No abstract

Hepatocellular carcinoma (HCC) occurring in nonfibrotic liver represents a rare, ill-defined subgroup of HCC without cirrhosis in which mechanisms of hepatocarcinogenesis remain unclear. The aim of our study was to assess epidemiological factors and detailed histopathologic changes in the nontumoral liver of patients developing such tumors. Of 330 HCCs resected in our institution between 1985 and 1998, we retrospectively analyzed 80 cases (53 men, 27 women; mean age, 51 ؎ 16 years) in which the nontumoral liver showed no (n ‫؍‬ 28) or minimal (n ‫؍‬ 52) portal fibrosis without any septal fibrosis. In the group with no portal fibrosis there was no male predominance, and patients were significantly younger (44 ؎ 19 years vs. 54 ؎ 14 years) than those with minimal portal fibrosis. Sixty-seven tumors were typical HCCs, 8 were of fibrolamellar type, and 5 were hepatocholangiocarcinomas. Mean tumor size was 10 ؎ 5 cm. Risk factors for HCC development were found in 30 patients: hepatitis B (n ‫؍‬ 17) or C (n ‫؍‬ 2) virus infections, alcohol consumption (n ‫؍‬ 11), and hemochromatosis (n ‫؍‬ 1). In the nontumoral liver, periportal and lobular necrosis, mild portal inflammation, steatosis, and iron overload were present in 15%, 57%, 52%, and 54% of cases, respectively. Liver cell changes were noted in 6%. This study emphasizes the need for strict criteria to classify HCC without cirrhosis. HCC in nonfibrotic liver is a distinct subgroup in which nontumoral liver shows nonspecific minimal changes without regeneration or premalignant lesion. Etiologic factors are often unidentified, although presence of HBV infection in 21% suggests a direct oncogenic role of this virus. (HEPATOLOGY 2000;32:200-204.)

Both obesity and alcohol can cause oxidative stress, cytokine induction, and steatohepatitis. To determine the consequences of their combination, we compared the hepatic effects of moderate ethanol binges in lean and obese ob/ob mice. Mice received water or ethanol (2.5 g/kg) by gastric intubation daily for 4 days, and were killed 2 hours after the last administration. Some obese mice also received pentoxifylline, an inhibitor of tumor necrosis factor-␣ (TNF-␣) production, before each ethanol administration. In lean mice, these moderate ethanol doses did not increase plasma TNF-␣ and hepatic caspase-3 activity, but triggered some apoptotic hepatocytes. Naive ob/ob mice had a few necrotic and apoptotic hepatocytes, but exhibited little oxidative stress, possibly because of adaptive increases in manganese superoxide dismutase, heat shock protein 70 (Hsp70), mitochondrial cytochrome c, and mitochondrial DNA. Alcohol administration to ob/ob mice did not increase oxidative stress despite increased CYP2E1, but increased plasma TNF-␣, further increased Hsp70, and profoundly decreased p65 nuclear factor B (NF-B) protein and DNA-binding activity in nuclear extracts. Caspase-3 was activated, and more apoptotic hepatocytes were found in intoxicated obese mice than naive obese mice. In intoxicated obese mice, pentoxifylline fully prevented the increase in plasma TNF-␣ the decrease in nuclear NF-B activity, and the increase in hepatic caspase-3, and it also decreased hepatic triglycerides. In conclusion, obese mice develop adaptations that may limit oxidative stress. Moderate ethanol intoxication does not increase oxidative stress in obese mice, but increases TNF-␣ and also decreases nuclear NF-B activity, thus unleashing the apoptotic effects of TNF-␣. Supplementary material for this article can be found on the HEPATOLOGY website (http://interscience.wiley.com/jpages/ 0270-9139/suppmat/index.html). (HEPATOLOGY 2005;42:1280-1290

The role of gender in language change, as discussed in Eckert (1989a) and Labov (1990), forms the context for an exploration of the role of gender in the development of Cajun English. Neither Principle I, Ia, or II predicts the role of gender in Cajun English, which leads us to question the generalizability of the principles to the specific sociolinguistic setting of this study—a closed cultural enclave. The study of four sociolinguistic variables and three generations of speakers reveals two patterns of language change: a curvilinear or v-shaped age pattern and a linear age pattern. These patterns relate in a complex way to changes from above and below the level of consciousness. We support Eckert's call for a finer specification of the social categories but suggest alternatives to the ethnographic method. Using a variety of sources of information on the social life and sociohistory of three generations, we find an intimate association between the sociohistory of this Cajun community and the linguistic behavior of each generation.

Intraductal papillary-mucinous tumours (IPMTs) of the pancreas are heterogeneous proliferations characterized by a malignant potential. The molecular mechanisms underlying the tumourigenesis process are not well understood. Recently, it has been shown that IPMTs secreting the mucin antigen MUC2 have a better prognosis, but the complete pattern of MUC gene expression has not yet been established. The aims of this study were to evaluate the mucin gene expression in 57 IPMTs and eight related lesions surgically resected and to relate MUC gene expression to the histological diagnosis. In situ hybridization (ISH) was performed in 28 cases with probes specific for the MUC1, MUC2, MUC3, MUC4, MUC5AC, MUC5B, MUC6, and MUC7 genes. An immunohistochemical analysis was carried in all 65 cases and in 90 conventional ductal adenocarcinomas of the pancreas using MUC1, MUC2, and MUC5AC antibodies. IPMTs of adenoma (dysplasia) type exhibited high expression of MUC2 (93%), MUC5AC (97%), and, to a lesser extent, of MUC4 (71%), all of which were also observed in colloid carcinomas associated with IPMTs. In contrast, IPMTs with simple hyperplasia, intraductal oncocytic papillary neoplasms, and pyloric glandular adenomas exhibited little or no expression of MUC2. The mucin expression profile supports the existence of two types of invasive tumour associated with IPMTs: a colloid and an ordinary form. The latter shows a pattern similar to the conventional ductal adenocarcinomas with a loss of MUC2 and a gain of MUC1 and has a greater tendency to metastasize. In conclusion, the altered expression of mucin, characteristic of IPMT of adenoma type and of colloid carcinomas, may contribute to the better clinical outcome of these neoplasms, compared to conventional pancreatic ductal adenocarcinomas.

The study of the 2700 occurrences of phrase-terminal extension particles (e.g., tout ça ‘all that’, des affaires de même ‘things like that’) in two large corpora of Montréal French reveals that they are typically formed of some combination of a quantifier, a generic and a comparative, and that the particle is optionally prefaced by a connector (the conjunctions puis, et ‘and’, ou ‘or’). The 76 particle types (not counting minor variations) also include a good number of fixed forms (e.g., et cetera) often having an onomatopoeic aspect (e.g., patati patata). Extension particles can be characterized through prosodic, syntactic, and semantic criteria. The analysis bears on the sociodemographic conditioning of overall rates of particle use; of choices within the quantifier, generic, and comparative categories; and of preference for each of four major classes of particle: those containing a universal quantifier, those containing an existential quantifier, those consisting of just a generic and a comparative, and fixed forms. The discourse insertion of the four classes is also analyzed in terms of connector, type of discourse transition, the complexity of the term(s) semantically “extended” by the particle, and the discourse genre. The clearest result pertaining to overall rates of use is an age-grading effect, whereby speakers use fewer particles as they grow older. Within the components, women use more quantifiers than men, and both generics and comparatives are sharply stratified by social class and age. The reconstituted particles tend to favor certain co-occurrence patterns and avoid others more than could be predicted from the component distributions, consistent with a stylistic concord effect. As for the four classes of particle, it is the presence and nature of the connector that have the strongest effects, where puis contrasts with both ou and the null connector, while the complexity of the extended term distinguishes among the classes both by virtue of the number of terms and their syntactic complexity. As is predictable from functional considerations the sociodemographic factors do not contrast the two semantically most distinct classes, involving universal versus existential quantifiers. The linguistic validity of the four classes is confirmed by the fact that their quantitative conditioning is not predictable from the strong sociodemographic conditioning of their component elements, but rather reflects their differential suitability for various discourse functions.

Newly graduated nurses need to demonstrate high levels of competencies when they enter the workplace. A competency-based approach to their education is recommended to ensure patients' needs are met. A continuing education intervention consistent with the competency-based approach to education was designed and implemented in eight care units in two teaching hospitals. It consists of a series of 30-min reflective practice groups on clinical events that newly graduated nurses encountered in their practice. It was evaluated using a descriptive longitudinal evaluative research design, combining individual and group interviews with stakeholders, the analysis of facilitators' journal entries, and a research assistant's field notes. The results suggest that issues associated with the implementation of the continuing education intervention revolved around leadership for managers, flexibility for nursing staff, and role shifting for the facilitators. Newly graduated nurses who participated in the study noted that the reflective practice sessions contributed to the development of both clinical reasoning and leadership. Nursing managers stated the advantages of the intervention on nurses' professional development and for the quality and safety of care. Following the end of the study, participants from two units managed to pursue the activity during their work time.

No abstract