tbuckley/cabot-search huggingface dataset:
PAIN AND ITS THERAPEUSIS.
Authors: S. V. CLEVENGER
Journal: JAMA (1897)

What is pain? The question to the mass of suffering humanity would appear absurd. The one who has experienced pain fancies that he knows what it is, just as "The primrose by the river's brim A yellow primrose is to him, And nothing more." But to the philosopher, and especially to the physiologist, the nature of pain, in common with the nature of all other life phenomena, has a significance unknown to those not given to such analysis. Consciousness is requisite in pain appreciation as well as any kind of feeling. The suppression or blunting of consciousness notoriously suppresses or blunts pain. The cognizance of pain being a cerebral process involving consciousness, cutting off the route to the brain by which pain is conveyed to consciousness disposes of the pain, but not of the cause originating it. Too many pain alleviators are mere deadeners of sensation. The inebriate "drives dull
Ventricular diastolic pressure-volume relations and the pericardium. Effects of changes in blood volume and pericardial effusion in dogs.
Authors: H Refsum, M Jünemann, M J Lipton, C Skiöldebrand, E Carlsson, J V Tyberg
Journal: Circulation (1981)

We investigated the role of the pericardium in the mechanism of shifts in the left ventricular (LV) diastolic pressure-volume relation produced by changes in circulating blood volume and by pericardial effusion. Twelve closed-chest anesthetized dogs were instrumented with pericardial and pleural balloons and intracardiac catheters for pressure measurements. We measured the volumes of the pericardium and the left and right ventricles by computed tomography (CT), integrating the area of CT cross-sections measured at 1-cm intervals from the cardiac apex to the aortic arch. The volumes of the pericardium and the cardiac chambers were changed by infusing 40 and 80 ml of dilute contrast medium into the pericardial space, by bleeding, and by rapidly infusing saline intravenously. Pericardial effusions of 80 ml reduced mean right ventricular volumes to 59% of control, whereas LV volumes were less severely compromised (81% of control). Total pericardial volume and pressure increased. Intravenous saline infusions, which raised right atrial pressure 10-15 mm Hg, produced increases of this magnitude in pericardial pressure. This was also the magnitude of the upward displacement in the LV diastolic pressure-volume relation after infusion. However, LV diastolic transmural pressure-volume coordinates fell along a single curve. Similar behavior was observed for the right ventricular diastolic pressure-volume relation. Pericardial transmural pressure-volume curves were described. When cardiac volume was altered by volume load and pericardial effusion, acute shifts in the LV diastolic pressure-volume relation were caused by changes in pericardial pressure, which, in turn, corresponded to changes in pericardial volume.
The effect of anti-α-fetoprotein-adriamycin conjugate on a human hepatoma
Authors: Eithan Galun, Daniel Shouval, Ruth Adler, Michal Shahaar, Meir Wilchek, Esther Hurwitz, Michael Sela
Journal: Hepatology (1990)

Conjugates between chemotherapeutic agents and antibodies, linked by a dextran bridge, were previously shown to be effective in suppression of hepatoma growth in vitro and in vivo . However, scaling up of production of such conjugates may lead to a high degree of variation in molar ratios of drug to antibody in different batches. In this study, an alternative link between drug and antibody was evaluated. A conjugate between adriamycin and murine IgGl monoclonal antibodies to human α–fetoprotein was prepared using a polyglutamic–acid bridge. The simple and reproducible method of linking adriamycin to a specific site on the antibody enabled the binding of the drug to α–fetoprotein with a high yield (63% to 68%); the molar ratio of drug/antibody was in the range of 110: 1 to 120: 1. The conjugate retained its capacity to bind to purified α–fetoprotein. Incorporation of [ 3 H]–thymidine or [ 3 H]–leucine into hepatoma cells, which express α–fetoprotein, was inhibited by the conjugate, compared with unconjugated antibody. Furthermore, 90% of this pharmacological activity was preserved, compared with free adriamycin. In vitro , the inhibitory activity of the polyglutamic acid conjugate was higher than that of a conjugate in which dextran was used as the linker between drug and antibody. In vivo , both conjugates were equally effective in suppression of hepatoma growth transplanted subcutaneously in athymic mice. However, this effect lasted only during the treatment period of 2 to 3 wk. Six days after discontinuation of therapy, reacceleration of tumor growth was observed regardless of the conjugate used. These preliminary results suggest that polyglutamic acid may be used as an alternative link to dextran for conjugation of anti–α–fetoprotein to adriamycin. However, use of monoclonal anti–α–fetoprotein for delivery of adriamycin to the hepatocellular carcinoma transplanted in athymic mice causes only partial remission of tumor growth. Therefore conjugates containing monoclonal antibodies to different cell surface antigens, administered sequentially or simultaneously, may have to be evaluated as well.(HEPATOLOGY 1990; 11:578:584.)
US hit by massive West Nile virus outbreak centred around Texas
Authors: B. Roehr
Journal: BMJ (2012)

Texas is at the epicentre of an outbreak of West Nile virus in the United States. At the latest count (17 August) there had been 551 reported cases and 21 deaths in the state this year, compared with only two deaths last year.

The first case of West Nile in Texas was reported on 25 May and the first death on 5 July, Jim Schuermann, a staff epidemiologist with the Texas Department of State Health, told the BMJ . Cases with neuroinvasive disease (305 patients) have outnumbered cases where only fever was reported (246 patients).

It can be difficult …
IgM turnover in Crohn's disease
Authors: K. B. Jensen, N. Goltermann, S. Jarnum, B. Weeke, H. Westergaard
Journal: Gut (1970)

Simultaneous turnover studies with radioiodine-labelled IgM and IgG were made in 12 patients with Crohn9s disease. Intestinal protein loss was estimated by means of <sup>59</sup>Fe-labelled iron dextran. The serum levels of IgM, IgG, and IgA were normal in most cases. The catabolic rate of IgM was increased in all but one case. A positive correlation was present between the catabolic rate and serum concentration of IgM, an observation which, so far, has been made only in Crohn9s disease. The synthetic rate of IgM was raised or high normal in four cases with an intraabdominal abscess. It was normal in the remaining cases. A strong positive correlation was found between the synthetic rates of IgM and IgG. The size of the protein loss was unrelated to the raised catabolic rates of IgM and IgG. Faecal radioiodine excretion from labelled IgM and IgG bore no relation to faecal <sup>59</sup>Fe excretion, nor did it indicate the site of the intestinal lesion. However, a close correlation was observed between faecal excretion of the labels from IgM and IgG.
Different adhesion types and active sensitivity of platelet subpopulations
Authors: B. Zhao, T. J. Filler, C. H. Rickert, J. F. Liu, A. D. Skholl-Engberts, V. Gurevich
Journal: American Journal of Hematology (1996)

Two different adhesion patterns of blood platelets with different sensitivity to adenosine were demonstrated by means of reflection contrast microscopy with consecutive image analysis and cell affinity chromatography. High-performance liquid chromatography revealed that thrombin-induced serotonin release of adenosine-sensitive platelets was lower than that of adenosine-resistant cells. Our results indicate platelet heterogeneity and suggest that the platelets with lower adenosine sensitivity may be actively involved in the early interaction between platelets and injured endothelium. © 1996 Wiley-Liss, Inc.
Low-Level Fiber-induced Radiographic Changes Caused by Libby Vermiculite
Authors: Amy M. Rohs, James E. Lockey, Kari K. Dunning, Rakesh Shukla, Huihao Fan, Tim Hilbert, Eric Borton, Jerome Wiot, Cristopher Meyer, Ralph T. Shipley, Grace K. LeMasters, Vikas Kapil
Journal: American Journal of Respiratory and Critical Care Medicine (2007)

From 1921 to 1990, vermiculite ore from Libby, Montana, was shipped worldwide for commercial and residential use. A 1980 study of a manufacturing facility using Libby vermiculite was the first to demonstrate a small but significant prevalence of pleural chest radiographic changes associated with amphibole fibers contained in the ore.This follow-up study of the original cohort evaluated the extent of radiographic changes and cumulative fiber exposure (CFE) 25 years after cessation of exposure.From the original cohort of 513 workers, 431 (84%) were living and available for participation and exposure reconstruction. Of these, 280 (65%) completed both chest radiographs and interviews. Primary outcomes were pleural and/or interstitial changes.Pleural and interstitial changes were demonstrated in 80 (28.7%) and 8 (2.9%) participants, respectively. Of those participants with low lifetime CFE of less than 2.21 fiber/cc-years, 42 (20%) had pleural changes. A significant (P < 0.001) exposure-response relationship of pleural changes with CFE was demonstrated, ranging from 7.1 to 54.3% from the lowest to highest exposure quartile. Removal of individuals with commercial asbestos exposure did not alter this trend.This study indicates that exposure within an industrial process to Libby vermiculite ore is associated with pleural thickening at low lifetime CFE levels. The propensity of the Libby amphibole fibers to dramatically increase the prevalence of pleural changes 25 years after cessation of exposure at low CFE levels is a concern in view of the wide national distribution of this ore for commercial and residential use.
The Great Fallout Controversy-Reply
Authors: Marshall Brucer
Journal: JAMA (1962)

To the Editor:—   editorial, The Great Fallout Controversy, has provoked comments. These have been complimentary comments by a ratio of 4 to 1. Just before the First World War, Max Steinitzer (a music critic) wrote: We live in times which are both infinitely primitive and infinitely complex.  realities of life in our day cannot provide us with a firm  hand...  more I read history, the more I am convinced that nobody has ever lived in normal times.  purpose of a critic (or an editorialist in medicine, politics, or music) is to make a distinction between the guiding hand and the unguiding foot. Physical facts are not a  hand. They can be misused to misguide.  fact that strontium-90 has a half-life of 28 years and is found in cow's milk is incidental and uncommunicative. Strontium-90 does not have a biological half-time of 28 years:
The tumor suppressor axis p53/miR-34a regulates Axl expression in B-cell chronic lymphocytic leukemia: implications for therapy in p53-defective CLL patients
Authors: J Boysen, S Sinha, T Price-Troska, S L Warner, D J Bearss, D Viswanatha, T D Shanafelt, N E Kay, A K Ghosh
Journal: Leukemia (2013)
Growth of a Meningioma in a Transsexual Patient after Estrogen–Progestin Therapy
Authors: Roberto Gazzeri, Marcelo Galarza, Giovanni Gazzeri
Journal: New England Journal of Medicine (2007)

A 28-year-old male-to-female transsexual patient, who was taking hormone therapy, presented with severe headache and visual disturbances. MRI revealed a giant olfactory-groove meningioma.
PARP and Cancer — If It's Broke, Don't Fix It
Authors: Lisa A. Carey, Norman E. Sharpless
Journal: New England Journal of Medicine (2011)

With apologies to Nietzsche, who once said "that which does not kill us makes us stronger," sometimes that which does not kill weakens us so the next blow will be lethal. In this issue of the Journal, O'Shaughnessy and colleagues1 describe a study in which poly(adenosine diphosphate–ribose) polymerase (PARP) inhibition was added to cytotoxic chemotherapy in an effort to set breast cancers up for that "next blow" (ClinicalTrials.gov number, NCT00540358). PARP inhibitors represent an exciting new therapeutic direction in oncology: the rational targeting of tumor-cell vulnerability during DNA repair.Cellular DNA is under constant assault; over 150 genes, in multiple . . .
HIGHER NEUROHORMONAL ACTIVATION IS ASSOCIATED WITH A POSITIVE RESPONSE TO CARVEDILOL IN PATIENTS WITH SYSTOLIC HEART FAILURE
Authors: Roberto Spoladore, Gabriele Fragasso, Altin Palloshi, Angelo Corti, Guido Lattuada, Barbara Colombo, Massimo Locatelli, Anna Salerno, Alberto Margonato
Journal: Journal of the American College of Cardiology (2010)
Purine Nucleoside Phosphorylase Deficiency: Improved Metabolic and Immunologic Function with Erythrocyte Transfusions
Authors: Kenneth C. Rich, Edwin Mejias, Irving H. Fox
Journal: New England Journal of Medicine (1980)

DEFICIENCY of the purine enzyme nucleoside phosphorylase is associated with a severe T-lymphocyte immune deficiency.1 2 3 4 5 6 The abnormality in the immune system results from the accumulation of purine metabolites that inhibit lymphocyte function.7 8 9 10 11 Correction of T-lymphocyte deficiencies by stem-cell transplantation is limited by the availability of suitable donors, but treatment of the metabolic disorder by enzyme-replacement therapy may provide a useful alternative.Transfusion therapy is effective for about half the patients with severe combined immunodeficiency associated with adenosine deaminase deficiency.12 13 14 In nucleoside phosphorylase deficiency transfusion therapy has been reported to produce partial improvement or no improvement in immune function.4 , 15 16 17 In this . . .
Genetic Analysis of Inherited Leukodystrophies
Authors: Rita Guerreiro, Eleanna Kara, Isabelle Le Ber, Jose Bras, Jonathan D. Rohrer, Ricardo Taipa, Tammaryn Lashley, Céline Dupuits, Nicole Gurunlian, Fanny Mochel, Jason D. Warren, Didier Hannequin, Frédéric Sedel, Christel Depienne, Agnès Camuzat, Véronique Golfier, Foucaud Du Boisguéheneuc, Lucia Schottlaender, Nick C. Fox, Jonathan Beck, Simon Mead, Martin N. Rossor, John Hardy, Tamas Revesz, Alexis Brice, Henry Houlden
Journal: JAMA Neurology (2013)

The leukodystrophies comprise a clinically and genetically heterogeneous group of progressive hereditary neurological disorders mainly affecting the myelin in the central nervous system.Their onset is variable from childhood to adulthood and presentation can be with a variety of clinical features that include mainly for adult-onset cases cognitive decline, seizures, parkinsonism, muscle weakness, neuropathy, spastic paraplegia, personality/behavioral problems, and dystonia.Recently, Rademakers and colleagues identified mutations in the CSF1R gene as the cause of hereditary diffuse leukoencephalopathy with spheroids (HDLS), offering the possibility for an in-life diagnosis.The detection of mutations in this gene in cases diagnosed with different clinical entities further demonstrated the difficulties in the clinical diagnosis of HDLS.OBJECTIVE To better understand the genetic role of mutations in this gene, we sequenced a large cohort of adult-onset leukodystrophy cases.DESIGN Whole-exome sequencing and follow up-screening by Sanger sequencing.
Possible Association of Cutaneous Rosai-Dorfman Disease and Chronic Crohn Disease
Authors: Katrin A. Salva, Melissa Stenstrom, Jonith Y. Breadon, Paul Blair Odland, Daniel Bennett, Jack Longley, Gary S. Wood
Journal: JAMA Dermatology (2013)

<h3>Importance</h3> Cutaneous Rosai-Dorfman disease (CRDD), a variant of Rosai-Dorfman disease limited to the skin, has a wide range of clinical presentations. Rosai-Dorfman disease is believed to result from an aberrant response to antigens, caused by immunosuppressive macrophages. Macrophage-mediated immunosuppression is also implicated in the pathogenesis of Crohn disease, linking these otherwise unrelated entities. To our knowledge, the coexistence of these disorders has been described in only 2 cases, 1 of them confined to the skin and soft tissue. <h3>Observations</h3> We present a series of 3 patients who developed purely CRDD in the context of long-standing Crohn disease. Statistical estimates suggested that the association of these 2 disorders is not due to chance (<i>P</i> &lt; .001). <h3>Conclusions and Relevance</h3> Our case series provides the clinical correlate to the pathogenetic parallels between CRDD and Crohn disease. Crohn disease is frequently complicated by various skin manifestations, which may be mimicked by CRDD. Therefore, it may be prudent for clinicians to include CRDD in the list of differential diagnoses when examining skin lesions in patients with Crohn disease.
Case-control study of intrapartum care, cerebral palsy, and perinatal death
Authors: G Gaffney, S Sellers, V Flavell, M Squier, A Johnson
Journal: BMJ (1994)

<h3>Abstract</h3> <b>Objective</b>: To investigate the relation between suboptimal intrapartum obstetric care and cerebral palsy or death. <b>Design</b>: Case-control study. <b>Setting</b>: Oxford Regional Health Authority. Subjects - 141 babies who subsequently developed cerebral palsy and 62 who died intrapartum or neonatally, 1984-7. All subjects were born at term of singleton pregnancies and had no congenital anomaly. Two controls, matched for place and time of birth, were selected for each index case. Main outcome measures - Adverse antenatal factors and suboptimal intrapartum care (by using predefined criteria). <b>Results</b>: Failure to respond to signs of severe fetal distress was more common in cases of cerebral palsy (odds ratio 4.5; 95% confidence interval 2.4 to 8.4) and in cases of death (26.1; 6.2 to 109.7) than among controls. This association persisted even after adjustment for increased incidence of a complicated obstetric history in cases of cerebral palsy. Neonatal encephalopathy is regarded as the best clinical indicator of birth asphyxia; only two thirds (23/33) of the children with cerebral palsy in whom there had been a suboptimal response to fetal distress, however, had evidence of neonatal encephalopathy; these 23 formed 6.8% of all children with cerebral palsy born to residents of the region in the four years studied. <b>Conclusion</b>: There is an association between quality of intrapartum care and death. The findings also suggest an association between suboptimal care and cerebral palsy, but this seems to have a role in only a small proportion of all cases of cerebral palsy. The contribution of adverse antenatal factors in the origin of cerebral palsy needs further study.
Molecular mechanisms of DNA damage initiated by alpha, beta-unsaturated carbonyl compounds as criteria for genotoxicity and mutagenicity.
Authors: E Eder, C Hoffman, H Bastian, C Deininger, S Scheckenbach
Journal: Environmental Health Perspectives (1990)

alpha, beta-Unsaturated carbonyl compounds are important not only from a theoretical but also a practical standpoint. These ubiquitous compounds can interact with DNA through various mechanisms. The predominant interaction is the formation of cyclic 1,N2-deoxyguanosine adducts; 7,8-cyclic guanine adducts are also found. We have synthesized and characterized the stereoisomers of adducts formed by about 20 alpha, beta-unsaturated carbonyl compounds. The different types of adducts and the mutagenic and genotoxic response can be explained by the molecular structures of the agents. Compounds forming saturated cyclic adducts are mutagenic in S. typhimurium strain TA100 and to a lesser extent in TA1535. Substances with a leaving group at the C-3 position form unsaturated conjugated cyclic adducts and are mutagenic only in the His D3052 frameshift strains with an intact excision repair system (no urvA mutation). Metabolic epoxidation of the double bond and other metabolic activation, e.g., activation of the nitrogroups via nitroreductases, were also found to contribute to genotoxic and mutagenic activities. Our results have further elucidated the genotoxic mechanisms of these compounds; however, additional investigations are required for a complete understanding of the genotoxic activity of this class of compounds.
T Lymphocytes: Ontogeny, Function, and Relevance to Clinical Disorders
Authors: H D Royer, E L Reinherz
Journal: New England Journal of Medicine (1987)

T-lymphocytes, unlike B lymphocytes, predominantly recognize antigen when it is associated with membrane-bound products of the major histocompatibility complex (MHC).1 2 3 This "dual" recognition (i.e., for both antigen and the MHC) is important for activation of both cytotoxic effector T cells and immunoregulatory T cells. Cytotoxic T cells lyse specific target cells, including tumor cells and cells infected with virus, whereas immunoregulatory T cells act as inducers or suppressors for interactions among T cells, B cells, macrophages, and other cells.The exquisite specificity of T cells has long been thought to be determined by unique, clonally distributed (clonotypic) cell-surface receptors. Because . . .
Permissive effect of nitric oxide in arachidonic acid induced dilation in isolated rat arterioles
Authors: E Bakker
Journal: Cardiovascular Research (1998)

Objective: Prostaglandins and nitric oxide play an important role in the regulation of arteriolar tone. l-Arginine analogues inhibit nitric oxide formation, but may also inhibit arachidonic-acid induced dilation. Nitric oxide was found to stimulate cyclooxygenase activity in cultured endothelial cells. Therefore, we hypothesized that the non-specific inhibition of prostaglandin-related dilation by l-arginine analogues is a consequence of the absence of nitric oxide. Methods: To test this hypothesis, arteriolar segments from rat cremaster muscle were studied in a pressure myograph at 75 mmHg. Segments developed spontaneous tone, the diameter reduced from 179±3 to 98±3 μm (n=41). In this condition, responses to exogenous arachidonic acid (1 μM) were recorded and compared with responses after addition of l-NNA, and addition of either SNAP, nitroprusside or 8-Br-cGMP in the presence of l-NNA. Results: Inhibition of basal nitric oxide production with l-NNA (0.1 mM) reduced arachidonic acid-induced dilation (from 52±9 to 31±6 μm). In the presence of l-NNA, responses to arachidonic acid were augmented when exogenous nitric oxide was also present (SNAP, 31±6 μm vs. 75±5 μm; nitroprusside, 31±8 μm vs. 42±7 μm). Responses were not augmented with the second messenger of nitric oxide-mediated dilation 8-Br-cGMP (37±9 μm vs. 32±9 μm). Conclusions: These results indicate that nitric oxide directly increases arachidonic acid-induced dilation. Thus, the non-specific effect of l-arginine analogues can be explained by a permissive effect of nitric oxide on endothelial arachidonic acid metabolism.
Expression and Function of Survivin in Canine Osteosarcoma
Authors: Jenette K. Shoeneman, E.J. Ehrhart, Jens C. Eickhoff, J.B. Charles, Barbara E. Powers, Douglas H. Thamm
Journal: Cancer Research (2011)

Osteosarcoma has a high mortality rate and remains in need of more effective therapeutic approaches. Survivin is an inhibitor of apoptosis family member protein that blocks apoptosis and drives proliferation in human cancer cells where it is commonly elevated. In this study, we illustrate the superiority of a canine osteosarcoma model as a translational tool for evaluating survivin-directed therapies, owing to the striking similarities in gross and microscopic appearance, biologic behavior, gene expression, and signaling pathway alterations. Elevated survivin expression in primary canine osteosarcoma tissue correlated with increased histologic grade and mitotic index and a decreased disease-free interval (DFI). Survivin attenuation in canine osteosarcoma cells inhibited cell-cycle progression, increased apoptosis, mitotic arrest, and chemosensitivity, and cooperated with chemotherapy to significantly improve in vivo tumor control. Our findings illustrate the utility of a canine system to more accurately model human osteosarcoma and strongly suggest that survivin-directed therapies might be highly effective in its treatment.