tbuckley/cabot-search huggingface dataset:
Predicting Relapse of Human Leukemia by Means of Premature Chromosome Condensation
Authors: Walter N. Hittelman, Lowanda C. Broussard, Gary Dosik, Kenneth B. McCredie
Journal: New England Journal of Medicine (1980)

We attempted to determine whether the technique of premature chromosome condensation (PCC) could be used to predict relapse in patients with acute leukemia in complete remission. Nineteen patients received chemotherapy and were studied serially with the PCC technique. Of the 19 patients in this pilot study, 14 relapsed, and the PCC technique predicted relapse in 11 of these 14. The median time from an elevation in the fraction of G1 cells in the late G1 phase (a high proliferative-potential index) to the development of clinical evidence of relapse was 3.5 months. On the other hand, the median time from a low proliferative-potential index to relapse or to the end of the study was eight months. The incidence of false-positive or false-negative measurements was low. two patients had high index values just before chemotherapy, and remission was estimated to be prolonged by 2.5 and six months by our therapeutic protocol. These results suggest that the PCC technique is useful and accurate in the early prediction of relapse in human leukemia. (N Engl J Med. 1980; 303:479–84.)
Case 25-1987
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely
Journal: New England Journal of Medicine (1987)

Case Records of the Massachusetts General Hospital from The New England Journal of Medicine — Case 25-1987 — A Seven-Year-Old Japanese-American Boy with Persistent Right-Ear Drainage despite Antibiotic Therapy
M11 A preliminary biopsychosocial model of Vocal Cord Dysfunction (VCD)
Authors: CC Maskell, N Pargeter, J Fellows, A Mansur, R Howard
Journal: Thorax (2015)

control and were potentially at risk of severe exacerbations, hospital admission and early progression to COPD.Four further LHOp studies are planned: a pharmacy based intervention to improve asthma control/uptake of preventive interventions (smoking cessation; vaccinations); a case control study of GP asthma medication prescribing; prospective prognostic respiratory health cohort studies; and a qualitative study of asthmatic OMUs' perspectives on respiratory health and inhaler use.
Polycystic Ovaries and Hyperandrogenism in Women Taking Valproate for Epilepsy
Authors: Jouko Isojarvi, Timo J. Laatikainen, Arto J. Pakarinen, Kaisa Juntunen, Vilho V. Myllyla
Journal: New England Journal of Medicine (1993)

Reproductive endocrine disorders are more common among women with epilepsy than among normal women. These disorders have been attributed to epilepsy itself, but could be related to antiepileptic-drug therapy.
Disease Caused by a Marine Vibrio
Authors: Paul A. Blake, Michael H. Merson, Robert E. Weaver, Dannie G. Hollis, Peter C. Heublein
Journal: New England Journal of Medicine (1979)

We studied the clinical characteristics and epidemiology of disease associated with a rare, unnamed halophilic lactose-fermenting Vibrio species in 39 persons from whom the organism had been isolated. Two distinct clinical presentations were seen. In the first, the illness began with septicemia, often within 24 hours after raw oysters had been eaten; 18 of 24 such patients had pre-existing hepatic disease, and 11 of the 24 died. In the second, there was a wound infection after exposure to seawater or an injury incurred during the handling of crabs; none of these persons had pre-existing hepatic disease, and one of 15 died. Most cases (85 per cent) occurred during relatively warm months (May to October) in men (90 per cent) 40 or more years of age (95 per cent). This Vibrio species is a pathogen and should be considered in the differential diagnosis of septicemia with secondary skin lesions and of wound infections after exposure to seawater.
Strategies for the Global Eradication of Poliomyelitis by the Year 2000
Authors: Peter F. Wright, Robert J. Kim-Farley, Ciro A. de Quadros, Susan E. Robertson, Robert McN. Scott, Nicholas A. Ward, Ralph H. Henderson
Journal: New England Journal of Medicine (1991)

IN May 1988, the World Health Assembly declared that the World Health Organization was committed to the global eradication of poliomyelitis by the year 2000.1 The eradication of poliomyelitis, as with smallpox, involves the additional criterion of the elimination of indigenous transmission of wild virus. This paper reviews the progress that has been achieved, outlines current objectives, and highlights the research and development required to meet the target of global eradication. Background The initiative for the global eradication of poliomyelitis is being coordinated by the Expanded Programme on Immunization (EPI), established by the World Health Assembly in 1974. The initial . . .
CXCR4/SDF-1 Axis Promotes EMT Mediated Fibrosis in Eosinophilic Esophagitis (EoE)
Authors: Chandrashekara Puthanapura Mahadevappa, Sathisha Upparahalli Venkateshaiah, Murli Manohar, Anil Mishra
Journal: Journal of Allergy and Clinical Immunology (2016)
The Girl with the Curl
Authors: Giuseppe Remuzzi, Eliana Gotti
Journal: New England Journal of Medicine (1995)

A 47-year-old woman was admitted to the hospital because of fever (temperature, 38°C) during the previous 24 hours, without chills, cough, or dysuria. Forty days before admission, she had received a kidney transplant from a cadaver because of renal failure due to lupus nephritis. She was receiving daily treatment with cyclosporine (8 mg per kilogram of body weight), azathioprine (1.5 mg per kilogram), and prednisone (25 mg). The post-transplantation course had not been unusual, and there had been no episodes of acute rejection. On admission the physical examination was unremarkable, and the blood pressure was normal.Isolated fever, . . .
145P: Perspectives in oligometastatic brain lesions in non-small cell lung cancer (NSCLC)
Authors: C. Salvador Coloma, C. Escoin Pérez, O.M. Niño, D. Akhoundova Sanoyan, M. Melián, E. Navarro, J. Gomez Codina, J. Montalar, O. Juan
Journal: Journal of Thoracic Oncology (2016)
A Controlled Trial of Cyclosporine in the Treatment of Primary Biliary Cirrhosis
Authors: Russell H. Wiesner, Jurgen Ludwig, Keith D. Lindor, Roberta A. Jorgensen, William P. Baldus, Henry A. Homburger, E. Rolland Dickson
Journal: New England Journal of Medicine (1990)

Primary biliary cirrhosis is a progressive disease of the liver characterized by the immunologic destruction of bile ducts; effective therapy is lacking. We therefore evaluated the safety and efficacy of low-dose cyclosporine in 29 patients with primary biliary cirrhosis without evidence of damage to the lobular architecture (precirrhotic disease) or portal hypertension. The patients were randomly assigned to receive either cyclosporine (4 mg per kilogram of body weight per day) or placebo.
Extracellular matrix remodelling in response to venous hypertension: proteomics of human varicose veins
Authors: Javier Barallobre-Barreiro, Rahmi Oklu, Marc Lynch, Marika Fava, Ferheen Baig, Xiaoke Yin, Temo Barwari, David N. Potier, Hassan Albadawi, Marjan Jahangiri, Karen E. Porter, Michael T. Watkins, Sanjay Misra, Julianne Stoughton, Manuel Mayr
Journal: Cardiovascular Research (2016)

Extracellular matrix remodelling has been implicated in a number of vascular conditions, including venous hypertension and varicose veins. However, to date, no systematic analysis of matrix remodelling in human veins has been performed. To understand the consequences of venous hypertension, normal and varicose veins were evaluated using proteomics approaches targeting the extracellular matrix. Varicose saphenous veins removed during phlebectomy and normal saphenous veins obtained during coronary artery bypass surgery were collected for proteomics analysis. Extracellular matrix proteins were enriched from venous tissues. The proteomics analysis revealed the presence of >150 extracellular matrix proteins, of which 48 had not been previously detected in venous tissue. Extracellular matrix remodelling in varicose veins was characterized by a loss of aggrecan and several small leucine-rich proteoglycans and a compensatory increase in collagen I and laminins. Gene expression analysis of the same tissues suggested that the remodelling process associated with venous hypertension predominantly occurs at the protein rather than the transcript level. The loss of aggrecan in varicose veins was paralleled by a reduced expression of aggrecanases. Chymase and tryptase β1 were among the up-regulated proteases. The effect of these serine proteases on the venous extracellular matrix was further explored by incubating normal saphenous veins with recombinant enzymes. Proteomics analysis revealed extensive extracellular matrix degradation after digestion with tryptase β1. In comparison, chymase was less potent and degraded predominantly basement membrane-associated proteins. The present proteomics study provides unprecedented insights into the expression and degradation of structural and regulatory components of the vascular extracellular matrix in varicosis.
Data mining-high content screening pipeline for discovery and validation of novel targetable oncogenes
Authors: Wendy Soon, Yi Fang Lee, Kartiki Desai, Lance Miller
Journal: Clinical Cancer Research (2008)

AACR Centennial Conference: Translational Cancer Medicine-- July 20-23, 2008; Monterey, CA

A28 

Secretory factors and extracellular receptors that drive cancer progression make attractive immunotherapeutic targets. To discover novel targetable oncogenes, we used a whole-genome data-mining approach that takes advantage of large independent microarray studies of breast tumors annotated for clinical outcomes. First, the Gene Ontology database (www.geneontology.org) was used to identify all genes encoding known and predicted transmembrane receptors and secreted growth factors represented on the Affymetrix U133A and U133B genechips (~33,000 well annotated genes). The expression patterns of these genes across breast tumors were then correlated by Cox proportional-hazards regression to the distant metastasis-free survival of patients among 5 independent breast cancer cohorts. Of the resultant 25 genes significantly associated with cancer recurrence in multiple cohorts, a handful of secretory factors without previous implication in breast cancer were identified. A semi-high throughput high-content screening strategy was then applied to assess the phenotypic consequences of altering candidate gene expression. Using siRNA-mediated gene silencing, a number of novel candidate oncogenes were found to contribute to proliferation, anchorage-independent growth and apoptotic resistance in multiple breast cancer cell lines. Although preliminary, these findings suggest that the extrapolation of specific oncogene candidates from massive gene expression-patient survival association data, coupled with semi-high throughput and high content screening methods holds promise in elucidating functionally relevant breast cancer targets.
P161 HOW HAS THE SURGICAL TREATMENT OF LUNG CANCER IN THE UK EVOLVED OVER THE LAST TWO DECADES? – An illustrative surgeon’s experience
Authors: R Bilancia, A Paik, A Sharkey, D Waller
Journal: Thorax (2015)

<h3>Background/introduction</h3> The practice of lung cancer surgery in UK has seen many changes over the last 20 years, with innovations in surgical technique and investigatory modalities together with significant organisational changes. <h3>Aims/objectives</h3> To assess how these changes have impacted on an individual Consultant surgical practice spanning this era. <h3>Method</h3> We have retrospectively reviewed a single-surgeon practice from consultant appointment to the present (1997–2015) comprising 1708 consecutive lung cancer operations: 962 (56%) lobectomy, 296 (17%) sublobar resection, 250 (15%) extended resection, 157 (9%) pneumonectomy, 43 (3%) open/close. Concurrently, 710 surgical staging procedures were performed. We analysed trends with time in type of procedure; open/close rates and in-hospital mortality. <h3>Results</h3> 1557 anatomic resections were performed (87 cases/year, 67–130) with no significant decrease in the annual workload. There were significant changes in the types of surgical procedures performed over the time period: a significant decrease in pneumonectomy rate (p &lt; 0.001), mirrored by an increasing use of sleeve-resections (p = 0.088); an increase in the proportion of anatomical resections by video assisted thoracic surgery (VATS) (p &lt; 0.001), an overall increasing number of anatomical segmentectomies (p &lt; 0.001), with a stable rate of wedge resections (mean 6.3%, p = 0.908). There has been a significant decrease in surgical mediastinal staging, particularly after 2010 (p &lt; 0.001) with a significant reduction in the open/close rate, particularly after 2004 (4.8 vs. 0.65%, p &lt; 0.001). Overall the in-hospital mortality rate has significantly decreased (from 7.1% in 1998 to 2.9% in 2015, p = 0.004). <h3>Conclusion</h3> There has been significant evolution in lung cancer surgery over the last two decades, which are illustrated in this individual surgeon’s practice. Whilst increased surgical experience may partly explain the changes, other important factors include: a change in the biology of lung cancer from central squamous to peripheral adenocarcinomas with earlier tumour detection, facilitating more VATS and lung-sparing surgery; improved perioperative care and the use of lesser resections, reducing mortality; and new techniques in staging (CT-PET, EBUS) reducing the need for surgical staging and the number of futile thoracotomies.
Elevated Plasma Procaine Concentrations after Administration of Procaine Penicillin G
Authors: Richard L. Green, John E. Lewis, Stephen J. Kraus, Evan L. Frederickson
Journal: New England Journal of Medicine (1974)

Plasma procaine concentrations were measured in 26 patients immediately after the intramuscular administration of 4.8 million units of procaine penicillin G for the treatment of gonorrhea. The values ranged from 3.6 to 11.0 μg per milliliter. Three different lots were also checked for the presence of free procaine in bottles stored at 4°C. The values ranged from 8.3 to 11.0 μg per milliliter and were increased with storage at room temperature or heating to 56°C. These levels probably account for the high frequency (0.9 per cent in our clinic population) of abnormal behavioral and neurologic reactions that occur after the administration of procaine penicillin G. Although 8.3 to 11.0 μg per milliliter free procaine was found in three different lots stored at 4°C, and though these values were increased at higher temperatures, these small amounts of free procaine in the mixture under different physical conditions were not a prerequisite to the inducement of the syndrome. Therefore, instantaneous liberation of toxic quantities of procaine from the mixture apparently occurs in vivo. (N Engl J Med 291:223–226, 1974)
Phase III study of taxane chemotherapy with lapatinib or trastuzumab as first-line therapy for women with HER2/neu-positive metastatic breast cancer (BC) (NCIC Clinical Trials Group (NCICCTG)MA.31/GSK EGF 108919).
Authors: W. Parulekar, J. W. Chapman, S. Aparicio, Y. Murray, F. M. Boyle, A. Di Leo, B. Kaufman, C. Levy, A. Manikhas, M. Martin, K. I. Pritchard, L. S. Schwartzberg, M. J. Burnell, S. Dent, S. Ellard, K. S. Tonkin, T. J. Whelan, J. Lemieux, L. Bordeleau, K. A. Gelmon
Journal: Journal of Clinical Oncology (2011)

TPS108 Background: The EGFR pathways are important therapeutic targets in HER2/neu+ BC. Lapatinib (L) a dual, inhibitor of EGFR and HER2/neu tyrosine kinase activity improves overall survival (OS) in patients with metastatic BC when added to paclitaxel (SABCS 2010:P3-1424).The relative efficacy of L + taxane compared to trastuzumab (T) + taxane in the metastatic setting is unknown. Further research using standardized methodology is required to define prognostic and predictive molecular markers. Methods: NCIC CTG led, international randomized, open label phase III trial comparing: L 1250 mg po daily + taxane therapy* x 24 weeks followed by L 1500 mg po daily vs T (standard dose) + taxane therapy* x 24 weeks followed by T *docetaxel 75 mg/m2 q 3 wk or paclitaxel 80 mg/m2 q wkly 3/4). Eligibility criteria: HER2/neu+ (local or central lab) metastatic BC and no CNS metastases. No prior chemotherapy for metastatic BC. Prior taxane or anti-HER2/nue therapy in (neo)adjuvant setting only. Adequate organ function and PS Endpoints: Primary: progression free survival (PFS). Secondary: OS, incidence and time to CNS metastases, RR, adverse events, QOL, economic evaluation (health utilities and healthcare utilization). Correlative studies will include: Central lab confirmation of HER2/neu, ER/PR, EGFR, Ki67 and CK5/6; PTEN, IGFR, phosphorylated EGFR pathway biomarkers, DNA analysis for genetic mutations (e.g. TP53, P13KCA, HEr1-4, PTEN) predictive of response to therapy; pharmacogenetic analysis for predictors of outcome and toxicity. A substudy will examine tumor molecular changes at progression. Statistical Methods: Planned accrual is 536 patients with HER2/neu+ (central lab) BC over 2 years with 1 more year of follow-up. The primary test is non inferiority (L+taxane)/ T+taxane using a target hazard ratio 1.25 (1 sided alpha 2.5%). If noninferiority is demonstrated, superiority will be tested. An interim analysis is planned. Conduct to Date: Study activation: July 2008. Current accrual: 440. In Nov 2010 the DSMC review supported trial continuation. Supported by GlaxoSmithKline ClinicalTrials.gov: NCT00667251.
Inherited Metabolic Myopathy and Hemolysis Due to a Mutation in Aldolase A
Authors: Joachim Kreuder, Arndt Borkhardt, Reinald Repp, Arnulf Pekrun, Barbara Göttsche, Urda Gottschalk, Heinz Reichmann, Walter Schachenmayr, Kurt Schlegel, Fritz Lampert
Journal: New England Journal of Medicine (1996)

Glycolysis is the most important source of energy in red cells and working muscles. Inherited defects of glycolysis can cause hemolytic anemia, neurologic abnormalities, and myopathy with exercise ...
Using Multigene Tests to Select Treatment for Early-Stage Breast Cancer
Authors: Rodrigo Goncalves, Ron Bose
Journal: Journal of the National Comprehensive Cancer Network (2013)

Oncotype DX, PAM50, and MammaPrint are multigene tests that are being used clinically for early-stage breast cancer to predict recurrence risk and guide adjuvant chemotherapy decisions. These tests have been validated in multiple retrospective studies, and prospective clinical trials are in progress. The TAILORx trial uses the Oncotype DX recurrence score to assign estrogen receptor–positive (ER+), node-negative patients to chemotherapy plus hormonal therapy versus hormonal therapy alone. The RxPONDER (SWOG S1007) trial uses Oncotype DX in a similar approach but on node-positive patients, and it includes the PAM50 test as a secondary analysis. The MINDACT trial uses Mamma-Print and Adjuvant! Online for treatment arm assignments. MINDACT has very broad eligibility criteria and 2 secondary randomizations for selecting chemotherapy and hormonal therapy regimens. This article discusses how the latest results on cancer genome sequencing apply to early-stage breast cancer. Several hundred breast cancers have already undergone genome sequencing, and the somatic DNA changes found in the tumor, compared with the patient's normal DNA, have been identified. Higher rates of point mutations and chromosomal translocations are found in aromatase inhibitor–resistant ER+ cancers and in the basal-like and HER2-enriched breast cancer subtypes. Correlations of somatic mutations with neoadjuvant aromatase inhibitor response are discussed. Genome sequencing can potentially identify the molecular abnormalities that underlie the poor risk identified by multigene tests and provide potential new targets for therapy, but more clinical trials correlating clinical outcome and somatic DNA changes are needed.
Implementation of a direct patient callback system improves compliance for additional breast imaging and early breast cancer detection
Authors: D. Richard-Kowalski, D. Termeulen, M. Reed, R. Reyes, M. Kuliga, D. Sanjurjo, A. E. Hirsch
Journal: Journal of Clinical Oncology (2006)

6073 Background: Existing patient recall systems usually involve contacting the referring physician who then notifies the patient to schedule a return visit for further imaging. We set out to determine whether a direct patient callback system would improve patient compliance in returning for additional imaging including magnification, spot compression, and ultrasound, and whether that would translate to an improvement in early breast cancer detection. Methods: Beginning on 4/1/2004, we prospectively identified all patients whose screening mammograms were read as having an incomplete assessment that required additional imaging (ACR BIRADS 0). Those patients were contacted directly via telephone to return for additional views. Results: Between 11/1/2002 and 3/31/3004, 1142 patients with incomplete screening mammography were identified and the referring physicians were contacted. 956 of 1142 (84%) patients returned and underwent additional breast imaging. Between 4/1/2004 and 12/31/2005, 1,336 patients with incomplete screening mammography were contacted directly to return for additional imaging. 1,307 of 1,336 (98%) patients returned and underwent additional breast imaging. (p &lt; 0.0001, Fisher’s exact test). 125 of the 1,307 (8.5%) of the subsequent exams were found to be suspicious and biopsy was recommended (ACR BIRADS 4 or 5). Conclusions: Our new system of contacting patients with incomplete mammography has significantly increased our recall rate. Implementation of this system has enabled us to identify those patients whose mammograms are suspicious and ultimately diagnose breast cancer earlier. Direct patient callback has become standard policy and we are recommending this system for all radiology recall examinations. No significant financial relationships to disclose.
Prolonged Cough Suppression
Authors: Edward H. Townsend
Journal: New England Journal of Medicine (1958)

NOCTURNAL coughing spasms are most distressing not only for the child but also for the parents, and drugstores are replete with antitussive agents — many of them the so-called "narcotic-exempt" variety — designed to spare the patient the necessity of seeking a physician's prescription. A survey of local drugstores reveals that 50 to 60 antitussive preparations are stocked by the average pharmacy, consisting of various expectorants, emollients, herbs, sedatives and narcotics (especially codeine and dihydrocodeinone). These preparations enjoy variable popularity, depending upon flavor more than antitussive properties.Patients search for effective agents that will act over a prolonged period. This . . .
IGHV Mutation Status Does Not Add Prognostic Information In The Background Of Mutations In TP53 and SF3B1, and Deletions Of 17p and 11q, Which Are Independent Adverse Prognostic Parameters In CLL
Authors: Claudia Haferlach, Sabine Jeromin, Sandra Weissmann, Frank Dicker, Wolfgang Kern, Susanne Schnittger, Alexander Kohlmann, Torsten Haferlach
Journal: Blood (2013)