tbuckley/cabot-search huggingface dataset:
Operative Risk Factors in Patients with Left Main Coronary-Artery Disease
Authors: Bernard R. Chaitman, Willliam J. Rogers, Kathryn Davis, Denis H. Tyras, Robert Berger, Martial G. Bourassa, Lloyd Fisher, Vicki Stover Hertzberg, Melvin P. Judkins, Michael B. Mock, Thomas Killip
Journal: New England Journal of Medicine (1980)

To identify the factors associated with operative mortality, we evaluated clinical, angiographic, and surgical variables in 1172 patients with left main coronary-artery stenoses of at least 50 per cent, who underwent coronary-bypass procedures in the Collaborative Study in Coronary Artery Surgery (CASS). The operative mortality was 4.2 per cent overall and was less than 3 per cent in seven of the 15 participating hospitals. Historical variables associated with an increase in operative mortality were age, female sex, and duration and severity of angina. Other variables associated most closely with poor survival were urgency of operation, left coronary-artery dominance, severity of left main coronary-artery stenosis, and impairment of left ventricular contraction. The results of this multicenter study show that aortocoronary bypass surgery in patients with left main coronary-artery disease can be performed with a low mortality and that patients at high risk can often be identified before surgery.
Case 9-2009
Authors: David G. Forcione, Hasan B. Alam, Sanjeeva P. Kalva, Joseph Misdraji
Journal: New England Journal of Medicine (2009)

An 81-year-old man was admitted to the hospital because of acute and massive rectal bleeding associated with hypotension. Two episodes of rectal bleeding had occurred in the previous 2 years, and evaluation had disclosed colonic diverticula and duodenal erosions. Bleeding continued and hypotension persisted despite the administration of fluid and red cells. A diagnostic procedure was performed.
Interaction of isoflavones and vitamin E with irradiation in androgen independent PC-3 human prostate cancer cells
Authors: Kathleen T. Shiverick, Lori Rice, Renita Handayani, Theresa Medrano, Brandon Mauldin, Charles J. Rosser
Journal: Cancer Research (2006)

578   Studies have reported that soy isoflavones and vitamin E (VE), respectively, inhibit growth in a number of carcinoma cell lines. Our study investigated possible radiosensitizing effects of a soy isoflavone concentrate (ISF) and VE succinate (VES) in PC-3 human prostate cancer cells, which are androgen-insensitive and p53 null. Methods: DNA synthesis was analyzed by 3 H-thymidine incorporation, and cell cycle proteins by Western immunoblot. Clonogenic survival assays were conducted at 2 different cell concentrations in quadruplicate sets. After growth for 2-4 weeks, cells were stained with gentian violet and colonies of >50 cells counted. Percent clonogenic survival was calculated by dividing the number of colonies/group by the number of cells seeded. Results: ISF and VES, respectively, inhibited DNA synthesis in a dose-dependent manner with IC 50  values for ISF of 53 ug/ml and VE of 27uM. Levels of p21 CIP1  protein, a major cyclin-dependent kinase inhibitor, were significantly increased by ISF and VES involving a p53-independent mechanism. Low cytostatic concentrations of ISF and VES showed additive effects on p21 induction and DNA synthesis inhibition. In a clonogenic survival assay, cells treated with IC 50  doses of ISF or VE showed a substantial decrease in long-term survival. Experiments next evaluated if the cytotoxic response to ionizing radiation (IR) would be enhanced by antioxidant exposure, comparing separate treatment windows before vs after IR. A single dose of IR decreased survival from 17% for sham-IR cells to 2% at 4 Grey (Gy), and to less than 1% at 6 Gy. Antioxidant pretreatment for 48 hr before IR further reduced clonogenic survival by 50% from controls. At the high dose of IR (6 Gy), cell survival was statistically reduced from control across all treatment groups (ISF p
Does time-to-antibiotics predict outcome of febrile neutropenia in pediatric cancer?
Authors: M. B. Fletcher, H. Hodgkiss, R. Browning, T. Hoffman, C. Hadden, N. J. Winick, T. L. McCavit
Journal: Journal of Clinical Oncology (2011)

9076 Background: Prolonged time-to-antibiotic administration (TTA) has been associated with poor outcomes in adults with bacterial meningitis, pneumonia, and sepsis. For pediatric oncology patients with febrile neutropenia (FN), TTA has been suggested as a quality-of-care (QOC) measure, but no prior reports have correlated TTA with outcome in pediatric FN. We sought to determine whether TTA is associated with adverse events in a cohort of pediatric FN patients. Methods: We designed a retrospective cohort study of all FN admissions at our institution from 2001-2009. Inclusion criteria were cancer treatment at our institution, fever, and neutropenia (ANC<500). Exclusion criteria were prior hematopoietic stem cell transplantation, severe sepsis on presentation, and transfer from an outside facility. The primary outcome measure was a composite of any in-hospital mortality, transfer to the pediatric intensive care unit (PICU), and receipt of ≥ 40ml/kg of fluid resuscitation within 24 hours of presentation. Age, gender, oncologic diagnosis, temperature, total white blood cell (tWBC) count, bacteremia, viral infection, presentation location, empiric antibiotics, and weekend admission were analyzed as covariates with TTA. TTA was log transformed. Random effects mixed logistic regression was used for both bivariable and multivariable analyses for the composite outcome. Results: We identified 653 subjects with 1,628 admissions for FN from 2001-2009. Median TTA was 114 minutes (range 10-536). 181 (11.1%) admissions met the composite outcome criteria (mortality-0.6%, PICU transfer – 4.7%, fluid resuscitation – 10.1%). In bivariable analysis, prolonged TTA was associated with poor outcome (Odds Ratio (OR) 1.26 [95%Confidence Interval (CI), 1.02,1.49], p=.037). In a multivariable regression model, age, temperature, bacteremia, tWBC count, viral infection, empiric antibiotics, oncologic diagnosis and presentation location were independently associated with the composite outcome, but TTA was not (OR 0.99 [95%CI, 0.73,1.34], p=.96). Conclusions: As a QOC measure, TTA may adequately measure the process of care but is not independently associated with outcome in pediatric cancer patients with FN.
Safety of a C1 Esterase Inhibitor Concentrate in Pregnant Women with Hereditary Angioedema: Findings from the International Berinert Patient Registry
Authors: James A. Fox, Inmaculada Martinez-Saguer, Arthur B. Vegh, Walter A. Wuillemin, Jonathan M. Edelman, Debora Williams-Herman, Mikhail Rojavin, Tanja Rosenberg
Journal: Journal of Allergy and Clinical Immunology (2016)
Significance of anti-E2 in the diagnosis of HCV infection in patients on maintenance hemodialysis
Authors: D S Lee, R R Lesniewski, Y C Sung, W K Min, S G Park, K H Lee, H S Kim
Journal: Journal of the American Society of Nephrology (1996)

A routine screening test used in the diagnosis of hepatitis C virus (HCV) infection is the anti-HCV antibody (anti-HCV) test containing core, NS3, NS4, and NS5 antigens of HCV. When HCV infection occurs in immunocompromised hosts, antibody formation against core, NS3, or NS4 antigens may be weak in the presence of HCV viremia and cannot be detected by routine anti-HCV tests. This study proposed that in immunocompromised hosts such as patients with chronic renal failure (whose capacity to form antibodies is diminished), antibody formation against the E2 region would be preserved, because the E2/NS1 region of HCV is strongly immunogenic. The aim of this study is to evaluate the significance of anti-E2 in the diagnosis of HCV infection among patients on maintenance hemodialysis who are anti-HCV-negative, using a conventional third-generation enzyme immunoassay (EIA) kit. The E2/NS1 gene of HCV encoding the amino acid sequence 388-664 was molecularly cloned into a vector containing an SV 40 promotor and was expressed in Chinese Hamster ovary cells. Using this E2 protein, the anti-E2 test was performed by EIA on 100 patients on maintenance hemodialysis, and on 50 patients with chronic hepatitis C who were anti-HCV-positive, to evaluate the antigenecity of the E2 protein. Of the 100 hemodialysis patients, 15 (15.0%) tested anti-HCV-positive using a third generation anti-HCV ELISA kit. Of the 85 patients who tested negative for anti-HCV, nine (10.6%) were anti-E2-positive and six (66.7%) of these anti-E2 positive patients showed HCV RNA viremia by HCV reverse transcription-polymerase chain reaction. Fourty-two (84.0%) of 50 patients with chronic hepatitis C were anti-E2-positive. As a control group, we tested for anti-E2 among 30 blood donors who were anti-HCV-negative, and also among 85 patients with hepatocellular carcinoma who were anti-HCV-negative, but in both groups, none (0%) was anti-E2-positive. In conclusion, these data suggest that the E2 protein of HCV should be included in a diagnostic anti-HCV kit for the detection of HCV infection in immunocompromised patients.
A phase II study of sunitinib in patients with advanced hepatocellular carcinoma
Authors: A. X. Zhu, D. V. Sahani, E. di Tomaso, D. Duda, V. Sindhwani, S. S. Yoon, L. S. Blaszkowsky, J. W. Clark, D. P. Ryan, R. K. Jain
Journal: Journal of Clinical Oncology (2007)

4637 Background: Patients (pts) with advanced hepatocellular carcinoma (HCC) have a poor prognosis. HCC is a highly vascular tumor with increased levels of angiogenic factors including VEGF and VEGFR. Sunitinib is an oral multitargeted receptor tyrosine kinase inhibitor with activity against VEGFR, PDGFR, and c-KIT. We performed a phase II study to evaluate the efficacy and toxicity of sunitinib in advanced HCC. Methods: Eligibility criteria included unresectable or metastatic measurable HCC, 0–1 prior chemotherapy regimens, performance status = 1, CLIP score = 3, and adequate organ functions. Pts were treated with sunitinib at 37.5 mg po qd on a standard 4 weeks on, 2 weeks off regimen (6 weeks/cycle). Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) was performed to assess changes in tumor permeability. Plasma angiogenic markers were assayed by multiplex array. The primary endpoint of the study is progression-free survival (PFS). Results: 19 pts have been enrolled since May 2, 2006: median age = 59 (30–77), M/F = 16/3, ECOG 0/1 = 7/12, CLIP 1/2/3=7/7/5. The treatment was generally well tolerated. Grade 3/4 toxicities included neutropenia (n=4, 21%), lymphopenia (n=3, 16%), SGOT/SGPT (n=3, 16%), fatigue (n=2, 11%), rash (n=2, 11%), and thrombocytopenia (n=2, 11%). One pt had a partial response and 8 pts had stable disease of at least 12 weeks; 8 pts currently remain on study. The median number of treatment cycles received per patient was 2 (range 1–6). The mean tumor permeability (K trans ) following 2 weeks of sunitinib administration in 13 pts decreased from mean baseline value of 3.77 to 1.06 (an average of 52% decrease). Of the 15 pts analyzed, changes in plasma angiogenic markers from baseline to day 15 following sunitinib treatment were observed as follows: sVEGFR1 remained constant in 15 pts; 8/15 had decreased sVEGFR2 levels; 13/15 and 11/15 pts had increased PlGF and VEGF levels respectively; bFGF levels decreased in 9 and increased in 5 patients. Conclusions: Sunitinib administered in the current dose schedule can be safely given with close monitoring in HCC patients. Preliminary evidence of antitumor activity was observed. Changes in angiogenic parameters on DCE-MRI and in blood markers were seen following sunitinib administration. [Table: see text]
Neurocysticercosis in an Orthodox Jewish Community in New York City
Authors: P M Schantz, A C Moore, J L Muñoz, B J Hartman, J A Schaefer, A M Aron, D Persaud, E Sarti, M Wilson, A Flisser
Journal: New England Journal of Medicine (1992)

From June 1990 through July 1991, intracerebral infection with the larval stage of the pork tapeworm Taenia solium was diagnosed in four unrelated persons in an Orthodox Jewish community in New York City. None of the patients had eaten pork, and only one had traveled to a country in which T. solium infection was endemic. We investigated this outbreak, screened serum samples from family members and household contacts for antibodies to cysticercosis, and examined stool specimens from household employees for eggs of taenia species.The four patients had recurrent seizures and brain lesions that were radiologically consistent with the presence of cysticerci. The diagnosis was confirmed in two patients by a brain biopsy, and in two by immunoblot assays for cysticercus antibodies. Of 17 immediate family members screened serologically, 7 from two families had cysticercus antibodies. Magnetic resonance imaging of the brain showed cystic lesions in two of the seropositive family members, one of whom had had a seizure. Examinations of six domestic employees from all four households revealed an active infection with taenia species in one and a positive serologic test in another. Since these women had recently emigrated from Latin American countries where T. solium infection is endemic, they were the most likely sources of infection in the members of these households.A diagnosis of neurocysticercosis should be considered in patients with seizures and radiologic evidence of cystic brain lesions, even in those who do not eat pork and who have not traveled to a country in which T. solium infection is endemic. Recent emigrants from countries in which T. solium infection is endemic should be screened for tapeworm infection in their stools before they are employed as housekeepers or food handlers.
Microbiome mediation of infections in the cancer setting
Authors: Ying Taur, Eric G. Pamer
Journal: Genome Medicine (2016)

Infections encountered in the cancer setting may arise from intensive cancer treatments or may result from the cancer itself, leading to risk of infections through immune compromise, disruption of anatomic barriers, and exposure to nosocomial (hospital-acquired) pathogens. Consequently, cancer-related infections are unique and epidemiologically distinct from those in other patient populations and may be particularly challenging for clinicians to treat. There is increasing evidence that the microbiome is a crucial factor in the cancer patient's risk for infectious complications. Frequently encountered pathogens with observed ties to the microbiome include vancomycin-resistant Enterococcus, Enterobacteriaceae, and Clostridium difficile; these organisms can exist in the human body without disease under normal circumstances, but all can arise as infections when the microbiome is disrupted. In the cancer patient, such disruptions may result from interventions such as chemotherapy, broad-spectrum antibiotics, or anatomic alteration through surgery. In this review, we discuss evidence of the significant role of the microbiome in cancer-related infections; how a better understanding of the role of the microbiome can facilitate our understanding of these complications; and how this knowledge might be exploited to improve outcomes in cancer patients and reduce risk of infection.
Genetic lineage tracing analysis of the cell of origin of hepatotoxin‐induced liver tumors in mice
Authors: Soona Shin, Kirk J. Wangensteen, Monica Teta‐Bissett, Yue J. Wang, Elham Mosleh‐Shirazi, Elizabeth L. Buza, Linda E. Greenbaum, Klaus H. Kaestner
Journal: Hepatology (2016)

The expression of biliary/progenitor markers by hepatocellular carcinoma (HCC) is often associated with poor prognosis and stem cell‐like behaviors of tumor cells. Hepatocellular adenomas (HCAs) also often express biliary/progenitor markers and frequently act as precursor lesions for HCC. However, the cell of origin of HCA and HCC that expresses these markers remains unclear. Therefore, to evaluate if mature hepatocytes give rise to HCA and HCC tumors and to understand the molecular pathways involved in tumorigenesis, we lineage‐labeled hepatocytes by injecting adeno‐associated virus containing thyroxine‐binding globulin promoter‐driven causes recombination ( AAV‐TBG‐Cre ) into RosaYFP mice. Yellow fluorescent protein (YFP) was present in &gt;96% of hepatocytes before exposure to carcinogens. We treated AAV‐TBG‐Cre ; RosaYFP mice with diethylnitrosamine (DEN), followed by multiple injections of carbon tetrachloride to induce carcinogenesis and fibrosis and found that HCA and HCC nodules were YFP + lineage‐labeled; positive for osteopontin, SRY (sex determining region Y)‐box 9, and epithelial cell adhesion molecule; and enriched for transcripts of biliary/progenitor markers such as prominin 1, Cd44, and delta‐like 1 homolog. Next, we performed the converse experiment and lineage‐labeled forkhead box protein L1(Foxl1)‐positive hepatic progenitor cells simultaneously with exposure to carcinogens. None of the tumor nodules expressed YFP, indicating that Foxl1‐expressing cells are not the origin for hepatotoxin‐induced liver tumors. We confirmed that HCA and HCC cells are derived from mature hepatocytes and not from Foxl1‐Cre ‐marked cells in a second model of toxin‐induced hepatic neoplasia, using DEN and 3,3′,5,5′‐tetrachloro‐1,4‐bis(pyridyloxy)benzene (TCPOBOP). Conclusion : Hepatocytes are the cell of origin of HCA and HCC in DEN/carbon tetrachloride and DEN/TCPOBOP induced liver tumors. (H epatology 2016;64:1163‐1177)
ATPS-81SINGLE-AGENT TARGETING OF Eph RECEPTORS A2, A3, B2 AND INTERLUKIN-13 RECEPTOR ALPHA 2 IN GLIOBLASTOMA
Authors: Poonam Sonawane, Sara Ferluga, Denise Herpai, Waldemar Debinski
Journal: Neuro-Oncology (2015)

Glioblastoma (GBM), is the most common and aggressive primary tumor of the central nervous system, with few treatment options and poor patient outcome. We and others demonstrated that A2, A3 and B2 receptors of the Eph family of protein tyrosine kinase receptors and Interlukin-13 receptor alpha 2 (IL-13RA2), are overexpressed in GBM tumors, but not normal brain. These receptors play important roles in GBM tumor progression and resistance to therapies involving both initiating and differentiating tumor cells, infiltrating tumor cells, tumor-associated macrophages (TAMs), and neovasculature. To this end, we have designed and constructed a bi-valent protein which would recognize all these four receptors using a human IgG1 scaffold. The bi-valent protein (eA5-Fc-IL-13.E13K) consists of ephrin-A5 (eA5, which acts as a ligand for the three Eph receptors), the Fc region of IgG1 followed by a modified IL-13, IL-13.E13K. The bi-valent protein was expressed in Sf9 insect cells using the baculovirus expression system and purified from the cell media to homogeneity using affinity Protein G column. The non-reduced and reduced SDS-PAGE showed the expected size bands of 125 and 65 kDa, respectively. The bi-valent binding and function of protein was tested in GBM cells. The bi-valent protein specifically bound, internalized and down-regulated EphA2 receptor in GBM cells, mimicking the action of eA5 alone. Using the PMS/MTS cell viability assay, we determined that the bi-valent protein effectively prevented an IL-13.E13K based cytotoxin from binding to and killing GBM cells by competing for the cytokine binding sites. Thus, we have generated a bi-valent compound capable of recognizing four receptor targets: IL-13RA2, EphA2, EphA3 and EphB2 that are over-expressed in most of the pathobiologically important tumor compartments in all GBM patients. Therefore, the protein under investigation represents a novel therapeutic route to be exploited in the treatment of patients with a heterogeneous disease like GBM.
Furosemide Promotes Patent Ductus Arteriosus in Premature Infants with the Respiratory-Distress Syndrome
Authors: Thomas P. Green, Theodore R. Thompson, Dana E. Johnson, James E. Lock
Journal: New England Journal of Medicine (1983)

Furosemide stimulates the renal synthesis of prostaglandin E2, a potent dilator of the ductus arteriosus. We administered this drug to 33 premature infants with the respiratory-distress syndrome, to determine whether it increased the incidence of patent ductus arteriosus. Chlorothiazide, a diuretic that does not stimulate prostaglandin E synthesis, was used as the control drug in 33 other infants. During the study, the incidence of patent ductus arteriosus was significantly higher (P<0.02) in the furosemide group (18 of 33 infants) than in the chlorothiazide group (8 of 33). Eleven infants in the furosemide group and seven in the chlorothiazide group required ductal ligation (P>0.2). An additional six infants (all from the furosemide group) who did not have evidence of a patent ductus during the study were later found to have one. Overall survival was 76 and 61 per cent in the furosemide and chlorothiazide groups, respectively (P>0.2). Small (less than twofold) increases in the urinary excretion of prostaglandin E were seen after the initial dose of both drugs. When the analysis was repeated after the fifth day of life, prostaglandin E excretion tripled after furosemide administration, whereas no increase occurred with chlorothiazide. We conclude that furosemide increases the incidence of patent ductus arteriosus in premature infants with the respiratory-distress syndrome, probably through a prostaglandin-mediated process. (N Engl J Med. 1983; 308:743–8.)
Antibody Responses to<i>Haemophilus influenzae</i>Type b Vaccines in Men with Human Immunodeficiency Virus Infection
Authors: Mark C. Steinhoff, Barry S. Auerbach, Kenrad E. Nelson, David Vlahov, Rebecca L. Becker, Neil M.H. Graham, David H. Schwartz, Alexander H. Lucas, Richard E. Chaisson
Journal: New England Journal of Medicine (1991)

Persons with human immunodeficiency virus (HIV) infection are at increased risk for serious infections caused by Haemophilus influenzae, yet there are few data on their antibody responses to the H. influenzae type b vaccines.
Reovirus Type 3 Associated with Fatal Pneumonia
Authors: James R. Tillotson, A. Martin Lerner
Journal: New England Journal of Medicine (1967)

REOVIRUSES have been isolated from specimens obtained from children or adults who appear well1 or have had upper-respiratory-tract infection,2 3 4 5 6 7 pneumonia,8 , 9 nonspecific febrile illness,5 exanthem,3 , 8 , 10 , 11 diarrhea,5 , 6 , 12 hepatitis,8 meningoencephalitis,4 , 8 , 13 , 14 and Burkitt's lymphoma.15 In some of these cases a concomitant rise in type-specific antibodies to reoviruses has been documented. 2 , 7 , 8 , 10 , 14 However, their role in human disease is still unclear. Rarely have deaths been associated with these infections.8 , 13 We report below the first definitive association of reovirus infection with fatal nonbacterial pneumonia.Case ReportL.J. a 5-year-old Negro girl, entered the Detroit General Hospital on February 19, 1965, with fever, rhinorrhea and a nonproductive cough. . . .