tbuckley/cabot-search huggingface dataset:
EMA/CO for High-Risk Gestational Trophoblastic Neoplasia: Good Outcomes With Induction Low-Dose Etoposide-Cisplatin and Genetic Analysis
Authors: Constantine Alifrangis, Roshan Agarwal, Delia Short, Rosemary A. Fisher, Neil J. Sebire, Richard Harvey, Philip M. Savage, Michael J. Seckl
Journal: Journal of Clinical Oncology (2012)

Patients with high-risk (International Federation of Gynecology and Obstetrics score ≥ 7) gestational trophoblastic neoplasia (GTN) frequently receive etoposide, methotrexate, and dactinomycin alternating weekly with cyclophosphamide and vincristine (EMA/CO). Between 1979 and 1995, overall survival (OS) with this regimen at our institute was 85.4% with a significant proportion of early deaths (< 4 weeks). Here, we determine whether survival rates have improved in a more recent patient cohort (1995 to 2010).Patients receiving EMA/CO were identified using the Charing Cross GTN database. Genetic analysis identified nongestational trophoblastic tumors (nGTTs). The use of induction low-dose etoposide 100 mg/m(2) and cisplatin 20 mg/m(2) (EP; days 1 and 2 every 7 days) since 1995 to reduce early deaths before commencing EMA/CO was noted.Four hundred thirty-eight patients received EMA/CO between 1995 and 2010. Six patients had nGTTs, 140 had high-risk disease, and 250 had relapsed/resistant low-risk GTN. OS was 94.3% in high-risk patients (90.4% including nGTTs) and 99.6% in the low-risk group, with a median follow-up time of 4.2 years. All patients with nGTT and seven patients with high-risk GTNs died as a result of drug-resistant disease. EP induction chemotherapy was given to 23.1% of high-risk patients (33 of 140 patients) with a large disease burden, and the early death rate was only 0.7% (n = 1; 95% CI, 0.1% to 3.7%) compared with 7.2% (n = 11 of 151 patients; 95% CI, 4.1% to 12.6%) in the pre-1995 cohort.OS after EMA/CO for high-risk GTN has increased by nearly 9%. This reflects a more accurate estimate of OS by excluding nGTTs (3.9%) in patients with atypical presentations using genetic diagnosis. Low-dose induction EP in selected individuals also allows near complete elimination of early deaths. The latter should be considered routinely in high-risk GTN.
Metallothioneins in antarctic fish: evidence for independent duplication and gene conversion
Authors: L. Bargelloni, R. Scudiero, E. Parisi, V. Carginale, C. Capasso, T. Patarnello
Journal: Molecular Biology and Evolution (1999)

In the present paper, we examine eight species of Antarctic fish belonging to the suborder Notothenioidei, using reverse-transcriptase polymerase chain reaction, to investigate the presence of mRNAs encoding metallothionein (MT) isoforms. A total of 168 bp from the coding region and the complete (133-165 bp) 3' untranslated region (UTR) was obtained for all species (for three of them, we also sequenced the full-length cDNA, including the 5' UTR). Phylogenetic analyses carried out on the MT-coding region suggest monophyly for Antarctic fish MTs with respect to other teleost MT genes. Analyses also revealed that notothenioid MTs can be divided into at least two groups of paralogy, MT-1 and MT-2. These results indicate that notothenioid MT isoforms arose from at least one gene duplication event occurring in the ancestral lineage of the Notothenioidei. This duplication occurred independent of the one which gave origin to two metallothionein isoforms in the rainbow trout. In addition, an instance of gene conversion was observed between MT-1 and MT-2 genes in Notothenia coriiceps. Analyses of the 5' UTR, combined with quantitative assay of differential expression of MT-1 and MT-2, indicate that only the 3' UTR underwent a gene conversion event in the mentioned species. These findings, together with the observation of a differential pattern of expression for the two MT isoforms, disclose an unexpected complexity in the evolution and function of notothenioid MTs; as in most teleost species examined (apart from the rainbow trout), a single MT form is present.
Analytical and Theranostic Applications of Gold Nanoparticles and Multifunctional Nanocomposites
Authors: Nikolai Khlebtsov, Vladimir Bogatyrev, Lev Dykman, Boris Khlebtsov, Sergey Staroverov, Alexander Shirokov, Larisa Matora, Vitaly Khanadeev, Timofey Pylaev, Natalia Tsyganova, Georgy Terentyuk
Journal: Theranostics (2013)

Gold nanoparticles (GNPs) and GNP-based multifunctional nanocomposites are the subject of intensive studies and biomedical applications.This minireview summarizes our recent efforts in analytical and theranostic applications of engineered GNPs and nanocomposites by using plasmonic properties of GNPs and various optical techniques.Specifically, we consider analytical biosensing; visualization and bioimaging of bacterial, mammalian, and plant cells; photodynamic treatment of pathogenic bacteria; and photothermal therapy of xenografted tumors.In addition to recently published reports, we discuss new data on dot immunoassay diagnostics of mycobacteria, multiplexed immunoelectron microscopy analysis of Azospirillum brasilense, materno-embryonic transfer of GNPs in pregnant rats, and combined photodynamic and photothermal treatment of rat xenografted tumors with gold nanorods covered by a mesoporous silica shell doped with hematoporphyrin.
Videomicrometry of lung slices: a glimpse of the dynamic airway parenchyma interaction in emphysematous lungs
Authors: C. Y. Seow
Journal: European Respiratory Journal (2007)

Emphysematous and fibrotic remodelling of lung tissue associated with chronic obstructive pulmonary disease (COPD) is known to alter the mechanical properties of the parenchyma and the airways, as well as the mechanical interdependence between them. This is thought to contribute to increased airway resistance in COPD 1. Due to its dynamic nature, attempts to directly characterise the in vivo airway–parenchyma interaction have yet to produce satisfactory results. Although some airways can be visualised (and their lumen areas quantified) in vivo with high-resolution computed tomography (HRCT) 2, 3, the time resolution of HRCT is inadequate to capture rapid events associated with the airway–parenchyma interaction in the dynamic lung environment. In addition, the spatial resolution of HRCT precludes it from imaging sub-millimeter airways. In vitro studies of airway segments 4 and parenchymal strips 5, 6 suffer from their inability to reproduce the in vivo mechanical interdependence. With high temporal and spatial resolution, videomicrometry of “live” lung slices could finally allow us to examine the dynamic airway–parenchyma interaction under conditions close to that of the native lung environment. Earlier use of videomicrometry was confined to relatively static conditions, in which airway diameters were measured under steady or semi-steady states 7–9 …
British Thoracic Society guideline for diagnostic flexible bronchoscopy in adults: accredited by NICE
Authors: I A Du Rand, J Blaikley, R Booton, N Chaudhuri, V Gupta, S Khalid, S Mandal, J Martin, J Mills, N Navani, N M Rahman, J M Wrightson, M Munavvar
Journal: Thorax (2013)

### Monitoring, precautions and complications

### Hypoxaemia

### Cardiac arrhythmias

### Bleeding complications
Selective Abrogation of Major Histocompatibility Complex Class II Expression on Extrahematopoietic Cells in Mice Lacking Promoter IV of the Class II Transactivator Gene
Authors: Jean-Marc Waldburger, Tobias Suter, Adriano Fontana, Hans Acha-Orbea, Walter Reith
Journal: The Journal of Experimental Medicine (2001)

MHC class II (MHCII) molecules play a pivotal role in the induction and regulation of immune responses. The transcriptional coactivator class II transactivator (CIITA) controls MHCII expression. The CIITA gene is regulated by three independent promoters (pI, pIII, pIV). We have generated pIV knockout mice. These mice exhibit selective abrogation of interferon (IFN)-γ–induced MHCII expression on a wide variety of non-bone marrow–derived cells, including endothelia, epithelia, astrocytes, and fibroblasts. Constitutive MHCII expression on cortical thymic epithelial cells, and thus positive selection of CD4+ T cells, is also abolished. In contrast, constitutive and inducible MHCII expression is unaffected on professional antigen-presenting cells, including B cells, dendritic cells, and IFN-γ–activated cells of the macrophage lineage. pIV−/− mice have thus allowed precise definition of CIITA pIV usage in vivo. Moreover, they represent a unique animal model for studying the significance and contribution of MHCII-mediated antigen presentation by nonprofessional antigen-presenting cells in health and disease.
Screening Outcomes in Older US Women Undergoing Multiple Mammograms in Community Practice: Does Interval, Age, or Comorbidity Score Affect Tumor Characteristics or False Positive Rates?
Authors: Dejana Braithwaite, Weiwei Zhu, Rebecca A. Hubbard, Ellen S. O’Meara, Diana L. Miglioretti, Berta Geller, Kim Dittus, Dan Moore, Karen J. Wernli, Jeanne Mandelblatt, Karla Kerlikowske
Journal: JNCI Journal of the National Cancer Institute (2013)

Uncertainty exists about the appropriate use of screening mammography among older women because comorbid illnesses may diminish the benefit of screening. We examined the risk of adverse tumor characteristics and false positive rates according to screening interval, age, and comorbidity. From January 1999 to December 2006, data were collected prospectively on 2993 older women with breast cancer and 137 949 older women without breast cancer who underwent mammography at facilities that participated in a data linkage between the Breast Cancer Surveillance Consortium and Medicare claims. Women were aged 66 to 89 years at study entry to allow for measurement of 1 year of preexisting illnesses. We used logistic regression analyses to calculate the odds of advanced (IIb, III, IV) stage, large (>20 millimeters) tumors, and 10-year cumulative probability of false-positive mammography by screening frequency (1 vs 2 years), age, and comorbidity score. The comorbidity score was derived using the Klabunde approximation of the Charlson score. All statistical tests were two-sided. Adverse tumor characteristics did not differ statistically significantly by comorbidity, age, or interval. Cumulative probability of a false-positive mammography result was higher among annual screeners than biennial screeners irrespective of comorbidity: 48.0% (95% confidence interval [CI] = 46.1% to 49.9%) of annual screeners aged 66 to 74 years had a false-positive result compared with 29.0% (95% CI = 28.1% to 29.9%) of biennial screeners. Women aged 66 to 89 years who undergo biennial screening mammography have similar risk of advanced-stage disease and lower cumulative risk of a false-positive recommendation than annual screeners, regardless of comorbidity.
<i>Circulation Research</i> Editors’ Annual Report for 2007
Authors: Eduardo Marbán, Kara Hansell Keehan, Lisa Lunt
Journal: Circulation Research (2008)

of Circulation Research throughout 2007, in this eighth year of the present editorship.The overall composition of our editorial team has remained quite stable, but, this year, several changes are worth noting.First, as previously reported, 1 we recruited Ingrid Fleming to succeed Rudi Busse after his untimely death.Second,
Sildenafil Improves Exercise Capacity and Quality of Life in Patients With Systolic Heart Failure and Secondary Pulmonary Hypertension
Authors: Gregory D. Lewis, Ravi Shah, Khurram Shahzad, Janice M. Camuso, Paul P. Pappagianopoulos, Judy Hung, Ahmed Tawakol, Robert E. Gerszten, David M. Systrom, Kenneth D. Bloch, Marc J. Semigran
Journal: Circulation (2007)

Background— Patients with systolic heart failure (HF) who develop secondary pulmonary hypertension (PH) have reduced exercise capacity and increased mortality compared with HF patients without PH. We tested the hypothesis that sildenafil, an effective therapy for pulmonary arterial hypertension, would lower pulmonary vascular resistance and improve exercise capacity in patients with HF complicated by PH. Methods and Results— Thirty-four patients with symptomatic HF and PH were randomized to 12 weeks of treatment with sildenafil (25 to 75 mg orally 3 times daily) or placebo. Patients underwent cardiopulmonary exercise testing before and after treatment. The change in peak V̇ o 2 from baseline, the primary end point, was greater in the sildenafil group (1.8±0.7 mL · kg −1 · min −1 ) than in the placebo group (−0.27 mL · kg −1 · min −1 ; P =0.02). Sildenafil reduced pulmonary vascular resistance and increased cardiac output with exercise ( P &lt;0.05 versus placebo for both) without altering pulmonary capillary wedge or mean arterial pressure, heart rate, or systemic vascular resistance. The ability of sildenafil treatment to augment peak V̇ o 2 correlated directly with baseline resting pulmonary vascular resistance ( r =0.74, P =0.002) and indirectly with baseline resting right ventricular ejection fraction ( r =−0.64, P =0.01). Sildenafil treatment also was associated with improvement in 6-minute walk distance (29 m versus placebo; P =0.047) and Minnesota Living With Heart Failure score (−14 versus placebo; P =0.01). Subjects in the sildenafil group experienced fewer hospitalizations for HF and a higher incidence of headache than those in the placebo group without incurring excess serious adverse events. Conclusions— Phosphodiesterase 5 inhibition with sildenafil improves exercise capacity and quality of life in patients with systolic HF with secondary PH.
Histologic conversion in the non-Hodgkin's lymphomas.
Authors: B Acker, R T Hoppe, T V Colby, R S Cox, H S Kaplan, S A Rosenberg
Journal: Journal of Clinical Oncology (1983)

Between July 1, 1971 and December 31, 1978, 150 patients with favorable subtypes of non-Hodgkin's lymphoma [nodular poorly differentiated lymphocytic (NLPD), nodular mixed, or diffuse well differentiated lymphocytic] were entered into prospective randomized clinical trials at Stanford University. Treatments included involved field, total lymphoid, or whole body irradiation, single alkylating agent chemotherapy, combination chemotherapy with cyclophosphamide, vincristine and prednisone (CVP) or with cyclophosphamide, vincristine, procarbazine, and prednisone (C-MOPP), or various combinations of chemotherapy and irradiation. The initial complete response rate (CR) was 79%. Among patients who achieved a CR, 31% later relapsed. There were 78 patients who either failed to achieve a CR or achieved a CR and later relapsed. Histologic conversion (change from initially favorable to an unfavorable subtype of non-Hodgkin's lymphoma) was documented in 22/78 patients (28%). However, the actuarial risk for conversion was actually much greater (60% at 8 yr). The median time to documentation of conversion was 51 mo. The most common type of histologic conversion was from NLPD to diffuse histiocytic lymphoma. Documented histologic conversion was often associated with a more aggressive clinical behavior of the lymphoma, and the median survival after conversion was less than 1 yr. However, those patients who achieved a CR after conversion had a more favorable outcome (actuarial survival 75% at 5 yr). No specific risk factors predictive of histologic conversion could be identified.
Hospital mortality league tables: influence of place of death
Authors: Valerie Seagroatt, Michael J Goldacre
Journal: BMJ (2004)

able outcomes; severe disability, vegetative state, or death were unfavourable.We used the 2 test to compare the unfavourable outcome rates of the two units and the time periods (up to or after 1995), and we used logistic regression to include age and presenting condition (according to the World Federation of Neurological Surgeons' (WFNS) grading 4 ).The rate of an unfavourable outcome was 35% in Newcastle and 19% in Nottingham.This difference was significant (P < 0.0001).The results in Newcastle worsened over time.These differences disappeared when the effects of age and presenting condition were included.Newcastle operated a less selective admissions policy than Nottingham because it did not have the deficiency of beds that Nottingham had.Between 1992 and 1998 Newcastle became progressively less selective, admitting more patients with a poor WFNS grading and more older patients.The table shows the independent effects of age, WFNS grade, and neurosurgery unit.
Doxorubicin‐Induced Cardiotoxicity: From Bioenergetic Failure and Cell Death to Cardiomyopathy
Authors: Filipa S. Carvalho, Ana Burgeiro, Rita Garcia, António J. Moreno, Rui A. Carvalho, Paulo J. Oliveira
Journal: Medicinal Research Reviews (2013)

Abstract Doxorubicin (DOX) is an anticancer anthracycline that presents a dose‐dependent and cumulative cardiotoxicity as one of the most serious side effects. Several hypotheses have been advanced to explain DOX cardiac side effects, which culminate in the development of life‐threatening cardiomyopathy. One of the most studied mechanisms involves the activation of DOX molecule into a more reactive semiquinone by mitochondrial Complex I, resulting in increased oxidative stress. The present review describes and critically discusses what is known about some of the potential mechanisms of DOX‐induced cardiotoxicity including mitochondrial oxidative damage and loss of cardiomyocytes. We also discuss alterations of mitochondrial metabolism and the unique characteristics of DOX delayed toxicity, which can also interfere on how the cardiac muscle handles a “second‐hit stress.” We also present pharmaceutical and nonpharmaceutical approaches that may decrease DOX cardiac alterations in animal models and humans and discuss the limitations of each strategy.
Ventricular mass index using magnetic resonance imaging accurately estimates pulmonary artery pressure
Authors: T.S. Saba, J. Foster, M. Cockburn, M. Cowan, A.J. Peacock
Journal: European Respiratory Journal (2002)

Magnetic resonance imaging (MRI) can provide accurate anatomical measurements of the cardiac ventricles. This study investigated whether a calculated ventricular mass index (VMI) would provide an accurate means of estimating pulmonary artery pressure noninvasively, and compared the results with conventional Doppler echocardiography and invasive measurement. A total of 26 subjects referred for investigation of pulmonary hypertension were studied by MRI and echocardiography within 2 weeks of cardiac catheterisation. The correlations for mean pulmonary artery pressure were as follows: VMI (ratio of right ventricular mass over left ventricular mass) r=0.81; pulmonary artery systolic pressure (echocardiography) r=0.77. The confidence intervals for the VMI were narrower than for echocardiography. Sensitivity and specificity for pulmonary hypertension were 84 and 71% respectively for the VMI compared with 89 and 57% for echocardiography. The calculated ventricular mass index provides an accurate and practical means of estimating pulmonary artery pressure noninvasively in pulmonary hypertension and may provide a more accurate estimate than Doppler echocardiography. This may be because it reflects the right ventricular response to sustained pulmonary hypertension over a long period and is not influenced by short-term physiological variables affecting echocardiography, such as heart rate, posture, hydration status and oxygen supplementation.
Impaired enterocyte proliferation in aquaporin-3 deficiency in mouse models of colitis
Authors: J. R Thiagarajah, D. Zhao, A S Verkman
Journal: Gut (2007)

Recent evidence has implicated the involvement of aquaporins (AQPs) in cellular functions that are unrelated to transepithelial water transport. Although AQPs are expressed in the gastrointestinal tract, their importance has so far been unclear. AQP3 is a water/glycerol transporter expressed at the basolateral membrane of colonic epithelial cells. The aim of this study was to investigate the involvement of AQP3 in enterocyte proliferation using mouse models of inflammatory bowel disease.Expression and function of AQP3 in mouse colonic epithelium were established. Colitis was induced in wild-type and AQP3 null mice by oral dextran sulphate administration or intracolonic acetic acid administration. Outcome measures included clinical disease severity, survival, pathology and cellular responses. Some mice were administered glycerol to test whether disease progression could be altered.AQP3 null mice given dextran sulphate developed severe colitis after 3 days, with colonic haemorrhage, marked epithelial cell loss and death. Wild-type mice, which had comparable initial colonic damage as assessed by cell apoptosis, developed remarkably less severe colitis, surviving to >8 days. Cell proliferation was greatly reduced in AQP3 null mice. Oral glycerol administration significantly improved survival and reduced the severity of colitis in AQP3 null mice. Survival was also reduced in AQP3 null mice in the acetic acid model.The results implicate a novel role for AQP3 in enterocyte proliferation that is probably related to its glycerol-transporting function. AQP3 is thus a potential target for therapy of intestinal diseases associated with enterocyte destruction.
Proapoptotic Activity of New Glutathione <i>S</i>-Transferase Inhibitors
Authors: Paola Turella, Claudia Cerella, Giuseppe Filomeni, Angela Bullo, Francesca De Maria, Lina Ghibelli, Maria Rosa Ciriolo, Maurizio Cianfriglia, Maurizio Mattei, Giorgio Federici, Giorgio Ricci, Anna Maria Caccuri
Journal: Cancer Research (2005)

Abstract Selected 7-nitro-2,1,3-benzoxadiazole derivatives have been recently found very efficient inhibitors of glutathione S-transferase (GST) P1-1,55G. Ricci et al. 7-Nitro-2,1,3-benzoxadiazole derivatives: a new class of suicide inhibitors for glutathione S-transferases, submitted for publication. an enzyme which displays antiapoptotic activity and is also involved in the cellular resistance to anticancer drugs. These new inhibitors are not tripeptide glutathione-peptidomimetic molecules and display lipophylic properties suitable for crossing the plasma membrane. In the present work, we show the strong cytotoxic activity of these compounds in the following four different cell lines: K562 (human myeloid leukemia), HepG2 (human hepatic carcinoma), CCRF-CEM (human T-lymphoblastic leukemia), and GLC-4 (human small cell lung carcinoma). The LC50 values are in the micromolar/submicromolar range and are close to the IC50 values obtained with GSTP1-1, suggesting that the target of these molecules inside the cell is indeed this enzyme. The cytotoxic mechanism of 6-(7-nitro-2,1,3-benzoxadiazol-4-ylthio)hexanol, the most effective GSTP1-1 inhibitor, has been carefully investigated in leukemic CCRF-CEM and K562 cell lines. Western blot and immunoprecipitation analyzes have shown that 6-(7-nitro-2,1,3-benzoxadiazol-4-ylthio)hexanol promotes in both cell lines the dissociation of the GSTP1-1 in a complex with c-jun NH2-terminal kinase (JNK). This process triggers a reactive oxygen species (ROS)–independent activation of the JNK-mediated pathway that results in a typical process of apoptosis. Besides this main pathway, in K562 cells, a ROS-mediated apoptosis partially occurs (about 30%) which involves the p38MAPK signal transduction pathway. The low concentration of this new compound needed to trigger cytotoxic effects on tumor cells and the low toxicity on mice indicate that the new 7-nitro-2,1,3-benzoxadiazole derivatives are promising anticancer agents.