse au traitement que pour le profil d'effets indésirables. * Il n'est pas encore établi si le TDM de l'imatinib doit être utilisé que dans le cas de problèmes cliniques ou si les patients LMC peuvent déjà profiter d'un contrôle préventif systématique «de routine» - de manière à garder la concentration plasmatique dans des marges thérapeutiques. Cela est toujours plus recommandé ces derniers temps. * Pour répondre à cette question, une étude suisse prospective, randomisée et contrôlée recrute des patients LMC traités par imatinib depuis moins de 5 ans et propose en outre le TDM pour tous les patients en cas de problèmes cliniques. - * Monitoring spielt eine wichtige Rolle zur Therapieevaluierung und Behandlungsentscheidung - solange es auf der Basis der Messung von entsprechenden klinischen oder validierten Surrogat-Markern stattfindet. * Im Hinblick auf die Imatinib-Therapie scheint das «Therapeutische Drug-Monitoring» (TDM) ein nützlicher Ansatz zum Therapie-Monitoring der CML-Behandlung zu sein, welches die Plasmakonzentration des Arzneimittels als Marker zur Therapieüberwachung verwendet. * Imatinib-Plasmakonzentrationen variieren beträchtlich von Patient zu Patient unter dem gleichen Dosierungsschema, aufgrund der interindividuell unterschiedlichen Pharmakokinetik des Arzneimittels. Für die Plasmaexposition wurde gezeigt, dass sie mit dem klinischen Outcome von CML-Patienten korreliert - sowohl im Bezug auf das Therapieansprechen als auch auf das Nebenwirkungsprofil. * Es ist noch unklar, ob das TDM von Imatinib nur im Falle von klinischen Problemen Verwendung finden sollte oder ob CML-Patienten bereits von einem systematischen, präventiven «Routine»-Monitoring zur Therapieindividualisierung - zur Steuerung der Plasmakonzentration in einen therapeutischen Bereich - profitieren könnten, welches in letzter Zeit immer häufiger empfohlen wird. * Um diese Fragestellung zu beantworten, nimmt eine prospektive, randomisiert kontrollierte Schweizer Studie CML-Patienten auf, die seit weniger als 5 Jahren mit Imatinib behandelt werden, und bietet das TDM zudem für alle Patienten im Falle von klinischen Problemen an.

La versification françoise ou L'art de bien faire et de bien tourner les vers ([Reprod.]) / par P. Richelet

Collection : Archives de la linguistique française ; 348

Mielipiteitä LTY: n kirjastosta - Kyselyraportti

Lappeenrannan teknillisen yliopiston kirjastossa suoritettiin maaliskuussa 2003 asiakaskysely, jonka tarkoituksena oli selvittää asiakkaiden mielipiteitä kirjastosta, sen palveluista ja mahdollisista kehittämiskohteista. Kysely lähetettiin 731 työntekijälle ja 576 opiskelijalle. Vastausprosentiksi saatiin 16%. Vastausten perusteella kirjastossa käytiin keskimäärin muutaman kerran kuukaudessa. Yleisimmin kirjastossakäytiin lainaamassa kirjastomateriaalia, etsimässä tietoa tai lukemassa lehtiä.Kirjaston tiloihin oltiin suurelta osin tyytyväisiä. Suurimmaksi tilaa koskevaksi ongelmaksi vastaajat kokivat hyllyjärjestyksen epäselvyyden sekä opiskeluun tarkoitetun tilan puutteen. Kirjaston tarjoamista palveluista ja aineistoista käytettiin eniten kirjojen lainausta (92%), lehtikiertoa (henkilökunnalle suunnattupalvelu, 73%), tiedonhakua kirjaston lehdistä ja kirjoista (70%) sekä käsikirjastoa (67%). Vastaajista 1% ei ollut käyttänyt kirjaston aineistoja ja palveluita. Kirjojen lainaus, kirjaston oma Wilma- tietokanta, verkkotietokannat ja kirjojen varaus koettiin tärkeimmiksi kirjaston palvelumuodoiksi. Wilma- tietokanta osoittautui myös hyödyllisimmäksi tietolähteeksi vastausten perusteella. Mielikuvakirjastosta oli vastaajien mielestä yleisesti myönteinen tai melko myönteinen. Tietoa hakevat vastaajat olivat useimmiten saaneet hakemansa tiedon LTY: n kirjastosta. Kyselyssä vastaajille annettiin myös mahdollisuus esittää toiveita, minkälaisia palveluita he kaipaavat, sekä minkälaisia ongelmia he kokevat liittyen kirjaston palveluihin.

Comisiones de la verdad y justicia penal en contextos de transición

Una de las cuestiones más controvertidas en la problemática de la justicia de transición es la relativa a las Comisiones de la Verdad. En este artículo se analizan estos órganos de investigación desde el prisma de la obligación de proveer justicia ante las graves violaciones de derechos humanos y se plantea en qué condiciones una fórmula basada en la verdad y la reparación puede servir a los fines de la justicia penal.

Non-native English-speaking English language teachers: history and research

Although the majority of English language teachers worldwide are non-native English speakers, no research was conducted on these teachers until recently. After the pioneering work of Robert Phillipson in 1992 and Peter Medgyes in 1994, nearly a decade had to elapse for more research to emerge on the issues relating to non-native English teachers. The publication in 1999 of George Braine's book Nonnative educators in English language teaching appears to have encouraged a number of graduate students and scholars to research this issue, with topics ranging from teachers' perceptions of their own identity to students' views and aspects of teacher education. This article compiles, classifies, and examines research conducted in the last two decades on this topic, placing a special emphasis on World Englishes concerns, methods of investigation, and areas in need of further attention.

Short-term effects of particulate matters on pulse pressure in two general population studies.

OBJECTIVES: To explore the association of short-term exposure to particulate matter with aerodynamic diameters less than 10 μm (PM10) with pulse pressure, SBP, and DBP taking outdoor temperature into account in two large population-based studies in Switzerland. METHODS: We used data from the Bus Santé study including 5605 adults in Geneva and the CoLaus study including 6183 adults in Lausanne. PM10 and meteorological data were measured from fixed monitoring stations. We analyzed the association of short-term exposure to PM10 (on the day of examination visit and up to 7 days before) with pulse pressure, SBP, and DBP by linear regression, controlling for potential confounders and effect modifiers. RESULTS: Average PM10 levels were 22.4 μg/m in Geneva and 31.7 μg/m in Lausanne. In adjusted models, for each 10 μg/m increase in 7-day PM10 average, pulse pressure and SBP increased by 0.583 (95% confidence interval, 0.296-0.870) mmHg and 0.490 (0.056-0.925) mmHg in Geneva, and 0.183 (0.017-0.348) mmHg and 0.036 (0.042-0.561) mmHg in Lausanne, respectively. Stronger associations of pulse pressure and SBP with PM10 were observed when outdoor temperature was above 5°C. CONCLUSION: Positive associations of pulse pressure and SBP with short-term exposure to PM10 were found and replicated in the Swiss adult population. Our results suggest that even low levels of air pollution may substantially impact cardiovascular risk in the general population.

Fórmulas estadísticas de resistencia al flujo para hidráulica fluvial

El empleo en hidráulica en lámina libre de las ecuaciones de resistencia al flujo de Gauckler-Manning o Darcy-Weisbach requiere la determinación de un coeficiente de resistencia; determinación que si bien es suficientemente precisa con un reducido esfuerzo y coste en cauces artificiales, resulta mucho más difícil y cara en ríos. Con objeto de eliminar la necesidad de una estimación independiente del coeficiente de resistencia se han desarrollado estadísticamente una serie de ecuaciones para flujo permanente y uniforme en ríos, en las que se prescinde de dicho coeficiente. El presente artículo pretende ser una revisión de las fórmulas de este último tipo más difundidas en la práctica de la hidráulica fluvial.

'Una túnica per al poble': un comentari a 'El Polític' de Plató

Plató té, en Aristòfanes i en Homer, dos usos anteriors de l"art del tissatge com a paradigma de la política. El diferent sentit que té aquest art femení en tots tres autors es desplega en Plató sobretot atenent a la narració homèrica de la mort dels pretendents al tron d"Ítaca que ha estat salvat pel teixir i desteixir de Penèlope. La hipòtesi a partir de la qual s"interpreta El polític pren en consideració precisament aquests antecedents i la variació platònica respecte del que és femení.

Comblike poly(a-alkyl g glutamate)s: computer simulation studies of an intermediate thermal phase.

Monte Carlo (MC) simulations have been used to study the structure of an intermediate thermal phase of poly(R-octadecyl ç,D-glutamate). This is a comblike poly(ç-peptide) able to adopt a biphasic structure that has been described as a layered arrangement of backbone helical rods immersed in a paraffinic pool of polymethylene side chains. Simulations were performed at two different temperatures (348 and 363 K), both of them above the melting point of the paraffinic phase, using the configurational bias MC algorithm. Results indicate that layers are constituted by a side-by-side packing of 17/5 helices. The organization of the interlayer paraffinic region is described in atomistic terms by examining the torsional angles and the end-to-end distances for the octadecyl side chains. Comparison with previously reported comblike poly(â-peptide)s revealed significant differences in the organization of the alkyl side chains.

Eosinophilic fasciitis: Typical abnormalities, variants and differential diagnosis of fasciae abnormalities using MR imaging.

Eosinophilic fasciitis is a rare condition. It is generally limited to the distal parts of the arms and legs. MRI is the ideal imaging modality for diagnosing and monitoring this condition. MRI findings typically evidence only fascial involvement but on a less regular basis signal abnormalities may be observed in neighboring muscle tissue and hypodermic fat. Differential diagnosis of eosinophilic fasciitis by MRI requires the exclusion of several other superficial and deep soft tissue disorders.

Traitement percutané de la thrombose veineuse profonde aiguë [Catheter-based treatment for acute deep vein thrombosis].

Plus de la moitié des patients présentant une thrombose veineuse profonde des membres inférieurs développent un syndrome post-thrombotique. Le risque est particulièrement élevé en cas de thrombose de l'axe principal de drainage veineux comprenant la veine fémorale commune et les veines iliaques. Plusieurs études ont démontré que l'incidence du syndrome post-thrombotique peut être diminuée si une recanalisation des veines ilio-fémorales est obtenue dans la phase aiguë. A l'heure actuelle, des techniques de recanalisation percutanées sont proposées à des patients sélectionnés présentant une thrombose ilio-fémorale. Cet article a pour but de résumer les connaissances actuelles sur la recanalisation percutanée de la thrombose veineuse profonde aiguë. Nearly half of patients with acute lower limb deep vein thrombosis (DVT) develop a post-thrombotic syndrome (PTS). This risk is particularly high in case of proximal DVT of the common femoral and iliac vein, the major lower limbs venous outflow vessel. Several studies have demonstrated that PTS incidence can be reduced with early vein recanalisation. Currently, catheter-based recanalisation therapies can be offered to selected patients with acute ilio-femoral deep vein thrombosis. Aim of the present article is to summarize current knowledge on these catheter-based recanalisation therapies.

Avaluació-tècnica i educació-eròtica en 'El Polític' de Plató (306a-311c)

Allò que ha definit el Foraster, en El Polític de Plató, com a obra del tissatge polític, no és la ciutat, sinó la constitució o formació (paideia) d"uns tipus d"ànima virtuosa als posseïdors de la qual, relligats en comunitat, lliurar el poder de la ciutat. El veritable saber polític se"ns descobreix com un saber que procura l"educació d"aquells que han de tenir cura en comú del poder. S"entén d"aquesta manera que, pròpiament, el saber polític faci i no faci res.

Frequency of and Risk Factors for Depression among Participants in the Swiss HIV Cohort Study (SHCS).

OBJECTIVES: We studied the incidence and prevalence of, and co-factors for depression in the Swiss HIV Cohort Study. METHODS: Depression-specific items were introduced in 2010 and prospectively collected at semiannual cohort visits. Clinical, laboratory and behavioral co-factors of incident depression among participants free of depression at the first two visits in 2010 or thereafter were analyzed with Poisson regression. Cumulative prevalence of depression at the last visit was analyzed with logistic regression. RESULTS: Among 4,422 participants without a history of psychiatric disorders or depression at baseline, 360 developed depression during 9,348 person-years (PY) of follow-up, resulting in an incidence rate of 3.9 per 100 PY (95% confidence interval (CI) 3.5-4.3). Cumulative prevalence of depression during follow-up was recorded for 1,937/6,756 (28.7%) participants. Incidence and cumulative prevalence were higher in injection drug users (IDU) and women. Older age, preserved work ability and higher physical activity were associated with less depression episodes. Mortality (0.96 per 100 PY, 95% CI 0.83-1.11) based upon 193 deaths over 20,102 PY was higher among male IDU (2.34, 1.78-3.09), female IDU (2.33, 1.59-3.39) and white heterosexual men (1.32, 0.94-1.84) compared to white heterosexual women and homosexual men (0.53, 0.29-0.95; and 0.71, 0.55-0.92). Compared to participants free of depression, mortality was slightly elevated among participants with a history of depression (1.17, 0.94-1.45 vs. 0.86, 0.71-1.03, P = 0.033). Suicides (n = 18) did not differ between HIV transmission groups (P = 0.50), but were more frequent among participants with a prior diagnosis of depression (0.18 per 100 PY, 95%CI 0.10-0.31; vs. 0.04, 0.02-0.10; P = 0.003). CONCLUSIONS: Depression is a frequent co-morbidity among HIV-infected persons, and thus an important focus of care.

Oxidative stress in gastric mucosa of asymptomatic humans infected with Helicobacter pylori: effect of bacterial eradication.

BACKGROUND: Inducible nitric oxide synthase (iNOS) and interleukin 8 (IL-8) are positive in approximately 50% of Helicobacter pylori-related diseases but it is not clear whether oxidative stress is also present in H. pylori asymptomatic humans. Our aim was to study the expression of iNOS, superoxide dismutase, catalase and IL-8 production in H. pylori-infected asymptomatic humans, and to investigate the effect of eradication of H. pylori. MATERIALS AND METHODS: Biopsies of corpus and antrum of asymptomatic H. pylori positive and negative humans served for determination of the gastritis score and H. pylori status; iNOS was measured by reverse transcriptase polymerase chain reaction and immunohistochemistry and superoxide dismutase and catalase by immunohistochemistry. IL-8 in biopsies was assessed by enzyme-linked immunosorbent assay. RESULTS: Immunostaining of iNOS, catalase and superoxide dismutase was significantly associated with H. pylori infection and was localized to inflammatory cells. IL-8 concentrations were greater in the H. pylori positive than H. pylori negative group and decreased after bacterial eradication. A decrease in staining for iNOS and catalase was observed after H. pylori eradication. CONCLUSIONS: INOS and antioxidant enzymes are present in gastric biopsies of asymptomatic H. pylori positive humans. Eradication caused a significant decrease in staining for iNOS and catalase. These results indicate that oxidative stress occurs in asymptomatic patients and can be modulated by H. pylori eradication.

Määritelmäjuristi historian käsitteiden kimpussa : keskustelua

Keskustelua. Vastine artikkeliin: Kuuluuko autonominen Suomen valtio historiatietoisuuteemme? / Aki Rasilainen / Historiallinen aikakauskirja (2005) : 3, s. 338-348