tbuckley/cabot-search huggingface dataset:
ATPS-29INTRANASAL DELIVERY OF THERAPEUTIC NEURAL STEM CELLS TO TARGET INTRACEREBRAL GLIOMA
Authors: Margarita Gutova, Davit Shahmanyan, Diana Oganesyan, Yelena Abramyants, Lusine Danielyan, William Frey, Vazgen Khankaldyyan, Joseph Najbauer, Irina Balyasnikova, Rex Moats, Maciej Lesniak, Michael Barish, Karen Aboody
Journal: Neuro-Oncology (2015)

Despite aggressive multimodal therapy and advances in imaging, surgical and radiation techniques, high-grade gliomas remain incurable, with patient survival often measured in months. Treatment failure is largely attributable to the invasive nature of glioma cells, ineffective delivery of chemotherapeutic agents across the blood-brain barrier, and dose-limiting systemic toxicities. Neural stem cells (NSCs) have inherent tumor-tropic properties that can be exploited for targeted delivery of anti-cancer agents. However, current intracranial and intravenous injection approaches for administering NSCs are not optimal, especially for repeat administrations, because the methods are invasive and may lead to complications. We hypothesized that intranasal administration of NSCs would circumvent these challenges. In this study, we evaluated the biodistribution of NSCs administered intranasally to plasma esterase-deficient (Es1e) SCID mice bearing orthotopic xenografts of U251.eGFP.ffluc human gliomas. Histological imaging and 3D reconstruction revealed that NSCs selectively localized to tumor sites, but not to non-tumor areas of the brain. Importantly, mice treated with intranasally administered NSCs that were genetically modified to express carboxylesterase, a prodrug-activating enzyme, in combination with CPT-11 (irinotecan) showed increased survival and reduced tumor growth rate. These results support further development of intranasal delivery of NSCs as a new approach to treating glioma and possibly other invasive brain tumors.
The cardiac effects of therapeutic plasma concentrations of imipramine
Authors: S J Kantor, A H Glassman, J T Bigger, J M Perel, E V Giardina
Journal: American Journal of Psychiatry (1978)

The authors studied the effects of imipramine hydrochloride at plasma concentrations associated with antidepressant activity in seven patients hospitalized for severe depressive illness. They found that the drug usually produced prolongation of intraventricular cardiac conduction. Although this was generally well tolerated, the authors suggest that patients with preexisting conduction system disease may be at increased risk when taking tricyclic antidepressants. They feel that the orthostatic hypotension seen in all seven patients represents a potentially serious problem with tricyclic antidepressants. They discuss the antiarrhythmic properties associated with imipramine and significant interactions between imipramine and drugs taken by patients with cardiovascular disease.
Case 5-1985
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, Betty U. McNeely, Mark E. Molitch, E. Tessa Hedley-Whyte
Journal: New England Journal of Medicine (1985)

Presentation of CaseA 33-year-old woman was admitted to the hospital because of a question of a pituitary tumor.She was well until one year earlier, when she began to experience fatigue and occasional hot flashes. Discomfort appeared in the anterior region of the chest after exercise classes, and she took large doses of aspirin daily. During the next few months her menses became scantier but remained regular, with premenstrual molimina. Three months before admission epigastric burning pain developed; aspirin was discontinued, and cimetidine was administered, with improvement. A menstrual period was overdue by two weeks, but a pregnancy test . . .
Transcriptional Repression Of CDKN2D by PML/RARα Contributes To The Altered Proliferation and Differentiation Block Of Acute Promyelocytic Leukemia Cells
Authors: Xiaohong Jia, Yun Tan, Yewei Wang, Xuehua Zhu, Xianwen Yang, Wen Jin, Ji Zhang, Kankan Wang
Journal: Blood (2013)
Long-Term Outcome of Preemptive Immunotherapy Based on Post-Transplant Chimerism and MRD Monitoring after Allogeneic Stem Cell Transplantation in Children with Acute Lymphoblastic Leukemia: A Single Center Experience
Authors: Eva Rettinger, Michael Merker, Hermann Kreyenberg, Thomas Krenn, Matthias Dürken, Jörg Faber, Sabine Huenecke, Claudia Brehm, Melanie Bremm, Shahrzad Bakhtiar, Andre Manfred Willasch, Andrea Jarisch, Jan Soerensen, Thomas Klingebiel, Peter Bader
Journal: Blood (2014)
Topologic Assessment by Use of Wholemounts of Mitotic Activity in the Hamster Mammary Gland During the Estrous Cycle
Authors: Dallas M. Purnell, Gregory C. Saggers
Journal: JNCI Journal of the National Cancer Institute (1974)

Stained wholemounts of inguinal mammary glands prepared from colchicine-treated LSH/SsLAK hamsters killed at different phases of the estrous cycle were used to determine the temporal and topologic distribution (ducts vs. lobulo-alveolar structures) of mitoses in the mammary gland during the estrous cycle. Two periods, 1 early and 1 late in relation to the event of ovulation, of increased mitotic activity in the mammary gland were identified. These 2 periods differed distinctly from each other in relation to the distribution of mitoses between ducts and lobulo-alveolar structures. The results are discussed in relation to our previous studies of the hamster mammary gland and to fluctuations in ovarian hormones during the estrous cycle.
Cancer Screening After Unprovoked Venous Thromboembolism
Authors: Faizan Khan, Marc Carrier, Marc Rodger
Journal: JAMA Internal Medicine (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Response to a Respiratory Survey
Authors: D O ANDERSON, R ZICKMANTEL, B G FERRIS
Journal: JAMA (1963)

Respondents to a respiratory survey of Berlin, New Hampshire, residents in 1961 have been studied to assess the relationship between co-operation and respiratory disease prevalence. Two hundred and forty-three unco-operative subjects, interviewed at home, had significantly more morning phlegm and a lower vital capacity than carefully matched subjects who attended the central clinic. Fifty-one volunteers had the same prevalence of respiratory disease symptoms and physiological abnormalities as carefully matched subjects drawn from a probability sample of the city.It is concluded that respiratory disease prevalence will be underestimated if calculated from studies of co-operative subjects who attend a clinic. Case-finding by respiratory disease screening clinics will also miss many persons who suffer from chronic bronchitis.
Preemptive therapy of cetuximab-induced skin rash using doxycycline, sunscreen, hydrocortisone, and moisturizer in colorectal and head and neck cancer patients.
Authors: Rebecca Ann Redman, Cesar Augusto Perez, Lauren Sledjeski, Mika Kessans Knable, Vivek R. Sharma
Journal: Journal of Clinical Oncology (2015)

TPS796 Background: Toxicities associated with the use of cetuximab include infusion reactions, dermatologic toxicity and electrolyte disturbances. Of these, skin toxicity including acneiform rash, dry skin and fissuring, paronychial inflammation, infectious sequelae and hypertrichosis occur most commonly, with acneiform rash developing in 76-88% of patients. These skin toxicities are rarely life-threatening, but they impact the quality of life of patients receiving therapy and directly affect adherence. The purpose of this study is to determine if preemptive therapy with doxycycline, sunscreen, hydrocortisone 1% cream, and moisturizer will reduce the incidence and severity of &gt; grade 2 acneiform rash according to CTCAE v.4 in patients with colorectal and head and neck cancer receiving therapy with cetuximab. Methods: This is a single-institution, prospective, open-label, randomized study of 100 patients with colorectal and head and neck cancer receiving cetuximab in the locally advanced or metastatic setting. Those randomized to preemptive therapy will receive doxycycline 100 mg twice daily, sunscreen SPF 30, hydrocortisone 1% cream, and moisturizer beginning three days prior to the first dose of cetuximab for a duration of 8 weeks. Those randomized to standard of care will receive treatment of skin toxicity per national guidelines and treating physician discretion. Objectives are to evaluate the incidence of cetuximab-induced rash, compare the severity of cetuximab-induced rash between the preemptive treatment group and the standard care group, and monitor the toxicity of the preemptive therapy. Secondary objectives include quality of life, adherence rates, disease-specific outcomes, and survival. Patients will be evaluated at enrollment, 3 weeks into treatment and at the end of treatment for adherence, side effects and quality of life. They will be followed for up to two years for treatment outcomes and survival. With alpha of 0.05 and a power of 80%, we will be able to detect if the incidence of skin rash differs by 24% between the two groups using a two-sample one-sided binomial test. As of September 2014, 15 of 100 patients have been enrolled. Clinical trial information: NCT01874860.
Abstract 9556: Effect of High Intensity Interval Training in Heart Transplant Recipients - A Randomized Controlled Trial
Authors: Kari Nytrøen, Lene Annette Rustad, Pål Aukrust, Thor Ueland, Jostein Hallén, Inger Holm, Katrine Rolid, Tove Lekva, Arnt Fiane, Jan P Amlie, Svend Aakhus, Lars Gullestad
Journal: Circulation (2012)

BACKGROUND High intensity interval training (HIIT) is an efficient form of exercise training in patients with coronary heart disease and heart failure, while heart transplant (HTx) recipients, mainly because of denervation, traditionally have not been exposed to HIIT. Even if many studies have documented effect of exercise in HTx recipients, VO 2peak remain below normal: 50 to 70% of predicted. Our hypothesis was that HIIT is an applicable and safe form of exercise in heart transplant (HTx) recipients, and that it would markedly improve VO 2peak. Secondarily, we wanted to evaluate central and peripheral mechanisms behind a potential VO 2peak increase. METHODS Forty-eight clinically stable HTx recipients &gt;18 years old and 1-8 years after HTx underwent maximal exercise testing on a treadmill, muscle strength testing, echocardiography and quality of life questionnaires. They were randomized to either exercise group (a one-year HIIT-program) or control group (usual care). RESULTS The mean±SD age was 51±16 years, 71% were male and time since HTx was 4.1±2.2 years. The mean VO 2peak difference between groups at follow-up was 3.6 [2.0, 5.2] mL/kg/min ( p&lt; 0.001). The exercise group had achieved 89.0±17.5% of predicted VO 2peak vs. 82.5±20.0% in the control group ( p&lt; 0.001). In addition, the exercise group improved their muscular exercise capacity significantly ( p&lt; 0.001) and had subjectively significant better general health ( p&lt; 0.001). There were no changes in cardiac function measured by echocardiography. CONCLUSIONS The present study documents that a long-term, partly supervised and community-based HIIT-program is an applicable, effective and safe way to improve VO 2peak , muscular exercise capacity and quality of life in HTx recipients. The results indicate that HIIT should be more frequently used among stable HTx recipients in the future.
Phase I study of MGCD265 administered intermittently to patients with advanced malignancies (Study 265–102)
Authors: D. Hong, P. LoRusso, R. Kurzrock, C. Maroun, M. Mehran, M. Drouin, R. Martell, J. Wheler
Journal: Journal of Clinical Oncology (2009)

e14516 Background: MGCD265 is an orally-available small molecule designed to inhibit c-Met, VEGFR-1, -2, -3, Tie-2 and Ron kinases. These targets are potentially relevant for the treatment of a variety of cancers. The objective of this Phase I study is to evaluate the safety, pharmacokinetics (PK) and pharmacodynamics (PD) of MGCD265 using an intermittent schedule of administration in patients with solid tumors. Methods: This is a multicenter, open-label, dose escalation study of oral MGCD265 administered on days 1–7 and 15–21 (1 week on, 1 week off schedule) of each 28-day cycle. Cohorts of 3–4 patients were enrolled per dose level, initially with dose doubling between cohorts, followed by smaller increments once grade 2 drug-related toxicity is observed. Dose limiting toxicity (DLT) was defined as: grade 4 neutropenia; grade 4 thrombocytopenia; any &gt; grade 3 nonhematologic toxicity; severe/sustained hypertension; or any toxic effect leading to a patient missing &gt; 4 doses of MGCD265. Treatment would continue until disease progression or toxicity. Results: Eleven patients with advanced solid tumors have been treated. Characteristics: age range 40–72; gender: 3 M/8F; ECOG: 1 (7 patients); 2 (4 patients). At dose levels of 24, 48 and 96 mg/m 2 , no DLTs nor grade 2 or greater drug-related AEs have been reported during cycle 1. Six patients received treatment for 2 or more cycles. Preliminary PK profile after the first dose of administration shows a dose dependent increase in AUC and C max (Table below) with an approximate mean half-life of 30 hours and an approximate mean T max of 7 hours. At the 96 mg/m 2 dose, exposure was in the range of the lower end of the efficacious exposure in certain xenograft models. PD markers including plasma HGF and VEGF and shed/soluble receptors s-Met and s-VEGFR2 have been evaluated. Conclusions: Intermittent administration of MGCD265 was found to be well tolerated at doses of 24, 48, and 96 mg/m 2 . Treatment of patients at 192 mg/m 2 is underway. [Table: see text] [Table: see text]
Zika virus study in<i>The BMJ</i>was different from the one reported in the<i>New England Journal of Medicine</i>
Authors: Maria de Fatima Vasco Aragao
Journal: BMJ (2016)

I would like to clarify that our paper, which was published in The BMJ ,1 is a new and completely different study from that published in a letter to the editor of the New England Journal of Medicine on 6 April 2016.2

The letter, which …
Apolipoprotein E4 Causes Age-Dependent Disruption of Slow Gamma Oscillations during Hippocampal Sharp-Wave Ripples
Authors: Anna K. Gillespie, Emily A. Jones, Yuan-Hung Lin, Mattias P. Karlsson, Kenneth Kay, Seo Yeon Yoon, Leslie M. Tong, Philip Nova, Jessie S. Carr, Loren M. Frank, Yadong Huang
Journal: Neuron (2016)
Ventilation Heterogeneity Of Peripheral Airways (Sacin*VT) Assessed By Nitrogen Multiple Breath Washout (N2-MBW) Is An Accurate and Sensitive Marker Of Bronchiolitis Obliterans Following Haematopoietic Stem Cell Transplantation Recipients
Authors: Federica De Giacomi, Maria Teresa Lupo-Stanghellini, Alessia Orsini, Elena Guggiari, Consuelo Corti, Alessandra Forcina, Simona Piemontese, Francesca Pavesi, Jacopo Peccatori, Massimo Bernardi, Andrea Assanelli, Chiara Bonini, George Cremona, Fabio Ciceri
Journal: Blood (2013)
Radioulnar Synosteosis of Traumatic Origin
Authors: Harold G. Lee
Journal: New England Journal of Medicine (1945)

AN EXTENSIVE review of the medical literature reveals that there are few recorded cases of synosteosis of the forearm bones, although this is always mentioned as a possible complication in discussions of radial and ulnar fractures. The purpose of this report is to present a case of radioulnar cross-union that occurred as a sequela to comminuted fractures of the forearm bones, which were accompanied by a great deal of damage to the soft tissues.Case ReportA large, muscular 44-year-old man, while at work in a factory on January 7, 1941, caught his forearm in a moving belt, sustaining an . . .
Effect of tranexamic acid in traumatic brain injury: a nested randomised, placebo controlled trial (CRASH-2 Intracranial Bleeding Study)
Journal: BMJ (2011)

<b>Objective </b>To assess the effect of tranexamic acid (which reduces bleeding in surgical patients and reduces mortality due to bleeding in trauma patients) on intracranial haemorrhage in patients with traumatic brain injury. <b>Methods</b> A nested, randomised, placebo controlled trial. All investigators were masked to treatment allocation. All analyses were by intention to treat. <b>Patients</b> 270 adult trauma patients with, or at risk of, significant extracranial bleeding within 8 hours of injury, who also had traumatic brain injury. <b>Interventions</b> Patients randomly allocated to tranexamic acid (loading dose 1 g over 10 minutes, then infusion of 1 g over 8 hours) or matching placebo. <b>Main outcome measures</b> Intracranial haemorrhage growth (measured by computed tomography) between hospital admission and then 24–48 hours later, with adjustment for Glasgow coma score, age, time from injury to the scans, and initial haemorrhage volume. <b>Results</b> Of the 133 patients allocated to tranexamic acid and 137 allocated to placebo, 123 (92%) and 126 (92%) respectively provided information on the primary outcome. All patients provided information on clinical outcomes. The mean total haemorrhage growth was 5.9 ml (SD 26.8) and 8.1 mL (SD 29.2) in the tranexamic acid and placebo groups respectively (adjusted difference –3.8 mL (95% confidence interval −11.5 to 3.9)). New focal cerebral ischaemic lesions occurred in 6 (5%) patients in the tranexamic acid group versus 12 (9%) in the placebo group (adjusted odds ratio 0.51 (95% confidence interval 0.18 to 1.44)). There were 14 (11%) deaths in the tranexamic acid group and 24 (18%) in the placebo group (adjusted odds ratio 0.47 (0.21 to 1.04)). <b>Conclusions </b>This trial shows that neither moderate benefits nor moderate harmful effects of tranexamic acid in patients with traumatic brain injury can be excluded. However, the analysis provides grounds for further clinical trials evaluating the effect of tranexamic acid in this population. <b>Trial registration</b>ISRCTN86750102.
Distinct patterns of somatic genome alterations in lung adenocarcinomas and squamous cell carcinomas
Authors: Joshua D Campbell, Anton Alexandrov, Jaegil Kim, Jeremiah Wala, Alice H Berger, Chandra Sekhar Pedamallu, Sachet A Shukla, Guangwu Guo, Angela N Brooks, Bradley A Murray, Marcin Imielinski, Xin Hu, Shiyun Ling, Rehan Akbani, Mara Rosenberg, Carrie Cibulskis, Aruna Ramachandran, Eric A Collisson, David J Kwiatkowski, Michael S Lawrence, John N Weinstein, Roel G W Verhaak, Catherine J Wu, Peter S Hammerman, Andrew D Cherniack, Gad Getz, Maxim N Artyomov, Robert Schreiber, Ramaswamy Govindan, Matthew Meyerson
Journal: Nature Genetics (2016)
Microbiome therapeutics — Advances and challenges
Authors: Mark Mimee, Robert J. Citorik, Timothy K. Lu
Journal: Advanced Drug Delivery Reviews (2016)

The microbial community that lives on and in the human body exerts a major impact on human health, from metabolism to immunity. In order to leverage the close associations between microbes and their host, development of therapeutics targeting the microbiota has surged in recent years. Here, we discuss current additive and subtractive strategies to manipulate the microbiota, focusing on bacteria engineered to produce therapeutic payloads, consortia of natural organisms and selective antimicrobials. Further, we present challenges faced by the community in the development of microbiome therapeutics, including designing microbial therapies that are adapted for specific geographies in the body, stable colonization with microbial therapies, discovery of clinically relevant biosensors, robustness of engineered synthetic gene circuits and addressing safety and biocontainment concerns. Moving forward, collaboration between basic and applied researchers and clinicians to address these challenges will poise the field to herald an age of next-generation, cellular therapies that draw on novel findings in basic research to inform directed augmentation of the human microbiota.
Contribution of Tumor Burden and Body Composition Parameters As Prognostic Factors of Metastatic Renal Cell Carcinoma (Mrcc) Treated By Targeted Therapy
Authors: E. Lanoy, S. Antoun, R. Iacovelli, Y. Loriot, M. Merad, C. Massard, K. Fizazi, M. Dipalma, B. Escudier
Journal: Annals of Oncology (2014)
Analysis of the effects of vitamin K1 cream on cetuximab-induced acne-like rash.
Authors: N. Radovics, G. Kornek, F. Thalhammer, F. Weihsengruber, C. Pietrzak, G. Resch, A. L. Petzer, I. Hauser, C. Wogritsch, R. Greil
Journal: Journal of Clinical Oncology (2010)

e19671 Background: Cetuximab is an IgG1 monoclonal antibody that targets the epidermal growth factor receptor. Acne-like rash is a common side effect of cetuximab. Methods: From September 2008 120 patients (pts) were treated with cetuximab in combination with chemotherapy for different indications, most frequently metastatic colorectal cancer and head and neck squamous cell carcinoma. Skin care with vitamin K1 cream was started at the beginning of the cetuximab treatment or at the first occurrence of acne-like rash. The use of vitamin K1 cream was unspecified with regard to the start of treatment (prophylactic or at time of rash occurrence) and the way in which it was applied (lesional vs. extensive). Results: Of the 64 evaluable pts: 0% developed grade 4 rash, 8 % grade 3 rash, 41 % grade 2 rash and 51% grade 1 rash. An Independent Review Committee (IRC) comprising a dermatologist, an infection specialist and an oncologist evaluated the photographs of all 64 pts for response to treatment with vitamin K1 cream. An interesting finding was the different classifications of the IRC and the treating physicians with regard to the grading of rash. In general, IRC members voted for a higher grading: 4% grade 4 rash, 20% grade 3 rash, 49% grade 2 rash and 27% grade 1 rash. Median time to improvement of rash was 5 weeks. Cetuximab treatment was ongoing throughout the course of treatment with vitamin K1 cream. Rash scoring was evaluated separately by treating physicians and pts. Interestingly, pt assessment showed a more favorable trend regarding pain relief and complications, indicating that the benefit of the vitamin K1 cream might be even greater for the pt - 8 pts also documented a positive effect on pruritus. Conclusions: The effect of the vitamin K1 cream was assessed as beneficial from the perspectives of both the pts and the treating physicians. A follow-up project is planned to evaluate specifically the subjective impact of the vitamin K1 cream focusing on pruritus, pain and the benefit of a combination of vitamin K1 cream and antibiotics. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen, Merck GmbH, Merck Serono, Roche Amgen, Merck Serono, Pfizer, Roche, sanofi-aventis
Modulation of splicing catalysis for therapeutic targeting of leukemia with mutations in genes encoding spliceosomal proteins
Authors: Stanley Chun-Wei Lee, Heidi Dvinge, Eunhee Kim, Hana Cho, Jean-Baptiste Micol, Young Rock Chung, Benjamin H Durham, Akihide Yoshimi, Young Joon Kim, Michael Thomas, Camille Lobry, Chun-Wei Chen, Alessandro Pastore, Justin Taylor, Xujun Wang, Andrei Krivtsov, Scott A Armstrong, James Palacino, Silvia Buonamici, Peter G Smith, Robert K Bradley, Omar Abdel-Wahab
Journal: Nature Medicine (2016)