Removable quadhelices and transpalatal arches.

Abstract

A mixed dentition treatment can efficiently and effectively be provided using a 2×4 appliance. The indications for early treatment are discussed and advantages of fixed appliances over traditionally used removable appliances illustrated using four case reports.     

Evolution of biomarkers of liver fibrosis and liver insufficiency in hepatitis C virus-infected patients treated with pegylated interferon plus ribavirin and rituximab

Therapeutic options in hepatitis C virus (HCV)-related vasculitis may target the viral trigger using antiviral therapy [pegylated interferon plus ribavirin (PEG-IFN/RBV)], and/or the downstream B-cell arm of autoimmunity with rituximab (RTX). To date, no study has compared the efficacy of RTX combined with PEG-IFN/RBV on biomarkers of liver insufficiency in patients with severe liver fibrosis. Twenty-eight untreated HCV-related vasculitis patients with severe liver fibrosis (Metavir F3-F4) were included: 14 patients received RTX plus PEG-IFN/RBV and 14 patients PEG-IFN/RBV. The main clinical and biological data were recorded and compared at baseline, month 3 (M3), M12 and M24 of follow-up. Baseline epidemiological, clinical, virological and immunological features were similar between the groups. The virological response did not differ between cases and controls. The alanine aminotransferase (ALT) level and HCV viral load did not increase in patients treated with RTX. Serum albumin levels increased in patients treated with RTX at M3 and M6 (108% and 111% of baseline value; P = 0.06 and P = 0.13), whereas it was stable in patients treated without RTX. FibroTest values decreased from 0.70 at baseline to 0.59 at M3 (P = 0.5) and returned to 0.69 at M24 in the RTX-PEG-IFN/RBV group, whereas they were stable in the PEG-IFN/RBV group. RTX is safe in patients with severe HCV liver fibrosis and vasculitis. No beneficial effects of RTX were evidenced on liver fibrosis progression, but we found interesting correlations with the serum albumin level, FibroTest values and B-cell count.     

吻合器痔上黏膜环形切除术治疗重度混合痔的临床体会

目的总结吻合器痔上黏膜环形切除术（PPH）治疗重度混合痔的临床效果及关键环节的操作技巧。方法回顾性分析2006年8月至2012年11月期间在我院接受PPH治疗的183例重度混合痔或环形内痔患者的临床资料。结果本组患者手术时间为（28.5±3.1）min。所有患者均一次性完成手术。平均住院时间5.2 d,无一例患者术后出现大出血、大便失禁、感染等情况。随访1个月～3年,平均随访时间26个月,均无复发及再出血、肛门狭窄、大便失禁等并发症出现。结论 PPH作为一种微创精细手术,其操作过程中的每一个细节我们都应该掌握好,才能更有效地提高重度混合痔患者的临床治疗效果及减少并发症的发生。     

Anti‐LFA‐1 or rapamycin overcome costimulation blockade‐resistant rejection in sensitized bone marrow recipients

While costimulation blockade‐based mixed chimerism protocols work well for inducing tolerance in rodents, translation to preclinical large animal/nonhuman primate models has been less successful. One recognized cause for these difficulties is the high frequency of alloreactive memory T cells (Tmem) found in the (pre)clinical setting as opposed to laboratory mice. In the present study, we therefore developed a murine bone marrow transplantation (BMT) model employing recipients harboring polyclonal donor‐reactive Tmem without concomitant humoral sensitization. This model was then used to identify strategies to overcome this additional immune barrier. We found that B6 recipients that were enriched with 3 × 10⁷ T cells isolated from B6 mice that had been previously grafted with Balb/c skin, rejected Balb/c BM despite costimulation blockade with anti‐CD40L and CTLA4Ig (while recipients not enriched developed chimerism). Adjunctive short‐term treatment of sensitized BMT recipients with rapamycin or anti‐LFA‐1 mAb was demonstrated to be effective in controlling Tmem in this model, leading to long‐term mixed chimerism and donor‐specific tolerance. Thus, rapamycin and anti‐LFA‐1 mAb are effective in overcoming the potent barrier that donor‐reactive Tmem pose to the induction of mixed chimerism and tolerance despite costimulation blockade.     

Ischemic preconditioning via epsilon protein kinase C activation requires cyclooxygenase-2 activation in vitro

The signaling pathway of cyclooxygenase-2 (COX-2) induction following ischemic preconditioning (IPC) in brain remains undefined. To determine role of COX-2 in ischemic preconditioning, we used two in vitro models: mixed cortical neuron/astrocyte cell cultures and organotypic hippocampal slice cultures. We simulated IPC by exposing cell or slice cultures to 1 h or 15 min of oxygen/glucose deprivation (OGD), respectively, 48 h prior to ischemia. To mimic ischemia in vitro, we exposed cell or slice cultures to OGD of 4 h or 40 min, respectively. In cell cultures, these experiments revealed that COX-2 induction peaked at 24 h following IPC in cell culture. Inhibition of COX-2 activation with 50 microM NS-398 (a COX-2 selective inhibitor) abolished IPC-mediated neuroprotection in both in vitro models. Next, we tested whether epsilon protein kinase C (epsilonPKC) and extracellular signal regulated kinase 1/2 (ERK1/2) activation was involved in IPC-mediated neuroprotection and COX-2 expression in cell culture. Cell cultures were treated with an epsilonPKC-specific activating peptide (psiepsilonRACK, 100 nM) for 1 h, and 48 h later were exposed to OGD. epsilonPKC activation increased ERK1/2 phosphorylation and COX-2 induction and conferred neuroprotection similar to IPC. Additionally, inhibition of either epsilonPKC or ERK1/2 activation abolished COX-2 expression and neuroprotection due to ischemic preconditioning. These results demonstrate a crucial role for the epsilonPKC-->ERK1/2-->COX-2 pathway in the induction of neuroprotection via ischemic preconditioning.     

Toluene and methylethylketone: effect of combined exposure on their metabolism in rat

1.?Multiple exposures are ubiquitous in industrial environments. In this article, we highlight the risks faced by workers and complete the data available on the metabolic impact of a common mixture: toluene (TOL) and methylethylketone (MEK).

2.?Rats were exposed by inhalation under controlled conditions either to each solvent individually, or to mixtures of the two. How the interaction between the two solvents affected their fate in the blood and brain, their main relevant urinary metabolites (o-cresol, benzylmercapturic acid for TOL and 2,3-butanediols for MEK) and their hepatic metabolism were investigated.

3.?Although the cytochrome P450 concentration was unchanged, and the activities of CYP1A2 and CYP2E1 isoforms were not additively or synergistically induced by co-exposure, TOL metabolism was inhibited by the presence of MEK (and vice versa). Depending on the relative proportions of each compound in the mixture, this sometimes resulted in a large increase in blood and brain concentrations. Apart from extreme cases (unbalanced mixtures), the amount of o-cresol and benzylmercapturic acid (and to a lesser extent 2,3-butanediols) excreted were proportional to the blood solvent concentrations.

4.?In a co-exposure context, ortho-cresol and benzylmercapturic acid can be used as urinary biomarkers in biomonitoring for employees to relatively accurately assess TOL exposure.     

Functional Mixed Effects Model for the Analysis of Dose-Titration Studies

Functional data analysis, which analyzes data that can be represented by curves or images, has many potential applications in clinical trials. Motivated by a real example, this study constructs a functional mixed effects model for analyzing a clinical outcome that is observed continuously over a long period of time. A penalized spline (P-spline)-based method is applied to obtain the estimators of the mean function and the time-varying coefficients. Simulation studies are conducted to investigate the consistency, efficiency, and robustness of the method. To illustrate the use of the method, a real data analysis is performed and produces interpretable results.     

Direct-acting antiviral agents for hepatitis C virus-mixed cryoglobulinaemia: dissociated virological and haematological responses

The hepatitis C virus-positive (HCV+) mixed cryoglobulinaemia (MC) is associated with haematological alterations such as monoclonal B-cell lymphocytosis or non-Hodgkin lymphomas (NHLs). Antiviral therapy for MC, based on interferon and ribavirin, has been shown to be able to eliminate the viral replication as well as the B-cell monoclonal alterations. Many studies have reported the efficacy of direct-acting antivirals (DAAs) in the treatment of HCV+ MC. However, some authors noticed the persistence of haematological diseases despite HCV eradication. To verify the effects of DAAs on B-cell proliferation, we evaluated 67 patients with HCV+ MC. Six patients had an overt NHL and 30% had monoclonal B-lymphocytosis. In 20% of the patients, the mutation L265P of the myeloid differentiation factor 88 (MYD88) gene was detected in peripheral blood. All patients had negative HCV viraemia at week 12; one had a breakthrough, while two cases relapsed. A complete clinical response of vasculitis was seen in 60% of the patients. Among the six patients with NHL, one showed a complete response, whereas in the others there were no changes in the number and size of the nodes. Among the patients carrying a clonal population in peripheral blood, only 22% became negative. These data indicate that DAAs are not able to eliminate the clonal alterations induced by HCV in a large proportion of cases.