tbuckley/cabot-search huggingface dataset:
Patient selection in high-dose trials of breast cancer.
Authors: D R Adkins, R A Brown, J F DiPersio
Journal: Journal of Clinical Oncology (1998)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1998.16.3.1238 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 9508217 Patient selection in high-dose trials of breast cancer. D R AdkinsxD R AdkinsSearch for articles by this author , R A BrownxR A BrownSearch for articles by this author , J F DiPersioxJ F DiPersioSearch for articles by this author https://doi.org/10.1200/JCO.1998.16.3.1238 PDF "Patient selection in high-dose trials of breast cancer.." Journal of Clinical Oncology, 16(3), pp. 1238–1239© 1998 by American Society of Clinical Oncology
Metabolically Healthy Obesity and Development of Chronic Kidney Disease
Authors: Yoosoo Chang, Seungho Ryu, Yuni Choi, Yiyi Zhang, Juhee Cho, Min-Jung Kwon, Young Youl Hyun, Kyu-Beck Lee, Hyang Kim, Hyun-Suk Jung, Kyung Eun Yun, Jiin Ahn, Sanjay Rampal, Di Zhao, Byung-Seong Suh, Eun Cheol Chung, Hocheol Shin, Roberto Pastor-Barriuso, Eliseo Guallar
Journal: Annals of Internal Medicine (2016)

Background: The risk for chronic kidney disease (CKD) among obese persons without obesity-related metabolic abnormalities, called metabolically healthy obesity, is largely unexplored. Objective: To investigate the risk for incident CKD across categories of body mass index in a large cohort of metabolically healthy men and women. Design: Prospective cohort study. Setting: Kangbuk Samsung Health Study, Kangbuk Samsung Hospital, Seoul, South Korea. Participants: 62 249 metabolically healthy, young and middle-aged men and women without CKD or proteinuria at baseline. Measurements: Metabolic health was defined as a homeostasis model assessment of insulin resistance less than 2.5 and absence of any component of the metabolic syndrome. Underweight, normal weight, overweight, and obesity were defined as a body mass index less than 18.5 kg/m2, 18.5 to 22.9 kg/m2, 23 to 24.9 kg/m2, and 25 kg/m2 or greater, respectively. The outcome was incident CKD, defined as an estimated glomerular filtration rate less than 60 mL/min/1.73 m2. Results: During 369 088 person-years of follow-up, 906 incident CKD cases were identified. The multivariable-adjusted differences in 5-year cumulative incidence of CKD in underweight, overweight, and obese participants compared with normal-weight participants were −4.0 (95% CI, −7.8 to −0.3), 3.5 (CI, 0.9 to 6.1), and 6.7 (CI, 3.0 to 10.4) cases per 1000 persons, respectively. These associations were consistently seen in all clinically relevant subgroups. Limitation: Chronic kidney disease was identified by a single measurement at each visit. Conclusion: Overweight and obesity are associated with an increased incidence of CKD in metabolically healthy young and middle-aged participants. These findings show that metabolically healthy obesity is not a harmless condition and that the obese phenotype, regardless of metabolic abnormalities, can adversely affect renal function. Primary Funding Source: None.
Induction of γ-Glutamyltransferase-Positive and Nonspecific Esterase-Positive Foci in Rat Liver by Partial Hepatectomy Following Single Injection of &lt;italic&gt;N&lt;/italic&gt;-Nitrosodiethylamine
Authors: N Hirota, S Moriyama, T Yokoyama
Journal: JNCI Journal of the National Cancer Institute (1982)

The effect of partial hepatectomy (PH) on alteration of liver foci induced by N-nitrosodiethylamine (DENA) was studied in inbred F344 male rats. As early as 2 weeks after PH was performed 6 hours after an injection of 100 mg DENA/kg, gamma-glutamyltransferase-positive hepatocellular foci were induced, whereas DENA alone induced no foci until 12 weeks after PH. The focus counts of the group with PH performed 6 hours after an injection of 100 mg DENA/kg were consistently greater than those of a group with PH performed at 24 hours following DENA injection. At 3 and 6 weeks after PH was done at 12 weeks following treatment with 100 or 200 mg DENA/kg, the focus count was significantly increased compared with that in nonhepatectomized groups. The results indicate that increased liver cell proliferation resulting from PH enhances the conversion of persisting DNA damage to a permanent alteration in DNA. The effect at 12 weeks after exposure supports the concept that DNA damage in hepatocytes is highly persistent.
Abstract 12773: Ethnicity and Primary PCI for ST-Elevation Myocardial Infarction: Data From the First "Nationwide" Primary PCI Program
Authors: Abdorrazzak Gehani, Jassim Al Suwaidi, Omer Tamimi, Salah Arafa, Awad Al Quhtani, Abdulrahman Arabi, Ihsan Rafie, Abulrahman Nabti, Salem Abujalala, Reem Elsousy, Magdi Yacoub
Journal: Circulation (2014)

Introduction: The Middle East is posed to witness one of the highest rise in Coronary Artery Disease (CAD) in the world and at younger age. Multi-Ethnic society is a prominent feature in the Gulf. A nationwide 24/7 Primary PCI (PPCI) program was established for all for STEMI patients. This analysis compares the two most dominant ethnic groups in the gulf, namely Arabs and Asians. Methods: Primary PCI was performed in 496 patients with STEMI, 121 Arabs and 375 Asians. Asians were 6 years younger (48±8 vs 54±12 year, p&lt;0.001), and had fewer females (2.6% vs 11%). Conversely, Arabs had more frequent Diabetes (42% vs 32% in Asians) and Smoking (37% vs 30% respectively). However, in-hospital mortality was similar (1.1 vs 1%). Results: The Door to Balloon Time (DBT) was similar, Asians (55.5 ±19) vs Arabs (56±25 min), p&lt;0.13) and 93% achieved DBT&lt;90min in both groups. Ejection fraction (EF) was also similar (44±8% vs 45.5%), but Asians with DBT&gt;90min had lower EF (42%) than Arab counterparts (48%). This may indicate greater myocardial vulnerability with delay in Asians. Further total coronary Occlusion (TIMI-0) at presentation was seen more frequently in Asians (60%) than in Arabs (48%), p&lt;0.01, but TIMI-III from TIMI-0 was achieved in similar proportion (85% vs 87%). However, in the range of TIMI flow (0-II), TIMI-III was achieved in fewer Asians (94%) compared to Arabs (97%). First ECG on arrival was normal in 5.6% Asians and 2.7% Arabs, however, TIMI-0 flow was found in 60% and 44% respectively. There was a trend towards longer Out of Hospital Delay (OHD, i.e. time from symptoms to arrival to hospital) in Asians (265min) vs 234min in Arabs, particularly in Asian females (409min) vs 330min in Arab females. Radial access was used similarly in Asians vs Arabs (48% vs 45%), and a fall of ≥2gr of Hemoglobin (13% in both). Length of stay was similar (2.7 vs 2.6 days respectively). Conclusion: The age of our STEMI patients is one of the youngest worldwide. It is even younger in Asians than Arabs. Despite greater risk profile and relatively older age in Arabs, in-hospital mortality in Primary PCI was similar. There was similar and excellent DBT in both, but Out of Hospital Delay was greater in Asians, especially females. Time delay appear to have greater adverse effect on the Ejection Fraction in Asians.
Convergent Substitutions in a Sodium Channel Suggest Multiple Origins of Toxin Resistance in Poison Frogs
Authors: Rebecca D Tarvin, Juan C Santos, Lauren A O'Connell, Harold H Zakon, David C Cannatella
Journal: Molecular Biology and Evolution (2016)

Abstract Complex phenotypes typically have a correspondingly multifaceted genetic component. However, the genotype–phenotype association between chemical defense and resistance is often simple: genetic changes in the binding site of a toxin alter how it affects its target. Some toxic organisms, such as poison frogs (Anura: Dendrobatidae), have defensive alkaloids that disrupt the function of ion channels, proteins that are crucial for nerve and muscle activity. Using protein-docking models, we predict that three major classes of poison frog alkaloids (histrionicotoxins, pumiliotoxins, and batrachotoxins) bind to similar sites in the highly conserved inner pore of the muscle voltage-gated sodium channel, Nav1.4. We predict that poison frogs are somewhat resistant to these compounds because they have six types of amino acid replacements in the Nav1.4 inner pore that are absent in all other frogs except for a distantly related alkaloid-defended frog from Madagascar, Mantella aurantiaca. Protein-docking models and comparative phylogenetics support the role of these replacements in alkaloid resistance. Taking into account the four independent origins of chemical defense in Dendrobatidae, phylogenetic patterns of the amino acid replacements suggest that 1) alkaloid resistance in Nav1.4 evolved independently at least five times in these frogs, 2) variation in resistance-conferring replacements is likely a result of differences in alkaloid exposure across species, and 3) functional constraint shapes the evolution of the Nav1.4 inner pore. Our study is the first to demonstrate the genetic basis of autoresistance in frogs with alkaloid defenses.
Data transparency is the only way
Authors: Fiona Godlee
Journal: BMJ (2016)

The BMJ has been accused, with some justification, of being against the drug industry. The industry’s record on subverting medical education, practice, and research in its own rather than the public interest has been a key object of study for the past 20 years and more. But once in a while it’s nice to be able to show that we can be equally critical of academia. Our aim in all cases is to support unconflicted and open science.

When it comes to hiding and misreporting clinical trial data, the industry has a long string of inglorious scandals to its name: oseltamivir (Roche), reboxetine …
Abstract 159: The Impact of Hypothermia Treatment on Survival to Hospital Discharge for Patients with Out-of-Hospital Cardiac Arrest in the Circulation Improving Resuscitation Care (CIRC) Trial
Authors: Lars Wik, Jan-Aage Olsen, David Persse, Fritz Sterz, Michael Lozano, Marc A Brouwer, Mark Westfall, Chris M Souders, Reinhard Malzer, Pierre M van Grunsven, David Travis, Ulrich R Herken, E Brooke Lerner
Journal: Circulation (2012)

Background: Therapeutic hypothermia (TH) has been associated with increased survival after out-of-hospital cardiac arrest (OHCA). There is ongoing debate over when TH should be applied to a patient...
Spontaneous Myxosarcoma in a Cottontail Rabbit (Sylvilagus floridanus): Observation of Tubular Structures in the Endoplasmic Reticulum of Tumor Cells
Authors: Zsuzsa Schaff, Philip M. Grimley, Herman J. Michelitch, William G. Banfield
Journal: JNCI Journal of the National Cancer Institute (1973)

Ultrastructural examination of a spontaneous myxosarcoma in a 6-year-old cottontail rabbit (Sylvilagus floridanus) disclosed geometrically packed tubules (250 Å diameter) in the endoplasmic reticulum of >10% of tumor cell sections. The tubules were indistinguishable from structures previously described in virus encephalitis of rabbits and in virus-induced neoplasms of other experimental animals. They were also similar in dimensions and location to structures described in the cells of patients with connective tissue diseases. Present observations and review of the literature suggest that the tubular structures appear in two general forms: a tightly packed geometric or "crystalline" form presently identified and a less compact "tubuloreticular" form. Although their significance in the endoplasmic reticulum remains obscure, these tubular structures appear to have a limited distribution in mammalian tissues and usually are found in neoplasia or conditions associated with virus infection.
Non-Hodgkin's Lymphoma in Childhood: Epidemiologic Features
Authors: Gordon W. Grundy, Edward T. Creagan, Joseph F. Fraumeni
Journal: JNCI Journal of the National Cancer Institute (1973)

Death certificates of 2642 U.S. children who died of non-Hodgkin's lymphoma, 1960–67, and hospital charts of 900 children with these neoplasms were studied. Lymphosarcoma showed the highest morbidity throughout childhood, with small age peaks at 3–5 years for both sexes. In contrast, reticulum cell sarcoma increased gradually with age. For all cell types combined, non-Hodgkin's lymphoma was 2½ times more common among males than females under age 15. The highest sex ratio characterized lymphosarcoma of the gastrointestinal tract (6:1 male excess). As a feature shared by Hodgkin's disease in childhood, male preponderance seems to reflect a sexrelated susceptibility common to all forms of solid lymphoreticular neoplasms. Transitions to adult age and sex patterns occurred in late childhood. There was no geographic or temporal variation in mortality to suggest major environmental influences. Mortality time trends between 1950–69 revealed a significant decline in lymphosarcoma and increase for reticulum cell sarcoma and other cell types. In the hospital series, a few children had altered immune states, celiac malabsorption, or radiation exposure. Sibs of children with non-Hodgkin's lymphoma showed an increased risk for lymphoma, leukemia, and brain neoplasms. The frequency of leukemic transformation in non-Hodgkin's lymphoma was greatest in early childhood, affecting 34% of children under 5 years. Epidemiologic comparison between childhood lymphoma and leukemia showed similarities as well as important differences.
A phase II study of Gemcitabine (LY 188011) in patients with advanced squamous cell carcinoma of the head and neck
Authors: G Catimel, J B Vermorken, M Clavel, P de Mulder, I Judson, C Sessa, M Piccart, U Bruntsch, J Verweij, J Wanders
Journal: Annals of Oncology (1994)
Production and Susceptibility to Interferon of Polyoma Virus Variants of High and Low Oncogenic Properties&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Tamar Gotlieb-Stematsky, Zeev Rotem, Shulamit Karby
Journal: JNCI Journal of the National Cancer Institute (1966)

Interferon production by polyoma virus variants C−H+ and C+H0 in mouse embryo cells has been studied. The less cytopathic and more oncogenic C−H+ variant induced 4- to 12-fold greater interferon production in mouse cells and was more susceptible to the action of interferon. The C+H0 variant, which is more cytopathic and less oncogenic, produced smaller amounts of interferon, and was less susceptible to its action. It is suggested that the production and sensitivity to interferon render the cells resistant to the cytopathogenic effect of the virus and thus contributes to the establishment of the oncogenic relationship between the polyoma virus and the mouse cell.
NRP1 function and targeting in neurovascular development and eye disease
Authors: Claudio Raimondi, James T. Brash, Alessandro Fantin, Christiana Ruhrberg
Journal: Progress in Retinal and Eye Research (2016)

Neuropilin 1 (NRP1) is expressed by neurons, blood vessels, immune cells and many other cell types in the mammalian body and binds a range of structurally and functionally diverse extracellular ligands to modulate organ development and function. In recent years, several types of mouse knockout models have been developed that have provided useful tools for experimental investigation of NRP1 function, and a multitude of therapeutics targeting NRP1 have been designed, mostly with the view to explore them for cancer treatment. This review provides a general overview of current knowledge of the signalling pathways that are modulated by NRP1, with particular focus on neuronal and vascular roles in the brain and retina. This review will also discuss the potential of NRP1 inhibitors for the treatment for neovascular eye diseases.
Finding the Balance of Less is More—Reply
Authors: Meghan O’Brien
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
A simple one-tube assay for immunophenotypical quantification of leukemic stem cells in acute myeloid leukemia
Authors: W Zeijlemaker, A Kelder, Y J M Oussoren-Brockhoff, W J Scholten, A N Snel, D Veldhuizen, J Cloos, G J Ossenkoppele, G J Schuurhuis
Journal: Leukemia (2015)
Critical Genomic Networks and Vasoreactive Variants in Idiopathic Pulmonary Arterial Hypertension
Authors: Anna R. Hemnes, Min Zhao, James West, John H. Newman, Stuart Rich, Stephen L. Archer, Ivan M. Robbins, Timothy S. Blackwell, Joy Cogan, James E. Loyd, Zhongming Zhao, Christa Gaskill, Christopher Jetter, Jonathan A. Kropski, Susan M. Majka, Eric D. Austin
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

Idiopathic pulmonary arterial hypertension (IPAH) is usually without an identified genetic cause, despite clinical and molecular similarity to bone morphogenetic protein receptor type 2 mutation-associated heritable pulmonary arterial hypertension (PAH). There is phenotypic heterogeneity in IPAH, with a minority of patients showing long-term improvement with calcium channel-blocker therapy.We sought to identify gene variants (GVs) underlying IPAH and determine whether GVs differ in vasodilator-responsive IPAH (VR-PAH) versus vasodilator-nonresponsive IPAH (VN-PAH).We performed whole-exome sequencing (WES) on 36 patients with IPAH: 17 with VR-PAH and 19 with VN-PAH. Wnt pathway differences were explored in human lung fibroblasts.We identified 1,369 genes with 1,580 variants unique to IPAH. We used a gene ontology approach to analyze variants and identified overrepresentation of several pathways, including cytoskeletal function and ion binding. By mapping WES data to prior genome-wide association study data, Wnt pathway genes were highlighted. Using the connectivity map to define genetic differences between VR-PAH and VN-PAH, we found enrichment in vascular smooth muscle cell contraction pathways and greater genetic variation in VR-PAH versus VN-PAH. Using human lung fibroblasts, we found increased stimulated Wnt activity in IPAH versus controls.A pathway-based analysis of WES data in IPAH demonstrated multiple rare GVs that converge on key biological pathways, such as cytoskeletal function and Wnt signaling pathway. Vascular smooth muscle contraction-related genes were enriched in VR-PAH, suggesting a potentially different genetic predisposition for VR-PAH. This pathway-based approach may be applied to next-generation sequencing data in other diseases to uncover the contribution of unexpected or multiple GVs to a phenotype.
Microbiome-based companion diagnostics: no longer science fiction?
Authors: J Raes
Journal: Gut (2016)

In the last decade, our knowledge on the role of the gut microbiome in health and disease has greatly increased, accompanied by an unseen hype around both its diagnostic and therapeutic potential. Yet, one application area of the microbiome has thus far remained understudied: its role as guidance for therapeutic decisions, treatment monitoring and prediction of response.

In this issue of Gut , Mondot et al 1 investigate to what extent the microbiome can both inform us on as well as contribute to treatment outcome in resection surgery for Crohn's disease (CD). Although often the only resort next to dilatation,2 this intervention is not curative, with first-year endoscopic recurrence rates at 28–93% and frequent necessity of reoperation.3 As such, there is an important need for effective postoperative maintenance strategies and predictions for postoperative outcome.

In a longitudinal study of both the faecal and mucosa-adherent microbiota in 20 patients undergoing resection surgery, Mondot et al describe the microbial groups recolonising the intestinal lining around the anastomosis and show different trajectories in recurring patients versus those in remission; the latter were found to exhibit …
Predicting outcome of epilepsy after meningioma resection
Authors: Hans-Georg Wirsching, Corinne Morel, Corinne Gmür, Marian Christoph Neidert, Christian Richard Baumann, Antonios Valavanis, Elisabeth Jane Rushing, Niklaus Krayenbühl, Michael Weller
Journal: Neuro-Oncology (2015)

Surgical excision is the standard treatment for intracranial meningiomas. Epilepsy is a major cause of morbidity in meningioma patients, but postoperative control of epilepsy is not achieved in a substantial fraction of patients. The purpose of this study was to define risk factors for postoperative epilepsy.Patients treated for histologically confirmed intracranial meningioma at the University Hospital Zurich between 2000 and 2013 were retrospectively analyzed. Demographic, clinical, imaging, and electroencephalographic data were assessed. A binary regression model was applied to identify risk factors for postoperative epilepsy.Of the 779 patients analyzed, epileptic seizures occurred in 244 (31.3%) patients before surgery and in 204 (26.6%) patients after surgery. Of the 244 patients with preoperative epilepsy, 144 (59.0%) became seizure-free after surgery; of the 535 patients without preoperative seizures, 104 (19.4%) suffered from epilepsy after surgery. Risk factors for postoperative epilepsy were preoperative epilepsy (odds ratio [OR]: 3.46 [95% confidence interval {CI}: 2.32-5.16]), major surgical complications including CNS infections (OR: 5.89 [95% CI: 1.53-22.61]), hydrocephalus (OR: 3.27 [95% CI: 1.35-7.95]), recraniotomy (OR: 2.91 [95% CI: 1.25-6.78]), and symptomatic intracranial hemorrhage (OR: 2.60 [95% CI: 1.17-5.76]) as well as epileptiform EEG potentials (OR: 2.52 [95% CI: 1.36-4.67]), younger age (OR: 1.74 [(95% CI: 1.18-2.58]), and tumor progression (OR: 1.92 [95% CI: 1.16-3.18]). Postoperative improvement or recovery from preoperative neurologic deficits was associated with improved seizure control (OR: 0.46 [95% CI: 0.25-0.85], P = .013).We suggest prospective validation of a score ("STAMPE2") based on clinical findings, EEG, and brain-imaging measures to estimate postoperative seizure risk and guide anticonvulsant treatment in meningioma patients.