Diastolic cardiac dysfunction is a predictor of dismal prognosis in patients with liver cirrhosis

Background and purpose

Left ventricular diastolic dysfunction (LVDD) constitutes the prominent characteristic of cirrhotic cardiomyopathy, but its relevance on the clinical course of cirrhotic patients has not been clearly defined. The aim of the study was to evaluate the relationship of LVDD with the severity and etiology of liver disease and to investigate whether it affects the outcome of cirrhotic patients.

Methods

Cardiac function of 45 cirrhotics was studied by a tissue Doppler imaging echocardiography. Diagnosis of LVDD was made according to the latest guidelines of the American Society of Echocardiography. All patients were followed up for a period of 2 years. Death or liver transplantation was the endpoint of the study.

Results

LVDD was found in 17 (38 %) of 45 patients. Its presence was not found to be associated with the etiology and stage of cirrhosis, but its severity was directly correlated with the Child-Pugh score. At the end of follow-up, 14 patients had died; 9 had LVDD (9/17, 53 %) and 5 had not (5/28, 18 %). Patients who died at the beginning of observation period had a higher Child-Pugh and MELD score, higher BNP, lower albumin and more prolonged QTc. On Kaplan-Meier analysis, patients with LVDD had statistically significantly worse prognosis compared to those without (p = 0.013, log rank: 5.495). Low albumin values (p = 0.003) and presence of LVDD (p = 0.017) were independent predictive factors of mortality.

Conclusions

LVDD is a common complication of cirrhosis. As its development seems to be related to a worse prognosis, patients with LVDD must be under a strict follow-up.     

Glucocorticoid and proteasome inhibitor impact on the leukemic lymphoblast: multiple, diverse signals converging on a few key downstream regulators

Twenty years ago a proteasome inhibitor was suggested as therapy for glucocorticoid-resistant multiple myeloma, a disease that involves terminally differentiated B cells. Since then, research has proven that it has utility on a number of tumors resistant to chemotherapy. Hematologic malignancy, however, often involves lesser differentiated cells, which have a high potential to modulate their intrinsic machinery and thereby activate alternative rescue pathways. A corresponding multiplicity of therapies is not always practical. One approach to conditions with heterogeneous physiology is to identify key biochemical mediators, thereby reducing the number of treatment targets. Results from several ongoing studies indicate convergence of genomically diverse signal pathways to a limited number of key downstream regulators of apoptosis. Convergence of pathways can be exploited to address the problem of genetic heterogeneity in acute leukemia: this would mean treating multiple molecular aberrations with fewer drugs and enhanced therapeutic benefit.     

Enamel gloss changes induced by orthodontic bonding

ABSTRACT

Objective: The purpose of this study was to assess enamel gloss changes induced by orthodontic bracket bonding with a light-cured composite or a light-cured resin-reinforced glass ionomer cement.

Setting: The Department of Biomaterials, School of Dentistry, National and Kapodistrian University of Athens, Greece.

Design: Laboratory study.

Methods: A total of twenty extracted upper human first premolars were included in this study and each tooth served as a control for itself. Their buccal surfaces were subjected to 60^o-angle gloss measurement (G%60) with a standardized and secure repeated analysis of the same site. After baseline evaluation, a bracket was bonded on the buccal surface of each tooth. Half of the specimens were bonded with acid-etching and a light-cured composite whereas the other half with a light-cured resin-reinforced glass ionomer cement without prior enamel conditioning. Gloss measurements were repeated after bracket debonding and removal of the composite/glass ionomer cement with an 18-fluted carbide bur. Gloss differences between the two measurement conditions (baseline and post-debonding) were analyzed through linear regression with standard errors derived using the bootstrap method. Level of significance was set at a?<?0.05.

Results: A statistically significant difference was detected between the tested groups for the outcome of interest. Teeth bonded with light-cured composite exhibited larger enamel gloss changes as compared to resin-reinforced glass ionomer cement (β?=?0.74; 95% CIs: 0.10, 1.38; p?=?0.02).

Conclusions: Bracket bonding with two common bonding protocols (acid-etching with a light-cured composite vs. no etching with resin reinforced glass-ionomer cement) and subsequently debonding and adhesive removal with an 18-fluted carbide bur induced enamel gloss changes.     

Differential expression of the TL1A/DcR3 system of TNF/TNFR-like proteins in large vs. small intestinal Crohn's disease

Background

TNF-like cytokine 1A provides co-stimulatory signals to activated lymphocytes through binding to death-domain receptor-3. Decoy receptor-3 inhibits death-domain receptor-3 signalling, rendering immunocytes resistant to apoptosis. These functions may be important for the pathogenesis of Crohn's disease.

Aims

To study the mucosal and systemic expression of Decoy receptor-3 and TNF-like cytokine 1A in Crohn's disease, in relation to disease activity, localization, and response to treatment.

Methods

Soluble Decoy receptor-3 and TNF-like cytokine 1A were measured by ELISA in active or quiescent Crohn's disease. Relative mRNA expression in non-affected and inflamed intestinal mucosa was determined by real-time RT-PCR.

Results

We found significant upregulation of Decoy receptor-3 and its ligands TNF-like cytokine 1A and FasL in inflamed intestinal mucosa of Crohn's disease patients. During active disease, Decoy receptor-3 and TNF-like cytokine 1A were detected in the serum in the majority of patients. Intestinal inflammation was strongly associated with these elevations as they were absent during remission and significantly reduced with anti-inflammatory treatment. Regional diversity was observed as Decoy receptor-3 was upregulated in colonic and ileal sites, whereas TNF-like cytokine 1A was preferentially induced in the large bowel mucosa and systemic circulation of patients with colonic involvement.

Conclusions

TNF-like cytokine 1A and Decoy receptor-3 are upregulated during active Crohn's disease and may participate in disease pathogenesis and offer novel therapeutic opportunities.