tbuckley/cabot-search huggingface dataset:
Fluorouracil, doxorubicin, and mitomycin combination versus PELF chemotherapy in advanced gastric cancer: a prospective randomized trial of the Italian Oncology Group for Clinical Research.
Authors: G Cocconi, M Bella, S Zironi, R Algeri, F Di Costanzo, V De Lisi, G Luppi, B Mazzocchi, C Rodinò, M Soldani
Journal: Journal of Clinical Oncology (1994)

The combination of cisplatin, epirubicin, and leucovorin preceding fluorouracil (PELF) includes three novel agents compared with the standard combination of fluorouracil, doxorubicin, and mitomycin (FAM) in the treatment of advanced gastric carcinoma. We report the results of a prospective randomized comparison of the two combinations in previously untreated patients.One hundred thirty assessable patients were entered onto the trial; 52 received FAM and 85 PELF. A 1:2 unbalanced randomization in favor of the experimental treatment was chosen. Approximately 90% of patients had measurable tumor masses.The overall response rates (complete responses [CRs] and partial responses [PRs]) were 15% and 43% for the FAM and the PELF regimens, respectively, with a statistically significant advantage for the experimental treatment (P = .001). Time to progression (median, 2.6 and 4.7 months), duration of response (median, 10.7 and 10.2 months), and survival durations (median, 5.6 and 8.1 months) were not significantly different between the FAM and PELF regimens, respectively. The PELF combination was more toxic compared with FAM, but generally tolerable.This study showed that the PELF combination is about three times more effective than the FAM combination in inducing objective responses. Due to tolerability, it is not recommended for routine clinical use. However, it should be considered, among other second-generation chemotherapy combinations, in future randomized studies aimed to improve the therapeutic outcome in gastric carcinoma.
Erdheim-Chester Disease
Authors: GILLES DEVOUASSOUX, SYLVIE LANTUEJOUL, PATRICK CHATELAIN, ELISABETH BRAMBILLA, CHRISTIAN BRAMBILLA
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

Erdheim-Chester disease (ECD) is a rare focal or systemic infiltrative disorder resulting from xanthogranulomatous tissue deposition. Usually, bone marrow involvement affects long bone metaphyses symmetrically, but it spares the epiphyses. Retroperitoneal space, periaortic area, skin, and brain involvement have been described. Pulmonary involvement is frequent, occurring in 20% of cases. Reported histologic features in the lung include an infiltration of so-called lipid-laden macrophages and granulomatous lesions with fibrosis. Lung function outcome is unpredictable, but terminal respiratory failure is the most frequent cause of death. No effective treatment strategies have been described. We report a new case with lung and bone involvement occurring in a symptomatic woman. Histologic and electron microscopic analysis of the pulmonary infiltrate showed abnormal macrophages devoid of lipids forming nodular granulomas and rendering the previous hypothesis of this disease as a primary lipid storage disorder unlikely. These findings suggest that ECD histogenesis is instead based on a primary macrophage cell disease.
<scp>ExtraHF</scp> survey: the first European survey on implementation of exercise training in heart failure patients
Authors: Massimo F. Piepoli, Simone Binno, Ugo Corrà, Petar Seferovic, Viviane Conraads, Tiny Jaarsma, Jean‐Paul Schmid, Gerasimos Filippatos, Piotr P. Ponikowski
Journal: European Journal of Heart Failure (2015)
Exercise-induced bronchoconstriction in a school-age cohort: Prevalence, risk factors and utility of the Cooper test for its routine detection
Authors: Hernan Iannella, Sebastián Rost Vence, Juan Ignacio Enghelmayer, Carlos Luna
Journal: European Respiratory Journal (2014)

Background : Exercise-induced bronchoconstriction (EIB) is a prevalent condition that is frequently underdiagnosed and affects athletic performance, even in subjects without a previous diagnosis of asthma. We hypothesized that the Cooper test could be useful for the routine detection of EIB in the school-age population.   Methods : Observational study that included students aged 11-17 who attend a private school in Lavallol, Buenos Aires. The Cooper test was performed in an outdoor setting, and spirometry was performed in each subject before and 10-30 minutes after running. EIB was diagnosed if there was a fall in FEV 1  ≥ 10% from the pre-exercise level.   Results : 176 subjects were able to perform a spirometric maneuver and completed the Cooper test, and were included in the analysis. Of these, 45 (25.5%) met EIB criteria. Significant differences were found between the two groups for the presence of a previous diagnosis of asthma (5 vs 3, P=0.014), with a prevalence of EIB in asthmatic patients of 62.5%. No significant differences were found for the remaining variables (Table 1).   Conclusions : The Cooper test was able to detect EIB in a significant number of asymptomatic students. Most of the subjects did not have a known diagnosis of asthma. This test could be useful for the routine detection of EIB in schools.
Consolidation therapy with antimetabolite-based therapy in standard-risk acute lymphocytic leukemia of childhood: a Pediatric Oncology Group Study.
Authors: M B Harris, J J Shuster, D J Pullen, M J Borowitz, A J Carroll, F G Behm, V J Land
Journal: Journal of Clinical Oncology (1998)

PURPOSE To develop antimetabolite-based consolidation regimens that minimize acute and long-term toxicities and improve the survival rate of children with standard-risk B-lineage acute lymphocytic leukemia (ALL). PATIENTS AND METHODS Seven hundred twenty-seven eligible patients with standard-risk early pre-B ALL were registered onto the study. Seven hundred sixteen patients attained a complete remission (CR) after induction therapy. Of these, 114 patients were randomized to a different regimen and were the subject of a separate report. Six hundred two patients were randomized to receive one the following regimens: intermediate-dose methotrexate (IDMTX) with leucovorin rescue on weeks 7, 10, 13, 16, 19, and 22 (regimen A); regimen A plus asparaginase (ASP) administered intramuscularly (i.m.) weekly for 24 weeks (regimen B); or regimen A plus a 24-hour infusion of cytarabine (AraC) with each IDMTX (regimen C). After consolidation, patients were placed on maintenance therapy through week 156. Regimens A and C were opened in February 1986, and regimen B in May 1987. Comparisons are based on concurrently randomized patients (May 1987 to January 1991 between regimens A and B, and February 1986 to January 1991 between regimens A and C). RESULTS The 5-year continuous CR (CCR) rates were not significantly different: A versus B, 78.1% (3.9 +/- SE) versus 83.3% +/- 3.5% and A versus C, 79.4% +/- 3.2% versus 83.5% +/- 2.9%; P by one-sided log-rank tests were .27 and .34, respectively. Significant treatment differences were not found with regard to sex, rate of testicular and CNS relapse, or CNS complications. During consolidation, regimen C had significantly more bacterial infections (P = .0032) and days spent in the hospital (P &lt; .001) compared with regimen A. CONCLUSION We were unable to show a statistical advantage of adding either ASP or AraC to IDMTX in terms of improvement in event-free survival (EFS).
Multiplatform comprehensive kinase analysis of penile squamous cell carcinoma (PSCC) to identify drivers and potentially actionable therapeutic targets.
Authors: Amitkumar N. Mehta, Eddy Shih-Hsin Yang, Christopher Douglas Willey, Michael Crowley, Dongquan Chen, Joshua Anderson, Gurudatta Naik, Tiffiny Cooper, Guru Sonpavde
Journal: Journal of Clinical Oncology (2015)

389 Background: PSCC is an orphan malignancy with poorly understood biology and suboptimal systemic therapy. Given that kinases may be drivers of disease and readily actionable, we performed comprehensive multiplatform analysis of kinases in PSCC tumor tissue and adjacent normal tissue. Methods: We collected fresh frozen tumors from 10 patients with PSCC, of whom 3 had adjacent normal tissue available. After macrodissection to demarcate tumor from normal tissue, the samples underwent analysis of kinases using platforms to assess DNA, RNA and kinase activity. Next Generation Sequencing of 515 kinase genes was performed using the Agilent Kinome capture and run on the Illumina HiSeq2500 at PE100bp. The Nanostring nCounter platform analyzed the expression (RNA) of 519 kinase genes. Global kinase activity of tissue lysates was measured using Pamstation@12 high-content phospho-peptide substrate microarray system (PamGene International). Upstream kinase prediction was performed and network mapping was done with GeneGo MetaCore. Ingenuity pathway analysis data was performed to integrate over-expression at the activity and gene expression level with coexisting missense mutations at DNA level. Results: Top pathways observed to be upregulated in both the kinase activity and gene expression platforms were PTEN Signaling, STAT3 Pathway, GNRH Signaling, IL8 Signaling and B Cell Receptor Signaling. Potentially relevant missense mutations were seen in 176 kinase genes, with the top altered pathways overlapping with gene overexpression being GNRH Signaling, NF-kB Signaling, and STAT3 pathways. ERBB2, ERBB3 and SYK were altered on gene sequencing and also showed elevated kinase activity. Kinases previously implicated in prostate cancer (PAK4, TNK2), breast cancer (ERBB2) and genital dysplasia (ROR2) also demonstrated mutations. Conclusions: Multiplatform comprehensive analysis of kinases at the DNA, RNA and protein activity levels discovered several potential drivers of PSCC and actionable therapeutic targets. Further validation in preclinical and translational trials is warranted to make advances in this rare malignancy with substantial unmet needs.
Words matter: The term “side effects” trivialises unwanted effects
Authors: Jean Mossman
Journal: BMJ (1998)

Editor—Smart points out that patients with kidney failure may be distressed by the term “end stage kidney failure.”1 CancerBACUP, a charity that provides information, counselling, and support for all those affected by cancer, has had similar feedback from patients with cancer. Recently, when revising our booklet “Understanding cancer of the prostate,” we sought the advice of, among others, members of a prostate cancer support group. They expressed the view that the term “side effects,” widely used in association with treatment, trivialised what they considered to be important, unwanted effects: impotence and incontinence. We have changed our booklet accordingly.
Biosimilars: Are They Ready for Primetime in the United States?
Authors: Bradford R. Hirsch, Gary H. Lyman
Journal: Journal of the National Comprehensive Cancer Network (2011)

The introduction of alternative versions of biologic products, also known as biosimilars, into the United States market has been gaining increasing visibility as patents for many agents are nearing expiration. Unlike generics, which are regulated under the Hatch-Waxman legislation passed in 1984, the approval process for biosimilars in the United States has not been defined. In 2004, the European Union established a regulatory pathway for these agents, and the FDA is now following suit. The economic implications are large, with $66.9 billion spent on the top 20 biologics in 2009. Of the top 10 biologics, 6 are routinely used in oncology. As the regulatory requirements are debated, several critical issues must be resolved. The most obvious is that the agents must be shown to be comparable to the original biologic they intend to replace. Knowledge of pharmacokinetic parameters alone will not be adequate, but the amount of clinical data required by the FDA remains unclear. The regulations will define the ease with which a biosimilar can be brought to market, and the associated costs of trials will influence the ultimate price of the medications. Balancing the needs of the relevant stakeholders is critical to ensure patient safety while controlling costs, improving access, and encouraging innovation. This is not an easy balance to strike.
Native T 1 Mapping by 3-T CMR Imaging for Characterization of Chronic Myocardial Infarctions
Authors: Avinash Kali, Eui-Young Choi, Behzad Sharif, Young Jin Kim, Xiaoming Bi, Bruce Spottiswoode, Ivan Cokic, Hsin-Jung Yang, Mourad Tighiouart, Antonio Hernandez Conte, Debiao Li, Daniel S Berman, Byoung Wook Choi, Hyuk-Jae Chang, Rohan Dharmakumar
Journal: JACC. Cardiovascular imaging (2015)
Epigenetic alterations in the circulating DNA from blood of patients with COPD and lung cancer
Authors: Anastasia Ponomaryova, Elena Rykova, Nadezda Cherdyntseva, Tatiana Skvortsova, Alexey Dobrodeev, Alexander Zav'yalov, Sergey Tuzikov, Valentin Vlassov, Pavel Laktionov
Journal: European Respiratory Journal (2013)

Background: Epigenetic changes were shown to be detectable in DNA, circulating in blood (cirDNA) of cancer patients, indicating the resources to create the minimally invasive diagnostic tests based on tumor-specific DNA markers.  Methods: Blood samples were taken from 60 untreated patients with non-small-cell lung cancer (NSCLC), 30 patients with chronic obstructive pulmonary disease (COPD) and 32 healthy subjects. Methylation level of tumor suppressor genes (RARB2, RASSF1A) and repetitive elements (LINE-1) in the cirDNA from blood plasma and cirDNA eluated from blood cell surface (csb-cirDNA) with PBS/EDTA and trypsin solutions was assessed by quantitative methylation-specific PCR.  Results: Methylation level of RASSF1A and RARB2 genes were 2-3 fold higher in cirDNA from NSCLC patients compared with healthy subjects (Mann-Whitney U test, P
Association between breastfeeding and lung volumes and alveolar size
Authors: Cristian M. Dogaru, Manjith Narayanan, Marie-Pierre F. Strippoli, Anina M. Pescatore, Ben D. Spycher, Caroline S. Beardsmore, Michael Silverman, John Owers-Bradley, Claudia E. Kuehni
Journal: European Respiratory Journal (2011)

Aim: In a previous study we found that non-breastfed children of asthmatic mothers (CAM) had lower FVC and FEV1 compared with non-breastfed children of non-asthmatic mothers (CnAM), but breastfeeding (BF) compensated, improving these values in CAM (Dogaru 2010 ERJ 678s). We extended this study, analyzing plethysmographic lung volumes (LV) and alveolar size in a different group.

Method: In 132 UK-born subjects (7-21yrs) we measured FRC and TLC by plethysmography and Apparent Diffusion Coefficient (ADC, proxy for alveolar size) by He3-magnetic resonance. We used linear regressions adjusting for LV predictors and potential confounders and stratified by maternal asthma (MA).

Results: 32 (24%) of children were not BF, 38 (29%) were BF ≤3mo and 53 (40%) BF>3mo; 24 (18%) had asthmatic mothers. We found no significant associations between BF and alveolar size, FRC or TLC in the whole group. However, stratification by MA showed a) that non-breastfed CAM have lower FRC and TLC but similar ADC means compared with non-breastfed CnAM and b) a trend for higher FRC and TLC in CAM if breastfed (Table).

![Figure][1] 



Conclusion: These results support previous findings that reduced LV in non-BF CAM compared with non-BF CnAM are compensated by BF. Since alveolar size was similar in CAM and CnAM, we suggest that alveolar number is reduced in CAM without BF, but can be partially increased with BF. Confirmation will require larger samples.

Funding: Asthma UK 07/048; SNF 3200B0-122341.

 [1]: pending:yes
Accountability for Sexual Violence
Authors: M. J. Friedrich
Journal: JAMA (2015)

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
Observations on the responsiveness of human subjects to human growth hormone
Authors: Daniel Rudman, Samuel B. Chyatte, Joseph H. Patterson, Glynda G. Gerron, Irma O'Beirne, Joan Barlow, Peter Ahmann, Ashby Jordan, Robert C. Mosteller
Journal: Journal of Clinical Investigation (1971)

The effect of human growth hormone (HGH) on the N, P, Na, and K balance, and on the body weight (BW) of three groups of subjects was measured. In group I were nine cases (age 6-69) with HGH deficiency; in group II, eight cases (age 9-79) with normal endogenous HGH; in group III, four cases with myotonic dystrophy (age 45-51). After a 7 day control period, the hormone was administered for 7 days. Each subject was tested with three doses of HGH: dose A, 0.0168 U/kg BW3/4 per day; dose B, 0.0532 U/kg BW3/4 per day; dose C, 0.168 U/kg BW3/4 per day.
Effects of sitting time on dyspnea, quality of life, and BODE score in chronic obstructive pulmonary disease
Authors: Sema Savci, Deniz Inal-Ince, Melda Saglam, Naciye Vardar-Yagli, Ebru Calik, Hulya Arikan, Lutfi Coplu, Meral Bosnak-Guclu
Journal: European Respiratory Journal (2013)

Purpose:  Sitting time is emerging as a distinct factor for chronic disease. The purpose of this study was to compare dyspnea, quality of life, and BODE score in patients with chronic obstructive pulmonary disease (COPD) having lower and higher volume of sitting time.   Methods:  Fifty-five patients with COPD participated in this study (47M, 8F, age=60.6±8.4 years). Pulmonary function test was performed. Dyspnea (Medical Research Council dyspnea scale, MMRC), quality of life (St George Respiratory Questionnaire, SGRQ), exercise capacity (6-min walk test, 6MWT), and physical activity level (International Physical Activity Questionnaire Short Form, IPAQ) were measured. Sitting time was recorded as lower (   Results:  The MMRC, SGRQ symptom score, and BODE score were significantly lower in patients with lower volume of sitting time than the patients with higher volume of sitting time (p   Conclusion:  Higher volume of sitting are associated with increased dyspnea perception and multidimensional disease severity, and impaired lung function, physical activity and quality of life in COPD. Whether sitting time may differentiate among COPD phenotypes needs further investigation.
Abstract 2365: Pharmacogenomic Application Of The Haptoglobin Genotype To Identify Individuals With Diabetes Mellitus Who Benefit From Vitamin E Supplementation: A Prospective Randomized, Double-blind, Placebo Controlled Trial
Authors: Uzi Milman, Shany Blum, Chen Shapira, Doron Aronson, Rachel Miller-Lotan, Yefim Anbinder, Junia Alshiek, Lawrence Bennett, Maria Kostenko, Michele Landau, Shlomo Keidar, Yishai Levy, Alexander Khemlin, Arman Radan, Andrew P Levy
Journal: Circulation (2007)

Background. Large clinical trials of antioxidant therapy with vitamin E have failed to demonstrate a decrease in cardiovascular events. However, these studies did not address possible benefit to subgroups with increased oxidative stress. Haptoglobin (Hp), a major anti-oxidant protein, is a determinant of cardiovascular events in patients with diabetes mellitus (DM). The Hp gene is polymorphic with two common alleles, 1 and 2. The Hp 2 allelic protein product provides inferior anti-oxidant protection as compared to the Hp 1 allelic product. In a retrospective analysis of HOPE participants with DM and the Hp 2–2 genotype, vitamin E significantly reduced the incidence of myocardial infarction and cardiovascular death. We sought to validate this observation in a prospective trial. Methods and Results. 984 DM individuals with the Hp 2–2 genotype were randomized and treated with either natural source vitamin E (400IU/day) or placebo. The primary composite outcome was non-fatal myocardial infarction, stroke and cardiovascular death. The study was intended to last 4 years with initial evaluation of endpoints scheduled 12 months after enrollment of the first patient. At the initial evaluation, the primary composite outcome was significantly reduced in patients receiving vitamin E compared to placebo (1.0% vs. 3.8%, p=0.004). This was predominately due to a significant decrease in the incidence of non-fatal myocardial infarction (0.2% vs. 2.1%, p=0.004) and led to early termination of the study. Conclusions . Vitamin E supplementation appears to reduce cardiovascular events in individuals with DM and the Hp 2–2 genotype. (ClinicalTrials.gov number NCT00220831 ).
Abstract 94: Comparison of Ultrasound and Compact MRI for the Assessment of Cardiac Function in Mice
Authors: Tonya Coulthard, Jun Wu
Journal: Circulation Research (2014)

Introduction: Ultrasound (US) is a standard for the assessment of cardiovascular function. Pre-clinically, this is due the modality’s translational potential, its high temporal resolution and the absence of infrastructure. Recent advancements in novel high-performance compact MRI has made cardiac MRI a more accessible technique for assessing a variety of pathologies in murine models of CVD while reducing the complexity and costs traditionally associated with superconducting MRI systems. These developments may allow compact MRI to overcome some of the limitations of US meanwhile producing viable solutions for quantification along with new capabilities for cardiovascular biomarker assessment. Hypothesis: This study explores the relative capabilities of novel compact high-performance MRI compared to HFU for phenotypic analysis of mouse models of CVD. Methods: Four normal and one induced myocardial infarct C57BL/6 mice were imaged using both US and MRI. MI mice were prepared by ligation of the left anterior descending artery. In order to assess the ability of each modality to qualitatively and quantitatively characterize cardiac function, CINE loops of long axis and short axis slices were acquired with both systems and analyzed offline. In addition to traditional measures of cardiac function, strain analysis was performed using the HARP method for compact MRI and using speckle tracking for US. Finally, a cardiac MRI method for mapping and measuring infarct extent using gadolinium (Gd) contrast agents is described. Results and Conclusions: Although compact MRI has lower temporal resolution, when compared with US, it still provides many advantages in pre-clinical CVD imaging. In particular, because MRI signal is not attenuated by dense tissue or air, compact MRI can successfully generate artefact-free imaging of pathologies difficult or impossible to image with US, such as clearly visualizing and quantifying endo and epicardial borders. It also provides a whole body image and a “whole heart” image, making pre-clinical CV imaging easier for biologists and helping to reduce inter-operator variability. Finally, high sensitivity to Gd-based contrast agent with compact MRI enable new applications such as infarct quantification.