Myocardial calcinosis in chronic renal failure.

The authors are presenting an 18 year old male with history of end stage renal disease and rejected renal transplant. In his workup echocardiogram and non contract CT of chest revealed diffuse endocardial and myocardial calcifications. Extensive cardiac calcification is a rare but important entity in relation to end stage renal disease as it may cause complications such as valvular dysfunction and fatal arrhythmia.

Regional differences in the use of sentinel lymph node biopsy for melanoma: a potential quality measure.

Sentinel lymph node biopsy (SLNB) provides accurate nodal staging in patients with melanoma. However, its prevalence across geographic regions is unknown. Our aim was to determine if SLNB for melanoma has been widely adopted throughout the United States. All patients in the Surveillance, Epidemiology and End Results (SEER) cancer registry for 2004 with melanoma were evaluated. Data were collected for demographics, depth of melanoma, and type of nodal evaluation (regional lymph node dissection vs SLNB). Registry sites were categorized into West, Midwest, Northeast, and Southeast. Chi2 analysis was performed to identify regional differences in receipt of SLNB. Overall, the West region (n = 2352) had a higher use of SLNB compared with the Midwest (n = 497), Northeast (n = 630), and Southeast (n = 268) regions (82.1% vs 77.9%, 65.4%, and 60.1%, respectively; P < 0.001). Intermediate-thickness (1 to 4 mm) melanomas had differences in SLNB use between the West and Midwest (83.6% and 81.4%) versus the Northeast and Southeast (66.3% and 60.2%) (P < 0.05). This population-based analysis shows low use of SLNB for melanoma in some U.S. regions. Further studies need to address the reasons for these differences and target ways to improve rates. Results suggest that SLNB may be considered as a potential quality measure.

Diagnosis of variants of single right coronary trunk using 64 multidetector computed tomography.

Single coronary anomalies are one of the rarest variants of coronary anatomy. Widespread use of coronary CT angiography has made it possible to diagnose these variants with increasing incidence. We report two cases of single right coronary trunk with different anatomic course of the left coronary artery; one anterior to the main pulmonary artery and the second between the main pulmonary artery and ascending aorta and then coursing within the interventricular septum.

TNF alpha reduces tachykinin, PGE2-dependent, relaxation of the cultured mouse trachea by increasing the activity of COX-2.

1. Chronic inflammation is a central feature of asthma. The inflammatory cytokine tumour necrosis factor alpha (TNFalpha) has been implicated in this disease, and is known to alter airway smooth muscle functionally. 2. The aim of this study was to investigate the influence of TNFalpha on tachykinin-induced airway relaxation. Mouse tracheae were cultured in the absence and presence of TNFalpha for 1 or 4 days. 3. In the absence of TNFalpha, substance P (SP) and neurokinin A (NKA) induced comparable levels of relaxation in fresh and cultured segments. Functional studies with selective antagonists/inhibitors indicated that the relaxation was mediated by the NK(1) receptor coupled to cyclooxygenase (COX)-2 activation and subsequent release of prostaglandin E(2) (PGE(2)). TNFalpha attenuated SP- and NKA-induced relaxation in a time- and concentration-dependent manner, decreasing the ability of PGE(2) to relax tissues. 4. Further studies indicated that TNFalpha elevated COX-2 activity and that concomitant inhibition of COX-2 reversed TNFalpha-attenuated PGE(2) relaxation. Culture with PGE(2) decreased SP- and PGE(2)-mediated relaxation, further implicating the activity of COX-2 in the attenuation of tachykinin signalling. 5. Gene expression analysis demonstrated that TNFalpha increased the expression of smooth muscle COX-2, PGE(2) synthase and EP(2) receptor mRNA, and decreased the expression of the EP(4) receptor. 6. Overall, these results show that NK(1) receptor-mediated relaxation induced by PGE(2) is attenuated by prolonged TNFalpha stimulation. Increased COX-2 activity induced by TNFalpha appears to be central to this process.

Cell lines for drug discovery: elevating target-protein levels using engineered transcription factors.

Drug discovery requires high-quality, high-throughput bioassays for lead identification and optimization. These assays are usually based on immortalized cell lines, which express the selected drug target either naturally or as a consequence of transfection with the cDNA encoding the target. Natural untransfected cell lines often fail to achieve the levels of expression required to provide assays of sufficient quality with a high enough signal-to-noise ratio. Unfortunately, the use of cDNA is increasingly restricted, as the sequences for more and more genes become subject to patent restrictions. To overcome these limitations, the authors demonstrate that engineered transcription factors with Cys2-His2 zinc finger DNA-binding domains can be used to effectively activate an endogenous gene of interest without the use of isolated cDNA of the target gene. Using this approach, the authors have generated a cell line that provides a high-quality and pharmacologically validated G-protein-coupled receptor bioassay. In principle, this technology is applicable to any gene of pharmaceutical importance in any cell type.