tbuckley/cabot-search huggingface dataset:
Autologous stem-cell transplantation and purging.
Authors: B Löwenberg, P Voogt
Journal: Journal of Clinical Oncology (1996)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1996.14.8.2194 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 8708707 Autologous stem-cell transplantation and purging. B LöwenbergxB LöwenbergSearch for articles by this author , P VoogtxP VoogtSearch for articles by this author https://doi.org/10.1200/JCO.1996.14.8.2194 First Page PDF © 1996 by American Society of Clinical Oncology
Abstract 13849: Advanced Glycation Endproduct Carboxymethyl-Lysine (CML) and Risk of Atrial Fibrillation in Older Adults
Authors: Farbod Raiszadeh, Traci Bartz, Susan J Zieman, Kenneth J Mukamal, Joachim H Ix, Luc Djousse, David Siscovick, Russell P Tracy, Susan R Heckbert, Anne B Newman, Ayman Hussein, John S Gottdiener, Jorge R Kizer
Journal: Circulation (2013)

Background: Advanced glycation endproducts (AGEs) form through chemical modification of proteins from hyperglycemia or increased oxidative stress, as occurs in diabetes, chronic kidney disease (CKD...
Escalator Avulsions
Authors: Michael J. Cahill, Anthony Shaw, Vincent J. Fontana
Journal: New England Journal of Medicine (1964)

ESCALATOR accidents resulting in serious injury are relatively uncommon and have received little attention in the medical literature. For example, in a recent article by Aitken1 on the etiology of traumatic amputations in children, six main subdivisions include childhood recreation, thermal, household, railroad, vehicular, gunshot explosion and power or farm-tool implements as a cause. Injuries due to escalators are not listed. The analysis of a large group of accidents among preschool children in the Boston area by Meyer et al.2 considers only broad categories of trauma, as do many other articles dealing with accidental injury to children. Similarly, in the . . .
BUPA and the tobacco industry
Authors: F. Howell, M. O'Rourke
Journal: BMJ (1998)

Editor—I was delighted to see that Wald and Watt, from the BUPA Epidemiological Research Group, were able to state conclusively that there were no conflicts of interest evident in their study on smoking related diseases.1 In the same issue of the BMJ the BUPA Foundation advertised generous research awards for communication, epidemiology, health at work, and research. Could this be the same BUPA that has recently established a division in the Republic of Ireland and has had the foresight to appoint one of our most successful businesswomen, Dr Margaret Downes, as its chairperson? That she is also the chairperson of one of the biggest tobacco producers in the Republic of Ireland (Gallaher) seems to be irrelevant to BUPA. One cannot readily criticise Dr Downes for accepting the offer to chair BUPA Ireland—after all, being chairperson of BUPA must offer some degree of respectability, and the tobacco industry is in short supply of that. Furthermore, it is probably the best each-way bet one could hope for (especially if you work for the tobacco industry)—profits when the smokers are smoking and profits when the smokers are dying. 

Surely someone in BUPA can see the potential conflicts of interest in this appointment. If they have difficulty in doing so, perhaps some of the recipients of their largesse in the United Kingdom would point out the hard realities to them and do us all a favour.
Abstract MP046: Gestational Hypertension in Minorities: Can Racial and Ethnic Disparities Be Attributed to Socio-Economic Status?
Authors: Alexander V Sergeev, Christina M Nyirati
Journal: Circulation (2012)

Background: Gestational hypertension (GHTN) remains a compelling clinical and public health problem. It can increase risks of intrauterine growth restriction, low-birth weight, and stillbirth. Little is known about whether racial and ethnic minorities and lower socio-economic status (SES) population groups are more vulnerable to GHTN. Hypothesis: We hypothesized that racial and ethnic disparities in GHTN exist beyond the scope of SES-related health disparities. Methods: A case-control study of GHTN was conducted using the data of 114,298 births in the year 2010 in Ohio. The comprehensive births data were obtained from Ohio Department of Health. Cases were identified as those with GHTN. Controls were identified as those without GHTN. Mothers utilizing Medicaid or the Federal Special Supplemental Nutrition Program for Women, Infants and Children were considered of low SES. Odds ratios of GHTN in relation to mother’s race, ethnicity, and SES were obtained using multivariable logistic regression (SAS software), adjusting for known confounders - gestational age, mother’s age, pre-pregnancy and pregnancy smoking status, pre-pregnancy or gestational diabetes, and plurality. Results: GHTN was statistically significantly associated with maternal race and ethnicity, even after adjustment for SES. Compared to non-Hispanic whites, non-Hispanic blacks were more likely to develop GHTN (adjusted OR = 1.867, 95% CI 1.663–2.096, p&lt;0.001), while Asian women were less likely to develop GHTN (adjusted OR = 0.538, 95% CI 0.426–0.679, p&lt;0.001). Hispanic white women were less likely to develop GHTN than non-Hispanic white women, although the difference between them did not reach a conventional p&lt;0.05 level of statistical significance (adjusted OR = 0.651, 95% CI 0.395–1.076, p=0.09). Adjusted for maternal race, ethnicity, age, and known clinical confounders, women of lower SES were more likely to develop GHTN (adjusted OR = 1.475, 95% CI 1.32–1.647, p&lt;0.001). Conclusions: Non-Hispanic black women are at the highest risk of developing GHTN, while Asian women are at the lowest. The Hispanic paradox phenomenon extends to the issue of GHTN. Racial and ethnic disparities cannot be attributed to low SES only; other mechanisms need to be investigated further.
A Randomized, Open-Label, Multicenter, Phase III Study of Epoetin Alfa Versus Best Standard of Care in Anemic Patients With Metastatic Breast Cancer Receiving Standard Chemotherapy
Authors: Brian Leyland-Jones, Igor Bondarenko, Gia Nemsadze, Vitaliy Smirnov, Iryna Litvin, Irakli Kokhreidze, Lia Abshilava, Mikheil Janjalia, Rubi Li, Kuntegowda C. Lakshmaiah, Beka Samkharadze, Oksana Tarasova, Ranjan Kumar Mohapatra, Yaroslav Sparyk, Sergey Polenkov, Vladimir Vladimirov, Liang Xiu, Eugene Zhu, Bruce Kimelblatt, Kris Deprince, Ilya Safonov, Peter Bowers, Els Vercammen
Journal: Journal of Clinical Oncology (2016)

Purpose An open-label, noninferiority study to evaluate the impact of epoetin alfa (EPO) on tumor outcomes when used to treat anemia in patients receiving chemotherapy for metastatic breast cancer. Methods Women with hemoglobin ≤ 11.0 g/dL, receiving first- or second-line chemotherapy for metastatic breast cancer, were randomly assigned to EPO 40,000 IU subcutaneously once a week or best standard of care. The primary end point was progression-free survival (PFS). Secondary end points included overall survival, time to tumor progression, overall response rate, RBC transfusions, and thrombotic vascular events. Results In 2,098 patients randomly assigned, median PFS (based on investigator-determined disease progression [PD]) was 7.4 months in both groups (hazard ratio [HR], 1.089; 95% CI, 0.988 to 1.200); upper bound exceeded prespecified noninferiority margin of 1.15. Median PFS per independent review committee–determined PD was 7.6 months in both groups (HR, 1.028; 95% CI, 0.922 to 1.146); upper bound did not exceed prespecified noninferiority margin. Median overall survival at clinical cutoff (1,337 deaths) was 17.2 months in the EPO and 17.4 months in the best standard of care group (HR, 1.057; 95% CI, 0.949 to 1.177), median time to tumor progression was 7.5 months in both groups (HR, 1.094; 95% CI, 0.991 to 1.209), and overall response rate was 50% versus 51% (odds ratio, 0.950; 95% CI, 0.799 to 1.130). RBC transfusions were 5.8% versus 11.4% (P &lt; .001), and thrombotic vascular events were 2.8% versus 1.4% (P = .038), respectively. Conclusion The primary end point, PFS based on investigator-determined PD, did not meet noninferiority criteria. As a consistency assessment with the primary finding, PFS based on independent review committee–determined PD met noninferiority criteria. Overall, this study did not achieve noninferiority objective in ruling out a 15% increased risk in PD/death. RBC transfusion should be the preferred approach for the management of anemia in this population.
Phase I/II study of MKC-1 and pemetrexed (PEM) as second-line therapy in patients (pts) with advanced non-small cell lung cancer (NSCLC)
Authors: N. H. Hanna, D. Estes, J. Arnott, S. Marcotte, A. Hannah, C. F. Sidor, H. West, G. Clamon, T. Hoang
Journal: Journal of Clinical Oncology (2009)

e19005 Background: MKC-1 is a novel oral cell cycle inhibitor with preclinical activity against NSCLC cell lines including multi-drug resistant lines, and single agent activity in NSCLC pts. Binding targets of MKC-1 include microtubules, members of the importin-β family and AKT-mTOR. This phase 1/2 study evaluated MKC-1 in combination with PEM as second-line therapy in pts with advanced NSCLC. Methods: Eligible pts had NSCLC previously treated with one regimen for metastatic disease or disease progression within one year following adjuvant and neoadjuvant therapy. Phase 1 dose escalation used 3+3 design. Phase 2 pts were treated with MKC-1 at 75 mg/m 2 given p.o. BID for 14 days along with PEM at 500 mg/m 2 given i.v. on day 1 of each 21 day cycle. Following 4 cycles of combined treatment, single agent MKC-1 was continued as maintenance therapy. An interim analysis after 17 pts in phase 2 would allow accrual to continue provided one response was confirmed. Results: 27 pts were enrolled (8 in phase 1 and 19 in phase 2). Median age/PS for phase 2 is 64/1 and 89% had adenocarcinoma. Total # of treatment cycles to date for phase 2 pts is 95, with a median of 4 cycles. Of the 19 phase 2 pts, 18 were evaluable for tumor response. The best response was confirmed PR, noted in 3 pts. 5 additional pts (4 confirmed) had minor responses (&gt;10% but &lt;30% shrinkage). One additional pt continues on study with stable disease for &gt;18 months. In phase 2 (n=19), all grade toxicities were anorexia (59%), fatigue (63%), nausea (58%), and dyspnea (48%). Grade 3/4 toxicities included fatigue (26%); neutropenia (22%); dyspnea, anorexia, AST and ALT elevation (11% each); nausea and constipation (5% each). 7 pts had at least one dose reduction of both PEM and MKC-1 and 3 additional pts had only MKC-1 reduced. Median PFS was 86 days with two pts continuing on study (treated for 530+ days and 140+ days, respectively). Conclusions: The phase 2 dose of MKC-1 (75 mg/m 2 BID) and PEM (500 mg/m 2 ) has been defined. The combination is well tolerated with 17% of patients achieving a confirmed PR thus far. A decision to proceed with additional accrual in this single arm study versus initiating a randomized phase 2 study of this combination is pending. [Table: see text]
Abstract 113: SUMO1 Gene Transfer Rescues Cardiac Function in a Large Animal Model of Heart Failure
Authors: Lisa M Tilemann, Kiyotake Ishikawa, Changwon Kho, Ahyoung Lee, Jaime Aguero, Kleopatra Rapti, Carlos Santos Gallego, Erik Kohlbrenner, Kenneth M Fish, Roger J Hajjar
Journal: Circulation Research (2012)

Recently, small ubiquitin-related modifier 1 (SUMO1) was found to enhance the activity and stability of the cardiac sarcoplasmic reticulum Ca2+ ATPase, SERCA2a. In both, human and rodent models of heart failure (HF), the total amount of myocardial SUMO1 is decreased and its knock down results in severe HF. Adeno-associated vector (AAV) mediated SUMO1 gene transfer significantly improves cardiac function in murine models of HF. As a critical step towards clinical translation, we evaluated the effects of SUMO1 gene transfer in a swine model of ischemic heart failure. One month after balloon occlusion of the proximal LAD, 21 animals were randomized to receive either AAV1.SUMO1 at two doses, AAV1.SERCA2a, AAV1.SUMO1+AAV1.SERCA2a, or saline via antegrade coronary infusion. In addition, three pigs served as controls and underwent sham procedures. The ejection fraction and the maximum dP/dt significantly increased after gene transfer of SUMO1 at both doses, SERCA2a and the combination of SUMO1 and SERCA2a (p=0.034, p=0.028) compared to saline infusion. The increase in maximum dP/dt was most pronounced in the group that received both SUMO1 and SERCA2a. Furthermore, the increase in end-systolic and end-diastolic volumes was normalized in the treatment groups, while they further deteriorated in the saline group (p=0.001, p=0.022). SUMO1 and SERCA2a gene transfer significantly improved cardiac function and concomitant gene delivery of SUMO1 and SERCA2a had a synergistic effect on improving these parameters in the HF animals. These results strongly support the critical role of SUMO1 for SERCA2a function and underline the therapeutic potential in heart failure patients.
LDH is a prognostic factor in stage IV melanoma patients (pts) but is a predictive factor only for bcl2 antisense treatment efficacy: Re-analysis of GM301 and EORTC18951 randomized trials
Authors: U. Keilholz, S. Suciu, A. Y. Bedikian, C. J. Punt, M. Gore, W. Kruit, A. C. Pavlick, A. Spatz, E. Gilles, A. M. Eggermont
Journal: Journal of Clinical Oncology (2007)

8552 Background: Two large studies with identical eligibility criteria and using serum LDH as stratification for randomization were re-analyzed in order to 1) confirm the prognostic importance of LDH in advanced melanoma; 2) to assess whether an interaction between LDH and treatment efficacy exists. Methodology: Oblimersen (OBL) trial GM301 randomized 771 pts between DTIC vs. DTIC+OBL, whereas EORTC trial 18951 randomized 365 pts between biochemotherapy vs biochemotherapy+IL2 (JCO, 2004). LDH was divided into 5 groups: 5 UNL. Cox model was used to asses the prognostic importance of LDH, treatment difference and LDH-treatment interaction regarding the main endpoint, overall survival (OS). Results: In each study LDH appeared to be of strong and incremental prognostic importance (p&lt;0.0001): the higher the LDH the shorter the OS. Median OS in pts with LDH&lt;0.8 UNL was ±1 yr vs. 5 UNL. In both trials, pts with LDH 0.8–1.1 UNL had already a shorter median OS (± 9 months) as compared to the &lt;0.8 group. In each study, overall, treatment differences were not significant. However, an interaction between LDH and treatment difference was observed in GM301 (p=0.01), but not in 18951 (p=0.51). In GM301, the largest benefit in favor of OBL was confined to the LDH &lt;0.8 UNL subgroup (see table ), whereas in EORTC18951 the trend for an IL2 advantage was spread over several LDH groups. The observation was consistent also for response and PFS, and was not related to known confounding variables including metastatic disease site and PS. Conclusion: LDH is a biomarker with remarkable prognostic value for OS in advanced melanoma, and our analysis provides evidence for its prognostic value already below the UNL. Furthermore, OBL only had an effect in pts with low pretreatment LDH levels representing more favorable biology. No significant financial relationships to disclose. [Table: see text]
Collagen receptor α2β1 integrin is overexpressed on CD4 and CD8 peripheral blood T lymphocytes in long-lasting clinically stable asthma
Authors: Joanna Zuk, Stanislawa Bazan-Socha, Jacek Musial
Journal: European Respiratory Journal (2011)

Background: Recruitment of the inflammatory cells from blood to the airways in asthma is mediated by adhesive molecules – e.g. selectins and integrins. In cells trafficking the best known integrins are molecules containing α4 and β2 subunits. We hypothesized that also integrins α1β1 and α2β1 may play a role in asthma pathogenesis.

Objective, material and methods: The aim of the study was to assess expression of several very late antigen (VLA) integrin subunits (α1, α2, α4 and β1) on blood CD4 and CD8 T lymphocytes by flow cytometry in 25 adult atopic asthmatics (mild to moderate persistent asthma in a stable clinical condition) and 15 healthy controls.

Results: Expression of both α4 and β1 on CD4 T cells was significantly higher in asthma subjects than in controls. The α1 subunit was absent from blood lymphocytes. The α2 chain hardly detected on lymphocytes from healthy subjects was apparently present in asthmatics. Surprisingly, in subjects suffering from asthma for over 4 years (n=15) statistically significant overexpression of α2, α4 and β1 subunits on both CD4 and CD8 T cells was observed as compared to controls.

Conclusion: Expression of certain VLA integrin subunits on blood T cells may depend on asthma duration. In long-lasting disease α2, α4 and β1 subunits are overexpressed on both CD4 and CD8 T lymphocytes. The biological role of α2β1 integrin in asthma is unknown. This integrin has been described as a stimulator of collagen accumulation in the airways and in chronic disease may be at least in part, responsible for asthma airway remodelling.
Abstract 18312: In vivo Selection of Ghrelin as a Powerful Cardioprotective Factor After Myocardial Infarction
Authors: Giulia Ruozi, Francesca Bortolotti, Antonella Falcione, Matteo Dal Ferro, Lorena Zentilin, Serena Zacchigna, Mauro Giacca
Journal: Circulation (2013)

Introduction: By applying an innovative selection procedure based on in vivo gene transfer of AAV libraries coding for the entire mouse secretome, we discovered that the neurohormone ghrelin exerts a powerful protective effect against skeletal muscle damage. In particular, an AAV9 expressing ghrelin protected muscle fibers from severe hind limb ischemia and promoted muscle regeneration. Hypothesis: Based on the established similarities between biology and functional regulation of cardiomyocytes and muscle cells, we wanted to assess the hypothesis that ghrelin was also an effective protective factor in a mouse model of myocardial infarction (MI). Methods: A group of CD1 mice (n=20 per group) underwent permanent left descendent coronary artery ligation and were immediately injected into the peri-infarcted area with 1x10^11 viral particles of an AAV9 vector expressing ghrelin or a control AAV9 empty vector. Cardiac function after MI was monitored by echocardiography, morphometric, histological and molecular analysis. Results: Cardiac gene delivery of AAV9-Ghrelin after MI determined a marked improvement of cardiac function (LVEF: 51±3% vs. 31±3% for AAV9-Ghrelin vs. AAV9-Control vector; LVFS: 26±1% vs. 15±2%) at day 90 after MI (p&lt;0.001 in both cases), while significantly reducing infarct size (27±2 vs. 51±5%; p&lt;0.001). The marked improvement in cardiac contractility was paralleled by a reduced apoptotic rate at early times after MI (31±5% vs 8±4%, p&lt;0.005) and reduced inflammatory cells infiltration in the peri-infarctual region. Moreover, ghrelin counteracted the induction of markers of cardiac damage (in particular, miR21 and MMP-2) and prevented the deregulated expression of pathological left ventricle remodelling markers, such ad bMHC, BNP and others. Conclusions: In conclusion, these results demonstrate the efficacy of ghrelin as a powerful molecule conferring protection from skeletal muscle degeneration and providing benefit upon cardiac damage.
Commission emphasises nutritional value of meat in booklet for new mothers
Authors: J. R Glynn
Journal: BMJ (1996)

these animals had died of bovine spongiform encephalopathy,7 although the details of the experiment have not been published.Furthermore, since the ban on cannibalistic feeding was imposed in 1988 over 22000 animals have been bom that have subsequently developed bovine spongiform encephalopathy; one was born as recently as June 1993.Interestingly, the range of ages at which the disease was diagnosed in these animals is virtually the same as that in animals born before the ban (table).Distribution of ages of animals with confirmed bovine spongiform encephalopathy bom before and after feed containing recycled animal remains was banned in July 1988.Figures are numbers (percentages) Born before ban, Born after ban, Age disease diagnosed disease diagnosed (years) 19893
Cyclin A overexpression and survival in node-negative (N-) breast cancer patients
Authors: E. Baldini, A. Camerini, T. Prochilo, F. Pasqualetti, C. Orlandini, A. Capodanno, B. Salvadori, P. Collecchi
Journal: Journal of Clinical Oncology (2005)

589 Background: Risk factors such as hormone receptor status, primary tumor volume and grading often fail to identify node-negative breast cancer patients with poor prognosis. The search for new molecular risk markers is of primary importance in clinical practice. Changes in cell cycle control mechanisms are frequently described in human neoplasms and their prognostic significance need to be evaluated. Methods: We analysed the expression of Cyclin A in 75 consecutive node-negative breast cancer patients: 17 out of 75 (22.6%) relapsed within 5 years from diagnosis while the others did not. We correlate the expression of Cyclin A with Ki67, E2F1, tumor size, grading, estrogen receptor status (ER) and RFS (median follow-up 10 yrs). Cyclin A, Ki67 and E2F1 were determined by IHC. The median values of expression of each parameter were used as cut-off. Results: Cyclin A was overexpressed in 34 of 75 patients (45.3%) and it directly correlated with tumor size (p = 0.0009), high Ki67 (p = 0.0001) and high E2F1 (p = 0.036) levels. No relationship with age, ER status and tumor grade was observed. 12/17 pts (71%) with early relapse (within 5 yrs) showed Cyclin A overexpression in comparison with 22/58 pts (38%) who did not (p = 0.02). DFS curves for pts with Cyclin A overexpression vs no-overexpression were significantly different (p = 0.012). DFS was also different for low vs high Ki67 expression (p = 0.003) and low vs high E2F1levels (p = 0.019). Conclusions: Significantly poorer DFS was observed in cyclin A overexpressing patients. The strong relationship observed between Cyclin A overexpression, high proliferation index and large tumor size might identify breast cancers with more aggressive phenotypes and consequently patients at increased risk of relapse. No significant financial relationships to disclose.