Investigation of mediastinitis due to coagulase-negative staphylococci after cardiothoracic surgery.

Six cases of coagulase-negative staphylococcal mediastinitis were identified in the latter half of 1999. A new preoperative cleansing solution was suspected by hospital staff to be a factor in the outbreak. We evaluated this possible risk factor along with other known and suspected surgical site infection risk factors in this case-control study

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

The impact of mucosal infections on acquisition and progression of tuberculosis

More than one-third of the world\u27s population, or over 2 billion people, are infected with Mycobacterium tuberculosis, the causative pathogen of tuberculosis in humans. Why only 10% of those infected develop active disease while the remainder harbor latent infection remains one of the greatest scientific and public health mysteries. Bacterial persistence is characterized by a dynamic state of immunological tolerance between pathogen and host. The critical role of CD4(+) T cells in defense against intracellular pathogens became evident during epidemiological studies of HIV-1 infection, which showed a clear inverse relationship between CD4(+) T-cell count in peripheral blood and increased risk of infection with M. tuberculosis, pneumocystis and Toxoplasma gondii. There is also growing evidence of a common mucosal immune system, whereby immune cells activated at one mucosal site may disseminate to remote effector sites. In this commentary, we review emerging evidence from human studies that the outcome of M. tuberculosis infection is influenced by concurrent mucosal infections, using Helicobacter pylori and geohelminths as examples. Understanding how the complexity of microbial exposures influences host immunity may have important implications for vaccine development and therapeutic interventions

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

The effect of Staphylococcus aureus carriage in late pregnancy on antibody levels to staphylococcal toxins in cord blood and breast milk.

We investigated the effect of carriage of Staphylococcus aureus in the later stages of pregnancy on levels of antibody specific to the S. aureus toxins, staphylococcal enterotoxin B (SEB), staphylococcal enterotoxin C (SEC) and toxic shock syndrome toxin-1 (TSST-1), in cord blood and breast milk and also explored the relationship between levels of antibody in antenatal serum and cord blood. Nasopharyngeal swabs and stool samples were collected on two occasions, from 96 women, during the last 6 weeks of pregnancy. Samples were cultured and S. aureus isolates were identified. Antenatal and cord blood samples from the same women and their infants were analysed for IgG antibody to SEB, SEC and TSST-1 by enzyme-linked immunosorbent assay. Breast milk samples were analysed for IgA antibody to the same toxins. We found that S. aureus carriage in pregnancy is common and exposure to a toxin-producing isolate boosts immunity. Over 89% of women and infants have some protective antibody to the toxins, and antitoxin IgG levels are higher in cord blood samples compared with antenatal samples. Levels of cord blood IgG and breast milk IgA specific for the staphylococcal toxins vary. Some infants lack protection and could be at risk of toxin-induced disease

Acute WNT signalling activation perturbs differentiation within the adult stomach and rapidly leads to tumour formation

A role for WNT signalling in gastric carcinogenesis has been suggested due to two major observations. First, patients with germline mutations in adenomatous polyposis coli (APC) are susceptible to stomach polyps and second, in gastric cancer, WNT activation confers a poor prognosis. However, the functional significance of deregulated WNT signalling in gastric homoeostasis and cancer is still unclear. In this study we have addressed this by investigating the immediate effects of WNT signalling activation within the stomach epithelium. We have specifically activated the WNT signalling pathway within the mouse adult gastric epithelium via deletion of either glycogen synthase kinase 3 (GSK3) or APC or via expression of a constitutively active β-catenin protein. WNT pathway deregulation dramatically affects stomach homoeostasis at very short latencies. In the corpus, there is rapid loss of parietal cells with fundic gland polyp (FGP) formation and adenomatous change, which are similar to those observed in familial adenomatous polyposis. In the antrum, adenomas occur from 4 days post-WNT activation. Taken together, these data show a pivotal role for WNT signalling in gastric homoeostasis, FGP formation and adenomagenesis. Loss of the parietal cell population and corresponding FGP formation, an early event in gastric carcinogenesis, as well as antral adenoma formation are immediate effects of nuclear β-catenin translocation and WNT target gene expression. Furthermore, our inducible murine model will permit a better understanding of the molecular changes required to drive tumourigenesis in the stomach

Severe Sepsis: Variation in Resource and Therapeutic Modality use Among Academic Centers

Background: Treatment of severe sepsis is expensive, often encompassing a number of discretionary modalities. The objective of the present study was to assess intercenter variation in resource and therapeutic modality use in patients with severe sepsis. Methods: We conducted a prospective cohort study of 1028 adult admissions with severe sepsis from a stratified random sample of patients admitted to eight academic tertiary care centers. The main outcome measures were length of stay (LOS; total LOS and LOS after onset of severe sepsis) and total hospital charges. Results: The adjusted mean total hospital charges varied from $69 429 to US$237 898 across centers, whereas the adjusted LOS after onset varied from 15.9 days to 24.2 days per admission. Treatments used frequently after the first onset of sepsis among patients with severe sepsis were pulmonary artery catheters (19.4%), ventilator support (21.8%), pressor support (45.8%) and albumin infusion (14.4%). Pulmonary artery catheter use, ventilator support and albumin infusion had moderate variation profiles, varying 3.2-fold to 4.9-fold, whereas the rate of pressor support varied only 1.92-fold across centers. Even after adjusting for age, sex, Charlson comorbidity score, discharge diagnosis-relative group weight, organ dysfunction and service at onset, the odds for using these therapeutic modalities still varied significantly across centers. Failure to start antibiotics within 24 hours was strongly correlated with a higher probability of 28-day mortality (r2 = 0.72). Conclusion: These data demonstrate moderate but significant variation in resource use and use of technologies in treatment of severe sepsis among academic centers. Delay in antibiotic therapy was associated with worse outcome at the center level