tbuckley/cabot-search huggingface dataset:
Relation of Hemorrhage and Thrombosis to Prothrombin during Treatment with Coumarin-Type Anticoagulants
Authors: Herbert S. Sise, Sean M. Lavelle, Dionysios Adamis, Robert Becker
Journal: New England Journal of Medicine (1958)

THE increasing enthusiasm for treating thromboembolic diseases with prothrombin-reducing drugs for long periods in ambulatory patients has emphasized the lack of clear definition of the therapeutic range of anticoagulation. These are now more often older patients with vascular disease who are difficult to manage, sometimes follow instructions poorly and are more prone to bleeding complications than the younger patients, who are usually treated for recurrent phlebitis, pulmonary embolism or peripheral embolism from heart disease.Control of therapy has traditionally been carried on with the "prothrombin-time" test of Quick.∥ This test has proved remarkably satisfactory considering the great variation of opinion . . .
Candidate biomarker analyses in gastric or gastro-esophageal junction carcinoma: REGARD trial of single-agent ramucirumab (RAM) vs. placebo (PL).
Authors: Charles S. Fuchs, Josep Tabernero, Jiri Tomasek, Ian Chau, Bohuslav Melichar, Howard Safran, Mustapha Ali Tehfe, Filip Dumitru, Eldar Topuzov, Luis Schlittler, Anghel Adrian Udrea, William Campbell, Stephen Brincat, Michael Emig, Symantha A. Melemed, Rebecca R. Hozak, David Ferry, William Caldwell, Jaffer A. Ajani
Journal: Journal of Clinical Oncology (2015)

4029 Background: Vascular endothelial growth factors (VEGFs) are key regulators of tumor angiogenesis. RAM, a recombinant human IgG1 monoclonal antibody specific for VEGF receptor 2 (VEGFR2), inhibits VEGF-A, -C and -D binding to VEGFR2 and inhibits ligand-induced mitogenesis of human endothelial cells. We evaluated candidate tumor (HER2, VEGFR2) and serum (VEGF-C, -D, and soluble [s] VEGFR1 and 3) biomarkers for correlation with overall survival (OS) and progression-free survival (PFS) in patients from the randomized phase 3 REGARD trial (NCT00917384) that demonstrated survival benefits for RAM vs. PL. Methods: Of 355 patients randomized to RAM or PL in REGARD, there was at least one evaluable biomarker result for 152 (43%) patients using VEGFR2 immunohistochemistry (IHC) or HER2 (IHC or fluorescence in situ hybridization [FISH]) in baseline tumor tissue samples. For 32 (9%) patients, baseline serum samples were analyzed using VEGF-C, -D, sVEGFR1 or 3 validated assays. Assay analyses were blinded. Results: The table provides the results of the HER2 analyses in tumor tissue (N = 147) and VEGFR2 analyses in tumor blood vessels (N = 143). The small number of patients with serum samples limited interpretation for candidate circulating biomarkers. Conclusions: Exploratory candidate biomarker analysis of tumor biopsies and serum from REGARD patients did not identify a significant predictive marker for RAM efficacy. Further examination of the role of VEGFR2 pathway biomarkers is warranted in ongoing RAM trials. Clinical trial information: NCT00917384. HER2+a RAM n=16 HER2+a PL n=5 HER2- a RAM n=80 HER2- a PL n=46 mOSb 5.1 2.8 6.6 4.5 95% CI 1.3-9.6 1.3-6.7 5.5-8.5 2.5-6.4 High VEGFR2c RAM n=49 High VEGFR2c PL n=23 HR Low VEGFR2c RAM n=46 Low VEGFR2c PL n=25 HR mOS b 6.6 2.3 0.69 5.6 4.5 0.73 95% CI 5.0-9.3 1.5-4.8 0.38-1.22 3.4-7.1 2.6-6.7 0.42-1.26 mPFS b 2.8 1.3 0.35 2.2 1.9 0.73 95% CI 1.5-4.1 1.1-1.3 0.20-0.59 1.4-2.8 1.3-2.7 0.42-1.27 Note: Treatment-by-VEGFR2 interaction p-values, not adjusted for multiplicity, were 0.878 for mOS and 0.051 for mPFS. Abbreviations: CI=confidence interval; HR=hazard ratio; m=median. aBang et al. 2010 criteria. bin months. cHigh= ≥ median H-score (35); low= <35.
The t(9;14)(p13;q32) chromosomal translocation associated with lymphoplasmacytoid lymphoma involves the PAX-5 gene
Authors: S Iida, PH Rao, P Nallasivam, H Hibshoosh, M Butler, DC Louie, V Dyomin, H Ohno, RS Chaganti, R Dalla-Favera
Journal: Blood (1996)
FRI0070 Prevalence and Evolution of Monoclonal Gammapathy of Undetermined Significance in Patients with Rheumatoid Arthritis Patients Treated with Abatacept: Data from the ORA Registry
Authors: C. Salliot, C. Beaudoin, K. Chauffier, M. Gilson, R. Séror, C. Sordet, L. Sparsa, I. Pane, P. Ravaud, J.E. Gottenberg
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Monoclonal gammapathy of undetermined significance (MGUS) is premalignant plasma-cell disorder. Its prevalence is about 3.2% of the general population older than 50 years. In patients with rheumatoid Arthritis (RA), little is known about the prevalence of MGUS and its evolution under biologics. <h3>Objectives</h3> To assess the prevalence of MGUS in longstanding RA, the characteristics of patients with MGUS, and the evolution of MGUS under abatacept. <h3>Methods</h3> ORA (Orencia and Rheumatoid arthritis) is a French prospective 7-year registry which included 1017 RA patients at abatacept initiation. Data on disease characteristics, biologic abnormalities including the presence of a monoclonal gammapathy, and the occurrence of severe adverse events, including cancers such as lymphomas, myelomas are collected at enrollment and every 6 months. <h3>Results</h3> Among the 1017 RA patients included in ORA registry, 38 had a MGUS (3.7%). Baseline disease characteristics (gender, age, RA duration, positivity for anti-CCP and rheumatoid factors, DAS28ESR) were not significantly different between patients with or without MGUS. In RA patients with MGUS, mean age and RA duration were 58.2±13.6 and 13.8±9.5 years, respectively. 76.3% were women 52.6% and 55.2% had anti-cyclic citrullinated peptide (anti-CCP) and rheumatoid factors (RF), respectively. 92.1% of patients previously received biological treatments (with a mean of 2.5±1.3 biologics): 89.5% previously received anti-TNFs and 42.1% receive rituximab As concomitant treatment, 47.3% received methotrexate and 84.2% corticosteroids. During the follow-up of 1.50±1.10 years, no significant change in the blood level of the monoclonal component was observed. Two patients developed a multiple myeloma;. For the first patient, Immunoglobulin G Kappa stade 3 myeloma was diagnosed only 83 days after abatacept initiation. For the second patient, immunoglobuline G myeloma stade 1 was diagnosed 1 year after abatacept initiation. No lymphoma nor amyloidosis occurred. <h3>Conclusions</h3> The prevalence of MGUS in this population with longstanding RA was similar to that observed in the general population (∼3%). No significant effect of abatacept on the blood level of the monoclonal component was observed after 2 years of prospective follow-up. Although no signal has been observed, a longer follow-up is needed to evaluate the effect of abatacept on the risk of malignant transformation of MGUS. <h3>References</h3> Kyle RA et al. Prevalence of MGUS, N Engl J Med 2006;354:1362-9. Smale SW et al. Scand J Rheumatol. 2007;36: 405-6. <h3>Disclosure of Interest</h3> None declared
Ventricular-Assist Pumping in Patients with Cardiogenic Shock after Cardiac Operations
Authors: William S. Pierce, Grant V. S. Parr, John L. Myers, Walter E. Pae, Anthony P. Bull, John A. Waldhausen
Journal: New England Journal of Medicine (1981)

A ventricular-assist pump was used to support the circulation in eight patients who could not be separated from cardiopulmonary bypass after open-heart operations. In five patients with left ventricular failure, the systemic circulation was maintained with pumping from the left atrium to the aorta for 7.0 +/- 1.8 days (mean +/- S.E.M.); three of these patients were well four to 17 months after surgery. In two patients with biventricular failure, right and left ventricular bypass supported the circulation, but neither patient survived. One other patient had isolated right ventricular failure; pumping from the right atrium to the pulmonary artery maintained the pulmonary circulation for 2.2 days. This patient lived for 18 months. Use of the ventricular-assist pump in our patients provided complete support of the systemic or pulmonary circulation or both. Profoundly depressed ventricular function is potentially reversible if technical problems in employing the pump can be avoided.
Clinical and Biochemical Manifestations of Depression
Authors: Philip W. Gold, Frederick K. Goodwin, George P. Chrousos
Journal: New England Journal of Medicine (1988)

(Second of Two Parts)Neurohormonal HypothesesThe cardinal biologic manifestations of major affective disorder consist of alterations in the hypothalamic centers that govern food intake, libido, circadian rhythms, and the synthesis and release of hypothalamic hormones into hypophysial portal blood and the systemic circulation. Patients with melancholia typically have anorexia, decreased sexual interest, altered timing of the cycle of rest and activity (i.e., early-morning awakening), diurnal variation in mood, and endocrine abnormalities such as hypercortisolism.4, 84 , 85 In a typical depression, the defining characteristics include hyperphagia and hypersomnia.8 The first neuroendocrine investigations into major affective disorder rested on the demonstration that monoaminergic . . .
Risk of Congenital Abnormality after Inadvertent Rubella Vaccination of Pregnant Women
Authors: John F. Modlin, Kenneth Herrmann, A. D. Brandling-Bennett, Donald L. Eddins, Gregory F. Hayden
Journal: New England Journal of Medicine (1976)

The risk to a fetus after rubella vaccination of its mother is unknown. The Center for Disease Control has compiled information from the pregnancies of 343 women inadvertently given rubella vaccine shortly before or after conception. The pregnancies of 145 women were terminated by therapeutic abortion, and rubella vaccine virus was recovered from the products of conception of nine women, including six of the 28 known to be seronegative to rubella at the time of vaccination. None of the 172 infants carried to term had either clinical or serologic evidence of rubella infection, including 38 infants of women known to be susceptible and 12 additional women estimated to be susceptible at the time of rubella vaccination. On the basis of the binomial distribution, the maximum risk of fetal infection after maternal rubella vaccination is between 5 and 10 per cent. The actual risk is probably less. (N Engl J Med 294:972–974, 1976)
Phase II study of ZD1839 in patients with newly diagnosed grade 4 astrocytoma
Authors: J. H. Uhm, K. V. Ballman, C. Giannini, J. C. Krauss, J. C. Buckner, D. James, B. W. Scheithauer, J. R. O'Fallon, K. A. Jaeckle
Journal: Journal of Clinical Oncology (2004)

1505 Background: Amplification of the EGFR represents one of the most frequent gene alterations in glioblastoma (GBM). In the current study, our objectives were to evaluate ZD1839 (Iressa), a potent EGFR inhibitor, in the treatment of adults with newly diagnosed GBM, and to correlate response with tumor EGFR status. Methods: By the end of the study, 98 patients (96 evaluable) were accrued. All were newly diagnosed GBM patients who were radiographically stable/improved following radiation treatment (enrollment within in 5 weeks of radiation completion). No prior chemotherapy was permitted. EGFR amplification/mutation, as assessed by FISH and immunohistochemistry, was not required for treatment with ZD1839 but was studied when tissues were available. ZD1839 was administered at 500mg QD; for patients receiving dexamethasone and/or enzyme-inducing (CYP3A4) agents, dose was escalated to a maximum of 1000mg QD. Treatment cycles were repeated at 4-week intervals with tumor response assessed by brain MRI at 8-week intervals. Results: Survival (calculated from time of initial surgery) at 1 year (primary endpoint) with ZD1839 was 54.2%, which was not statistically different compared to that of historical control population (48.9%, 3 previous phase III NCCTG studies of newly diagnosed GBM patients). Progression-free status at 1 year post-RT (13.3%) was also not statistically different to that of historical controls (16.1%). EGFR amplification, as assessed by FISH and immunohistochemistry, was not associated with survival or progression-free survival. Fatigue (41%), rash (62%), and loose stools (58%) constituted the most frequent adverse events, the majority of these being limited to Grade 1/2. Conclusions: Modest activity of ZD1839 and other EGFR inhibitors have been previously suggested in relatively smaller studies with recurrent GBM. In our current study of nearly one hundred patients with newly diagnosed GBM, treatment with ZD1839 was not associated with significant improvement in overall- nor progression-free survival. Whether EGFR inhibitor therapy in combination with other treatments, such as concurrent radiation, will show synergy is being addressed in ongoing studies. No significant financial relationships to disclose.
Declining Incidence of Nephropathy in Insulin-Dependent Diabetes Mellitus
Authors: Mats Bojestig, Hans J. Arnqvist, Goran Hermansson, Bengt E. Karlberg, Johnny Ludvigsson
Journal: New England Journal of Medicine (1994)

The high relative mortality among patients with insulin-dependent diabetes mellitus results mainly from diabetic nephropathy. The cumulative incidence of nephropathy of 25 to 30 percent among patients who had had diabetes for 25 years remained stable from 1950 to the early 1980s. In a population study, we assessed recent trends in the incidence of diabetic nephropathy.
Establishment and Characterization of Two Human Mixed Mesodermal Tumor Cell Lines From the Same Patient
Authors: Isao Ono, Isamu Ishiwata, Akio Tashiro, Akio Mihara, Takenori Nakaguchi, Shigetake Ito, Naohiko Tokita, Susumu Nakajima, Chieko Ishiwata, Masayuki Soma, Hiroshi Ishikawa
Journal: JNCI Journal of the National Cancer Institute (1984)

A cell line designated HIRS-BM was established from fluid aspirated from the sternal bone marrow of a 16-year-old female. Another cell line (HIRS-PB) was derived from the peripheral blood of the same patient. Both lines grew well, multilayering rapidly without contact inhibition, and 62 serial passages were successively done within 28 months. Both cultures contained spindle- or fibrous-shaped cells that revealed neo-plastic and pleomorphic features, and these cells were characterized as possessing cross-striations in the cytoplasm. The cross-striations were detected by phosphotungstic acid hematoxylin stain. Some elongated cells were stained positively with anti-myoglobin by use of periodic acid-Schiff methods. The primary tumor in the uterus was diagnosed as a mixed mesodermal tumor composed of adenocarcinoma and rhabdomyosarcoma cells. The karyotype exhibited hyperploidy and large submetacentric marker chromosomes, and the modal chromosome number was 84. No difference was found between the 2 cell lines except for growth behavior and heterotransplantability. HIRS-BM cells grew more rapidly and were highly transplantable. The HIRS-BM cells were transplanted into the subcutis of BALB/c nude mice and produced mixed mesodermal tumors resembling the uterine tumor, while the HIRS-PB cells could not be transplanted. Due to the histo-genesis of the mixed mesodermal tumor being's obscure with histologic observations only, this study was performed to obtain data by tissue culture of the tumor and resulted in support of the combination theory reported in the literature in regard to tumor.
High serum erythropoietin levels are related to heart failure development in subjects from the general population with albuminuria: data from PREVEND
Authors: Niels Grote Beverborg, Haye H. van der Wal, IJsbrand T. Klip, Adriaan A. Voors, Rudolf A. de Boer, Wiek H. van Gilst, Dirk J. van Veldhuisen, Ron T. Gansevoort, Hans L. Hillege, Pim van der Harst, Stephan J.L. Bakker, Peter van der Meer
Journal: European Journal of Heart Failure (2016)
Effects of Large Doses of Chloramphenicol on Human Subjects
Authors: Irwin H. Krakoff, David A. Karnofsky, Joseph H. Burchenal
Journal: New England Journal of Medicine (1955)

WEN chloramphenicol first became available for general use in 1948, as one of the earliest broad-spectrum antibiotics, it was regarded as an important contribution to the treatment of infectious diseases. During 1950–52, however, numerous reports1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 appeared suggesting a relation between the administration of chloramphenicol and the development of aplastic anemia and pancytopenia. A direct causal relation could not be established in most of the cases, but considerable alarm was engendered concerning the hazards of using this drug.17 18 19 20 This attitude toward chloramphenicol has recently been somewhat modified. It was estimated that 8,000,000 Americans had received chloramphenicol before 1953 without increase in . . .
ALDH1A3, the Major Aldehyde Dehydrogenase Isoform in Human Cholangiocarcinoma Cells, Affects Prognosis and Gemcitabine Resistance in Cholangiocarcinoma Patients
Authors: Ming-Huang Chen, Jing-Jie Weng, Chi-Tung Cheng, Ren-Chin Wu, Shih-Chiang Huang, Chiao-En Wu, Yi-Hsiu Chung, Chun-Yu Liu, Mu-Hsin Chang, Ming-Han Chen, Kun-Chun Chiang, Ta-Sen Yeh, Yeu Su, Chun-Nan Yeh
Journal: Clinical Cancer Research (2016)

Intrahepatic cholangiocarcinoma is a fatal primary liver cancer resulting from diagnosis at an advanced stage. Understanding the mechanisms of drug resistance and metastasis of cholangiocarcinoma may improve the disease prognosis. Enhanced aldehyde dehydrogenase (ALDH) activity is suggested to be associated with increased drug resistance and the metastasis. This study aims to investigate the roles of the ALDH isoforms in cholangiocarcinoma.Aldefluor assays, RT-PCR, and Western blot analysis were used to identify the major ALDH isoforms contributing to Aldefluor activity in human cholangiocarcinoma cell lines. We manipulated isoform expression in HuCCT1 cells to elucidate the role of ALDH1A3 in the malignant progression of these cells. Finally, we used immunohistochemical staining to evaluate the clinical significance of ALDH1A3 in 77 hepatectomized cholangiocarcinoma patients and an additional 31 patients with advanced cholangiocarcinoma who received gemcitabine-based therapy.ALDH(high) cholangiocarcinoma cells not only migrated faster but were more resistant to gemcitabine. Among the 19 ALDH isoforms studied, ALDH1A3 was found to be the main contributor to Aldefluor activity. In addition, we also found that knockdown of ALDH1A3 expression in HuCCT1 cells markedly reduced not only their sensitivity to gemcitabine, which might be attributed to a decreased expression of ribonucleotide reductase M1, but also their migration. Most importantly, this enzyme was also identified as an independent poor prognostic factor for patients with intrahepatic cholangiocarcinoma, as well as a prognostic biomarker of gemcitabine-treated patients.ALDH1A3 plays an important role in enhancing malignant behavior of cholangiocarcinoma and serves as a new therapeutic target. Clin Cancer Res; 22(16); 4225-35. ©2016 AACR.
Calcific Aortic Stenosis
Authors: Charles A. Hufnagel, Peter W. Conrad
Journal: New England Journal of Medicine (1962)

THE transventricular and transaortic approaches, with visualization of the valve, to correct calcareous aortic stenosis were logical and progressive strides in the development of the surgical management of this disease.1 2 3 4 However, these procedures at best were limited to attempts to increase the size of the orifice by blind instrumental or digital splitting of the commissural zones. In the presence of the usual extensive calcification or fibrosis, or both, incision or avulsion along one or two lines of fusion did not necessarily increase markedly the area for blood flow. These closed technics were also complicated by embolization and aortic insufficiency, since . . .
Re-Examining Risk of Repeated HLA Mismatch in Kidney Transplantation
Authors: Kathryn J. Tinckam, Caren Rose, Sundaram Hariharan, John Gill
Journal: Journal of the American Society of Nephrology (2016)

Kidney retransplantation is a risk factor for decreased allograft survival. Repeated mismatched HLA antigens between first and second transplant may be a stimulus for immune memory responses and increased risk of alloimmune damage to the second allograft. Historical data identified a role of repeated HLA mismatches in allograft loss. However, evolution of HLA testing methods and a modern transplant era necessitate re-examination of this role to more accurately risk-stratify recipients. We conducted a contemporary registry analysis of data from 13,789 patients who received a second kidney transplant from 1995 to 2011, of which 3868 had one or more repeated mismatches. Multivariable Cox proportional hazards modeling revealed no effect of repeated mismatches on all-cause or death-censored graft loss. Analysis of predefined subgroups, however, showed that any class 2 repeated mismatch increased the hazard of death-censored graft loss, particularly in patients with detectable panel-reactive antibody before second transplant (hazard ratio [HR], 1.15; 95% confidence interval [95% CI], 1.02 to 1.29). Furthermore, in those who had nephrectomy of the first allograft, class 2 repeated mismatches specifically associated with all-cause (HR, 1.30; 95% CI, 1.07 to 1.58) and death-censored graft loss (HR, 1.41; 95% CI, 1.12 to 1.78). These updated data redefine the effect of repeated mismatches in retransplantation and challenge the paradigm that repeated mismatches in isolation confer increased immunologic risk. We also defined clear recipient categories for which repeated mismatches may be of greater concern in a contemporary cohort. Additional studies are needed to determine appropriate interventions for these recipients.
Immune Deficiencies, Aplastic Anemia and Abnormalities of Lymphoid Tissue in Thymoma
Authors: David Korn, Albert Gelderman, Gary Cage, Donald Nathanson, Arthur J. L. Strauss
Journal: New England Journal of Medicine (1967)

THERE is a wealth of clinical information documenting the association of thymoma with a variety of disorders of the hematopoietic1 2 3 and lymphoid systems, immunoglobulin metabolism4 5 6 and neuromuscular transmission.7 , 8 Although recent studies have emphasized the crucial role of the thymus in the ontogeny of the lymphoid system, and in the genesis and modulation of the immune response,9 , 10 there is still no clear understanding of the relation between the pathologically altered thymus and the diverse clinical derangements that often accompany it.This report presents a case of thymoma and associated hematologic and immunologic disorders whose clinical and histologic features appear in several . . .
Thymic Stromal Lymphopoietin Controls Prostaglandin D2 Generation in Aspirin-Exacerbated Respiratory Disease
Authors: Kathleen M. Buchheit, Katherine N. Cahill, Howard Katz, Katherine Murphy, Chunli Feng, Kathleen Lee-Sarwar, Juying Lai, Neil Bhattacharyya, Elliot Israel, Joshua A. Boyce, Tanya M. Laidlaw
Journal: Journal of Allergy and Clinical Immunology (2016)