tbuckley/cabot-search huggingface dataset:
A prospective randomized repeat-crossover comparison of antitachycardia pacing with low-energy cardioversion.
Authors: G H Bardy, J E Poole, P J Kudenchuk, G L Dolack, D Kelso, R Mitchell
Journal: Circulation (1993)

BACKGROUND Multiprogrammable antiarrhythmia devices can treat monomorphic ventricular tachycardia (VT) with autodecremental overdrive pacing and/or with low-energy cardioversion. These two methods provide the opportunity to decrease patient discomfort typically experienced with high-energy pulses. Although both therapies are known to be effective, controversy persists over their relative safety and efficacy. METHODS AND RESULTS The purpose of this study was to examine the safety and efficacy of autodecremental overdrive pacing and low-energy cardioversion in reproducibly terminating monomorphic VT in 24 patients with multiprogrammable antiarrhythmia devices. The protocol required that identical ECG morphology VT be reproducibly induced four times to assess the outcome of antitachycardia pacing and cardioversion twice for each patient in a randomized fashion. Each episode of VT was induced via the implanted device. Autodecremental overdrive pacing initially began with seven stimuli at 97% of the VT cycle length, decrementing by 10 msec per stimulus to a minimum coupling interval of 200 msec. If ineffective, autodecremental overdrive pacing was allowed to iterate three more times for a total of four pacing interventions. With each iteration, one stimulus was added to the pacing train. Similarly, with low-energy cardioversion, up to four therapeutic attempts were made, beginning with a 0.2-J pulse. If ineffective, pulse energy was increased to 0.4, 1.0, and finally 2.0 J. All interventions were automatic without human interference. VT (cycle length, 306 +/- 42 msec) was repeatedly terminated in 15 of 24 patients (63%) by autodecremental overdrive pacing and in 18 of 24 patients (75%) by low-energy cardioversion (p = 0.53). Eight of the 24 patients (33%) had their VT terminated repeatedly by both therapies. VT accelerated to faster VT or ventricular fibrillation by autodecremental overdrive pacing in four of 24 patients (17%) and by low-energy cardioversion in five of 24 (21%) (p = 0.88). Only one of the 24 patients (4%) accelerated with both therapies. No patient was unaffected by either therapy. CONCLUSIONS In the manner programmed, autodecremental overdrive pacing and low-energy cardioversion have similar efficacy and acceleration rates. Response to one therapy does not predict response to the other.
Estrogen decreases TNF gene expression by blocking JNK activity and the resulting production of c-Jun and JunD
Authors: Sunil Srivastava, M. Neale Weitzmann, Simone Cenci, F. Patrick Ross, Stuart Adler, Roberto Pacifici
Journal: Journal of Clinical Investigation (1999)

Central to the bone-sparing effect of estrogen (E2) is its ability to block the monocytic production of the osteoclastogenic cytokine TNF-α (TNF). However, the mechanism by which E2 downregulates TNF production is presently unknown. Transient transfection studies in HeLa cells, an E2 receptor–negative line, suggest that E2 inhibits TNF gene expression through an effect mediated by estrogen receptor β (ERβ). We also report that in RAW 264.7 cells, an E2 receptor–positive murine monocytic line, E2 downregulates cytokine-induced TNF gene expression by decreasing the activity of the Jun NH2-terminal kinase (JNK). The resulting diminished phosphorylation of c-Jun and JunD at their NH2-termini decreases the ability of these nuclear proteins to autostimulate the expression of the c-Jun and JunD genes, thus leading to lower production of c-Jun and JunD. The consequent decrease in the nuclear levels of c-Jun and JunD leads to diminished binding of c-Jun/c-Fos and JunD/c-Fos heterodimers to the AP-1 consensus sequence in the TNF promoter and, thus, to decreased transactivation of the TNF gene.
Validation of a Model of Lung Cancer Risk Prediction Among Smokers
Authors: Kathleen A. Cronin, Mitchell H. Gail, Zhaohui Zou, Peter B. Bach, Jarmo Virtamo, Demetrius Albanes
Journal: JNCI Journal of the National Cancer Institute (2006)

The Bach model was developed to predict the absolute 10-year risk of developing lung cancer among smokers by use of participants in the Carotene and Retinol Efficacy Trial of lung cancer prevention. We assessed the validity of the Bach model among 6239 smokers from the placebo arm of the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study. The expected numbers of lung cancer cases and deaths without lung cancer were calculated from the Bach model and compared with the observed numbers of corresponding events over 10 years. We found that the risk model slightly underestimated the observed lung cancer risk (number of lung cancers expected/number observed = 0.89, 95% confidence interval [CI] = 0.80 to 0.99) over 10 years. The competing risk portion of the model substantially underestimated risk of non-lung cancer mortality (number of non-lung cancer deaths expected/number observed = 0.61, 95% CI = 0.57 to 0.64) over 10 years. The age-specific concordance indices for 10-year predictions were 0.77 (95% CI = 0.70 to 0.84), 0.59 (95% CI = 0.53 to 0.65), 0.62 (95% CI = 0.57 to 0.67), and 0.57 (95% CI = 0.49 to 0.67) for the age groups 50-54, 55-59, 60-64, and 65-69 years, respectively. Periodic radiographic screening in the ATBC Study may explain why slightly more cancers were observed than expected from the Bach model.
Health inequalities are worsening across Europe, says WHO
Authors: A. Gulland
Journal: BMJ (2013)

Despite improvements in health overall in Europe, health inequalities are worsening, a report by the World Health Organization has found.1

The report, which covers the 53 countries of WHO’s European region, warned that the global financial crisis has brought “conditions of great hardship to parts of the region.” It said that the crisis was more “profound and extended than most people predicted” and “exposed stark social and economic inequities within and between countries.”

Health inequities are worse in the eastern part of the region, said Michael Marmot, chairman of the review and director of the Institute of Health Equity at University College London, in the foreword to …
Respiratory muscle function in infants
Authors: C Gaultier
Journal: European Respiratory Journal (1995)

In newborns and infants a variety of respiratory disorders lead to ventilatory failure. In early life the ventilatory response to loaded breathing is limited. The risk factors of ventilatory failure are related to the developing respiratory pump because of the immaturity of the chest wall, respiratory muscles and coupling between thoracic and abdominal movements. Assessment of respiratory muscle function in infants is limited, due to the objections to using invasive techniques. However, measurement of airway pressures during crying may provide an index of respiratory muscle strength in infants. Real-time ultrasonography allows investigation of diaphragmatic movements. Pattern of thoracoabdominal motion can be assessed using uncalibrated respiratory inductive plethysmography. Finally, electromyographic recording of respiratory muscles by surface electrodes is of clinical usefulness during sleep studies.
Estimates of the Number of U.S. Women Who Could Benefit From Tamoxifen for Breast Cancer Chemoprevention
Authors: Andrew N Freedman, Barry I Graubard, Sowmya R Rao, Worta McCaskill-Stevens, Rachel Ballard-Barbash, Mitchell H Gail
Journal: JNCI Journal of the National Cancer Institute (2003)

The Breast Cancer Prevention Trial demonstrated that tamoxifen treatment produced a 49% reduction in the risk of invasive breast cancer among women at elevated risk for the disease. The U.S. Food and Drug Administration (FDA) subsequently approved tamoxifen for women aged 35 years or older with a 5-year breast cancer risk of 1.67% or higher for breast cancer chemoprevention. However, tamoxifen use has been associated with adverse outcomes, and not all eligible women have a positive benefit/risk ratio.We used weighted data from the year 2000 National Health Interview Survey Cancer Control Module to estimate the total number of U.S. women, aged 35-79 years, who were eligible for tamoxifen chemoprevention based on the FDA eligibility criteria. We also estimated the numbers of white and black women who would benefit from tamoxifen chemoprevention on the basis of a positive benefit/risk index developed by Gail et al.Of the 65,826,074 women aged 35-79 years without reported breast cancer in the United States in 2000, 10,232 816 women (15.5%, 95% confidence interval [CI] = 14.7% to 16.3%) would be eligible for tamoxifen chemoprevention. The percentage of U.S. women who would be eligible varied dramatically by race, with 18.7% (95% CI = 17.8% to 19.7%) of white women, 5.7% (95% CI = 4.3% to 7.5%) of black women, and 2.9% (95% CI = 2.1% to 3.9%) of Hispanic women being eligible. Of the 50,104,829 white U.S. women aged 35-79 years, 2,431,911 (4.9%, 95% CI = 4.3% to 5.4%) would have a positive benefit/risk index for tamoxifen chemoprevention. Of the 7,481,779 black U.S. women aged 35-79 years, only 42,768 (0.6%, 95% CI = 0.2% to 1.3%) would have a positive benefit/risk index. Among white women, 28,492 (95% CI = 24,693 to 32,292) breast cancers would be prevented or deferred if those women who have a positive net benefit index took tamoxifen over the next 5 years.A substantial percentage of U.S. women would be eligible for tamoxifen chemoprevention according to FDA criteria, but a much smaller percentage would have an estimated net benefit. Nevertheless, this latter percentage corresponds to more than two million women.
The molecular regulation of GADD153 in apoptosis of cultured vascular smooth muscle cells by cyclic mechanical stretch
Authors: Wen-Pin Cheng, Huei-Fong Hung, Bao-Wei Wang, Kou-Gi Shyu
Journal: Cardiovascular Research (2007)

AimsThe expression of GADD153 (growth arrest and DNA damage-inducible gene 153), an apoptosis-regulated gene, increases during endoplasmic reticulum (ER) stress. How mechanical stretch affects the regulation of GADD153 in vascular smooth muscle cells (VSMCs) during apoptosis is not fully understood. We aimed to test the hypothesis that mechanical stretch induces GADD153 expression in VSMCs undergoing apoptosis.
Developmental changes in cardiac myocyte calcium regulation.
Authors: T K Chin, W F Friedman, T S Klitzner
Journal: Circulation Research (1990)

Developmental changes in the contributions of transsarcolemmal Ca2+ influx and Ca2+ release from intracellular storage sites to myocardial contraction were evaluated in isolated ventricular myocytes from neonatal (aged 1-7 days) and adult (aged 8-10 weeks) New Zealand White rabbits. Contractions ceased in one beat when extracellular Ca2+ was decreased from 1mM to micromolar levels using a rapid perfusion technique. On reperfusion with 1 mM Ca2+, recovery of control contraction amplitude occurred after significantly fewer beats in neonatal myocytes compared with adult myocytes, and after 1 minute compared with 5 minutes of reduced Ca2+. After 15 minutes of perfusion with either 1 or 10 microM ryanodine, contraction amplitude decreased in both age groups, but the decrease was significantly greater in adults than in neonates. These experiments indicate that isolated ventricular myocytes may be used in the study of developmental changes in intracellular Ca2+ regulation. Results suggest that cardiac contraction in neonates is relatively more dependent on transsarcolemmal Ca2+ influx. Furthermore, although Ca2+ release from intracellular storage sites is present in both neonates and adults, its role in cardiac contraction is more significant in adults.
Early Childhood Electronic Media Use as a Predictor of Poorer Well-being
Authors: Trina Hinkley, Vera Verbestel, Wolfgang Ahrens, Lauren Lissner, Dénes Molnár, Luis A. Moreno, Iris Pigeot, Hermann Pohlabeln, Lucia A. Reisch, Paola Russo, Toomas Veidebaum, Michael Tornaritis, Garrath Williams, Stefaan De Henauw, Ilse De Bourdeaudhuij
Journal: JAMA Pediatrics (2014)

Identifying associations between preschool-aged children's electronic media use and their later well-being is essential to supporting positive long-term outcomes.To investigate possible dose-response associations of young children's electronic media use with their later well-being.The IDEFICS (Identification and Prevention of Dietary- and Lifestyle-Induced Health Effects in Children and Infants) study is a prospective cohort study with an intervention component. Data were collected at baseline from September 1, 2007, through June 30, 2008, and at follow-up from September 1, 2009, through May 31, 2010, in 8 European countries participating in the IDEFICS study. This investigation is based on 3604 children aged 2 to 6 years who participated in the longitudinal component of the IDEFICS study only and not in the intervention.Early childhood electronic media use.The following 6 indicators of well-being from 2 validated instruments were used as outcomes at follow-up: Peer problems and Emotional problems subscales from the Strengths and Difficulties Questionnaire and Emotional well-being, Self-esteem, Family functioning, and Social networks subscales from the KINDLR (Questionnaire for Measuring Health-Related Quality of Life in Children and Adolescents-Revised Version). Each scale was dichotomized to identify those children at risk for poorer outcomes. Indicators of electronic media use (weekday and weekend television and electronic game [e-game]/computer use) from baseline were used as predictors.Associations varied between boys and girls; however, associations suggested that increased levels of electronic media use predicted poorer well-being outcomes. Television viewing on weekdays or weekends was more consistently associated with poorer outcomes than e-game/computer use. Across associations, the likelihood of adverse outcomes in children ranged from a 1.2- to 2.0-fold increase for emotional problems and poorer family functioning for each additional hour of television viewing or e-game/computer use depending on the outcome examined.Higher levels of early childhood electronic media use are associated with children being at risk for poorer outcomes with some indicators of well-being. Further research is required to identify potential mechanisms.
Chronic flexor tenosynovitis: missed diagnosis for a decade.
Authors: L Morris, A Stevens, M Doherty
Journal: Annals of the Rheumatic Diseases (1996)

Chronic flexor tenosynovits more exotic injury from sea urchin spines, date palm fronds, and cactus'5 may need to be con- sidered.The lesson * The acute inflammation of penetrating spine or thorn injury is often self-limiting and misdiagnosed as sepsis.* The history of prior injury may be forgotten or overlooked at the time of presentation with chronic synovitis * Investigations are usually unhelpful.* Surgical removal is necessary for diagnosis and is curative.
Phase 1 Clinical and Pharmacokinetics Evaluation of Oral CI-1033 in Patients with Refractory Cancer
Authors: John Nemunaitis, Irene Eiseman, Casey Cunningham, Neil Senzer, Adrienne Williams, Peter F. Lenehan, Stephen C. Olson, Paul Bycott, Michael Schlicht, Rebecca Zentgraff, Dong M. Shin, Ralph G. Zinner
Journal: Clinical Cancer Research (2005)

Abstract Purpose: To determine the tolerability and pharmacokinetics of oral CI-1033, a pan-erbB tyrosine kinase inhibitor, administered over 14 consecutive days of a 21-day cycle. Design: Phase 1, multicenter trial involving patients with solid tumors that are refractory to standard therapy. CI-1033 was administered initially at 300 mg/day to a minimum cohort of three patients. Dose escalation proceeded at ≤40% increments. Patients were evaluated for toxicity, pharmacokinetic profile, and evidence of response. Results: Thirty-two patients entered the trial and were evaluable for safety assessment. Dose-limiting toxicity (diarrhea, rash, and/or anorexia) occurred at the 560 mg dose level; the maximum tolerated dose was 450 mg. No patients achieved objective responses and six patients achieved stable disease. Plasma CI-1033 concentrations increased with increasing dose. CI-1033 was not eliminated in urine to any appreciable extent. Conclusions: CI-1033 is suitable for phase 2 testing at the 450 mg/day dose level when administered for 14 days in a 21-day cycle. The pharmacokinetic profile is consistent with biologically relevant plasma concentrations over the dosing interval.
High-Dose Sirolimus and Immune-Selective Pentostatin plus Cyclophosphamide Conditioning Yields Stable Mixed Chimerism and Insufficient Graft-versus-Tumor Responses
Authors: Miriam E. Mossoba, David C. Halverson, Roger Kurlander, Bazetta Blacklock Schuver, Ashley Carpenter, Brenna Hansen, Seth M. Steinberg, Syed Abbas Ali, Nishant Tageja, Frances T. Hakim, Juan Gea-Banacloche, Claude Sportes, Nancy M. Hardy, Dennis D. Hickstein, Steven Z. Pavletic, Hanh Khuu, Marianna Sabatini, David Stroncek, Bruce L. Levine, Carl H. June, Jacopo Mariotti, Olivier Rixe, Antonio Tito Fojo, Michael R. Bishop, Ronald E. Gress, Daniel H. Fowler
Journal: Clinical Cancer Research (2015)

Abstract Purpose: We hypothesized that lymphoid-selective host conditioning and subsequent adoptive transfer of sirolimus-resistant allogeneic T cells (T-Rapa), when combined with high-dose sirolimus drug therapy in vivo, would safely achieve antitumor effects while avoiding GVHD. Experimental Design: Patients (n = 10) with metastatic renal cell carcinoma (RCC) were accrued because this disease is relatively refractory to high-dose conditioning yet may respond to high-dose sirolimus. A 21-day outpatient regimen of weekly pentostatin (P; 4 mg/m2/dose) combined with daily, dose-adjusted cyclophosphamide (C; ≤200 mg/d) was designed to deplete and suppress host T cells. After PC conditioning, patients received matched sibling, T-cell–replete peripheral blood stem cell allografts, and high-dose sirolimus (serum trough target, 20–30 ng/mL). To augment graft-versus-tumor (GVT) effects, multiple T-Rapa donor lymphocyte infusions (DLI) were administered (days 0, 14, and 45 posttransplant), and sirolimus was discontinued early (day 60 posttransplant). Results: PC conditioning depleted host T cells without neutropenia or infection and facilitated donor engraftment (10 of 10 cases). High-dose sirolimus therapy inhibited multiple T-Rapa DLI, as evidenced by stable mixed donor/host chimerism. No antitumor responses were detected by RECIST criteria and no significant classical acute GVHD was observed. Conclusions: Immune-selective PC conditioning represents a new approach to safely achieve alloengraftment without neutropenia. However, allogeneic T cells generated ex vivo in sirolimus are not resistant to the tolerance-inducing effects of in vivo sirolimus drug therapy, thereby cautioning against use of this intervention in patients with refractory cancer. Clin Cancer Res; 21(19); 4312–20. ©2015 AACR.
An atlas of bovine gene expression reveals novel distinctive tissue characteristics and evidence for improving genome annotation
Authors: Gregory P Harhay, Timothy PL Smith, Leeson J Alexander, Christian D Haudenschild, John W Keele, Lakshmi K Matukumalli, Steven G Schroeder, Curtis P Van Tassell, Cathy R Gresham, Susan M Bridges, Shane C Burgess, Tad S Sonstegard
Journal: Genome biology (2010)

A comprehensive transcriptome survey, or gene atlas, provides information essential for a complete understanding of the genomic biology of an organism. We present an atlas of RNA abundance for 92 adult, juvenile and fetal cattle tissues and three cattle cell lines. The Bovine Gene Atlas was generated from 7.2 million unique digital gene expression tag sequences (300.2 million total raw tag sequences), from which 1.59 million unique tag sequences were identified that mapped to the draft bovine genome accounting for 85% of the total raw tag abundance. Filtering these tags yielded 87,764 unique tag sequences that unambiguously mapped to 16,517 annotated protein-coding loci in the draft genome accounting for 45% of the total raw tag abundance. Clustering of tissues based on tag abundance profiles generally confirmed ontology classification based on anatomy. There were 5,429 constitutively expressed loci and 3,445 constitutively expressed unique tag sequences mapping outside annotated gene boundaries that represent a resource for enhancing current gene models. Physical measures such as inferred transcript length or antisense tag abundance identified tissues with atypical transcriptional tag profiles. We report for the first time the tissue-specific variation in the proportion of mitochondrial transcriptional tag abundance. The Bovine Gene Atlas is the deepest and broadest transcriptome survey of any livestock genome to date. Commonalities and variation in sense and antisense transcript tag profiles identified in different tissues facilitate the examination of the relationship between gene expression, tissue, and gene function.
Activation In Vitro of Mouse Macrophages by Syngeneic, Allogeneic, or Xenogeneic Lymphocyte Supernatants2
Authors: Isaiah J. Fidler
Journal: JNCI Journal of the National Cancer Institute (1975)

Macrophages from normal C57BL/6 mice, those with a subcutaneous B16 melanoma, and mice immunized against the tumor were examined for in vitro cytotoxicity to B16 tumor cells. Macrophages were treated by incubation with supernatants from B16 cells grown either in unmixed cultures or in cultures containing syngeneic, normal, or sensitized allogeneic (A mouse), or xenogeneic (rat) lymphocytes. The various treated and untreated macrophages were then cultured for 5 days with viable B16 cells prelabeled with 125l-5-iodo-2′deoxyuridine; the cultures were terminated, and the extent of destruction of the B16 target cells was determined from the amounts of radioactivity remaining in adherent tumor cells. Of the untreated macrophages, only those from immunized mice were cytotoxic to the tumor cells; macrophages from normal and tumor-bearing mice became cytotoxic by incubation with supernatants from cultures containing lymphocytes from immunized syngeneic mice, sensitized allogeneic mice, or sensitized rats; and macrophages incubated with supernatants from cultures containing normal nonsensitized allogeneic or xenogeneic lymphocytes showed no cytotoxicity. These results suggested that macrophages from tumor-bearing animals are potentially cytotoxic to their syngeneic tumors and can be activated by mediators released from sensitized syngeneic, allogeneic, and/or xenogeneic lymphocytes in vitro.