Fabry disease and vascular risk factors: future strategies for patient-based studies and the knockout murine model

Fabry disease is secondary to deficiency of the lysosomal enzyme α-galactosidase A, leading to altered glycosphingolipid metabolism and accumulation that is often associated with endothelial dysfunction. Current evidence suggests that there is impairment of the vascular nitric oxide pathway, with abnormalities evident in the cerebral circulation and in the dermal vasculature of patients with Fabry disease. Some of these findings have been confirmed in a mouse model of Fabry disease. The murine model, however, allows investigation of Fabry disease at a non-clinical level and a near complete investigation of biological processes within an affected tissue. This is of particular utility in allowing gene expression analysis of clinically inaccessible tissues such as the aorta.
Conclusion: Future developments in array technology for proteins and DNA single nucleotide polymorphism analysis, together with gene expression microarray analysis, may open a new chapter in our understanding of the biology of lysosomal storage disorders.     

Acoustic reflectometry profiles of endotracheal and esophageal intubation

BACKGROUND: Acoustic reflectometry can be used to create a "one-dimensional image" of a cavity, such as the airway and lung, with the image displayed as an area-length curve. This pilot study was undertaken to determine whether acoustic reflectometry could be used to distinguish between an endotracheal and an esophageal intubation. METHODS: Ten adult patients underwent general endotracheal anesthesia and neuromuscular blockade. The reflectometer wavetube was attached to an endotracheal tube, and a reflectometric profile was obtained of the endotracheal tube and the airway and lung cavity. After confirmation of tracheal intubation, a second endotracheal tube was placed in the esophagus. After four breaths were administered, a reflectometric profile of the endotracheal tube-esophagus cavity was obtained. RESULTS: The acoustic reflectometric profiles for tracheal and esophageal intubation profiles were distinctive and characteristic. For an endotracheal tube-airway cavity, the profile shows a constant cross-sectional area throughout the length of the endotracheal tube, followed by a rapid rise in the area past the carina. For an esophageal intubation, the profile shows constant cross-sectional area throughout the length of the endotracheal tube, followed by a sudden decrease in the cross-sectional area to zero. CONCLUSIONS: In this pilot study, acoustic reflectometry within seconds, and without resort to capnography, was able to generate characteristic and distinctive area-length profiles for both endotracheal and esophageal intubation. Acoustic reflectometry may have a role in the emergency imaging of the airway, and in the immediate detection of esophageal intubations, particularly in cases of cardiopulmonary arrest in which the usual techniques for confirmation of breathing tube placement fail.     

Impact of EGFR expression on colorectal cancer patient prognosis and survival.

BACKGROUND: Epidermal growth factor receptor (EGFR) is overexpressed in many types of cancers, especially colorectal cancer (CRC), and seems to reflect more aggressive histological and clinical behaviors. The aim of this study was to evaluate EGFR immunohistochemical reactivity in CRC biopsies, and to analyze its relationship with various histological and clinical characteristics and survival. PATIENTS AND METHODS: A composite EGFR score, obtained by multiplying the grade (% positive cells) by the intensity of labeling (0-9) was used to define patients with low or high EGFR expression whose clinicopathological features were then compared. Univariate tests and multivariate Cox proportional hazards model were applied for data analysis. RESULTS: Tissue sections from 150 CRC patients with a median follow-up of 40 months were examined. Median patient age at diagnosis was 70 years (range 38-89 years). EGFR reactivity was positive for 143 patients (97%) and high for 118 (80%). According to multivariate analysis, EGFR overexpression was significantly associated with tumor stage, with a higher percentage of EGFR overexpression in T3 than T4 (P=0.003) and not with overall survival. CONCLUSIONS: EGFR was overexpressed in this CRC patient population and was significantly associated with TNM (tumor-node-metastasis) stage T3. In the context of a new therapeutic strategy using EGFR-targeted therapies, although EGFR remains a controversial prognostic factor, this expression-stage association may play a crucial role in a decision to initiate an adjuvant treatment.