Left atrial function is impaired in cirrhosis: a speckle tracking echocardiographic study

Purpose

Abnormalities in left ventricular systolic and diastolic function have been described in patients with cirrhosis. There are no studies on left atrial (LA) function in these patients. We aimed to evaluate LA function in cirrhosis patients using myocardial deformation imaging.

Methods

We included 111 hospitalized and ambulatory patients with cirrhosis and 18 healthy controls. A comprehensive echocardiographic evaluation was performed; LA strain was assessed using velocity vector imaging.

Results

Peak atrial longitudinal strain at the end of ventricular systole was lower in patients [41.9 % (34.4–51.0) vs. 48.0 % (42.0–57.1), p = 0.02]. No differences were found in atrial strain before atrial contraction in patients and controls [17.5 % (14.3–22.4) vs. 20.7 % (14.1–26.3), p = 0.14]. On multivariate linear regression analysis, E′ velocity was the only variable independently associated with peak atrial longitudinal strain (R ² = 47 %). No correlation was found between the LA volume index (LAVI) and peak atrial longitudinal strain (r = ?0.136, p = 0.219). Peak atrial longitudinal strain performed better than LAVI in identifying patients with elevated filling pressures (AUC = 0.81 vs. 0.52).

Conclusions

Patients with cirrhosis have abnormal atrial reservoir function, which may be related to the same factors associated with impaired ventricular relaxation. LA enlargement in cirrhosis may not reflect elevated filling pressures and should not be used as an isolated marker of diastolic dysfunction. The atrial “pump” function does not seem to be affected in cirrhosis patients.     

Effects of short-term high-fat overfeeding on genome-wide DNA methylation in the skeletal muscle of healthy young men

Aims/hypothesis

Energy-dense diets that are high in fat are associated with a risk of metabolic diseases. The underlying molecular mechanisms could involve epigenetics, as recent data show altered DNA methylation of putative type 2 diabetes candidate genes in response to high-fat diets. We examined the effect of a short-term high-fat overfeeding (HFO) diet on genome-wide DNA methylation patterns in human skeletal muscle.

Methods

Skeletal muscle biopsies were obtained from 21 healthy young men after ingestion of a short-term HFO diet and a control diet, in a randomised crossover setting. DNA methylation was measured in 27,578 CpG sites/14,475 genes using Illumina's Infinium Bead Array. Candidate gene expression was determined by quantitative real-time PCR.

Results

HFO introduced widespread DNA methylation changes affecting 6,508 genes (45%), with a maximum methylation change of 13.0 percentage points. The HFO-induced methylation changes were only partly and non-significantly reversed after 6–8 weeks. Alterations in DNA methylation levels primarily affected genes involved in inflammation, the reproductive system and cancer. Few gene expression changes were observed and these had poor correlation to DNA methylation.

Conclusions/interpretation

The genome-wide DNA methylation changes induced by the short-term HFO diet could have implications for our understanding of transient epigenetic regulation in humans and its contribution to the development of metabolic diseases. The slow reversibility suggests a methylation build-up with HFO, which over time may influence gene expression levels.     

Combined cytoplasmic and membranous EGFR and p53 overexpression is a poor prognostic marker in early stage oral squamous cell carcinoma

J Oral Pathol Med (2012) 41 : 559–567 Objective: Our aim was to evaluate the expression of several molecules that regulate growth, the cell cycle and signalling pathways including EGFR, p53, p16 and p27 in oral squamous cell carcinomas (OSCC). We examined their utility as prognostic markers by relating to clinicopathological characteristics and the clinical outcome. Patients and methods: Using tissue microarray technology, we analysed 67 primary OSCC and examined immunohistochemical expression of EGFR, p53, p16 and p27. Multivariate analysis was conducted to examine their role in survival. Results: Many of the markers were highly expressed in these cancers. Membranous EGFR expression in 95.2%, both membrane and cytoplasm expression in 35%, p53 expression in 61.6%, p27 expression in 89.5% and p16 expression in 27.9% of cases. In the multivariate analysis, independent prognostic influence of a lower overall survival was determined only for advanced tumour stage (P < 0.001), p53 overexpression (P = 0.004), EGFR cytoplasm and membrane co‐expression location (P = 0.002) and p16 reduced expression (P = 0.002). When considering a subgroup of early stage tumours, p53 overexpression (P = 0.028) and combined membranous and cytoplasm EGFR co‐expression (P = 0.039) were indicators of a lower overall survival. For disease‐free survival, in addition to these three factors, the histological grade (P = 0.011) showed independent prognostic values. Conclusion: The independent value of EGFR subcellular location (cytoplasm and membrane) and p53 overexpression in overall survival even in early stages of OSCC suggests that these markers may serve as reliable biological markers to identify high‐risk subgroups and to guide therapy.     

Rehabilitative treatment of cleft lip and palate: experience of the Hospital for Rehabilitation of Craniofacial Anomalies/USP (HRAC/USP)--Part 1: overall aspects

Cleft lip and palate is the most common among craniofacial malformations and causes several esthetic and functional implications that require rehabilitation. This paper aims to generally describe the several aspects related to this complex pathology and the treatment protocol used by the Hospital for Rehabilitation of Craniofacial Anomalies, University of S?o Paulo (HRAC-USP) along 40 years of experience in the treatment of individuals with cleft lip and palate.     

The Number of Bleaching Sessions Influences Pulp Tissue Damage in Rat Teeth

Introduction

Hydrogen peroxide tooth bleaching is claimed to cause alterations in dental tissue structures. This study investigated the influence of the number of bleaching sessions on pulp tissue in rats.

Methods

Male Wistar rats were studied in 5 groups (groups 1S–5S) of 10 each, which differed by the number (1–5) of bleaching sessions. In each session, the animals were anesthetized, and 35% hydrogen peroxide gel was applied to 3 upper right molars. Two days after the experimental period, the animals were killed, and their jaws were processed for light microscope evaluation. Pulp tissue reactions were scored as follows: 1, no or few inflammatory cells and no reaction; 2, <25 cells and a mild reaction; 3, between 25 and 125 cells and a moderate reaction; and 4, 125 or more cells and a severe reaction. Results from each experimental group were compared between groups and within groups to the corresponding unbleached upper left molars and analyzed for significant differences using the Kruskal-Wallis test (P < .05).

Results

All tissue sections showed significant bleaching-induced changes in the dental pulp. After 1 bleaching session, necrotic tissue in the pulp horns and underlying inflammatory changes were observed. The extent and intensity of these changes increased with the number of bleaching sessions. After 5 sessions, the changes included necrotic areas in the pulp tissue involving the second third of the radicular pulp and intense inflammation in the apical third.

Conclusions

The number of bleaching sessions directly influenced the extent of pulp damage.