tbuckley/cabot-search huggingface dataset:
Case 11-2007
Authors: David M. Greer, Pamela W. Schaefer, Scott R. Plotkin, Robert P. Hasserjian, Allen C. Steere
Journal: New England Journal of Medicine (2007)

A 59-year-old man was admitted to this hospital with fever and the subacute onset of progressive neurologic symptoms that included multiple cranial-nerve palsies. Magnetic resonance imaging of the brain and spine showed leptomeningeal enhancement. Analysis of the cerebrospinal fluid disclosed a lymphocytic pleocytosis and elevated protein and glucose levels. Respiratory failure developed, requiring intubation and mechanical ventilation. The result of a diagnostic test was received.
CMR Guidance for Recanalization of Coronary Chronic Total Occlusion
Authors: Chiara Bucciarelli-Ducci, Dominique Auger, Carlo Di Mario, Didier Locca, Joanna Petryka, Rory O'Hanlon, Agata Grasso, Christine Wright, Karen Symmonds, Ricardo Wage, Eleni Asimacopoulos, Francesca Del Furia, Jonathan C. Lyne, Peter D. Gatehouse, Kim M. Fox, Dudley J. Pennell
Journal: JACC. Cardiovascular imaging (2016)
In-Hospital Exercise after Myocardial Infarction Does Not Improve Treadmill Performance
Authors: Erika S. Sivarajan, Robert A. Bruce, Mary Jane Almes, Bert Green, Laurent Bélanger, Bronwen D. Lindskog, Katherine M. Newton, Louise W. Mansfield
Journal: New England Journal of Medicine (1981)

Prolonged bed rest after myocardial infarction is thought to result in deconditioning, manifested by increased heart-rate and blood-pressure responses to exercise and decreased functional capacity. We studied the effects of early, supervised exercises in preventing deconditioning after acute myocardial infarction. Eighty-four patients were randomized to a control group and 174 to an exercise group. Enrollment in the exercise program occurred an average of 4.5 days after admission (range, one to nine). Discharge from the hospital occurred an average of 10.3 days after admission in the control group and 10.4 days in the exercise group. Most patients had a low-level treadmill test on the day before hospital discharge. There were no differences between the two groups in the clinical, hemodynamic, or electrocardiographic responses to the treadmill test. Incidences of complications and deaths (one death in each group) during hospitalization were not significantly different in the two groups, although six patients (3 per cent, all in the exercise group) required cardiac surgery--four because of recurrent chest pain and two because of rupture of heart muscle. Thus, we were unable to demonstrate any significant beneficial or deleterious effects of an early, in-hospital exercise program.
GENO-10LOSS OF IDH MUTATION IN PATIENT-DERIVED BRAIN TUMOR INITIATING CELLS
Authors: Charles Chesnelong, H. Artee Luchman, J. Gregory Cairncross, Samuel Weiss
Journal: Neuro-Oncology (2015)

Mutation of the IDH1 gene is found in virtually every grade II–III glioma and secondary GBM. IDH mutation is currently hypothesized as the initiating event leading to gliomagenesis, by maintaining an immature proliferative state in a common precursor cell of the astrocytic and oligodendroglial lineage, through epigenetic regulation. Our group has been working for several years to establish brain tumor initiating cell (BTIC) lines from IDH mutated gliomas. We find that IDH mutant BTICs, in addition to being refractory to in vitro culture conditions, systematically lose the IDH mutant phenotype via genetic alterations of chromosome 2, which leads to the loss of either the IDH wild type or mutant allele. Furthermore, we also observed gradual loss of chromosome 2 and IDH mutation in vivo, in a serial orthotopic xenograft model of patient-derived glioma cells. Of note, disappearance, at recurrence, of a pre-existing IDH mutation has been reported in the literature. We confirm the loss of IDH mutation and show that various chromosome 2 alterations affecting the IDH1 locus arise in a subset of cells that are being selected both in vitro and in vivo, suggesting proliferation/survival advantages. Based on our observations, we propose that even though the IDH mutation is essential for tumor initiation, it may be dispensable once a durable transformed state is acquired through the acquisition of additional mutations. The loss of IDH mutation not only represents a potential mechanism of resistance to future IDH mutant-specific therapies, but also raises the intriguing possibility that such therapeutic strategies may increase the selection pressure against the IDH mutation and may eventually lead to a more aggressive phenotype. A larger study focusing on the loss of the IDH mutation in the clinic, at recurrence, will be essential to evaluate the frequency and clinical relevance of this phenomenon.
Spontaneous Atlantoaxial Dislocation
Authors: Herbert Lourie, William A. Stewart
Journal: New England Journal of Medicine (1961)

A Serious and often unrecognized complication of rheumatoid arthritis or ankylosing spondylitis is that of spontaneous atlantoaxial dislocation. Two such cases have come under our care during the past year. The lesion in both patients went unrecognized for many months. We believe that a report of these cases may stress the need for an awareness of this condition by physicians treating arthritic patients. A description of our cases and a review of the pertinent literature comprise the subject matter of this report.Case ReportsCase 1. A 26-year-old man was first admitted to the Neurosurgical Service of the Syracuse Veterans . . .
Impact of the 7th Edition AJCC Staging Classification on the NCCN Clinical Practice Guidelines in Oncology for Gastric and Esophageal Cancers
Authors: Vivian E. Strong, Thomas A. D’Amico, Lawrence Kleinberg, Jaffer Ajani
Journal: Journal of the National Comprehensive Cancer Network (2013)

The 7th edition of the AJCC Cancer Staging Manual has attempted to harmonize gastric and esophageal cancers, including management of gastroesophageal junction (GEJ)-type tumors. The treatment of complex tumor types is best guided by a staging classification that reliably groups patients according to prognosis and therapy. This article reviews and discusses these changes with the goal of elucidating key features of the staging system and outlining how these changes relate to the NCCN Clinical Practice Guidelines in Oncology with regard to the care and treatment of patients. The 7th edition of the AJCC Cancer Staging Manual has certainly improved harmonization of gastric and distal esophageal/GEJ-type adenocarcinomas, although issues persist, particularly regarding the optimal neoadjuvant treatment for the management of GEJ carcinomas.
Clinical Value of a Tracing of Forced Expiration (Expirogram)
Authors: William Franklin, Alan L. Michelson, Francis C. Lowell, Irving W. Schiller
Journal: New England Journal of Medicine (1955)

THE accessibility of the lungs to physical and roentgenologic examination has enabled clinicians to diagnose and manage a great many pulmonary diseases without resort to measurements of pulmonary function. There are many cases, however, in which physical examination and x-ray studies do not give enough information for proper management.Tests have been developed that are at least as informative about the various functions of the lungs as those widely used in cardiac, liver and renal disease. Nevertheless, pulmonary function is rarely assessed as part of routine clinical management unless an interested group and a specially equipped laboratory are readily available. . . .
Gallbladder Disease in Pima Indians
Authors: Richard E. Sampliner, Peter H. Bennett, Leonard J. Comess, Frederick A. Rose, Thomas A. Burch
Journal: New England Journal of Medicine (1970)

An American Indian population was investigated to determine the true prevalence of gallbladder disease, to examine its relation to suggested etiologic factors and to identify high-risk persons. From an age–sexstratified random sample of 596 Pima Indians 15 to 74 years of age. subjects with clinically documented gallbladder disease were identified by review of medical records. An attempt was then made to examine the remainder of the sample by cholecystography. The overall prevalence of gallbladder disease was 48.6 per cent, which greatly exceeded that based on clinical diagnosis alone. The prevalence was significantly higher in females and increased with age in both sexes. No association was demonstrated between gallbladder disease and obesity, serum cholesterol level, diabetes or parity. Pima females 15 to 20 years of age were shown to be at high risk of early development of gallbladder disease and to offer unusual opportunities for further epidemiologic and clinical studies.
Topical Treatment with Nerve Growth Factor for Corneal Neurotrophic Ulcers
Authors: Alessandro Lambiase, Paolo Rama, Stefano Bonini, Giancarlo Caprioglio, Luigi Aloe
Journal: New England Journal of Medicine (1998)

Corneal neurotrophic ulcers associated with impairment of sensory innervation of the cornea may lead to loss of vision, and there is no effective treatment for these ulcers. We evaluated the effects of nerve growth factor in patients with this disorder.Twelve patients (14 eyes) with severe neurotrophic corneal ulcers associated with corneal anesthesia were treated with topical nerve growth factor 10 times daily for two days and then 6 times daily until the ulcers healed. Treatment continued for 2 weeks after the ulcers healed, and the patients were then followed for up to 12 months. The evolution of the corneal disease during treatment and follow-up was evaluated by slit-lamp examination, photography, fluorescein-dye testing, and tests of corneal sensitivity and best corrected visual acuity.Corneal healing began 2 to 14 days after the initiation of treatment with nerve growth factor, and all patients had complete healing of their corneal ulcers after 10 days to 6 weeks of treatment. Corneal sensitivity improved in 13 eyes, and returned to normal in 2 of the 13 eyes. Corneal integrity and sensitivity were maintained during the follow-up period (range, 3 to 12 months). Best corrected visual acuity increased progressively during treatment and follow-up in all patients. There were no systemic or local side effects of treatment.In this preliminary, uncontrolled study, topically applied exogenous nerve growth factor restored corneal integrity in patients with corneal neurotrophic ulcers.
Plasma levels of estrone sulfate (ES) in postmenopausal women with breast cancer (BC) during letrozole (L) treatment: Association with single nucleotide polymorphisms (SNPs) of CYP19A1
Authors: G. Lunardi, L. Del Mastro, M. Serra, P. Driol, C. Boni, F. Cognetti, R. Ponzone, M. Porpiglia, M. Venturini, P. Pronzato
Journal: Journal of Clinical Oncology (2009)

555 Background: The CYP19A1 gene encodes aromatase, a key enzyme for estrogen biosynthesis. We investigated the association between four CYP19A1 SNPs, affecting different circulating estrogen levels (rs10046 C&gt;T, rs4646 G&gt;T, rs749292 C&gt;T, rs727479 T&gt;G), and suppression of plasma ES levels induced by 6 weeks (time needed to reach L steady-state concentrations) of L (25 mg/d). Methods: Patients were enrolled into a prospective, italian multi-centre trial (GIM5) testing the correlation of CYP19A1 SNPs with the efficacy of L adjuvant therapy, after 5 years of tamoxifen, in postmenopausal early BC patients. Blood samples for hormone measurements were obtained immediately before starting L (baseline) and following 6 wks of treatment. SNPs were identified from DNA obtained from peripheral blood cells by Hexaprimer Amplification Refractory Mutation System PCR (H-ARMS-PCR). Plasma ES levels were evaluated by Radio Immuno Assay (RIA). Results: SNPs and hormone levels were evaluated in at least 129 patients. SNPs of CYP19A1 were associated with different baseline plasma ES levels. Mean inhibition of aromatase activity induced by L ranges from 71% to 79%, as a function of the SNPs. After 6 weeks of L no difference in ES levels was observed between patients with different SNPs (Table). Conclusions: L therapy induces a higher aromatase suppression in patients with SNPs associated with higher baseline plasma ES levels. The difference in ES levels associated with genetic variation at the CYP19A1 locus disappeared after L therapy. [Table: see text] [Table: see text]
Environmental surveillance of viruses by tangential flow filtration and metagenomic reconstruction
Authors: Vyacheslav Furtak, Merja Roivainen, Olga Mirochnichenko, Tatiana Zagorodnyaya, Majid Laassri, Sohail Z Zaidi, Lubna Rehman, Muhammad M Alam, Vladimir Chizhikov, Konstantin Chumakov
Journal: Eurosurveillance (2016)

An approach is proposed for environmental surveillance of poliovirus by concentrating sewage samples with tangential flow filtration (TFF) followed by deep sequencing of viral RNA. Subsequent to testing the method with samples from Finland, samples from Pakistan, a country endemic for poliovirus, were investigated. Genomic sequencing was either performed directly, for unbiased identification of viruses regardless of their ability to grow in cell cultures, or after virus enrichment by cell culture or immunoprecipitation. Bioinformatics enabled separation and determination of individual consensus sequences. Overall, deep sequencing of the entire viral population identified polioviruses, non-polio enteroviruses, and other viruses. In Pakistani sewage samples, adeno-associated virus, unable to replicate autonomously in cell cultures, was the most abundant human virus. The presence of recombinants of wild polioviruses of serotype 1 (WPV1) was also inferred, whereby currently circulating WPV1 of south-Asian (SOAS) lineage comprised two sub-lineages depending on their non-capsid region origin. Complete genome analyses additionally identified point mutants and intertypic recombinants between attenuated Sabin strains in the Pakistani samples, and in one Finnish sample. The approach could allow rapid environmental surveillance of viruses causing human infections. It creates a permanent digital repository of the entire virome potentially useful for retrospective screening of future discovered viruses.
Case 38-2010
Authors: Madhusmita Misra, Sareh Parangi, Douglas S. Ross, Randheer Shailam, Peter M. Sadow
Journal: New England Journal of Medicine (2010)

A 13-year-old girl was seen in the pediatric endocrinology clinic because of an enlarging neck mass. The thyroid gland was diffusely enlarged; levels of thyrotropin and antithyroglobulin antibodies were elevated. Ultrasonography revealed diffusely abnormal parenchyma with calcifications.
Abstract 5485: Potent Antithrombotic Activity of EP224283, a Dual Factor Xa Inhibitor and GPIIb-IIIa Antagonist, in Arterial Thrombosis in Mice
Authors: Beatrice Hechler, Monique Freund, Nadia Riehl, Jean-Pierre Cazenave, Maurice Petitou, Christian Gachet
Journal: Circulation (2009)

Arterial thrombosis results from combined platelet activation and coagulation at sites of vascular injury. In acute ischemic events, the cornerstone of treatment is the association of antiplatelet drugs with anticoagulants. Here we investigated the effects of EP224283, a molecule combining antithrombin-dependent factor Xa (FXa) and GPIIb-IIIa inhibition, in several thrombosis models including systemic thromboembolism, localized laser-induced thrombosis of mesenteric arterioles and carotid thrombosis after atherosclerotic plaque rupture in ApoE−/− mice. IV infusion of EP224283 produced dose-dependent anti-FXa activity and inhibition of ADP-induced platelet aggregation (PA). Specifically, 10 nmol/kg EP224283 exhibited plasmatic anti-FXa activity of 0.61±0.01 U/ml without detectable inhibition of PA, while 300 nmol/kg EP224283 exhibited both strong anti-FXa activity (7.6±0.5 U/ml) and 90% PA inhibition, 15 min after infusion. In systemic thromboembo-lism induced by collagen+adrenaline, where thrombin generation is minimal, 85% of control mice died. EP224283 (10 nmol/kg) had no effect on mortality, while all mice receiving EP224283 (300 nmol/kg) survived. When thromboembolism was induced by tissue factor, generating high amounts of active thrombin, mice injected with EP224283 (10 nmol/kg) displayed 40% reduced mortality while all mice injected with EP224283 (300 nmol/kg) survived. These results suggest that the antithrombotic effect is due to both the antiplatelet and anticoagulant properties of EP224283. In a model of localized thrombosis of mesenteric arterioles triggered by laser injury, where both platelet activation and thrombin generation are involved, EP224283 (10 nmol/kg) reduced thrombus stability, while EP224283 (300 nmol/kg) profoundly decreased thrombosis. In this model, high dose hirudin or clopidogrel do not completely inhibit thrombus formation. Thus the dual properties of EP224283 explain its efficacy in this model. Finally, in a model of atherosclerotic plaque rupture induced by ultrasounds, EP224283 (10 nmol/kg) reduced thrombosis by 80%. These results suggest that combining antiplatelet and anticoagulant activities in a single compound is a promising strategy in treatment of acute atherothrombosis.
Addition of Liraglutide to Insulin in Patients With Type 1 Diabetes: A Randomized Placebo-Controlled Clinical Trial of 12 Weeks
Authors: Nitesh D. Kuhadiya, Sandeep Dhindsa, Husam Ghanim, Aditya Mehta, Antoine Makdissi, Manav Batra, Sartaj Sandhu, Jeanne Hejna, Kelly Green, Natalie Bellini, Min Yang, Ajay Chaudhuri, Paresh Dandona
Journal: Diabetes Care (2016)

To investigate whether addition of three different doses of liraglutide to insulin in patients with type 1 diabetes (T1D) results in significant reduction in glycemia, body weight, and insulin dose.We randomized 72 patients (placebo = 18, liraglutide = 54) with T1D to receive placebo and 0.6, 1.2, and 1.8 mg liraglutide daily for 12 weeks.In the 1.2-mg and 1.8-mg groups, the mean weekly reduction in average blood glucose was -0.55 ± 0.11 mmol/L (10 ± 2 mg/dL) and -0.55 ± 0.05 mmol/L (10 ± 1 mg/dL), respectively (P < 0.0001), while it remained unchanged in the 0.6-mg and placebo groups. In the 1.2-mg group, HbA1c fell significantly (-0.78 ± 15%, -8.5 ± 1.6 mmol/mol, P < 0.01), while it did not in the 1.8-mg group (-0.42 ± 0.15%, -4.6 ± 1.6 mmol/mol, P = 0.39) and 0.6-mg group (-0.26 ± 0.17%, -2.8 ± 1.9 mmol/mol, P = 0.81) vs. the placebo group (-0.3 ± 0.15%, -3.3 ± 1.6 mmol/mol). Glycemic variability was reduced by 5 ± 1% (P < 0.01) in the 1.2-mg group only. Total daily insulin dose fell significantly only in the 1.2-mg and 1.8-mg groups (P < 0.05). There was a 5 ± 1 kg weight loss in the two higher-dose groups (P < 0.05) and by 2.7 ± 0.6 kg (P < 0.01) in the 0.6-mg group vs. none in the placebo group. In the 1.2- and 1.8-mg groups, postprandial plasma glucagon concentration fell by 72 ± 12% and 47 ± 12%, respectively (P < 0.05). Liraglutide led to higher gastrointestinal adverse events (P < 0.05) and ≤1% increases (not significant) in percent time spent in hypoglycemia (<55 mg/dL, 3.05 mmol/L).Addition of 1.2 mg and 1.8 mg liraglutide to insulin over a 12-week period in overweight and obese patients with T1D results in modest reductions of weekly mean glucose levels with significant weight loss, small insulin dose reductions, and frequent gastrointestinal side effects. These findings do not justify the use of liraglutide in all patients with T1D.
ATPS-16IDENTIFICATION OF CLINICALLY RELEVANT DRUGS FOR GLIOBLASTOMA WITH SPECIFIC MOLECULAR SIGNATURE USING CHEMICAL BIOLOGY FINGERPRINTING
Authors: Harshil Dhruv, Darren Finlay, Lisa Evers, Sen Peng, Jeff Kiefer, Seungchan Kim, Jeffrey Raizer, Kristiina Vouri, Michael Berens
Journal: Neuro-Oncology (2015)

Translating molecular subtyping of glioblastoma (GBM) into therapeutically actionable guidance remains an unfulfilled opportunity. A central challenge is to discover therapeutic targets matched to agents (drugs or tool compounds) that are predictably present in subclasses of GBM. Transcriptional patterns in GBM cases in TCGA can identify 12 distinct molecular contexts (mC), where, across a subset of genes and tumors, conditional dependencies of gene expression (signal & echo relationships) consistently emerge. We deployed a panel of 64 patient-derived xenografts from GBM patients whose gene expression profiles allow mapping against the same 12 molecular contexts identified from TCGA cases. These clinically-relevant, preclinical models afford bioinformatics mining for actionable targets as well as chemical library screening for activity against short-term cultures derived from the PDX models. Utilizing a technique we term Chemical Biology Fingerprinting (CBF), we interrogated a series of GBM PDX models using a small chemical library (650 compounds) of clinically relevant anti-cancer agents to uncover context-specific chemovulnerabilities. Preliminary data demonstrated that, mC14 GBM (GBM59, SF7300, GBM116), characterized by mt-P53 and transcriptional similarity to GBM proneural subtype, show distinct vulnerability to Arsenic Trioxide (ATO) as compared to mC4 GBM (GBM91, GBM102), characterized by CHEK2 and NF1 mutations and transcriptional patterns similar to GBM mesenchymal subtype. To clinically-validate an ATO vulnerability signature, we acquired 22 treatment naive archival patient samples, who were part of Phase I/II clinical trial to study efficacy of ATO and Temozolomide (TMZ) in combination with radiation in treatment of high grade gliomas (NCT00275067) and which exhibited varied survival with ATO treatment (91 days to >1000 days), and determined their molecular context classification using whole transcriptome sequencing (RNAseq). In summary, we demonstrate a subclassification of GBM into novel contexts and we also show that these contexts are differentially sensitive to clinically relevant drugs. Supported by NIH U01CA168397.
Effect of Lifetime Administration of 2-Hydroxyethylhydrazine on Tumorigenesis in Hamsters and Mice2
Authors: Hidesuke Shimizu, Bela Toth
Journal: JNCI Journal of the National Cancer Institute (1974)

Journal Article Effect of Lifetime Administration of 2-Hydroxyethylhydrazine on Tumorigenesis in Hamsters and Mice Get access Hidesuke Shimizu, Hidesuke Shimizu 3The Eppley Institute for Research in Cancer, University of Nebraska Medical Center, 42nd Street and Dewey Avenue, Omaha, Nebr. 68105. Search for other works by this author on: Oxford Academic PubMed Google Scholar Bela Toth Bela Toth 3The Eppley Institute for Research in Cancer, University of Nebraska Medical Center, 42nd Street and Dewey Avenue, Omaha, Nebr. 68105.4Recipient of Public Health Service Research Career Development Award K04-42,552 from the National Cancer Institute. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 52, Issue 3, March 1974, Pages 903–906, https://doi.org/10.1093/jnci/52.3.903 Published: 01 March 1974 Article history Received: 06 September 1973 Accepted: 02 November 1973 Published: 01 March 1974