Paracetamol in therapeutic dosages and acute liver injury: causality assessment in a prospective case series

Background: Acute liver injury (ALI) induced by paracetamol overdose is a well known cause of emergency hospital admission and death. However, there is debate regarding the risk of ALI after therapeutic dosages of the drug. The aim is to describe the characteristics of patients admitted to hospital with jaundice who had previous exposure to therapeutic doses of paracetamol. An assessment of the causality role of paracetamol was performed in each case. Methods: Based on the evaluation of prospectively gathered cases of ALI with detailed clinical information, thirty-two cases of ALI in non-alcoholic patients exposed to therapeutic doses of paracetamol were identified. Two authors assessed all drug exposures by using the CIOMS/RUCAM scale. Each case was classified into one of five categories based on the causality score for paracetamol. Results: In four cases the role of paracetamol was judged to be unrelated, in two unlikely, and these were excluded from evaluation. In seven of the remaining 26 cases, the RUCAM score associated with paracetamol was higher than that associated with other concomitant medications. The estimated incidence of ALI related to the use of paracetamol in therapeutic dosages was 0.4 per million inhabitants older than 15 years of age and per year (99%CI, 0.2-0.8) and of 10 per million paracetamol users-year (95% CI 4.3-19.4). Conclusions:Our results indicate that paracetamol in therapeutic dosages may be considered in the causality assessment in non-alcoholic patients with liver injury, even if the estimated incidence of ALI related to paracetamol appears to be low

Case-control study for colorectal cancer genetic susceptibility in EPICOLON: previously identified variants and mucins

<p>Abstract</p> <p>Background</p> <p>Colorectal cancer (CRC) is the second leading cause of cancer death in developed countries. Familial aggregation in CRC is also important outside syndromic forms and, in this case, a polygenic model with several common low-penetrance alleles contributing to CRC genetic predisposition could be hypothesized. Mucins and GALNTs (N-acetylgalactosaminyltransferase) are interesting candidates for CRC genetic susceptibility and have not been previously evaluated. We present results for ten genetic variants linked to CRC risk in previous studies (previously identified category) and 18 selected variants from the mucin gene family in a case-control association study from the Spanish EPICOLON consortium.</p> <p>Methods</p> <p>CRC cases and matched controls were from EPICOLON, a prospective, multicenter, nationwide Spanish initiative, comprised of two independent stages. Stage 1 corresponded to 515 CRC cases and 515 controls, whereas stage 2 consisted of 901 CRC cases and 909 controls. Also, an independent cohort of 549 CRC cases and 599 controls outside EPICOLON was available for additional replication. Genotyping was performed for ten previously identified SNPs in <it>ADH1C</it>, <it>APC</it>, <it>CCDN1</it>, <it>IL6</it>, <it>IL8</it>, <it>IRS1</it>, <it>MTHFR</it>, <it>PPARG</it>, <it>VDR </it>and <it>ARL11</it>, and 18 selected variants in the mucin gene family.</p> <p>Results</p> <p>None of the 28 SNPs analyzed in our study was found to be associated with CRC risk. Although four SNPs were significant with a <it>P</it>-value < 0.05 in EPICOLON stage 1 [rs698 in <it>ADH1C </it>(OR = 1.63, 95% CI = 1.06-2.50, <it>P</it>-value = 0.02, recessive), rs1800795 in <it>IL6 </it>(OR = 1.62, 95% CI = 1.10-2.37, <it>P</it>-value = 0.01, recessive), rs3803185 in <it>ARL11 </it>(OR = 1.58, 95% CI = 1.17-2.15, <it>P</it>-value = 0.007, codominant), and rs2102302 in <it>GALNTL2 </it>(OR = 1.20, 95% CI = 1.00-1.44, <it>P</it>-value = 0.04, log-additive 0, 1, 2 alleles], only rs3803185 achieved statistical significance in EPICOLON stage 2 (OR = 1.34, 95% CI = 1.06-1.69, <it>P</it>-value = 0.01, recessive). In the joint analysis for both stages, results were only significant for rs3803185 (OR = 1.12, 95% CI = 1.00-1.25, <it>P</it>-value = 0.04, log-additive 0, 1, 2 alleles) and borderline significant for rs698 and rs2102302. The rs3803185 variant was not significantly associated with CRC risk in an external cohort (MCC-Spain), but it still showed some borderline significance in the pooled analysis of both cohorts (OR = 1.08, 95% CI = 0.98-1.18, <it>P</it>-value = 0.09, log-additive 0, 1, 2 alleles).</p> <p>Conclusions</p> <p><it>ARL11</it>, <it>ADH1C</it>, <it>GALNTL2 </it>and <it>IL6 </it>genetic variants may have an effect on CRC risk. Further validation and meta-analyses should be undertaken in larger CRC studies.</p

A proposal for a shallow ontologization of WordNet

En este artículo se presenta el trabajo que se está realizando para la llamada ontologización superficial de WordNet, una estructura orientada a superar muchos de los problemas estructurales de la popular base de conocimiento léxico. El resultado esperado es un recurso multilingüe más apropiado que los ahora existentes para el procesamiento semántico a gran escala.This paper presents the work carried out towards the so-called shallow ontologization of WordNet, which is argued to be a way to overcome most of the many structural problems of the widely used lexical knowledge base. The result shall be a multilingual resource more suitable for large-scale semantic processing

Paracetamol in therapeutic dosages and acute liver injury: causality assessment in a prospective case series

Background: Acute liver injury (ALI) induced by paracetamol overdose is a well known cause of emergency hospital admission and death. However, there is debate regarding the risk of ALI after therapeutic dosages of the drug. The aim is to describe the characteristics of patients admitted to hospital with jaundice who had previous exposure to therapeutic doses of paracetamol. An assessment of the causality role of paracetamol was performed in each case. Methods: Based on the evaluation of prospectively gathered cases of ALI with detailed clinical information, thirty-two cases of ALI in non-alcoholic patients exposed to therapeutic doses of paracetamol were identified. Two authors assessed all drug exposures by using the CIOMS/RUCAM scale. Each case was classified into one of five categories based on the causality score for paracetamol. Results: In four cases the role of paracetamol was judged to be unrelated, in two unlikely, and these were excluded from evaluation. In seven of the remaining 26 cases, the RUCAM score associated with paracetamol was higher than that associated with other concomitant medications. The estimated incidence of ALI related to the use of paracetamol in therapeutic dosages was 0.4 per million inhabitants older than 15 years of age and per year (99% CI, 0.2-0.8) and of 10 per million paracetamol users-year (95% CI 4.3-19.4). Conclusions: Our results indicate that paracetamol in therapeutic dosages may be considered in the causality assessment in non-alcoholic patients with liver injury, even if the estimated incidence of ALI related to paracetamol appears to be low

Publicaciones del Instituto de Biología Aplicada. Tomos 52-53

[Tomo 52] María del Pilar Gracia. — Contribución al estudio de las tecamebas amebas (Protozoa, Thecamoeboidea). Tecamebas esfagnícolas de la Península Ibérica. Enrique Gadea. — Algunas consideraciones sobre el poblamiento nematódico muscícola de Menorca. F. Español.—Notas sobre anóbidos (col.). Manuel González. — Contribución al conocimiento de los curculiónidos del Mediterráneo occidental. - XII. Los Barynotus ibéricos. María Concepción Rigau y Miguel Berbel. — Correlaciones de los pigmentos foliares con el crecimiento y la producción. - II. Estudio de las correlaciones existentes entre los pigmentos clorofila a y carotinoide y la producción en Lolium perenne L. Alejandro Palomo González. — Sobre alguno-; nematodos muscícolas de la zona de Ledesma (prov. Salamanca). Javier Fernández Casas. — Gypsophila niontserratii, nueva especie del Sur de España. Linnavuori. — A new species of the genus CompsidoIon Rt. (Het. Miridae) from Spain. Carmen Bach-Piella. — Tisanuros de la fauna española. Nota sobre Machilidae de Marchagaz (Cáceres).[Tomo 53] María del Pilar Gracia. — Tecamebas muscícolas de la Península Ibérica. A. Casinos. — Algunas consideraciones sobre la anatomía funcional del cráneo de los teleósteos. M. Dolores Romero Duque. — Algunos focos de infección de Heterodera schachtii Schmidt (Nematoda) en remolacha, en la región española de Levante. Enrique Gadea. — Algunas consideraciones en torno a la nematofauna muscícola de la isla de Zákynthos (Grecia). C. Altimira. — Notas malacológicas. J. Nadal. — Efecto del tiofosfato de 0-0 dimetilo y 0-(metilo-3 metil tio-4 fenilo) sobre una población Chlidonias hybrida (Pall) en La Encañizada (provincia de Tarragona). J. Gosálbez. — Primer coloquio sobre Mastozoología Ibérica. F. Español. — Notas sobre anóbidos (Col.). Carmen Bach Piella. — Sobre algunos caracteres faunísticos y ecológicos de los Machiladae de la Cordillera Central y provincia de Salamanca. J. Andrés. — Variaciones cronológicas de la intensidad del crecimiento longitudinal en plantas de maíz y avena.Peer reviewe