Pacemaker Clinic

Pacemaker longevity is a serious problem to overcome. However, our immediate concern is to get as much useful life from a pacemaker as possible. On the average, pacemakers fail in about 23 months. The only pacemaker that lasted much longer was a fixed-rate unit, the Medtronic 5860, which is no longer available. A past suggestion in handling this problem has been to change the pacemaker electively at an arbitrary time, but that time has varied tremendously as the manufacturers once selected 30 months, and more recently 15 months. If a pacemaker is replaced at 15 months, very few of them will actually be near the end of their life span

Emergency Management of Pacemaker Failure

The purpose of this report is to describe the more common problems encountered with permanent pacemakers and their management

Cofactors of the p65-Mediator Complex

Regulation of gene expression is an essential process in all organisms. Research within the last decade has elucidated the central importance of the Mediator complex in the fundamentals of gene expression. Mediator has been shown to adopt various structural changes when bound to different transcriptional activators. As a part of the NF-κB family of proteins, p65 (RelA) is a diverse transcriptional activator highly involved in inflammation and immune response as well as other essential signaling pathways. Mediator and p65 have been shown to interact through the activation domain of p65. To further explore this interaction, the p65-Mediator complex was purified in vitro and analyzed by mass spectrometry to identify cofactors of the complex. Evidence is provided for the identification of both novel and previously described interactions

Cardiac pacing in the 1980s: Treatment and techniques in transition

AbstractThe pacemaker of the 1980s is designed to maintain atrioventricular synchrony through dual-chamber pacing. This pacemaker is multiprogrammable and capable of telemetric transmission of biologic, electronic and electrophysiologic data. Several developments have made this therapeutic modality possible: 1) the cumulative survival rate of many lithium-battery pacemakers exceeds 95% at 5 years; 2) lead and connector problems are rare; 3) atrial and ventricular electrode malfunctions occur in less than 2% of implants; and 4) new introducer techniques have simplified implantation (mortality and major morbidity rates are 0.5 and 0.4%, respectively). With multiprogrammability, pacemaker function can be optimized for the patient's needs, and about 20% of reoperations can be avoided.Ninety-six dual-chamber (DDD) pacemakers, 55 of which have been followed up for more than 3 months, have provided trouble-free performance and have yielded salutary clinical results, particularly when implanted to replace previous ventricular inhibited units. Problems with these pacemakers have included unusual pacing electrocardiograms, pacemaker eccentricities, programmer maintenance, pacing and follow-up complexities and costs.In the 1980s, effort will be required to find a balance between rapidly evolving technology and the clinical need for complex pacing systems. From 1978 to 1981, the rate of pacemaker implantation grew from 309 to 513 implants per million population per year, and there are now approximately 500,000 patients with implanted pacemakers living in the United States. Indications for pacing are ill-defined, because in many cases the assessment of clinical response to pacing is largely subjective, lacking satisfactory quantitative indexes. This decade will be a time of reappraisal of the extent of clinical applicability of new techniques, particularly the multi-programmable dual-chamber system which, after 3 years of clinical trial, shows promise of being the predominant pacemaker of the immediate future

Rna Recognition by the Glucocorticoid Receptor Dna-Binding Domain

Regulation of gene expression by transcription factors (TFs) and their co-regulatory molecules forms much of the basis of how cells interact with their environment. Long noncoding RNAs (lncRNAs) are emerging as a new class of co-regulatory factors, exploiting diverse sequence and structure motifs to interact directly with TFs. An outstanding prototype of this model is glucocorticoid receptor (GR), a TF which binds multiple RNAs in vivo and typifies the molecular decoy model&mdash;competitive binding between RNA and DNA at the TF DNA-binding domain. For example, GR binds the noncoding RNA Gas5, a tumor suppressor and growth arrest-specific RNA, via its DNA-binding domain (DBD) with functional implications in pro-apoptosis signaling. Here we report a comprehensive in vitro binding study where we have determined that GR-DBD is a robust structure-specific RNA-binding domain. GR-DBD binds to a diverse range of RNA hairpin motifs, both synthetic and biologically derived, with apparent mid-nanomolar affinity while discriminating against uniform dsRNA. As opposed to dimeric recognition of dsDNA, GR-DBD binds to RNA as a monomer and confers high affinity primarily through electrostatic contacts. GR-DBD adopts a discrete RNA-bound state, as assessed by NMR, distinct from both free and DNA-bound. NMR and alanine mutagenesis suggest a heightened involvement of the C-terminal &alpha;-helix of GR-DBD in RNA-binding. RNA competes for binding with dsDNA and occurs in a similar affinity range as dimer binding to the canonical DNA element. Given the prevalence of RNA hairpins within the transcriptome, our findings strongly suggest that many RNAs have potential to impact GR biology.</p

The 1981 United States survey of cardiac pacing practices

A survey of physicians implanting pacemakers was conducted to obtain a profile of permanent cardiac pacing practices in the United States during 1981. Questionnaires were mailed to 5,832 implanters with 765 responses (13%) received and 680 analyzed. It was estimated that there were approximately 5,600 physicians, 66% surgeons and 34% nonsurgeons, implanting pacemakers at 3,670 centers. About 118,000 new primary implants were performed, or 518 per million population. Only 17% of implantation procedures in 1981 were replacements compared with 31% in 1978. Roughly half the respondents worked in teams, most implanting from 46 to 55 pacemakers annually.The chief indications for permanent pacing were sick sinus syndrome (48%) and impairment of conduction in the atrioventricular node and His-Purkinje system (42%). Ninety-five percent of pacing leads were implanted transvenously. Seventy percent of the respondents had had experience with atrial and dual-chamber pacemakers, used largely to increase cardiac output. The use of ventricular demand (VVI) pacing decreased accordingly from 91% in 1975 to 84% in 1981. Although approximately 90% of primary pacemakers were programmable to some degree, almost half were not reprogrammed within the first 3 months after implantation and 30% were never reprogrammed. Most patients (85%) were followed up by transtelephonic electrocardiographic monitoring, 68% in conjunction with private office visits. The respondents estimated that dual-chamber pacing, accounting for 10% of implants in 1981, would increase to 37% by 1985.Early electrode malfunctions were less frequent when implantation was performed by high volume and solo implanters, and in public and community hospitals. It is concluded that periodic surveys of this type disclose important trends in the practice of cardiac pacing