tbuckley/cabot-search huggingface dataset:
Vaccines to Prevent Viral Hepatitis
Authors: Stanley M. Lemon, David L. Thomas
Journal: New England Journal of Medicine (1997)

At least five different viruses cause hepatitis in humans. Two — hepatitis A virus (HAV) and hepatitis E virus (HEV) — are nonenveloped RNA viruses that are spread predominantly by fecal–oral transmission and cause acute self-limited disease.1,2 The others — hepatitis B virus (HBV), hepatitis delta virus (HDV), and hepatitis C virus (HCV) — are enveloped viruses with various tendencies to cause persistent infection, chronic hepatitis, and, in the case of HBV and HCV, hepatocellular carcinoma.35 Fecal–oral transmission does not occur with these viruses, because their lipid envelopes preclude the passage of viable virus from the liver through . . .
Pelger–Huët Anomaly of the Leukocytes
Authors: Arthur Klein, Allen E. Hussar, Siegbert Bornstein
Journal: New England Journal of Medicine (1955)

IN 1928, Pelger,1 a Dutch physician and specialist in tuberculosis, examined the blood smear of a tuberculous patient and noted the absence of the usual nuclear segmentation in the granulocytic leukocytes. A large percentage of the cells were stab forms. The rest showed only two segments, and a few showed three segments but none more than three. In spite of this apparent immaturity, the nuclear chromatin was coarse, grouped into irregular clumps and obviously quite mature. In 1931, he had another case, again in a patient with tuberculosis, and thus the condition was first associated with this disease.2 Later in . . .
Genome Wide Association Study (Gwas) for Identification of Single Nucleotide Polymorphisms (Snps) Associated with Individuals Presenting Extreme Phenotypes of Tobacco Induced Non-Small Cell Lung Cancer (Nsclc) Risk
Authors: J.L. Perez-Gracia, M.J. Pajares, M.P. Andueza, G. Pita, J.P. De Torres, C. Casanova, J. Zulueta, A. Gurpide, J.M. Lopez-Picazo, R. Baz Davila, R. Alonso, N. Alvarez, R. Pio, I. Melero, M.F. Sanmamed, A. Agudo, C. Gonzalez, J. Benitez, L. Montuenga, A. Gonzalez-Neira
Journal: Annals of Oncology (2014)
Isolated Hypoaldosteronism in Adults
Authors: Morris Schambelan, Jan R. Stockigt, Edward G. Biglieri
Journal: New England Journal of Medicine (1972)

Abstract To clarify the mechanism causing isolated hypoaldosteronism in adults, we studied six patients with unexplained hyperkalemia. On a normal sodium intake, excretion of tetrahydrodeoxycorticosterone, tetrahydrocorticosterone, and 17-hydroxycorticoids was normal and increased normally with ACTH stimulation. Excretion of metabolites of aldosterone and 18-hydroxycorticosterone was subnormal or barely normal, and aldosterone excretion failed to respond normally to sodium depletion and ACTH. Plasma renin activity (PRA) and concentration were subnormal and failed to increase normally with upright posture and sodium depletion; furosemide increased PRA in only one patient. Restoration of normal serum potassium with cation exchange resin failed to increase PRA in the three patients studied. Plasma renin substrate was normal or slightly elevated. The patients studied differ from patients with Addison's disease and infants with enzymatic defects in aldosterone biosynthesis in whom PRA is increased. The data su...
Chromosome Studies on Patients (in Vivo) and Cells (in Vitro) Treated with Lysergic Acid Diethylamide
Authors: Margaret J. Corey, J. C. Andrews, M.Josephine McLeod, J. Ross MacLean, W. E. Wilby
Journal: New England Journal of Medicine (1970)

In a prospective study of 10 patients given d-lysergic acid diethylamide 25, there was no difference in frequency of chromosome breakage between samples obtained immediately before and 24 hours after treatment. In 11 patients, treated over periods ranging from 24 hours to eight years before sampling, the frequency of chromosomal breaks did not differ from that found in untreated controls. In an in vitro study the frequency of chromosomal breaks was increased in replicate cultures from each of 10 subjects when 1 μg per milliliter of d-lysergic acid diethylamide 25 was added during the last 24 hours of culture. There is no cytogenetic evidence that d-lysergic acid diethylamide 25 given therapeutically produces chromosomal damage. The chromosomal aberrations found after illicit use of the drug remain unexplained.
Are Metformin Doses Used in Murine Cancer Models Clinically Relevant?
Authors: Navdeep S. Chandel, Dania Avizonis, Colleen R. Reczek, Samuel E. Weinberg, Stephan Menz, Roland Neuhaus, Sven Christian, Andrea Haegebarth, Carolyn Algire, Michael Pollak
Journal: Cell Metabolism (2016)
NHS plans sugar tax on food and drink sold in hospitals by 2020
Authors: Gareth Iacobucci
Journal: BMJ (2016)

The NHS in England is to impose its own “sugar tax” on sweetened food and drink sold in hospitals in England, as part of radical new plans to tackle the obesity crisis.

Simon Stevens, chief executive of NHS England, said that the NHS would consult on introducing the charge in hundreds of acute care, mental health, and community health services by 2020 in a bid to improve the health of staff and patients.

The plan would see hospitals and other premises across England charging more for sugary drinks and food sold in cafes and vending machines, in an effort to drive behavioural change among staff, patients, and visitors.

A rolling programme of supplier contract renegotiations will also be …
Case 4-1975
Authors: Boris Senior, Stanley H. Robboy
Journal: New England Journal of Medicine (1975)

Presentation of Case First admission. A two-and-a-half-year-old girl was admitted to the hospital because of sexual precocity.She was born at 42 weeks of gestation, with a birth weight of 2.4 kg. Café-au-lait spots were noted at birth. Vaginal spotting of blood was observed at six months of age and irregularly during the succeeding year, and breast enlargement was noticed at 12 months of age. During the year before admission vaginal bleeding occurred almost every month for two or three days, and there was progressive enlargement of the breasts. Two months before entry the luteinizing hormone (LH) was 1.4 . . .
Brentuximab Vedotin Plus Bendamustine: A Highly Active Salvage Treatment Regimen for Patients with Relapsed or Refractory Hodgkin Lymphoma
Authors: Ann S. LaCasce, Gregory Bociek, Ahmed Sawas, Paolo F. Caimi, Edward Agura, Jeffrey Matous, Stephen Ansell, Howland Crosswell, Miguel Islas-Ohlmayer, Caroline Behler, Eric Cheung, Andres Forero-Torres, Julie Vose, Owen A. O'Connor, Neil Josephson, Ranjana Advani
Journal: Blood (2015)
Abstract 19604: Global Longitudinal Strain in Different Right Ventricular Walls Using Alternate Right Ventricular Apical Views: Validation and Establishment of Normal Values in Children
Authors: Amanda Hauck, Bruce Landeck, Cedric Manlhiot, Andreea Dragulescu, Mark Friedberg, Adel Younoszai, Luc Mertens
Journal: Circulation (2014)

Introduction: Right ventricular (RV) function is an important prognostic factor in congenital and acquired heart disease. Quantitative measures of RV lateral wall function obtained from the apical 4 chamber (A4C) view are used to extrapolate global RV function. We aimed to use non-standard views of the RV to establish normal global longitudinal strain (GLS) in additional walls of the RV in healthy children to allow a more comprehensive RV assessment. Methods: A total of 88 healthy children (age 5-17 years) were recruited in a prospective, multi-institutional study. Images were acquired with the Vivid E-9 with post-processing performed using EchoPac (GE Ultrasound). RV views similar to LV apical 2 chamber (A2C) and apical 3 chamber (A3C) views were performed with care taken to exclude septal myocardium. GLS in the RV lateral (A4C), inferior (A2C) and posterior (A3C) walls were averaged over 3 cardiac cycles and calculated if at least 2 of 3 wall segments tracked. A global RV strain assessment was calculated by averaging the 3 available walls. Intraobserver variability was assessed. Results: GLS was measurable in 67% of lateral, 75% of inferior and 45% of posterior walls analyzed. The normal ranges for GLS across the pediatric age group are shown in figure 1. Overall, we observed a decrease in lateral wall GLS with increasing age; inferior and posterior GLS changed less with age. Average global RV strain was -31.3% +/- 2.4%. Intraobserver reliability in 15 patients showed coefficient of variance of 5.2%, 3.9% and 4% with no significant bias in the lateral, inferior and posterior walls. Conclusions: This report establishes reference values for inferior and posterior RV wall strain in children. We show that speckle tracking strain analysis is feasible in alternate walls of the RV allowing for more global assessment of RV function. Establishment of normal values in a larger cohort including younger children may improve future assessment of dysfunction in RV pathology.
Diagnosis and Classification of Myocarditis by Endomyocardial Biopsy
Authors: John J. Fenoglio, Philip C. Ursell, Collins F. Kellogg, Ronald E. Drusin, Melvin B. Weiss
Journal: New England Journal of Medicine (1983)

Myocarditis was diagnosed by endomyocardial biopsy in 34 patients with otherwise unexplained heart failure. On the basis of both clinical and histologic findings these patients were divided into three groups. Seven patients had acute myocarditis (mean age, 20 years; mean ejection fraction, 22 per cent) characterized by an interstitial inflammatory infiltrate and extensive, acute cell damage. Five of these patients died after a mean duration of illness of eight weeks. Eighteen patients had rapidly progressive myocarditis (mean age, 35 years; mean ejection fraction, 19 per cent) characterized by patchy acute and healing cell damage and fibrosis; 17 of them died after a mean duration of illness of 23 months. Nine patients had chronic myocarditis (mean age, 31 years; mean ejection fraction, 31 per cent) characterized by focal inflammation and cell damage. All nine were alive after a mean follow-up period of 39 months. In four of these nine, clinical and hemodynamic improvement occurred after one month of immunosuppressive therapy. Our study suggests that a clinically useful classification of myocarditis can be accomplished by endomyocardial biopsy. (N Engl J Med. 1983; 308:12–8.)
Effect of Camptothecin and Adriamycin on Bleomycin-Induced Tritiated Thymidine Triphosphate Incorporation in a Rat Nuclear System2
Authors: George P. Sartiano, Mona L. Coetzee, Katherine Klein, Peter Ove
Journal: JNCI Journal of the National Cancer Institute (1977)

We investigated the effect of camptothecin and adriamycin on [3H]TTP incorporation and bleomycin-stimulated [3H]TTP incorporation in host liver and hepatoma nuclei of rats. Camptothecin neither stimulated nor inhibited incorporation in the regular nuclear incorporating system. Bleomycin stimulated incorporation to a much greater extent in host liver nuclei and slow-growing hepatomas than it did in the fast-growing hepatoma 7777. Addition of camptothecin to bleomycin stimulated incorporation of [3H]TTP even further. This camptothecin stimulation was slightly greater in hepatoma nuclei than it was in host liver nuclei. Adriamycin inhibited (3H)TTP incorporation in the regular system as well as the bleomycin-induced incorporation. Hepatoma nuclei were more sensitive to this inhibition than were host liver nuclei. Sucrose density gradients indicated that camptothecin caused DNA strand scissions in addition to those produced by bleomycin. Camptothecin alone produced some single-strand but no double-strand scissions. The action of bleomycin was dependent on sulfhydryl-reducing agents. Camptothecin could partially substitute for this requirement. Adriamycin did not produce DNA breaks, as determined by neutral or alkaline sucrose density gradients. Despite complete inhibition of bleomycin-induced [3H)TTP incorporation, adriamycin did not prevent bleomycin-induced DNA breaks. The inhibitory effect of adriamycin might have been on the repair system.
A phase I combination study of olaparib (AZD2281; KU-0059436) and cisplatin (C) plus gemcitabine (G) in adults with solid tumors.
Authors: G. Giaccone, A. Rajan, R. J. Kelly, M. Gutierrez, S. Kummar, M. Yancey, J. J. Ji, Y. Zhang, R. E. Parchment, J. H. Doroshow
Journal: Journal of Clinical Oncology (2010)

3027 Background: Poly (ADP-ribose) polymerase (PARP) group of NAD+-dependent enzymes participate in multiple DNA- related functions. Increased PARP activity can lead to drug resistance. Olaparib (O), a potent oral inhibitor of PARP-1 and PARP-2 may partially overcome resistance to C and G when used in combination. Methods: Eligibility: histologically confirmed metastatic or unresectable solid tumors, PS 0–2, normal organ functions. Treatment at dose level 1 (DL1): O 100 mg orally bid on days (D) −2 to 2, G 500 mg/m2/h on D1 and D8, C 60 mg/m2 on D1 after G; q21 days ×6. Doses (same schedule) at DL −1: O 100 mg once daily, G 400 mg/m2/h, C 50 mg/m2. Peripheral blood mononuclear cells (PBMCs) were collected and processed within 2 hours and poly (ADP-ribose) (PAR) concentration determined by immunoassay. Results: From 5/2008 to 11/2009, 23 patients (pts) enrolled; 14 males, median age 52 yrs (25- 88). Tumor types: 8 NSCLC; 3 ovarian; 3 pancreatic; 2 esophageal; 2 thymic ca; 1 mesothelioma; 1 adrenocortical ca; 1 head and neck ca; 1 angiosarcoma, 1 small cell lung ca. 3 pts were treated at DL1; 2 hematological (heme) dose limiting toxicities (DLTs) were seen. Protocol was amended (A1) to treat at DL −1 and enroll pts treated with <2 prior severely myelosuppressive chemotherapy regimens. No DLTs were seen in 6 pts at DL −1. Then 6 pts were treated at DL1, with 3 heme DLTs. Protocol was amended further (A2) to treat pts with O on D1 only (bid) (doses and schedule of C and G unchanged). 6 pts were treated at DL1 with no heme DLTs. Then 2 pts were enrolled at DL2 (C 75 mg/m2, rest unchanged); both had non-heme DLTs. Responses: In 19 evaluable patients, 2 partial responses (PRs), 7 stable disease (SD) and 10 progressive disease (PD). 2 pts withdrew from study. O inhibited its primary target (PAR) in surrogate (PBMCs) and tumor tissue. Conclusions: Combination of O with C and G was associated with significant myelosuppression. Treatment at DL1 was better tolerated with O given on D1 only. Significant non-heme toxicity was seen at DL2. The study is now closed to accrual. The maximum tolerated dose (MTD) was established as DL1 with O dosed on D1 only. No significant financial relationships to disclose.
Death from Sulfadiazine with Agranulocytosis, Jaundice and Hepatosis
Authors: Hrolfe R. Ziegler, James N. Patterson, William A. Johnson
Journal: New England Journal of Medicine (1945)

THE occurrence of various types of toxic reactions to the sulfonamides is now common knowledge, and all have been fully described in the medical literature1 2 3 4 5 in recent years. There have been reported a sufficient number of severe reactions producing death to make the medical profession fully conscious of this danger and of its obligations in this respect. Reactions from the newer compounds have been fewer than those from the older ones. Thus, those seen following the use of sulfathiazole are much less frequent than are those from sulfanilamide, and those resulting from sulfadiazine appear to be still fewer in number. . . .
Recurrent<i>NRAS</i>mutations in pulmonary Langerhans cell histiocytosis
Authors: Samia Mourah, Alexandre How-Kit, Véronique Meignin, Dominique Gossot, Gwenaël Lorillon, Emmanuelle Bugnet, Florence Mauger, Celeste Lebbe, Sylvie Chevret, Jörg Tost, Abdellatif Tazi
Journal: European Respiratory Journal (2016)

The mitogen-activated protein kinase (MAPK) pathway is constantly activated in Langerhans cell histiocytosis (LCH). Mutations of the downstream kinases BRAF and MAP2K1 mediate this activation in a subset of LCH lesions. In this study, we attempted to identify other mutations which may explain the MAPK activation in nonmutated BRAF and MAP2K1 LCH lesions.We analysed 26 pulmonary and 37 nonpulmonary LCH lesions for the presence of BRAF, MAP2K1, NRAS and KRAS mutations. Grossly normal lung tissue from 10 smoker patients was used as control. Patient spontaneous outcomes were concurrently assessed.BRAF(V600E) mutations were observed in 50% and 38% of the pulmonary and nonpulmonary LCH lesions, respectively. 40% of pulmonary LCH lesions harboured NRAS(Q61K) (/R) mutations, whereas no NRAS mutations were identified in nonpulmonary LCH biopsies or in lung tissue control. In seven out of 11 NRAS(Q61K) (/R)-mutated pulmonary LCH lesions, BRAF(V600) (E) mutations were also present. Separately genotyping each CD1a-positive area from the same pulmonary LCH lesion demonstrated that these concurrent BRAF and NRAS mutations were carried by different cell clones. NRAS(Q61K) (/R) mutations activated both the MAPK and AKT (protein kinase B) pathways. In the univariate analysis, the presence of concurrent BRAF(V600E) and NRAS(Q61K) (/R) mutations was significantly associated with patient outcome.These findings highlight the importance of NRAS genotyping of pulmonary LCH lesions because the use of BRAF inhibitors in this context may lead to paradoxical disease progression. These patients might benefit from MAPK kinase inhibitor-based treatments.
Transplantation of Anergic Histoincompatible Bone Marrow Allografts
Authors: Eva C. Guinan, Vassiliki A. Boussiotis, Donna Neuberg, Lisa LaVita Brennan, Naoto Hirano, Lee M. Nadler, John G. Gribben
Journal: New England Journal of Medicine (1999)

Successful allogeneic bone marrow transplantation relies on global immunosuppression or elimination of T cells. In contrast, the induction of anergy can inactivate specific sets of alloreactive T cells in the donor marrow. Previous work has shown that anergy can be induced by blocking the interaction of the B7 molecule on the surface of antigen-presenting cells with the CD28 molecule on the surface of T cells, thus preventing key signaling events essential for the activation of T cells. To investigate the feasibility of this approach with respect to transplantation of histoincompatible bone marrow, we undertook a clinical trial of ex vivo induction of anergy in T cells present in donor marrow to recipient alloantigens.
Primary Hyperoxaluria and Oxalosis
Authors: John T. Godwin, Major F. Fowler, Eleanor F. Dempsey, Philip H. Henneman
Journal: New England Journal of Medicine (1958)

THE purpose of this paper is to record a case of a rare disease termed oxalosis in which urinary oxalate excretion was measured. Apparently, the first case reported was by Lepoutre1 in 1925. Since that time 25 additional cases have been recorded.It is hoped that this report will call attention to the possibility of this disease in patients with renal stones or nephrocalcinosis and stimulate further research in oxalate metabolism.Case ReportJ.F., a 10-year-old boy at the time of death, had enjoyed good health until the age of 5 years, when he passed a renal calculus. radiologic examination . . .
Myocarditis of Obscure Etiology Associated with Pregnancy
Authors: Frederick F. Becker, Harry Taube
Journal: New England Journal of Medicine (1962)

WITHIN the broad but intriguing classification of "heart disease of unknown etiology" can be listed the series of cases presented as "post-partum myocarditis or myocardosis." Virchow, as noted by Gouley, McMillan and Bellet,1 described the presence of myocardial degeneration in deaths during pregnancy. Blacker2 and Campbell3 also mentioned this type of change in the hearts of post-partum females. It was not until the descriptions of Gouley et al.1 and Hull and Hafkesbring4 that the pathology and uniform clinical picture were pointed out in detail. However, one continues to question both the etiology and the legitimacy of designating this combination of . . .
An in Vitro Predictive Test for Graft versus Host Disease in Patients with Genotypic HLA-Identical Bone Marrow Transplants
Authors: Georgia B. Vogelsang, Allan D. Hess, Aron W. Berkman, Peter J. Tutschka, Evan R. Farmer, Paul J. Converse, George W. Santos
Journal: New England Journal of Medicine (1985)

Acute graft versus host disease remains a major cause of morbidity and mortality in allogeneic bone marrow transplantation. To date, no clinically useful test has been reported that will predict the occurrence of graft versus host disease in genotypic HLA-identical donor-recipient pairs. We have developed a skin-explant model using donor lymphocytes that have been sensitized against recipient lymphocytes in vitro and cocultured with the recipient's skin. Histologic changes compatible with acute graft versus host disease are found in the positive explants. To date 32 patients have been tested in a prospective manner. Among the 18 recipient-donor pairs that were positive, 16 patients were found to have histologic Grade 2 or higher graft versus host disease of the skin on biopsy. Among the 14 negative pairs, only 3 patients had histologic Grade 2 or higher graft versus host disease of the skin on biopsy. Thus, the model has a sensitivity of 84 per cent and a specificity of 85 per cent, and is a significant predictor of the histologic occurrence of graft versus host disease (P less than 0.0005 by chi-square test). The test may be useful in the selection of donors for bone marrow transplantation and in the planning of prophylaxis against graft versus host disease.
To B(MP-2) or Not To B(MP-2): Cytokines and Tumor Surgery—Response
Authors: Kurt R. Weiss
Journal: Clinical Cancer Research (2015)

In response to my editorial, the authors state that they “in principle” agree that survival should trump orthopedic outcomes. They attempt to distract the readership from the safety concerns of BMP-2 in osteosarcoma patients by proposing that multiagent chemotherapy has not improved survival, and our efforts should therefore focus on functional outcomes. They argue that it is “hypocritical” to suggest that BMP-2 is not ready for clinical trial in osteosarcoma, and that clinical trials are “the only manner with which to answer these questions.”I am acquainted with the limitations of systemic treatment in osteosarcoma, but do not subscribe to the authors' nihilism. Conventional chemotherapy has likely reached its zenith, but there is myriad evidence that novel treatments hold promise. Meyers and colleagues (1) reported that muramyl tripeptide, an immune therapy, statistically improved survival in a study of 662 osteosarcoma patients. SARC (Sarcoma Alliance through Research and Collaboration) has initiated an anti–PD-1 antibody clinical trial. The authors themselves recently published that GD2 is expressed in osteosarcoma metastases and suggested a phase II clinical trial of anti-GD2 antibody (2). If improved survival through systemic treatment is doomed to failure, why bother? This might also be considered hypocrisy.The authors' reply has not strengthened their case for a clinical trial of BMP-2 to improve allograft union in osteosarcoma patients. They have neither addressed the absence of evidence that BMP-2 improves structural allograft union, nor the mountain of safety and ethical concerns surrounding BMP-2 (3). They failed to use cell lines with known metastatic rates and thus cannot tell us if BMP-2 altered metastases (4). They have ignored evidence that BMP-2 enhances the metastatic potential of osteosarcoma cells (5). They did not challenge that BMP-2 poses unacceptable risks for unknown benefit in a limited subset of patients, and have never defined the scope of this problem for the CCR readership.Additional preclinical research is required before BMP-2 can be used as an investigational agent in osteosarcoma. The authors' claim that clinical trial is “the only way” to answer these questions is false and displays inadequate respect for the potential dangers of this potent growth factor. I fear that using BMP-2 in osteosarcoma patients is the oncologic equivalent of pouring gasoline on a fire, and will continue to harbor these misgivings until convinced otherwise by data. This is not unreasonable to ask and indeed demand in the name of safety for patients with osteosarcoma.See the original Letter to the Editor, p. 4022No potential conflicts of interest were disclosed.