Volume et profil de consommation d’alcool des élèves et des camarades scolaires comme prédicteurs de l’agression et de la victimisation: une analyse multiniveaux auprès d’adolescents suisses

Volume and profile of alcohol consumption among students and classmates as predictors of aggression and victimization: a multilevel analysis among Swiss adolescents

Objective:  

To test the effects of the volume of alcohol consumption and drinking patterns on alcohol-related aggression and victimization, both at the individual and class levels.     

Biliary stent causing colovaginal fistula: case report.

OBJECTIVES: Perforation of the bowel during placement of a biliary stent is a known complication of this procedure. We report the endoluminal loss of a biliary stent during routine stent extraction that ultimately led to a chronic colovaginal fistula. This case emphasizes the need for evaluation of fecal passage of stents in patients with a known dislodged prosthesis. CASE REPORT: A 65-year-old white female underwent biliary stent placement for an episode of choledocholithiasis. The stent was lost in the duodenum during routine extraction. The patient was managed expectantly. She denied ever passing this stent via the rectum and began to develop symptoms of colovaginal fistula. Evaluation found a retained biliary stent in the sigmoid colon and a fistula into the vagina. The patient underwent elective low anterior resection and colovaginal fistula repair. DISCUSSION: Reports exist of migration of stents that lead to acute colonic perforation and the need for emergent surgery. For this reason, it has been suggested that dropped or migrated stents be purposefully retrieved. However, if the option of expectant observation is used, it is important to clearly document the fecal passage of these stents and be prepared to retrieve these objects if they have a prolonged bowel transit time.     

Dual β-Catenin and γ-Catenin Loss in Hepatocytes Impacts Their Polarity through Altered Transforming Growth Factor-β and Hepatocyte Nuclear Factor 4α Signaling

Hepatocytes are highly polarized epithelia. Loss of hepatocyte polarity is associated with various liver diseases, including cholestasis. However, the molecular underpinnings of hepatocyte polarization remain poorly understood. Loss of β-catenin at adherens junctions is compensated by γ-catenin and dual loss of both catenins in double knockouts (DKOs) in mice liver leads to progressive intrahepatic cholestasis. However, the clinical relevance of this observation, and further phenotypic characterization of the phenotype, is important. Herein, simultaneous loss of β-catenin and γ-catenin was identified in a subset of liver samples from patients of progressive familial intrahepatic cholestasis and primary sclerosing cholangitis. Hepatocytes in DKO mice exhibited defects in apical-basolateral localization of polarity proteins, impaired bile canaliculi formation, and loss of microvilli. Loss of polarity in DKO livers manifested as epithelial-mesenchymal transition, increased hepatocyte proliferation, and suppression of hepatocyte differentiation, which was associated with up-regulation of transforming growth factor-β signaling and repression of hepatocyte nuclear factor 4α expression and activity. In conclusion, concomitant loss of the two catenins in the liver may play a pathogenic role in subsets of cholangiopathies. The findings also support a previously unknown role of β-catenin and γ-catenin in the maintenance of hepatocyte polarity. Improved understanding of the regulation of hepatocyte polarization processes by β-catenin and γ-catenin may potentially benefit development of new therapies for cholestasis.

A hallmark of epithelial cells is polarization, which is achieved by the orchestration of external cues, such as cellular contact, extracellular matrix, signal transduction, growth factors, and spatial organization.¹ Hepatocytes in the liver show a unique polarity by forming several apical and basolateral poles within a cell.² The apical poles of adjacent hepatocytes form a continuous network of bile canaliculi into which bile is secreted, whereas the basolateral membrane domain forms the sinusoidal pole, which secretes various components, such as proteins or drugs, into the blood circulation.³ Loss of hepatic polarity has been associated with several cholestatic and developmental disorders, including progressive familial intrahepatic cholestasis (PFIC) and primary sclerosing cholangitis (PSC).^4,5 Although the molecular mechanisms governing hepatocyte polarity have been extensively studied in the in vitro systems, there is still a significant gap in our understanding of how polarity is established within the context of tissue during development or maintained during homeostasis.^6,7 Similarly, the molecular pathways contributing to hepatic polarity are not entirely understood, and a better comprehension of hepatic polarity regulation is thus warranted.Previous studies have confirmed the role of hepatocellular junctions, such as tight and gap junctions, in the maintenance of hepatocyte polarity.^8,9 Studies done in vitro and in vivo have shown that loss of junctional proteins, such as zonula occludens protein (ZO)-1, junctional adhesion molecule-A, and claudins, lead to impairment of polarity and distorted bile canaliculi formation.10, 11, 12, 13 In addition, proteins involved in tight junction assembly, such as liver kinase B1, are also involved in polarity maintenance.¹⁴ Among adherens junction proteins, various in vitro cell culture models have confirmed the role of E-cadherin in the regulation of hepatocyte polarity, possibly through its interaction with β-catenin.^15,16 However, there is a lack of an in vivo model to study the role of adherens junction proteins in hepatocyte polarity and their misexpression contributing to various liver diseases.β-Catenin plays diverse functions in the liver during development, regeneration, zonation, and tumorigenesis.17, 18, 19 The relative contribution of β-catenin as part of the adherens junction is challenging to study because like in other tissues, γ-catenin compensates for the β-catenin loss in the liver.^20,21 To address this redundancy, we previously reported a hepatocyte-specific β-catenin and γ-catenin double-knockout (DKO) mouse model was reported.²² Simultaneous deletion of β-catenin and γ-catenin in mice livers led to cholestasis, partially through the breach of cell-cell junctions. However, more comprehensive understanding of the molecular underpinnings of the phenotype is needed.In the current study, prior preclinical findings of dual β-catenin and γ-catenin loss were extended to a subset of PFIC and PSC patients. In vivo studies using the murine model with hepatocyte-specific dual loss of β-catenin and γ-catenin showed complete loss of hepatocyte polarity compared to the wild-type controls (CONs). Loss of polarity in DKO liver was accompanied by epithelial-mesenchymal transition (EMT), activation of transforming growth factor (TGF)-β signaling, and reduced expression of hepatocyte nuclear factor 4α (HNF4α). Our findings suggest that β-catenin and γ-catenin and in turn adherens junction integrity, are critical for the maintenance of hepatocyte polarity, and any perturbations in this process can contribute to the pathogenesis of cholestatic liver disease.     

Multiple endocrine cell types in thyroid medullary carcinoma

Summary 10 cases of thyroid medullary carcinoma (TMC) have been studied ultrastructurally and histochemically. Well differentiated calcitonin-producing C cells were present in all tumours, being prevalent in 9 cases. 5-Hydroxytryptamine (5HT) storing cells were found in two cases, somatostatin immunoreactive cells in at least 5 cases and ACTH-immunoreactive cells in 4 cases. Ultrastructurally, at least 3 types of apparently non-C cells were observed. Type 1 cells with large, poorly osmiophilic granules resembling those of gastroenteropancreatic D cells, were present in 6 cases; they appeared to correlate well with somatostatin immunoreactive cells. Type 2 cells with large osmiophilic granules were found in 5 cases; they resembled ACTH-MSH cells of the human pituitary and may correspond to the ACTH-immunoreactive cells of light microscopy. Type 3 cells with small granules and an unknown function were found in 6 cases, always in scarce number. It is concluded that TMC, although mainly made up of C cells, usually contains large proportions of other endocrine cell types.Supported in part by grant N. 75.00630.04 from the Italian National Research Council (C.N.R.). P.F. is a fellow of the Fondazione Anna Villa Rusconi, Varese     

Colorectal polyposis with mixed juvenile and adenomatous patterns

Summary An unusual form of colorectal polyposis is described displaying juvenile, adenomatous and mixed patterns in a 17-year-old girl. Although juvenile polyposis is generally considered to be non-neoplastic in nature, in both the present and in other case reports histological findings support a neoplastic nature. Since an increase in the incidence of large bowel carcinomas has been found in subjects with a previous diagnosis of juvenile polyposis, these patients should be considered to be at risk, and submitted to follow up.     

The presence and possible role of monocyte infiltration in human chronic proliferative glomerulonephritides. Light microscopic, immunofluorescence, and histochemical correlations.

Twenty-seven cases of chronic glomerulonephritis with proliferative pattern (11 cases of primary mixed IgG-IgM cryoglobulinemia, 8 cases of SLE, and 8 cases of primary membranoproliferative glomerulonephritis) were studied with particular attention to the glomerular monocyte infiltration. The latter, detected by means of nonspecific esterase technique, was compared with the presence of hyaline thrombi and intraluminal immunoglobulin lumps. Monocyte infiltration was heavy and almost constant in cryoglobulinemia, less important in SLE, and practically absent in membranoproliferative glomerulonephritis. By means of immunofluorescence technique on paraffin embedded material, monocytes are shown to contain IgG and IgM, suggesting a phagocytic activity on some types of immune complexes. Since monocytes are migrant cells, and therefore easily removable from the glomeruli by the bloodstream, it seems that they could be responsible for regression of glomerular hypercellularity as reported in some patients with cryoglobulinemia showing clinical improvement.     

Intertubular capillary changes in kidney allografts: a morphologic investigation on 61 renal specimens.

A total of 61 kidney allograft specimens (51 biopsies and 10 nephrectomies) from 44 patients were investigated. Transplant glomerulopathy (TGP) was found in 38 specimens. Electron microscopy disclosed peculiar intertubular capillary changes (ITCC) in 47 specimens (all those showing TGP and nine without TGP). They were characterized by splitting and multilayering of the basement membranes. TGP and ITCC were graded and found mild (in 23 and 22 specimens), moderate (in 11 and 16 specimens), and severe (in four and nine specimens). Both worsened with time lapse from transplantation. When both were compared in single specimens, their grading was similar or, with a few exceptions, more severe for ITCC. TGP and ITCC were more frequent in biopsies with morphologic evidence of rejection and less frequent in patients treated with Cyclosporine A. Repeated biopsies and nephrectomies were studied in 10 patients and a somewhat more precocious appearance of ITCC than of TGP was found. Earlier and more severe ITCC were found in two patients who had had two transplants as compared to those with one. Morphologic similarities between TGP and ITCC suggest a common pathogenetic mechanism related to endothelial damage. The association to the histological evidence of rejection as well as the apparently protective activity of Cyclosporine A could support the involvement of an immune-mediated mechanism in agreement with what is reported in literature. The constant association of ITCC and TGP and its possible more precocious appearance enforce the diagnostic value of the former, which allows to infer the presence or the subsequent development of TGP even in biopsies where glomeruli are lacking.     

Hepatic histology of patients with HIV infection and chronic hepatitis C treated with interferon.

AIMS: To evaluate the histological changes seen in liver biopsies after interferon (IFN) treatment in patients with chronic hepatitis C and human immunodeficiency virus (HIV) infection. METHODS: Twenty four intravenous drug users with chronic hepatitis C were investigated histologically before beginning a 12 month course of IFN treatment and 18 months later. Twelve were HIV positive, without opportunistic or other viral infections (group A), and 12 were HIV negative (group B). RESULTS: According to alanine amino-transferase concentrations, four sustained responders and eight non-responders were found in group A; six sustained responders, five relapsers, and one non-responder were found in group B. HCV RNA became negative in one sustained responder of group A and in the six sustained responders of group B. When histological findings of biopsies performed before therapy and 18 months later were compared, no significant changes in the mean value of Knodell's index and subindices were found in group A, whereas in group B Knodell's index, piecemeal necrosis, and focal hepatocellular necrosis decreased significantly. CONCLUSIONS: In chronic hepatitis C, coinfection with HIV showed a tendency towards a lower response to IFN, although this did not reach statistical significance; however, none of the HIV positive patients developed cirrhosis during the follow up and this should be considered in clinical management of such patients.