Implantation of a colorectal stent as a therapeutic approach in the treatment of esophageal leakage

BACKGROUND: While the mortality of esophageal surgery has decreased due to technological advancements, there is still a complication rate of about 30%. One of the main complications is the anastomotic leakage associated with a significant rate of morbidity and mortality. To close the leakage the efficacy of self-expanding stents (SES) has been shown in different studies. However, the high rate of stent migration limits the use of commercial available stents. In our case we were faced with the problem that the diameter of all available stents was too small to attach tightly to the mucosal wall of the esophagogastric anastomosis. CASE PRESENTATION: We used, for the first time to our knowledge, a metal stent designed for colorectal application in an extensive anastomotic leak after esophageal resection in a patient with an esophageal cancer. After primary surgery with subtotal esohagectomy the anastomotic leak was stented endoscopically with a Polyflex self-expanding covered plastic stent after no response to intensive conventional management. Even though the stent was placed correctly, the diameter of the Polyflex stent was too small to attach onto the wall of the esophagogastric anastomosis. Again surgery was performed with a thoracal resection of the esophageal remnant and a hand made anastomosis. Unfortunately, again an anastomotic leak was detected soon after. To close the leak we decided to use a covered colorectal stent (Hanarostent) with an inner diameter of 30 mm. Sixteen weeks later the stent was extracted and complete mucosal healing of the esophageal leak was observed. CONCLUSION: The stent implantation with a large wide diameter offers a good chance to close more extensive leaks and prevent stent migration

HST Observations of the Serendipitous X-ray Companion to Mrk 273: Cluster at z=0.46?

We have used HST I-band images to identify Mrk 273X, the very unusual high-redshift X-ray-luminous Seyfert 2 galaxy found by ROSAT in the same field-of-view as Mrk 273. We have measured the photometric properties of Mrk 273X and have also analyzed the luminosity distribution of the faint galaxy population seen in the HST image. The luminosity of the galaxy and the properties of the surrounding environment suggest that Mrk 273X is the brightest galaxy in a relatively poor cluster at a redshift near 0.46. Its off-center location in the cluster and the presence of other galaxy groupings in the HST image may indicate that this is a dynamically young cluster on the verge of merging with its neighboring clusters. We find that Mrk 273X is a bright featureless elliptical galaxy with no evidence for a disk. It follows the de Vaucouleurs (r^{1/4}) surface brightness law very well over a range of 8 magnitudes. Though the surface brightness profile does not appear to be dominated by the AGN, the galaxy has very blue colors that do appear to be produced by the AGN. Mrk 273X is most similar to the IC 5063 class of active galaxies --- a hybrid Sy 2 / powerful radio galaxy.Comment: Accepted for publication in the Astrophysical Journal. 8 pages, including 4 postscript figures. Uses emulateapj.sty and psfig.sty. Higher quality version of Figure 1 is available at http://rings.gsfc.nasa.gov/~borne/fig1-markgals.gi

X-ray absorption and rapid variability of the dwarf Seyfert nucleus of NGC4395

We report the detection of an absorbed central X-ray source and its strong, rapid variability in NGC4395, the least luminous Seyfert nucleus known. The X-ray source exhibits a number of flares with factors of 3-4 flux changes during a half day ASCA observation. Such X-ray variability is in constrast to the behaviour of other low luminosity active galaxies. It provides further support for an accreting black hole model rather than an extreme stellar process in accounting for the nuclear activity of NGC4395. The soft X-ray emission below 3 keV is strongly attenuated by absorption. The energy spectrum in this absorption band shows a dramatic change in response to the variation in continuum luminosity. A variable warm absorber appears to be an explanation for the spectral change. The absorption-corrected 2-10 keV luminosity is 4e39 erg/s for a source distance of 2.6 Mpc, and at 1 keV is one order of magnitude above previous ROSAT estimates. Our X-ray results infer the nuclear source of NGC4395 to be a scaled-down version of higher luminosity Seyfert nuclei, with an intermediate mass (10^4-10^5 Msun) black hole, unlike the nearby low luminosity active galaxies in which underfed massive black holes are suspected to reside.Comment: 12 pages, accepted for publication in MNRA

The Distribution of Redshifts in New Samples of Quasi-stellar Objects

Two new samples of QSOs have been constructed from recent surveys to test the hypothesis that the redshift distribution of bright QSOs is periodic in $\log(1+z)$. The first of these comprises 57 different redshifts among all known close pairs or multiple QSOs, with image separations $\leq$ 10\arcsec, and the second consists of 39 QSOs selected through their X-ray emission and their proximity to bright comparatively nearby active galaxies. The redshift distributions of the samples are found to exhibit distinct peaks with a periodic separation of $\sim 0.089$ in $\log(1+z)$ identical to that claimed in earlier samples but now extended out to higher redshift peaks $z = 2.63, 3.45$ and 4.47, predicted by the formula but never seen before. The periodicity is also seen in a third sample, the 78 QSOs of the 3C and 3CR catalogues. It is present in these three datasets at an overall significance level $10^{-5}$ - $10^{-6}$, and appears not to be explicable by spectroscopic or similar selection effects. Possible interpretations are briefly discussed.Comment: submitted for publication in the Astronomical Journal, 15 figure

Selection-Independent Generation of Gene Knockout Mouse Embryonic Stem Cells Using Zinc-Finger Nucleases

Gene knockout in murine embryonic stem cells (ESCs) has been an invaluable tool to study gene function in vitro or to generate animal models with altered phenotypes. Gene targeting using standard techniques, however, is rather inefficient and typically does not exceed frequencies of 10−6. In consequence, the usage of complex positive/negative selection strategies to isolate targeted clones has been necessary. Here, we present a rapid single-step approach to generate a gene knockout in mouse ESCs using engineered zinc-finger nucleases (ZFNs). Upon transient expression of ZFNs, the target gene is cleaved by the designer nucleases and then repaired by non-homologous end-joining, an error-prone DNA repair process that introduces insertions/deletions at the break site and therefore leads to functional null mutations. To explore and quantify the potential of ZFNs to generate a gene knockout in pluripotent stem cells, we generated a mouse ESC line containing an X-chromosomally integrated EGFP marker gene. Applying optimized conditions, the EGFP locus was disrupted in up to 8% of ESCs after transfection of the ZFN expression vectors, thus obviating the need of selection markers to identify targeted cells, which may impede or complicate downstream applications. Both activity and ZFN-associated cytotoxicity was dependent on vector dose and the architecture of the nuclease domain. Importantly, teratoma formation assays of selected ESC clones confirmed that ZFN-treated ESCs maintained pluripotency. In conclusion, the described ZFN-based approach represents a fast strategy for generating gene knockouts in ESCs in a selection-independent fashion that should be easily transferrable to other pluripotent stem cells

Chandra X-ray Observations of the Spiral Galaxy M81

A Chandra X-Ray Observatory ACIS-S imaging observation is used to study the population of X-ray sources in the nearby Sab galaxy M81 (NGC 3031). A total of 177 sources are detected with 124 located within the D25 isophote to a limiting X-ray luminosity of 3e36 ergs/cm2/s. Source positions, count rates, luminosities in the 0.3-8.0 keV band, limiting optical magnitudes, and potential counterpart identifications are tabulated. Spectral and timing analysis of the 36 brightest sources are reported including the low-luminosity active galactic nucleus, SN 1993J, and the Einstein-discovered ultra-luminous X-ray source X6.Comment: 27 pages, 17 figures, 2 tables, submitted to Ap

Long-term safety and outcome of a temporary self-expanding metallic stent for achalasia: a prospective study with a 13-year single-center experience

To prospectively evaluate the long-term clinical safety and efficacy of a newly designed self-expanding metallic stent (SEMS) in the treatment of patients with achalasia. Seventy-five patients with achalasia were treated with a temporary SEMS with a 30-mm diameter. The SEMSs were placed under fluoroscopic guidance and removed by gastroscopy 4–5 days after stent placement. Follow-up data focused on dysphagia score, technique and clinical success, clinical remissions and failures, and complications and was performed at 6 months, 1 year, and within 3 to 5 years, 5 to 8 years, 8 to 10 years, and >10 years postoperatively. Stent placement was technically successful in all patients. Complications included stent migration (n = 4, 5.33%), chest pain (n = 28, 38.7%), reflux (n = 15, 20%), and bleeding (n = 9, 12%). No perforation or 30-day mortality occurred. Clinical success was achieved in all patients 1 month after stent removal. The overall remission rates at 6 months, 1, 1–3, 3–5, 5–8, 8–10, and >10 year follow-up periods were 100%, 96%, 93.9%, 90.9%, 100%, 100%, and 83.3%, respectively. Stent treatment failed in six patients, and the overall remission rate in our series was 92%. The median and mean primary patencies were 2.8 ± 0.28 years (95% CI: 2.25–3.35) and 4.28 ± 0.40 years (95% CI: 3.51–5.05), respectively. The use of temporary SEMSs with 30-mm diameter proved to be a safe and effective approach for managing achalasia with a long-term satisfactory clinical remission rate

Oncolytic measles viruses encoding interferon β and the thyroidal sodium iodide symporter gene for mesothelioma virotherapy

Mesothelioma usually leads to death within 8–14 months of diagnosis. To increase the potency of oncolytic measles viruses (MVs) for mesothelioma therapy, we inserted the interferon β (IFNβ) gene alone or with the human thyroidal sodium iodide symporter (NIS) gene into attenuated MV of the Edmonston lineage. The corresponding mouse IFNβ (mIFNβ) viruses, MV-mIFNβ and MV-mIFNβ-NIS, successfully propagated in human mesothelioma cells, leading to intercellular fusion and cell death. High levels of mIFNβ were detected in the supernatants of the infected cells, and radioiodine uptake was substantial in the cells infected with MV-mIFNβ-NIS. MV with mIFNβ expression triggered CD68-positive immune cell infiltration 2–4 times higher than MV-GFP injected into the tumor site. The numbers of CD31-positive vascular endothelial cells within the tumor were decreased at day 7 after intratumoral injection of MV-mIFNβ or MV-mIFNβ-NIS, but not after MV-GFP and PBS administration. Immunohistochemical analysis showed that MV-mIFNβ changed the microenvironment of the mesothelioma by increasing innate immune cell infiltration and inhibiting tumor angiogenesis. Oncolytic MVs coding for IFNβ effectively retarded growth of human mesotheliomas and prolonged survival time in several mesothelioma tumor models. The results suggest that oncolytic MVs that code for IFNβ and NIS will be potent and versatile agents for the treatment of human mesothelioma

Control of the induction of type I interferon by Peste des petits ruminants virus.

Peste des petits ruminants virus (PPRV) is a morbillivirus that produces clinical disease in goats and sheep. We have studied the induction of interferon-β (IFN-β) following infection of cultured cells with wild-type and vaccine strains of PPRV, and the effects of such infection with PPRV on the induction of IFN-β through both MDA-5 and RIG-I mediated pathways. Using both reporter assays and direct measurement of IFN-β mRNA, we have found that PPRV infection induces IFN-β only weakly and transiently, and the virus can actively block the induction of IFN-β. We have also generated mutant PPRV that lack expression of either of the viral accessory proteins (V&C) to characterize the role of these proteins in IFN-β induction during virus infection. Both PPRV_ΔV and PPRV_ΔC were defective in growth in cell culture, although in different ways. While the PPRV V protein bound to MDA-5 and, to a lesser extent, RIG-I, and over-expression of the V protein inhibited both IFN-β induction pathways, PPRV lacking V protein expression can still block IFN-β induction. In contrast, PPRV C bound to neither MDA-5 nor RIG-I, but PPRV lacking C protein expression lost the ability to block both MDA-5 and RIG-I mediated activation of IFN-β. These results shed new light on the inhibition of the induction of IFN-β by PPRV