tbuckley/cabot-search huggingface dataset:
Follow-Up for Patients With Colorectal Cancer After Curative-Intent Primary Treatment
Authors: Frank E. Johnson, Katherine S. Virgo, Roldano Fossati
Journal: Journal of Clinical Oncology (2004)

The introduction of effective anesthetics in the midnineteenth century permitted the rapid development of surgery, which remains the primary form of therapy for colorectal cancer. Some patients were rendered grossly disease-free by surgery, creating a population at risk for recurrence for the first time in history. A few decades later, surgical salvage of relapse was attempted and, in a few instances, patients were cured. This provided a rationale for trying to diagnose recurrence early, while resection was still feasible. It was known at that time that individuals with one cancer were unusually likely to develop another, particularly in the same tissue as the index lesion. This provided further justification for patient follow-up, but posttreatment surveillance strategies evolved unevenly and largely without clinical trials to demonstrate effectiveness. Efforts to diagnose and treat recurrent colorectal cancer reached a peak with planned “second-look” laparotomy for patients with various intra-abdominal cancers judged to be at high risk for local-regional relapse. 1 Over half of these patients had node-positive colorectal cancer and nearly 50% of them had relapse documented at exploration. Most importantly, some patients were rendered tumor-free at operation, and a few of these were long-term disease-free survivors. The very high morbidity and mortality rates (to say nothing of the costs) associated with this strategy soon became apparent, but the introduction of modern diagnostic tools such as computed tomography (CT) and carcino-embryonic antigen (CEA) measurement now permit clinicians to select patients for salvage attempts much more precisely. Many of the wealthier nations of the world are now able to provide access to modern medicine to all or most of their citizens, with concomitant increases in the duration and quality of life. A by-product of the increase in the average life span has been a large increase in the total number of people afflicted with colorectal cancer, as the incidence of the disease increases with age. Costs of care also have risen dramatically, and therein lies one of the conundrums of modern clinical practice: how to use costly resources wisely. In an attempt to rationalize care, the concept of the randomized trial was introduced in the mid-twentieth century. The results of one million randomized trials have been published since then, 2 but very few have dealt with follow-up of patients with colorectal carcinoma. This poses an important problem because there are many patients at risk and the costs of diagnosis (and treatment, if needed) are high. 3 The American Cancer Society predicts that, in the
Collagenous Colitis and Lymphocytic Colitis
Authors: John M. Zeroogian, Sanjiv Chopra
Journal: Annual Review of Medicine (1994)

Collagenous and lymphocytic colitis are newly recognized causes of choric watery diarrhea that typically affect middle-aged patients. Although endoscopic studies are normal, inflammatory changes and (in the case of collagenous colitis) collagen deposition occur histologically in the colonic mucosa. The pathogenesis of these disorders remains a mystery, but the possible causes are intriguing. Patients may experience spontaneous remissions and relapses, but treatment with sulfasalazine or prednisone is usually effective for patients with distressing symptoms.
Non-Hodgkin's Lymphoma and Sunlight
Authors: P. Hartge, S. S. Devesa, D. Grauman, T. R. Fears, J. F. Fraumeni
Journal: JNCI Journal of the National Cancer Institute (1996)

Incidence and mortality rates for nonHodgkin's lymphoma (NHL) continue to rise dramatically throughout the world (7,2). Changes in diagnostic practices and in levels of exposure to the established risk factors for NHL (including genetic predisposition, immunosuppression, infection with human immunodeficiency virus [HIV], and various occupational exposures) cannot account for the long-term, worldwide increases (3). On the basis of epidemiologic and experimental observations, some investigators (4,5) recently suggested that sunlight may contribute to the development of NHL and its upward trend. In particular, the rise in NHL incidence parallels the global rise in melanoma incidence (6), patients with NHL are at an elevated risk of developing melanoma (7-10), and experimental data show immunosuppressive effects of UV radiation that may predispose to melanoma or other cancers (//). The hypothesis that sunlight exposure may affect NHL risk (4Jj,10) prompted us to review the geographic patterns of mortality rates in the United States for the following three decades: 1950-1959, 1960-1969, and 1970-1980 (12). In white men and white women, NHL mortality was consistently lower in the southern half of the United States, particularly during the earliest period. In contrast, mortality from melanoma of the skin and nonmelanoma skin cancer A. White men
Parametric Response Map As an Imaging Biomarker to Distinguish Progression From Pseudoprogression in High-Grade Glioma
Authors: Christina Tsien, Craig J. Galbán, Thomas L. Chenevert, Timothy D. Johnson, Daniel A. Hamstra, Pia C. Sundgren, Larry Junck, Charles R. Meyer, Alnawaz Rehemtulla, Theodore Lawrence, Brian D. Ross
Journal: Journal of Clinical Oncology (2010)

To assess whether a new method of quantifying therapy-associated hemodynamic alterations may help to distinguish pseudoprogression from true progression in patients with high-grade glioma.Patients with high-grade glioma received concurrent chemoradiotherapy. Relative cerebral blood volume (rCBV) and blood flow (rCBF) maps were acquired before chemoradiotherapy and at week 3 during treatment on a prospective institutional review board-approved study. Pseudoprogression was defined as imaging changes 1 to 3 months after chemoradiotherapy that mimic tumor progression but stabilized or improved without change in treatment or for which resection revealed radiation effects only. Clinical and conventional magnetic resonance (MR) parameters, including average percent change of rCBV and CBF, were evaluated as potential predictors of pseudoprogression. Parametric response map (PRM), an innovative, voxel-by-voxel method of image analysis, was also performed.Median radiation dose was 72 Gy (range, 60 to 78 Gy). Of 27 patients, stable disease/partial response was noted in 13 patients and apparent progression was noted in 14 patients. Adjuvant temozolomide was continued in all patients. Pseudoprogression occurred in six patients. Based on PRM analysis, a significantly reduced blood volume (PRM(rCBV)) at week 3 was noted in patients with progressive disease as compared with those with pseudoprogression (P < .01). In contrast, change in average percent rCBV or rCBF, MR tumor volume changes, age, extent of resection, and Radiation Therapy Oncology Group recursive partitioning analysis classification did not distinguish progression from pseudoprogression.PRM(rCBV) at week 3 during chemoradiotherapy is a potential early imaging biomarker of response that may be helpful in distinguishing pseudoprogression from true progression in patients with high-grade glioma.
Flice-Inhibitory Protein Is a Key Regulator of Germinal Center B Cell Apoptosis
Authors: Ana Hennino, Marion Bérard, Peter H. Krammer, Thierry Defrance
Journal: The Journal of Experimental Medicine (2001)

Affinity maturation of the B cell response to antigen (Ag) takes place in the germinal centers (GCs) of secondary follicles. Two sequential molecular mechanisms underpin this process. First, the B cell repertoire is diversified through hypermutation of the immunoglobulin (Ig) variable region genes. Second, mutant B cell clones with improved affinity for Ag are positively selected by Ag and CD40 ligand (L). This selection step is contingent upon “priming” of GC B cells for apoptosis. The molecular means by which B cell apoptosis is initiated and controled in the GC remains unclear. Here, we show that GC B cell apoptosis is preceded by the rapid activation of caspase-8 at the level of CD95 death-inducing signaling complex (DISC). We found that GC B cells ex vivo display a preformed inactive DISC containing Fas-associated death domain–containing protein (FADD), procaspase-8, and the long isoform of cellular FADD-like IL-1β–converting enzyme-inhibitory protein (c-FLIPL) but not the CD95L. In culture, c-FLIPL is rapidly lost from the CD95 DISC unless GC B cells are exposed to the survival signal provided by CD40L. Our results suggest that (a) the death receptor signaling pathway is involved in the affinity maturation of antibodies, and (b) c-FLIPL plays an active role in positive selection of B cells in the GC.
Impact of Inspired Gas Mixtures on Preoperative Infants With Hypoplastic Left Heart Syndrome During Controlled Ventilation
Authors: Sarah Tabbutt, Chandra Ramamoorthy, Lisa M. Montenegro, Suzanne M. Durning, C. Dean Kurth, James M. Steven, Rodolfo I. Godinez, Thomas L. Spray, Gil Wernovsky, Susan C. Nicolson
Journal: Circulation (2001)

Management strategies for preoperative infants with hypoplastic left heart syndrome (HLHS) include increased inspired nitrogen (hypoxia) and increased inspired carbon dioxide (hypercarbia). There are no studies directly comparing these 2 therapies in humans. This study compares the impact of hypoxia versus hypercarbia on oxygen delivery, under conditions of fixed minute ventilation.Ten anesthetized and paralyzed preoperative infants with HLHS were evaluated in a prospective, randomized, crossover trial comparing hypoxia (17% FIO(2)) with hypercarbia (2.7% FICO(2)). Each patient was treated in a random order (10 minutes per condition) with a recovery period (15 to 20 minutes) in room air. Arterial (SaO(2)) and superior vena caval (SvO(2)) co-oximetry and cerebral oxygen saturation (ScO(2)) measurements were made at the end of each condition and recovery period. ScO(2) was measured by near infrared spectroscopy. Hypoxia significantly decreased both SaO(2) (-5.2+/-1.1%, P=0.0014) and SvO(2) (-5.6+/-1.7%, P=0.009) compared with baseline, but arteriovenous oxygen saturation (AVO(2)) difference (SaO(2)-SvO(2)) and ScO(2) remained unchanged. Hypercarbia decreased SaO(2) (-2.6+/-0.6%, P=0.002) compared with baseline but increased both ScO(2) (9.6+/-1.8%, P=0.0001) and SvO(2) (6+/-2.2%, P=0.022) and narrowed the AVO(2) difference (-8.5+/-2.3%, P=0.005). Both hypoxia and hypercarbia decreased the balance between pulmonary and systemic blood flow (Qp:Qs) compared with baseline.In preoperative infants with HLHS, under conditions of anesthesia and paralysis, although Qp:Qs falls in both conditions, oxygen delivery is unchanged during hypoxia and increased during hypercarbia. These data cannot differentiate cerebral from systemic oxygen delivery.
Pretargeted Molecular Imaging and Radioimmunotherapy
Authors: David M. Goldenberg, Chien-Hsing Chang, Edmund A. Rossi, William J. McBride, Robert M. Sharkey
Journal: Theranostics (2012)

Pretargeting is a multi-step process that first has an unlabeled bispecific antibody (bsMAb) localize within a tumor by virtue of its anti-tumor binding site(s) before administering a small, fast-clearing radiolabeled compound that then attaches to the other portion of the bsMAb.The compound's rapid clearance significantly reduces radiation exposure outside of the tumor and its small size permits speedy delivery to the tumor, creating excellent tumor/nontumor ratios in less than 1 hour.Haptens that bind to an anti-hapten antibody, biotin that binds to streptavidin, or an oligonucleotide binding to a complementary oligonucleotide sequence have all been radiolabeled for use by pretargeting.This review will focus on a highly flexible anti-hapten bsMAb platform that has been used to target a variety of radionuclides to image (SPECT and PET) as well as treat tumors.
Depression with the Use of Alpha-Methyldopa
Authors: WILLIAM T. MCKINNEY, FRANCIS J. KANE
Journal: American Journal of Psychiatry (1967)

We have reported a case of depression associated with alpha-methyldopa treatment in which there was a history of prior mood disturbances associated with the use of other drugs which can also alter catecholamine levels. Since most antihypertensive agents depend on the altered metabolism of catecholamines for their action, any such drugs can be expected to produce undesired psychic effects, particularly mood disturbances.
Leptin Induces Endothelin-1 in Endothelial Cells In Vitro
Authors: Peter Quehenberger, Markus Exner, Raute Sunder-Plassmann, Katharina Ruzicka, Christian Bieglmayer, Georg Endler, Claudia Muellner, Wolfgang Speiser, Oswald Wagner
Journal: Circulation Research (2002)

Leptin, a protein encoded by the obese gene, is produced by adipocytes and released into the bloodstream. In obese humans, serum leptin levels are increased and correlate with the individual’s body mass index and blood pressure. Elevated serum concentrations of endothelin-1 (ET-1), a potent vasoconstrictor and mitogen, were also observed in obese subjects. The pathomechanisms underlying this ET-1 increase in obesity are poorly understood. In the present study, we investigated the influence of the ob gene product leptin on the expression of ET-1 in human umbilical vein endothelial cells (HUVECs). Binding studies using 125 I-radiolabeled leptin revealed high- and low-affinity leptin binding sites on HUVECs (Kd1=13.1±3.1 nmol/L and Kd2=1390±198 nmol/L, respectively), mediating a time- and dose-dependent increase of ET-1 mRNA expression and protein secretion after incubation of HUVECs with leptin. This leptin-induced ET-1 expression was inhibited by preincubation of HUVECs with 0.75 μmol/L antisense phosphorothioate oligonucleotides directed against the leptin receptor Ob-Rb. Furthermore, after incubation with leptin, increased nuclear staining of c-fos and c-jun, the major components of the transcription factor AP-1, and increased AP-1 DNA binding were observed. Transient transfection studies with ET-1 promoter constructs showed that leptin-induced promoter activity was abolished in the absence of AP-1 binding sites or by cotransfection with a plasmid overexpressing a mutated jun, which is able to bind c-fos but not DNA. Thus, leptin upregulates ET-1 production in HUVECs via a mechanism potentially involving jun binding members of the bZIP family.
Birth Weight, Body Silhouette Over the Life Course, and Incident Diabetes in 91,453 Middle-Aged Women From the French Etude Epidemiologique de Femmes de la Mutuelle Générale de l'Education Nationale (E3N) Cohort
Authors: Blandine de Lauzon-Guillain, Beverley Balkau, Marie-Aline Charles, Isabelle Romieu, Marie-Christine Boutron-Ruault, Françoise Clavel-Chapelon
Journal: Diabetes Care (2009)

OBJECTIVE Obesity and increases in body weight in adults are considered to be among the most important risk factors for type 2 diabetes. Low birth weight is also associated with a higher diabetes incidence. We aimed to examine to what extent the evolution of body shape, from childhood to adulthood, is related to incident diabetes in late adulthood. RESEARCH DESIGN AND METHODS Etude Epidemiologique de Femmes de la Mutuelle Générale de l'Education Nationale (E3N) is a cohort study of French women born in 1925–1950 and followed by questionnaire every 2 years. At baseline, in 1990, women were asked to report their current weight, height, and body silhouette at various ages. Birth weight was recorded in 2002. Cases of diabetes were self-reported or obtained by drug reimbursement record linkage and further validated. RESULTS Of the 91,453 women who were nondiabetic at baseline, 2,534 developed diabetes over the 15 years of follow-up. Birth weight and body silhouette at 8 years, at menarche, and in young adulthood (20–25 years) were inversely associated with the risk of diabetes, independently of adult BMI during follow-up (all Ptrend &amp;lt; 0.001). In mid-adulthood (35–40 years), the association was reversed, with an increase in risk related to a larger body silhouette. An increase in body silhouette from childhood to mid-adulthood amplified the risk of diabetes. CONCLUSIONS Low birth weight and thinness until young adulthood may increase the risk of diabetes, independently of adult BMI during follow-up. Young women who were lean children should be especially warned against weight gain.
A Novel Means of Drug Delivery: Myoblast-Mediated Gene Therapy and Regulatable Retroviral Vectors
Authors: Clare R. Ozawa, Matthew L. Springer, Helen M. Blau
Journal: The Annual Review of Pharmacology and Toxicology (2000)

A potentially powerful approach to drug delivery in the treatment of disease involves the use of cells to introduce genes encoding therapeutic proteins into the body. Candidate genes for delivery include those encoding secreted factors that could have broad applications ranging from treatment of inherited single-gene deficiencies to acquired disorders of the vasculature or cancer. Myoblasts, the proliferative cell type of skeletal muscle tissues, are potent tools for stable delivery of a gene of interest into the body, as they become an integral part of the muscle into which they are injected, in close proximity to the circulation. The recent development of improved tetracycline-inducible retroviral vectors allows for fine control of recombinant gene expression levels. The combination of ex vivo gene transfer using myoblasts and regulatable retroviral vectors provides a powerful toolbox with which to develop gene therapies for a number of human diseases.
Enhanced survival of lung granulocytes in an animal model of asthma: evidence for a role of GM-CSF activated STAT5 signalling pathway
Authors: R K Turlej
Journal: Thorax (2001)

Background-As granulocyte/macrophage colony stimulating factor (GM-CSF) mediated delay of granulocyte apoptosis contributes to the accumulation of inflammatory cells at the site of inflammation in many diseases, we sought to determine whether asthma is also associated with a GM-CSF dependent increase in lung granulocyte survival.Moreover, because GM-CSF mediates its eVects through activation of signal transducer and activator of transcription 5 (STAT5), we also investigated the potential role of STAT5 in allergic inflammation.Methods-Blood granulocytes were recovered from six healthy and six heaves aVected horses, a model of asthma.Lung granulocytes were obtained by bronchoalveolar lavage (BAL) from the same horses.Granulocytes were cultured in the presence or absence of anti-GM-CSF receptor antibodies for diVerent times and apoptosis was determined using the Annexin-V/propidium iodide detection method.Nuclear protein extracts from cultured granulocytes were analysed for STAT5 binding activity by electrophoretic mobility shift assay.Results-BAL fluid granulocytes from heaves aVected horses demonstrated a significant delay in apoptosis compared with blood granulocytes from the same horses and blood and BAL fluid granulocytes from healthy horses.Conversely, the rate of apoptosis in blood granulocytes from healthy and heaves aVected horses was comparable.The enhanced survival of BAL fluid granulocytes from aVected horses was suppressed in the presence of antibodies directed against GM-CSF receptors.Increased levels of active STAT5 were found in BAL fluid granulocytes from heaves aVected horses and were markedly reduced after treatment with anti-GM-CSF receptor antibodies.Conclusions-These data indicate that granulocyte survival is enhanced in the lung of heaves aVected horses and suggest a role for a GM-CSF activated STAT5 pathway in delaying apoptosis of lung granulocytes in this model of asthma.
Evidence that mesothelial cells regulate the acute inflammatory response in talc pleurodesis
Authors: E. Marchi, F. S. Vargas, M. M. Acencio, L. Antonangelo, E. H. Genofre, L. R. Teixeira
Journal: European Respiratory Journal (2006)

Intrapleural instillation of talc is used to produce pleurodesis in cases of recurrent malignant pleural effusions. The mechanisms by which pleurodesis is produced remain unknown but may involve either injury or activation of the mesothelium. The aim of the current study was to assess the inflammatory response of pleural mesothelial cells to talc in an experimental model in rabbits. A group of 10 rabbits were injected intrapleurally with talc (200 mg.kg(-1)) and undiluted pleural fluid was collected after 6, 24 or 48 h for measurement of interleukin (IL)-8, vascular endothelial growth factor (VEGF) and transforming growth factor (TGF)-beta1. Samples of pleura were studied to assess the inflammatory infiltrate and mesothelial cell viability. The pleural fluid IL-8 concentration peaked at 6 h, whereas VEGF and TGF-beta1 concentrations increased steadily over 48 h. Immunohistochemistry for cytokeratin showed a preserved layer of mesothelial cells despite the intense inflammatory pleural reaction. In conclusion, it is proposed that the mesothelial cell, although injured by the talc, may actively mediate the primary inflammatory pleural response in talc-induced pleurodesis.
Mild Hypertension: The Question of Treatment
Authors: D R Labarthe
Journal: Annual Review of Public Health (1986)

Mild hypertension is a major public health problem, not only in the US , but in many other areas of the world. It is a predictor and an important causal factor for a large proportion of premature mortality and morbidity as well, due principally to cardiovascular complications. Its prevalence is such that millions of adults, in the US alone, are currently or potentially affected by policies and practices concerning its treatment to prevent these complications. The feasibility of reducing the risks of complications, as reported from controlled clinical trials, appears to be accepted generally, though not universally. Guidelines to accom­ plish this on a national and even international scale have been published, and they have been adopted widely in some countries. Thus, in the US for example, the proportion of persons detected and classified as hypertensive who are under treatment with effective blood pressure reduction has increased markedly since the early 1970s. Still, in some demographic groups with especially high prevalence, hypertension (predominantly mild) remains largely uncontrolled (89). From the public health point of view, we are thus confronted with a problem of great importance, the availability of an effective response, and the evident need to bring further efforts to bear, if progress is to continue toward reduction of avoidable risks in the population at large. Treatment of mild hypertension is not a matter free of controversy, howev­ er. The recent literature reflects differences of judgment in several areas, including: (a) the true benefit of blood pressure reduction in relation to particu­ lar levels of pressure at the start of treatment; (b) the nature and extent of adverse consequences of treatment, chiefly from antihypertensive drugs; and (c) the proper role of nonpharmacologic therapy. The importance of these