tbuckley/cabot-search huggingface dataset:
A Randomized, Double-Blinded, Placebo-Controlled Phase II Trial of Recombinant Human Leukemia Inhibitory Factor (rhuLIF, Emfilermin, AM424) to Prevent Chemotherapy-Induced Peripheral Neuropathy
Authors: Ian D. Davis, Lynette Kiers, Lachlan MacGregor, Michael Quinn, Joseph Arezzo, Michael Green, Mark Rosenthal, Michael Chia, Michael Michael, Peter Bartley, Leonie Harrison, Michael Daly
Journal: Clinical Cancer Research (2005)

Abstract Purpose: To determine whether recombinant human leukemia inhibitory factor (rhuLIF, AM424, emfilermin) can prevent or ameliorate the development of chemotherapy-induced peripheral neuropathy (CIPN) after treatment with carboplatin (AUC 6) and paclitaxel (175 mg/m2 over 3 hours). Experimental Design: Randomized double-blind placebo-controlled phase II clinical trial. Eligible patients had solid tumors for which treatment with carboplatin/paclitaxel was appropriate. The primary end point was a standardized composite peripheral nerve electrophysiology (CPNE) score, based on nerve velocities and amplitudes, measured at baseline and after four cycles of chemotherapy. Secondary efficacy end points included CPNE score at last cycle and at exit evaluation, vibration perception threshold, H-reflex latency, symptom scores, and quantitative assessment of neurologic signs. Study drug was given s.c. daily for 7 days starting the day before chemotherapy. Patients were randomized to receive low-dose rhuLIF (2 μg/kg), high-dose rhuLIF (4 μg/kg), or placebo. Results: Patients (n = 117) were randomized across seven neurology test centers. Thirty-six patients received low dose rhuLIF (2 μg/kg), 39 received high dose rhuLIF (4 μg/kg) and 42 received placebo. rhuLIF was well tolerated with 95% compliance and no adverse effects on quality of life. No differences between groups in CPNE or any of the individual neurologic testing variables were observed between baseline and cycle 4 or by the secondary efficacy variables. Conclusions: rhuLIF is not effective in preventing CIPN caused by carboplatin and paclitaxel. CPNE is a reliable and valid tool that was sensitive to the onset and progression of CIPN.
Genomic chart guiding embryonic stem cell cardiopoiesis
Authors: Randolph S Faustino, Atta Behfar, Carmen Perez-Terzic, Andre Terzic
Journal: Genome biology (2008)

Embryonic stem cells possess a pluripotent transcriptional background with the developmental capacity for distinct cell fates. Simultaneous expression of genetic elements for multiple outcomes obscures cascades relevant to specific cell phenotypes. To map molecular patterns critical to cardiogenesis, we interrogated gene expression in stem cells undergoing guided differentiation, and defined a genomic paradigm responsible for confinement of pluripotency.Functional annotation analysis of the transcriptome of differentiating embryonic stem cells exposed downregulated components of DNA replication, recombination and repair machinery, cell cycling, cancer mechanisms, and RNA post-translational modifications. Concomitantly, cardiovascular development, cell-to-cell signaling, cell development and cell movement were upregulated. These simultaneous gene ontology rearrangements engaged a repertoire switch that specified lineage development. Bioinformatic integration of genomic and gene ontology data further unmasked canonical signaling cascades prioritized within discrete phases of cardiopoiesis. Examination of gene relationships revealed a non-stochastic network anchored by integrin, WNT/beta-catenin, transforming growth factor beta and vascular endothelial growth factor pathways, validated by manipulation of selected cascades that promoted or restrained cardiogenic yield. Moreover, candidate genes within anchor pathways acted as nodes that organized correlated expression profiles into functional clusters, which collectively orchestrated and secured an overall cardiogenic theme.The present systems biology approach reveals a dynamically integrated and tractable gene network fundamental to embryonic stem cell specification, and represents an initial step towards resolution of a genomic cardiopoietic atlas.
Air transport and the fate of pneumothorax in pleural adhesions.
Authors: M M Haid, P Paladini, M Maccherini, M Di Bisceglie, G Biagi, G Gotti
Journal: Thorax (1992)

Air travel is contraindicated in patients with a pneumothorax but was necessary because of the exigencies of war in three patients. Three patients with high velocity missile injuries to the chest and pleural adhesions are reported. All had to be evacuated by air, without an intercostal drain or oxygen supplement, from the war stricken area of Northern Somalia (Horn of Africa) to Mogadishu. Two patients with a partial pneumothorax flew on military transport aeroplanes at an altitude of 3000 m in a non-pressurised cabin and recovered rapidly after a few days in hospital. One patient, transported on a small Cessna aeroplane, died after developing bilateral tension pneumothoraces.
IMMUNE RESPONSE TO CHEMICALLY MODIFIED FLAGELLIN
Authors: C. R. Parish
Journal: The Journal of Experimental Medicine (1971)

Flagellin (mol.wt. 40,000) from S. adelaide organisms and a series of acetoacetyl derivatives of flagellin were tested for their ability to induce humoral and cell-mediated immunity in adult rats. It was found that unmodified flagellin was an excellent inducer of antibody formation but a poor inducer of delayed-type hypersensitivity. In contrast, increasing acetoacetylation steadily destroyed the ability of flagellin to initiate antibody formation but enhanced the capacity of the molecule to induce flagellin-specific cell-mediated immunity and antibody tolerance. In fact, it appeared that in adult rats antibody formation and cell-mediated immunity may well be opposing immunological processes. Furthermore, the affinity of the acetoacetyl flagellins for anti-flagellin antibodies appeared to determine the type of immune response which predominated. High affinity antigen produced antibody formation whereas low affinity antigen induced cell-mediated immunity and antibody tolerance. The importance of affinity was further evidenced by the fact that a CNBr digest of flagellin induced humoral and cellular immune responses identical to an acetoacetylated flagellin of comparable antigenic activity. From these studies it was proposed that both humoral and cell-mediated immunity can be directed against the same antigenic determinants but that the specificity requirements for delayed hypersensitivity (and antibody tolerance) are less than those required for antibody formation. Some remarkable immunological features of the flagellin system were revealed. Flagellin induced comparable delayed-type hypersensitivity when injected in either saline or FCA. Furthermore, FCA only slightly enhanced the delayed responses induced by the acetoacetyl flagellins and in fact these preparations produced antibody tolerance whether injected in saline or adjuvant. Finally, in contrast to the adult tolerance induced by the acetoacetylated flagellins, which existed only at the antibody level, tolerance in neonatal rats existed at the level of both humoral and cell-mediated immunity. This finding is the first indication of a fundamental difference between neonatal and adult tolerance. The significance of these findings is discussed in the light of current immunological concepts and a hypothesis proposed to explain these phenomena.
Methyldopa-induced granulomatous hepatitis
Authors: A. C. Miller
Journal: JAMA (1976)

METHYLDOPA has been an effective and usually well-tolerated antihypertensive agent in clinical practice. However, hypersensitivity reactions to the drug are well documented and have been manifested by fever, constitutional complaints, and liver disease.<sup>1-7</sup>We report a case of granulomatous hepatitis due to methyldopa therapy. To our knowledge, similar histopathologic changes have not been reported previously. <h3>Report of a Case</h3> A 49-year-old woman with previously well-documented essential hypertension was admitted to Carraway Methodist Medical Center in June 1973 with a five-day history of generalized repetitive chills, temperature of 39 to 40 C, myalgias, mild watery diarrhea, and severe nausea and vomiting. Her past medical history was unremarkable except for hypertension, which had been managed with hydrochlorothiazide for two years. Two days prior to the onset of her clinical illness, methyldopa, 250 mg twice daily, was added to her antihypertensive regimen. On physical examination, she was alert, acutely ill, and dehydrated
Immune and Inflammatory Cell Involvement in the Pathology of Idiopathic Pulmonary Arterial Hypertension
Authors: Rajkumar Savai, Soni S. Pullamsetti, Julia Kolbe, Ewa Bieniek, Robert Voswinckel, Ludger Fink, Axel Scheed, Christin Ritter, Bhola K. Dahal, Axel Vater, Sven Klussmann, Hossein A. Ghofrani, Norbert Weissmann, Walter Klepetko, Gamal A. Banat, Werner Seeger, Friedrich Grimminger, Ralph T. Schermuly
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

Pulmonary arterial hypertension (PAH) is characterized by vasoconstriction and vascular remodeling. Recent studies have revealed that immune and inflammatory responses play a crucial role in pathogenesis of idiopathic PAH.To systematically evaluate the number and cross-sectional distribution of inflammatory cells in different sizes of pulmonary arteries from explanted lungs of patients with idiopathic PAH versus healthy donor lungs and to demonstrate functional relevance by blocking stromal-derived factor-1 by the Spiegelmer NOX-A12 in monocrotaline-induced pulmonary hypertension in rats.Immunohistochemistry was performed on lung tissue sections from patients with idiopathic PAH and healthy donors. All positively stained cells in whole-lung tissue sections, surrounding the vessels, and in the different compartments of the vessels were counted. To study the effects of blocking SDF-1, rats with monocrotaline-induced pulmonary hypertension were treated with NOX-A12 from Day 21 to Day 35 after monocrotaline administration.We found a significant increase of the perivascular number of macrophages (CD68(+)), macrophages/monocytes (CD14(+)), mast cells (toluidine blue(+)), dendritic cells (CD209(+)), T cells (CD3(+)), cytotoxic T cells (CD8(+)), and helper T cells (CD4(+)) in vessels of idiopathic PAH lungs compared with control subjects. FoxP3(+) mononuclear cells were significantly decreased. In the monocrotaline model, the NOX-A12-induced reduction of mast cells, CD68(+) macrophages, and CD3(+) T cells was associated with improvement of hemodynamics and pulmonary vascular remodeling.Our findings reveal altered perivascular inflammatory cell infiltration in pulmonary vascular lesions of patients with idiopathic pulmonary arterial hypertension. Targeting attraction of inflammatory cells by blocking stromal-derived factor-1 may be a novel approach for treatment of PAH.
Blood groups ABO and Rh (D) factor in the rheumatic diseases.
Authors: I Stoia, R Ramneantu, M Poitas
Journal: Annals of the Rheumatic Diseases (1967)

The researches of Cohen, Boyd, Goldwasser, Cathcart, and Heisler (1963) on a small number of patients with chronic joint disease of different clinical types showed that there was no association between the ABO blood groups and the chronic rheumatic diseases, but that there was a deficiency of Rh factor.
Treatment of Staphylococcus aureus in cystic fibrosis
Authors: J S ELBORN
Journal: Thorax (1999)

A number of treatments for cystic fibrosis have evolved over the past four decades, based on the experience of clinicians involved in the care of these patients. Some of these treatments were developed without the benefit of large randomised controlled trials which would have been difficult to perform at the time. The value of prophylactic antibiotic treatment against Staphylococcus aureus in the management of infants and children is an example of a logical practice which has developed on the basis of experience, but which requires careful review as to its efficacy and potential deleterious effects.

Pulmonary infection with S aureus is a frequent problem in patients with cystic fibrosis, particularly during the first decade of life.1 Cross sectional studies show that in this age group, 25−30% of patients culture S aureus from sputum.2 This may be an underestimate as cough swabs in children unable to expectorate are often negative and infection may only be detected by bronchoalveolar lavage in such circumstances.3 Infection with S aureus is usually associated with symptoms, but asymptomatic carriage is also common.

The approach to the treatment of patients with cystic fibrosis with S aureus infection of the …
Leveraging Epidemiology and Clinical Studies of Cancer Outcomes: Recommendations and Opportunities for Translational Research
Authors: Joanne W Elena, Lois B Travis, Naoko I Simonds, Christine B Ambrosone, Rachel Ballard-Barbash, Smita Bhatia, James R Cerhan, Patricia Hartge, Rebecca S Heist, Lawrence H Kushi, Timothy L Lash, Lindsay M Morton, Kenan Onel, John P Pierce, Leslie L Robison, Julia H Rowland, Deborah Schrag, Thomas A Sellers, Daniela Seminara, Xiao Ou Shu, Nancy E Thomas, Cornelia M Ulrich, Andrew N Freedman
Journal: JNCI Journal of the National Cancer Institute (2012)

As the number of cancer survivors continues to grow, research investigating the factors that affect cancer outcomes, such as disease recurrence, risk of second malignant neoplasms, and the late effects of cancer treatments, becomes ever more important. Numerous epidemiologic studies have investigated factors that affect cancer risk, but far fewer have addressed the extent to which demographic, lifestyle, genomic, clinical, and psychosocial factors influence cancer outcomes. To identify research priorities as well as resources and infrastructure needed to advance the field of cancer outcomes and survivorship research, the National Cancer Institute sponsored a workshop titled "Utilizing Data from Cancer Survivor Cohorts: Understanding the Current State of Knowledge and Developing Future Research Priorities" on November 3, 2011, in Washington, DC. This commentary highlights recent findings presented at the workshop, opportunities to leverage existing data, and recommendations for future research, data, and infrastructure needed to address high priority clinical and research questions. Multidisciplinary teams that include epidemiologists, clinicians, biostatisticians, and bioinformaticists will be essential to facilitate future cancer outcome studies focused on improving clinical care of cancer patients, identifying those at high risk of poor outcomes, and implementing effective interventions to ultimately improve the quality and duration of survival.
Histidine-rich glycoprotein inhibits the antiangiogenic effect of thrombospondin-1
Authors: Ronit Simantov, Maria Febbraio, René Crombie, Adam S. Asch, Ralph L. Nachman, Roy L. Silverstein
Journal: Journal of Clinical Investigation (2001)

Angiogenesis is critical for the growth and proliferation of tumors as well as for normal development. We now describe a novel role for histidine-rich glycoprotein (HRGP) in the modulation of angiogenesis. HRGP is a plasma protein that circulates in relatively high concentrations (1.5 μM), but has no known function in vivo. We have shown previously that HRGP binds with high affinity to thrombospondin-1 (TSP-1), a homotrimeric glycoprotein that is a potent inhibitor of angiogenesis. The antiangiogenic activity of TSP-1 is mediated by the binding of properdin-like type I repeats to the receptor CD36. We found that binding of HRGP to TSP-1 was similarly mediated by TSP type I repeats. HRGP colocalized with TSP-1 in the stroma of human breast cancer specimens, and this interaction masked the antiangiogenic epitope of TSP-1. In assays performed in vitro of endothelial cell migration and tube formation, and in vivo corneal angiogenesis assays, HRGP inhibited the antiangiogenic effect of TSP-1. These studies suggest that HRGP can modulate the antiangiogenic activity of TSP-1, and identify a potential mechanism of resistance to the antiangiogenic effect of TSP-1.
Detection of oncostatin M in synovial fluid from patients with rheumatoid arthritis
Authors: W. Hui, M. Bell, G. Carroll
Journal: Annals of the Rheumatic Diseases (1997)

<h3>OBJECTIVE</h3> To measure oncostatin M (OSM) in synovial fluid from patients with rheumatoid arthritis (RA) and osteoarthritis (OA). <h3>METHODS</h3> 20 samples of synovial fluid from patients with RA and 10 samples from patients with OA were examined using an OSM specific sandwich ELISA. <h3>RESULTS</h3> OSM was detected at concentrations ranging from 2.36 to 901.82 pg/ml in 18 (90%) of 20 samples of synovial fluid from RA patients. There was no detectable OSM in synovial fluid from OA patients. In the RA patients, the OSM concentration in synovial fluid correlated significantly with the synovial fluid white blood cell count (<i>r</i>=0.67, p&lt;0.01), but not with other laboratory parameters of disease activity. <h3>CONCLUSION</h3> These findings suggest that OSM may contribute to joint inflammation in RA.
Destructive arthropathy in chondrocalcinosis articularis.
Authors: A J Richards, E B Hamilton
Journal: Annals of the Rheumatic Diseases (1974)

Itisnowwellrecognized thatidiopathic chondrocalcinosis articularis, aswell asbeing associated with acute episodes ofpyrophosphate arthropathy, may lead topremature degenerative changes inthejoints involved. Someworkers havealsomadeoccasional reference tothepresence ofjuxta-articular osteolytic lesions (McCarty, Kohn,andFaires, 1962; Currey, 1970.) Morerecently there havebeenreports of destructive joint changes which canbethecauseof considerable disability (Robinson, 1971;Menkes, Simon,Chouraki, Ecoffet, Amor,andDelbarre, 1973). Fivepatients (4womenand1man), fromaseries of eighty patients withidiopathic chondrocalcinosis seen atKing's College Hospital, havedeveloped asevere destructive arthropathy. Innoneofthemwasthere evidence ofhaemochromatosis orhyperparathyroidism andserological tests forsyphilis andfor rheumatoid factor werenegative. Oneofthefive patients hasrecently developed diabetes mellitus and another hasPaget's disease, although neither ofthese conditions iscausing symptoms. Casereports Patient 1,a75-year-old man,wasfirst seenin1969complaining ofpainandswelling ofbothhandsandpainin theright kneeandneck. Investigations showed anormal erythrocyte sedimentation rate (ESR), anegative WaalerRosetest, andwidespread chondrocalcinosis inradiographs ofhiships, knees, andlumbar spine. Theserum calcium wasinthenormal range butthealkaline phosphatase wasraised at99i.u./litre (normal range30-85), andPaget's disease ofthepelvis wasseenradiologically. Apart fromthechondrocalcinosis there weredegenerative changes inthehips, knees, andspine. Theradiographs of thehandsareinteresting inthattheyshowunusual destructive changes, especially intheright hand(Fig. 1), andfaint calcification ofhyaline cartilage ispresent inthe metacarpophalangeal joint ofthemiddle finger. The destructive change atthisjoint isobvious withcyst formation andcrumbling ofthejoint surface, butmarginal erosions asseeninrheumatoid arthritis arenotpresent. Patient 2,a 69-year-old woman,developed painand swelling oftheleft shoulder. Aneffusion oftheleft shoulder joint wasaspirated andcalcium pyrophosphate crystals
Door-to-Balloon Time and Mortality among Patients Undergoing Primary PCI
Authors: Daniel S. Menees, Eric D. Peterson, Yongfei Wang, Jeptha P. Curtis, John C. Messenger, John S. Rumsfeld, Hitinder S. Gurm
Journal: New England Journal of Medicine (2013)

Current guidelines for the treatment of ST-segment elevation myocardial infarction recommend a door-to-balloon time of 90 minutes or less for patients undergoing primary percutaneous coronary intervention (PCI). Door-to-balloon time has become a performance measure and is the focus of regional and national quality-improvement initiatives. However, it is not known whether national improvements in door-to-balloon times have been accompanied by a decline in mortality.We analyzed annual trends in door-to-balloon times and in-hospital mortality using data from 96,738 admissions for patients undergoing primary PCI for ST-segment elevation myocardial infarction from July 2005 through June 2009 at 515 hospitals participating in the CathPCI Registry. In a subgroup analysis using a linked Medicare data set, we assessed 30-day mortality.Median door-to-balloon times declined significantly, from 83 minutes in the 12 months from July 2005 through June 2006 to 67 minutes in the 12 months from July 2008 through June 2009 (P<0.001). Similarly, the percentage of patients for whom the door-to-balloon time was 90 minutes or less increased from 59.7% in the first year to 83.1% in the last year (P<0.001). Despite improvements in door-to-balloon times, there was no significant overall change in unadjusted in-hospital mortality (4.8% in 2005-2006 and 4.7% in 2008-2009, P=0.43 for trend) or in risk-adjusted in-hospital mortality (5.0% in 2005-2006 and 4.7% in 2008-2009, P=0.34), nor was a significant difference observed in unadjusted 30-day mortality (P=0.64).Although national door-to-balloon times have improved significantly for patients undergoing primary PCI for ST-segment elevation myocardial infarction, in-hospital mortality has remained virtually unchanged. These data suggest that additional strategies are needed to reduce in-hospital mortality in this population. (Funded by the National Cardiovascular Data Registry of the American College of Cardiology Foundation.).
B1a B Lymphocytes Are Atheroprotective by Secreting Natural IgM That Increases IgM Deposits and Reduces Necrotic Cores in Atherosclerotic Lesions
Authors: Tin Kyaw, Christopher Tay, Surendran Krishnamurthi, Peter Kanellakis, Alex Agrotis, Peter Tipping, Alex Bobik, Ban-Hock Toh
Journal: Circulation Research (2011)

Rationale: Aggravated atherosclerosis in B lymphocyte-deficient chimeric mice and reduced atherosclerosis after transfer of unfractionated spleen B lymphocytes into splenectomized mice have led to the widely held notion that B lymphocytes are atheroprotective. However, B lymphocytes can be pathogenic, because their depletion by anti-CD20 antibody ameliorated atherosclerosis, and transfer of B2 lymphocytes aggravated atherosclerosis. These observations raise the question of the identity of the atheroprotective B-lymphocyte population. Objective: The purpose of the study was to identify an atheroprotective B-lymphocyte subset and mechanisms by which they confer atheroprotection. Methods and Results: Splenectomy of apolipoprotein E–deficient mice selectively reduced peritoneal B1a lymphocytes, plasma IgM, and oxidized low-density lipoprotein IgM levels and lesion IgM deposits. These reductions were accompanied by increased oil red O–stained atherosclerotic lesions and increased necrotic cores, oxidized low-density lipoproteins, and apoptotic cells in lesions. Plasma lipids, body weight, collagen, and smooth muscle content were unaffected. Transfer of B1a lymphocytes into splenectomized mice increased peritoneal B1a lymphocytes; restored plasma IgM, oxidized low-density lipoprotein IgM levels, and lesion IgM deposits; and potently attenuated atherosclerotic lesions, with reduced lesion necrotic cores, oxidized low-density lipoprotein, and apoptotic cells. In contrast, transfer of B1a lymphocytes that cannot secrete IgM failed to protect against atherosclerosis development in splenectomized mice despite reconstitution in the peritoneum. Conclusions: B1a lymphocytes are an atheroprotective B-lymphocyte population. Our data suggest that natural IgM secreted by these lymphocytes offers protection by depositing IgM in atherosclerotic lesions, which reduces the necrotic cores of lesions.