Relationship between treatment delay and final infarct size in STEMI patients treated with abciximab and primary PCI

Background Studies on the impact of time to treatment on myocardial infarct size have yielded   conflicting results. In this study of ST-Elevation Myocardial Infarction (STEMI) treated   with primary percutaneous coronary intervention (PCI), we set out to investigate the   relationship between the time from First Medical Contact (FMC) to the demonstration   of an open infarct related artery (IRA) and final scar size. Between February 2006 and September 2007, 89 STEMI patients treated with primary PCI   were studied with contrast enhanced magnetic resonance imaging (ceMRI) 4 to 8 weeks   after the infarction. Spearman correlation was computed for health care delay time   (defined as time from FMC to PCI) and myocardial injury. Multiple linear regression   was used to determine covariates independently associated with infarct size. Results An occluded artery (Thrombolysis In Myocardial Infarction, TIMI flow 0-1 at initial   angiogram) was seen in 56 patients (63%). The median FMC-to-patent artery was 89 minutes.   There was a weak correlation between time from FMC-to-patent IRA and infarct size,   r = 0.27, p = 0.01. In multiple regression analyses, LAD as the IRA, smoking and an occluded vessel   at the first angiogram, but not delay time, correlated with infarct size. Conclusions In patients with STEMI treated with primary PCI we found a weak correlation between   health care delay time and infarct size. Other factors like anterior infarction, a   patent artery pre-PCI and effects of reperfusion injury may have had greater influence   on infarct size than time-to-treatment per se

The AIMSS Project – III. The Stellar Populations of Compact Stellar Systems

In recent years, a growing zoo of compact stellar systems (CSSs) have been found whose physical properties (mass, size, velocity dispersion) place them between classical globular clusters (GCs) and true galaxies, leading to debates about their nature. Here we present results using a so far underutilized discriminant, their stellar population properties. Based on new spectroscopy from 8–10m telescopes, we derive ages, metallicities, and [α/Fe] of 29 CSSs. These range from GCs with sizes of merely a few parsec to compact ellipticals (cEs) larger than M32. Together with a literature compilation, this provides a panoramic view of the stellar population characteristics of early-type systems. We find that the CSSs are predominantly more metal rich than typical galaxies at the same stellar mass. At high mass, the cEs depart from the mass–metallicity relation of massive early-type galaxies, which forms a continuous sequence with dwarf galaxies. At lower mass, the metallicity distribution of ultracompact dwarfs (UCDs) changes at a few times 107 M⊙, which roughly coincides with the mass where luminosity function arguments previously suggested the GC population ends. The highest metallicities in CSSs are paralleled only by those of dwarf galaxy nuclei and the central parts of massive early types. These findings can be interpreted as CSSs previously being more massive and undergoing tidal interactions to obtain their current mass and compact size. Such an interpretation is supported by CSSs with direct evidence for tidal stripping, and by an examination of the CSS internal escape velocities

Longitudinal peak strain detects a smaller risk area than visual assessment of wall motion in acute myocardial infarction

<p>Abstract</p> <p>Background</p> <p>Opening of an occluded infarct related artery reduces infarct size and improves survival in acute ST-elevation myocardial infarction (STEMI). In this study we performed tissue Doppler analysis (peak strain, displacement, mitral annular movement (MAM)) and compared with visual assessment for the study of the correlation of measurements of global, regional and segmental function with final infarct size and transmurality. In addition, myocardial risk area was determined and a prediction sought for the development of infarct transmurality ≥50%.</p> <p>Methods</p> <p>Twenty six patients with STEMI submitted for primary percutaneous coronary intervention (PCI) were examined with echocardiography on the catheterization table. Four to eight weeks later repeat echocardiography was performed for reassessment of function and magnetic resonance imaging for the determination of final infarct size and transmurality.</p> <p>Results</p> <p>On a global level, wall motion score index (WMSI), ejection fraction (EF), strain, and displacement all showed significant differences (p ≤ 0.001, p ≤ 0.001, p ≤ 0.001 and p = 0.03) between the two study visits, but MAM did not (p = 0.17). On all levels (global, regional and segmental) and both pre- and post PCI, WMSI showed a higher correlation with scar transmurality compared to strain. We found that both strain and WMSI predicted the development of scar transmurality ≥50%, but strain added no significant information to that obtained with WMSI in a logistic regression analysis.</p> <p>Conclusions</p> <p>In patients with acute STEMI, WMSI, EF, strain, and displacement showed significant changes between the pre- and post PCI exam. In a ROC-analysis, strain had 64% sensitivity at 80% specificity and WMSI around 90% sensitivity at 80% specificity for the detection of scar with transmurality ≥50% at follow-up.</p

Botulinum toxin in gastric submucosa reduces stimulated HCl production in rats

BACKGROUND: Botulinum toxin blocks acetylcholine release from nerve endings and acts as a long term, reversible inhibitor of muscle contraction as well as of salivary, sweat gland, adrenal and prostatic secretions. The aim of the present study is to investigate whether gastric submucosal injection of botulinum toxin type A reduces stimulated gastric production of HCl. METHODS: Sixty-four rats were randomized in two groups and laparotomized. One group was treated with botulinum toxin-A 10 U by multiple submucosal gastric injections, while the second group was injected with saline. Two weeks later, acid secretion was stimulated by pyloric ligation and acid output was measured. Body weight, food and water intake were also recorded daily. RESULTS: HCl production after pyloric ligation was found to be significantly lower in botulinum toxin-treated rats (657 ± 90.25 micromol HCl vs. 1247 ± 152. P = 0.0017). Botulinum toxin-treated rats also showed significantly lower food intake and weight gain. CONCLUSIONS: Botulinum toxin type A reduces stimulated gastric acidity. This is likely due either to inhibition of the cholinergic stimulation of gastric parietal cells, or to an action on the myenteric nervous plexuses. Reduction of growth and food intake may reflect both impaired digestion and decreased gastric motility

Drug-eluting stents appear superior to bare metal stents for vein-graft PCI in vessels up to a stent diameter of 4 mm.

BACKGROUND: Research trials have shown improved short-term outcome with drug-eluting stents (DES) over bare metal stents (BMS) in saphenous vein graft (SVG) percutaneous coronary intervention (PCI), primarily by reducing target vessel revascularization (TVR) for in-stent restenosis. We compared the outcomes in patients undergoing SVG stent implantation treated with DES or BMS. In exploratory analyses we investigated the influence of stent generation and diameter. METHODS: Data were obtained from a prospective database of 657 patients who underwent PCI for SVG lesions between 2003 and 2011. A total of 344 patients had PCI with BMS and 313 with DES. Propensity scores were developed based on 15 observed baseline covariates in a logistic regression model with stent type as the dependent variable. The nearest-neighbour-matching algorithm with Greedy 5-1 Digit Matching was used to produce two patient cohorts of 313 patients each. We assessed major adverse cardiac events (MACE) out to a median of 3.3 years (interquartile range: 2.1-4.1). MACE was defined as all-cause mortality, myocardial infarction (MI), TVR and stroke. RESULTS: There was a significant difference in MACE between the two groups in favour of DES (17.9% DES vs. 31.2% BMS group; p = 0.0017) over the 5-year follow-up period. MACE was driven by increased TVR in the BMS group. There was no difference in death, MI or stroke. Adjusted Cox analysis confirmed a decreased risk of MACE for DES compared with BMS 0.75 (95% confidence interval (CI) 0.52-0.94), with no difference in the hazard of all-cause mortality (hazard ratio: 1.08; 95% CI: 0.77-1.68). However, when looking at stent diameters greater than 4 mm, no difference was seen in MACE rates between BMS and DES. CONCLUSIONS: Overall in our cohort of patients who had PCI for SVG disease, DES use resulted in lower MACE rates compared with BMS over a 5-year follow-up period; however, for stent diameters over 4 mm no difference in MACE rates was seen

Accounting for the mortality benefit of drug-eluting stents in percutaneous coronary intervention: a comparison of methods in a retrospective cohort study

<p>Abstract</p> <p>Background</p> <p>Drug-eluting stents (DES) reduce rates of restenosis compared with bare metal stents (BMS). A number of observational studies have also found lower rates of mortality and non-fatal myocardial infarction with DES compared with BMS, findings not observed in randomized clinical trials. In order to explore reasons for this discrepancy, we compared outcomes after percutaneous coronary intervention (PCI) with DES or BMS by multiple statistical methods.</p> <p>Methods</p> <p>We compared short-term rates of all-cause mortality and myocardial infarction for patients undergoing PCI with DES or BMS using propensity-score adjustment, propensity-score matching, and a stent-era comparison in a large, integrated health system between 1998 and 2007. For the propensity-score adjustment and stent era comparisons, we used multivariable logistic regression to assess the association of stent type with outcomes. We used McNemar's Chi-square test to compare outcomes for propensity-score matching.</p> <p>Results</p> <p>Between 1998 and 2007, 35,438 PCIs with stenting were performed among health plan members (53.9% DES and 46.1% BMS). After propensity-score adjustment, DES was associated with significantly lower rates of death at 30 days (OR 0.49, 95% CI 0.39 - 0.63, <it>P </it>< 0.001) and one year (OR 0.58, 95% CI 0.49 - 0.68, <it>P </it>< 0.001), and a lower rate of myocardial infarction at one year (OR 0.72, 95% CI 0.59 - 0.87, <it>P </it>< 0.001). Thirty day and one year mortality were also lower with DES after propensity-score matching. However, a stent era comparison, which eliminates potential confounding by indication, showed no difference in death or myocardial infarction for DES and BMS, similar to results from randomized trials.</p> <p>Conclusions</p> <p>Although propensity-score methods suggested a mortality benefit with DES, consistent with prior observational studies, a stent era comparison failed to support this conclusion. Unobserved factors influencing stent selection in observational studies likely account for the observed mortality benefit of DES not seen in randomized clinical trials.</p

Cost-effectiveness analysis of PCR for the rapid diagnosis of pulmonary tuberculosis

<p>Abstract</p> <p>Background</p> <p>Tuberculosis is one of the most prominent health problems in the world, causing 1.75 million deaths each year. Rapid clinical diagnosis is important in patients who have co-morbidities such as Human Immunodeficiency Virus (HIV) infection. Direct microscopy has low sensitivity and culture takes 3 to 6 weeks <abbrgrp><abbr bid="B1">1</abbr><abbr bid="B2">2</abbr><abbr bid="B3">3</abbr></abbrgrp>. Therefore, new tools for TB diagnosis are necessary, especially in health settings with a high prevalence of HIV/TB co-infection.</p> <p>Methods</p> <p>In a public reference TB/HIV hospital in Brazil, we compared the cost-effectiveness of diagnostic strategies for diagnosis of pulmonary TB: Acid fast bacilli smear microscopy by Ziehl-Neelsen staining (AFB smear) plus culture and AFB smear plus colorimetric test (PCR dot-blot).</p> <p>From May 2003 to May 2004, sputum was collected consecutively from PTB suspects attending the Parthenon Reference Hospital. Sputum samples were examined by AFB smear, culture, and PCR dot-blot. The gold standard was a positive culture combined with the definition of clinical PTB. Cost analysis included health services and patient costs.</p> <p>Results</p> <p>The AFB smear plus PCR dot-blot require the lowest laboratory investment for equipment (US$20,000). The total screening costs are 3.8 times for AFB smear plus culture versus for AFB smear plus PCR dot blot costs (US$ 5,635,760 versus US$1,498, 660). Costs per correctly diagnosed case were US$ 50,773 and US$13,749 for AFB smear plus culture and AFB smear plus PCR dot-blot, respectively. AFB smear plus PCR dot-blot was more cost-effective than AFB smear plus culture, when the cost of treating all correctly diagnosed cases was considered. The cost of returning patients, which are not treated due to a negative result, to the health service, was higher in AFB smear plus culture than for AFB smear plus PCR dot-blot, US$ 374,778,045 and US$ 110,849,055, respectively.</p> <p>Conclusion</p> <p>AFB smear associated with PCR dot-blot associated has the potential to be a cost-effective tool in the fight against PTB for patients attended in the TB/HIV reference hospital.</p

Differential regulation of iron chelator-induced IL-8 synthesis via MAP kinase and NF-κB in immortalized and malignant oral keratinocytes

Abstract Background Interleukin-8 (IL-8) is a cytokine that plays an important role in tumor progression in a variety of cancer types; however, its regulation is not well understood in oral cancer cells. In the present study, we examined the expression and mechanism of IL-8 in which it is involved by treating immortalized (IHOK) and malignant human oral keratinocytes (HN12) cells with deferoxamine (DFO). Methods IL-8 production was measured by an enzyme-linked immunoabsorbent assay and reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. Electrophoretic mobility shift assays was used to determine NF-κB binding activity. Phosphorylation and degradation of the I-κB were analyized by Western blot. Results IHOK cells incubated with DFO showed increased expression of IL-8 mRNA, as well as higher release of the IL-8 protein. The up-regulation of DFO-induced IL-8 expression was higher in IHOK cells than in HN12 cells and was concentration-dependent. DFO acted additively with IL-1β to strongly up-regulate IL-8 in IHOK cells but not in HN12 cells. Accordingly, selective p38 and ERK1/2 inhibitors for both kinases abolished DFO-induced IL-8 expression in both IHOK and HN12 cells. Furthermore, DFO induced the degradation and phosphorylation of IκB, and activation of NF-κB. The IL-8 inducing effects of DFO were mediated by a nitric oxide donor (S-nitrosoglutathione), and by pyrrolidine dithiocarbamate, an inhibitor of NF-κB, as well as by wortmannin, which inhibits the phosphatidylinositol 3-kinase-dependent activation of NAD(P)H oxidase. Conclusion This results demonstrate that DFO-induced IL-8 acts via multiple signaling pathways in immortalized and malignant oral keratinocytes, and that the control of IL-8 may be an important target for immunotheraphy against human oral premalignant lesions.</p