tbuckley/cabot-search huggingface dataset:
Cardioversion from Atrial Fibrillation without Prolonged Anticoagulation with Use of Transesophageal Echocardiography to Exclude the Presence of Atrial Thrombi
Authors: Warren J. Manning, David I. Silverman, Stephen Gordon, Harlan M. Krumholz, Pamela S. Douglas
Journal: New England Journal of Medicine (1993)

Because atrial thrombi are poorly detected by conventional noninvasive techniques such as transthoracic echocardiography, patients with prolonged atrial fibrillation usually receive several weeks of oral anticoagulation therapy before cardioversion is attempted. We wondered whether transesophageal echocardiography, an accurate method of detecting atrial thrombi, would allow early cardioversion to be performed safely if no thrombi were identified.
DDEL-14THE RELATIONSHIP BETWEEN APOPTOSIS AND STMN1 REGULATING THE CHEMOSENSITIVITY OF GLIOMA CELLS TO TMZ
Authors: Jie Ma, Feili Liu
Journal: Neuro-Oncology (2015)

OBJECTIVE: To investigate the role of autophagy in the process of STMN1 regulating glioma chemosensitivity to TMZ. METHODS: Using TEM observe autophagy ultrastructure-autophagolysosome after TMZ induction in U251-MG (RNAi-STMN1). Western-blot was used to detect protein expression. To observe the TMZ-induced autophagic vacuoles in U251-MG through GFP-LC3B tracer method under laser scanning confocal microscope (RNAi-STMN1), as well as fluorescence intensity changes after the suppression of autophagy by 3-MA or bafilomycin A1. And qRT-PCR and western-blot are used to detect gene and protein expression levels. Finally, the sensitivity to TMZ of U251-MG (RNAi-STMN1) is assayed by CCK-8 kits after the inhibition of autophagy by 3-MA and/or bafilomycin A1 early and late. RESULTS: After TMZ induction, autophagic vacuoles emerge in cytoplasm of U251-MG. For U251-MG (Si-STMN1), The degree of cell damage is worse than U251-MG and U251-MG(Scramble), and autophagic vacuoles in the cytoplasm increase after TMZ induction. In U251-MG and A172 cell lines, LC3, Beclin1 and ATG5 mRNA and protein expression level significantly increase(P   0.05). CONCLUSION: TMZ can induce autophagy in U251-MG and U251-MG (Si-STMN1), autophagy-related genes / proteins significantly increase after TMZ induction.
Treatment of bulimia with brief psychoeducational group therapy
Authors: M E Connors, C L Johnson, M K Stuckey
Journal: American Journal of Psychiatry (1984)

Two groups of 10 normal-weight bulimic women received short-term, structured group treatment beginning 3 weeks apart in a multiple baseline design. The multifaceted treatment approach incorporated education, self-monitoring, goal setting, assertion training, relaxation, and cognitive restructuring. Results showed an overall reduction of 70% in binge/purge episodes. There were significant improvements in psychological functioning, including self-esteem, depression, assertiveness, and pathological attitudes about eating.
Rare and complex mutations of epidermal growth factor receptor (EGFR) and efficacy of tyrosine kinase inhibitor (TKI) in patients with non-small cell lung cancer (NSCLC).
Authors: Bhumsuk Keam, Dong-Wan Kim, Jin Hyun Park, Jeong-Ok Lee, Tae Min Kim, Se-Hoon Lee, Yoon-Kyung Jeon, Doo Hyun Chung, Dae Seog Heo
Journal: Journal of Clinical Oncology (2012)

7566 Background: Other than in-frame deletional mutation (MT) in exon 19 and Leu858Arg point MT in EGFR gene, there are many rare and complex MT. The purpose of this study was to investigate was to clarify the clinical significance of rare and complex MT, and the efficacy of EGFR TKI in these patients. Methods: Rare MTs were defined any MT other than deletional MT in exon 19, Leu858Arg in exon 21, and Thr790Met in exon 20. Complex MT was defined two different EGFR MTs co-occurring within the single tumor sample. We have analyzed consecutive database of NSCLC patients who were treated with either gefitinib or erlotinib at Seoul National University Hospital between Jan. 2002 and Dec. 2011. For analysis of EGFR MT, coding sequences from exon 18 to 21 were amplified by nested PCR and subjected to direct sequencing methods. Results: Among the 1,159 TKI treated patients, 301 patients had EGFR MT (177 patients (58.8%) with del-19, 104 patients (34.6%) with Leu858Arg, and 20 patients (6.6%) with rare MT). Twenty-three (7.6%) patients have complex MT, and 55 (18.3%) patients have Gln787Gln polymorphism particularly associated with Leu858Arg MT. Identified rare MT were follows; exon 18: Leu692Phe, Glu707Lys, Glu709Gly, Lys714Asn, Gly7Ala, Thr725Thr, exon 19: Ala755Asp Lys737Thr, exon 20: Val786Met, exon21: Ala871Gly, Gly873Gln, Leu833Val, Val834Leu, Arg836Cys, Pro848Leu, Ala859Thr, Leu861Gln. When categorizing 3 groups (group A: classic MT alone, group B: complex MT with classic + rare MT, group C: rare MT alone or complex MT with rare MTs), response rate (RR) to TKI was different between each groups (RR= 78.7% in group A vs. 69.2% in group B vs. 38.5% in group C, respectively, P &lt; 0.001). Progression-free survival (PFS) was also poorer in rare MT (median PFS: 12.1 mo vs. 7.6 mo vs. 2.1 mo, respectively, P= 0.020,). Gln787Gln polymorphism of exon 21 was not associated with RR or PFS (P= 0.101, P= 146, respectively) Conclusions: In this large case series, NSCLC patients who harboring rare MT other than del-19 and Leu858Arg, does not seems response to EGFR TKI. However, complex MT with the classical MT showed similar treatment efficacy toward EGFR TKI with that of classical MT alone.
Serologic Responses to Heterologous Escherichia Serogroups in Women with Pyelonephritis
Authors: Mary Jo Carter, N. Joel Ehrenkranz, Joseph Burns, Janet C. Cassady
Journal: New England Journal of Medicine (1968)

Hemagglutinating antibody levels to 11 heterologous escherichia serogroups (01, 04, 06, 07, 014, 018, 025, 075, 077, 086 and 0119) measured in 61 women with pyelonephritis and 48 control women, showed significantly higher mean levels to 04, 06 and 086 in those with pyelonephritis. Individual levels to 04 and 06 often exceeded 1:100 in them. No escherichia organisms were recovered from the urine of a third of the persons with pyelonephritis, and yet in half of these elevated (1:100 or higher) levels to serogroup 04 or 06 were present. Elevated levels to 06 in particular, and to multiple escherichia serogroups in general, occurred primarily in younger women (under 50 years old) with pyelonephritis. Escherichia antibody patterns could not be attributed to nosocomial infection. It is concluded that elevated hemagglutinin levels to heterologous escherichia serogroups constitute an indicator of pyelonephritis that may be particularly useful in the study of asymptomatic conditions and in infections partially treated by antimicrobial therapy.
DNA Polymorphism of the C4 Genes
Authors: Alexander S. Whitehead, Derek E. Woods, Ellen Fleischnick, Janice E. Chin, Edmond J. Yunis, Aubrey J. Katz, Park S. Gerald, Chester A. Alper, Harvey R. Colten
Journal: New England Journal of Medicine (1984)

Polymorphisms of the proteins encoded by genes that lie within the major histocompatibility complex (MHC) have served as useful markers for organ transplantation and in genetic analysis of a large number of MHC-linked diseases. To extend the range of MHC polymorphic markers, we used a complementary-DNA probe specific for the fourth component of human complement (C4) to identify a new variant within the MHC. Polymorphic variants at the DNA level were detected among subjects with identical phenotypes of the corresponding protein. C4 genomic polymorphisms are inherited with the segment of the short arm of chromosome 6 that carries the HLA-DR and complement loci. The autosomal codominant mode of inheritance of this genetic marker and its utility for evaluation of 21-hydroxylase–deficiency congenital adrenal hyperplasia, one of the many MHC-linked diseases, were established. (N Engl J Med 1984; 310:88–91.)
Establishment and molecular characteristics of PC-9 derived erlotinib resistant cell lines
Authors: M. Jida, H. Yamamoto, T. Kubo, T. Hayashi, H. Otani, Y. Sano, S. Toyooka
Journal: Journal of Clinical Oncology (2009)

e22193 Background: EGFR mutation is closely associated with tumor responsiveness to EGFR tyrosine kinase inhibitors (TKIs), gefitinib or erlotinib. However, many non-small cell lung cancer (NSCLC) cases with EGFR mutation that had responded to EGFR-TKIs finally acquire resistance to EGFR-TKIs. It has been reported that T790M mutation and MET amplification caused resistance to EGFR-TKIs . Recent study suggested that overexpression of HGF was also related to resistance to EGFR-TKIs. However, the whole mechanism of acquired resistance to TKIs is still not fully known. Methods: We established 5 clones of elrotinib resistant PC-9 cell line (harboring EGFR exon 19 deletion) (designated as PC-9ER1–5) by exposing PC-9 to low-dose erlotinib. The protein expression of EGFR-related molecules was examined by Western blotting. Array comparative genomic hybridization (aCGH) or real time quantitative PCR (qPCR) assay was performed to examine copy numbers of EGFR-related genes. Results: In MTS assay, the IC 50 value for the parental PC-9 cells was 0.02 μmol/L. By contrast, those for PC-9ER1–5 were more than 33μmol/L. All 5 resistant cell lines retained exon19 deletions and did not obtain T790M mutation. The qPCR assay and aCGH showed no MET amplification in PC-9 or PC-9ER1–5. HGF protein was not overexpressed in PC-9ER1–5 by ELISA. The protein expressions of several molecules in the EGFR-Akt signaling pathway were examined by western blotting after erlotinib treatment. Although phospho-EGFR was suppressed in both PC-9 and PC-9ER1–5 with 2-μmol/L erlotinib, phospho-Akt was not suppressed in PC-9ER1–5. PTEN expression was not down-regulated in PC-9ER1–5. The combination of erlotinib and PHA-665752, MET tyrosine kinase inhibitor, did not suppress phospho-Akt or cell proliferation in PC-9ER1–5. Conclusions: As common molecular features of our EGFR-TKI resistant cell lines, phospho-Akt was not suppressed with exposure to erlotinib. These cell lines did not show previously reported features of resistant cell lines including T790M mutation, MET amplification or HGF overexpression. Our results indicated that other mechanisms leading to Akt activation caused resistance to EGFR-TKIs. No significant financial relationships to disclose.
MTR-10PHARMACOLOGICAL NOTCH BLOCKADE IN GLIOMAS INDUCES AUTOPHAGY AND COMBINATION TREATMENT WITH AN AUTOPHAGY INHIBITOR INCREASES TUMOR CELL DEATH
Authors: Manabu Natsumeda, Hiroaki Miyahara, Harpreet Kaur, Charles Eberhart
Journal: Neuro-Oncology (2015)

BACKGROUND: Induction of autophagy has been identified as a potential mechanism for chemotherapeutic resistance, and its manipulation has increasingly been explored as a treatment strategy in many cancers. However, there is minimal data on the effects of the Notch pathway on autophagy in cancer, and none in gliomas. We examined if Notch pathway blockade using a gamma-secretase inhibitor (GSI) MRK003 would induce autophagy in glioma neurosphere lines and studied the effects of chloroquine (CQ), a late-stage autophagy inhibitor, in combination with the GSI. METHODS: 500,000 cells from 2 neurosphere lines (JHH520 and HSR-GBM1), maintained in Neural Stem Cell medium with EGF and FGF, were treated with DMSO, 0.5-5 µM levels of MRK003, and/or 10 µM CQ for 24-72 hours. Western blotting was performed to detect alterations in protein levels of LC3B, pAkt, Akt, p62 and cleaved PARP. MTS, Ki-67, Annexin V, cell cycle and soft agar assays were performed to look at the combinatorial effects of MRK003 and CQ. RESULTS: An LC3B-II band, suggesting induction of autophagy, was observed after Notch pathway blockade in a dose dependent manner in the 2 neurosphere lines. Reduction of pAkt was seen in GBM1, suggesting mTORC2 inhibition. Decreased growth (MTS assay both p <0.001), proliferation (Ki-67 assay: both p <0.05), increased apoptosis (increased sub-G1 population: JHH520 p <0.005, HSR-GBM1 p <0.05; increased Annexin V percentage: JHH520 p <0.05, HSR-GBM1 p <0.01, increased cleaved PARP protein expression), and decreased clonogenicity (soft agar assay) were seen after combination MRK003 and CQ treatment compared to DMSO. CONCLUSIONS: Induction of autophagy, possibly through mTORC2 inhibition, occurs after Notch inhibition in glioma neurospheres using a GSI. Inhibition of autophagy using CQ caused increased cytotoxicity. These results suggest a possible resistance mechanism to Notch inhibition in malignant gliomas and pave the way for a new treatment strategy.
Patterns of Amyloidosis and Their Association with Plasma-Cell Dyscrasia, Monoclonal Immunoglobulins and Bence-Jones Proteins
Authors: Takashi Isobe, Elliott F. Osserman
Journal: New England Journal of Medicine (1974)

The frequency of monoclonal immunoglobulins and Bence-Jones proteins was studied in 100 cases of amyloidosis classified according to the patterns of distribution of amyloid. Monoclonal immunoglobulins, Bence-Jones proteins (or both) were documented in all 50 Pattern I ("primary-type") cases, nine of 17 Pattern II ("secondary-type") cases, 26 of 30 Mixed Pattern I and II cases and in all three cases of localized amyloidosis. Forty-six per cent of the patients with amyloidosis (all patterns) had Bence-Jones protein only, without a monoclonal immunoglobulin, as compared with 21 per cent of cases of myeloma without associated amyloidosis. There was a higher proportion of λ-type Bence-Jones proteins in the amyloidosis group, and amyloid-related proteins were relatively more anionic than nonamyloid-related proteins. It is postulated that amyloid-related monoclonal immunoglobulins and Bence-Jones proteins may be autoantibodies or fragments of autoantibodies directed against normal tissue constituents. (N Engl J Med 290:473–477, 1974)
Family history of anxiety disorders in control subjects with lactate- induced panic attacks
Authors: R Balon, M Jordan, R Pohl, V K Yeragani
Journal: American Journal of Psychiatry (1989)

The authors infused 45 control subjects with sodium lactate. Eight of 10 subjects with lactate-induced panic attacks and 26 of 35 without panic attacks were interviewed. An investigator, blind to the outcome of the infusion study, obtained family histories of 160 relatives. There was a high prevalence of anxiety disorders among first-degree relatives of subjects with panic attacks. There was no significant difference in the prevalence of mood disorders and substance abuse between first-degree relatives of subjects with (N = 45) and without (N = 115) panic attacks. The results suggest that individuals with a family history of anxiety disorders may be vulnerable to lactate-induced panic attacks.
A Preliminary Evaluation of a Recombinant Circumsporozoite Protein Vaccine against<i>Plasmodium falciparum</i><i>Malaria</i>
Authors: José A. Stoute, Moncef Slaoui, D. Gray Heppner, Patricia Momin, Kent E. Kester, Pierre Desmons, Bruce T. Wellde, Nathalie Garçon, Urszula Krzych, Martine Marchand, W. Ripley Ballou, Joe D. Cohen
Journal: New England Journal of Medicine (1997)

The candidate vaccines against malaria are poorly immunogenic and thus have been ineffective in preventing infection. We developed a vaccine based on the circumsporozoite protein of Plasmodium falciparum that incorporates adjuvants selected to enhance the immune response.
Stopping Medication in Children with Epilepsy
Authors: Ronald Emerson, Bernard J. D'Souza, Eileen P. Vining, Kenton R. Holden, E. David Mellits, John M. Freeman
Journal: New England Journal of Medicine (1981)

Anticonvulsant therapy was discontinued in 68 children with epilepsy who had had no seizures for four years, in an attempt to find the risk of relapse and the factors predictive of recurrence. In this population the probability of remaining free of seizures for four years after discontinuation of medication was 69 per cent. Children were more likely to have recurrent seizures if they were mentally retarded, if their seizures had begun before two years of age, if they had had many generalized seizures before control, or if they had had a definitely abnormal electroencephalogram before medication was discontinued. Multivariate analysis showed that the best predictors of outcome were the electroencephalogram taken at cessation of medication and the number of seizures before control. We conclude that in the normal child who has not had many seizures and whose electroencephalogram is normal or mildly abnormal, the risks of discontinuing medication after four seizure-free years are acceptable.
Trends in Enrollment, Clinical Characteristics, Treatment, and Outcomes According to Age in Non–ST-Segment–Elevation Acute Coronary Syndromes Clinical Trials
Authors: Kristian Kragholm, Sarah A. Goldstein, Qinghong Yang, Renato D. Lopes, Phillip J. Schulte, Gwen M. Bernacki, Harvey D. White, Kenneth W. Mahaffey, Robert P. Giugliano, Paul W. Armstrong, Robert A. Harrington, Pierluigi Tricoci, Frans Van de Werf, John H. Alexander, Karen P. Alexander, L. Kristin Newby
Journal: Circulation (2016)

Background— Representation by age ensures appropriate translation of clinical trial results to practice, but, historically, older patients have been underrepresented in clinical trial populations. As the general population has aged, it is unknown whether clinical trial enrollment has changed in parallel. Methods and Results— We studied time trends in enrollment, clinical characteristics, treatment, and outcomes by age among 76 141 patients with non–ST-segment–elevation acute coronary syndrome enrolled in 11 phase III clinical trials over 17 years (1994–2010). Overall, 19.7% of patients were ≥75 years; this proportion increased from 16% during 1994 to 1997 to 21% during 1998 to 2001 and 23.2% during 2002 to 2005, but declined to 20.2% in 2006 to 2010. The number of comorbidities increased with successive time periods irrespective of age. There were substantial increases in the use of evidence-based medication in-hospital and at discharge regardless of age. Although predicted 6-month mortality increased slightly over time, observed 6-month mortality declined significantly in all age strata (1994–1997 versus 2006–2010: &lt;65 years: 3.0% versus 1.9%; 65–74 years: 7.5% versus 3.4%; 75–79 years: 13.0% versus 6.5%; 80–84 years: 17.6% versus 8.2%; and ≥85 years: 24.8% versus 12.6%). Conclusions— The distribution of enrollment by age in phase III non–ST-segment–elevation acute coronary syndrome trials was unchanged over time. Irrespective of age, post–myocardial infarction mortality decreased significantly over time, concurrent with increased evidence-based care and despite increasing comorbidities. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00089895.
Non-Small Cell Lung Cancer'S Burden of Disease in Portugal
Authors: M.F. Borges, M. Gouveia, J. Alarcão, R. Sousa, F. Barata, E. Laranjeira, F. Lopes, B. Parente, L. Pinheiro, M.E. Teixeira, A. Vaz-Carneiro, J. Costa
Journal: Annals of Oncology (2014)
Case 35-1979
Authors: Richard C. Cabot, Robert E. Scully, James J. Galdabini, Betty U. McNeely, George A. Jacoby, Newton E. Hyslop
Journal: New England Journal of Medicine (1979)

Presentation of CaseA 40-year-old woman was admitted to the hospital because of fever.At the age of 14 years she had rheumatic fever, which was followed by the appearance of a faint heart murmur. Erythromycin prophylaxis was prescribed because of a rash that complicated the administration of penicillin. At the age of 20 years renal tuberculosis was diagnosed. Isoniazid, para-aminosalicylic acid and streptomycin were administered during the next three years. At the age of 30 years the patient was seen at another hospital because of acute pyelonephritis; an intravenous pyelographic examination was negative. Four months before admission she began . . .
Relation between Preoperative Inspiratory Lung Resistance and the Outcome of Lung-Volume–Reduction Surgery for Emphysema
Authors: Edward P. Ingenito, Randall B. Evans, Stephen H. Loring, David W. Kaczka, Jennifer D. Rodenhouse, Simon C. Body, David J. Sugarbaker, Steven J. Mentzer, Malcolm M. DeCamp, John J. Reilly
Journal: New England Journal of Medicine (1998)

Surgery to reduce lung volume has recently been reintroduced to alleviate dyspnea and improve exercise tolerance in selected patients with emphysema. A reliable means of identifying patients who are likely to benefit from this surgery is needed.
Conditioned-Reflex Treatment of Chronic Alcoholism
Authors: Paul O'Hollaren, Frederick Lemere
Journal: New England Journal of Medicine (1948)

THE conditioned-reflex treatment of chronic alcoholism, as employed at the Shadel Sanitarium, consists of establishing an aversion to the sight, taste, smell and thought of all types of alcoholic beverages. This is accomplished by repeated conditioning seances, which may number four to eight before the desired aversion is established.An individual seance consists of the administration of a nauseant drug, emetine, which, acting as the unconditioned stimulus, elicits an unconditioned reflex. Immediately before the onset of nausea a patient is given various types of alcoholic beverages (the conditioned stimulus). After the repetition of several such seances a conditioned-reflex aversion against . . .
IRAK-M Expression in Tumor Cells Supports Colorectal Cancer Progression through Reduction of Antimicrobial Defense and Stabilization of STAT3
Authors: Rebecca Kesselring, Joachim Glaesner, Andreas Hiergeist, Elisabeth Naschberger, Helmut Neumann, Stefan M. Brunner, Anja K. Wege, Caroline Seebauer, Gudrun Köhl, Susanne Merkl, Roland S. Croner, Christina Hackl, Michael Stürzl, Markus F. Neurath, André Gessner, Hans-Juergen Schlitt, Edward K. Geissler, Stefan Fichtner-Feigl
Journal: Cancer Cell (2016)
Case 19-1994
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, Alan W. Hackford, Fiona Graeme-Cook
Journal: New England Journal of Medicine (1994)

Presentation of CaseA 47-year-old woman was admitted to the hospital because of intermittent abdominal pain, vomiting, and weight loss.The patient had been well until six years earlier, when she began to experience intermittent bouts of crampy periumbilical pain radiating to the back. The episodes typically began after a meal but were sometimes unrelated to the intake of food; they lasted from a few minutes to several days but most often subsided after about four hours. Episodes of pain were accompanied by abdominal distention and vomiting of mucus and bile, with temporary constipation that often subsided with the passage . . .