tbuckley/cabot-search huggingface dataset:
Significance of the number of stimuli to initiate ouabain-induced arrhythmias in the intact heart.
Authors: M A Vos, A P Gorgels, J D Leunissen, R T van Deursen, H J Wellens
Journal: Circulation Research (1991)

Ouabain-induced arrhythmias are a well-known model used to study triggered activity resulting from delayed afterdepolarizations. In the intact heart, initiation of these arrhythmias is promoted by pacing, especially at fast rates. However, the relevance of the number of stimuli is unknown. In conscious dogs with formalin-induced atrioventricular block, we investigated the effect of variations in pacing mode on 1) the behavior of nonsustained triggered rhythms at progressive levels of ouabain intoxication, and 2) the induction of sustained ventricular tachycardia (VT). Twenty experiments were analyzed. Ouabain was administered as a bolus of 40 micrograms/kg followed by continuous infusion. Every 15 minutes the pacing protocol was repeated, with a maximum of 10, until completion or induction of VT. When VT could not be initiated, the experiment was repeated at least 1 week later, adding 5-10 micrograms/kg ouabain to the bolus and increasing the infusion rate correspondingly. This was repeated until VT could be induced. Four interstimulus intervals (200, 400, 600, and 800 msec) and seven numbers of stimuli (5, 10, 20, 35, 50, 100, and 150) were given in two pacing protocols. The effect of these protocols on 1) the number of induced beats per stimulation train, 2) their first postpacing interval, and 3) induction of VT were studied. Initiation of VT occurred after 75 +/- 42 minutes. The bolus of ouabain needed to induce VT was inversely related to the body weight of the animals. Progression of ouabain intoxication resulted in 1) a significant increase in the number of induced beats per stimulation train and 2) a significant shortening of the first postpacing interval. Stimulation at a faster rate and/or more stimuli resulted in 1) a significantly pronounced increase in the number of induced beats at the higher levels and 2) a significantly shorter first postpacing interval at successive levels of ouabain intoxication.(ABSTRACT TRUNCATED AT 250 WORDS)
Deficiency of CCAAT/enhancer binding protein family DNA binding prevents malignant conversion of adenoma to carcinoma in NNK-induced lung carcinogenesis in the mouse
Authors: Shioko Kimura, Jorge Paiz, Mitsuhiro Yoneda, Taketomo Kido, Charles Vinson, Jerrold M Ward
Journal: Molecular Cancer (2012)

The CCAAT/enhancer binding proteins (C/EBPs) play important roles in carcinogenesis of many tumors including the lung. Since multiple C/EBPs are expressed in lung, the combinatorial expression of these C/EBPs on lung carcinogenesis is not known. A transgenic mouse line expressing a dominant negative A-C/EBP under the promoter of lung epithelial Clara cell secretory protein (CCSP) gene in doxycycline dependent fashion was subjected to 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung carcinogenesis bioassay in the presence and absence of doxycycline, and the effect of abolition of DNA binding activities of C/EBPs on lung carcinogenesis was examined. A-C/EBP expression was found not to interfere with tumor development; however, it suppressed the malignant conversion of adenoma to carcinoma during NNK-induced lung carcinogenesis. The results suggested that Ki67 may be used as a marker for lung carcinomas in mouse. The DNA binding of C/EBP family members can be used as a potential molecular target for lung cancer therapy.
Tiling of R7 Axons in the Drosophila Visual System Is Mediated Both by Transduction of an Activin Signal to the Nucleus and by Mutual Repulsion
Authors: Chun-Yuan Ting, Tory Herman, Shinichi Yonekura, Shuying Gao, Jian Wang, Mihaela Serpe, Michael B. O'Connor, S. Lawrence Zipursky, Chi-Hon Lee
Journal: Neuron (2007)
Phase I study of direct gene transfer of an allogeneic histocompatibility antigen, HLA-B7, in patients with metastatic melanoma.
Authors: A T Stopeck, E M Hersh, E T Akporiaye, D T Harris, T Grogan, E Unger, J Warneke, S F Schluter, S Stahl
Journal: Journal of Clinical Oncology (1997)

PURPOSE To determine the safety, toxicity, and efficacy of direct intratumoral injection of an allogeneic major histocompatibility complex (MHC) class I gene, HLA-B7, in a cationic lipid vector (Allovectin-7; Vical Inc, San Diego, CA) in patients with metastatic melanoma. PATIENTS AND METHODS Seventeen HLA-B7-negative patients were treated with intralesional injection of Allovectin-7. Twelve patients received a single intralesional injection containing 10 micrograms (four patients), 50 micrograms (five patients), or 250 micrograms (three patients) of plasmid DNA. Five patients received two or three injections of 10 micrograms DNA to a single tumor site at 2-week intervals. Tumor biopsies pretherapy and 2 and 4 weeks after gene injection were obtained to determine expression of the plasmid by polymerase chain reaction (PCR), reverse transcriptase (RT)-PCR, flow cytometry, and immunohistochemistry. RESULTS Toxicities were related to technical aspects of the injections or biopsies. These included pain, hemorrhage, pneumothorax, and hypotension. Two patients were hospitalized overnight for observation. Seven patients (50%) had tumor responses insofar as the injected nodule decreased &gt; or = 25% by radiologic or physical examination. One patient with a single site of disease achieved a complete remission. Ninety-three percent of the patients' post-gene therapy biopsies contained HLA-B7 plasmid DNA, mRNA, or protein. CONCLUSION Intratumoral injection of the allogeneic histocompatibility gene, HLA-B7, in a lipid vector can be performed safely at plasmid DNA doses &lt; or = 250 micrograms. The safety profile and biologic activity of this therapy warrants further studies to define the mechanism of action, predictors of response, and antitumor efficacy of this approach.
Cardiovascular Depression in Rats Exposed to Inhaled Particulate Matter and Ozone: Effects of Diet-Induced Metabolic Syndrome
Authors: James G. Wagner, Katryn Allen, Hui-yu Yang, Bin Nan, Masako Morishita, Bhramar Mukherjee, J. Timothy Dvonch, Catherine Spino, Gregory D. Fink, Sanjay Rajagopalan, Qinghua Sun, Robert D. Brook, Jack R. Harkema
Journal: Environmental Health Perspectives (2013)

High ambient levels of ozone (O3) and fine particulate matter (PM2.5) are associated with cardiovascular morbidity and mortality, especially in people with preexisting cardiopulmonary diseases. Enhanced susceptibility to the toxicity of air pollutants may include individuals with metabolic syndrome (MetS).
The Relationship between Hyperinsulinemia, Hypertension and Progressive Renal Disease
Authors: Fadi A. El-Atat, Sameer N. Stas, Samy I. McFarlane, James R. Sowers
Journal: Journal of the American Society of Nephrology (2004)

The incidence of end-stage renal disease (ESRD) has risen dramatically in the past decade, mainly due to the increasing prevalence of diabetes mellitus, and both impaired glucose tolerance and hypertension are important contributors to rising rates of ESRD. Obesity, especially the visceral type, is associated with peripheral resistance to insulin actions and hyperinsulinemia, which predisposes to development of diabetes. A common genetic predisposition to insulin resistance and hypertension and the coexistence of these two disorders predisposes to premature atherosclerosis. A constellation of metabolic and cardiovascular derangements, which also includes dyslipidemia, dysglycemia, endothelial dysfunction, fibrinolytic and inflammatory abnormalities, left ventricular hypertrophy, microalbuminuria, and increased oxidative stress, is referred to as the cardiometabolic syndrome. The components of this syndrome, individually and interdependently, substantially increase the risk of renal disease, cardiovascular disease (CVD) and mortality. Similar findings and cardiorenal risk factors can occur in subjects with android obesity without excess body weight.Recently, microalbuminuria has been gaining momentum as a component and marker for the cardiometabolic syndrome, in addition to being an early marker for progressive renal disease in patients with this syndrome or in those with diabetes. Furthermore, it is now established as an independent predictor of CVD and CVD mortality. This review examines the relationship between insulin resistance/hyperinsulinemia and hypertension in the context of cardiometabolic syndrome, progressive renal disease and accelerated CVD. The importance of microalbuminuria as an early marker for the cardiometabolic syndrome is also discussed in this review.
Inhibition of overactivated p38 MAPK can restore hematopoiesis in myelodysplastic syndrome progenitors
Authors: Tony A. Navas, Mani Mohindru, Myka Estes, Jing Ying Ma, Lubomir Sokol, Perry Pahanish, Simrit Parmar, Edwin Haghnazari, Li Zhou, Robert Collins, Irene Kerr, Aaron N. Nguyen, Yin Xu, Leonidas C. Platanias, Alan A. List, Linda S. Higgins, Amit Verma
Journal: Blood (2006)
Psychiatric consequences of road traffic accidents. Loss of memory is protective.
Authors: M O'Brien
Journal: BMJ (1993)

fear of the dark, sleep disturbance, reluctance to cross roads or travel by car, and a preoccupation with road safety.Those involved in the psychological treatment of adult survivors of road traffic accidents should be aware of the possible significance of behavioural disturbance in children in the survivors' families.As children's symptoms may be closely linked to parental psychopathology (for example, post- traumatic stress disorder in a parent impedes the long term recovery of affected children5), we suggest that it may sometimes be appropriate to refer affected parents and children to children's mental health services, which emphasises a family perspective in assessment and treatment.
Clinically Defined Type 2 Diabetes Mellitus and Prognosis in Early-Stage Breast Cancer
Authors: Kirsten Erickson, Ruth E. Patterson, Shirley W. Flatt, Loki Natarajan, Barbara A. Parker, Dennis D. Heath, Gail A. Laughlin, Nazmus Saquib, Cheryl L. Rock, John P. Pierce
Journal: Journal of Clinical Oncology (2010)

Self-reported diabetes has been associated with poor breast cancer outcomes. Research is needed to investigate the relationship between biologically determined glycemic control and breast cancer prognosis.
Overnight transcutaneous carbon dioxide monitoring in eucapneic patients with obstructive sleep apnea syndrome
Authors: Banu Salepci, Ali Fidan, Benan Caglayan, Elif Torun Parmaksiz, Ülkü Aka Aktürk, Nesrin Kiral, Sevda Comert, Gulsen Sarac
Journal: European Respiratory Journal (2013)

It is well-known that 11-43% of obstructive sleep apnea syndrome (OSAS) patients experience daytime hypercapnia and they also have elevated pCO2 during sleep. We aimed to monitor pCO2 during sleep by transcutaneous pCO2(PtcCO2) measurements and find out its relationship with polysomnographic data. Between October-2011 and December-2012, 139 patients underwent PtcCO2 monitoring. All cases were evaluated with arterial blood gases and pulmonary function tests. Thirteen cases with COPD and/or daytime hypercapnia and 29 cases whose PtcCO2 records could not be evaluated were excluded. Chi-square, Fisher’s exact test, Mann Whitney U Test, Student’s T test and Pearson correlation tests were used in statistical analysis. Mean age of 59(60.8%) male and 38(39.2%) female cases was 46.8±10.3. Mean overnight PCO2 was ≤45 mmHg in 84(86.6%) and >45 mmHg in 13(13.4%) cases. Number of cases with AHI >15 was higher in PCO2>45 group when compared to PCO2 ≤45 group without statistical significance (76.9% vs. 59.5% respectively, p=0.078). Mean apnea period, apnea/interapnea periods were similar. Mean PtcCO2 values were found to be correlated with time spent during SpO2 15 (moderate to severe OSAS) and 37(37.2%) had AHI 45 mmHg, while this ratio was 8.1% in the latter group but the difference was not statistically significant (p=0.359). In AHI>15 group, highest PCO2 were significantly higher (p
Essential and Instructive Roles of GATA Factors in Eosinophil Development
Authors: Ryutaro Hirasawa, Ritsuko Shimizu, Satoru Takahashi, Mitsujiro Osawa, Shu Takayanagi, Yuko Kato, Masafumi Onodera, Naoko Minegishi, Masayuki Yamamoto, Katashi Fukao, Hideki Taniguchi, Hiromitsu Nakauchi, Atsushi Iwama
Journal: The Journal of Experimental Medicine (2002)

GATA transcription factors are major regulators of hematopoietic and immune system. Among GATA factors, GATA-1, GATA-2, and GATA-3 play crucial roles in the development of erythroid cells, hematopoietic stem, and progenitor cells, and T helper type 2 (Th2) cells, respectively. A high level of GATA-1 and GATA-2 expression has been observed in eosinophils, but their roles in eosinophil development remain uncertain both in vitro and in vivo. Here we show that enforced expression of GATA-1 in human primary myeloid progenitor cells completely switches myeloid cell fate into eosinophils. Expression of GATA-1 exclusively promotes development and terminal maturation of eosinophils. Functional domain analyses revealed that the COOH-terminal finger is essential for this capacity while the other domains are dispensable. Importantly, GATA-1–deficient mice failed to develop eosinophil progenitors in the fetal liver. On the other hand, GATA-2 also showed instructive capacity comparable to GATA-1 in vitro and efficiently compensated for GATA-1 deficiency in terms of eosinophil development in vivo, indicating that proper accumulation of GATA factors is critical for eosinophil development. Taken together, our findings establish essential and instructive roles of GATA factors in eosinophil development. GATA-1 and GATA-2 could be novel molecular targets for therapeutic approaches to allergic inflammation.
The Role of Stepdown Beds in Hospital Care
Authors: Meghan Prin, Hannah Wunsch
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

Section:ChooseTop of pageAbstract <<Definition of a Stepdown ...Patient Selection for SDU...Location of SDU BedsStaffingSDU Care and Patient Outc...Economics of SDUsConclusionsReferencesCITING ARTICLES
Reconsidering the Approach to Prevention Recommendations for Older Adults
Authors: Rosanne M. Leipzig
Journal: Annals of Internal Medicine (2010)

The U.S. Preventive Services Task Force (USPSTF) bases its recommendations on an evidence-based model of clinical prevention that focuses on specific diseases, well-defined preventive interventions, and evidence of improved health outcomes. Applying this model to prevention for very old patients has been problematic for several reasons: Many geriatric disorders have multiple risk factors, interventions, and expected outcomes; older adults are not often represented in clinical trials; and important outcomes may not be measured and reported in ways that are conducive to evidence synthesis and interpretation. In 2005, the USPSTF convened a geriatrics workgroup to refine USPSTF methodology and processes to better address the preventive needs of older adults. The USPSTF has begun to apply these new approaches to the review and recommendation on interventions to prevent falls in older adults.
Fish Oil and Postoperative Atrial Fibrillation
Authors: Dariush Mozaffarian, Roberto Marchioli, Alejandro Macchia, Maria G. Silletta, Paolo Ferrazzi, Timothy J. Gardner, Roberto Latini, Peter Libby, Federico Lombardi, Patrick T. O’Gara, Richard L. Page, Luigi Tavazzi, Gianni Tognoni, for the OPERA Investigators
Journal: JAMA (2012)

Postoperative atrial fibrillation or flutter (AF) is one of the most common complications of cardiac surgery and significantly increases morbidity and health care utilization. A few small trials have evaluated whether long-chain n-3-polyunsaturated fatty acids (PUFAs) reduce postoperative AF, with mixed results.To determine whether perioperative n-3-PUFA supplementation reduces postoperative AF.The Omega-3 Fatty Acids for Prevention of Post-operative Atrial Fibrillation (OPERA) double-blind, placebo-controlled, randomized clinical trial. A total of 1516 patients scheduled for cardiac surgery in 28 centers in the United States, Italy, and Argentina were enrolled between August 2010 and June 2012. Inclusion criteria were broad; the main exclusions were regular use of fish oil or absence of sinus rhythm at enrollment.Patients were randomized to receive fish oil (1-g capsules containing ≥840 mg n-3-PUFAs as ethyl esters) or placebo, with preoperative loading of 10 g over 3 to 5 days (or 8 g over 2 days) followed postoperatively by 2 g/d until hospital discharge or postoperative day 10, whichever came first.Occurrence of postoperative AF lasting longer than 30 seconds. Secondary end points were postoperative AF lasting longer than 1 hour, resulting in symptoms, or treated with cardioversion; postoperative AF excluding atrial flutter; time to first postoperative AF; number of AF episodes per patient; hospital utilization; and major adverse cardiovascular events, 30-day mortality, bleeding, and other adverse events.At enrollment, mean age was 64 (SD, 13) years; 72.2% of patients were men, and 51.8% had planned valvular surgery. The primary end point occurred in 233 (30.7%) patients assigned to placebo and 227 (30.0%) assigned to n-3-PUFAs (odds ratio, 0.96 [95% CI, 0.77-1.20]; P = .74). None of the secondary end points were significantly different between the placebo and fish oil groups, including postoperative AF that was sustained, symptomatic, or treated (231 [30.5%] vs 224 [29.6%], P = .70) or number of postoperative AF episodes per patient (1 episode: 156 [20.6%] vs 157 [20.7%]; 2 episodes: 59 [7.8%] vs 49 [6.5%]; ≥3 episodes: 18 [2.4%] vs 21 [2.8%]) (P = .73). Supplementation with n-3-PUFAs was generally well tolerated, with no evidence for increased risk of bleeding or serious adverse events.In this large multinational trial among patients undergoing cardiac surgery, perioperative supplementation with n-3-PUFAs, compared with placebo, did not reduce the risk of postoperative AF. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00970489.
Clinically Useful Estimates of Insulin Sensitivity During Pregnancy
Authors: John P. Kirwan, Larraine Huston-Presley, Satish C. Kalhan, Patrick M. Catalano
Journal: Diabetes Care (2001)

OBJECTIVE—We examined whether selected indexes of insulin sensitivity derived from an oral glucose tolerance test (ISOGTT) or fasting glucose/insulin levels (ISQUICKI and ISHOMA) can be used to predict insulin sensitivity in women before and during pregnancy. RESEARCH DESIGN AND METHODS—A 2-h euglycemic-hyperinsulinemic clamp (5 mmol/l glucose, 40 mU · m−2 · min−1 insulin) and a 120-min oral glucose tolerance test (75 g load pregravid, 100 g pregnant) were repeated on 15 women (10 with normal glucose tolerance [NGT] and 5 with gestational diabetes mellitus [GDM]) pregravid and during both early (12–14 weeks) and late (34–36 weeks) pregnancy. An index of insulin sensitivity derived from the clamp (ISCLAMP) was obtained from glucose infusion rates adjusted for change in fat-free mass and endogenous glucose production measured using [6,6-2H2]glucose. RESULTS—Univariate analysis using combined groups and periods of pregnancy resulted in significant correlations between ISCLAMP and ISOGTT (r2 = 0.74, P &amp;lt; 0.0001), ISQUICKI (r2 = 0.64, P &amp;lt; 0.0001), and ISHOMA (r2 = 0.53, P &amp;lt; 0.0001). The ISOGTT provided a significantly better correlation (P &amp;lt; 0.0001) than either ISQUICKI or ISHOMA. Multivariate analysis showed a significant group effect (P &amp;lt; 0.0003) on the prediction model, and separate equations were developed for the NGT (r2 = 0.64, P &amp;lt; 0.0001) and GDM (r2 = 0.85, P &amp;lt; 0.0001) groups. When subdivided by period of pregnancy, the correlation between ISCLAMP and ISOGTT pregravid was r2 = 0.63 (P = 0.0002), during early pregnancy was r2 = 0.80 (P &amp;lt; 0.0001), and during late pregnancy was r2 = 0.64 (P = 0.0002). CONCLUSIONS—Estimates of insulin sensitivity from the ISOGTT during pregnancy were significantly better than from fasting glucose and insulin values. However, separate prediction equations are necessary for pregnant women with NGT and women with GDM.
Predictors of Tamoxifen Discontinuation Among Older Women With Estrogen Receptor–Positive Breast Cancer
Authors: Cynthia Owusu, Diana S.M. Buist, Terry S. Field, Timothy L. Lash, Soe Soe Thwin, Ann M. Geiger, Virginia P. Quinn, Floyd Frost, Marianne Prout, Marianne Ulcickas Yood, Feifei Wei, Rebecca A. Silliman
Journal: Journal of Clinical Oncology (2007)

Five years of adjuvant tamoxifen therapy for estrogen receptor (ER) -positive breast cancer is more effective than 2 years of use. However, information on tamoxifen discontinuation is scanty. We sought to identify predictors of tamoxifen discontinuation among older women with breast cancer.Within six health care delivery systems, we identified women >or= 65 years old diagnosed with stage I to IIB ER-positive or indeterminant breast cancer between 1990 and 1994 who had filled a prescription for adjuvant tamoxifen. We observed them for 5 years after initial tamoxifen prescription. We used automated pharmacy records to validate tamoxifen prescription information abstracted from medical records. The primary end point was tamoxifen discontinuation, operationalized as ever discontinuing tamoxifen during 5 years of follow-up. We used Cox proportional hazards to identify predictors of tamoxifen discontinuation.Of 961 women who were prescribed tamoxifen, 49% discontinued tamoxifen before the completion of 5 years. Discontinuers were more likely to be aged 75 to less than 80 years (v < 70 years; hazard ratio [HR] = 1.41; 95% CI, 1.06 to 1.87), be aged >or= 80 years (HR = 2.02; 95% CI, 1.53 to 2.66), have an increase in Charlson Comorbidity Index at 3 years from diagnosis (HR = 1.52; 95% CI, 1.18 to 1.95), have an increase in the number of cardiopulmonary comorbidities at 3 years (HR = 1.75; 95% CI, 1.34 to 2.28), have indeterminant ER status (v ER-positive status; HR = 1.36; 95% CI, 1.00 to 1.85), and have received breast-conserving surgery (BCS) without radiotherapy (v mastectomy; HR = 1.62; 95% CI, 1.18 to 2.22).Attention to nonadherence among older women at risk of discontinuation, particularly those receiving BCS without radiotherapy, might improve breast cancer outcomes for these women.
CpG island methylator phenotype underlies sporadic microsatellite instability and is tightly associated with BRAF mutation in colorectal cancer
Authors: Daniel J Weisenberger, Kimberly D Siegmund, Mihaela Campan, Joanne Young, Tiffany I Long, Mark A Faasse, Gyeong Hoon Kang, Martin Widschwendter, Deborah Weener, Daniel Buchanan, Hoey Koh, Lisa Simms, Melissa Barker, Barbara Leggett, Joan Levine, Myungjin Kim, Amy J French, Stephen N Thibodeau, Jeremy Jass, Robert Haile, Peter W Laird
Journal: Nature Genetics (2006)