tbuckley/cabot-search huggingface dataset:
Abstract 10837: Brain Natriuretic Peptide, but Not Calprotectin or the Long Pentraxin 3 Independently Predicts Stroke in Long-Term Follow-up of Patients With Acute Coronary Syndrome.
Authors: Volker Ponitz, Trygve Brugger- Andersen, Heidi Grundt, Oistein Mjelva, Harry Staines, Dennis W Nilsen
Journal: Circulation (2010)

Background: Besides its predictive utility for mortality, Brain Natriuretic Peptide (BNP) also predicts stroke in a general population, patients with heart failure and in patients undergoing haemodialysis. Less evidence exists whether BNP or the novel cardiac biomarkers Calprotectin and The Long Pentraxin 3 (PTX3) may predict stroke in patients admitted with acute coronary syndrome (ACS). Methods: Admission BNP, PTX3 and Calprotectin were measured in 795 patients admitted with symptoms suspective of an ACS. Multivariate analysis was performed using a Cox Proportional Hazard Ratio model. Variables included in the model were BNP, Calprotectin, PTX3 and 18 conventional risk factors for cardiovascular disease including heart failure, hypertension and hs-CRP. Results: 27 out of 795 patients had an incident of stroke during the follow-up time of two years. Admission level of BNP above the median (median 95pg/mL) significantly predicted stroke (HR 6.7; 95% CI 2.3–19.6, p&lt;0.001, KM survival plot displayed in figure). Following adjustment in the multivariate analysis, BNP remained an independent predictor for stroke (HR 3.2; 95% CI 1.0–9.7, p&lt;0.05). In contrast, neither Calprotectin nor PTX3 provided independent prognostic information for stroke. Conclusions: Admission level of BNP but not of Calprotectin or PTX3 independently predicts stroke in long term follow-up of patients admitted with chest pain suspective of an ACS.
Childhood separation anxiety disorder in patients with adult anxiety disorders
Authors: J D Lipsitz, L Y Martin, S Mannuzza, T F Chapman, M R Liebowitz, D F Klein, A J Fyer
Journal: American Journal of Psychiatry (1994)

The authors examined the relation between retrospectively reported childhood separation anxiety disorder and adult DSM-III-R anxiety disorders in 252 outpatients at an anxiety disorders research clinic. The prevalence of childhood separation anxiety disorder was significantly greater among patients with two or more lifetime adult anxiety disorder diagnoses than it was among patients with only one anxiety disorder, suggesting that childhood separation anxiety disorder may be a risk factor for multiple anxiety syndromes in adulthood.
Chemotherapy-free interval following initial chemotherapy in patients with stage IV colorectal cancer
Authors: G. Melmed, C. Becerra, G. Saracino, E. Bowman, A. D. McCollum
Journal: Journal of Clinical Oncology (2009)

e15096 Background: Patients with metastatic colorectal cancer (mCRC) have improved survival due to recent advances in systemic therapy. It remains unclear whether patients responding to initial chemotherapy can be offered a chemotherapy free interval (CFI) without compromising survival. An initial CFI is potentially beneficial from a quality of life and health care economics standpoint. Methods: We studied patients with mCRC treated at Baylor University Medical Center (Dallas, TX) who had a CFI after first-line chemotherapy. Eligible patients had unresectable mCRC and had stable or responding disease after initial chemotherapy. Records were analyzed to record patient characteristics, chemotherapy details, initial response, duration of CFI, progression free survival (PFS), and overall survival (OS). Results: We identified 29 eligible patients treated between 11/02 and 11/08. Analyses are based on data from 8/08. Patient characteristics included: median age 63 (range 34–81), M/F 16/13, ECOG PS 0 (9) or 1 (20), and median number of sites of disease 2 (range 1–7). Initial chemotherapy regimens included mFOLFOX6 with or without bevacizumab (10), FOLFIRI/bevacizumab (12), XELOX/bevacizumab (2), 5-fluorouracil/leucovorin/bevacizumab (3), and capecitabine with or without bevacizumab (2). With a median follow-up of 31.1 months, the median duration of CFI was 8.0 months (95% CI: 4.3–9.6). In addition, the median OS was 33.7 months (95% CI: 27.8 -56.3) and PFS was 15.0 months (95% CI: 9.4–21.4). Conclusions: In this selected group of patients with mCRC, we found a CFI of 8 months. The OS nearing 34 months and PFS of 15 months compares favorably with other studies of patients treated for mCRC. An initial CFI may reduce the medical and financial burden of therapy for patients with mCRC without compromising outcomes and warrants further study. [Table: see text]
Abstract 14574: Who is at Risk for Exhaustion Post-Cardiac Surgery
Authors: Pamela S Miller, Lorraine S Evangelista, Joyce Newman Giger, Teresita Corvera-Tindel, Otoniel Martinez-Maza, Kathleen Dracup, Lynn V Doering
Journal: Circulation (2011)

Background: Vital exhaustion (VE), a psychological state characterized by extreme fatigue, is an independent prognostic indicator of future cardiac events. Despite its prognostic value, little is k...
Abstract 18658: Endothelial Overexpression of a Conditional Fas-Induced Apoptosis Construct in Transgenic Mice Triggers Pulmonary Hypertension with Complex Vascular Lesions
Authors: Jin-Yi Jiang, Paul Jurasz, David W Courtman, Yupu Deng, Anli Yang, Kursad Turksen, Duncan J Stewart
Journal: Circulation (2010)

Introduction: Pulmonary arterial hypertension (PAH) is a lethal disorder characterized by lung arteriolar remodeling and obliteration. Endothelial cell (EC) apoptosis has been suggested to be an initiating event in PAH, possibly leading to the emergence of highly proliferative, apoptosis resistant vascular cells that contribute to the characteristic plexiform lesions. Therefore, we assessed whether the induction of a defined level of EC apoptosis would be sufficient to produce PAH, as well as proliferative, plexiform-like arteriolar lesions using a novel conditional transgenic mouse model. Methods: The Fas-Induced Apoptosis (FIA) construct contains the cytoplasmic death domain of the Fas receptor together with 2 copies of the FK506-binding peptide (FKBP) domain. This construct was targeted to ECs using the Tie2 promoter in transgenic (i.e. EFIA) mice. Apoptosis was induced by a small molecule dimerizing agent, AP20187, which binds tightly to the FKBP domain, and assessed by TUNEL staining. Right ventricul...
Neutrophil elastase inhibitor sivelestat ameliorates gefitinib-induced acute pneumonitis in mice
Authors: Hironori Mikumo, Ichiro Inoshima, Saiko Ogata, Yuichi Mizuta, Kunihiro Suzuki, Tetsuya Yokoyama, Naoki Hamada, Yoichi Nakanishi
Journal: European Respiratory Journal (2014)

INTRODUCTION: Gefitinib, one of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI), is an effective therapeutic agent for non-small cell lung cancer with EGFR mutations. It is well known that gefitinib can cause severe acute pneumonitis in some patients. We previously demonstrated that mice with naphthalene-induced airway epithelial injury developed severe gefitinib-induced pneumonitis and that neutrophil plays important roles in the development of the disease. (Harada C  et al .  Am J Respir Crit Care Med . 2011).  AIMS and OBJECTIVES: The aim of this study is to investigate the effects of neutrophil elastase inhibitor sivelestat (ONO-5046) on gefitinib-induced pneumonitis in mice.  METHODS: C57BL/6J mice received naphthalene (200 mg/kg) intraperitonially on day 0. Gefitinib (250 or 300 mg/kg) was orally given to mice from day 1 until 13. Sivelestat (150 mg/kg) was given intraperitoneally from day 1 until 13. Bronchoalveolar lavage fluid (BALF) and lung tissues were obtained on day14.  RESULTS: Sivelestat treatment significantly reduced the protein level and neutrophil count in BALF, and severity of histopathologic findings on day 14 of mice given 250 mg/kg of gefitinib. Moreover, sivelestat treatment significantly improved survival of mice given 300 mg/kg of gefitinib.  CONCLUSIONS: The present results indicate that sivelestat may be one of the promising therapeutic agents for severe acute pneumonitis caused by gefitinib.
In vivo T‐cell depletion with pretransplant low‐dose antithymocyte globulin is associated with reduced transplant‐related mortality and improved clinical outcome in patients receiving allogeneic hematopoietic stem cell transplantation from unrelated and partially matched related donors
Authors: Alessandro Busca, Franco Locatelli, Simona Emilia Flonta, Gianni Ciccone, Ileana Baldi, Stefano D'Ardia, Bernardino Allione, Michele Falda
Journal: American Journal of Hematology (2010)

Graft versus host disease (GVHD) represents one of the major limiting factors to the successful applicability of hematopoietic stem cells transplantation (HSCT). In particular, allogeneic HSCT from alternative donors with unmanipulated graft results in an increased risk of both acute and chronic GVHD compared with matched sibling donor transplants [1]. At the present, none of the GVHD prophylactic strategies currently in use, including calcineurin inhibitors [2], T-lymphocyte depletion, and monoclonal antibodies [3,4], have been proven to be of superior efficacy over another.
Induction of helper T-cell 1-dominant state by an immunotherapeutic agent OK-432, 5-fluorouracil and radiation: Involvement of suppressor of cytokine signaling −1 and −3.
Authors: Masato Okamoto, Tetsuya Oshikawa, Tomoyuki Tano, Sharif U. Ahmed, Akiko Sasai, Shin Kan, Mitsunobu Sato
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

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Background and objective: We have reported that the therapy by an immunotherapeutic agent OK-432 and 5-fluorouracil (FU) in combination with radiation exhibits a marked therapeutic effect in the patients with head and neck cancer. Although it is important in anti-cancer immunity to polarize T-cell response to helper T-cell 1 (Th1)-dominant state, CD4+T cells are able to differentiate to Th2 as well as to regulatory T cells (Treg), and produce interleukin (IL)-10 and transforming growth factor (TGF)-β, which decrease anti-cancer immunity. In the current study, we conducted the in vitro study to examine the effect of 5-FU and X-irradiation in the OK-432-induced cytokine production and expression of the molecules related to cytokine balance. Methods: Human peripheral blood mononuclear cells (PBMCs) were stimulated with OK-432 (1μg/ml), 5-FU (5μg/ml) or X-ray (2Gy). Twenty-four hours later, cytokines in the supernatants were measured by ELISA, expression of the genes for T-bet, GATA-3 and Foxp3 which are pivotal transcription factors for Th1, Th2 and Treg, respectively, and for suppressor of cytokine signaling (SOCS)-1 and SOCS-3 which are negative regulators for cytokine signaling, on the PBMCs, was evaluated by reverse transcription-polymerase chain reaction. Results: Stimulation of PBMCs with OK-432 induced Th1-type cytokines (interferon-γ, tumor necrosis factor-α, IL-12, IL-18) as well as IL-10 and TGF-β. When PBMCs were stimulated by 5-FU and/or X-ray in combination with OK-432, production of IL-10 and TGF-β was significantly inhibited. No significant change in the production of Th1-type cytokines was observed. Although OK-432 enhanced the expression of the genes encoding T-bet, GATA-3 and Foxp3, 5-FU and X-irradiation inhibited the increased expression of GATA-3 and Foxp3 genes but not of T-bet gene. Gene expression of negative regulators, SOCS-1 and SOCS-3, was augmented by OK-432, however, this was also inhibited by 5-FU and X-irradiation. OK-432-induced IL-10 and TGF-β, but not Th1-type cytokines, was significantly reduced by addition of antisense oligonucleotide for SOCS-1 or that for SOCS-3. Conclusions: Radiation and 5-FU induce Th1-dominant state by inhibiting the OK-432-induced production of IL-10 and TGF-β mediated by regulation of negative regulators, SOCS-1 and SOCS-3, and are strongly suggested to increase anti-cancer immunity.
Abstract 6: Quantitative assessment of BCL-2:BIM complexes as a pharmacodynamic marker for venetoclax (ABT-199)
Authors: Sha Jin, Paul Tapang, Donald J. Osterling, Wenqing Gao, Daniel H. Albert, Andrew J. Souers, Joel D. Leverson, Darren C. Phillips, Jun Chen
Journal: Cancer Research (2015)

Abstract The BCL-2-selective inhibitor venetoclax (ABT-199) binds with high affinity to the BH3-binding groove of BCL-2, thereby competing for binding with the BH3-only protein BIM (Souers et al., 2013). Venetoclax is currently being evaluated in clinical trials for CLL, AML, multiple myeloma and NHL. To facilitate these studies, we developed and validated a 384-well electrochemiluminescent ELISA (MSD, Gaithersburg, MD,USA) that quantifies expression of BCL-2, BCL-XL, and MCL-1protein alone or in complex with BIM. We subsequently quantified expression of BCL-2 and BCL-2:BIM complexes in 16 hematologic tumor cell lines. We found the EC50 of venetoclax in these tumor cell lines to correlate strongly with baseline BCL-2:BIM complex levels. This correlation was superior to the correlation between venetoclax EC50 and absolute BCL-2 expression. We also applied the assay to measure disruption of BCL-2:BIM complexes in vivo. Treatment of the Non-Hodgkin's Lymphoma (NHL) xenograft model SU-DHL-4 with a BCL-2-selective inhibitor resulted in disruption of tumor BCL-2:BIM complexes that aligned with serum and tumor concentrations of inhibitor. Collectively, these data demonstrate that quantifying BCL-2:BIM complexes offers an accurate means of assessing target engagement by venetoclax and, potentially, predicting its efficacy. The utility of this assay is currently being assessed in clinical trials. Citation Format: Sha Jin, Paul Tapang, Donald J. Osterling, Wenqing Gao, Daniel H. Albert, Andrew J. Souers, Joel D. Leverson, Darren C. Phillips, Jun Chen. Quantitative assessment of BCL-2:BIM complexes as a pharmacodynamic marker for venetoclax (ABT-199). [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 6. doi:10.1158/1538-7445.AM2015-6
A Phase II Study (Biov-121) of Clofarabine Monotherapy First Line in Patients Aged 65 Years or Older with Acute Myeloid Leukemia for Whom Standard Intensive Chemotherapy Is Not Considered Suitable.
Authors: Alan K. Burnett, M. Baccarani, Peter Johnson, John Yin, Andrew Saunders, Nigel Russell, Robert K. Hills
Journal: Blood (2006)
Abstract 1577: Transmural Dyssynchrony of Myofiber Shortening is Determined by Depolarization Sequence within Myocardial Layers
Authors: Viatcheslav Gurev, Jason Constantino, Natalia A Trayanova
Journal: Circulation (2008)

The delay in myofiber shortening (MS) onset between the endocardial and epicardial layers is greater than the electrical activation delay during sinus rhythm (SR) and decreases at the location of the pacing site during epicardial pacing (EP). The goal of this study is to demonstrate that increased transmural mechanical delay during SR is determined by the electrical activation sequence within the myocardial layers, rather than the transmural activation pattern. We employed a novel 3D anatomically-accurate electromechanical model of the rabbit ventricles that incorporated a detailed model of cardiac myofilament dynamics. MS was calculated throughout the ventricular volume during SR and for EP at the left ventricular anterior wall. Onset of MS followed the direction of electrical activation for both SR and EP, as shown in Figure . However, transmural delay in MS onset was greater during SR, consistent with experiments (28ms-SR vs. 19ms-EP). Difference in the MS delay could not be explained by changes in transmural electrical activation delay (19ms-SR vs. 25ms-EP). Examination of the mechanisms revealed a longer apex-to-base electrical activation delay on the epicardium as compared to that on the endocardium during SR. “Prestretching” of the late-activated epicardial myofibers at the base by the shortening of the early-activated apical region increased MS delay. No prestretching was observed following EP. This finding indicates that transmural MS delay strongly depends on the electrical and mechanical activation sequence within the myocardial layers. This research has received full or partial funding support from the American Heart Association, AHA Mid-Atlantic Affiliate (Maryland, North Carolina, South Carolina, Virginia &amp; Washington, DC).
Panic disorder and suicidal ideation and behavior: discrepant findings in psychiatric outpatients
Authors: A T Beck, R A Steer, W C Sanderson, T M Skeie
Journal: American Journal of Psychiatry (1991)

Previous investigators found that persons who had ever met criteria for panic disorder or panic attacks reported more lifetime suicide attempts and ideation than persons who had ever met criteria for other psychiatric disorders. To determine whether outpatients with current panic disorders also report such differences, this study examined the suicide attempt rates, levels of suicidal ideation, and levels of hopelessness among four groups of psychiatric outpatients.Structured clinical interviews were used to assign diagnoses to 900 consecutive psychiatric outpatients. These patients were administered the Scale for Suicide Ideation and the Beck Hopelessness Scale and were also questioned in detail about previous suicide attempts and past and present suicidal ideation.None (0.0%) of the 73 patients with primary panic disorder without agoraphobia reported having made suicide attempts during their lifetimes. One (1.3%) of the 78 patients who had panic disorder with agoraphobia, 34 (7.0%) of the 485 patients who had mood disorders, and four (1.5%) of the 264 patients who had other psychiatric disorders reported suicide attempts. The mean scores on the Scale for Suicide Ideation and the Beck Hopelessness Scale of the patients with panic disorders and other disorders were significantly lower than the mean scores of the patients with mood disorders.The rates of suicidal ideation and behavior for psychiatric outpatients who had panic disorders were discrepant with those reported by the earlier group of investigators for a random community sample of persons who reported ever having had panic attacks or met criteria for panic disorders.
The impact of voiding symptoms on the diagnosis of prostate cancer
Authors: Kelly Healy, John Hall, Michael Goodman, Kelly Ward, Fray F. Marshall, Muta M. Issa, Chad Ritenour, John A. Petros
Journal: Cancer Research (2005)

Proc Amer Assoc Cancer Res, Volume 46, 2005

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Introduction: Because patients with a modestly elevated serum PSA are more likely to have benign than malignant pathology, it would be beneficial to identify those clinical characteristics that correlate with biopsy results. When benign prostatic disorders are symptomatically evident, it may be less likely that cancer is responsible for the abnormal PSA. To define this issue quantitatively we have examined the relationship between the International Prostate Symptoms Score (IPSS) and prostate biopsy results. Methods: An IPSS was obtained from all men prior to transrectal ultrasound and biopsy of the prostate performed for standard indications. Voiding symptoms were classified into four categories: absent (IPSS=0), mild (1-7), moderate (8-19), or severe (20-35). The relationship between the symptom score and biopsy result was examined by calculating series of crude, stratified, and adjusted odds ratios (OR) with corresponding 95% confidence intervals (95% CI). Results: A total of 1017 men underwent prostate biopsy during a 42-month period (November 2000-July 2004). The mean age was 64.8 years and mean IPSS was 11.3. Biopsies were positive in 456 (44.8%) and negative in 561 (55.2%). Men with moderate to severe symptoms (IPSS=8-35) were significantly less likely (OR 0.64, 95% CI: 0.50-0.83) to have a positive biopsy compared to those who were asymptomatic or mildly symptomatic (IPSS≤7). When adjusted for age, this association remained significant (OR=0.69, 95% CI: 0.53-0.89). In patients with modestly elevated PSA (4-10 ng/mL) and moderate to severe symptoms, there was a 40% less likelihood of a positive biopsy compared to those with mild or no symptoms (OR=0.60, 95% CI: 0.42-0.86). The observed association was less pronounced among patients with lower and higher PSA levels. Conclusions: Men with a modestly elevated PSA (4-10 ng/mL) are less likely to have prostate cancer on biopsy if they have moderate to severe voiding symptoms compared to those with mild or no symptoms. Thus significant voiding symptoms (IPSS=8-35) behave as a surrogate for benign prostatic conditions (BPH and prostatitis) commonly responsible for a modest PSA elevation.
TOTAL ACID-BASE EQUILIBRIUM OF PLASMA IN HEALTH AND DISEASE
Authors: John P. Peters, A. Maurice Wakeman, Carter Lee
Journal: Journal of Clinical Investigation (1929)

In the preceding article (1) it was pointed out that one of the electrolyte disturbances most frequently encountered in the serum of patients with nephritis with uremia was deficiencyof the total electro- lyte (base) concentration of the serum and that this was apparently instrumental in the determination of acidosis (reduction of bicarbon- ate) in a certain and rather large proportion of cases.It was also pointed out that chloride as well as bicarbonate was diminished in most of the cases with deficient base.Statistically a definite correla- tion between Cl and base reductions was demonstrated.It was also shown that slightly better correlation was obtained between Cl + HCO3 and base, indicating that base reductions were compensated by both Cl and HCO3.The correlation between base and HCO3 was not clear because HCO3 also yielded base to other acids, including Cl, which at times, accumulated in excess in the serum.This is an illustration of what Gamble (2) has called the "mendicant position of bicarbonate."It was stated that reductions of Cl and base were encountered usually when: (a) vomiting was a serious symptom or (b) patients had received limited amounts of salt and had excreted large amounts of fluid.It was suggested that these patients have a tendency to waste salt through the kidneys and also, possibly, by extrarenal channels.The present article is intended to present in more detail the evidence on which these hypotheses were based. METHODSThe procedures for collection and analysis of blood have already been discussed at some length.Fluids without salt After salt poor diet.Negative Cl balance from urine alone After 7 days with low fluids and 7 grams of extra salt After 2 days of salt poor diet with high fluids 2 days before death.Stuporous, taking no fluids On admission After salt poor diet with forced fluids Records inadequate Salt poor diet, high fluids.Negative Cl balance Negative Cl balance Negative Cl balance Negative Cl balance Subcutaneous saline on March 2 and 3 Deep stupor Taking no food, 12 hours before death fluids nor salt