tbuckley/cabot-search huggingface dataset:
Correlation between deletion of the CDKN2 gene and tyrosine kinase inhibitor resistance in adult Philadelphia chromosome-positive acute lymphoblastic leukemia
Authors: Na Xu, Yu-ling Li, Xuan Li, Xuan Zhou, Rui Cao, Huan Li, Lin Li, Zi-yuan Lu, Ji-xian Huang, Zhi-ping Fan, Fen Huang, Hong-sheng Zhou, Song Zhang, Zhi Liu, Hong-qian Zhu, Qi-fa Liu, Xiao-li Liu
Journal: Journal of Hematology & Oncology (2016)

Frequency relapses are common in Philadelphia chromosome-positive (Ph-positive) acute lymphoblastic leukemia (ALL) following tyrosine kinase inhibitors (TKIs). CDKN2A/B is believed to contribute to this chemotherapy resistance. To further investigate the association between CDKN2 status and TKI resistance, the prevalence of CDKN2 deletions and its correlation with a variety of clinical features was assessed in 135 Ph-positive ALL patients using interphase fluorescence in situ hybridization (I-FISH). Results showed that no difference occurred between patients with CDKN2 deletion (44/135) and wild-type patients in sex, age, and complete remission (CR) rate following induction chemotherapy combined with tyrosine kinase inhibitors (TKIs). However, CDKN2 deletion carriers demonstrated higher white blood cell (WBC) count, enhanced rates of hepatosplenomegaly (P = 0.006), and upregulation of CD20 expression (P = 0.001). Moreover, deletions of CDKN2 resulted in lower rates of complete molecular response (undetectable BCR/ABL), increased cumulative incidence of relapse, short overall survival (OS), and disease-free survival (DFS) time (P < 0.05) even though these patients received chemotherapy plus TKIs followed by allogenic hematopoietic stem cell transplantation (Allo-HSCT). In the case of 44 patients who presented with CDKN2 deletion, 18 patients were treated with dasatinib treatment, and another 26 patients were treated with imatinib therapy, and our study found that there were no differences associated with OS (P = 0.508) and DFS (P = 0.555) between the two groups. CDKN2 deletion is frequently acquired during Ph-positive ALL progression and serves as a poor prognostic marker of long-term outcome in Ph-positive ALL patients with CDKN2 deletion even after the second-generation tyrosine kinase inhibitor treatment.
Effects of Vesnarinone on Morbidity and Mortality in Patients with Heart Failure
Authors: Arthur M. Feldman, Michael R. Bristow, William W. Parmley, Peter E. Carson, Carl J. Pepine, Edward M. Gilbert, John E. Strobeck, Grady H. Hendrix, Eric R. Powers, Raymond P. Bain, B.G. White
Journal: New England Journal of Medicine (1993)

Inotropic therapy, other than with digitalis glycosides, has had limited success in patients with chronic congestive heart failure. We investigated whether vesnarinone, a new positive inotropic agent, reduces morbidity and mortality and improves the quality of life of patients with symptomatic heart failure.
Testicular Function after Orchiopexy for Unilaterally Undescended Testis
Authors: Larry I. Lipshultz, Raul Caminos-Torres, Carol S. Greenspan, Peter J. Snyder
Journal: New England Journal of Medicine (1976)

Testicular function was determined in 29 men, 21 to 35 years old, who had undergone orchiopexy for unilaterally undescended testis at four to 12 years of age. Serum testosterone and dialyzable testosterone concentrations of these men were not significantly different from those of a control group of 30 normal men, and their basal serum luteinizing hormone concentrations and serum luteinizing hormone responses to synthetic gonadotropin-releasing hormone were only slightly higher than those of the normal men. The mean sperm density of the patients, however, was only one third of that of the normal men (p less than 0.001). The mean serum follicle stimulating hormone response ro gonadotropin-releasing hormone of the patients was doubled that of the normal men (p less than 0.001). The data indicate that spermatogenesis may be abnormal after orchipexy, and suggest that men with unilaterally undescended testis may have bilateral testicular abnormality.
Comparison between endoscopic mucosal resection and hot snare resection of large nonpedunculated colorectal polyps: a randomized trial
Authors: Akira Horiuchi, Toshiyuki Makino, Masashi Kajiyama, Naoki Tanaka, Kenji Sano, David Graham
Journal: Endoscopy (2016)

<b>Background and study aims:</b> It is unclear whether endoscopic mucosal resection (EMR) or hot snare resection is better for resecting large nonpedunculated polyps. The aim of this study was to determine a cutoff size of nonpedunculated neoplastic colorectal polyps at which the risk of incomplete resection differed between EMR and hot snare resection. <b>Patients and methods:</b> Patients with nonpedunculated neoplastic polyps (10 – 25 mm in diameter) were randomly assigned to undergo endoscopic resection using EMR (52 patients with 63 polyps) or hot snare resection (52 patients with 62 polyps). EMR included submucosal injection of saline before resection. The primary outcome measure was the proportion with complete polyp resection determined by histopathology. The secondary outcome was total procedure time. <b>Results:</b> Patient characteristics were similar between groups. EMR achieved complete resection more frequently than hot snare resection (89 % vs. 73 %; <i>P</i> = 0.02), particularly for polyps ≥ 20 mm (75 % [9 /12] vs. 18 % [2 /11]; <i>P</i> = 0.006). A complete resection rate of > 90 % was achieved for polyps of size < 19 mm with EMR, and for polyps of size ≤ 14 mm with hot snare resection. In multivariate analysis, incomplete resection was associated with hot snare resection (odds ratio [OR] 2.8, 95 % confidence interval (95 %CI) 1.0 – 8.3; <i>P</i> = 0.04) and polyp size ≥ 15 mm (OR 4.0, 95 %CI 1.3 – 14; <i>P</i> = 0.01). Total procedure time was shorter with hot snare resection than with EMR (mean 14.8 min vs. 17.2 min; <i>P</i> < 0.001). <b>Conclusions:</b> EMR and hot snare resection appear to achieve similar complete resection rates for polyps up to 14 mm; however, EMR may be superior for larger polyps, particularly for those ≥ 20 mm. Registered at Clinicaltrials.gov: NCT 01950117
Problems in the Distribution of Medical Care
Authors: Dean A. Clark
Journal: New England Journal of Medicine (1946)

IT IS no accident that the Harvard Medical School has decided to hold these lectures on medical sociology. Never before has there been such widespread interest and activity in the social aspects of medicine among all groups of people — not only medical students and practicing physicians but farmers, members of labor organizations, businessmen and government officials. Ten years ago it would not have occurred to anyone to have such a lecture series, but today it seems the most natural thing imaginable.Indeed, the question of how better to distribute medical service is constantly present. Among groups of physicians, for . . .
Clonal Origin of Bladder Cancer
Authors: David Sidransky, Philip Frost, Andy Von Eschenbach, Ryoichi Oyasu, Antonette C. Preisinger, Bert Vogelstein
Journal: New England Journal of Medicine (1992)

Patients with cancer of the urinary bladder often present with metachronous tumors, appearing at different times and at different sites in the bladder. This observation has been attributed to a "field defect" in the bladder that allows the independent transformation of epithelial cells at a number of sites. We tested this hypothesis using molecular genetic techniques.We examined 13 tumors from cystectomy specimens from four women, using a method that analyzes the pattern of X-chromosome inactivation to determine whether the tumors were derived from the same precursor cell. In addition, we analyzed allelic loss on autosomes to determine whether different tumors had the same genetic alterations. The alterations evaluated included the loss of chromosome 9q sequences (commonly found in superficial bladder tumors) and the loss of 17p and 18q sequences (usually found only in advanced tumors).For each patient studied, all the tumors had inactivation of the same X chromosome, whereas normal bladder mucosa cells had random patterns of inactivation. Moreover, each tumor that could be evaluated from a given patient had lost the same allele on chromosome 9q, suggesting that the loss of this allele preceded the spread of neoplastic cells elsewhere in the bladder. The losses of chromosome 17p and 18q alleles, which are late events in tumor progression, were not common to different tumors from the same patient.A number of bladder tumors can arise from the uncontrolled spread of a single transformed cell. These tumors can then grow independently with variable subsequent genetic alterations.
123P: Impact of the primary tumor metabolic volume (PT-MV) changes in the course of multimodality treatment on overall survival in patients with locally-advanced non-small cell lung cancer
Authors: O. Roengvoraphoi, C. Wijaya, C. Eze, W. Fendler, S. Gerum, C. Belka, F. Manapov
Journal: Journal of Thoracic Oncology (2016)
The Atypical-Mole Syndrome and Predisposition to Melanoma
Authors: Rachel C. Wachsmuth, Mark Harland, Julia A. Newton Bishop
Journal: New England Journal of Medicine (1998)

To the Editor: Abnormal melanocytic nevi are a potent risk factor for sporadic melanoma. In persons with a family history of melanoma, the presence of this phenotype is commonly used to identify ca...
A phase II multicenter, double-blind, randomized trial to compare anastrozole plus gefinitib with anastrozole plus placebo in postmenopausal women with hormone receptor-positive (HR+) metastatic breast cancer (MBC)
Authors: M. Cristofanilli, V. Valero, A. Mangalik, I. Rabinowitz, F. P. Arena, J. F. Kroener, E. Curcio, C. Watkins, P. Magill
Journal: Journal of Clinical Oncology (2008)

1012 Background: Preclinical data provide evidence that suggests crosstalk between growth factor receptor pathways and the estrogen receptor (ER). Inhibition of both epidermal growth factor receptor and ER signalling may thus be a potential intervention to overcome hormonal resistance. We performed a phase II study to evaluate efficacy and tolerability of anastrozole (Arimidex) plus gefitinib (IRESSA) [A+G] vs. anastrozole plus placebo [A+P] for treatment of newly diagnosed HR+ MBC in postmenopausal women. Methods: A total of 94 women with newly diagnosed HR+ MBC were randomized (1:1) (one woman died prior to treatment) to receive anastrozole 1 mg/day and either gefitinib 250 mg/day or placebo (50 to A+P; 43 to A+G). Hormone receptor status was reviewed at a central laboratory. Primary endpoint was progression-free survival (PFS) and secondary endpoints included objective response rate (RECIST criteria) and clinical benefit rate (CBR; defined as objective response or stable disease ≥24 weeks), overall survival, safety and tolerability. Enrollment was stopped early due to slow recruitment and hence limited statistical analyses were performed. Results: A marked PFS advantage was seen for A+G over A+P (hazard ratio [A+G:A+P] 0.55, 95% CI 0.32–0.94, median 14.5 m vs 8.2 m). A numerical advantage in CBR was seen for A+G vs. A+P. Safety and tolerability profiles showed no unexpected findings. Treatment-related adverse events (AE) were seen in 79% of patients in the A+G arm vs. 38% in the A+P arm and were mostly mild. Two patients in the A+G arm and 1 patient in the A+P arm experienced an AE with outcome of death; none were considered treatment related. Conclusions: Anastrozole plus gefitinib was well tolerated and associated with a marked advantage in PFS vs. anastrozole plus placebo in postmenopausal women with newly diagnosed HR+ MBC. The data suggests the need for further investigation of this combination. Anastrozole plus gefitinib (n = 43) Anastrozole plus placebo (n = 50) Complete response (CR), n (%) 1 (2) 1 (2) Partial response (PR), n (%) 0 (0) 5 (10) Stable disease ≥ 24 weeks (SD), n (%) 20 (47) 11 (22) Clinical benefit rate (CR+PR+SD), n (%) 21 (49) 17 (34) 95% CI for clinical benefit rate 33–65 21–49 Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration AstraZeneca AstraZeneca AstraZeneca
A phase I study of clofarabine in combination with cyclophosphamide and etoposide: A new regimen in pediatric patients with refractory or relapsed acute leukemia
Authors: N. Hijiya, J. Franklin, M. Rytting, T. Cooper, R. Chu, E. Barry, C. McCarthy, R. Abichandani, W. Carroll
Journal: Journal of Clinical Oncology (2007)

9529 Background: Clofarabine is a promising new agent in the treatment of childhood leukemia as evidenced by single agent activity in previous phase I and II studies. We conducted a pilot phase I study of clofarabine used in combination with cyclophosphamide and etoposide to determine the maximum tolerated dose (MTD) and dose limiting toxicities (DLT). Methods: Patients between 1 and 21 years old with relapsed or refractory acute lymphoblastic leukemia (ALL) and acute myelogenous leukemia (AML) were enrolled. A standard 3+3 design was followed to determine the safe dose when used in combination. All drugs were administered by IV infusion daily for 5 consecutive days in induction and 4 days in consolidation. Patients received up to 2 induction cycles depending on the response, followed by consolidation cycles (maximum of 8 total cycles). The initial doses (cohort 1) were as follows: clofarabine: 20 mg/m 2 /day, etoposide 75 mg/m 2 /day and cyclophosphamide 340 mg/m 2 /day. Once etoposide and cyclophosphamide were escalated to their target dose (100 mg/m 2 /day and 440 mg/m 2 /day respectively in cohort 3), clofarabine was then increased to 30 mg/m 2 /day in cohorts 4 and would be increased to 40 mg/m 2 /day in cohort 5. Results: Thirteen patients (10 ALL; 3 AML) were enrolled in the first 4 dose cohorts to this date. The median number of prior regimens was 2. Response data (based on investigator assessment) are available for the first 8 patients: 6 patients (including 1 patient with AML) achieved either complete remission (CR) or complete remission without platelet recovery (CRp), for an overall response rate of 75%. Four patients proceeded to HSCT. One patient in cohort 4 experienced a DLT which resolved (grade 3 elevation of lipase) and possible veno-occlusive disease leading to cohort expansion. Common toxicities noted include febrile neutropenia and fever. Conclusions: The phase I study is ongoing until determination of MTD for this combination but these early results indicate that this combination shows significant activity in children with refractory or relapsed acute leukemias and is well-tolerated. No significant financial relationships to disclose.
The Effects of Bis-Trimethylammonium Decane Diiodide and Dibromide on Neuromuscular Function and on Induced Convulsions in Man
Authors: David Grob, Duncan A. Holaday, A. McGehee Harvey
Journal: New England Journal of Medicine (1949)

BIS-TRIMETHYLAMMONIUM decane diiodide (C10 diiodide) has been found to be a potent agent that blocks neuromuscular transmission in animals1 , 2 and in man.3 , 4 As predicted by Paton and Zaimis2 C10 has proved to be a useful substitute for d-tubocurarine in the production of skeletal-muscle relaxation for certain clinical purposes. This communication describes the results of the administration of C10 to normal subjects and prior to electrically induced convulsions.C10 is a white crystalline substance easily prepared in pure form. It is freely soluble in water and can be sterilized by heat without any deterioration. It is miscible . . .
Natural history and management of esophagogastric varices in chronic noncirrhotic, nontumoral portal vein thrombosis
Authors: Carlos Noronha Ferreira, Susana Seijo, Aurelie Plessier, Gilberto Silva‐Junior, Fanny Turon, Pierre‐Emmanuel Rautou, Anna Baiges, Christophe Bureau, Jaime Bosch, Virginia Hernández‐Gea, Dominique Valla, Juan‐Carlos García‐Pagan
Journal: Hepatology (2016)

In patients with chronic noncirrhotic, nontumoral portal vein thrombosis (PVT), the usually recommended strategy for endoscopic screening and management of varices is the same as in cirrhosis. However, the efficacy of this policy in patients with PVT is unknown. We assessed the course of gastroesophageal varices in a large cohort of patients with chronic PVT. Patients prospectively registered in two referral centers for vascular liver disorders were eligible for the study. Endpoints were development and growth of varices and the incidence and outcome of portal hypertension‐related bleeding. Included were 178 patients with chronic PVT. Median follow‐up was 49 (1‐598) months. Variceal bleeding was the initial manifestation in 27 (15%) patients. Initial endoscopy in the remaining 151 patients showed no varices in 52 (34%), small esophageal varices in 28 (19%), large esophageal varices (LEVs) in 60 (40%), and gastric varices without LEVs in 11 (7%). Ascites and splenomegaly were independent predictors for the presence of varices. In patients without varices, the probability of developing them was 2%, 22%, and 22% at 1, 3, and 5 years, respectively. In those with small esophageal varices, growth to LEVs was observed in 13%, 40%, and 54% at 1, 3, and 5 years, respectively. In patients with LEVs on primary prophylaxis, probability of bleeding was 9%, 20%, and 32% at 1, 3, and 5 years, respectively. Nine (5%) patients died after a median 51 (8‐280) months, only one due to variceal bleeding. Conclusions : The course of varices in chronic noncirrhotic, nontumoral PVT appears to be similar to that in cirrhosis; using the same therapeutic approach as for cirrhosis is associated with a low risk of bleeding and death. (H epatology 2016;63:1640‐1650)
In Memoriam: Brigid Leventhal
Authors: Martin D. Abeloff, Curt I. Civin, Steven Piantadosi
Journal: Journal of Clinical Oncology (1994)

Article Tools In Memorium Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1994.12.6.1111 Journal of Clinical Oncology - published online before print September 21, 2016 In Memoriam: Brigid Leventhal Martin D. AbeloffxMartin D. AbeloffSearch for articles by this author , Curt I. CivinxCurt I. CivinSearch for articles by this author , Steven PiantadosixSteven PiantadosiSearch for articles by this author Show More The Johns Hopkins Oncology Center Baltimore, MD https://doi.org/10.1200/JCO.1994.12.6.1111 PDF "In Memoriam: Brigid Leventhal." Journal of Clinical Oncology, 12(6), pp. 1111–1112© 1994 by American Society of Clinical Oncology
Epithelial to mesenchymal transition by TGF-beta induced cancer stem-like properties in primary colorectal cancer
Authors: Michitaka Nakano, Hiroshi Ariyama, Shingo Tamura, Taichi Isobe, Kohta Miyawaki, Yuta Okumura, Hitoshi Kusaba, Takashi Ueki, Eishi Baba, Koichi Akashi
Journal: Annals of Oncology (2015)
Thyroglobulin Antibodies in Multiple Thyroid Diseases
Authors: Robert M. Blizzard, George J. Hamwi, Thomas G. Skillman, Warren E. Wheeler
Journal: New England Journal of Medicine (1959)

AUTOIMMUNIZATION to autogenously released thyroglobulin has recently been implicated as a causative factor in Hashimoto's thyroiditis and spontaneous myxedema. Circulating thyroglobulin antibodies have been demonstrated in the serum of patients with these diseases and serves as a basis for this hypothesis.1 2 3 4 5 Animal studies further support this thesis, for homologous thyroglobulin injection produces antibodies and lymphocytic destruction of thyroid tissue.3 , 6 7 8 Diseases other than thyroiditis and spontaneous myxedema seemed likely to offer opportunity for extrathyroidal circulation of thyroglobulin, and hence antibody formation. Accordingly we studied subjects with and without thyroid disease, determining the prevalence of circulating thyroglobulin antibodies in each group. The . . .
Screening and Informed Consent
Authors: J M Lee
Journal: New England Journal of Medicine (1993)

Before they participate in a screening program, patients must give informed consent. To do so, they need to understand the risk of a false positive result and the invasive procedures that may follow it. Rather than merely transmit expert recommendations, physicians should match the appropriate level of screening with each patient's unique attitude toward the risks of disease and the risks associated with the screening procedures.But to inform patients, physicians themselves must be informed. Stange et al. recently discovered that family physicians are more interventionist in their screening than the U.S. Preventive Services Task Force recommends1. The study . . .
Mother-to-Infant Transmission of HIV
Authors: Howard Minkoff, Tamar A. Bauer
Journal: New England Journal of Medicine (1997)

To the Editor: In her editorial (Nov. 28 issue), Dr. Wilfert1 presciently notes that research on mother-to-child transmission of the human immunodeficiency virus (HIV) has advanced to the point where the prevention of a large percentage of neonatal infections is now a realistic possibility. She also points out that through legislative and outreach initiatives, the government has recognized the need to translate the success in research settings into clinical practice. Unfortunately, while the government struggles to overcome barriers to the implementation of AIDS Clinical Trials Group Protocol 076, its enactment of welfare reform threatens to condemn future American neonates to . . .
Stomach Perforation by a Blister-Wrapped Capsule
Authors: Agnès Lurton, Jean Ntiruhungwa, Huguette Saillant, Jacqueline Surugue
Journal: New England Journal of Medicine (1996)

To the Editor: We describe a 63-year-old woman whose stomach was perforated after she ingested a blister-wrapped capsule while hospitalized for treatment of depression. She was treated with oral lormetazepam (Noctamid), paroxetine (Deroxat), buspirone (Buspar), and cyamemazine (Tercian) and with ranitidine (Azantac) for a previous duodenal ulcer. On the third hospital day she had vomiting, headache, and abdominal pain. She was afebrile. Hypertension (blood pressure, 250/120 mm Hg) and mild tachycardia (100 beats per minute) were detected. She was admitted to a cardiology service. Nifedipine (Adalate) was prescribed to treat the hypertension. The next day, she fainted twice in one . . .
The Risk Of BK Virus Haemorrhagic Cystitis After Allogeneic Hematopoietic Stem Cell Transplantation Is Increased With Myeloablative Conditioning, CMV Viremia and Acute Gvhd
Authors: Nada Hamad, Frcpa, Mohamed Shanavas, Fotios V. Michelis, Vikas Gupta, John Kuruvilla, Hans A. Messner, Jeffrey H. Lipton, Dennis Kim
Journal: Blood (2013)
Linking general health and mental health systems of care: conceptual models of implementation
Authors: H A Pincus
Journal: American Journal of Psychiatry (1980)

Recent political and scientific developments have contributed to a growing recognition of the need to move mental health into the mainstream of general health service delivery. It is important to systematically approach the development of a range of conceptual models that could link these two systems. The author defines such linkage relationships in terms of three basic elements: contractual, functional, and educational. He describes six models and presents specific examples of each. He suggests the factors that should be examined to select the most effective model for a given context and presents future research needs in the field.
The Temporary Thrombotic State
Authors: Stanford Wessler, Sidney Cohen, Felix G. Fleischner
Journal: New England Journal of Medicine (1956)

NOT infrequently the physician is confronted with a patient in whom massive recurrent pulmonary infarction occurs without an evident source for emboli or a recognized cause for local thrombosis. The management of this syndrome and its differentiation from other conditions, particularly pneumonia, is made difficult by the lack of a reliable clinical or laboratory test for the incipient or actively thrombotic state. It is the purpose of this report to present a concept — "the temporary thrombotic state" — that has proved helpful in the treatment of recurrent thromboembolism and pulmonary infarction; secondly, to summarize briefly the important diagnostic clinical, . . .