Treatment of chronic hepatitis c in 3 patients with hcv-induced severe thrombocytopenia

BACKGROUND: Thrombocytopenia has been described in HCV infection even in the absence of cirrhosis and splenomegaly. Different mechanisms have been proposed, including immunemediated platelet (plt) destruction. Here, we report on the treatment of 3 patients with HCV-HIV coinfection and HCVinduced severe thrombocytopenia. PATIENTS AND TREATMENT: All patients had an infection with HCV genotype 3, an intermediate fibrosis stage (Metavir F2 or F3), HIV infection controlled by antiretroviral combination therapy, and severe, steroid-refractory thrombocytopenia. Pegylated interferon-α2a (PEG-IFN-α2a) was started at 45 or 90 μg per week and doses were rapidly increased in the following, while ribavirin (RBV) was prescribed at standard doses. Treatment was pursued for 48 weeks. Two patients received intravenous immunoglobulins (IVIG) during the first weeks of PEG-IFN-α2a and RBV combination therapy. RESULTS: A significant increase in plt counts (from 17, 39 and 37 G/l, respectively, to > 100 G/l) was observed in the 3 patients while they experienced a virological response. Thrombocytopenia relapsed in one patient together with a relapse of chronic hepatitis C. The other 2 patients achieved a sustained virological response (SVR), with normal plt counts at follow-up in one and persistent mild thrombocytopenia in the other. CONCLUSIONS: Carefully titrated PEG-IFN-α2a and RBV combination therapy may be performed safely in this difficult-totreat patient population, with close monitoring and eventually concomitant IVIG during the first weeks. SVR can lead to normalization or significant improvement of plt counts, suggesting a causative role of HCV in this condition.

Effective exposure to solar UV in building workers: influence of local and individual factors.

Excessive exposure to solar UV light is the main cause of skin cancers in humans. UV exposure depends on environmental as well as individual factors related to activity. Although outdoor occupational activities contribute significantly to the individual dose received, data on effective exposure are scarce and limited to a few occupations. A study was undertaken in order to assess effective short-term exposure among building workers and characterize the influence of individual and local factors on exposure. The effective exposure of construction workers in a mountainous area in the southern part of Switzerland was investigated through short-term dosimetry (97 dosimeters). Three altitudes, of about 500, 1500 and 2500 m were considered. Individual measurements over 20 working periods were performed using Spore film dosimeters on five body locations. The postural activity of workers was concomitantly recorded and static UV measurements were also performed. Effective exposure among building workers was high and exceeded occupational recommendations, for all individuals for at least one body location. The mean daily UV dose in plain was 11.9 SED (0.0-31.3 SED), in middle mountain 21.4 SED (6.6-46.8 SED) and in high mountain 28.6 SED (0.0-91.1 SED). Measured doses between workers and anatomical locations exhibited a high variability, stressing the role of local exposure conditions and individual factors. Short-term effective exposure ranged between 0 and 200% of ambient irradiation, indicating the occurrence of intense, subacute exposures. A predictive irradiation model was developed to investigate the role of individual factors. Posture and orientation were found to account for at least 38% of the total variance of relative individual exposure, and were also found to account more than altitude on the total variance of effective daily exposures. Targeted sensitization actions through professional information channels and specific prevention messages are recommended. Altitude outdoor workers should also benefit from preventive medical examination.

Spiritual Kinship, Political Mobilization and Social Cooperation: a Swiss Alpine valley in the Eighteenth and Nineteenth Centuries

In this chapter I will present some observations and results about Ritual Kinship and political mobilization of popular groups in an Alpine valley: the Val de Bagnes, in the Swiss canton of Valais, - a mountain valley, well known today thanks to the tourist station of Verbier - where we can rely on excellent sources about local families. This region presents a particular political situation, because the 11 major villages of the valley form only one commune, which includes the whole valley.¦There are two major reasons to choose the Val de Bagnes for our inquiry on kinship and social networks in a rural society:¦A. The existence of sharp political and social conflicts during the 18th and the 19th centuries;¦B. The existence of almost systematic genealogical data between 1700 and 1900. (Casanova, Gard, Perrenoud 2005-08)¦The 18th century was characterized by the struggle of an important part of the community of Bagnes against the feudal lord, the abbot of St-Maurice. The culminating point was a local upheaval in 1745 in Le Châble, during which the abbot was forced to sign several documents in accordance with the wishes of the rebels (Guzzi-Heeb 2007). In the 19th century feudal lordship was abolished, but now the struggle confronted a liberal-radical faction and the conservative majority in the commune.¦The starting point of my presentation focuses on this question: which role did spiritual kinship play in the political mobilization of popular groups and in the organization of competing factions? This question allows us to shed light on some utilizations and meanings of spiritual kinship in the local society. Was spiritual kinship a significant instrument for economic cooperation? Or was it a channel for privileged social contacts and transactions?

The role of bile acid retention and a common polymorphism in the ABCB11 gene as host factors affecting antiviral treatment response in chronic hepatitis C.

Summary.  The outcome of hepatitis C virus (HCV) infection and the likelihood of a sustained virological response (SVR) to antiviral therapy depends on both viral and host characteristics. In vitro studies demonstrated that bile acids (BA) interfere with antiviral interferon effects. We investigate the influence of plasma BA concentrations and an ABCB11 polymorphism associated with lower transporter expression on viral load and SVR. Four hundred and fifty-one Caucasian HCV-patients treated with PEG-interferon and ribavirin were included in the study. ABCB11 1331T>C was genotyped, and plasma BA levels were determined. The 1331C allele was slightly overrepresented in HCV-patients compared to controls. In HCV-patients, a significant difference between patients achieving SVR vs non-SVR was observed for HCV-2/3 (5 vs 9 μm; P = 0.0001), while median BA levels in HCV-1 were marginally elevated. Normal BA levels <8 μm were significantly associated with SVR (58.3%vs 36.3%; OR 2.48; P = 0.0001). This difference was significant for HCV-2/3 (90.7%vs 67.6%; P = 0.002) but marginal in HCV-1 (38.7%vs 27.8%; P = 0.058). SVR rates were equivalent between ABCB11 genotypes for HCV-1, but increased for HCV-2/3 (TT 100%vs CC 78%; OR 2.01; P = 0.043). IL28B genotype had no influence on these associations. No correlation between BA levels and HCV RNA was detected for any HCV genotype. The higher allelic frequency of ABCB11 1331C in HCV-patients compared to controls may indirectly link increased BA to HCV chronicity. Our data support a role for BA as host factor affecting therapy response in HCV-2/3 patients, whereas a weaker association was found for HCV-1.

Participle Preposing and Other Related Phenomena in Old Spanish and Old Catalan

El participi i altres fenòmens relacionats en el Castellà i el Català antic

Análisis discursivo de ser y estar: aspectos de la periodización de sus usos y valores

En esta comunicación se presentan los resultados de un trabajo en curso cuyo objetivo es profundizar en la explicación de la naturaleza del cambio lingüístico que comporta la progresiva sustitución de ser por estar en castellano medieval y en la periodización de este cambio. La comunicación se organiza en cuatro apartados. El primero expone los aspectos generales del comportamiento de ser y estar en oraciones atributivas, pasivas resultativas y construcciones locativas. El segundo se centra en la descripción de la distribución de estos verbos en el Cantar de Myo Çid, obra en la que estar se atestigua únicamente en construcciones locativas. En el tercer apartado se examinan los datos del Calila e Dimna, los cuales ponen de manifiesto el avance de estar en detrimento de ser en oraciones atributivas cuyo predicado expresa estado, en algunas pasivas resultativas y en construcciones locativas. El último apartado presenta una propuesta de análisis en la línea de Roberts y Roussou (1999, 2002 y 2003) que es perfectamente compatible con las propuestas pragmáticas en la línea de la Teoría de la Relevancia

Pronoms àtons i tònics en funció d’objecte a les estructures de doblament de clític del català antic

En aquest treball descriurem algunes de les estructures que integren pronoms tònics en funció d’objecte directe o d’objecte indirecte i examinarem les dades relatives a les configuracions de doblament de clític i de pronom tònic aïllat en català antic. L’apartat 2 presenta la identificació i descripció de les dades que estudiarem, les quals han estat extretes del Corpus del Català Antic constituït sota el projecte Vers una Sintaxi Històrica del Català. A l’apartat 3 s’examina la freqüència de les estructures esmentades i les dues seccions següents se centren en l’estudi de la forma ell en contrast amb a ell. A 6 s’ofereix una explicació general de la posició que ocupen els pronoms tònics dins la frase i a 7 es fa una comparació de les dades del català antic amb les del portuguès antic. Finalment, a 8 se citen els resultats d’aquest estudi preliminar

L'expressió de la conseqüència en català antic: les consecutives d’intensitat - manera

Tradicionalment els gramàtics hem agrupat sota el rètol d’oracions consecutives estructures molt diverses que tenen en comú el fet que la segona de les dues proposicions relacionades expressa la conseqüència del que es diu a la primera. Dins d’aquestes estructures s’han distingit dos grans grups. D’una banda, les anomenades consecutives paratàctiques o il·latives, on la relació lògica establerta entre les dues proposicions té caràcter asindètic o bé es codifica mitjançant un marcador discursiu i, de l’altra, les consecutives subordinades, on la proposició que expressa la conseqüència s’introdueix a través de nexos subordinants. En aquest article volem tractar l’evolució d’un tipus d’oracions consecutives subordinades, les anomenades consecutives d’intensitat-manera que il·lustrem amb els exemples de català medieval

Los nexos causales y finales en el Curial e Güelfa: descripción de una sincronía histórica

En este estudio se examinan las estructuras que expresan causa yfinalidad en el Curial e Güelfa. El estudio cuantitativo de los nexossimples y compuestos evidencia que el autor sigue un modelo retóricoacotado por la tradición de la scripta medieval catalana. A diferenciade los primeros textos, la lengua del Curial es una prosa trabada,alejada de la oralidad, en la que los nexos no suelen ser ambiguos y,por tanto, no se precisan inferencias pragmáticas para interpretar lasrelaciones lógicas existentes entre las proposiciones

Foco oracional y polaridad: en torno a una asimetría entre el español y el catalán

En aquest estudi s’examina la perifèria esquerra del català antic en comparació amb la del castellà antic, i es descriuen les diferències més rellevants

Ordre de mots i estructura informativa a la llengua de Francesc Eiximenis

En aquest estudi s’examina la llengua d’alguns textos de Francesc Eiximenis (concretament, el ‘Dotzè del Crestià’ i les cartes autògrafes publicades per Martí 2002) per tal d’aprofundir en la distribució de l’estructura informativa i el consegüent ordre de mots que utilitza l’autor. L’objectiu d’aquesta comunicació és aprofundir en els casos d’ avantposició del català antic que correspon a una estructura de focalització feble (no contrastiva)

Variación y periferia izquierda: la Anteposición de Foco Débil en español y en catalán

El objetivo de éste estudio es el análisis diacrónico y comparativo {español-catalán} de la Anteposición de Foco Débil (AFD) en las lenguas románicas medievales

Mesoclitic Romance futures and conditionals vs participle preposing

(INFINITIVE + CLITIC + AUX) is an evidential configuration in Old Spanish and Old Catalan, whereas (PARTICIPLE + CLITIC + AUX) is an instance of weak or unmarked focus fronting. The evidentiality of mesoclitic structures can be put forward on the bases of three main arguments: a) mesoclisis is not compulsory (i.e., whenever you have a clitic, you can either have mesoclisis or proclisis/enclisis); b) mesoclitic futures and conditionals areattested in interrogative sentences (with wh- elements); and c) they are not found in derived adverbial clauses (which is what you expect if they have an evidential value, since they bring about intervention effects corresponding to the derivational account of conditional and temporal sentences, for example - see Haegeman 2007 and ff.), and are related to high modal expressions (thus interfering with MoodPIrrealis)

Long circulating half-life and high tumor selectivity of the photosensitizer meta-tetrahydroxyphenylchlorin conjugated to polyethylene glycol in nude mice grafted with a human colon carcinoma.

In a mode of nude mice bearing a human colon carcinoma xenograft, the biodistribution and tumor localization of metatetrahydroxyphenylchlorin (m-THPC) coupled to polyethylene glycol (PEG) were compared with those of the free form of this photosensitizer used in photodynamic therapy (PDT). At different times after i.v. injection of both forms of 125I-labeled photosensitizer, m-THPC-PEG gave on average a 2-fold higher tumor uptake than free m-THPC. In addition, at early times after injection, m-THPC-PEG showed a 2-fold longer blood circulating half-life and a 4-fold lower liver uptake than free m-THPC. The tumor to normal tissue ratios of radioactivity concentrations were always higher for m-THPC-PEG than for free m-THPC at any time point studied from 2 to 96 hr post-injection. Significant coefficients of correlation between direct fluorescence measurements and radioactivity counting were obtained within each organ tested. Fluorescence microscopy studies showed that m-THPC-PEG was preferentially localized near the tumor vessels, whereas m-THPC was more diffusely distributed inside the tumor tissue. To verify whether m-THPC-PEG conjugate remained phototoxic in vivo, PDT experiments were performed 72 hr after injection and showed that m-THPC-PEG was as potent as free m-THPC in the induction of tumor regression provided that the irradiation does for m-THPC-PEG conjugate was adapted to a well-tolerated 2-fold higher level. The overall results demonstrate first the possibility of improving the in vivo tumor localization of a hydrophobic dye used for PDT by coupling it to PEG and second that a photosensitizer conjugated to a macromolecule can remain phototoxic in vivo.

Intravenous iron in inflammatory bowel disease

The prevalence of anemia across studies on patients with inflammatory bowel disease (IBD) is high (30%). Both iron deficiency (ID) and anemia of chronic disease contribute most to the development of anemia in IBD. The prevalence of ID is even higher (45%). Anemia and ID negatively impact the patient's quality of life. Therefore, together with an adequate control of disease activity, iron replacement therapy should start as soon as anemia or ID is detected to attain a normal hemoglobin (Hb) and iron status. Many patients will respond to oral iron, but compliance may be poor, whereas intravenous (i.v.) compounds are safe, provide a faster Hb increase and iron store repletion, and presents a lower rate of treatment discontinuation. Absolute indications for i.v. iron treatment should include severe anemia, intolerance or inappropriate response to oral iron, severe intestinal disease activity, or use of an erythropoietic stimulating agent. Four different products are principally used in clinical practice, which differ in their pharmacokinetic properties and safety profiles: iron gluconate and iron sucrose (lower single doses), and iron dextran and ferric carboxymaltose (higher single doses). After the initial resolution of anemia and the repletion of iron stores, the patient's hematological and iron parameters should be carefully and periodically monitored, and maintenance iron treatment should be provided as required. New i.v. preparations that allow for giving 1000-1500 mg in a single session, thus facilitating patient management, provide an excellent tool to prevent or treat anemia and ID in this patient population, which in turn avoids allogeneic blood transfusion and improves their quality of life.