tbuckley/cabot-search huggingface dataset:
Immunologic Analysis of a Spinal Cord–Biopsy Specimen from a Patient with Human T-Cell Lymphotropic Virus Type I–Associated Neurologic Disease
Authors: Michael C. Levin, Tanya J. Lehky, Alfred N. Flerlage, David Katz, Douglas W. Kingma, Elaine S. Jaffe, John D. Heiss, Nicholas Patronas, Henry F. McFarland, Steven Jacobson
Journal: New England Journal of Medicine (1997)

Human T-cell lymphotropic virus type I (HTLV-I) is associated with adult T-cell leukemia and a chronic progressive neurologic disease, HTLV-I–associated myelopathy–tropical spastic paraparesis (hereafter referred to as HTLV-I–associated myelopathy).1–5 HTVL-I is endemic in Japan, the Caribbean, Africa, and South America.5 Risk factors for infection include sexual contact, exchange of blood products, and vertical transmission from mother to child.5 HTLV-I–associated myelopathy causes progressive myelopathy with atrophy of the spinal cord.5,6 Subcortical white-matter lesions are sometimes present on magnetic resonance imaging.5–7 Cerebrospinal fluid shows pleocytosis, elevated titers of IgG, and oligoclonal bands.8–10 Autopsy results correlate with neurologic findings . . .
PWE-302 Colorectal cancer lymph node retrieval number is associated with biological and institutional factors: a tertiary centre audit
Authors: CJ Deutsch, NR Hall, RJ Davies, NS Fearnhead, R Miller, MP Powar, JM Wheeler, SJ Buczacki
Journal: Gut (2015)

<h3>Introduction</h3> Increased numbers of lymph nodes (LN) retrieved within a colorectal cancer resection is positively associated with survival and as such, identification of ≥12 LN is considered to be a surgical quality indicator. Here we audited LN retrieval data to establish both quality compliance and identify factors affecting identification rates. <h3>Method</h3> All colorectal cancer resections from April 2012–October 2014 at our institution were identified from the hospital’s cancer registry. The primary outcome variable was the number of nodes identified within the resection. <h3>Results</h3> 398 cases were included with a median LN retrieval number of 16. Greater numbers of nodes were identified in laparoscopic versus open surgery (p &lt; 0.05), high versus low T stage (p &lt; 0.005) and by trainee versus consultant pathologists (p &lt; 0.005). Whilst higher lymph node numbers were associated with a higher nodal positivity rate, there was no evidence that this caused stage migration. Regression analysis identified pathologist grade, T stage and number of positive nodes as independent predictors of high LN yield. <h3>Conclusion</h3> Local compliance in the identification of ≥12 nodes was achieved. Audit analysis of LN retrieval data provides insight into the biology of colorectal cancer as well as identifying institutional specific predictors of LN yield. <h3>Disclosure of interest</h3> None Declared. <h3>References</h3> Berger AC, Sigurdson ER, LeVoyer T, Hanlon A, Mayer RJ, Macdonald JS, <i>et al</i>. Colon cancer survival is associated with decreasing ratio of metastatic to examined lymph nodes. J Clin Oncol. 2005;23(34):8706–12 Buczacki SJA and Davies RJ. Colon resection - is standard technique adequate? <i>Surg Oncol Clin N Am</i>. 2014 Jan;23(1):25–34 Chang GJ, Rodriguez-Bigas MA, Skibber JM, Moyer VA. Lymph node evaluation and survival after curative resection of colon cancer: systematic review. J Natl Cancer Inst. 2007;99(6):433–41 Gilchrist RK, David VC. Lymphatic Spread of Carcinoma of the Rectum. Ann Surg. 1938;108(4):621–42 Le Voyer TE, Sigurdson ER, Hanlon AL, Mayer RJ, Macdonald JS, Catalano PJ, <i>et al</i>. Colon cancer survival is associated with increasing number of lymph nodes analyzed: a secondary survey of intergroup trial INT-0089. J Clin Oncol. 2003;21(15):2912–9 Lykke J, Roikjaer O, Jess P. The relation between lymph node status and survival in Stage I-III colon cancer: results from a prospective nationwide cohort study. Colorectal Dis. 2013;15(5):559–65
PTPS-16DEVELOPMENT OF NOVEL THERAPEUTIC STRATEGY FOR NEUROBLASTOMA THROUGH IRON AND CHOLESTEROL METABOLISM PATHWAYS
Authors: Sang Lee, Becky Slagle-Webb, Cara-Lynne Schengrund, James Connor
Journal: Neuro-Oncology (2015)

Neuroblastoma (NB) is the most common extracranial solid cancer in childhood and about 50% are metastatic at the time of diagnosis. Therefore, it is difficult to treat successfully. We studied the relationship between iron and cholesterol metabolisms in human NB cell lines with the goal of identifying novel therapeutic targets. In general, iron levels in human NB cells increased during the time they were cultured (∼ 3 days) while cholesterol levels of cells maintained in medium containing 1% fetal bovine serum (FBS) or 10% lipoprotein deficient serum decreased. The drug resistant human NB CHLA-171 cells had the higher levels of total iron than other cells as well as significantly more total cholesterol than the other cells during the first 48 hours in culture. Among iron chelators, DpC showed the strongest cytotoxicity to drug resistant NB cells. In general, the drug resistant NB cells are more sensitive to simvastatin than drug sensitive NB cells. In addition, the drug resistant CHLA-171 cells are more vulnerable to serum deprivation or combination of cholesterol inhibitors compare to the other NB cells. The HFE genotype is known to impact both cholesterol and iron metabolism. When HFE expression was decreased by HFE siRNA, cholesterol levels were also decreased in CHLA-171 cells. There is a mild anti-tumor effect at 20 mg/kg (3 times a week) of simvastatin in subcutaneous NB tumor model. In summary, the current data suggest that the need for iron is enhanced during cell proliferation, while cellular cholesterol is used for building new cells or synthesized more slowly during cell growth. The present data also indicates that iron/cholesterol is essential for the growth of drug resistant NB cells, and the effect of inhibition of its synthesis has a significant impact on cell viability.
Use of serum SDF-1 as a predictive biomarker for outcomes in the NCIC CTG MA.14 trial of octreotide, a somatostatin analogue in postmenopausal breast cancer.
Authors: M. Basik, A. Aguilar-Mahecha, J. W. Chapman, K. Jahan, S. Hassan, L. Han, C. F. Wilson, K. I. Pritchard, L. E. Shepherd, M. N. Pollak
Journal: Journal of Clinical Oncology (2010)

551 Background: Stromal cell derived-factor 1 (SDF-1) is a chemokine implicated in various aspects of breast tumor growth and metastasis. Blood SDF-1 levels have a significant prognostic value in primary breast cancers. Methods: NCIC CTG MA.14 is a randomized phase III trial of tam 20 mg daily for 5 yr ± octreotide LAR for 2 yr. Stratification factors were adjuvant chemotherapy, axillary nodal status, and ER status. The primary endpoint was event-free survival (EFS), defined as time from randomization to recurrence, second malignancy, or death due to any cause, with a secondary endpoint of relapse-free survival (RFS). Serum was collected at prespecified timepoints throughout the trial. Four month SDF-1 serum levels were measured with a commercially available ELISA assay (R&D). To assess the effect of SDF-1 on EFS and RFS in the context of factors considered in the main trial, we used step-wise forward multivariate adjusted Cox modeling, adjusting by the stratification factors, and adding a factor if the likelihood ratio criterion was significant, p ≤ 0.05. Events for the analysis were those reported at ASCO 2008. Results: 667 women were accrued (333 to tam, 334 to tam + oct), and followed for a median 7.9 years. 508 (76%) were successfully assessed for SDF-1. Higher log (SDF-1) (p < 0.0001) had a significant step-wise multivariate association, with worse EFS. When the significant baseline factors from the main trial were forced into the Cox model, older age (p = 0.0002), larger tumour size (p = 0.05), higher number of positive lymph nodes (p = 0.02), higher C-peptide (p < 0.0001), and higher log (SDF-1; p < 0.0001) were all significantly associated with worse EFS. As well, the interaction of treatment and SDF-1 split at median was significant (p < 0.0001) with inclusion of the significant main trial factors. Conclusions: Serum SDF-1 levels had a predictive value in the postmenopausal adjuvant breast cancer population of MA.14 treated with octreotide LAR. No significant financial relationships to disclose.
Changes in Pressures in the Left Atrium and Pulmonary Artery Immediately before and after Mitral Valvuloplasty
Authors: Paul N. Yu, Frank W. Lovejoy, Robert E. Nye, Howard A. Joos, David C. Beatty, Earle B. Mahoney
Journal: New England Journal of Medicine (1954)

SIMULTANEOUS recording of pressures in the left atrium and pulmonary artery in patients with mitral stenosis at operation was first described by Munnel and Lam,1 who showed that successful mitral commissurotomy usually caused a marked decrease in the atrial and some decline in the pulmonary-artery pressure. Pressure changes in the left atrium before and after mitral valvulotomy have also been reported by Wynn and his associates.2 These authors described various pressure patterns in mitral stenosis before operation, and noted little change in the form of the pressure pulse after operation. Connolly and his co-workers,3 recording simultaneous pressure in the left . . .
Liver Disease in Pregnancy
Authors: Tamsin A. Knox, Lori B. Olans
Journal: New England Journal of Medicine (1996)

Liver disease is a rare complication of pregnancy, but when it occurs it may do so in a dramatic and tragic fashion for both mother and infant. Diseases such as acute fatty liver of pregnancy (AFLP) may begin innocuously with mild symptoms and liver-enzyme abnormalities but, if left untreated, can progress to jaundice, liver failure, and death.Some of the normal physiologic changes of pregnancy can mimic abnormalities associated with liver disease. In an uncomplicated pregnancy, many laboratory-test results may appear abnormal according to standards derived from a nonpregnant population. Serum albumin concentrations decrease from a mean of 4.2 g . . .
Low-Dose Cyclosporine for the Treatment of Crohn's Disease
Authors: Brian G. Feagan, John McDonald, James Rochon, Andreas Laupacis, Richard N. Fedorak, Douglas Kinnear, Fred Saibil, Aubrey Groll, Andre Archambault, Richard Gillies, Barbara Valberg, E. Jan Irvine
Journal: New England Journal of Medicine (1994)

Long-term corticosteroid therapy for Crohn's disease is associated with important types of morbidity, such as osteoporosis. Safe and effective alternative treatments are required. Although a short-term benefit of cyclosporine in active Crohn's disease has been suggested, the long-term safety and efficacy of this treatment have not been established.
The Relations between the Antinuclear, Rheumatoid and L.E.-Cell Factors in the Systemic Rheumatic Diseases
Authors: Arthur P. Hall, Wadi A. Bardawil, Theodore B. Bayles, Alma D. Mednis, Nora Galins
Journal: New England Journal of Medicine (1960)

INTEREST in the pathophysiology of the systemic rheumatic diseases has been revitalized by the discovery of the serum factors that produce the L.E. cell in disseminated lupus erythematosus and the agglutination of sheep cells or latex particles in rheumatoid arthritis and the factors that, with the use of the fluorescent-antibody technic, have been shown to bind to cell nuclei or their components. These factors have been shown to be globulins1 2 3 4 5 6 7 and have been thought to be relatively specific for the various pathologic states. In fact, as time has passed, what were at first described as interesting findings in patients with . . .
Radiation Sensitivity in a Preclinical Mouse Model of Medulloblastoma Relies on the Function of the Intrinsic Apoptotic Pathway
Authors: Andrew J. Crowther, Jennifer K. Ocasio, Fang Fang, Jessica Meidinger, Jaclyn Wu, Allison M. Deal, Sha X. Chang, Hong Yuan, Ralf Schmid, Ian Davis, Timothy R. Gershon
Journal: Cancer Research (2016)

While treatments that induce DNA damage are commonly used as anticancer therapies, the mechanisms through which DNA damage produces a therapeutic response are incompletely understood. Here we have tested whether medulloblastomas must be competent for apoptosis to be sensitive to radiotherapy. Whether apoptosis is required for radiation sensitivity has been controversial. Medulloblastoma, the most common malignant brain tumor in children, is a biologically heterogeneous set of tumors typically sensitive to radiation and chemotherapy; 80% of medulloblastoma patients survive long-term after treatment. We used functional genetic studies to determine whether the intrinsic apoptotic pathway is required for radiation to produce a therapeutic response in mice with primary, Shh-driven medulloblastoma. We found that cranial radiation extended the survival of medulloblastoma-bearing mice and induced widespread apoptosis. Expression analysis and conditional deletion studies showed that Trp53 (p53) was the predominant transcriptional regulator activated by radiation and was strictly required for treatment response. Deletion of Bax, which blocked apoptosis downstream of p53, was sufficient to render tumors radiation resistant. In apoptosis-incompetent, Bax-deleted tumors, radiation activated p53-dependent transcription without provoking cell death and caused two discrete populations to emerge. Most radiated tumor cells underwent terminal differentiation. Perivascular cells, however, quickly resumed proliferation despite p53 activation, behaved as stem cells, and rapidly drove recurrence. These data show that radiation must induce apoptosis in tumor stem cells to be effective. Mutations that disable the intrinsic apoptotic pathways are sufficient to impart radiation resistance. We suggest that medulloblastomas are typically sensitive to DNA-damaging therapies, because they retain apoptosis competence. Cancer Res; 76(11); 3211-23. ©2016 AACR.
Case 49-1981
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, Betty U. McNeely, Barry L. Fanburg, Eugene J. Mark
Journal: New England Journal of Medicine (1981)

Presentation of CaseA 15-year-old girl was admitted to the hospital because of a question of a cyst of the right lung.The patient was the second of three normal children born to a mother 21 years of age; the pregnancy was complicated by hyperemesis gravidarum. At the age of two years the patient began to have mild asthma; she was reported to be allergic to dust. During her ninth and tenth years she resided in Florida and was free of wheezing. At the age of 11 years she returned to the metropolitan-Boston area, and wheezing recurred. An x-ray film . . .
ATPS-08DISCOVERY OF NOVEL GLIOMA-TARGETING PEPTIDES USING A HIGH-THROUGHPUT MICROFLUIDIC MAGNETIC-ACTIVATED SORTER
Authors: Choi-Fong Cho, Fernanda Bononi, Justin Wolfe, Bradley Pentelute, Leonard Luyt, Mariano Viapiano, E. Antonio Chiocca, Sean Lawler
Journal: Neuro-Oncology (2015)

High-grade gliomas are associated with very poor survival. Aggressive brain tumor cells invade into the surrounding normal brain and are impossible to remove by surgery. These cells are protected inside the brain from cancer drugs, leading inevitably to tumor regrowth and ultimately, patient death. There is an urgent need to develop therapeutics that can effectively enter the brain and target cancer cells. A protein called B/bΔg is an ideal target because it is present only in glioma cells, and is absent from normal brain cells. One-bead-one-compound (OBOC) libraries, which are composed of tens of thousands to millions of beads, each coated with a unique compound are widely used tools for discovering novel targeting ligands. In a search for glioma-specific peptides, we have screened an OBOC peptide library by labeling positive ‘hit’ beads with small magnetic particles coated with a B/bΔg-derived peptide. To isolate the magnetized ‘hit’ beads, we have developed a cost-effective and reproducible microfluidic magnetic-activated bead sorter. We have demonstrated that this device can rapidly sort magnetized OBOC beads with high throughput (15,000 beads per hour), specificity (>96%) and sensitivity (>99%). We have isolated several hundred ‘hit’ beads that were then subjected to a secondary screen using B/bΔg-overexpressing cells. Using these strategies, we have isolated and identified 8 novel B/bΔg-targeted peptides. All 8 peptides displayed increased uptake by B/bΔg-overexpressing cells compared to control cells. This increase in cellular uptake was not observed when control peptides were used. Circular dichroism analyses and competition studies revealed that 3 of these peptides displayed specific binding to the B/bΔg-derived peptide. Binding kinetics analyses and in vivo tests are currently underway. These peptides have great potential to be developed into next-generation therapeutic agents against high-grade gliomas that can be translated to improve outcome and quality of life in brain cancer patients.
Major Surgery in the Aged
Authors: Thomas J. Anglem, Martin L. Bradford
Journal: New England Journal of Medicine (1953)

AN abundance of statistical data testify to the fact that the population of the United States is in a phase of rapid expansion and of simultaneous aging. The application of these two facts to the problem of surgery in the aged is immediately apparent from consideration of the numbers by decades of persons in this country past the age of seventy in the years 1900 and 1950 and projected figures for the year 1960 (Table 1).It is obvious that the problem of surgery in the aged has become one of major importance because of the sheer number of persons . . .
The Use of Ether in the Narcoanalysis of Patients with War Neuroses
Authors: Henry H. Brewster
Journal: New England Journal of Medicine (1946)

THIS report deals with the technic and utility of ether in the treatment of war neuroses. Comparing ether to Pentothal, as used by Grinker and Spiegel,1 Sargant and Shorvon2 and Kelley3 found the former more effective for ventilating repressed emotions in acute war neuroses. That ether is useful in psychotherapy for other reasons is suggested by Sargant and Shorvon and also by Rogerson4 in his account of nitrous oxide narco-analysis of civilian patients with acute and chronic anxiety. Between January and May, 1945, ether was used at the 5th General Hospital in France in the psychotherapy of 100 neuropsychiatrie patients. . . .
ATCT-09IDH1 R132H MUTATIONS IN NRG ONCOLOGY/RTOG 9802: PHASE III STUDY OF RADIATION THERAPY (RT) ALONE VS RT PLUS PROCARBAZINE, CCNU, AND VINCRISTINE (PCV) IN PATIENTS WITH LOW GRADE GLIOMA (LGG)
Authors: Jan Buckner, Edward Shaw, Stephanie Pugh, Mark Gilbert, Geoffrey Barger, Stephen Coons, Peter Ricci, Dennis Bullard, Paul Brown, Keith Stelzer, David Brachman, John Suh, Christopher Schultz, Jean-Paul Bahary, Barbara Fisher, Harold Kim, Albert Murtha, Erica Bell, Minhee Won, Minesh Mehta, Walter Curran, Arnab Chakravarti
Journal: Neuro-Oncology (2015)
Case 11-2016
Authors: Kevin R. Schwartz, Chadi M. El Saleeby, Katherine Nimkin, Alison M. Friedmann, Aeri Moon, Lawrence R. Zukerberg
Journal: New England Journal of Medicine (2016)

A 12-year-old boy presented with a 1-month history of fever and abdominal pain. Three months earlier, he had traveled to the Dominican Republic. Laboratory evaluation revealed anemia and an elevated C-reactive protein level. Diagnostic tests were performed.
Patients with seronegative RA have more inflammatory activity compared with patients with seropositive RA in an inception cohort of DMARD-naïve patients classified according to the 2010 ACR/EULAR criteria
Authors: Lena Bugge Nordberg, Siri Lillegraven, Elisabeth Lie, Anna-Birgitte Aga, Inge Christoffer Olsen, Hilde Berner Hammer, Till Uhlig, Maria Karolina Jonsson, Désirée van der Heijde, Tore K Kvien, Espen Andre Haavardsholm
Journal: Annals of the Rheumatic Diseases (2016)

To compare the presentation of seropositive and seronegative early rheumatoid arthritis (RA) in disease-modifying antirheumatic drug (DMARD)-naïve patients classified according to the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) criteria.All patients had symptom duration from first swollen joint <2 years and were DMARD naïve with an indication for DMARD treatment. Patients were stratified as seropositive (positive rheumatoid factor (RF)+ and/or anticitrullinated peptide antibody (ACPA)+) or seronegative (RF- and ACPA-), and disease characteristics were compared between groups.A total of 234 patients were included, and 36 (15.4%) were seronegative. Ultrasonography (US) scores for joints (median 55 vs 25, p<0.001) and tendons (median 3 vs 0, p<0.001), number of swollen joints (median 17 vs 8, p<0.001), disease activity score (DAS; mean 3.9 vs 3.4, p=0.03) and physician global assessment (mean 49.1 vs 38.9, p=0.006) were significantly higher in seronegative patients compared with seropositive. Total van der Heijde-modified Sharp score, Richie Articular Index and patient-reported outcome measures were similar between groups.Seronegative patients had higher levels of inflammation, assessed both clinically and by US, than seropositive patients. These differences may reflect the high number of involved joints required for seronegative patients to fulfil the 2010 ACR/EULAR classification criteria for RA.NCT01205854; Pre-results.
The Effect on Endogenous Thyroid Activity of Feeding Desiccated Thyroid to Normal Human Subjects
Authors: Monte A. Greer
Journal: New England Journal of Medicine (1951)

IT HAS been known for many years that a reciprocal relation appears to exist between the levels of circulating thyroxin and thyrotrophin in the vertebrate species so far investigated. Until recently, however, direct tests of thyroid activity in man have not been feasible. Within the last few years, radioactive iodine has provided a new method for the study of thyroid function, permitting observations that would otherwise be impossible. Using shielded G–M counters, it is possible to follow directly the accumulation of radioiodine in the thyroid gland. Studies in several clinics have indicated that this method is an accurate index of . . .
139PD: Lifetime incidence of brain metastases (BM) in EGFR-mutant (M+) lung cancer treated with first-line EGFR TKIs
Authors: D.Z. Ng, W.L. Tan, W.S. Ong, E.M. Gan, A. Jain, E.-H. Tan, D. Tan
Journal: Journal of Thoracic Oncology (2016)