Intriguing issues of EGFR targeting in head and neck cancer

We have read the recent comprehensive review by Cruz et al.[1] regarding the targeting of receptor tyrosine kinases andtheir therapeutic perspectives in head and neck squamous cellcarcinomas (HNSCC). The major focus of this report was epidermalgrowth factor receptor (EGFR) biology and targeting. However,we feel     

Myelin thickenings in val 102/fs null mutation of MPZ gene

Painful sensory neuropathies consist of a wide range of neuropathies that can involve large as well as small nerve fibres. Even if most cases remain of unknown cause, some of them may be associated with an underlying disorder such as diabetes, HIV, infections, amyloidosis, and Sjogren's syndrome. Since in some cases an autoimmune mechanism has been postulated, we investigated a panel of circulating autoantibodies including anti‐gliadin (AGA), anti‐endomysium (EmA), anti‐transglutaminase (tTGA) and anti‐nuclear (ANA) antibodies in the sera of patients with unexplained painful sensory neuropathies in order to identify other potentially treatable disorders. We tested the sera of 10 patients (4M; 6F) previously investigated for other causes of neuropathies, including anti‐nerve, onconeural, anti‐extractable nuclear, anti‐neutrophil cytoplasmic, anti‐thyroglobulin (TgA) and anti‐peroxidase (TPOA) antibodies. We found the presence of AGA positivity in 4 patients (40%), ANA in 7 (70%) and AGA + ANA in 4 (40%), two of whom were negative for celiac disease by gastrointestinal biopsy. None of the patients had EmA positivity. Three (30%) had TgA and TPOA and none had anti‐nerve or onconeural antibodies. Whether the presence of circulating autoantibodies in patients with unexplained painful neuropathy reflects an autoimmune involvement which may be amenable to immune therapy and not only to symptomatic treatment remains to be established.     

Real-time cine MRI of ventricular septal motion: a novel approach to assess ventricular coupling

The purpose of this study was to assess the feasibility of magnetic resonance imaging (MRI) to evaluate in real-time, the effects of respiration in ventricular septal motion and configuration in normal volunteers and cardiac patients. Real-time cine MRI studies, using the steady-state free precession (SSFP) technique, were performed in the cardiac short-axis during operator-guided deep inspiration and expiration in normal volunteers (N = 6), and in patients with constrictive pericarditis (CP; N = 6), restrictive cardiomyopathy (RCM; N = 4), chronic cor pulmonale (N = 5), and pericardial effusion. The respiratory effects on septal position and configuration during early ventricular filling were visually assessed. Results were compared with the short-axis breath-hold cine MRI studies, obtained at end-inspiration. In CP patients, onset of inspiration led to a leftward inversion in four of six patients and flattening of the septum in two of six patients during early ventricular filling. Septal abnormalities progressively disappeared during the following heartbeats. A similar pattern was found in one of six patients with pericardial effusion. The above pattern was absent in RCM patients. Although septal flattening during early inspiration was also found in two of six normal volunteers, flattening was minimal compared to that in CP patients. In all cor pulmonale patients, septal flattening or inversion was present, but this was not influenced by respiratory motion. Real-time cine MRI is a promising technique for determining the influence of respiration on septal motion and might be helpful in differentiating between different causes of impaired ventricular filling.     

Magnetic resonance imaging in the evaluation of the pericardium. A pictorial essay

Magnetic resonance (MR) is an ideal technique for the evaluation of the pericardium since it enables the combination of high resolution anatomical images of the pericardial layers with functional information concerning the impact of pathology on diastolic heart function and cardiac filling in particular. In comparison with echocardiography, which remains the first choice technique for the study of the pericardium, MR provides larger fields of view allowing the visualisation of the entire chest, higher spatial and contrast resolution and greater reproducibility. The technique becomes particularly useful when ultrasound imaging does not provide adequate diagnostic information or requires further characterisation; 'non-echoic' patients, loculated pericardial effusions, focal thickening of the layers and pericardial masses are usually better assessed with MR. The method also provides valuable diagnostic information for establishing the diagnosis of constrictive pericarditis and to differentiate this condition from restrictive cardiomyopathy. The aim of this paper is to present the role of MR imaging in the assessment of a patient with suspected pericardial disease, and discuss the MR technique, anatomy and the main pathological conditions.     

Different levels of polybrominated diphenyl ethers (PBDEs) and chlorinated compounds in breast milk from two U.K. Regions

Polybrominated diphenyl ether (PBDE) congeners are constituents of flame retardants, and there is growing concern regarding their persistence, bioaccumulation, and toxicity. We collected breast milk samples between late 2001 and early 2003 from 54 U.K.-resident mothers. Of these, 27 originated from southeast England (London), and the other 27 originated from northwest England (Lancaster). Analysis of milk-fat extracts by gas chromatography-mass spectrometry was performed to determine the levels of 15 PBDE congeners, 15 polychlorinated biphenyl (PCB) congeners, and other selected chlorinated compounds. PCB and organochlorine (OC) levels in southeast samples were consistently higher, and significant differences (p < 0.05) were observed. Sigma PBDE levels ranged from 0.3 to 69 ng/g lipid (geometric mean, 6.6 ng/g), and PBDE-47 was the most abundant congener. Sigma PCB levels ranged from 26 to 530 ng/g lipid (geometric mean, 150 ng/g) and were composed mainly of PCB-153 (26%), PCB-138 (20%), and PCB-180 (13%). OC levels for 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (p,p'-DDT) and its metabolites (Sigma DDX) ranged from 24 to 2,300 ng/g lipid (geometric mean, 160 ng/g);Sigma hexachlorocyclohexane levels ranged from 1.2 to 1,500 ng/g lipid (geometric mean, 16 ng/g). Using nuclear magnetic resonance-based metabonomics, samples (n = 7) containing the highest contaminant levels were compared with samples (n = 7) containing the lowest levels. Excellent separation along the first principal component implied that the chemical constituents of the two groups were significantly different. Although reasons for such differences remain obscure, lifestyle factors associated with a more heterogeneous London cohort could be responsible. Identifying primary routes of contaminant exposures and their biologic effects is of great importance. Key words: breast milk, flame retardants, gas chromatography-mass spectrometry, milk-fat extracts, organochlorines, PBDE-47, persistent contaminants, polybrominated diphenyl ethers, polychlorinated biphenyls, United Kingdom.     

Platelet-mediated inflammation in cardiovascular disease. Potential role of platelet-endothelium interactions

Inflammation of the vascular wall is considered as the principal underlying mechanism in the development of atherosclerosis. Besides their specific functions in haemostasis via thrombus formation after an endothelial injury, a growing body of evidence indicates that platelets play an important role in the inflammatory reactions occurring in the vascular wall as well as in the subsequent tissue repair mechanisms. Platelets interact with activated endothelium as well as with circulating leukocytes and progenitor cells. These interactions, involve direct cell-to-cell interactions as well as autocrine and paracrine pathways, which lead to activation of platelets and their respective cellular counterpart. An increasing body of evidence suggests that antiplatelet therapy may reduce vascular inflammation primarily by inhibiting platelet activation. The aim of the present review is to highlight the molecular basis of platelet-mediated inflammatory response, focusing on the mechanisms underlying the platelet-endothelial cell interaction. The anti-inflammatory effects of current antiplatelet therapies will be also discussed.