tbuckley/cabot-search huggingface dataset:
Graft-Versus-Lymphoma Effect for Aggressive T-Cell Lymphomas in Adults: A Study by the Société Française de Greffe de Moëlle et de Thérapie Cellulaire
Authors: Steven Le Gouill, Noel Milpied, Agnès Buzyn, Régis Peffault De Latour, Jean-Paul Vernant, Mohamad Mohty, Marie-Pierre Moles, Krimo Bouabdallah, Claude-Eric Bulabois, Jehan Dupuis, Bernard Rio, Nicole Gratecos, Ibrahim Yakoub-Agha, Michel Attal, Olivier Tournilhac, Didier Decaudin, Jean-Henry Bourhis, Didier Blaise, Christelle Volteau, Mauricette Michallet
Journal: Journal of Clinical Oncology (2008)

Aggressive T-cell lymphomas (ATCLs) represent 10% to 15% of non-Hodgkin's lymphomas (NHLs) in adults. ATCLs show a worse prognosis than B-cell lymphomas.On behalf of the Société Française de Greffe de Moëlle et de Thérapie Cellulaire, we conducted a retrospective analysis including 77 ATCL patients who underwent allogeneic stem-cell transplantation (alloSCT).The different diagnosis included anaplastic large-cell lymphoma (ALCL; n = 27), peripheral T-cell lymphoma not otherwise specified (PTCL-NOS; n = 27), angioimmunoblastic T-cell lymphoma (AITL; n = 11), hepatosplenic gamma/delta lymphoma (HSL; n = 3), T-cell granular lymphocytic leukemia (T-GLL; n = 1), nasal natural killer (NK)/T-cell lymphoma (nasal-NK/L; n = 3) or non-nasal NK/T-cell lymphoma (non-nasal-NK/L; n = 2), enteropathy-type T-cell (n = 1), and human T-lymphotropic virus (HTLV)-1 lymphoma (n = 2). Fifty-seven patients received a myeloablative conditioning regimen. Donors were human leukocyte antigen (HLA)-matched in 70 cases and related in 60 cases. Thirty-one patients were in complete remission (CR) at the time of alloSCT, whereas 26 were in partial response (PR). Five-year toxicity-related mortality (TRM) incidence was 33% (95% CI, 24% to 46%). The 5-year overall survival (OS) and event-free survival (EFS) rates were 57% (95% CI, 45% to 68%) and 53% (95% CI, 41% to 64%), respectively. In multivariate analysis, chemoresistant disease (stable, refractory, or progressing disease) at the time of alloSCT and the occurrence of severe grade 3 to 4 acute graft-versus-host disease (aGVHD) were the strongest adverse prognostic factors for OS (P = .03 and .03, respectively). Disease status at transplantation significantly influenced the 5-year EFS (P = .003), and an HLA-mismatched donor increased TRM (P = .04).We conclude that alloSCT is a potentially efficient therapy for NK/T lymphomas and is worth further investigation through prospective clinical trials.
Cancer Treatment–Related Cardiotoxicity: Current State of Knowledge and Future Research Priorities
Authors: Nonniekaye Shelburne, Bishow Adhikari, Joanna Brell, Myrtle Davis, Patrice Desvigne-Nickens, Andrew Freedman, Lori Minasian, Thomas Force, Scot C. Remick
Journal: JNCI Journal of the National Cancer Institute (2014)

Cardiotoxicity resulting from direct myocyte damage has been a known complication of cancer treatment for decades. More recently, the emergence of hypertension as a clinically significant side effect of several new agents has been recognized as adversely affecting cancer treatment outcomes. With cancer patients living longer, in part because of treatment advances, these adverse events have become increasingly important to address. However, little is known about the cardiovascular pathogenic mechanisms associated with cancer treatment and even less about how to optimally prevent and manage short- and long-term cardiovascular complications, leading to improved patient safety and clinical outcomes. To identify research priorities, allocate resources, and establish infrastructure required to address cardiotoxicity associated with cancer treatment, the National Cancer Institute (NCI) and National Heart, Lung and Blood Institute (NHLBI) sponsored a two-day workshop, "Cancer treatment–related cardiotoxicity: Understanding the current state of knowledge and future research priorities," in March 2013 in Bethesda, MD. Participants included leading oncology and cardiology researchers and health professionals, patient advocates and industry representatives, with expertise ranging from basic to clinical science. Attendees were charged with identifying research opportunities to advance the understanding of cancer treatment–related cardiotoxicity across basic and clinical science. This commentary highlights the key discussion points and overarching recommendations from that workshop.
Eleven Years of Community-Based Directly Observed Therapy for Tuberculosis
Authors: C. Patrick Chaulk
Journal: JAMA (1995)

To evaluate community-based directly observed therapy (DOT) for tuberculosis (TB) control.Ecological study.Three comparisons were made in this descriptive study. (1) An 11-year retrospective comparison of TB case rates, sputum conversion rates (SCRs), rates of therapy completion, and confounding factors (acquired immunodeficiency syndrome [AIDS], immigration, unemployment, and poverty) in Baltimore, Md, with those of the five major US cities having the highest TB incidence in 1981 but which did not have comprehensive DOT programs. (2) An 11-year trend of TB in Baltimore and the 19 major US cities with the highest TB incidence in 1981. (3) A 7-year trend in TB in both city groups between 1985 and 1992.Twenty US metropolitan cities with more than 250,000 residents.Since 1981, Baltimore experienced the greatest decline in TB incidence (35.6 cases per 100,000 population, 1981; 17.2 cases per 100,000 population, 1992 [-51.7%]), and city rank for TB (sixth in 1981, 28th in 1992). Conversely, the average incidence of TB increased 2.1% in the five-city cohort and increased 1.8% in the 19-city cohort. Since 1985, TB incidence increased 35.3% in the five-city cohort and 28.5% in the 19-city cohort, but declined 29.5% in Baltimore. From 1986 through 1992, Baltimore's DOT-managed cases had the highest annual SCRs at 3 months (mean, 90.7%), and the highest completion rates for standard anti-TB therapy (mean, 90.1%) when compared with the five cities. These trends could not be attributed to differentials in AIDS, immigration, poverty, or unemployment. Increasingly, more Baltimore cases were treated under DOT (86.5%, 1993) over time. Disease relapse rates remained low, even among HIV-infected patients. Within Baltimore, the documented SCR was significantly higher among DOT-managed cases compared with non-DOT-managed cases (P < .05); multidrug resistance remains rare (0.57%). Within Maryland, Baltimore accounted for 44.4% of all TB cases in 1981, compared with 28.7% in 1992 (P < .001).In contrast to the national TB upswing during the 1980s, Baltimore experienced a substantial decline in TB following implementation of community-based DOT, despite highly prevalent medicosocial risk factors. Directly observed therapy facilitated high treatment completion rates and bacteriologic evidence of cure. Directly observed therapy could help reduce TB incidence in the United States, particularly in cities with high case rates.
Plexiform neurofibromas, trial design, and the definitions of "progression" and "treatment failure"
Authors: M. D. Prados
Journal: Neuro-Oncology (2014)

The article by Widermann et al is timely. In the context of this study and recently reported trials in newly diagnosed Glioblastoma, the question of appropriate endpoints and outcome measures, along with trial design, has resurfaced as a critical discussion point, particularly as it relates to decisions concerning drug development. In the current trial children and young adults with progressive plexiform neurofibromas were treated with tipifarnib, a farnesyltransferase inhibitor, or placebo, and allowed a cross-over at progression to either treatment in a second stage. There are a number of unique aspects to the study, starting with the understanding that this is a disease with a poorly understood and studied natural history. These tumors grow slowly and variably over time, are difficult to measure, occur in multiple regions of the body, have a complex biology related to RAS signaling, and there is no effective treatment other than surgery done as an attempt to minimize morbidity. Besides the difficult choice of drug selection, the type(s) of endpoint needed to evaluate efficacy becomes problematic without good historical control studies. The authors chose to use progression as the primary endpoint rather than objective response, and added the placebo control arm because of the uncertain natural history of these tumors. When are plexiform neurofibromas “progressive”? As shown by
Association of Public Reporting for Percutaneous Coronary Intervention With Utilization and Outcomes Among Medicare Beneficiaries With Acute Myocardial Infarction
Authors: Karen E. Joynt, Daniel M. Blumenthal, E. John Orav, Frederic S. Resnic, Ashish K. Jha
Journal: JAMA (2012)

Context-Public reporting of patient outcomes is an important tool to improve quality of care, but some observers worry that such efforts will lead clinicians to avoid high-risk patients.Objective-To determine whether public reporting for percutaneous coronary intervention (PCI) is associated with lower rates of PCI for patients with acute myocardial infarction (MI) or with higher mortality rates in this population.Design, Setting, and Patients-Retrospective observational study conducted using data from fee-for-service Medicare patients (49,660 from reporting states and 48,142 from nonreporting states) admitted with acute Ml to US acute care hospitals between 2002 and 2010.Logistic regression was used to compare PCI and mortality rates between reporting states (New York, Massachusetts, and Pennsylvania) and regional nonreporting states (Maine, Vermont, New Hampshire, Connecticut, Rhode Island, Maryland, and Delaware).Changes in PCI rates over time in Massachusetts compared with nonreporting states were also examined.Main Outcome Measures-Risk-adjusted PCI and mortality rates.Results-In 2010, patients with acute MI were less likely to receive PCI in public reporting states than in nonreporting states (unadjusted rates, 37.7% vs. 42.7%,respectively; risk-adjusted odds ratio [OR], 0.82, 95% CI, 0.71-0.93,P=.003).Differences were greatest among the 6708 patients with ST-segment elevation Ml (61.8% vs 68.0%; OR, 0.73 [95% CI, 0.59-0.89];P=.002) and the 2194 patients with cardiogenic shock or cardiac arrest (41.5% vs 46.7%, OR 0.79 [0.64, 0.98], P=.030).In Massachusetts, odds of PCI for acute Ml were comparable with odds in nonreporting states prior to public reporting (40.6% versus 41.8%, OR 1.00 [0.71, 1.41]).However, after implementation of public reporting, odds of undergoing PCI in Massachusetts decreased compared with nonreporting states (41.1% versus 45.6%, OR 0.81 [0.47, 1.38], p=.030 for difference in differences).Differences were most pronounced for the 6081 patients with cardiogenic shock or cardiac arrest (pre-reporting, 44.2% versus 36.6%,OR 1.40 [0.85, 2.37] postreporting, 43.9% versus 44.8%, OR 0.92 [0.38, 2.22], p=.028 for difference in differences).
A laboratory comparison of four positive pressure ventilators used in the home
Authors: IE Smith, JM Shneerson
Journal: European Respiratory Journal (1996)

Four brands of ventilator used for noninvasive positive pressure ventilation in the home were assessed to determine their performance on a patient simulator. We tested the tidal volume (VT) preset Companion 2801 (Puritan Bennett), minute volume preset Monnal D (Taema), and two pressure preset ventilators, the Nippy (Friday Medical) and the Bilevel Positive Airway Pressure (BiPAP) (Respironics). A patient simulator was employed to investigate the relationships between VT, peak airway pressure (PAP) and mean airway pressure (MAP), the responses to an additional leak in the circuit and patient effort of a variable duration, which was modelled using a negative pressure pump. For equivalent VTs, &gt;300 mL, the Monnal D and Nippy generated a PAP up to 100% greater than the Companion 2801 and BiPAP. When an additional leak was introduced to the circuit, the VT of the Companion 2801 and Monnal D fell by &gt;50%, while the Nippy and the BiPAP responded by increasing flow and maintained VT close to the level achieved with no leak. When the ventilators were triggered by a simulated patient effort of 0.25 s duration with a frequency 33% greater than that of the ventilator, the minute volume increased by 41% for the Companion 2801, by 18% for the Monnal D (no change expected), and by 17% for the Nippy (less than expected), and fell by 7% for the BiPAP due to irregular triggering. When patient effort was prolonged to 1.5 s, a similar length to the inspiratory time of the ventilators, there was no further change in the minute volume of the Companion 2801 and Monnal D, while that of the Nippy and of the BiPAP increased by 38 and 71%, respectively, compared to baseline. These results show that distinct brands of ventilator respond to changes in the patient and patient circuit in different ways, which are not always predictable from a simple description of their operating principles. This should be borne in mind when choosing a positive pressure ventilator for noninvasive ventilation.
Demethylating Drugs as Novel Analgesics for Cancer Pain
Authors: Chi T. Viet, Dongmin Dang, Yi Ye, Kentaro Ono, Ronald R. Campbell, Brian L. Schmidt
Journal: Clinical Cancer Research (2014)

Abstract Purpose: In this study, we evaluated the analgesic potential of demethylating drugs on oral cancer pain. Although demethylating drugs could affect expression of many genes, we focused on the mu-opioid receptor (OPRM1) gene pathway, because of its role in pain processing. We determined the antinociceptive effect of OPRM1 re-expression in a mouse oral cancer model. Experimental Design: Using a mouse oral cancer model, we determined whether demethylating drugs produced antinociception through re-expression of OPRM1. We then re-expressed OPRM1 with adenoviral transduction and determined if, and by what mechanism, OPRM1 re-expression produced antinociception. To determine the clinical significance of OPRM1 on cancer pain, we quantified OPRM1 methylation in painful cancer tissues and nonpainful contralateral normal tissues of patients with oral cancer, and nonpainful dysplastic tissues of patients with oral dysplasia. Results: We demonstrated that OPRM1 was methylated in cancer tissue, but not normal tissue, of patients with oral cancer, and not in dysplastic tissues from patients with oral dysplasia. Treatment with demethylating drugs resulted in mechanical and thermal antinociception in the mouse cancer model. This behavioral change correlated with OPRM1 re-expression in the cancer and associated neurons. Similarly, adenoviral-mediated OPRM1 re-expression on cancer cells resulted in naloxone-reversible antinociception. OPRM1 re-expression on oral cancer cells in vitro increased β-endorphin secretion from the cancer, and decreased activation of neurons that were treated with cancer supernatant. Conclusion: Our study establishes the regulatory role of methylation in cancer pain. OPRM1 re-expression in cancer cells produces antinociception through cancer-mediated endogenous opioid secretion. Demethylating drugs have an analgesic effect that involves OPRM1. Clin Cancer Res; 20(18); 4882–93. ©2014 AACR.
A phase 2 study of imatinib in patients with relapsed or refractory Philadelphia chromosome-positive acute lymphoid leukemias
Authors: Oliver G. Ottmann, Brian J. Druker, Charles L. Sawyers, John M. Goldman, Jose Reiffers, Richard T. Silver, Sante Tura, Thomas Fischer, Michael W. Deininger, Charles A. Schiffer, Michele Baccarani, Alois Gratwohl, Andreas Hochhaus, Dieter Hoelzer, Sofia Fernandes-Reese, Insa Gathmann, Renaud Capdeville, Stephen G. O'Brien
Journal: Blood (2002)
Ultra-Low Contrast Volumes Reduce Rates of Contrast-Induced Nephropathy in Patients With Chronic Kidney Disease Undergoing Coronary Angiography
Authors: Garvan C. Kane, Brendan J. Doyle, Amir Lerman, Gregory W. Barsness, Patricia J. Best, Charanjit S. Rihal
Journal: Journal of the American College of Cardiology (2008)
Systematic Review of Adrenalectomy and Lymph Node Dissection in Locally Advanced Renal Cell Carcinoma
Authors: Hendrika J. Bekema, Steven MacLennan, Mari Imamura, Thomas B.L. Lam, Fiona Stewart, Neil Scott, Graeme MacLennan, Sam McClinton, T.R. Leyshon Griffiths, Andreas Skolarikos, Sara J. MacLennan, Richard Sylvester, Börje Ljungberg, James N'Dow
Journal: European Urology (2013)
Reticulum Cell Neoplasms Induced in C57BL/6 Mice by Cultured Virus Grown in Stromal Hematopoietic Cell Lines&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: M Haas, A Meshorer
Journal: JNCI Journal of the National Cancer Institute (1979)

Thirty-one adherent cell lines have been established from the spleens, lymph nodes, and bone marrow of C57BL/6 mice carrying radiation leukemia virus (Duplan isolate)-induced reticulum cell neoplasms (RCN). The cell lines had a stable epithelial or fibroblastoid morphology, Supernatant virus from these lines induced splenic and lymph node RCN in 100% of inoculated C57BL/6 mice within 30 days. The disease was generalized and involved many organs. The monolayer cells themselves were not tumor cells and induced RCN through infection of the host with RCN virus. Simultaneous inoculation of in vitro-grown RCN-inducing virus any thymic lymphosarcoma virus induced each disease independently with unaltered incidence, latency period, and organ involvement; no mutual enhancement or inhibition was found, thus two separate mechanisms of action were indicated. Reextraction of the viruses from spleen, lymph nodes, and thymus gland indicated the specific organotropism of each agent. All the adherent cell lines that were derived from hematopoietic tissues produced ample, potent RCN-inducing virus. This high success rate suggests that in the hematopoietic organs the stromal, fibroblastoid cells are a natural habitat for the RCN-inducing virus. The RCN-inducing virus species may well be synthesized in these hematopoietic stromal cells. RCN-inducing virus from culture supernatants contained high-titer infectious ecotropic and xenotropic virus that was titrated. The cultures are being used to clone the RCN-inducing virus and to establish the virologic and molecular properties that endow it with specific RCN-inducing capacity.
HEMOGLOBIN AND PLASMA PROTEIN
Authors: F. S. Robscheit-Robbins, L. L. Miller, G. H. Whipple
Journal: The Journal of Experimental Medicine (1943)

Given healthy dogs, fed abundant iron and protein-free or low protein diets, with sustained anemia due to bleeding, we can study the capacity of these animals to produce simultaneously new hemoglobin and plasma protein. The reserve stores of blood protein producing materials in this way are very largely depleted, and levels of 6 to 8 gm. per cent for hemoglobin and 4 to 5 gm. per cent for plasma protein can be maintained for considerable periods of time. These dogs are very susceptible to infection and to injury by many poisons. Under such conditions, these anemic and hypoproteinemic dogs will use very efficiently a variety of digests (serum, hemoglobin, and casein) and the growth mixture (Rose) of pure amino acids. Nitrogen balance is maintained and considerable new blood proteins are produced. Dog plasma by vein is used freely in these doubly depleted dogs to make new hemoglobin in abundance (Table 1). Serum digests by vein are well utilized to make new hemoglobin and plasma protein in the same dogs (Table 1). Serum digests by mouth are effectively used to make new blood proteins (Table 5). Dog or sheep hemoglobin given in large amounts intraperitoneally are remarkably well utilized to form hemoglobin and plasma protein (Table 6). It must be obvious that the globin of the hemoglobin is saved in these protein-depleted dogs and used to make large amounts of hemoglobin and plasma protein. Hemoglobin digests are also well utilized whether given by mouth (Table 7) or by vein (Table 8) and liberal amounts of plasma protein are manufactured from digests presumably ideally suited for hemoglobin production. Casein digests are well used (Table 8) and form as much new plasma protein as any material tested-even serum digests. Amino acid mixtures are of especial interest. The growth mixture of 10 amino acids (Rose) is well utilized by mouth or by vein and favors new hemoglobin production more than any material tested (Table 2). Cystine replacing methionine in the amino acid mixture increases the plasma protein-hemoglobin output ratio, that is it favors plasma protein production. Digests of various sorts and amino acid mixtures or combinations of digests and amino acid mixtures can be used rapidly and effectively to build new hemoglobin or plasma protein, to maintain nitrogen equilibrium, and to replete reserve protein stores. These experiments point to clinical problems. The unexplained preference given to hemoglobin production in these hypoproteinemic dogs is observed under all conditions, even when whole plasma or serum digests are given by vein. In general, 2 to 4 gm. of hemoglobin are formed for every gram of plasma protein. This all adds up to a remarkable fluidity in the use of plasma protein or hemoglobin which can contribute directly to the body protein pool from which are evolved, without waste of nitrogen, the needed proteins, whether hemoglobin, plasma protein, or tissue proteins.
Up-regulation of circulating adhesionmolecules in bronchiectasis
Authors: L. Zheng, G. Tipoe, W.K Lam, R.Y.H Leung, J.C Ho, I.H Shum, G.C Ooi, M.S Ip, K.W Tsang
Journal: European Respiratory Journal (2000)

Adhesion molecules are expressed on the surface of endothelial cells and leukocytes and are responsible for mediating the migration of intravascular leukocytes into inflamed tissue. Intensive recruitment of neutrophils into the airways occurs in bronchiectasis, although little is known about the role of adhesion molecules in this process. The authors, therefore, determined serum levels of E-selectin, intercellular adhesion molecule (ICAM)-1 and vascular adhesion molecule (VCAM)-1 in stable bronchiectasis patients (n=37) and healthy control subjects (n=17), and evaluated their relationship with clinical markers of disease severity in bronchiectasis. Serum levels of E-selectin, ICAM-1 and VCAM-1 in bronchiectasis patients were significantly higher than those in control subjects (p=0.02, &lt;0.0001 and 0.0002 respectively). Both E-selectin and ICAM-1 levels were inversely related to forced expiratory volume in one second (FEV1)% predicted (r=-0.57, p&lt;0.001; and r=-0.53, p=0.001 respectively), and FVC% predicted (r=-0.52, p=0.002; and r=-0.46, p=0.005). This was not the case for VCAM-1 levels. There was a correlation between serum ICAM-1 levels and 24 h sputum volume (r=0.34, p= 0.04). Serum E-selectin and ICAM-1, but not VCAM-1, levels showed correlation with the number of lung lobes affected by bronchiectasis (r=0.35, p=0.04 and r=0.34, p=0.04 respectively). These original observations strongly suggest that E-selectin, intercellular adhesion molecule-1 and Vascular adhesion molecule-1 could play a significant role in the pathogenesis of bronchiectasis.