tbuckley/cabot-search huggingface dataset:
Effect of antenatal multiple micronutrient supplementation on anthropometry and blood pressure in mid-childhood in Nepal: follow-up of a double-blind randomised controlled trial
Authors: Delan Devakumar, Shiva Shankar Chaube, Jonathan C K Wells, Naomi M Saville, Jon G Ayres, Dharma S Manandhar, Anthony Costello, David Osrin
Journal: The Lancet Global Health (2014)

In 2002-04, we did a randomised controlled trial in southern Nepal, and reported that children born to mothers taking multiple micronutrient supplements during pregnancy had a mean birthweight 77 g greater than children born to mothers taking iron and folic acid supplements. Children born to mothers in the study group were a mean 204 g heavier at 2·5 years of age and their systolic blood pressure was a mean 2·5 mm Hg lower than children born to mothers in the control group. We aimed to follow up the same children to mid-childhood (age 8·5 years) to investigate whether these differences would be sustained.For this follow-up study, we identified children from the original trial and measured anthropometry, body composition with bioelectrical impedance (with population-specific isotope calibration), blood pressure, and renal dimensions by ultrasound. We documented socioeconomic status, household food security, and air pollution. Main outcomes of the follow-up at 8 years were Z scores for weight-for-age, height-for-age, and body-mass index (BMI)-for-age according to WHO Child Growth Standards for children aged 5-19 years, and blood pressure. This study is registered with the International Standard Randomised Controlled Trial register, number ISRCTN88625934.Between Sept 21, 2011, and Dec 7, 2012, we assessed 841 children (422 in the control group and 419 in the intervention group). Unadjusted differences (intervention minus control) in Z scores were 0·05 for weight-for-age (95% CI -0·09 to 0·19), 0·02 in height-for-age (-0·10 to 0·15), and 0·04 in BMI-for-age (-0·09 to 0·18). We recorded no difference in blood pressure. Adjusted differences were similar for all outcomes.We recorded no differences in phenotype between children born to mothers who received antenatal multiple micronutrient or iron and folate supplements at age 8·5 years. Our findings did not extend to physiological differences or potential longer-term effects.The Wellcome Trust.
Saturable metabolism of continuous high-dose ifosfamide with Mesna and GM-CSF: A pharmacokinetic study in advanced sarcoma patients
Authors: T. Cerny, S. Leyvraz, T. von Briel, A. Küpfer, R. Schaad, S.-F. Hsu Schmitz, P. Honegger, C. Sessa, J. Brunner, A.V. Boddy
Journal: Annals of Oncology (1999)
Social influence and vulnerability
Authors: Joseph M. Boden
Journal: Behavioral and Brain Sciences (2008)

Abstract Redish et al. outline 10 vulnerabilities in the decision-making system that increase the risks of addiction. In this commentary I examine the potential role of social influence in exploiting at least one of these vulnerabilities, and argue that the needs satisfied by social interaction may play a role in decision-making with regard to substance use, increasing the risks of addiction.
A phase 1/2 trial of arginine butyrate and ganciclovir in patients with Epstein-Barr virus–associated lymphoid malignancies
Authors: Susan P. Perrine, Olivier Hermine, Trudy Small, Felipe Suarez, Richard O'Reilly, Farid Boulad, Joyce Fingeroth, Melissa Askin, Arthur Levy, Steven J. Mentzer, Massimo Di Nicola, Alessandro M. Gianni, Christoph Klein, Steven Horwitz, Douglas V. Faller
Journal: Blood (2006)
NOS1AP POLYMORPHISMS AFFECT NOS1AP RNA LEVELS IN CARDIAC TISSUE RECOVERED FROM EXTRACTED PACEMAKER AND DEFIBRILLATOR LEADS
Authors: Samir F. Saba, Haider Mehdi, Zahid Islam, Sammy Termanini, Reem Mahjoub, Ryan Aleong, Charles McTiernan, Barry London
Journal: Journal of the American College of Cardiology (2011)
Nationwide Improvements in Survival From Out-of-Hospital Cardiac Arrest in Japan
Authors: Tetsuhisa Kitamura, Taku Iwami, Takashi Kawamura, Masahiko Nitta, Ken Nagao, Hiroshi Nonogi, Naohiro Yonemoto, Takeshi Kimura
Journal: Circulation (2012)

Background— Little is known about the nationwide trend in the survival of out-of-hospital cardiac arrest (OHCA) in Japan and the differences in incidence and survival by age group and origin of arrest. Methods and Results— A nationwide, prospective, population-based observation covering the whole population of Japan and involving consecutive OHCA patients with resuscitation attempts was conducted from January 2005 to December 2009. The main outcome measure was 1-month survival with favorable neurological outcome. The nationwide trends in OHCA incidence and outcome by age and origin of arrest were assessed. Multiple logistic regression analysis for bystander-witnessed OHCA was used to adjust for factors that were potentially associated with favorable neurological outcome. During 5 years, 547 153 overall OHCAs and 169 360 bystander-witnessed OHCAs were enrolled. The annual incidence significantly increased among overall OHCAs and bystander-witnessed OHCAs. Neurologically favorable survival significantly increased from 1.6% (1676/102 737) in 2005 to 2.8% (3280/115 250) in 2009 ( P &lt;0.001), from 2.1% (638/30 556) to 4.3% (1558/36 361) ( P &lt;0.001), and from 9.8% (437/4461) to 20.6% (1215/5906) ( P &lt;0.001) among overall OHCA, bystander-witnessed OHCA, and bystander-witnessed ventricular fibrillation OHCA, respectively. Public-access automated external defibrillator use, either bystander-initiated chest compression–only cardiopulmonary resuscitation or conventional cardiopulmonary resuscitation, and earlier emergency medical services response time were associated with a better neurological outcome. Favorable neurological outcome among adult OHCA subjects significantly improved, but the outcome among younger children and very elderly subjects did not improve and was poor irrespective of origin of OHCA. Conclusions— Nationwide improvements of favorable neurological outcome from OHCA were observed in Japan and differed by age group and origin of OHCA.
Exertional haemoptysis: LAM and TSC
Authors: R A Badawi
Journal: Thorax (2003)

Tuberous sclerosis (TSC) is characterised by the occurrence of hamartomas in different organs. It is autosomal dominant with complete penetrance and variable expression. TSC is associated with epilepsy, learning difficulties, behavioural problems, and renal and dermatological pathology. Lymphangioleiomyomatosis (LAM) is principally a pulmonary condition characterised by smooth muscle ( leiomyo ) proliferation around lymphatics ( lymph ), blood vessels ( angio ), and alveolar airways. Cystic destruction of lung parenchyma results in the development of pneumothoraces. 50% of patients with LAM have renal angiomyolipomas which are …
Src blockade stabilizes a Flk/cadherin complex, reducing edema and tissue injury following myocardial infarction
Authors: Sara Weis, Satoshi Shintani, Alberto Weber, Rudolf Kirchmair, Malcolm Wood, Adrianna Cravens, Heather McSharry, Atsushi Iwakura, Young-sup Yoon, Nathan Himes, Deborah Burstein, John Doukas, Richard Soll, Douglas Losordo, David Cheresh
Journal: Journal of Clinical Investigation (2004)

Ischemia resulting from myocardial infarction (MI) promotes VEGF expression, leading to vascular permeability (VP) and edema, a process that we show here contributes to tissue injury throughout the ventricle. This permeability/edema can be assessed noninvasively by MRI and can be observed at the ultrastructural level as gaps between adjacent endothelial cells. Many of these gaps contain activated platelets adhering to exposed basement membrane, reducing vessel patency. Following MI, genetic or pharmacological blockade of Src preserves endothelial cell barrier function, suppressing VP and infarct volume, providing long-term improvement in cardiac function, fibrosis, and survival. To our surprise, an intravascular injection of VEGF into healthy animals, but not those deficient in Src, induced similar endothelial gaps, VP, platelet plugs, and some myocyte damage. Mechanistically, we show that quiescent blood vessels contain a complex involving Flk, VE-cadherin, and β-catenin that is transiently disrupted by VEGF injection. Blockade of Src prevents disassociation of this complex with the same kinetics with which it prevents VEGF-mediated VP/edema. These findings define a molecular mechanism to account for the Src requirement in VEGF-mediated permeability and provide a basis for Src inhibition as a therapeutic option for patients with acute MI.
Top-resolution frequency analysis of electrocardiogram with adaptive frequency determination. Identification of late potentials in patients with coronary artery disease.
Authors: R Haberl, H F Schels, P Steinbigler, G Jilge, G Steinbeck
Journal: Circulation (1990)

Frequency analysis of the electrocardiogram with Fourier transform is a sensitive method of detecting late potentials. However, information about localization of late potentials is lost, frequency resolution is poor, and window functions have to be applied. We therefore analyzed multiple segments (25 msec long) of the surface electrocardiogram ("spectrotemporal mapping") with adaptive frequency determination (AFD), an autoregressive algorithm that is characterized by high-frequency resolution in very short segments without the use of window functions. Results were compared with those from Fourier transform and the Simson method. We studied 38 patients after myocardial infarction (MI) with sustained ventricular tachycardia (VT), 21 patients after MI without VT, and 18 healthy subjects. Frequency peaks could be clearly differentiated until a minimal interval of 6 Hz; with fast Fourier transform (Blackman Harris window) in a much longer segment (80 msec), the spectral peaks merged into one another at an interval of about 30 Hz. AFD revealed high-frequency components as narrow peaks in the range of 40-160 Hz in 28 of 38 patients (74%) after MI with VT. Because of the short segment size, exact localization of late potentials was possible; in most of the patients, the peaks occurred in segments inside the QRS complex and ended 20 +/- 10 msec after termination of the QRS complex. In patients after MI without VT, only four of 21 patients (19%) had spectral peaks in segments after the end of the QRS complex; however, 13 of 21 patients demonstrated microvolt potentials in segments within the QRS complex. These potentials did not extend beyond the end of normal ventricular activation. Only two of 18 healthy subjects showed abnormal AFD results. Patients with bundle branch block did not need to be excluded. AFD allowed good differentiation between late potentials and noise by a characteristic pattern of the spectral peaks. For the Simson method, patients with bundle branch block had to be excluded, and overall sensitivity was 42%. In five cases, the cause of failure of the Simson method could be identified as incorrect determination of the QRS limits due to noise. Thus, AFD is a promising method for detailed analysis of late potentials; it combines the advantages of frequency analysis (good differentiation between signal and noise and high-pass filters not necessary) and time domain analysis (localization of late potentials).
Fibrinogen induces cytokine and collagen production in pancreatic stellate cells
Authors: A Masamune, K Kikuta, T Watanabe, K Satoh, M Hirota, S Hamada, T Shimosegawa
Journal: Gut (2008)

<h3>Objective:</h3> Fibroblasts in the area of fibrosis in chronic pancreatitis and of the desmoplastic reaction associated with pancreatic cancer are now recognised as activated pancreatic stellate cells (PSCs). Recent studies have shown strong expression of fibrinogen, the central protein in the haemostasis pathway, in the stromal tissues of pancreatic cancer and chronic pancreatitis, suggesting that PSCs are embedded in and exposed to abundant fibrinogen in these pathological settings. The effects of fibrinogen on cell functions in PSCs were examined here. <h3>Methods:</h3> PSCs were isolated from human pancreas tissues of patients undergoing operations for pancreatic cancer, and from rat pancreatic tissues. The effects of fibrinogen on key cell functions and activation of signalling pathways in PSCs were examined. <h3>Results:</h3> Fibrinogen induced the production of interleukin 6 (IL6), interleukin 8 (IL8), monocyte chemoattractant protein-1, vascular endothelial growth factor, angiopoietin-1 and type I collagen, but not proliferation or intercellular adhesion molecule-1 expression. Fibrinogen increased α-smooth muscle actin expression and induced the activation of nuclear factor-κB (NF-κB), Akt and three classes of mitogen-activated protein kinases (extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase and p38 mitogen-activated protein kinase (MAPK)). Fibrinogen-induced IL6 and IL8 production was inhibited by antibodies against α<sub>v</sub>β<sub>3</sub> and α<sub>5</sub>β<sub>1</sub> integrins, suggesting that these integrins worked as counter receptors for fibrinogen in PSCs. In addition, fibrinogen-induced production of these cytokines was abolished by an inhibitor of NF-κB, and partially inhibited by inhibitors of ERK and p38 MAPK. <h3>Conclusion:</h3> Fibrinogen directly stimulated profibrogenic and proinflammatory functions in PSCs.
AZD8931, an Equipotent, Reversible Inhibitor of Signaling by Epidermal Growth Factor Receptor, ERBB2 (HER2), and ERBB3: A Unique Agent for Simultaneous ERBB Receptor Blockade in Cancer
Authors: D. Mark Hickinson, Teresa Klinowska, Georgina Speake, John Vincent, Cath Trigwell, Judith Anderton, Sarah Beck, Gayle Marshall, Sara Davenport, Rowena Callis, Elizabeth Mills, Konstantina Grosios, Paul Smith, Bernard Barlaam, Robert W. Wilkinson, Donald Ogilvie
Journal: Clinical Cancer Research (2010)

To test the hypothesis that simultaneous, equipotent inhibition of epidermal growth factor receptor (EGFR; erbB1), erbB2 (human epidermal growth factor receptor 2), and erbB3 receptor signaling, using the novel small-molecule inhibitor AZD8931, will deliver broad antitumor activity in vitro and in vivo.A range of assays was used to model erbB family receptor signaling in homodimers and heterodimers, including in vitro evaluation of erbB kinase activity, erbB receptor phosphorylation, proliferation in cells, and in vivo testing in a human tumor xenograft panel, with ex vivo evaluation of erbB phosphorylation and downstream biomarkers. Gefitinib and lapatinib were used to compare the pharmacological profile of AZD8931 with other erbB family inhibitors.In vitro, AZD8931 showed equipotent, reversible inhibition of EGFR (IC(50), 4 nmol/L), erbB2 (IC(50), 3 nmol/L), and erbB3 (IC(50), 4 nmol/L) phosphorylation in cells. In proliferation assays, AZD8931 was significantly more potent than gefitinib or lapatinib in specific squamous cell carcinoma of the head and neck and non-small cell lung carcinoma cell lines. In vivo, AZD8931 inhibited xenograft growth in a range of models while significantly affecting EGFR, erbB2, and erbB3 phosphorylation and downstream signaling pathways, apoptosis, and proliferation.AZD8931 has a unique pharmacologic profile providing equipotent inhibition of EGFR, erbB2, and erbB3 signaling and showing greater antitumor activity than agents with a narrower spectrum of erbB receptor inhibition in specific preclinical models. AZD8931 provides the opportunity to investigate whether simultaneous inhibition of erbB receptor signaling could be of utility in the clinic, particularly in the majority of solid tumors that do not overexpress erbB2.
Impact of IL-1 signalling on experimental uveitis and arthritis
Authors: Stephen R. Planck, April L. Woods, Jenna S. Clowers, Martin J. Nicklin, James T. Rosenbaum, Holly L. Rosenzweig
Journal: Annals of the Rheumatic Diseases (2012)

Uveitis, or inflammatory eye disease, is a common extra-articular manifestation of many systemic autoinflammatory diseases involving the joints. Anakinra (recombinant interleukin (IL)-1 receptor antagonist (Ra)) is an effective therapy in several arthritic diseases; yet, few studies have investigated the extent to which IL-1 signalling or IL-1Ra influences the onset and/or severity of uveitis.To seek possible links between arthritis and uveitis pathogenesis related to IL-1 signalling.The eyes of IL-1Ra-deficient BALB/c mice were monitored histologically and by intravital videomicroscopy to determine if uveitis developed along with the expected spontaneous arthritis in ankles and knees. Expression levels of IL-1R and its negative regulators (IL-1Ra, IL-1RII, IL-1RAcP and single Ig IL-1R-related molecule) in eye and joint tissues were compared. Differences in uveitis induced by intraocular injection of lipopolysaccharide (LPS) in mice lacking IL-1R or IL-1Ra were assessed.Deficiency in IL-1Ra predisposes to spontaneous arthritis, which is exacerbated by previous systemic LPS exposure. The eye, however, does not develop inflammatory disease despite the progressive arthritis or LPS exposure. Organ-specific expression patterns for IL-1Ra and negative regulators of IL-1 activity were observed that appear to predict predisposition to inflammation in each location in IL-1Ra knockout mice. The eye is extremely sensitive to locally administered LPS, and IL-1Ra deficiency markedly exacerbates the resulting uveitis.This study demonstrates that IL-1Ra plays an important role in suppressing local responses in eyes injected with LPS and that there is discordance between murine eyes and joints in the extent to which IL-1Ra protects against spontaneous inflammation.
KINK-1, a Novel Small-Molecule Inhibitor of IKKβ, and the Susceptibility of Melanoma Cells to Antitumoral Treatment
Authors: Margarete Schön, B. Gregor Wienrich, Susanne Kneitz, Helga Sennefelder, Katharina Amschler, Verena Vöhringer, Olaf Weber, Thorsten Stiewe, Karl Ziegelbauer, Michael P. Schön
Journal: JNCI Journal of the National Cancer Institute (2008)

Increasing the efficacy of chemotherapeutics by reducing chemoresistance may be a useful strategy in cancer therapy. Constitutive activation of nuclear factor-kappa B (NF-kappaB) is a hallmark of various cancers, including melanoma, which is almost universally resistant to chemotherapy. NF-kappaB is regulated by inhibitory kappaB (IkappaB) proteins, which are in turn phosphorylated by the IkappaB kinase (IKK) complex.The effect on NF-kappaB activity of a novel small-molecule inhibitor of the beta subunit of IKK (KINK-1; kinase inhibitor of nuclear factor-kappaB-1) was assessed by measuring phosphorylation of the alpha subunit of IkappaB by immunoblotting, DNA binding by electrophoretic mobility shift assays, and nuclear translocation of NF-kappaB using immunofluorescence. Regulation of NF-kappaB-dependent gene expression was determined by microarray analysis, real-time and semiquantitative reverse transcription polymerase chain reaction (RT-PCR), and Western blot analyses. The effects of KINK-1 (alone and in combination with cytostatic agents) on melanoma cells were characterized by assessing proliferation, soft agar colony formation, and markers of apoptosis. The antitumoral efficacy of KINK-1 in combination with the cytostatic agents doxorubicin or camptothecin (all injected intraperitoneally) was tested in vivo by measuring lung weight and counting metastases in C57BL6 mice (groups of six) bearing metastases of melanoma cells. All statistical tests were two-sided. Results KINK-1 strongly suppressed both constitutive and induced NF-kappaB activity in melanoma cells. It reduced the expression of NF-kappaB-dependent gene products that regulate proliferation, cytokine production, and antiapoptotic responses but exhibited little antiproliferative or proapoptotic activity at the cellular level. However, KINK-1 markedly increased the activities of some cytostatic agents in vitro and abrogated doxorubicin-induced NF-kappaB activation. Combined treatment of C57BL6 mice that had been injected with melanoma cells with KINK-1 and doxorubicin or camptothecin reduced metastases and pulmonary tumor mass compared with either treatment alone (mean lung weight 19 days after injection of melanoma cells of mice treated with 3 mg/kg KINK-1 alone, 1 mg/kg doxorubicin alone, and 1 mg/kg doxorubicin plus 3 mg/kg KINK-1 = 260 mg, 95% confidence interval (CI) = 216 to 305 mg; 268 mg, 95% CI = 224 to 313 mg; and 181 mg, 95% CI = 171 to 192 mg, respectively, P < .001 from t tests comparing mean lung weight of double-treated mice to that in mice treated with either compound alone).Inhibition of constitutive and induced IKKbeta-activity through treatment with KINK-1 might increase tumor susceptibility to chemotherapy.
Hospital Variables Associated With Quality of Care for Breast Cancer Patients
Authors: Roger Hand
Journal: JAMA (1991)

<h3>Objective.</h3> —To determine the degree of compliance with clinical standards among hospitals for care of breast cancer patients and account for variations in compliance. <h3>Design.</h3> —Analysis of cancer registry data submitted to the American Cancer Society, Illinois Division, Chicago, for a concurrent prospective descriptive study of breast cancer, supplemented by other hospital data from public sources. <h3>Setting.</h3> —Ninety-nine Illinois hospitals evenly distributed among rural counties, counties with small cities outside the Chicago metropolitan area, exurban counties in the Chicago metropolitan area, suburban Cook County, and urban Chicago. <h3>Patients.</h3> —A total of 5766 newly diagnosed patients with histologically confirmed breast cancer in 1988, representing 84% of the estimated 6900 new cases in the state for that year. <h3>Main Outcome Measures.</h3> —Descriptive statistics and multiple linear regression analyses of five dependent quality variables from clinical indicators related to early diagnosis, hormone receptor determination, adjuvant therapy, radiation therapy, and axillary lymph node dissection. <h3>Results.</h3> —At the hospitals studied, (1) late stage (IIb through IV) at diagnosis was associated with urban location, higher proportion of poorly insured patients, fewer breast cancer cases treated, and lower oncology charges (proportion of variance explained,<i>R</i><sup>2</sup>=.50,<i>P</i>&lt;.00001); (2) omission of hormone receptor test for stages II through IV was associated with urban location and higher proportion of poorly insured patients (<i>R</i><sup>2</sup>=.18,<i>P</i>&lt;.00003); and (3) omission of indicated radiation therapy was associated with urban location and fewer breast cancer cases (<i>R</i><sup>2</sup>=.21,<i>P</i>&lt;.00001). Omission of adjuvant therapy and omission of axillary lymph node dissection were not significantly associated with any of the hospital variables examined. Conclusions. —The findings suggest that there is a group of urban hospitals, generally small and marginally reimbursed, where comprehensive diagnosis and treatment of breast cancer are not obtained. (<i>JAMA</i>. 1991;266:3429-3432)
Is there any role for tumour necrosis factor related apoptosis inducing ligand-osteoprotegerin (TRAIL-OPG) interaction in rheumatoid arthritis?
Authors: G Castellino, F Corallini, F Trotta, P Secchiero
Journal: Annals of the Rheumatic Diseases (2008)

We read with great interest the article “Baseline serum RANKL levels may serve to predict remission in patients with rheumatoid arthritis treated with TNF antagonists” by Gonzalez-Alvaro, recently published in Annals of Rheumatic Diseases .1 Other reports have previously shown increased serum levels of RANKL (receptor activator for nuclear factor κB ligand), as well as of osteoprotegerin (OPG), in patients affected by rheumatoid arthritis (RA), and the upregulation of OPG has been usually interpreted as a compensatory mechanism to limit bone erosion due to RANKL activity.2–4 In addition, Gonzalez-Alvaro et al stated that low serum levels of baseline RANKL and the RANKL:OPG …