Practice of ALARA in the pediatric interventional suite

As interventional procedures have become progressively more sophisticated and lengthy, the potential for high patient radiation dose has increased. Staff exposure arises from patient scatter, so steps to minimize patient dose will in turn reduce operator and staff dose. The practice of ALARA in an interventional radiology (IR) suite, therefore, requires careful attention to technical detail in order to reduce patient dose. The choice of imaging modality should minimize radiation when and where possible. In this paper practical steps are outlined to reduce patient dose. Further details are included that specifically reduce operator exposure. Challenges unique to pediatric intervention are reviewed. Reference is made to experience from modern pediatric interventional suites. Given the potential for high exposures, the practice of ALARA is a team responsibility. Various measures are outlined for consideration when implementing a quality assurance (QA) program for an IR service

Association of Polymorphisms in Oxidative Stress Genes with Clinical Outcomes for Bladder Cancer Treated with Bacillus Calmette-Guérin

Genetic polymorphisms in oxidative stress pathway genes may contribute to carcinogenesis, disease recurrence, treatment response, and clinical outcomes. We applied a pathway-based approach to determine the effects of multiple single nucleotide polymorphisms (SNPs) within this pathway on clinical outcomes in non-muscle-invasive bladder cancer (NMIBC) patients treated with Bacillus Calmette-Guérin (BCG). We genotyped 276 SNPs in 38 genes and evaluated their associations with clinical outcomes in 421 NMIBC patients. Twenty-eight SNPs were associated with recurrence in the BCG-treated group (P<0.05). Six SNPs, including five in NEIL2 gene from the overall and BCG group remained significantly associated with recurrence after multiple comparison adjustments (q<0.1). Cumulative unfavorable genotype analysis showed that the risk of recurrence increased with increasing number of unfavorable genotypes. In the analysis of risk factors associated with progression to disease, rs3890995 in UNG, remained significant after adjustment for multiple comparison (q<0.1). These results support the hypothesis that genetic variations in host oxidative stress genes in NMIBC patients may affect response to therapy with BCG

IFITM3 Inhibits Influenza A Virus Infection by Preventing Cytosolic Entry

To replicate, viruses must gain access to the host cell's resources. Interferon (IFN) regulates the actions of a large complement of interferon effector genes (IEGs) that prevent viral replication. The interferon inducible transmembrane protein family members, IFITM1, 2 and 3, are IEGs required for inhibition of influenza A virus, dengue virus, and West Nile virus replication in vitro. Here we report that IFN prevents emergence of viral genomes from the endosomal pathway, and that IFITM3 is both necessary and sufficient for this function. Notably, viral pseudoparticles were inhibited from transferring their contents into the host cell cytosol by IFN, and IFITM3 was required and sufficient for this action. We further demonstrate that IFN expands Rab7 and LAMP1-containing structures, and that IFITM3 overexpression is sufficient for this phenotype. Moreover, IFITM3 partially resides in late endosomal and lysosomal structures, placing it in the path of invading viruses. Collectively our data are consistent with the prediction that viruses that fuse in the late endosomes or lysosomes are vulnerable to IFITM3's actions, while viruses that enter at the cell surface or in the early endosomes may avoid inhibition. Multiple viruses enter host cells through the late endocytic pathway, and many of these invaders are attenuated by IFN. Therefore these findings are likely to have significance for the intrinsic immune system's neutralization of a diverse array of threats

Combination of adenoviral virotherapy and temozolomide chemotherapy eradicates malignant glioma through autophagic and apoptotic cell death in vivo

Conditionally replicative adenoviruses (CRAds) represent a novel treatment strategy for malignant glioma. Recent studies suggest that the cytopathic effect elicited by these vectors is mediated through autophagy, a form of programmed cell death. Likewise, temozolomide (TMZ), a chemotherapeutic agent used for the treatment of malignant gliomas, also triggers autophagic cell death. In this study, we examined the potential to combine the two treatments in the setting of experimental glioma. In vitro, pretreatment with TMZ followed by CRAd-Surivin-pk7 enhanced cytotoxicity against a panel of glioma cell lines. Western blot analysis showed increased expression of BAX and p53, decreased expression of BCL2 and elevated level of APG5. Treatment with TMZ followed by CRAd-Survivin-pk7 (CRAd-S-pk7) led to a significant over-expression of autophagy markers, acidic vesicular organelles and light-chain 3 (LC3). These results were further evaluated in vivo, in which 90% of the mice with intracranial tumours were long-term survivors (>100 days) after treatment with TMZ and CRAd-S-pk7 (P<0.01). Analysis of tumours ex vivo showed expression of both LC3 and cleaved Caspase-3, proving that both autophagy and apoptosis are responsible for cell death in vivo. These results suggest that combination of chemovirotherapy offers a powerful tool against malignant glioma and should be further explored in the clinical setting

Effect of methylene blue on the genomic response to reperfusion injury induced by cardiac arrest and cardiopulmonary resuscitation in porcine brain

<p>Abstract</p> <p>Background</p> <p>Cerebral ischemia/reperfusion injury is a common secondary effect of cardiac arrest which is largely responsible for postresuscitative mortality. Therefore development of therapies which restore and protect the brain function after cardiac arrest is essential. Methylene blue (MB) has been experimentally proven neuroprotective in a porcine model of global ischemia-reperfusion in experimental cardiac arrest. However, no comprehensive analyses have been conducted at gene expression level.</p> <p>Methods</p> <p>Pigs underwent either untreated cardiac arrest (CA) or CA with subsequent cardiopulmonary resuscitation (CPR) accompanied with an infusion of saline or an infusion of saline with MB. Genome-wide transcriptional profiling using the Affymetrix porcine microarray was performed to 1) gain understanding of delayed neuronal death initiation in porcine brain during ischemia and after 30, 60 and 180 min following reperfusion, and 2) identify the mechanisms behind the neuroprotective effect of MB after ischemic injury (at 30, 60 and 180 min).</p> <p>Results</p> <p>Our results show that restoration of spontaneous circulation (ROSC) induces major transcriptional changes related to stress response, inflammation, apoptosis and even cytoprotection. In contrast, the untreated ischemic and anoxic insult affected only few genes mainly involved in intra-/extracellular ionic balance. Furthermore, our data show that the neuroprotective role of MB is diverse and fulfilled by regulation of the expression of soluble guanylate cyclase and biological processes accountable for inhibition of apoptosis, modulation of stress response, neurogenesis and neuroprotection.</p> <p>Conclusions</p> <p>Our results support that MB could be a valuable intervention and should be investigated as a therapeutic agent against neural damage associated with I/R injury induced by cardiac arrest.</p

DNA repair: the culprit for tumor-initiating cell survival?

The existence of “tumor-initiating cells” (TICs) has been a topic of heated debate for the last few years within the field of cancer biology. Their continuous characterization in a variety of solid tumors has led to an abundance of evidence supporting their existence. TICs are believed to be responsible for resistance against conventional treatment regimes of chemotherapy and radiation, ultimately leading to metastasis and patient demise. This review summarizes DNA repair mechanism(s) and their role in the maintenance and regulation of stem cells. There is evidence supporting the hypothesis that TICs, similar to embryonic stem (ES) cells and hematopoietic stem cells (HSCs), display an increase in their ability to survive genotoxic stress and injury. Mechanistically, the ability of ES cells, HSCs and TICs to survive under stressful conditions can be attributed to an increase in the efficiency at which these cells undergo DNA repair. Furthermore, the data presented in this review summarize the results found by our lab and others demonstrating that TICs have an increase in their genomic stability, which can allow for TIC survival under conditions such as anticancer treatments, while the bulk population of tumor cells dies. We believe that these data will greatly impact the development and design of future therapies being engineered to target and eradicate this highly aggressive cancer cell population

A propos de quelques Ancyloceratidae nouveaux ou peu connus du Barrémien sommital de La Bédoule (B. du Rh., France) : position stratigraphique et systématique

The recent study, in the uppermost Barremian of La Bédoule (Bouches du Rhône -France) of a rich Pseudocrioceras level, (unambiguously équivalent of the Busnardo Pseudocrioceras coquandi Zone -1984) allowed us to precise the exact stratigraphical position of this genus, at the top of the Martelites sarasini Zone and in the immediately underlying beds of the Barrcmian/Aptian boundary, defined by the FAD of the first Deshayesites of the Deshayesites tuarkyricus Zone (Delanoy et alii, 1997 Ropolo et alii, 1999, Ropolo et alii -Gonnet el alii, in press). New investigations, led us to discover three new species of Ancyloceratidae : Gill, 1871 : Pseudocrioceras massei nov. sp., Pseudocrioceras rawsoni nov. sp. et Pseudocrioceras mickali nov. sp.. The presence in these same beds of two georgian species : Pseudocrioceras densecostatum Kakabadze, Pseudocrioceras aff. abichi (Anthula), adding further to the others previously described (Ropolo et alii, 1999, Ropolo et alii, in press) permits us to assert once more the strong potentiel of correlation of this horizon which should access the status of Sub-Zone in the Tcthyan Realm. The dimorphism of Pseudocrioceras breve (d'Orbigny), found in these same level, is proposed.La récente étude dans le Barrémien sommital de la Bédoule, (Bouches du Rhône -France), d'un riche niveau à Pseudocrioceras, (équivalant sans ambiguïté à la Zone à Pseudocrioceras coquandi de Busnardo -1984), a permis de préciser la situation stratigraphique de ce genre, au sommet de la zone à Martelites sarasini et juste en dessous de la limite Barrémien/Aptien, (définie par le FAD des premiers Deshayesites de la Zone à Deshayesites tuarkyricus) (Delanoy et alii, 1997 -Ropolo et alii, 1999, Ropolo et alii -Gonnet et alii sous presse). De nouvelles recherches, nous ont conduit à découvrir trois nouvelles espèces d' Ancyloceratidae, Gill, 1871 : Pseudocrioceras massei nov. sp., Pseudocrioceras rawsoni nov. sp. et Pseudocrioceras mickali nov. sp.. La présence dans ces mômes niveaux de deux espèces géorgiennes : Pseudocrioceras densecostatum Kakabadze, et Pseudocrioceras aff. abichi (Anthula), venant s'ajouter à celles déjà décrites à la Bédoule (Ropolo et alii, 1999, Ropolo et alii sous presse) nous permet d'affirmer une fois encore le potentiel de corrélation de cet horizon qui devrait accéder au statut de sous-zone dans le domaine téthysien. Le dimorphisme de Pseudocrioceras breve (d'Orbigny), qui appartient aussi à ces niveaux, est proposé.Ropolo P., Gonnet R. A propos de quelques Ancyloceratidae nouveaux ou peu connus du Barrémien sommital de La Bédoule (B. du Rh., France) : position stratigraphique et systématique. In: Géologie Méditerranéenne. Tome 25, numéro 2, 1998. pp. 117-143