tbuckley/cabot-search huggingface dataset:
Abstract 12391: High Density Lipoprotein in Coronary Artery Disease Impairs Vascular Endothelial Growth Factor- Induced Angiogenesis
Authors: Jingsong Ou, Feng-Jun Chang, Zhi-Jun Ou, Xiao-Xia Hu, Jia-Yun Wu, Hai-Yun Yuan, Yu-Gang Dong, Zhi-Ping Wang, Xi Zhang, Shen-Ming Wang
Journal: Circulation (2014)

Aims: Previous clinical trials designed to stimulate coronary vascular growth (therapeutic angiogenesis) using growth factors, e.g, vascular endothelial growth factor (VEGF), in patients with coronary artery disease (CAD) were unsuccessful. Although many reasons were postulated for the failure, e.g., endothelial dysfunction, refractory response to VEGF, no consensus was achieved to explain these unsuccessful attempts. To further interrogate this conundrum, we found that high density lipoprotein from healthy subjects (nHDL) is pro-angiogenic; however, HDL from patients with CAD (pHDL) has oxidative modifications. Accordingly we postulate that this modified pHDL is proinflammatory and “switches” to an anti-angiogenic effect. To test this possibility we determined the angiogenic capacity of pHDL and of pHDL on VEGF induced-angiogenesis. Methods and Results: Human umbilical vein endothelial cells (HUVECs) were cultured; murine hearts were isolated and sectioned, and the sections were cultured under condition in which endothelial cells sprout from the sections. HUVECs and the heart sections were treated with nHDL (100 μg/ml) or pHDL (100 μg/ml) with or without VEGF stimulation. We measured proliferation, migration, tube formation of HUVECs, and number and length of sprouts from the sections. pHDL (compared to nHDL) reduced endothelial cell proliferation, migration, tube formation, and the length of the sprouts from the sections under basal conditions and also in response to VEGF (all P&lt;0.05). To elucidate the mechanism of this negative effect of pHDL, we measured nitric oxide (NO) production, superoxide anion (O2[[Unable to Display Character: &amp;#729;]] − ) generation, phosphorylation of endothelial nitric oxide synthase (eNOS), and Akt in HUVECs. Compared to nHDL, pHDL reduced the phosphorylation of eNOS, and Akt; and, also inhibited NO production, but increased eNOS-dependent O2[[Unable to Display Character: &amp;#729;]] − generation. Conclusions: HDL from patients with CAD impaired VEGF-induced angiogenesis via eNOS/Akt signaling pathway. Taken together, our findings suggest that oxidatively modified HDL from patients with CAD may be a contributing factor to reasons why therapeutic angiogenesis trials failed using VEGF recombinant protein or VEGF gene therapy.
Laparoscopic Nephrectomy for Atrophic Kidney Associated with Ectopic Ureter in a Child
Authors: Kazuo Suzuki, Hiroyuki Ihara, Yutaka Kurita, Shinji Kageyama, Daisuke Ueda, Tomomi Ushiyama, Yoshihisa Ohtawara, Kazuki Kawabe
Journal: European Urology (1993)
A Phase I Study of Gefitinib and irinotecan (IRN) in pediatric patients with refractory solid tumors
Authors: W. L. Furman, N. C. Daw, K. R. Crews, C. F. Stewart, B. McCarville, V. M. Santana, D. Hawkins, C. Rodriguez-Galindo, F. Navid, P. J. Houghton
Journal: Journal of Clinical Oncology (2004)

8521 Background: Gefitinib (Iressa), an oral Epidermal Growth Factor receptor (EGFR) inhibitor that has been well tolerated in adults, modulates intracellular drug effects through inhibition of efflux pumps (e.g., BCRP). In xenograft models of pediatric solid tumors it has additive/synergistic activity with IRN, which was independent of EGFR status. We are conducting a Phase I study of this combination in children with refractory solid tumors. Methods: Our objectives are to estimate the maximum tolerated dose and dose-limiting toxicities (DLT) of gefitinib administered daily × 21 days in combination with protracted intravenous IRN [day 1- 5, day 8 - 12]. Pharmacokinetic (PK) studies of IRN and metabolites were obtained with and without concurrent gefitinib. PK studies of gefitinib were obtained on days –1 and 8. Courses are repeated every 21 days in the absence of DLT or disease progression. Results: At present, 2 cohorts have been evaluated (age 3 –15 yrs, median 5 yrs). Cohort 1 (n = 5) received continuous daily gefitinib at 150 mg/m2/d and IRN at 15 mg/m2/d. Dose-limiting diarrhea was seen in 2 patients. In cohort 2 (n = 3), gefitinib was de-escalated to 112.5 mg/m2/d; DLTs were experienced by 2 patients (1 grade 4 anorexia, 1 grade 4 transaminitis). The onset of all DLTs was on day 10 or greater of the first 21 day course. Concomitant gefitinib administration was associated with decreased IRN lactone systemic clearance (P<0.05). Steady-state gefitinib concentrations approximates the IC50 for BCRP inhibition. One patient with Ewing sarcoma had a partial response, one with anaplastic Wilms tumor had a decrease in multiple (<1 cm each) pulmonary nodules, one with adrenocortical carcinoma had stable disease (SD) for 4 courses and one with neuroblastoma has SD for 3+ courses. Because of delayed onset of these DLTs, the study is being amended to administer gefitinib for the first 12 days of each course only. Conclusions: Our data suggest a shorter schedule of gefitinib in combination with IRN may be better tolerated and will maintain the apparent synergy of these agents. This combination warrants further study in children with refractory solid tumors. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca
American Board of Internal Medicine Maintenance of Certification Program
Authors: Wendy Levinson, Talmadge E King, Lee Goldman, Allan H Goroll, Bruce Kessler
Journal: New England Journal of Medicine (2010)

This interactive feature allows readers to make a decision on the basis of a vignette that is followed by specific options, none of which can be considered either correct or incorrect. In short essays, experts in thefield then arguefor each of the options. In the online version of this feature, available at NEJM.org, readers can participate in forming community opinion by choosing one of the options and, if they like, providing their reasons.
Abstract 20395: High Incidence of Elevated Panel Reactive Antibodies in Patients Supported with HeartMate II Left Ventricular Assist Devices
Authors: Sang-Woo Pak, Nir Uriel, Elizabeth Burke, Sarah A Cappleman, Evelyne M Sutton, Hiroo Takayama, Farhana Latif, Paolo Colombo, Yoshifumi Naka, Donna Mancini, Ulrich P Jorde
Journal: Circulation (2010)

Background:  A high prevalence of panel reactive antibodies (PRA) has been described in patients supported with pulsatile HeartMate I left ventricular assist devices (LVAD). Elevated PRA negatively impact wait times and transplantation outcomes. We examined changes in PRA profiles of patients supported with continuous flow HeartMate II (HMII) LVADs.   Methods:  We performed a retrospective review of prospectively collected immunology data on all patients supported with HMII LVADs from January 2004 to June 2010 at our center. Pre-transplant PRA levels >10% and any detectable PRA after transplant defined “sensitization.”   Results:  Data for 80 HMII patients were analyzed. Of these, 11.6% were sensitized prior to implant, and 32.0% were newly sensitized during device support. Patient sex, age, and duration of support were major risk factors for PRA development: pre-LVAD, 5 of 19 female and 3 of 50 male patients had PRA>10% (p-value=0.019). During LVAD support, 13 of 18 female (72%) and 11 of 57 (19.3%) male patients developed PRA>10% (p-value   Conclusions:  Allosensitization occurs in a significant number of patients supported with HMII LVADs, and is associated with longer LVAD support duration, younger age, and female gender. Age and gender should be taken into consideration when evaluating risk/benefit profiles of LVAD as bridge to transplantation.
Abstract 8927: Subclinical LV Systolic and Diastolic Dysfunction in Uncomplicated Patients With Impaired Glucose Tolerance and Type 2 Diabetes Mellitus: Findings From 2-dimensional Speckle Tracking Echocardiography
Authors: Hiroto Utsunomiya, Eiji Kunita, Toshiharu Oka, Ryo Yamazato, Takayuki Hidaka, Tomohiko Kisaka, Yumiko Iwamoto, Ken Ishibashi, Kenji Nishioka, Tomoki Shokawa, Satoshi Kurisu, Yukiko Nakano, Hideya Yamamoto, Takafumi Ishida, Yasuki Kihara
Journal: Circulation (2010)

Background: Longstanding diabetes mellitus (DM) affects left ventricular (LV) dysfunction regardless of hypertension and coronary artery disease (CAD). However, regional LV dysfunction in a group of uncomplicated and normotensive patients with impaired glucose tolerance (IGT) or DM has not been well documented. Methods: Study population consisted of 100 patients with normal LV ejection fraction who underwent 2-dimensional speckle tracking echocardiography (2DST) and cardiac computed tomography (CT). Mean values of global longitudinal and circumferential strain profiles were determined from 2DST analyses. IGT or DM was determined in all patients by oral glucose tolerance test. The exclusion criteria included known DM, HbA1c > 8.5%, blood pressure of > 150/85 mm Hg, and diabetes-related complications (proliferative retinopathy, autonomic neuropathy, and microalbuminuria). The presence of significant CAD was also excluded by negative findings on cardiac CT. In addition, plain abdominal CT scans were performe...
Abstract 14243: Risk of Cerebrovascular Events and Atrial Fibrillation After Typical Atrial Flutter Ablation
Authors: Todd T Tomson, Suraj Kapa, Rupa Bala, Michael P Riley, David Lin, Andrew E Epstein, Rajat Deo, Sanjay Dixit
Journal: Circulation (2011)

Introduction: There are a paucity of data on the incidence of and risk factors for cerebrovascular events (CVE) and atrial fibrillation (AF) after radiofrequency ablation of typical atrial flutter ...
Abstract 18535: Rare Variants Identified With Whole Exome Chip Genotyping Are Associated With Insulin Resistance and Glycemic Control
Authors: Svati H Shah, Lydia Kwee, Nathan Stitziel, Elizabeth R Hauser, Carol Haynes, Sekar Kathiresan, Simon G Gregory, William E Kraus
Journal: Circulation (2013)

Background: Insulin resistance (IR) and type 2 diabetes mellitus (DM) are heritable. Application of genome mapping for these traits, primarily with common variants, has incompletely characterized the genetic architecture. We hypothesized that rare coding variants are associated with IR in individuals without DM, and with glycemic control in individuals with DM. Methods: Extracted DNA from 611 Caucasian individuals enrolled in the CATHGEN cardiovascular biorepository at Duke University was genotyped on the Illumina Infinium HumanExome BeadChip (241465 single nucleotide variants [SNVs]). Linear regression was used to test each variant for association with glycated albumin (GA) measured in frozen, fasting plasma (a surrogate for hemoglobin A1c and thus a marker of glycemic control in individuals with DM and of IR in individuals without DM), adjusting for age, sex, batch, and principal component-derived ethnicity. Results: In individuals without DM, one SNV in an uncharacterized protein ( KIAA1614 , p=3.1x10 -8 ) met genomewide significance (p&lt;10 -7 ). Other lesser significant SNVs included genes reporting on ribosomal function ( MRPL44 p=5.5x10 -5 , LACTB p=1.7x10 -4 ), cellular processes ( CENPP p=2.6x10 -5 ; MEGF6 p=1.6x10 -4 ), ion channels ( KCNT1 p=2.0x10 -5 ), protein degradation ( ASB10 p=8.1x10 -5 ), and in insulin receptor ( INSR p=9.4x10 -5 ) and carbonyl reductase ( CBR1 p=6.6x10 -5 ). In individuals with DM, several SNVs met genomewide significance: WDR27 (p=8.1x10 -12 ), HELQ (p=2.0x10 -9 ), genes involved in cell cycle processes ( NUP214 p=9.8x10 -9 , PTPRJ p=1.6x10 -8 ), cell-cell interactions ( CHST9 p=2.6x10-8, multiple protocadherin [ PCDHG ] genes, p=3.3x10 -8 ), ion channels ( CACAN1A , p=4.2x10 -8 ), MMP13 (p=4.7x10 -8 ), and FBLN5 (p=9.1x10 -8 ), involved in vascular development and remodeling. Conclusions: We have identified several rare variants in biologically plausible genes reporting on diverse cellular processes that are associated with IR in individuals without DM, and with glycemic control in individuals with DM, that would not have been identified using traditional genomewide association (GWAS) screens. These may serve as novel biomarkers and identify novel pathways of IR and DM pathogenesis.
A phase II trial of thalidomide plus tegafur/uracil for patients with advanced/metastatic hepatocellular carcinoma (HCC): Final report
Authors: C. Hsu, Z. Lin, K. Lee, K. Yeh, C. Hsiao, Y. Shen, D. Chang, S. Wang, C. Hsu, A. Cheng
Journal: Journal of Clinical Oncology (2009)

e15533 Background: Thalidomide (T) is an anti-angiogenic agent with modest activity in advanced/metastatic HCC. Tegafur/uracil (UFT) is an oral prodrug of 5-fluorouracil with activity against various gastrointestinal cancers. Metronomic chemotherapy has been shown to have anti-angiogenic and anti-cancer effect in preclinical and clinical models. This study evaluated the efficacy and safety of the combination of T and metronomic UFT as first-line therapy for advanced HCC. Methods: Patients (Pts) with advanced HCC not treatable by surgery or other loco-regional therapies received T 100mg bid and UFT 125mg/m 2 (based on tegafur) bid continuously. Treatment was continued in the absence of disease progression or unacceptable toxicity. Primary endpoint was response rate (RR) by RECIST; secondary endpoints were disease control rate (CR+PR+SD), progression-free survival (PFS), overall survival (OS), and safety. Results: Between Jul 2006 and Jul 2008, 43 intent-to-treat pts (M/F 41/2, median age 55) were enrolled. Baseline characteristics were HBsAg(+)/anti-HCV(+)/both(+) /both(-) 31/6/1/7; AJCC stage II/III/IV 2/18/23; BCLC stage B/C 1/42; CLIP score ≤3/4 27/16; portal vein thrombosis 65%; extrahepatic metastasis 58%; prior local treatment 72%. There were 4 PR (9.3%) and 10 SD (23.3%), with a disease control rate of 32.6%. Median OS was 4.6 (95% CI, 3.5–7.3) months and median PFS was 1.9 (95% CI, 1.8–2.6) months. The OS and PFS for pts with CLIP score ≤3 were 7.6 and 2.6 months, respectively. Grade 3 leucopenia developed in 1 (2.3%) pt. The most common treatment-related grade 3 non-hematologic toxicities were somnolence (n=4, 9.3%), GI bleeding (n=3, 7.0%), and elevated transaminase (n=2, 4.7%). No grade 4 toxicities occurred. Conclusions: The combination of T with metronomic UFT is a well-tolerated regimen with moderate activity for advanced HCC, and worth further exploration in pts with CLIP score ≤3. [Table: see text]
Measles
Authors: Evelyn Lilly, Bhaskar Srivastava
Journal: New England Journal of Medicine (2015)

A 54-year-old woman presented with fever, cough, and rhinorrhea after returning from the Philippines. Examination revealed an exanthem involving the head, neck, and shoulders, small white papules on buccal mucosa bilaterally, conjunctivitis, and cervical lymphadenopathy.
Abstract 2447: The Optimal Relationship between Oxygen Saturation and Hemoglobin in Adult Patients with Cyanotic Congenital Heart Disease can be Determined and Correlates with Exercise Capacity.
Authors: Craig Broberg, Ranjith Jayaweera, Gerhard Diller, Sanjay Prasad, Swee Thein, John Burman, Michael A Gatzoulis
Journal: Circulation (2006)

Background:  Erythrocytosis in cyanotic heart disease is affected by many factors that alter oxygen saturation (O 2sat ) or hemoglobin (Hb) and disrupt their expected relationship. We sought to determine the optimal Hb for a given O 2sat .   Methods:  Adults with cyanotic heart disease were studied prospectively with blood tests and exercise. Non-optimal Hb was defined as any evidence of inadequate erythropoiesis; namely iron, folate, or B 12  deficiency, raised erythropoietin, reticulocytosis, or right-shifted oxygen-Hb curve. For patients with optimal Hb, a plot of Hb vs.O 2sat  was used to mathematically predict optimal Hb for all patients, and calculate the difference between measured and predicted (Hb diff ).   Results:  Of 61 patients studied, 17 met all criteria for optimal Hb. For all patients there was no correlation between O 2sat  and Hb (r=−0.19), whereas there was a strong linear correlation for those with optimal Hb (r=−0.86, p diff  and exercise capcity. Those with optimal Hb had better treadmill exercise duration (6.9±2.6 vs. 5.1±2.0 min, p=0.018) and 6-min walk distance (429±88 vs. 336±107 m, p=0.005).   Conclusions:  A strong relationship between O 2sat  and Hb can be shown in those defined to have optimal Hb. Optimal Hb patients have better exercise capacity. This relationship may be useful in defining anemia or excess viscosity in this group.
Abstract 1102: Integrated genomic analysis of clear-cell ovarian cancer identifies PRKCI as a therapeutic target
Authors: Tsun Yee Tsang, Gayatry Mohapatra, Hiroaki Itamochi, Samuel C. Mok, Michael J. Birrer
Journal: Cancer Research (2015)

Abstract Clear-cell ovarian cancer (CCOC) is the third most common subtype of ovarian cancer. CCOC is more resistant to standard chemotherapy and has a poorer prognosis than serous and endometrioid histotypes. Through a comprehensive genomic approach, genes that are responsible for the aggressive behavior of CCOC were identified and their mechanism explored. Genome-wide DNA copy number alterations were measured in 13 CCOC cell lines using high-resolution oligonucleotide array comparative genomic hybridization (Agilent 105k Human Genome CGH Microarray). Genomic identification of significant targets in cancer (GISTIC) analysis identified 16 amplicons containing 391 genes. Integrating whole genome expression data from human CCOC tumor specimens and normal ovarian surface epithelium specimen revealed 45 amplified genes showed mRNA overexpression in CCOC tumor specimens. Among the 45 genes, protein kinase C iota (PRKCI) was amplified in 9/13 CCOC cell lines and was overexpressed (6.7 fold) in CCOC tumor specimens. Cell proliferation, migration/invasion and tumorigenicity were suppressed by knockdown of PRKCI in PRKCI-overexpressing cells (KOC-7c and OVISE) and were enhanced by overexpression of PRKCI in cells with low endogenous levels of PRKCI (ES2 and TOV21G). Targeted inhibition of PRKCI with sodium aurothiomalate (ATM) suppressed cell growth, cell migration/invasion and tumorigenicity in CCOC cells. Western blot analysis revealed that PRKCI oncogenic function was mediated through MEK/ERK and PI3K/Akt signaling pathways. Thus, PKRCI can be considered as a potential novel CCOC-specific target; not only it inhibits malignant behavior of CCOC cells, but also induces the two major molecular pathways regulating cisplatin resistance. The results from the present study indicate that our comprehensive genomic analysis of CCOC allows identification of therapeutic targets responsible for the aggressive behavior specific of this ovarian cancer histotype and thus improve its therapeutic outcome. Citation Format: Tsun Yee Tsang, Gayatry Mohapatra, Hiroaki Itamochi, Samuel C. Mok, Michael J. Birrer. Integrated genomic analysis of clear-cell ovarian cancer identifies PRKCI as a therapeutic target. [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 1102. doi:10.1158/1538-7445.AM2015-1102
Abstract P174: Systematic Literature Review: Out-of-hospital Cardiac Arrests With Extracorporeal Cardiopulmonary Resuscitation in Japan
Authors: Naoto Morimura, Testuya Sakamoto, Ken Nagao, Yasuhumi Asai, Takahiro Atsumi, Hiroyuki Yokota, Yoshio Tahara, Mamoru Hase, Satoshi Nara
Journal: Circulation (2009)

Background: In addition to the literature review of extracorporeal cardiopulmonary resuscitation (ECPR) for out-of-hospital cardiac arrest in the 2008 Resuscitation Symposium, we collected and revi...
Treatment of sex offenders with antiandrogenic medication: conceptualization, review of treatment modalities, and preliminary findings
Authors: Fred S. Berlin, Carl F. Meinecke
Journal: American Journal of Psychiatry (1981)

Sexual deviation disorders, or paraphilias, are diagnosable psychiatric syndromes manifested by 1) recurrent fantasies about deviant sex, 2) intense associated cravings, and 3) stereotypic behavioral responses. Pedophiles seek out children in response to their erotic thoughts and urges, whereas exhibitionists expose themselves. Paraphiliac syndromes ordinarily follow a chronic course and may be associated with biological pathology, but etiological factors are poorly understood. Treatment becomes a consideration when the well-being or rights of others are compromised. Proposed treatments have included psychotherapy, behavior therapy, surgery, and medication. Medroxyprogesterone acetate, which reduces testosterone, may diminish sexual preoccupation and urges, making self-control easier.
Abstract 14407: Three Dimensional Speckle Tracking Strain Evaluation of Right Heart Function and Hemodynamics in Patients with Pulmonary Hypertension
Authors: Tetsuari Onishi, Toshinari Onishi, Toshikazu Tanaka, Stephanie C Haberman, Hunter Champion, John Gorcsan
Journal: Circulation (2012)

Background: Assessment of right ventricular (RV) function in pulmonary hypertension (PH) patients is difficult but clinically important. Objective: To compare novel 3-dimensional (3D) speckle track...
Abstract 1103: Integrin-linked Kinase and Laminin alpha 4 Mutations Cause Human Cardiomyopathy
Authors: Ralph Knöll, Ruben Postel, Ralph Krätzner, Gerrit Hennecke, Andrei M Vacaru, Padmanabhan Vakeel, Gudrun Knöll, Katrin Schäfer, Erik Bos, Jeroen den Hertog, Peter J Peters, Fredericus van Eeden, Jutta Schaper, Wolfgang Schaper, Gerd Hasenfuss, Heinz-Peter Schultheiss, Kenneth R Chien, Jeroen Bakkers
Journal: Circulation (2007)

Background - Dilated Cardiomyopathy (DCM) is a syndrome characterized by ventricular dilation, contractile dysfunction and symptoms of congestive heart failure. Extracellular matrix proteins such as laminins as well as endothelial cells are known to influence cardiomyocyte performance, however a molecular link between mutations in the ECM and DCM has not been provided. Methods and Results - Using a forward genetic screen in zebrafish to identify novel genes required for myocardial function we were able to identify the lost-contact (loc) mutant, encoding a nonsense mutation in the integrin-linked kinase (ILK) gene. This loc/ilk mutant is associated with both, a severe defect in cardiomyocytes as well as in endothelial cells leading to severe myocardial dysfunction. Additional experiments revealed the epistatic regulation between the ECM component laminin alpha 4 (LAMA4), integrin and ILK, which led us to screen for mutations in the human ILK and LAMA4 genes in patients with severe dilated cardiomyopathy (DCM). We identified two novel amino acid residue altering mutations (2828C&gt;T (Pro943Leu), 3217C&gt;T (Arg1073X)) in the integrin interacting domain of the LAMA4 gene and one mutation (785C&gt;T (Ala262Val)) in the ILK gene. BIAcore quantitative protein/protein interaction data, which have been used to determine the equilibrium dissociation constants, point to the loss of integrin binding capacity in case of the Pro943Leu (KD=5 +/− 3 uM) and Arg1073X lama 4 (KD=1 +/− 0.2 uM) mutants in comparison to the wildtype lama 4 protein (KD = 440 +/− 20 nM). Cell attachment assays point to a defect in endothelial cell adhesion when LAMA4 mutants have been expressed in vitro and used as a substrate. 785C&gt;T (Ala262Val) ILK did not change its affinity, as measured by GST pull down assays as well as by a yeast 2 hybrid analysis, to a well known interacting protein such as b-parvin but revealed a 63% decrease in kinase activity. Additional functional data point to the loss of endothelial cells in affected patients as a direct consequence of the mutant genes, leading ultimately to heart failure. Conclusions - We report the first human mutations in the LAMA4, integrin and ILK system and provide a new mechanistic basis for DCM in man, which involves endothelial cells as well as cardiomyocytes.