Citations

ABSTRACTThe RNA-dependent RNA polymerase 3Dpolis required for the elongation of positive- and negative-stranded picornavirus RNA. During the course of investigating the effect of the transgenic expression of viral genes on the host immune response, we evaluated the viral load present in the host after infection. To our surprise, we found that 3D transgenic expression in genetically susceptible FVB mice led to substantially lower viral loads after infection with Theiler's murine encephalomyelitis virus (TMEV). As a result, spinal cord damage caused by chronic viral infection in the central nervous system was reduced in FVB mice that expressed 3D. This led to the preservation of large-diameter axons and motor function in these mice. The 3D transgene also lowered early viral loads when expressed in FVB-Dbmice resistant to persistent TMEV infection. The protective effect of 3D transgenic expression was not altered in FVB-Rag−/−.3D mice that are deficient in T and B cells, thus ruling out a mechanism by which the overexpression of 3D enhanced the adaptive immune clearance of the virus. Understanding how endogenously overexpressed 3D polymerase inhibits viral replication may lead to new strategies for targeting therapies to all picornaviruses.

Purpose The purpose of the present article was to determine the changes in luminal vessel area, blood flow, and wall shear stress in both the inflow artery and the venous stenosis of arteriovenous polytetrafluoroethylene (PTFE) grafts. Methods and materials Polytetrafluoroethylene grafts were placed from the carotid artery to the ipsilateral jugular vein in 8 castrated juvenile male pigs. Contrast-enhanced magnetic resonance angiography (MRA) with cine phase-contrast magnetic resonance imaging (MRI) was performed 2 weeks after graft placement. Results The mean wall shear stress at the venous stenosis was 4 times higher than the control vein, while the inflow artery was only 2-fold higher. By day 14, venous stenosis had formed, which was characterized by narrowed area and elevated blood flow. Conclusion By day 14, there is venous stenosis formation in porcine arteriovenous PTFE grafts with increased shear stress with decreased area when compared to control vein.

Background— American College of Cardiology/American Heart Association guidelines recommend a door-to-balloon time (DTB) <90 minutes for nontransferred patients with ST-elevation myocardial infarction (STEMI) who undergo primary percutaneous coronary intervention. Systems of care to achieve and sustain this DTB performance over several years have not been previously reported. Methods and Results— The Mayo Clinic STEMI protocol was implemented in April 2004 and included activation of the cardiac catheterization laboratory by the emergency medicine physician; a single call system to activate the catheterization laboratory; catheterization laboratory staff arrival within 20 to 30 minutes of activation; and real-time performance feedback within 24 to 48 hours. Data were collected on nontransferred STEMI patients. The preimplementation group (June 2002 to March 2004) comprised 96 patients with a median DTB of 97 (interquartile range, 82, 130) minutes, and 40% had a DTB <90 minutes. The postimplementation group (May 2004 to March 2008) comprised 322 patients with a median DTB of 67 (interquartile range, 55, 82) minutes, and 81% had a DTB <90 minutes. Postimplementation DTB was significantly shorter than preimplementation DTB ( P <0.001). In the 4-year follow-up after protocol implementation, the DTB performance remained stable over time ( P =0.41). Conclusions— The Mayo Clinic STEMI protocol implemented strategies to reduce DTB for nontransferred patients with STEMI. DTB was significantly reduced, and the results were sustained over the 4-year follow-up period. Our experience demonstrates the effectiveness and durability of process changes targeting timeliness of primary percutaneous coronary intervention.

By the mid-1970s the autoimmune origin of myasthenia gravis had been well established. Once this feat had been accomplished, it also became apparent that myasthenic disorders occurring in a genetic or congenital setting had a different etiology. As a result, a number of distinct myasthenic syndromes have been recognized and investigated by electrophysiological and ultrastructural methods. The newly recognized disorders are conditioned by divergent causes, such as a failure of acetylcholine resynthesis or packaging, absence of acetylcholinesterase from the neuromuscular junction, abnormal gating properties of the acetylcholine receptor-associated ion channel, or an abnormality in the regulation of the density of acetylcholine receptor molecules in the postsynaptic membrane. These genetic defects either impair neuromuscular transmission directly or result in secondary derangements that eventually compromise the safety margin of neuromuscular transmission. ( J Child Neurol 1988;3:233-246).