tbuckley/cabot-search huggingface dataset:
Phase II study of bevacizumab and etoposide in patients with recurrent malignant glioma
Authors: J. N. Rich, A. Desjardins, S. Sathornsumetee, J. J. Vredenburgh, J. A. Quinn, S. Gururangan, A. H. Friedman, H. S. Friedman, D. A. Reardon
Journal: Journal of Clinical Oncology (2008)

2022 Background: Bevacizumab (BV), a neutralizing monoclonal antibody to vascular endothelial growth factor (VEGF), has demonstrated remarkable radiographic response and promising survival benefit in combination with irinotecan in patients with recurrent glioblastoma multiforme (GBM). In this study, we evaluate the efficacy of bevacizumab when combined with etoposide, a topoisomerase inhibitor, in patients with recurrent malignant glioma (MG). Methods: Recurrent patients with no more than three prior episodes of recurrence are eligible, while those with prior BV treatment or prior intracranial hemorrhage are excluded. The primary outcome measure is 6 month progression-free survival. BV is dosed at 10 mg/kg intravenously every other week. Etoposide is orally administered daily (50 mg/m2) for days 1–21 of each 28-day cycle. Results: Fifty-three patients have enrolled including 27 with GBM, 16 with anaplastic astrocytoma, 8 with anaplastic oligodendroglioma and 2 with malignant pleomorphic xanthoastrocytoma. The median age is 48.7 years (range, 25.2–71.2), and patients have had a median of 2 prior progressions (range, 1–3) and 2 prior therapeutic agents (range, 1–7). The most common significant toxicities include neutropenia (grade 3, n=8; grade 4, n=1), thrombosis (grade 3, n=2, grade 4, n=2; grade 5, n=1), hyponatremia (grade 3, n=3) and infection (grade 3, n=2). Two patients developed grade 1 intracranial hemorrhage. Best responses to date include complete response (n=1; 2%); partial response (n=9; 17%), stable disease (n=34; 60%); progressive disease (n=3; 6%). Six patients are too early to assess. Conclusions: Combination of bevacizumab and etoposide is well tolerated in recurrent MG patients and is associated with encouraging radiographic response. Further accrual, treatment and follow-up are ongoing. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Genentech™ BioOncology, Schering-Plough Genentech™ BioOncology Genentech™ BioOncology, Schering-Plough Genentech™ BioOncology
Where Exactly Does Ponatinib Fit in Chronic Myelogenous Leukemia?
Authors: Ellin Berman
Journal: Journal of the National Comprehensive Cancer Network (2014)

Ponatinib holds a unique place in the spectrum of drugs in use for the treatment of chronic myelogenous leukemia. It is perhaps the most active tyrosine kinase inhibitor (TKI) among those currently licensed; 51% of patients resistant to or intolerant of second-generation TKIs experienced a major cytogenetic response and 70% of patients with the highly resistant T315I BCR-ABL1 mutation experienced a major cytogenetic response. However, 1 year after its accelerated approval by the FDA, and midway through its phase III pivotal trial, a high number of vascular occlusive events began to be reported. The FDA put a partial clinical hold on the drug and the phase III trial was halted. Dose-reduction recommendations were made, and the drug is now used in patients for whom no alternative TKI is available and those who have the T315I mutation. Currently, the substantial and durable responses that this drug provides are difficult to balance against the late-in-course vascular occlusive events. The hope is that ongoing research into the mechanism of presumed endothelial damage will provide a better understanding of how to position this drug for optimal use.
Familial Hyperglucagonemia — An Autosomal Dominant Disorder
Authors: Guenther Boden, Oliver E. Owen
Journal: New England Journal of Medicine (1977)

Basal Immunoreactive glucagon was elevated in four of nine asymptomatic relatives of a patient with glucagonoma. Immunoreactive glucagon remained elevated throughout 22 to 25 hours of continuous observation. Glucagon responses to intravenous glucose and arginine or mixed meals (or both) were abnormal, whereas glucose and insulin responses were normal. Gel filtration of plasma revealed that over 85 per cent of the four relatives' immunoreactive glucagon had a molecular weight of >9000 daltons whereas that of 70 per cent of the patients with glucagonoma had a molecular weight of 3500 daltons, with the remainder eluting in the area of 9000 daltons. Pancreatic angiograms and hepatic scintiscans were normal in all four relatives. The data suggest an autosomal dominant transmission of hyperglucagonemia in this family. Immunoreactive glucagon with a molecular weight of 3500 or 9000 daltons appears to be required for the development of the clinical glucagonoma syndrome. (N Engl J Med 296:534–538, 1977
Case 24-1996
Authors: Andrew G. Villanueva, Eugene J. Mark
Journal: New England Journal of Medicine (1996)

Presentation of CaseA 54-year-old woman was admitted to the hospital because of radiologic evidence of pulmonary abnormalities.The patient had been well until one year earlier, when she began to have a dry cough and mild exertional dyspnea. The cough became incessant, keeping her awake at night.Six and a half months before admission, she was treated at another hospital for pneumonia. Radiographs of the chest (Figure 1) showed bilateral air-space opacities, especially in the left lower lobe, and hilar enlargement consistent with lymphadenopathy. No pleural effusion was evident, and the heart appeared normal. Her condition improved, and she . . .
Augmentation of the Adoptive Transfer of Specific Tumor Immunity by Nonspecifically Immunized Macrophages2
Authors: Stephan Ariyan, Richard K. Gershon
Journal: JNCI Journal of the National Cancer Institute (1973)

Journal Article Augmentation of the Adoptive Transfer of Specific Tumor Immunity by Nonspecifically Immunized Macrophages Get access Stephan Ariyan, M.D., Stephan Ariyan, M.D. Search for other works by this author on: Oxford Academic PubMed Google Scholar Richard K. Gershon, M.D. Richard K. Gershon, M.D. Departments of Surgery and Pathology, Yale University School of Medicine, New Haven, Conn. 06510 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 51, Issue 4, October 1973, Pages 1145–1148, https://doi.org/10.1093/jnci/51.4.1145 Published: 01 October 1973 Article history Received: 13 February 1973 Accepted: 07 June 1973 Published: 01 October 1973
A novel mutant-enriched liquidchip for detection of circulating EGFR mutations in advanced non-small cell lung cancer patients
Authors: S. Lu, H. Yang, X. Ye, X. Xu, Z. Li, L. Ren, Y. Xu, J. Xu
Journal: Journal of Clinical Oncology (2009)

e14526 Background: We developed a novel technology, Mutant-enriched liquidchip (MEL), which integrates the sensitive mutant enriched PCR and quantitative high throughput liquidchip (suspension array), to detect circulating EGFR mutations (Exon 19 deletion and exon 21 L858R mutation) in patients with advanced non-small cell lung cancer (NSCLC). Methods: To enrich mutant EGFR, a unique restriction site is introduced into the mutation alleles so that the wild type sequence can be selectively removed by restriction digestion, and the undigested mutated DNA is amplified by PCR. The product is then hybridized to complementary probes (including 15 types of exon 19 deletion and exon 21 L858R mutation) which had been conjugated to beads coding with different fluorescent dye, followed by measuring through Luminex 200 system. Plasmid DNA mixture with different EGFR genotypes was applied to determine the sensitivity and accuracy of MEL. Afterwards, the MEL was validated in 49 patients whose EGFR genotypes of tissue specimen had been tested with direct sequencing The circulating genomic DNA was obtained from serum sample of other 201 Chinese stage IIIB or IV NSCLC patients without EGFR-TKI administration, and the EGFR mutation status was analyzed by using of MEL. Results: The results shows that MEL is capable of detecting as few as 20 copies of mutant EGFR alleles with a sensitivity limit of at least mutant/wild-type ratio of 0.1%. It also shows that MEL can not only confirm EGFR mutations status in tissue specimens already known by direct sequencing (13/49), but also detect mutations in some of those showing wild type by sequencing (16/49). Overall, 54% of patients had circulating EGFR mutation. 34% of patients had an exon 19 deletion and 29.6% had L858R. 63.1% of mutations were found in females and 67.6% in never-smokers. Conclusions: This novel MEL method allows for highly sensitive and reproducible detection of human somatic mutations in heterogeneous specimens, and could be applicable to test EGFR mutations non-invasively in advanced NSCLC patients for predicting response to targeted therapy. No significant financial relationships to disclose.
Oxygen desaturation in 6-min walk test is a risk factor for adverse outcomes in COPD
Authors: Marie Waatevik, Ane Johannessen, Francisco Gomez Real, Marianne Aanerud, Jon Andrew Hardie, Per Sigvald Bakke, Tomas Mikal Lind Eagan
Journal: European Respiratory Journal (2016)

The 6-min walk test (6MWT) is an exercise test that measures functional status in chronic obstructive pulmonary disease (COPD) patients and provides information on oxygen desaturation. We investigated oxygen desaturation during 6MWT as a risk factor for important COPD outcomes: mortality, frequency of exacerbations, decline in lung function and decline in lean body mass. 433 COPD patients were included in the Bergen COPD Cohort Study 2006–2009, and followed-up for 3 years. Patients were characterised using spirometry, bioelectrical impedance measurements, Charlson comorbidity score, exacerbation history, smoking and arterial blood gases. 370 patients completed the 6MWT at the baseline of the study. Information on all-cause mortality was collected in 2011. Patients who experienced oxygen desaturation during the 6MWT had an approximately twofold increased risk of death (hazard ratio 2.4, 95% CI 1.2–5.1), a 50% increased risk for experiencing later COPD exacerbations (incidence rate ratio 1.6, 95% CI 1.1–2.2), double the yearly rate of decline in both forced vital capacity and forced expiratory volume in 1 s (3.2% and 1.7% versus 1.7% and 0.9%, respectively) and manifold increased yearly rate of loss of lean body mass (0.18 kg·m −2 versus 0.03 kg·m −2 among those who did not desaturate). Desaturating COPD patients had a significantly worse prognosis than non-desaturating COPD patients, for multiple important disease outcomes.
Fraud in Biomedical Research
Authors: Marcia Angell, Arnold S. Relman
Journal: New England Journal of Medicine (1988)

IN April the U.S. Congress held two sets of hearings to investigate the extent of fraud in biomedical research and the response of the scientific community to it. Clearly, some members of Congress believe that there is a good deal of fraud and, more important, that the scientific community's response to it has been inadequate. There have been suggestions that the biomedical-research enterprise requires some sort of policing by the government, since we have seemed unwilling or unable to police ourselves. Legislators have even suggested that a separate oversight agency be established for that purpose and that researchers thought guilty . . .
Endocardial Fibrosis Associated with Fenfluramine–Phentermine
Authors: Robert E. Fowles, Tom V. Cloward, Robert L. Yowell
Journal: New England Journal of Medicine (1998)

To the Editor: It has been previously reported that valvular heart disease may be associated with the use of anorectic drugs.1 We report a case of restrictive cardiomyopathy due to endocardial fibrosis after short-term use of fenfluramine–phentermine. A 35-year-old woman was hospitalized for congestive heart failure. Five months earlier she had begun taking 10 mg of fenfluramine three times a day and 15 mg of phentermine once a day, prescribed at her request because of obesity (height, 1.77 m; weight, 94.5 kg; body-mass index [calculated as the weight in kilograms divided by the square of the height in meters], 30.3). . . .
Proton Pump Inhibitors and Risk of Incident CKD and Progression to ESRD
Authors: Yan Xie, Benjamin Bowe, Tingting Li, Hong Xian, Sumitra Balasubramanian, Ziyad Al-Aly
Journal: Journal of the American Society of Nephrology (2016)

The association between proton pump inhibitors (PPI) use and risk of acute interstitial nephritis has been described. However, whether exposure to PPI associates with incident CKD, CKD progression, or ESRD is not known. We used Department of Veterans Affairs national databases to build a primary cohort of new users of PPI (n=173,321) and new users of histamine H2-receptor antagonists (H2 blockers; n=20,270) and followed these patients over 5 years to ascertain renal outcomes. In adjusted Cox survival models, the PPI group, compared with the H2 blockers group, had an increased risk of incident eGFR<60 ml/min per 1.73 m2 and of incident CKD (hazard ratio [HR], 1.22; 95% confidence interval [95% CI], 1.18 to 1.26; and HR, 1.28; 95% CI, 1.23 to 1.34, respectively). Patients treated with PPI also had a significantly elevated risk of doubling of serum creatinine level (HR, 1.53; 95% CI, 1.42 to 1.65), of eGFR decline >30% (HR, 1.32; 95% CI, 1.28 to 1.37), and of ESRD (HR, 1.96; 95% CI, 1.21 to 3.18). Furthermore, we detected a graded association between duration of PPI exposure and risk of renal outcomes among those exposed to PPI for 31-90, 91-180, 181-360, and 361-720 days compared with those exposed for ≤30 days. Examination of risk of renal outcomes in 1:1 propensity score-matched cohorts of patients taking H2 blockers versus patients taking PPI and patients taking PPI versus controls yielded consistent results. Our results suggest that PPI exposure associates with increased risk of incident CKD, CKD progression, and ESRD.
Experiences with Curare in Anesthesia
Authors: Sidney C. Wiggin, Philip E. Schultz, Peter Saunders
Journal: New England Journal of Medicine (1947)

THE use of curare in anesthesia has rapidly gained popularity within the past few years. Numerous papers, which agree on its usefulness, have been published since the initial study of Griffith.1 These papers describe different methods of administration, advantages, limitations and possible disadvantages of the drug.2 3 4 5 6 7 8 9 There have also been publications of experimental studies that give further information.10 11 12 13 14 The main purposes of this paper are to consider the indications for curare and its comparison with other agents and to present experience with the use of curare (Intocostrin¶) in 450 cases. The basis of discussion of the results in these cases . . .
What is the choice of treatment for hairy cell leukemia?
Authors: H M Golomb, M J Ratain, J Moormeier
Journal: Journal of Clinical Oncology (1989)

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.1989.7.2.156 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 2783730 What is the choice of treatment for hairy cell leukemia? H M GolombxH M GolombSearch for articles by this author , M J RatainxM J RatainSearch for articles by this author , J MoormeierxJ MoormeierSearch for articles by this author Show More University of Chicago Medical Center, Michael Reese Hospital and Medical Center. https://doi.org/10.1200/JCO.1989.7.2.156 First Page PDF © 1989 by American Society of Clinical Oncology
Treatment of Primary Hyperoxaluria with Calcium Carbimide
Authors: P. M. Zarembski, A. Hodgkinson, M. Cochran
Journal: New England Journal of Medicine (1967)

VARIOUS measures have been proposed to reduce the endogenous production of oxalic acid in patients with primary hyperoxaluria; these include the oral administration of sodium benzoate,1 pyridoxine,2 hydroxymethane sulfonic acid3 and allopurinol.4 Recently, Solomons and his colleagues5 have proposed the use of calcium carbimide on the grounds that this compound would inhibit the enzymic oxidation of glycolaldehyde to glycollic acid and hence the production of oxalic acid (Fig. 1). These authors reported that oxalate excretion was reduced to near normal values during the oral administration of citrated calcium carbimide (25 to 37.5 mg daily) to a patient with primary hyperoxaluria. . . .
Phase II trial of neoadjuvant fixed dose rate (FDR) gemcitabine with capecitabine (GX) combination chemotherapy in locally advanced pancreatic adenocarcinoma (LAPA)
Authors: J. Lee, S. Lee, T. Kim, J. Lee, D. Park, D. Seo, S. Lee, M. Kim, D. Han, S. Kim
Journal: Journal of Clinical Oncology (2009)

e15553 Background: To determine the efficacy and safety of fixed dose rate (FDR) gemcitabine and capecitaibne (GX) combination chemotherapy for locally advanced pancreatic adenocarcinoma Methods: Patients with histologically confirmed LAPA were eligible for this prospective phase II trial. Dynamic pancreas/pelvic CT, MRI and FDG-PET were undertaken to assess the resectability. EUS was also performed as needed basis. ‘Borderline resectable (BR)’ and ‘unresectable (UR)’ criteria developed by our pancreatico-biliary multidisciplinary management team (PBMMT) and NCCN criteria were used. After confirmation of resectability, patients received 3 cycles of FDR gemcitabine 1,250 mg/m 2 on D1 and D8 and capecitabine 950 mg/m 2 from D1-D14 every 3 weeks. Thereafter, staging was repeated and patients underwent surgery if the disease was not unresectable. For patients with R0 resection, additional 6 cycles of GX were administered. For patients with R1 resection, chemoradiotherapy (CRT) (54 Gy over 5 weeks with concurrent 5-FU and leucovorin or capecitabine) followed by FDR-GX was administered. Patients with stable or better response to chemotherapy but assessed unresectable at reassessment received additional chemotherapy up to 9 cycles followed by CRT. Results: Between August 2006 and July 2008, 38 eligible patients (14 with BR and 24 with UR based on NCCN criteria; 29 with BR and 9 with UR based on our PBMMT criteria) entered on this study. The median age was 61 yo (42–76) and 71% had cT4 disease. The response to neoadjuvant chemotherapy was PR in 6 (16%), SD in 26 (68%) and PD in 3 (8%). Metabolic response was achieved in 20 patients (53%) with 2 metabolic CR out of 31 evaluable patients. Grade 3 or worse adverse effects were mainly HFS (n=5) and gastrointestinal (n=3) with no grade 4 in severity. Surgery was performed in 9 patients (24.0%, R0=8, R1=1, 6 in NCCN-BR and 3 in NCCN-UR, 9 in PBMMT-BR) and five patients refused surgery although their diseases seemed not to be unresectable. The median PFS was 9.4 months (95% CI, 8.3–10.4) and estimated median OS was 13.5 months (95% CI, 12.4- 14.5). Conclusions: FDR-GX was effective as neoadjuvnat chemotherapy in LAPA with favorable toxicity profile. No significant financial relationships to disclose.
Diagnostic Imaging in the Evaluation of Suspected Aortic Dissection -- Old Standards and New Directions
Authors: Joaquin E. Cigarroa, Eric M. Isselbacher, Roman W. DeSanctis, Kim A. Eagle
Journal: New England Journal of Medicine (1993)

Acute aortic dissection is a life-threatening condition, and its prompt diagnosis remains essential for successful management. Although early mortality may be as high as 1 percent per hour1 among untreated patients, survival can be improved by the rapid institution of appropriate medical or surgical therapy (or both). The Stanford classification system2 divides aortic dissections anatomically into two types on the basis of location. A dissection in which there is involvement of the ascending aorta, regardless of the site of entry, is defined as type A (this includes De Bakey3 types I and II and is often described as a proximal . . .
Unexpected high rate of early tumor recurrence in patients with HCV-related HCC undergoing interferon-free therapy
Authors: María Reig, Zoe Mariño, Christie Perelló, Mercedes Iñarrairaegui, Andrea Ribeiro, Sabela Lens, Alba Díaz, Ramón Vilana, Anna Darnell, María Varela, Bruno Sangro, José Luis Calleja, Xavier Forns, Jordi Bruix
Journal: Journal of Hepatology (2016)
Effect of Age on the Response of the Left Ventricular Ejection Fraction to Exercise
Authors: Steven Port, Frederick R. Cobb, R. Edward Coleman, Robert H. Jones
Journal: New England Journal of Medicine (1980)

To assess the effects of age on the left ventricular ejection fraction (LVEF), we performed radio nuclide angiocardiography at rest and during upright bicycle exercise in 77 healthy volunteers 20 to 95 years of age. Radionuclide measurements included left ventricular ejection fraction, end-diastolic volume, and regional wall motion. Age did not appear to influence any of these indexes at rest. However, during exercise the ejection fraction was less than 0.60 in 45 per cent of subjects over age 60 as compared with 2 per cent of younger subjects (P<0.0001). In addition, there was a decline in the change in LVEF (exercise LVEF minus rest LVEF) with increase in age (r = -0.71). Wall-motion abnormalities during exercise occurred with increasing frequency in patients who were 50 and older. In the older subjects these age-related changes in ejection fraction during exercise were not associated with differences in end-diastolic volume or blood pressure. (N Engl J Med. 1980; 303:1133–7.)
Treatment with Bivalirudin (Hirulog) as Compared with Heparin during Coronary Angioplasty for Unstable or Postinfarction Angina
Authors: John A. Bittl, John Strony, Jeffrey A. Brinker, Waqar H. Ahmed, Clyde R. Meckel, Bernard R. Chaitman, John Maraganore, Ezra Deutsch, Burt Adelman
Journal: New England Journal of Medicine (1995)

Heparin is often administered during and after coronary angioplasty to prevent closure of the dilated vessel. However, ischemic or hemorrhagic complications occur in 5 to 10 percent of treated patients. We studied whether these complications could be prevented when the direct thrombin inhibitor bivalirudin (Hirulog) was used in place of heparin.We performed a double-blind, randomized trial in 4098 patients undergoing angioplasty for unstable or postinfarction angina. Patients were assigned to receive either heparin or bivalirudin immediately before angioplasty. The primary end point were death in the hospital, myocardial infarction, abrupt vessel closure, or rapid clinical deterioration of cardiac origin.In the total study group, bivalirudin did not significantly reduce the incidence of the primary end point (11.4 percent, vs. 12.2 percent for heparin) but did result in a lower incidence of bleeding (3.8 percent vs. 9.8 percent, P < 0.001). In the prospectively stratified subgroup of 704 patients with postinfarction angina, bivalirudin therapy resulted in a lower incidence of the primary end point (9.1 percent vs. 14.2 percent, P = 0.04) and a lower incidence of bleeding (3.0 percent vs. 11.1 percent, P < 0.001), but in a similar cumulative rate of death, myocardial infarction, and repeated revascularization in the six months after angioplasty (20.5 percent vs. 25.1 percent, P = 0.17).Bivalirudin was at least as effective as high-dose heparin in preventing ischemic complications in patients who underwent angioplasty for unstable angina, and it carried a lower risk of bleeding. Bivalirudin, as compared with heparin, reduced the risk of immediate ischemic complications in patients with postinfarction angina, but this difference was no longer apparent after six months.