tbuckley/cabot-search huggingface dataset:
Gene-Specific Therapy With Mexiletine Reduces Arrhythmic Events in Patients With Long QT Syndrome Type 3
Authors: Andrea Mazzanti, Riccardo Maragna, Alessandro Faragli, Nicola Monteforte, Raffaella Bloise, Mirella Memmi, Valeria Novelli, Paola Baiardi, Vincenzo Bagnardi, Susan P. Etheridge, Carlo Napolitano, Silvia G. Priori
Journal: Journal of the American College of Cardiology (2016)
Studies on Human Leukemia. III. Electron Microscopic Findings in Children With Acute Leukemia and in Children With Infectious Mononucleosis&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: Matilda Benyesh-Melnick, Kendall O. Smith, Donald J. Fernbach
Journal: JNCI Journal of the National Cancer Institute (1964)

The methods for negative staining of untreated human plasma or serum samples for electron microscopic examination were applied to the search for myxovirus-like particles in 24 children with acute leukemia, 12 children with infectious mononucleosis, 60 normal, healthy children, and 13 normal adults. Sixty-seven percent of the leukemic children had high concentrations of myxovirus-like particles (more than 20 particles per field) in their blood, as did 75 percent of the children with infectious mononucleosis, but only 3 percent of the normal, healthy children. None of the adults proved to be positive. Including the intermediate positives (10–19 particles per field), the figures for the 3 groups of children were 79, 100, and 20 percent, respectively. There was no significant morphological difference between the particles in the children with leukemia or infectious mononucleosis and the normal children. Great numbers of the same type of particles were observed in the supernatant fluids of bone marrow cultures that had undergone spontaneous lymphoblastoid transformation. The transformed cultures studied were derived from children with leukemia as well as from children with infectious mononucleosis.
OC-104 Long term effectiveness of short chain fermentable carbohydrate (FODMAP) restriction in patients with irritable bowel syndrome
Authors: L Martin, C van Vuuren, L Seamark, M Williams, H Staudacher, PM Irving, K Whelan, MC Lomer
Journal: Gut (2015)

P3 potentials evoked by spoken words were recorded from seven patients with disorders of recent memory and seven age-matched controls. Inclusion criteria included a clearly identifiable P3 to pure tone stimuli. Absence or marked decrement of P3 to word stimuli was seen in the patients even though they could perform the word task. The results are consistent with an encoding disorder and failure in elaboration of information processing.
Retinoic Acid: Enhancement of a Tumor and Inhibition of Interferon's Antitumor Action&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: S Baron, K M Kleyn, J K Russell, J E Blalock
Journal: JNCI Journal of the National Cancer Institute (1981)

The effect of trans-retinoic acid on the growth of P388 lymphoid tumors in inbred female DBA/2 mice in the presence or absence of interferon (IFN) treatment was studied. This acid derivative of vitamin A enhanced local tumor growth, trans-Retinoic acid also partially reversed IFN protection against tumor growth and mortality.
Lasting Influence of Early Caloric Restriction on Prevalence of Neoplasms in the Rat&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: Morris H. Ross, Gerrit Bras
Journal: JNCI Journal of the National Cancer Institute (1971)

The long-term influence of caloric restriction during the early postweaning period on tumor prevalence in later life was investigated in the rat. Large populations of animals were maintained on 3 dietary regimens: ad libitum throughout life, restricted intake throughout post-weaning life, and restricted intake for 7 weeks immediately after weaning followed by ad libitum feeding for the remainder of life. Tumor data were analyzed by actuarial methods and are presented in terms of age-specific incidence rates and relative tumor risk values. A period of restriction in food intake, even though followed by the ad libitum regimen which is normally conducive to a relatively high incidence of neoplasms,substantially reduced tumor risk. The extent of reduction, depending on tumor type, varied from 14–83%. Of the 25 taxonomic tumor types, miscellaneous malignant tumors and all tumors of hematopoietic and lymphoreticular tissues were least affected by a limited period of dietary restriction, by contrast, the risk of benign connective-tissue tumors and tumors of epithelial tissue, particularly adenomas of the endocrine organs, was markedly reduced by the early dietary restriction. Since early restriction in food intake permanently influenced the growth pattern of these rats, the relationship between body weight and tumor risk among the 3 dietary groups was also examined. Within each group, the incidence of every tumor form was consistently greater in heavier rats than in lighter ratsi among dietary groups, however, no uniform correlation was found. Except for papillomas of the bladder, in which the risk was directly related to body weight at maturity, the reduced risk of all other tumors appears to be attributable to the influence of the dietary regimen during early life.
Incidence, Morphology, and Ultrastructure of Spontaneous Thymoma—the Most Common Neoplasm in W/Nhg Rats
Authors: A B Murray, E Schäffer, M Nüssel, A Luz
Journal: JNCI Journal of the National Cancer Institute (1985)

Spontaneous thymoma was observed with an incidence of 97 and 36% in female and male rats, respectively, from an inbred Wistar/Neuherberg strain (W/Nhg). The thymomas often caused dyspnea and were occasionally the direct cause of death. The neoplasms resembled human thymomas and showed a variable cell composition, ranging from mainly lymphocytic to mainly epithelial. The detailed ultrastructural findings are described and compared with those in other rat thymomas and in human thymomas. A characteristic feature of all dividing lymphocytes was the presence of often multilayered, confronting cisternae. As in more than 50% of human thymomas, W/Nhg rat thymomas were not associated with myopathies or any other possibly autoimmune diseases. They may thus offer a useful model for the study of thymoma without associated parathymic syndromes.
Pressurized intraluminal aerosol chemotherapy with Dbait in the distal esophagus of swine
Authors: Nadja Khalili-Harbi, Nirmitha Herath, Wiebke Solass, Urs Giger-Pabst, Marie Dutreix, Marc Reymond
Journal: Endoscopy (2015)

<b>Background and study aims:</b> A novel therapeutic concept, pressurized intraluminal aerosol chemotherapy (PILAC), and a corresponding device for distributing drugs to the mucosa and submucosa of the distal esophagus are presented. <b>Materials and methods:</b> The endoscopic device that was designed consisted of (i) a double-balloon catheter, similar to a Sengstaken-Blakemore tube; (ii) a carbon dioxide (CO<sub>2</sub>) line, used to create a gaseous, pressurized environment; and (iii) a micropump, used to generate a therapeutic aerosol. The device was inserted into the distal esophagus in three narcotized Landrace pigs. Dbait (short interfering DNA, or siDNA) was aerosolized under pressure (12 mmHg) in CO<sub>2</sub> at 37 °C for 30 minutes. <b>Results:</b> The procedure was well tolerated by all animals. At autopsy, no mucosal or muscular tear was observed. Fluorescence microscopy revealed a homogeneous intramural distribution of Dbait–cyanine 5 in the esophageal wall down to the circular muscular layer (400 – 600 µm). <b>Conclusions:</b> PILAC is feasible in a large animal model and appears to be safe. Therapy of the entire “tissue at risk” for the development of cancer in the distal esophagus is possible without the prior endoscopic identification of diseased tissue.
Contributions of Two Distinct T Cell Subsets (CD4+, CD8+CD60+) to Induction of Specific Memory IgE Responses
Authors: Charles J. Kim, Bryan McCarthy, Jonathan I. Silverberg, Seto M. Chice, Yitzchok M. Norowitz, Maja Nowakowski, Stephan Kohlhoff, Rauno Joks, Tamar A. Smith-Norowitz, Helen G. Durkin
Journal: Journal of Allergy and Clinical Immunology (2016)
Abstract 14815: Progressive Hyponatremia during Heart Failure Treatment Provides Additional Long-Term Prognostic Information to Hyponatremia and Hypoalbuminemia in Patients Admitted with Acute Decompensated Heart Failure
Authors: Takahisa Yamada, Takashi Morita, Yoshio Furukawa, Yusuke Iwasaki, Masato Kawasaki, Atsushi Kikuchi, Takashi Naito, Tadao Fujimoto, Kentaro Ozu, Takumi Kondou, Kaoruko Sengoku, Hironori Yamamoto, Tsutomu Kawai, Satoshi Takahashi, Masatake Fukunami
Journal: Circulation (2012)

Backgrounds: Although hyponatremia and hypoalbuminemia have been shown to be predictors of adverse outcome in patients (pts) admitted with decompensated heart failure (ADHF), there is little inform...
Alcoholic hepatitis: Translational approaches to develop targeted therapies
Authors: Pranoti Mandrekar, Ramon Bataller, Hidekazu Tsukamoto, Bin Gao
Journal: Hepatology (2016)

Alcoholic liver disease is a leading cause of liver‐related mortality worldwide. In contrast to recent advances in therapeutic strategies for patients with viral hepatitis, there is a significant lack of novel therapeutic options for patients with alcoholic liver disease. In particular, there is an urgent need to focus our efforts on effective therapeutic interventions for alcoholic hepatitis (AH), the most severe form of alcoholic liver disease. AH is characterized by an abrupt development of jaundice and complications related to liver insufficiency and portal hypertension in patients with heavy alcohol intake. The mortality of patients with AH is very high (20%‐50% at 3 months). Available therapies are not effective in many patients, and targeted approaches are imminently needed. The development of such therapies requires translational studies in human samples and suitable animal models that reproduce the clinical and histological features of AH. In recent years, new animal models that simulate some of the features of human AH have been developed, and translational studies using human samples have identified potential pathogenic factors and histological parameters that predict survival. Conclusion : This review summarizes the unmet needs for translational studies on the pathogenesis of AH, preclinical translational tools, and emerging drug targets to benefit the AH patient. (H epatology 2016;64:1343‐1355)
Cost-effectiveness of Tyrosine Kinase Inhibitor Treatment Strategies for Chronic Myeloid Leukemia in Chronic Phase After Generic Entry of Imatinib in the United States
Authors: William V Padula, Richard A Larson, Stacie B Dusetzina, Jane F Apperley, Rudiger Hehlmann, Michele Baccarani, Ekkehard Eigendorff, Joelle Guilhot, Francois Guilhot, Rudiger Hehlmann, Francois-Xavier Mahon, Giovanni Martinelli, Jiri Mayer, Martin C Müller, Dietger Niederwieser, Susanne Saussele, Charles A Schiffer, Richard T Silver, Bengt Simonsson, Rena M Conti
Journal: JNCI Journal of the National Cancer Institute (2016)

We analyzed the cost-effectiveness of treating incident chronic myeloid leukemia in chronic phase (CML-CP) with generic imatinib when it becomes available in United States in 2016. In the year following generic entry, imatinib's price is expected to drop 70% to 90%. We hypothesized that initiating treatment with generic imatinib in these patients and then switching to the other tyrosine-kinase inhibitors (TKIs), dasatinib or nilotinib, because of intolerance or lack of effectiveness ("imatinib-first") would be cost-effective compared with the current standard of care: "physicians' choice" of initiating treatment with any one of the three TKIs. We constructed Markov models to compare the five-year cost-effectiveness of imatinib-first vs physician's choice from a US commercial payer perspective, assuming 3% annual discounting ($US 2013). The models' clinical endpoint was five-year overall survival taken from a systematic review of clinical trial results. Per-person spending on incident CML-CP treatment overall care components was estimated using Truven's MarketScan claims data. The main outcome of the models was cost per quality-adjusted life-year (QALY). We interpreted outcomes based on a willingness-to-pay threshold of $100 000/QALY. A panel of European LeukemiaNet experts oversaw the study's conduct. Both strategies met the threshold. Imatinib-first ($277 401, 3.87 QALYs) offered patients a 0.10 decrement in QALYs at a savings of $88 343 over five years to payers compared with physician's choice ($365 744, 3.97 QALYs). The imatinib-first incremental cost-effectiveness ratio was approximately $883 730/QALY. The results were robust to multiple sensitivity analyses. When imatinib loses patent protection and its price declines, its use will be the cost-effective initial treatment strategy for CML-CP.
Heterogeneity in 10-Year Course Trajectories of Moderate to Severe Major Depressive Disorder
Authors: Katherine L. Musliner, Trine Munk-Olsen, Thomas M. Laursen, William W. Eaton, Peter P. Zandi, Preben B. Mortensen
Journal: JAMA Psychiatry (2016)

Evidence suggests that long-term trajectories of major depressive disorder (MDD) are heterogeneous. The Danish Psychiatric Central Research Register (DPCRR) provides a rare opportunity to examine patterns and correlates of long-term trajectories in a large sample of patients with moderate to severe MDD.To characterize patterns and correlates of 10-year course trajectories of MDD in the DPCRR.A cohort containing 11 640 individuals born in Denmark in 1955 or later with their first recorded MDD diagnosis in the DPCRR between 1995 and 2002 was established. Patients were followed for 10 years from the date of their initial MDD diagnosis. Data were obtained from Danish civil and psychiatric national registers in June 2013 and were analyzed from April 4, 2014, to December 17, 2015. Correlates of trajectory class membership were sex, characteristics of the first recorded MDD episode (ie, age, severity, inpatient treatment, and record of suicide attempt or self-harm), and psychiatric diagnoses in parents (ie, depression, bipolar disorder, schizophrenia-spectrum disorders, substance abuse, and anxiety or somatoform disorders).The outcome variable was past-year contact at a psychiatric hospital with a main diagnosis of MDD during each of the 10 years following the initial MDD diagnosis. Trajectories were modeled using latent class growth analysis.The sample included 11 640 individuals (7493 [64.4%] women) aged 18 to 48 years (mean [SD], 31.4 [7.3]) at their first recorded MDD diagnosis. Four trajectory classes were identified: brief contact (77.0%) (characterized by low probability of contact after 2 years); prolonged initial contact (12.8%) (characterized by high decreasing probability of contact during the first 5 years); later reentry (7.1%) (characterized by moderate probability of contact during the second 5 years); and persistent contact (3.1%) (characterized by high or moderate probability of contact throughout). Female sex (odds ratio [OR] range, 1.82-2.22), inpatient treatment (OR range, 1.40-1.50), and severity at first recorded MDD episode (OR range: moderate, 1.61-1.84; severe, 1.93-2.23; and psychotic, 2.73-3.07) were associated with more severe trajectories. Parental anxiety (OR, 1.34 [95% CI, 1.10-1.63]) and depression (OR, 1.63 [95% CI, 1.28-2.09]) were associated with the prolonged initial contact and later reentry classes, respectively. Parental schizophrenia was associated with the persistent contact class (OR range, 2.55-3.04).Most people treated for moderate to severe MDD in Danish psychiatric hospitals do not receive additional MDD treatment after 2 years; however, a minority receive specialty treatment for up to a decade. Observable heterogeneity in the course may be indicative of underlying etiologic differences.
Endotypes of Difficult-to-Control Asthma in Inner City Children Differ By Race
Authors: Kari R. Brown, Rebecca A. Zabel, Agustin Calatroni, Cynthia Visness, Umasundari Sivaprasad, Elizabeth Matsui, Joseph B. West, Melanie M. Makhija, Michelle A. Gill, Haejin Kim, Meyer Kattan, Dinesh K. Pillai, James E. Gern, William W. Busse, Alkis Togias, Andrew H. Liu, Gurjit K. Khurana Hershey
Journal: Journal of Allergy and Clinical Immunology (2016)
Abstract MP101: Infection as a Trigger for Ischemic Stroke: The ARIC Study
Authors: Logan T Cowan, Alvaro Alonso, James S Pankow, Aaron R Folsom, Wayne D Rosamond, Rebecca F Gottesman, Kamakshi Lakshminarayan
Journal: Circulation (2016)

Background and Purpose: Acute triggers for ischemic stroke, which may include infection, are poorly understood, as is whether background cardiovascular disease (CVD) risk modifies such triggering. We hypothesized that recent infection increases acute stroke risk, especially among those with low background CVD risk. Methods: Hospitalized strokes and infections were identified during follow-up of the Atherosclerosis Risk in Communities (ARIC) cohort of 15,792 men and women aged 45-64 years at baseline (visit 1) in 1987-89 through 2013. A case-crossover design and conditional logistic regression were used to compare acute hospitalized infections among stroke patients (14, 30, 42, and 90 days prior to stroke) with corresponding control periods 1 year and 2 years prior. Background CVD risk was assessed using the ACC/AHA equations at both visit 1 and the visit most proximal to the stroke, with risk dichotomized at the median (10.0% estimated 10-year risk for visit 1 and 15.4% for most recent visit). Results: A total of 1,008 adjudicated incident ischemic strokes were included. Compared to control periods 1 and 2 years before stroke, hospitalized infection was more common within 2 weeks before stroke (14 day odds ratio (OR) = 7.7 (95% confidence interval=2.1, 27.3)); the strength of association declined with increasing time in the exposure window before stroke (30 day OR = 5.7 (2.3, 14.3), 42 day OR = 4.5 (2.0, 10.2), and 90 day OR = 3.6 (2.1, 6.5) see Table). Stroke risk was higher among those with low compared with high background CVD risk, with this interaction (between hospitalized infection and CVD risk) reaching statistical significance for some exposure periods. Conclusions: These results suggest that hospitalized infection is a trigger of ischemic stroke, and may explain some cryptogenic strokes. Infection control efforts may prevent some strokes. CVD preventive therapies, including antiplatelet agents and statins, may prevent strokes if used in the peri-infection period but clinical trials are needed to evaluate this.
Lack of Concordance of Growth Rates of Primary and Recurrent Breast Cancer<xref ref-type="fn" rid="FN2">2</xref>
Authors: B W Brown, E N Atkinson, J R Thompson, E D Montague
Journal: JNCI Journal of the National Cancer Institute (1987)

The degree of concordance of growth rates of primary tumors with corresponding recurrences was investigated by using data from 184 patients with breast cancer with measurable recurrences. For conduction of this examination, the detection processes of both the primary tumor and the recurrence were explored. The probability of detection of a recurrence per unit time was found to be nearly proportional to the tumor's diameter. Approximately 60,000 cells initiated the recurrence, and the distribution of doubling times of the recurrences was exponential, with a mean of 2.1 months. The probability of detection of the primary tumor per unit time was approximately proportional to its volume. The distribution of doubling times of primary tumors was nearly exponential; from other evidence, we inferred that the mean doubling time was also close to 2.1 months. Several techniques to measure growth rate agreement between the primary and recurrent tumors within individuals were developed, and all of them yielded the result that the growth rates are nearly unrelated.
ISOLD: A New Highly Sensitive Interleukin Score for Intraocular Lymphoma Diagnosis
Authors: Myrto Costopoulos, Valérie Touitou, Jean-Louis Golmard, Adil Darugar, Sylvain Fisson, Patrick Bonnemye, Marie-Laure Le Lez, Carole Soussain, Nathalie Cassoux, Thierry Lamy, Phuc Le Hoang, Bahram Bodaghi, Hélène Merle-Béral, Magali Le Garff-Tavernier
Journal: Ophthalmology (2016)
British Heart Foundation recommends early defibrillation
Authors: M C Colquhoun, B L Pentecost
Journal: BMJ (1995)

EDITOR,—Anthony Avery and Mike Pringle emphasise the need for general practitioners to be adequately equipped and trained to provide optimal care in medical emergencies.1 They emphasise the value of early defibrillation in the management of cardiac arrest, which in many cases could be provided by an appropriately equipped general practitioner. In recent …
New Antioxidant-Containing Topical Formulation for Treatment of Hand-Foot Syndrome in Cancer Patients: Physician'S and Patient'S Perspective
Authors: T.P. Nikitina, K.A. Kurbatova, I. Bazin, A. Belonogov, G. Kolesnikov, M. Panina, P. Borisov, T.I. Ionova
Journal: Annals of Oncology (2014)
Abstract 13962: Predictors of Early Withdrawal of Care in Post-Cardiac Arrest Patients: Prejudice or Process?
Authors: Shaker MEid, AihamAlbaeni, DhananjayVaidya, NishaChandra-Strobos
Journal: Circulation (2012)

Background: In patients (pts) who are admitted following cardiac arrest, care is often withdrawn by families. Little is known of the timing or the factors that guide this decision. Methods: We evaluated 170 survivors of out-of-hospital cardiac arrest (age 63 ± 16, 62.4% males) admitted from 2004 to 2010. Demographics and details of clinical care were analyzed. Analysis of variance was used to evaluate for statistical significance among three groups (early care withdrawal i.e. ≤72hrs, late withdrawal >72hrs and no care withdrawal). Univariate and multivariate logistic regression analyses were used for assessment of predictors of early (<72 hrs) care withdrawal. Data are reported as odds ratio and 95% CI. Results: Of 170 pts with cardiac arrest, 32 had advanced directives (19%) and 90 pts had care withdrawn (53%). Of these 90 pts, 21 (23%) had prior directives. Mean time to care withdrawal was 2.5 days; however, 52 (52/90 58%) had care withdrawn within 72 hours. Pts with care withdrawal, either early or lat...
Scientists call for moratorium on clinical use of human germline editing
Authors: Michael McCarthy
Journal: BMJ (2015)

An international group of scientists ended a three day forum in Washington, DC, USA, with a call for a moratorium on the clinical use of gene editing that involves alterations in the genomes of human germline cells.

The forum, the International Summit on Human Gene Editing, was prompted by recent advances in gene editing technologies, such as CRISPR-Cas9, that have made it much easier to make precise changes in the human genome.

The meeting was co-hosted by the US National Academy of Sciences, the US National Academy of Medicine, the Chinese Academy of Sciences, and the UK Royal Society. David Baltimore, president emeritus of the California Institute of Technology in Pasadena, California, was the summit’s chair.

In a statement …