tbuckley/cabot-search huggingface dataset:
Bevacizumab, a monoclonal antibody to the vascular endothelial growth factor (VEGF), and irinotecan for treatment of recurrent primary malignant brain tumors in adults
Authors: U. Lassen, K. Grunnet, M. Kosteljanetz, B. Hasselbalch, H. Laursen, H. S. Poulsen
Journal: Journal of Clinical Oncology (2007)

12503 Background: The prognosis of recurrent malignant brain tumors is poor, and no efficacious therapy exists in patients previously treated with radiotherapy and standard chemotherapy. Bevacizumab (B) binds to VEGF and inhibits tumor angiogenesis, and treatment with this drug might induce tumor regression and prolongation of life. Irinotecan (I) is a topoisomerase 1 inhibitor with modest effect on recurrent primary brain tumors. The combination of B and I in recurrent malignant gliomas was presented at ASCO 2006 and showed very encouraging responses. Methods: We report confirmatory results of the combination of B and I in a consecutive series of patients with primary malignant brain tumors recurring after standard primary and secondary treatment (surgery, radiotherapy and standard or secondline chemotherapy).With standard inclusion criteria, including PS 0–2, patients received B as 10mg/kg, and I 125 mg/m2 in patients not treated with enzyme inducing antiepileptic drugs (EIAED) or 340 mg/m2 in patients treated with EIAED every other week until progression or non-manageable toxicity. Response evaluation was performed by MacDonald criteria and MRI scans. Results: The results of 31 patients is presented, 15 with grade IV tumors (Glioblastoma multiforme), 7 with grade III anaplastic astrocytomas, 5 with anaplastic oligodendrogliomas, 1 with anaplastic ependymoma, 1 with hemangiopericytoma, 1 with prolactinoma, and 1 with medulloblastoma. Four patients had complete response, 3 grade IV tumors and 1 anaplastic oligodendroglioma. One patient had partial response (&gt; 50% tumor reduction), 12 had stable disease (3 had tumor reduction between 31 - 45 %). 14 progressed. No grade 4 toxicity was observed and most patients experienced grade 1–2 toxicity. Two tromboembolic events and 1 intestinal perforation were observed. Conclusion: The combination of B and I is safe, induces tumor regression in a substantial number of patients, and can be used as treatment to patients recurring after standard treatment. No significant financial relationships to disclose.
A phase I safety and pharmacokinetic (PK) study of PI3K/TORC1/TORC2 inhibitor XL765 (SAR245409) in combination with erlotinib (E) in patients (pts) with advanced solid tumors.
Authors: R. B. Cohen, P. A. Janne, J. A. Engelman, P. Martínez, Y. Nishida, S. Gendreau, B. Wu, E. Felip
Journal: Journal of Clinical Oncology (2010)

3015 Background: The PI3K pathway is frequently dysregulated in cancer cells and has been implicated as a mechanism of resistance to EGFR inhibitors. XL765 is an oral, selective inhibitor of Class I PI3Ks, TORC1, and TORC2. In preclinical studies, XL765 has demonstrated dose-dependent target modulation in tumor xenograft models. Methods: Pts with advanced solid tumors are enrolled in successive cohorts to receive escalating doses of XL765 in combination with E. After the preliminary MTD has been defined, 9-12 additional pts with NSCLC will be enrolled. Cycles consist of 28 days of XL765 qd or bid and E qd. Pts enrolled into the dose escalation cohorts have a 14-day E monotherapy run-in with PK sampling. Tumor response is evaluated every 8 weeks. Results: 21 pts with advanced solid tumors have been enrolled at four dose levels of XL765 (30, 50, and 70 mg qd and 20 mg bid) in combination with 100 mg E. Thirteen of the 14 NSCLC pts enrolled had prior treatment with E. No dose limiting toxicities have been reported. The most common (≥ 10%) treatment-related adverse events (AEs) were skin and subcutaneous tissue disorders (including rash) and diarrhea. Grade 3 AEs related to study treatment were observed in 1 pt: nausea, vomiting, anorexia and AST increased. No grade 4 events were reported. Based on comparison with historical single agent data, no major PK interaction between XL765 and E has been observed. In skin and tumor biopsies, substantial post-dose reductions were evident in phosphorylation of AKT, 4EBP1, ERK, and EGFR. For example, reductions in pAKT-T308 (57%), p4EBP1 (60%), pERK (61%), and pEGFR (38%) were evident in tumor biopsies from a NSCLC adenocarcinoma pt previously treated with E after administration of 30 mg qd XL765/100 mg E for 21 days. Four NSCLC pts with prior E (3 had progressed on E) have been on study for 16 to 45+ weeks. Conclusions: XL765 in combination with E is generally well tolerated at daily doses up to 50 mg XL765/100 mg E with no apparent PK interaction, and results in robust inhibition of PI3K and EGFR signaling in skin and tumor tissue. The MTD has not yet been determined. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Exelixis, Gatekeeper AVEO, Biogen Idec, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Genentech, MedImmune, Millennium, Novartis, OSI Pharmaceuticals, Pfizer, Roche, Schering-Plough, Syndax Pharmaceuticals Exelixis, Gatekeeper Exelixis, Novartis, Pfizer Genzyme
Abstract 1123: Critical Role Of Adipose Senescence In Insulin Resistance And Vascular Dysfunction
Authors: Masayuki Orimo, Tohru Minamino, Hideyuki Miyauchi, Kaoru Tateno, Sho Okada, Junji Moriya, Kentaro Miura, Ippei Shimizu, Aika Nojima, Issei Komuro
Journal: Circulation (2007)

Cellular senescence is originally described as the finite replicative lifespan of human somatic cells in culture. As a consequence of semi-conservative DNA replication, the extreme terminals of the chromosomes are not duplicated completely, resulting in successive shortening of telomeres with each cell division. Telomerase is a ribonucleoprotein that adds telomeres to the ends of chromosomes. Critically short telomeres are thought to trigger DNA damage response, thereby inducing cellular senescence. Accumulating evidence has suggested that senescent cells promote aging phenotypes or age-related pathologies. Here we show that adipose senescence is critically involved in the regulation of insulin resistance that underlies age-associated cardiovascular disease. The later generation of telomerase-deficient mice with short telomeres exhibited insulin resistance and vascular dysfunction when fed on a high-calorie diet. Adipose tissue of these mice revealed senescence-like phenotypes such as an increase in neutral β galactosidase activity and upregulation of p53 and pro-inflammatory cytokines. Serum levels of pro-inflammatory cytokines were markedly elevated in telomerase-deficient mice and treatment of these mice with a neutralizing antibody against TNF-α significantly improved insulin and glucose intolerance. Removal of senescent adipose tissue reduced serum levels of pro-inflammatory cytokines and thereby improved insulin resistance in telomerase-deficient mice. Conversely, implantation of senescent adipose tissue to wild-type mice impaired insulin sensitivity and glucose tolerance in recipients. Introduction of telomere dysfunction to young adipose tissue markedly upregulated p53 expression and increased the production of pro-inflammatory cytokines. Inhibition of p53 activity significantly improved senescence-like phenotypes of adipose tissue, insulin resistance, and vascular dysfunction in telomerase-deficient mice. These results disclose a novel mechanism of insulin resistance and suggest that adipose senescence is a potential therapeutic target for the treatment of diabetes and diabetic vasculopathy.
Wealth inequality and health: observational study
Authors: Hazel Inskip
Journal: BMJ (2008)

### This month's paper

“The global impact of income inequality on health by age: an observational study” by Danny Dorling and colleagues ( BMJ 2007;335:873 doi: 10.1136/bmj.39349.507315.DE).

#### Abstract

Objectives —To explore whether the apparent impact of income inequality on health, which has been shown for wealthier nations, is replicated worldwide, and whether the impact varies by age.

Design —Observational study.

Setting —126 countries of the world for which complete data on income inequality and mortality by age and sex were available around the year 2002 (including 94.4% of world human population).

Data sources —Data on mortality were from the World Health Organization and income data were taken from the annual reports of the United Nations Development Programme.

Main outcome measures —Mortality in 5-year age bands for each sex by income inequality and income level.

Results —At ages 15-29 and 25-39 variations in income inequality seem more closely correlated with mortality worldwide than do variations in material wealth. This relation is especially strong among the poorest countries in Africa. Mortality is higher for a given level of overall income in more unequal nations.

Conclusions —Income inequality seems to have an influence worldwide, especially for younger adults. Social inequality seems to have a universal negative impact on health.

Being poor is bad enough in itself, but is it worse for your health if there are far richer people around you than if everyone is poor? There is evidence for this in developed countries, where being poor is not at the level of starvation, but is it true worldwide?

The authors set out to assess whether national mortality varies more by wealth or by inequality. In other words, which leads to the higher national death rate: living in a poor county or living in …
Abstract 11180: Fibrin Patch-Based Transplantation of Cardiovascular Progenitor Cells Enhanced the Repair of the Infarcted Myocardium
Authors: Qiang Xiong, Lei Ye, Pengyuan Zhang, Michael Leplay, Cory Swingen, Dan S Kaufman, Jianyi Zhang
Journal: Circulation (2011)

Background: The optimal cell delivery method for stem cell-based cardiac repair remains to be explored. In this study, we aim to enhance the efficacy of cardiac repair by using a fibrin patch-based...
General Systematic Bacteriology: History, Nomenclature, Groups of Bacteria.
Authors: Robert Earle Buchanan
Journal: JAMA (1927)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Abstract 15545: Ca2+ Influx Through L-type Ca2+ Channels Activates Nuclear Factor of Activated T-cells Translocation in Neonatal Rat Ventricular Myocytes
Authors: Hui Gao, Fang Wang, Wei Wang, Hongyu Zhang, Hajime Kubo, Remus M Berretta, Larry A Barr, Jeffrey D Molkentin, Steven R Houser
Journal: Circulation (2011)

Introduction: In cardiomyocytes, pathological stress increases cytosolic Ca2+, which activates Calcineurin (Cn) that dephosphorylates nuclear factor of activated T-cells (NFAT), thus inducing nucle...
Abstract 511: Mitochondrial Complex I -Regulated Alteration of Carbohydrate Oxidation and Energy Metabolites Reduces Ischemia-reperfusion Injury in Hearts from Mice Exposed to Moderate Ethanol Intake
Authors: Hui-zhong Zhou, Xiaokui Ma, Gary Cecchini, Ursula Simonis, Mary O Gray
Journal: Circulation (2007)

Background: Moderate alcohol consumption is cardioprotective in large part through mechanisms that converge on mitochondria. As a primary entry point for reducing equivalents into the respiratory chain, the state of complex I activation has important consequences for overall mitochondrial function and cell homeostasis. Hypothesis : Complex I is a key control point in regulation of carbohydrate oxidation and energy production that influence the extent of cardiac injury in hearts from ethanol-fed animals subjected to ischemia-reperfusion (I/R). Methods and Results: Isolated hearts from C57BL/6 mice fed 10% ethanol (vol/vol) as drinking water for 16 weeks (E) and age-matched controls were subjected to 30 min global ischemia and 30 min reperfusion. Hemodynamics showed E hearts had better contractile recovery (left ventricular developed pressure 62±6 vs. 24±5 mmHg) and less cell damage (creatine kinase release 0.32±0.1 vs. 0.65±0.1 U/min/g) than controls after reperfusion. Mitochondrial NADH-Oxidase (1.2±0.2 vs.0.58±0.1 μg/m/mg), NADH-ubiquinone reductase (complex I, 1.04±0.2 vs. 0.48±0.1 μg/m/mg), state 3 oxygen consumption rates (266±28 vs. 152 ± 18 ngAtomO/m/mg), respiratory control ratios (5.2±0.4 vs. 3.1±0.2), aconitase activity (0.73±0.2 vs. 0.48±0.1 μmol/m/mg), and lipid peroxidation (MDA 216±22 vs. 348±14 nmol/g ) were significantly improved in E hearts after I/R compared to control hearts (all P&lt;0.05, n=3–12). EM showed that the severity of mitochondrial ultrastructure deformation in E hearts was attenuated. In addition, high resolution 1H NMR spectroscopy revealed that the myocardial metabolites alanine, glycine, creatine/phosphocreatine, NAD, total adenosine nucleotide, and ATP were better preserved, whereas lactate and succinate were reduced in E heart tissue extracts relative to control hearts. Conclusions: Moderate alcohol consumption reduces myocardial I/R injury. The mechanism of the cardioprotection in part depends on mitochondria -mediated survival pathways. Within the mitochondria, preservation of complex I activity is critical for maintaining overall respiratory function and cardiac energy generation.
Prolonged infusion of gemcitabine in patients with platinum resistant or refractory recurrent ovarian carcinoma: A phase II study Of GEICO (Spanish Group for investigation on ovarian cancer)
Authors: B. Ojeda, A. Gonzaléz-Martín, B. Mellado, I. Bover, X. Fabregat, M. J. Rubio, L. Alonso, P. Lianes, C. Churruca, A. Poveda
Journal: Journal of Clinical Oncology (2005)

5101 Background: Preclinical and clinical evidence suggests that a prolonged infusion may be more effective than the standard 30-minute infusion of gemcitabine. To investigate the activity and toxicity of gemcitabine infused over 2 hours in patients with platinum resistant or refractory recurrent ovarian carcinoma. Methods: A multi-center phase II study was conducted in patients with recurrent platinum-resistant or refractory ovarian carcinoma. Patients were to receive gemcitabine 1000 mg/m2 over 2 hours on days 1 and 8 every 21 days for at least 6 cycles unless disease progression or unacceptable toxicity occurs. Results: From August, 2003 to October, 2004, 39 patients have been included. Toxicity and efficacy data from first 20 patients are presented. Median age was 64 (range: 30–77). Median platinum-free interval was 3.65 months. 77 cycles have been administered (median of 3 cycles per patient, range: 1–10). Dose delay was required in 27% of cycles and dose reduction was indicated in 2 pts. Dose on day 8 was reduced in 26% of cycles and missed in 11.6% of cycles according to protocol dose modifications. Grade 3–4 haematological toxicities were (% of pts): anemia 20%, neutropenia 15%, and thrombocytopenia 5%. 2 pts had low-risk neutropenic fever. The most frequent non-haematological grade 2–3 toxicities were (% of pts): asthenia 25% (2 pts G2 and 3 pts G3) and nausea 15% (3 pts G2). There were 3 partial responses (15%; 95% CI: 0–30%) and no complete responses observed. Two patients had stable disease (10%) and 15 pts progressed on therapy (75%). Median time to progression was 2 months. Conclusions: These preliminary data suggest that the activity of a prolonged infusion of gemcitabine is comparable with the standard 30-min infusion. The recruitment will continue until the endpoint of 41 patients. Mature data of toxicity and efficacy will be presented. No significant financial relationships to disclose.
Abstract 17281: Programmed Necrosis of Ventricular Myocytes During Ischemic Stress Involves a Mitochondrial Regulated Bnip3- RIP-1- Cyclophilin D Signaling Pathway
Authors: Yan Wang, Joseph W Gordon, Rimpy Dhingra, Yan Hai, Christopher Baines, Lorrie A Kirshenbaum
Journal: Circulation (2011)

Recent animal studies suggest that programmed necrosis plays a critical role in ischemia/reperfusion induced cardiac cell death and in the progression to heart failure. This caspase-independent form of programmed cell death involves RIP1/RIP3 phosphorylation and activation, as well as the formation of the cyclophilin D (CypD)-dependent mitochondrial permeability transition pore (PTP). Our previous work, along with the work of others, suggests that the hypoxia-inducible death gene, Bnip3, may promote a caspase-independent form of cell demise. Therefore, we hypothesized that Bnip3 was capable of triggering programmed necrosis in ventricular myocytes. We demonstrate for the first time that Bnip3-dependent mitochondrial perturbations involving the inner mitochondrial membrane, and cell death, are blocked by the RIP1 inhibitor, necrostatin-1. Furthermore, forced expression of Bnip3 in post-natal cardiac myocytes increased the mitochondrial localization of phospho-RIP3, which was attenuated by deletion of the mitochondrial-targeting transmembrane domain of Bnip3 or in Bnip3-/- cells. In addition, a physical association between Bnip3, RIP1, and CypD by co-immunoprecipitation, was observed in hypoxic myocytes but not normoxic cells, while inhibition of CypD, by cyclosporine A, was sufficient to block Bnip3-induced necrotic-like death. Furthermore, Bnip3 was incapable of inducing PTP opening or cell death in CypD-/- MEFs, despite its ability to interact with RIP1. Thus, our findings implicate CypD as a critical regulator of Bnip3-induced mitochondrial regulated programmed necrosis, and highlight a novel relationship between RIP1- CypD and Bnip3 for programmed necrosis of ventricular myocytes during ischemic injury.
Abstract 636: Conduction Delay in Right Ventricle as a Marker for Identifying High-Risk Patients in Brugada Syndrome
Authors: Atsushi Doi, Masahiko Takagi, Keiko Maeda, Hiroaki Tatsumi, Kenji Shimeno, Minoru Yoshiyama, Eiichi Nakagawa
Journal: Circulation (2008)

BACKGROUND In Brugada syndrome (BS), abnormal conduction delay in right ventricle has been reported. However, the meaning of the conduction delay for risk stratification in BS is still unclear. OBJECTIVES To evaluate the significance of conduction delay in patients with BS as a marker for risk stratification. METHODS Twenty-four patients with BS in whom pilsicainide challenge test was performed (documented VF: N = 7, syncope: N = 7, and asymptomatic: N = 10) were paced from right ventricular apex (RVA), using a basic cycle length of 500ms (8 beats) and a single extrastimulus. A 2.5-French 16-electrode catheter was positioned into the coronary sinus and the great cardiac vein to record intracardiac electrograms on the epicardial sites in right ventricular outflow tract area (RVOT) and lateral left ventricle (l-LV). We measured the conduction time from the stimulus artifact at RVA to the epicardial ventricular electrogram at RVOT or l-LV. The conduction delay between RVA and RVOT (CD-RV) or between RVA and l-LV (CD-LV) was defined as the time interval between the ventricular response at RVOT (RV-V1V2) or at l-LV (LV-V1V2) and the stimulus coupling interval (S1S2) at RVA, respectively (CD-RV; RV-V1V2 minus S1S2, and CD-LV; LV-V1V2 minus S1S2). We also measured 12-lead ECG parameters at baseline and after pilsicainide challenge test, and evaluated the differences of the ECG parameters before and after pilsicainide challenge test. RESULTS Max CD-RV was significantly larger than max CD-LV in all patients (28±9 vs 19±7 ms, p&lt;0.05). Max CD-RV in patients with documented VF was significantly larger than that in patients without (35±10 vs 25±7 ms, p&lt;0.05). However, there was no significant difference in max CD-RV and CD-LV between patients with induced VF and those without (30±9 and 20±5 vs 26±7 and 21±7 ms, p=NS). There was significant positive correlation between max CD-RV and the differences in QRS duration in leads V1, V2, and V6 after pilsicainide administration (r = 0.51, 0.53, and 0.48, respectively, p&lt;0.05). CONCLUSIONS The conduction delay in right ventricle (RV) was a useful marker for identifying high-risk patients in BS. The conduction delay at RV may be related to depolarization abnormality due to sodium channel dysfunction in BS.
Prophylaxis for medical inpatients is not entirely proven
Authors: Domnick F D'Costa
Journal: BMJ (2007)

I have three concerns with regard to the editorial by Fitzmaurice and Murray.1 Firstly, a recent meta-analysis on anticoagulant prophylaxis to prevent symptomatic venous thromboembolism (VTE) in 19 958 hospitalised medical patients showed only modest benefit.2 The numbers needed to treat were 345 (absolute risk reduction 0.29%) to prevent one pulmonary embolism (PE) and 400 …
Pilot study of explicit grading criteria in the American Board of Psychiatry and Neurology. Part II. Examination
Authors: J F McDermott, J Streltzer, K Y Lum, C R Nordquist, G Danko
Journal: American Journal of Psychiatry (1996)

The purpose of this study was to identify specific competencies that differentiated passing from failing performance on the American Board of Psychiatry and Neurology Part II oral board certification examination.A total of 363 candidates were rated in 18 areas of competence defined by behavioral criteria. Data were analyzed to determine which areas best discriminated between passing and failing candidates.In both parts of the examination, the ability to develop a comprehensive treatment plan was most influential. After that, specific interview and observational skills discriminated best. Failing candidates had most difficulty detecting and following informational and affective cues in their interview of a patient and presenting a biopsychosocial formulation and comprehensive treatment plan.Specific candidate competencies related to passing and failing performances can be identified and assessed by a rating scale of observable behaviors on the board certification examination in psychiatry.
New Technique for Study of Viruses in Electron Microscope
Authors: Councilman Morgan, Richard A. Rifkind, Harry M. Rose
Journal: JAMA (1963)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal