The literature suggests that approximately 93% of all pacemaker lead fractures occur in the segment of the lead lateral to the venous entry, and costoclavicular compression has been implicated. While blood vessels can be compressed by movements of the clavicle, our research suggests that lead and catheter damage in that region is caused by soft tissue entrapment rather than bony contact. Dissection of eight cadavers with ten leads revealed that two entered the cephalic vein, and were not included in the study. Of the other eight leads, four passed through the subclavius muscle, two through the costoclavicular ligament, and two through both these structures before entering the subclavian, internal jugular, or brachiocephalic vein. Anatomical studies demonstrated that entrapment by the subclavius muscle or the costoclavicular ligament could cause repeated flexing of leads during movements of the pectoral girdle. Cineradiology of patients with position dependent catheter occlusion confirmed entrapment by the subclavius muscle. Soft tissue entrapment imposes a static load upon leads and catheters, and repeated flexure about the point of entrapment may be responsible for damage previously attributed to cyclic costoclavicular compression.

No abstract

Nuclear factor (NF)-κB is a major survival pathway engaged by the Human T-Lymphotropic Virus type 1 (HTLV-1) Tax protein. Tax1 activation of NF-κB occurs predominantly in the cytoplasm, where Tax1 binds NF-κB Essential Modulator (NEMO/IKKγ) and triggers the activation of IκB kinases. Several independent studies have shown that Tax1-mediated NF-κB activation is dependent on Tax1 ubiquitination. Here, we identify by co-immunoprecipitation assays NEMO-Related Protein (NRP/Optineurin) as a binding partner for Tax1 in HTLV-1 infected and Tax1/NRP co-expressing cells. Immunofluorescence studies reveal that Tax1, NRP and NEMO colocalize in Golgi-associated structures. The interaction between Tax1 and NRP requires the ubiquitin-binding activity of NRP and the ubiquitination sites of Tax1. In addition, we observe that NRP increases the ubiquitination of Tax1 along with Tax1-dependent NF-κB signaling. Surprisingly, we find that in addition to Tax1, NRP interacts cooperatively with the Tax1 binding protein TAX1BP1, and that NRP and TAX1BP1 cooperate to modulate Tax1 ubiquitination and NF-κB activation. Our data strongly suggest for the first time that NRP is a critical adaptor that regulates the assembly of TAX1BP1 and post-translationally modified forms of Tax1, leading to sustained NF-κB activation.

With the knowledge of NO as an antiadhesion molecule, we performed studies to investigate the effects of NO on postischemic polymorphonuclear leukocyte (PMN)-medicated myocardial contractile dysfunction. Studies were performed with isolated perfused rat hearts subjected to 20 minutes of global ischemia and 45 minutes of reperfusion. Human PMNs (50 million) were infused over the first 5 minutes of reperfusion, and the recovery of left ventricular function was compared with baseline values. Infusion of PMNs alone (n = 10) led to a 61% reduction in left ventricular developed pressure (LVDP) and a 57% reduction in the pressure-rate product (PRP) at 45 minutes of reperfusion. Infusion of an NO donor, CAS-754 (n = 9), resulted in 80.2 +/- 6.7% recovery of LVDP and 77.0 +/- 8.6% recovery of PRP. Treatment with L-arginine (2.5 mmol/L, n = 10) resulted in a similar improvement in the postischemic contractile state of the heart. In contrast, NG-nitro-L-arginine methyl ester (L-NAME) treatment (250 mumol/L, n = 10) resulted in an exacerbation of contractile dysfunction, as evidence by a 93% reduction in LVDP at 45 minutes of reperfusion and a 91% reduction in PRP. The deleterious effects of L-NAME were prevented by L-arginine coperfusion. We failed to observe any cardioprotective effects when NO or L-arginine was administered to hearts subjected to 25 minutes of ischemia and 45 minutes of reperfusion in the absence of PMNs. In conclusion, PMN-mediated myocardial contractile dysfunction is attenuated by NO and exacerbated by blockade of NO synthesis.

Survival and desferrioxamine in thalassaemia major B MODELL, E A LETSKY, D M FLYNN, R PETO, D J WEATHERALL Abstract A small randomised trial and observation of all patients homozygous for beta-thalassaemia in Britain born in or before 1963 indicated that those patients who had received average weekly doses of more than 4 g of desferrioxamine over the previous few years were less likely to die in the near future than were patients of similar ages who had received less, or no, desferrioxamine.