Overexpression of epidermal growth factor receptor in human head and neck squamous carcinoma cell lines correlates with matrix metalloproteinase-9 expression and in vitro invasion

Numerous reports have shown an association between overexpression of the epidermal growth factor receptor (EGFR), and poor prognosis in head and neck squamous cell carcinomas (HNSCC), however, the underlying mechanisms are still unclear. In the present study, we set out to determine whether EGFR expression was associated with in vitro invasive capacity in a panel of four established and ten newly derived HNSCC lines. Ten of the cell lines expressed high levels of EGFR as determined by a ligand-binding assay and dot blot analysis, whereas the remaining four showed weak overexpression or normal levels of EGFR. The ability of cells to invade through Matrigel was found to be higher in the EGFR overexpressing cell lines (p < 0. 0001). Expression levels of matrix metalloproteinases (MMP-1, MMP-2, MMP-3, MMP-7, MMP-9, MMP-10, MMP-11, MMP-13, MT1-MMP) and tissue inhibitors of MMP (TIMP-1, TIMP-2) were evaluated by semiquantitative RT-PCR, substrate zymography and western blot. We found a strong positive correlation between EGFR levels and the expression of MMP-9 mRNA (r(2) = 0.95; p < 0.0001), MMP-9 enzyme activity (r(2) = 0.8099; p < 0.0001) and an inverse correlation with TIMP-1 (r(2) = 0.48; p = 0.0059). In six selected HNSCC lines, in vitro invasion was assayed in the presence of an anti-EGFR monoclonal antibody, ICR62. A significant reduction of invasion in four selected EGFR-overexpressing cell lines was found with 30 nM ICR62 (from 50% to 70%; p < 0.001) but there was no effect in two cell lines with normal EGFR levels. Our results show that the in vitro invasive phenotype of HNSCC lines correlates with high EGFR and MMP-9 expression, and it is therefore suggested that the EGFR signaling pathway might play an important role in the invasive behavior of HNSCC via specific upregulation of MMP-9 and downregulation of TIMP-1.     

Spatiotemporal Effects of Syncytial Heterogeneities on Cardiac Far-Field Excitations During Monophasic and Biphasic Shocks

Far-Field Excitation Via Syncytial Heterogeneities. Introduction: It has recently been postulated that syncytial (anatomic) heterogeneities inherent within cardiac tissue might represent a significant mechanism underlying field-induced polarization of the bulk myocardium. This simulation study examines and characterizes the spatiotemporal excitatory dynamics associated with this newly hypothesized mechanism. Methods and Results: Two-dimensional regions of syncytially heterogeneous cardiac tissue were simulated with active membrane kinetics. Heterogeneities were manifested via random spatial variations of intracellular volume fractions over multiple length scales. Excitation thresholds were determined for uniform rectangular monophasic (M) and symmetric biphasic (B) far-field stimuli, from which strength-duration and strength-interval relationships were constructed. For regions measuring 5.4 × 5.4 mm, baseline diastolic thresholds for longitudinal (L) and transverse (T) shocks of 5-msec total duration averaged (in V/cm, n = 10) M-L = 2.87 ± 0.26. M-T = 6.71 ± 0.83, B-L = 3.22 ± 0.25, and B-T = 7.93 ± 0.51. These thresholds decreased by 15% to 25% when the region sizes were increased to 10.8 × 10.8 mm. Strength-duration relationships correlated strongly with the Weiss-Lapicque hyperbolic relationship, with rheobases and chronaxies of 2.33 V/cm and 1.15 msec for M-L stimuli, and 2.28 V/cm and 2.04 msec for B-L stimuli. Strength-interval relationships for M-I. and B-L stimuli decreased monotonically with increasing coupling intervals, with similar minimum coupling intervals at absolute refractoriness. However, the B-L thresholds were substantially less sensitive to changes in coupling intervals than their M-L counterparts. Conclusion: This study provides strong additional support for and understanding of the syncytial heterogeneity hypothesis and its manifested properties. Furthermore, these results predict that syncytial heterogeneities of even modest proportions could represent a significant mechanism contributing to the far-field excitation process.     

Modulation of Healthy Pig Coronary Arteries by Self-Expanding Stents

Objectives: To evaluate the expansion ratio of a self-expanding stem over time, and the chronic effect of stent pressure on the vessel wall . Methods: Self-expanding stents, developed by Medtronic Inc. (Minneapolis, MN, USA) and the Rouen group (Letac, Cribier, France), were implanted in 21 normal pig coronary arteries. Animals were sacrificed after recatheterization at 1 day (group I, n = 4), I week (group 2, n = 3), 3 weeks (group 3, n = 5), or 8 weeks (group 4, n = 4). Histological morphometry of the vessel medial and neointimal layers was performed. Changes were related to the, stent diameter and. its force on the vessel wall . Results: The stent expansion ratio gradually increased from 73% to 93% after 8 weeks, which implicates that radial force decreased concomitantly from 0.10 N to 0.03 N. Media compression under the rods ranged from 4l%-66% immediately after stent implantation. The mean compression was unrelated to stent expansion and remained nearly the same (40%-50%) during follow-up. Individual media rod compression ranged from 5%-95%. The neointimal layer on top of the rods increased until the third week after stent implant (neointimal thickness 211 ± 108 μm). The layer significantly decreased at 8 weeks (neointimal thickness 65 ± 9 μm). The cross-sectional neointimal area increased gradually only at the end of the stent during the 8-week follow-up . Conclusions: The self-expanding stent implanted in normal pig coronary arteries reached a gradual relaxation state 8 weeks after implantation due to the persistent radial force. This radial force induces medial wall compression, which was only positively related to the thickness of the neointimal layer at 3 weeks after implant . (J Interven Cardiol 1996;9:45–52)     

Multiplane Transthoracic Echocardiography: Image Orientation, Anatomic Correlation, and Clinical Experience with a Prototype Phased Array Multiplane Surface Probe

Multiplane transthoracic echocardiography provides numerous sequential images by rotation of the transducer imaging array through 180° with the surface probe at a fixed site. We explored the potential of this new technique with a 3.7/5-MHz prototype multiplane transthoracic probe. Echoanatomic correlations were first examined in ten explanted hearts. The transducer was then applied in 30 normal humans at transthoracic acoustic windows to determine the imaging planes available. Use of this probe in 76 patients with various cardiac disorders indicated that this probe eases the procedure of transthoracic echocardiographic examination, provides incremental information for improved delineation and understanding of cardiac pathology, and yields many novel insights to echocardiographic interpretation. Multiplane transthoracic echocardiography appears to expand the versatility of transthoracic two-dimensional echocardiography.     

Prozessoptimierung im „kranken Haus“

Starting January 1st 2004 the German diagnosis-related group (DRG) system was established for in-patient cases. Consequently, the detection and realization of cost-saving potentials are becoming more and more important. For a successful future, efficient allocation of resources is essential. Economically, anaesthesia-related time delays during perioperative work-flow should be minimized. Since numerous entities contribute to perioperative care, it is extremely complex to analyze and optimize this process flow. In this publication single steps leading to an optimized perioperative process flow will be presented: documentation of predefined time points, calculation of relevant time intervals and analysis of key numbers for complex settings. Single steps of the given process analysis will be demonstrated using data from surgical patients at the University Hospital Schleswig-Holstein, Campus Kiel. The attached data collection sheets can be used by interested hospital departments and are meant to serve as a template for further process analyses. Based on the shown analysis, an example will be given to develop an optimized work-flow as a standard operating procedure (SOP). The implementation of the SOP module in an interdisciplinary clinical pathway (CP), which defines efficient medical care from admission to discharge, is mainly responsible for decreased process costs but increased quality of care.     

Raynaud's phenomenon after radical radiotherapy for tumours of the head and neck

Endothelial cell injury is implicated in the development of radiation induced tissue damage and may also be involved in the pathophysiology of secondary Raynaud's phenomenon. Two patients are presented in whom the typical symptoms and signs of Raynaud's phenomenon developed as a late complication of radical radiotherapy. One had Raynaud's of the tongue and one of the lip. Both patients had a prior history of primary Raynaud's phenomenon and in each case the symptoms were repeatedly precipitated by sudden cold exposure. The possible pathogenesis of radiation induced Raynaud's phenomenon in the head and neck region is discussed.     

Leserbrief Zum Beitrag von W. Harth und R. Linse: “Botulinophilie” Der Hautarzt (2001) 52:312–316

Ohne Zusammenfassung